FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Liao, HS
Carvajal, N
Fu, X
Raftari, M
Jin, AJ
AF Liao, Hsien-Shun
Carvajal, Nicole
Fu, Xiao
Raftari, Maryam
Jin, Albert J.
TI Developing High-Speed AFM and Nanomechanical Characterizations for
Biomedical Investigations
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Liao, Hsien-Shun; Carvajal, Nicole; Fu, Xiao; Raftari, Maryam; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Liao, Hsien-Shun] Natl Taiwan Univ, Taipei 10764, Taiwan.
[Fu, Xiao] Beijing Inst Technol, Beijing 100081, Peoples R China.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 856-Pos
BP 171A
EP 171A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800344
ER
PT J
AU Abraham, SJ
Chavan, T
Cheng, RC
Fenollar-Ferrer, C
Han, W
Islam, SM
Jiang, T
Khantwal, CM
Mathews, II
Stein, RA
Roux, B
Forrest, LR
Mchaourab, HS
Tajkhorshid, E
Maduke, M
AF Abraham, Sherwin J.
Chavan, Tanmay
Cheng, Ricky C.
Fenollar-Ferrer, Cristina
Han, Wei
Islam, Shahidul M.
Jiang, Tao
Khantwal, Chandra M.
Mathews, Irimpan I.
Stein, Richard A.
Roux, Benoit
Forrest, Lucy R.
Mchaourab, Hassane S.
Tajkhorshid, Emad
Maduke, Merritt
TI An Outward-Facing Open Conformational State in a CLC Transporter
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Abraham, Sherwin J.; Chavan, Tanmay; Cheng, Ricky C.; Khantwal, Chandra M.; Maduke, Merritt] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Fenollar-Ferrer, Cristina; Forrest, Lucy R.] Natl Inst Neurol Disorders & Stroke, Computat Struct Biol Unit, NIH, Bethesda, MD USA.
[Han, Wei; Jiang, Tao; Tajkhorshid, Emad] Univ Illinois, Ctr Biophys & Computat Biol, Dept Biochem, Urbana, IL USA.
[Han, Wei; Jiang, Tao; Tajkhorshid, Emad] Univ Illinois, Beckman Inst, Urbana, IL USA.
[Islam, Shahidul M.; Roux, Benoit] Univ Chicago, Dept Biochem, Chicago, IL 60637 USA.
[Mathews, Irimpan I.] Stanford Univ, Stanford Synchrotron Radiat Lightsource, Stanford, CA 94305 USA.
[Stein, Richard A.; Mchaourab, Hassane S.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 891-Plat
BP 178A
EP 178A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800379
ER
PT J
AU Miranda, P
Giraldez, T
Holmgren, M
AF Miranda, Pablo
Giraldez, Teresa
Holmgren, Miguel
TI Selective Cation Binding to the Gating-Ring Triggers Independent RCK
Motions in the BK Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Miranda, Pablo; Holmgren, Miguel] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Giraldez, Teresa] Univ La Laguna, Ctr Biomed Res Canary Isl CIBICAN, Sch Med, Biomed Sci, E-38207 San Cristobal la Laguna, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 933-Plat
BP 187A
EP 187A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800421
ER
PT J
AU Lee, J
Joo, K
Joung, I
Lee, J
Lee, J
Lee, W
Brooks, B
Lee, SJ
AF Lee, Jooyoung
Joo, Keehyoung
Joung, InSuk
Lee, Jinhyuk
Lee, Jinwoo
Lee, Weontae
Brooks, Bernard
Lee, Sung Jong
TI Protein Structure Determination by Conformational Space Annealing using
NMR Geometric Restraints
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Lee, Jooyoung; Joung, InSuk] Korea Inst Adv Study, Sch Computat Sci, Seoul, South Korea.
[Joo, Keehyoung] Korea Inst Adv Study, Ctr Adv Computat, Seoul, South Korea.
[Lee, Jinhyuk] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr, Daejeon, South Korea.
[Lee, Jinwoo] Kwangwoon Univ, Dept Math, Seoul, South Korea.
[Lee, Weontae] Yonsei Univ, Dept Biochem, Seoul 120749, South Korea.
[Brooks, Bernard] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Sung Jong] Univ Suwon, Dept Phys, Hwaseong Si, South Korea.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 937-Plat
BP 188A
EP 188A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800425
ER
PT J
AU Kasprzak, WK
Kim, T
Afonin, KA
Gupta, K
Viard, M
Puri, A
Shapiro, BA
AF Kasprzak, Wojciech K.
Kim, Taejin
Afonin, Kirill A.
Gupta, Kshitij
Viard, Mathias
Puri, Anu
Shapiro, Bruce A.
TI Computational and Experimental Characterization of Novel Bolaamphiphiles
as RNA Nanostructure Delivery Agents
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kasprzak, Wojciech K.; Viard, Mathias; Puri, Anu] Leidos Biomed Res Inc, Basic Sci Program, Frederick, MD USA.
[Kim, Taejin; Gupta, Kshitij; Viard, Mathias; Shapiro, Bruce A.] NCI, GRCBL, NIH, Frederick, MD 21701 USA.
[Afonin, Kirill A.] Univ N Carolina, Dept Chem, Charlotte, NC 28223 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 996-Plat
BP 199A
EP 199A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800484
ER
PT J
AU Soubias, O
Sodt, AJ
Teague, WE
Hines, KG
Gawrisch, K
AF Soubias, Olivier
Sodt, Alexander J.
Teague, Walter E.
Hines, Kirk G.
Gawrisch, Klaus
TI Controlling GPCR Rhodopsin Function by Small, Physiologically Relevant
Changes in Bilayer Hydrophobic Thickness
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Soubias, Olivier; Sodt, Alexander J.; Teague, Walter E.; Hines, Kirk G.; Gawrisch, Klaus] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1021-Plat
BP 205A
EP 205A
PG 1
WC Biophysics
SC Biophysics
GA DK7GS
UT WOS:000375093800509
ER
PT J
AU Zhao, J
Krystofiak, E
Ferrer, CF
Morcillo, AB
van Itallie, C
Cui, RJ
Anderson, J
Forrest, L
Kachar, B
AF Zhao, Jun
Krystofiak, Evan
Ferrer, Cristina Fenollar
Morcillo, Angela Ballesteros
van Itallie, Christina
Cui, Runjia
Anderson, James
Forrest, Lucy
Kachar, Bechara
TI Probing the Intermolecular Interfaces between Claudin Protomers
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zhao, Jun; Krystofiak, Evan; Morcillo, Angela Ballesteros; Cui, Runjia; Kachar, Bechara] NIDCD, NIH, Bethesda, MD USA.
[Ferrer, Cristina Fenollar; Forrest, Lucy] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[van Itallie, Christina; Anderson, James] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1076-Pos
BP 216A
EP 216A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600054
ER
PT J
AU Sarkar, P
Veetil, JV
Davis, K
Puhl, HL
Nguyen, TA
Vogel, SS
AF Sarkar, Pabak
Veetil, Jithesh V.
Davis, Kaitlin
Puhl, Henry L., III
Nguyen, Tuan A.
Vogel, Steven S.
TI Deciphering CaMKII Multimerization using Holoenzyme Assembly Mutants,
FCS, and Concurrent Homo- and Hetero-FRET Analysis
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Sarkar, Pabak; Veetil, Jithesh V.; Davis, Kaitlin; Puhl, Henry L., III; Nguyen, Tuan A.; Vogel, Steven S.] NIAAA, SCB LMP, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1081-Pos
BP 217A
EP 217A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600059
ER
PT J
AU Lee, S
Bhattacharya, S
Mao, A
Grisshammer, R
Tate, C
Vaidehi, N
AF Lee, Sangbae
Bhattacharya, Supriyo
Mao, Allen
Grisshammer, Reinhard
Tate, Christopher
Vaidehi, Nagarajan
TI Insights into the Stability of GPCRs in Detergent Micelles
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Lee, Sangbae; Bhattacharya, Supriyo; Mao, Allen; Vaidehi, Nagarajan] City Hope Natl Med Ctr, Duarte, CA USA.
[Grisshammer, Reinhard] NIH, Rockville, MD USA.
[Tate, Christopher] Univ Cambridge, Cambridge, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1139-Pos
BP 229A
EP 229A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600117
ER
PT J
AU Jenkins, H
Whelan, F
Peters, D
Byrne, R
Konevega, A
Koonin, E
Antson, F
AF Jenkins, Huw
Whelan, Fiona
Peters, Daniel
Byrne, Robert
Konevega, Andrey
Koonin, Eugene
Antson, Fred
TI Recognition of Specific Uridines in tRNA Substrates by Dihydrouridine
Synthases
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Jenkins, Huw; Whelan, Fiona; Peters, Daniel; Byrne, Robert; Antson, Fred] Univ York, Dept Chem, York YO10 5DD, N Yorkshire, England.
[Konevega, Andrey] BP Konstantinov Petersburg Nucl Phys Inst, Gatchina, Russia.
[Koonin, Eugene] NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
RI Konevega, Andrey/B-7887-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1190-Pos
BP 239A
EP 239A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600168
ER
PT J
AU Mills, KM
Neuman, KC
AF Mills, K. Maria
Neuman, Keir C.
TI Single Molecule Measurements of DNA Decatenation by the Topoisomerase
III-RecQ Helicase Complex
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Mills, K. Maria; Neuman, Keir C.] NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1196-Pos
BP 240A
EP 241A
PG 7
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600174
ER
PT J
AU Sodt, AJ
Soubias, O
Gawrisch, K
Pastor, RW
AF Sodt, Alexander J.
Soubias, Olivier
Gawrisch, Klaus
Pastor, Richard W.
TI Lipid-Lipid Coupling to Membrane Curvature by Simulation and NMR
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Sodt, Alexander J.; Pastor, Richard W.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Soubias, Olivier; Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1210-Pos
BP 243A
EP 243A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600188
ER
PT J
AU Rubio, MA
Morin-Leisk, J
Hinshaw, JE
AF Rubio, Marisa A.
Morin-Leisk, Jeanne
Hinshaw, Jenny E.
TI Uncovering the Mechanism of Mitofusin 1 through Structural Studies
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Rubio, Marisa A.; Morin-Leisk, Jeanne; Hinshaw, Jenny E.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1235-Pos
BP 248A
EP 248A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600213
ER
PT J
AU Chlanda, P
Mekhedov, E
Waters, H
Schwartz, CL
Fischer, ER
Ryham, RJ
Cohen, FS
Blank, PS
Zimmerberg, J
AF Chlanda, Petr
Mekhedov, Elena
Waters, Hang
Schwartz, Cindi L.
Fischer, Elizabeth R.
Ryham, Rolf J.
Cohen, Fredric S.
Blank, Paul S.
Zimmerberg, Joshua
TI Structural Analysis of Hemagglutinin-Induced Hemifusion by Volta
Phase-Plate Cryo-Electron Tomography
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Chlanda, Petr; Mekhedov, Elena; Waters, Hang; Blank, Paul S.; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Schwartz, Cindi L.; Fischer, Elizabeth R.] NIAID, NIH, Hamilton, MT USA.
[Ryham, Rolf J.] Fordham Univ, Dept Math, Bronx, NY 10458 USA.
[Cohen, Fredric S.] Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA.
NR 1
TC 0
Z9 0
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1246-Pos
BP 250A
EP 251A
PG 6
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600224
ER
PT J
AU Sirenko, S
Yang, DM
Lakatta, EG
AF Sirenko, Syevda
Yang, Dongmei
Lakatta, Edward G.
TI Spontaneous, Local Diastolic Subsarcolemmal Ca2+ Releases (LCRS) in
Single Isolated Guinea-PIG Sinoatrial Nodal Cells (SANC) are Linked to
Their Spontaneous AP Firing
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Sirenko, Syevda; Yang, Dongmei; Lakatta, Edward G.] NIA, LCS, GRC, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1290-Pos
BP 259A
EP 260A
PG 7
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600268
ER
PT J
AU Maltsev, VA
Maltsev, AV
Juhaszova, M
Sirenko, S
Monfredi, O
Shroff, H
York, A
Sollott, SJ
Lakatta, EG
Stern, MD
AF Maltsev, Victor A.
Maltsev, Alexander V.
Juhaszova, Magdalena
Sirenko, Syevda
Monfredi, Oliver
Shroff, Hari
York, Andrew
Sollott, Steven J.
Lakatta, Edward G.
Stern, Michael D.
TI Cardiac Pacemaker Cell Function at a Super-Resolution Scale of SIM:
Distribution of RyRs, Calcium Dynamics, and Numerical Modeling
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Maltsev, Victor A.; Maltsev, Alexander V.; Juhaszova, Magdalena; Sirenko, Syevda; Monfredi, Oliver; Sollott, Steven J.; Lakatta, Edward G.; Stern, Michael D.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Monfredi, Oliver] Univ Manchester, Manchester, Lancs, England.
[Shroff, Hari] NIBIB, NIH, Bethesda, MD USA.
[York, Andrew] Calico Labs, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1321-Pos
BP 267A
EP 267A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600299
ER
PT J
AU Monfredi, OJ
Maltsev, A
Parsons, S
Ziman, B
Lakatta, E
Stern, MD
Maltsev, VA
AF Monfredi, Oliver J.
Maltsev, Alexander
Parsons, Sean
Ziman, Bruce
Lakatta, Edward
Stern, Michael D.
Maltsev, Victor A.
TI Relative Contribution of Local Ca2+ Releases (LCRS) and AP-Induced Ca2+
Transient Decay to Diastolic Depolarization in Rabbit Sa Node Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Monfredi, Oliver J.] Univ Manchester, Dept Cardiac Electrophysiol, Manchester, Lancs, England.
[Maltsev, Alexander; Ziman, Bruce; Lakatta, Edward; Stern, Michael D.; Maltsev, Victor A.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
[Parsons, Sean] McMaster Univ, Hamilton, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1322-Pos
BP 267A
EP 267A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600300
ER
PT J
AU Vinogradova, TM
Lukyanenko, Y
Tarasov, KV
Sirenko, S
Lyashkov, AE
Li, Y
Lakatta, EG
AF Vinogradova, Tatiana M.
Lukyanenko, Yevgeniya
Tarasov, Kirill V.
Sirenko, Syevda
Lyashkov, Alexey E.
Li, Yue
Lakatta, Edward G.
TI Concurrent PDE3 and PDE4 Activation Suppresses Local Ca2+ Releases (LCR)
to Regulate Normal Spontaneous Firing of Sinoatrial Node Cells (SANC)
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Vinogradova, Tatiana M.; Lukyanenko, Yevgeniya; Tarasov, Kirill V.; Sirenko, Syevda; Lyashkov, Alexey E.; Li, Yue; Lakatta, Edward G.] NIA, GRC, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1350-Pos
BP 273A
EP 274A
PG 7
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600328
ER
PT J
AU Tsutsui, K
Monfredi, OJ
Wirth, AN
Kim, MS
Bychkov, R
Maltsev, VA
Lakatta, EG
AF Tsutsui, Kenta
Monfredi, Oliver J.
Wirth, Ashley N.
Kim, Mary S.
Bychkov, Rostislav
Maltsev, Victor A.
Lakatta, Edward G.
TI Heterogeneity in Beating and Response to Beta Adrenergic Receptor
Stimulation in Isolated Single Sinoatrial Nodal Cells (SANC)
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Tsutsui, Kenta; Wirth, Ashley N.; Kim, Mary S.; Bychkov, Rostislav; Maltsev, Victor A.; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Baltimore, MD 21224 USA.
[Monfredi, Oliver J.] Univ Manchester, Inst Cardiovasc Sci, Manchester, Lancs, England.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1351-Pos
BP 274A
EP 274A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600329
ER
PT J
AU Jara-Oseguera, A
Bae, C
Swartz, KJ
AF Jara-Oseguera, Andres
Bae, Chanhyung
Swartz, Kenton J.
TI Extracellular Sodium is Required for Temperature-Dependent Gating in
TRPV1 Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Jara-Oseguera, Andres; Bae, Chanhyung; Swartz, Kenton J.] NINDS, Mol Physiol Biophys, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1400-Pos
BP 284A
EP 284A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600378
ER
PT J
AU Bae, C
Anselmi, C
Kalia, J
Jara-Oseguera, A
Schwieters, CD
Krepkiy, D
Lee, CW
Il Kim, J
Faraldo-Gomez, JD
Swartz, KJ
AF Bae, Chanhyung
Anselmi, Claudio
Kalia, Jeet
Jara-Oseguera, Andres
Schwieters, Charles D.
Krepkiy, Dmitriy
Lee, Chul Won
Il Kim, Jae
Faraldo-Gomez, Jose D.
Swartz, Kenton J.
TI Structure of a Double-Knot Tarantula Toxin Bound to the TRPV1 Channel at
the Protein-Lipid Interface
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Bae, Chanhyung; Anselmi, Claudio; Kalia, Jeet; Jara-Oseguera, Andres; Schwieters, Charles D.; Krepkiy, Dmitriy; Faraldo-Gomez, Jose D.; Swartz, Kenton J.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Chul Won] Chonnam Natl Univ, Gwangju, South Korea.
[Il Kim, Jae] GIST, Gwangju, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1406-Pos
BP 285A
EP 285A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600384
ER
PT J
AU Zhang, F
Hanson, SM
Pearce, L
Krepkiy, D
Jara-Oseguera, A
Blumberg, PM
Newstead, S
Swartz, KJ
AF Zhang, Feng
Hanson, Sonya M.
Pearce, Larry
Krepkiy, Dmitriy
Jara-Oseguera, Andres
Blumberg, Peter M.
Newstead, Simon
Swartz, Kenton J.
TI Engineering Vanilloid-Sensitivity into the TRPV2 Channel
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zhang, Feng; Hanson, Sonya M.; Krepkiy, Dmitriy; Jara-Oseguera, Andres; Swartz, Kenton J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Hanson, Sonya M.; Newstead, Simon] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
[Pearce, Larry] NCI, NIH, Bethesda, MD 20892 USA.
[Blumberg, Peter M.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1411-Pos
BP 286A
EP 286A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600389
ER
PT J
AU Li, MF
Silberberg, SD
Swartz, KJ
AF Li, Mufeng
Silberberg, Shai D.
Swartz, Kenton J.
TI Expression Level Dependence of the Gating and Permeation Properties of
P2X Receptor Channels
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Li, Mufeng; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1416-Pos
BP 287A
EP 287A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600394
ER
PT J
AU Matthies, D
Dalmas, O
Borgnia, M
Dominik, P
Merk, A
Rao, P
Reddy, B
Islam, S
Bartesaghi, A
Perozo, E
Subramaniam, S
AF Matthies, Doreen
Dalmas, Olivier
Borgnia, Mario
Dominik, Pawel
Merk, Alan
Rao, Prashant
Reddy, Bharat
Islam, Shahidul
Bartesaghi, Alberto
Perozo, Eduardo
Subramaniam, Sriram
TI Structures of the Mg2+ Channel Cora in the Open State by Cryo Electron
Microscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Matthies, Doreen; Borgnia, Mario; Merk, Alan; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NIH, Cell Biol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Dalmas, Olivier; Dominik, Pawel; Reddy, Bharat; Islam, Shahidul; Perozo, Eduardo] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1435-Pos
BP 291A
EP 291A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600413
ER
PT J
AU Zhou, WC
Nief, C
Faraldo-Gomez, JD
AF Zhou, Wenchang
Nief, Corrine
Faraldo-Gomez, Jose D.
TI Is the C-Subunit Ring of the F1Fo ATP Synthase the Elusive Mitochondrial
Permeability Transition Pore?
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zhou, Wenchang; Nief, Corrine; Faraldo-Gomez, Jose D.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1522-Pos
BP 310A
EP 310A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600500
ER
PT J
AU De la Fuente, S
Vail, C
Agra, EJ
Holmstrom, K
Sun, J
Mishra, J
Finkel, T
Murphy, E
Joseph, SK
Sheu, SS
Csordas, G
AF De la Fuente, Sergio
Vail, Caitlin
Agra, Elorm J.
Holmstrom, Kira
Sun, Junhui
Mishra, Jyotsna
Finkel, Toren
Murphy, Elisabeth
Joseph, Suresh K.
Sheu, Shey-Shing
Csordas, Gyorgy
TI Strategic Composition and Enrichment of the Mitochondrial Ca2+ Uniporter
at Mitochondria-SR Associations Creates Hotspots for Mitochondrial Ca2+
Uptake in the Cardiac Muscle
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [De la Fuente, Sergio; Vail, Caitlin; Agra, Elorm J.; Mishra, Jyotsna; Joseph, Suresh K.; Sheu, Shey-Shing; Csordas, Gyorgy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Holmstrom, Kira; Finkel, Toren] NHLBI, Mol Biol Lab, NIH, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA.
[Sun, Junhui; Murphy, Elisabeth] NHLBI, Lab Cardiac Physiol, NIH, Syst Biol Ctr, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1530-Pos
BP 312A
EP 312A
PG 1
WC Biophysics
SC Biophysics
GA DK7XZ
UT WOS:000375141600508
ER
PT J
AU Pourmousa, M
Venable, RM
Pastor, RW
AF Pourmousa, Mohsen
Venable, Richard M.
Pastor, Richard W.
TI Calcium Parameters in CHARMM Force Field Revisited
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Pourmousa, Mohsen; Venable, Richard M.; Pastor, Richard W.] NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1612-Pos
BP 327A
EP 328A
PG 7
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200079
ER
PT J
AU Zhao, HY
Patterson, G
Schuck, P
AF Zhao, Huaying
Patterson, George
Schuck, Peter
TI A New Dimension of Detection in Analytical Ultracentrifugation with
Fluorescence Detection using Photoswitchable FPs as Time Domain Probes
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zhao, Huaying; Patterson, George; Schuck, Peter] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1712-Plat
BP 347A
EP 347A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200182
ER
PT J
AU Tolun, G
Vijayasarathy, C
Huang, R
Zeng, Y
Li, Y
Sieving, PA
Heymann, JB
Steven, AC
AF Tolun, Gokhan
Vijayasarathy, Camasamudram
Huang, Rick
Zeng, Yong
Li, Yan
Sieving, Paul A.
Heymann, J. Bernard
Steven, Alasdair C.
TI Retinoschisin at 4 angstrom Resolution from cryo-EM: A Junctional Model
of Back-to-Back Octamers for Adhesion in the Retina
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Tolun, Gokhan; Huang, Rick; Heymann, J. Bernard; Steven, Alasdair C.] NIAMS, Struct Biol Res Lab, NIH, Bethesda, MD USA.
[Vijayasarathy, Camasamudram; Zeng, Yong] NIDCD, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD USA.
[Li, Yan] NINDS, Prot Peptide Sequencing Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1715-Plat
BP 348A
EP 348A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200185
ER
PT J
AU Iyer, VR
Monfredi, O
Maltsev, V
Lavorato, M
Stern, M
Franzini-Armstrong, C
AF Iyer, V. Ramesh
Monfredi, Oliver
Maltsev, Victor
Lavorato, Manuela
Stern, Michael
Franzini-Armstrong, Clara
TI SR Contribution to Calcium Cycling in Sino-Atrial Node Cells: As seen
from Nanoscale Electron Microscopy and Numerical Modeling
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Iyer, V. Ramesh] Childrens Hosp Philadelphia, Div Cardiol, Pediat, Philadelphia, PA 19104 USA.
[Iyer, V. Ramesh] Univ Penn, Dept Pediat Cardiol, Philadelphia, PA 19104 USA.
[Monfredi, Oliver; Maltsev, Victor; Stern, Michael] NIA, NIH, IRP, Baltimore, MD 21224 USA.
[Lavorato, Manuela; Franzini-Armstrong, Clara] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1774-Plat
BP 359A
EP 359A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200244
ER
PT J
AU Roche, J
AF Roche, Julien
TI Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape
of HIV-1 Protease
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Roche, Julien] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1817-Plat
BP 368A
EP 369A
PG 8
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200285
ER
PT J
AU Anfinrud, P
Schotte, F
Cho, HS
AF Anfinrud, Philip
Schotte, Friedrich
Cho, Hyun Sun
TI Watching Proteins Function with Time-Resolved X-ray Diffraction
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Anfinrud, Philip; Schotte, Friedrich; Cho, Hyun Sun] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1846-Wkshp
BP 375A
EP 375A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200314
ER
PT J
AU Lundquist, K
Mayclin, SJ
Buchanan, SK
Gumbart, JC
AF Lundquist, Karl
Mayclin, Stephen J.
Buchanan, Susan K.
Gumbart, James C.
TI Structure and Dynamics of the LPS Insertase LptD/E in a Realistic
Outer-Membrane Model
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Lundquist, Karl; Gumbart, James C.] Georgia Inst Technol, Sch Phys, Atlanta, GA 30332 USA.
[Mayclin, Stephen J.; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1893-Pos
BP 383A
EP 384A
PG 7
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200361
ER
PT J
AU Ma, J
Zhao, HY
Sandmaier, J
Liddle, JA
Schuck, P
AF Ma, Jia
Zhao, Huaying
Sandmaier, Julia
Liddle, J. Alexander
Schuck, Peter
TI Gravitational Sweep Sedimentation Velocity
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Ma, Jia; Zhao, Huaying; Schuck, Peter] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Sandmaier, Julia; Liddle, J. Alexander] NIST, Gaithersburg, MD 20899 USA.
RI Liddle, James/A-4867-2013
OI Liddle, James/0000-0002-2508-7910
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1897-Pos
BP 384A
EP 384A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200365
ER
PT J
AU Ma, J
Zhao, HY
Rainey, K
Patterson, G
Schuck, P
AF Ma, Jia
Zhao, Huaying
Rainey, Kristin
Patterson, George
Schuck, Peter
TI Study Molecular Interactions in whole Cell Extracts by
Fluorescence-Detected Analytical Ultracentrifugation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Ma, Jia; Zhao, Huaying; Rainey, Kristin; Patterson, George; Schuck, Peter] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1896-Pos
BP 384A
EP 384A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200364
ER
PT J
AU Plummer, AM
Peterson, JH
Bernstein, HD
Fleming, KG
AF Plummer, Ashlee M.
Peterson, Janine H.
Bernstein, Harris D.
Fleming, Karen G.
TI Selective Pressure for Rapid Membrane Integration Constrains the
Sequence of Bacterial Outer Membrane Proteins
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Plummer, Ashlee M.; Fleming, Karen G.] Johns Hopkins Univ, Biophys, Baltimore, MD USA.
[Peterson, Janine H.; Bernstein, Harris D.] NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1949-Pos
BP 394A
EP 394A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200417
ER
PT J
AU Hategan, AP
Karnaukhova, E
Dimitriadis, EK
Bianchet, MA
Nath, A
AF Hategan, Alina Popescu
Karnaukhova, Elena
Dimitriadis, Emilios K.
Bianchet, Mario A.
Nath, Avindra
TI Molecular Study of HIV-Tat Aggregation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Hategan, Alina Popescu; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Karnaukhova, Elena] US FDA, CBER, Silver Spring, MD USA.
[Dimitriadis, Emilios K.] NIBIB, Scanning Probe Microscopy Unit, NIH, Bethesda, MD USA.
[Bianchet, Mario A.] Johns Hopkins Sch Med, Dept Neurol & Struct Enzymol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1976-Pos
BP 400A
EP 400A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200444
ER
PT J
AU Sackett, DL
AF Sackett, Dan L.
TI Tubulin Tails are Intrinsically Disordered Polyanions that Regulate
Binding to other Proteins by Sequence as Well as Charge
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Sackett, Dan L.] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 1983-Pos
BP 401A
EP 401A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200451
ER
PT J
AU Kim, C
Lee, OC
Kim, JY
Sung, W
Lee, NK
AF Kim, CheolHee
Lee, O-Chul
Kim, Jae-Yeol
Sung, Wookyung
Lee, Nam Ki
TI Dynamic Release of Bending Stress in Short Double-Stranded DNA by Two
Types of Deformation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kim, CheolHee; Lee, O-Chul] Pohang Univ Sci & Technol, Phys, Pohang, South Korea.
[Kim, Jae-Yeol] NIH, Chem Phys, Bldg 10, Bethesda, MD 20892 USA.
[Sung, Wookyung] Pohang Univ Sci & Technol, IBS Ctr Self Assembly & Complex, Pohang, South Korea.
[Lee, Nam Ki] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Phys, Pohang, South Korea.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2003-Pos
BP 405A
EP 405A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200471
ER
PT J
AU Shaytan, AK
Armeev, GA
Goncearenco, A
Zhurkin, VB
Landsman, D
Panchenko, AR
AF Shaytan, Alexey K.
Armeev, Grigory A.
Goncearenco, Alexander
Zhurkin, Victor B.
Landsman, David
Panchenko, Anna R.
TI Nucleosome Dynamics at Microsecond Timescale: DNA-Protein Interactions,
Water-Mediated Interactions and Nucleosome Formation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Shaytan, Alexey K.; Goncearenco, Alexander; Landsman, David; Panchenko, Anna R.] NCBI, NIH, Bethesda, MD USA.
[Armeev, Grigory A.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow, Russia.
[Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
RI Goncearenco, Alexander/M-3946-2015; Shaytan, Alexey/D-7306-2012
OI Goncearenco, Alexander/0000-0002-9738-7146; Shaytan,
Alexey/0000-0003-0312-938X
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2004-Pos
BP 405A
EP 405A
PG 1
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200472
ER
PT J
AU Norouzi, D
Katebi, A
Nikitina, T
Zhurkin, V
AF Norouzi, Davood
Katebi, Ataur
Nikitina, Tatiana
Zhurkin, Victor
TI Topological Diversity of Chromatin Fibers: Interplay Between Nucleosome
Repeat Length, DNA Linking Number and the Level of Transcription
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Norouzi, Davood; Katebi, Ataur; Nikitina, Tatiana; Zhurkin, Victor] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2016-Pos
BP 407A
EP 408A
PG 7
WC Biophysics
SC Biophysics
GA DK7YE
UT WOS:000375142200484
ER
PT J
AU Batishchev, OV
Shilova, LA
Kachala, MV
Tashkin, VY
Sokolov, VS
Fedorova, NV
Baratova, LA
Knyazev, DG
Zimmerberg, J
Chizmadzhev, YA
AF Batishchev, Oleg V.
Shilova, Liudmila A.
Kachala, Michael V.
Tashkin, Vsevolod Yu
Sokolov, Valerij S.
Fedorova, Natalia V.
Baratova, Liudmila A.
Knyazev, Denis G.
Zimmerberg, Joshua
Chizmadzhev, Yury A.
TI Electrostatic Forces Govern Assembly and Disintegration of the Influenza
Virus Protein Scaffold to Provide Tension for Membrane Fusion
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Batishchev, Oleg V.; Shilova, Liudmila A.; Kachala, Michael V.; Tashkin, Vsevolod Yu; Sokolov, Valerij S.; Chizmadzhev, Yury A.] RAS IPCE RAS, AN Frumkin Inst Phys Chem & Electrochem, Moscow, Russia.
[Batishchev, Oleg V.; Shilova, Liudmila A.] Moscow Inst Phys & Technol, Dolgoprudnyi, Russia.
[Fedorova, Natalia V.; Baratova, Liudmila A.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow, Russia.
[Knyazev, Denis G.] Johannes Kepler Univ Linz, Inst Biophys, Linz, Austria.
[Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular & Membrane Biophys, Program Phys Biol, NIH, Bethesda, MD USA.
RI Batishchev, Oleg/L-1976-2013
OI Batishchev, Oleg/0000-0002-9581-2233
NR 0
TC 0
Z9 0
U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2086-Pos
BP 421A
EP 421A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700056
ER
PT J
AU Somasundaram, A
Taraska, JW
AF Somasundaram, Agila
Taraska, Justin W.
TI Investigating Protein Dynamics at Sites of Exocytosis in Live Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Somasundaram, Agila; Taraska, Justin W.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2127-Pos
BP 429A
EP 429A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700096
ER
PT J
AU Kim, MS
Maltseva, LA
Maltsev, AV
Parsons, SP
Monfredi, O
Tsutsui, K
Sirenko, S
Ziman, B
Lakatta, EG
Maltsev, VA
AF Kim, Mary S.
Maltseva, Larissa A.
Maltsev, Alexander V.
Parsons, Sean P.
Monfredi, Oliver
Tsutsui, Kenta
Sirenko, Syevda
Ziman, Bruce
Lakatta, Edward G.
Maltsev, Victor A.
TI Synchronization of Local Calcium Releases (LCRs) in Guinea Pig Single,
Isolated SA Node Cells Contributes to Generation of Rhythmic Action
Potential-Induced Ca2+ Transients
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kim, Mary S.; Maltseva, Larissa A.; Maltsev, Alexander V.; Monfredi, Oliver; Tsutsui, Kenta; Sirenko, Syevda; Ziman, Bruce; Lakatta, Edward G.; Maltsev, Victor A.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
[Parsons, Sean P.] McMaster Univ, Farncombe Inst, Hamilton, ON, Canada.
[Monfredi, Oliver] Univ Manchester, Dept Cardiac Electrophysiol, Manchester, Lancs, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2152-Pos
BP 434A
EP 435A
PG 6
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700121
ER
PT J
AU Maltsev, AV
Parsons, S
Lakatta, EG
Stern, MD
Maltsev, VA
Monfredi, OJ
AF Maltsev, Alexander V.
Parsons, Sean
Lakatta, Edward G.
Stern, Michael D.
Maltsev, Victor A.
Monfredi, Oliver J.
TI Novel Insights into Sinoatrial Nodal Cell Local Calcium Releases (LCRs)
from Automated Computer Analysis in Spontaneously Beating Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Maltsev, Alexander V.; Lakatta, Edward G.; Stern, Michael D.; Maltsev, Victor A.; Monfredi, Oliver J.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
[Parsons, Sean] McMaster Univ, Farncombe Inst, Hamilton, ON, Canada.
[Monfredi, Oliver J.] Univ Manchester, Dept Cardiac Electrophysiol, Manchester, Lancs, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2151-Pos
BP 434A
EP 434A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700120
ER
PT J
AU Garten, M
Kachman, MM
Glushakova, S
Zimmerberg, J
AF Garten, Matthias
Kachman, Marika M.
Glushakova, Svetlana
Zimmerberg, Joshua
TI Calcium-Activated Potassium Channels in the Malaria Parasite Erythrocyte
Cycle
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Garten, Matthias; Kachman, Marika M.; Glushakova, Svetlana; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2212-Pos
BP 448A
EP 448A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700181
ER
PT J
AU Gurnev, P
Hoogerheide, D
Rostovtseva, T
Bezrukov, S
AF Gurnev, Philip
Hoogerheide, David
Rostovtseva, Tatiana
Bezrukov, Sergey
TI Membrane-Binding Peptide Inhibits Blockage of Mitochondrial VDAC by
Alpha-Synuclein: In Search of A-Synuclein Toxicity Prevention
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Gurnev, Philip; Hoogerheide, David; Rostovtseva, Tatiana; Bezrukov, Sergey] NICHHD, Bethesda, MD 20892 USA.
[Gurnev, Philip] Univ Massachusetts, Phys, Amherst, MA 01003 USA.
[Hoogerheide, David] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2320-Pos
BP 471A
EP 471A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700289
ER
PT J
AU Elliott, AD
Diao, FC
Wu, YC
Shah, S
Shroff, H
White, B
AF Elliott, Amicia D.
Diao, Feici
Wu, Yicong
Shah, Sarav
Shroff, Hari
White, Benjamin
TI Imaging Paradigm for Studying Brain-Wide Activity Patterns in a
Drosophila Neural Circuit
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Elliott, Amicia D.] NIGMS, NIH, Bethesda, MD USA.
[Diao, Feici; Shah, Sarav; White, Benjamin] NIMH, NIH, Bethesda, MD 20892 USA.
[Wu, Yicong; Shroff, Hari] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2372-Pos
BP 481A
EP 481A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700341
ER
PT J
AU Hong, JS
Murugesan, S
Hammer, JA
AF Hong, Jinsung
Murugesan, Sricharan
Hammer, John A.
TI Myosin II Facilitates Ligand Discrimination during T Cell Activation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Hong, Jinsung; Murugesan, Sricharan; Hammer, John A.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2523-Plat
BP 511A
EP 511A
PG 1
WC Biophysics
SC Biophysics
GA DK7YI
UT WOS:000375142700492
ER
PT J
AU Ganji, M
Docter, M
Le Grice, SFJ
Abbondanzieri, E
AF Ganji, Mahipal
Docter, Margreet
Le Grice, Stuart F. J.
Abbondanzieri, Elio
TI Flipping by DNA Bound Proteins Occurs through Rapid Rebinding
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Ganji, Mahipal; Docter, Margreet; Abbondanzieri, Elio] Delft Univ Technol, Bionanosci, Delft, Netherlands.
[Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2538-Plat
BP 515A
EP 515A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000002
ER
PT J
AU Verma, SK
Leikina, E
Melikov, K
Chernomordik, LV
AF Verma, Santosh K.
Leikina, Evgenia
Melikov, Kamran
Chernomordik, Leonid V.
TI Cell Fusion Stage in Osteoclast Formation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Verma, Santosh K.; Leikina, Evgenia; Melikov, Kamran; Chernomordik, Leonid V.] NICHD, Sect Membrane Biol, Program Phys Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2564-Plat
BP 520A
EP 520A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000028
ER
PT J
AU Knittel, LL
Hassan, SA
Aronova, MA
Schuck, P
Leapman, RD
Sousa, AA
AF Knittel, Luiza L.
Hassan, Sergio A.
Aronova, Maria A.
Schuck, Peter
Leapman, Richard D.
Sousa, Alioscka A.
TI Biointeractions of Ultrasmall Gold Nanoparticles: Influence of
Nanoparticle Size and Surface Chemistry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Knittel, Luiza L.; Sousa, Alioscka A.] Univ Fed Sao Paulo, Biochem, Sao Paulo, Brazil.
[Hassan, Sergio A.] NIH, CIT, Bldg 10, Bethesda, MD 20892 USA.
[Aronova, Maria A.; Schuck, Peter; Leapman, Richard D.] NIBIB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2609-Plat
BP 530A
EP 530A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000073
ER
PT J
AU Liao, HS
Stark, C
Yao, JB
Garimella, H
Smith, PD
Meuse, CW
Jin, AJ
AF Liao, Hsien-Shun
Stark, Catherine
Yao, James B.
Garimella, Havisha
Smith, Paul D.
Meuse, Curtis W.
Jin, Albert J.
TI Assembly Mechanism and Nanomechanics of A beta in Alzheimer's Disease
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Liao, Hsien-Shun; Stark, Catherine; Yao, James B.; Garimella, Havisha; Smith, Paul D.; Jin, Albert J.] NIBIB, NIH, Bethesda, MD USA.
[Stark, Catherine] Yale Univ, New Haven, CT USA.
[Meuse, Curtis W.] NIST, Gaithersburg, MD 20899 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2634-Pos
BP 534A
EP 534A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000098
ER
PT J
AU Hoppe, TA
Tian, PF
Best, R
AF Hoppe, Travis A.
Tian, Pengfei
Best, Robert
TI Enhancing the Coevolutionary Signal
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Hoppe, Travis A.; Tian, Pengfei; Best, Robert] NIDDK, LCP, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2637-Pos
BP 535A
EP 535A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000100
ER
PT J
AU Kumari, V
Holland, RJ
Luthers, CE
Dyba, MA
Tarasov, SG
Saavedra, JE
Keefer, LK
Ji, XH
AF Kumari, Vandana
Holland, Ryan J.
Luthers, Christina E.
Dyba, Marzena A.
Tarasov, Sergey G.
Saavedra, Joseph E.
Keefer, Larry K.
Ji, Xinhua
TI Cancer Cell-Directed Drug Delivery and Chemopotentiating Effects by
GSTP1-Activated Nitric Oxide (NO)-Releasing Prodrug
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Kumari, Vandana; Holland, Ryan J.; Luthers, Christina E.; Dyba, Marzena A.; Tarasov, Sergey G.; Saavedra, Joseph E.; Keefer, Larry K.; Ji, Xinhua] NCI, MCL, Ctr Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2670-Pos
BP 541A
EP 541A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000134
ER
PT J
AU Gopich, IV
Szabo, A
AF Gopich, Irina V.
Szabo, Attila
TI Influence of Diffusion on the Kinetics of Multisite Phosphorylation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Gopich, Irina V.; Szabo, Attila] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2712-Pos
BP 550A
EP 550A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000176
ER
PT J
AU Toal, S
DeWitt, D
Trexler, A
Brown, M
Rhoades, E
AF Toal, Siobhan
DeWitt, David
Trexler, Adam
Brown, Mark
Rhoades, Elizabeth
TI Assessing N-Terminal Modifications on Alpha-Synuclein Structure and
Function
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Toal, Siobhan; Rhoades, Elizabeth] Univ Penn, Chem, Philadelphia, PA 19104 USA.
[DeWitt, David] Washington State Univ, Integrat Physiol and Neurosci, Pullman, WA 99164 USA.
[Trexler, Adam] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brown, Mark] Yale Univ, Mol Biophys & Biochem, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2724-Pos
BP 552A
EP 552A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000188
ER
PT J
AU Ma, BY
Wei, GH
Zhen, J
Nussinov, R
AF Ma, Buyong
Wei, Guanghong
Zhen, Jie
Nussinov, Ruth
TI Dancing with Strings: The Conformational Dynamics of VQIXXK Motifs
within Tau Protein in Monomer, Fibril and Hyper-Phosphorylated Filament
States
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
ID AGGREGATION
C1 [Ma, Buyong; Nussinov, Ruth] NCI Frederick, Leidos Biomed, NIH, Frederick, MD USA.
[Wei, Guanghong] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
[Zhen, Jie] Univ Akron, Dept Chem & Biomol Engn, Akron, OH 44325 USA.
NR 5
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2730-Pos
BP 553A
EP 554A
PG 6
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000194
ER
PT J
AU Chung, HS
Meng, F
Kim, JY
Louis, JM
AF Chung, Hoi Sung
Meng, Fanjie
Kim, Jae-Yeol
Louis, John M.
TI Multi-Color Single Molecule FRET Study of Intrinsically Disordered
Protein Binding
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Chung, Hoi Sung; Meng, Fanjie; Kim, Jae-Yeol; Louis, John M.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2740-Pos
BP 555A
EP 556A
PG 11
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000204
ER
PT J
AU Zerze, GLH
Best, RB
Mittal, J
AF Zerze, Gu L. H.
Best, Robert B.
Mittal, Jeetain
TI Dynamics of Contact Formation in Disordered Polypeptides
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Zerze, Gu L. H.; Mittal, Jeetain] Lehigh Univ, Chem & Biomol Engn, Bethlehem, PA 18015 USA.
[Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2748-Pos
BP 557A
EP 557A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000212
ER
PT J
AU Fisher, GL
Pastrana, CL
Taylor, JA
Butterer, A
Sobott, F
Moreno-Herrero, F
Dillingham, MS
AF Fisher, Gemma L.
Pastrana, Cesar L.
Taylor, James A.
Butterer, Annika
Sobott, Frank
Moreno-Herrero, Fernando
Dillingham, Mark S.
TI Recognition and Condensation of the Bacterial Centromere by ParB
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Fisher, Gemma L.; Dillingham, Mark S.] Univ Bristol, Sch Biochem, Bristol, Avon, England.
[Pastrana, Cesar L.] Ctr Nacl Biotecnol, Dept Macromol Struct, Madrid, Spain.
[Taylor, James A.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Butterer, Annika] Univ Antwerp, Dept Chem, B-2020 Antwerp, Belgium.
[Sobott, Frank] Univ Antwerp, B-2020 Antwerp, Belgium.
[Moreno-Herrero, Fernando] Ctr Nacl Biotecnol, Madrid, Spain.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2774-Pos
BP 562A
EP 562A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000238
ER
PT J
AU Campbell, SL
Thompson, PM
Tolbert, CE
Case, L
Ramachandran, S
Pershad, M
Dokholyan, N
Burridge, K
Waterman, C
AF Campbell, Sharon L.
Thompson, Peter M.
Tolbert, Caitlin E.
Case, Lindsay
Ramachandran, Srinivas
Pershad, Mihir
Dokholyan, Nikolay
Burridge, Keith
Waterman, Clare
TI Role of PIP2-Dependent Membrane Interactions in Vinculin Activation,
Motility and Force Transmission
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Campbell, Sharon L.; Thompson, Peter M.; Ramachandran, Srinivas; Pershad, Mihir; Dokholyan, Nikolay] Univ N Carolina, Biochem & Biophys, Chapel Hill, NC USA.
[Tolbert, Caitlin E.; Burridge, Keith] Univ N Carolina, Cell Biol, Chapel Hill, NC USA.
[Case, Lindsay; Waterman, Clare] NHLBI, Cell & Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2840-Pos
BP 575A
EP 575A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000304
ER
PT J
AU Hoogerheide, DP
Noskov, S
Rostovtseva, TK
Bezrukov, SM
Nanda, H
AF Hoogerheide, David P.
Noskov, Sergei
Rostovtseva, Tatiana K.
Bezrukov, Sergey M.
Nanda, Hirsh
TI Orientation of Dimeric Tubulin on Lipid Membranes Studied using Neutron
Reflectometry
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Hoogerheide, David P.; Nanda, Hirsh] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Noskov, Sergei] Univ Calgary, Dept Biochem, Calgary, AB, Canada.
[Rostovtseva, Tatiana K.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Nanda, Hirsh] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2841-Pos
BP 575A
EP 575A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000305
ER
PT J
AU Taylor, JA
Vecchiarelli, AG
Neuman, KC
Mizuuchi, K
AF Taylor, James A.
Vecchiarelli, Anthony G.
Neuman, Keir C.
Mizuuchi, Kiyoshi
TI Transportation of an Artifical Cargo by a Par-Min Hybrid System
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Taylor, James A.; Vecchiarelli, Anthony G.; Mizuuchi, Kiyoshi] NIDDK, LMB, Bethesda, MD 20892 USA.
[Neuman, Keir C.] NHLBI, LSMB, Bldg 10, Bethesda, MD 20892 USA.
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2844-Pos
BP 576A
EP 576A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000308
ER
PT J
AU Barros, M
Heinrich, F
Datta, SAK
Rein, A
Losche, M
AF Barros, Marilia
Heinrich, Frank
Datta, Siddartha A. K.
Rein, Alan
Losche, Mathias
TI Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer
Composition and Protein Lipidation
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Barros, Marilia; Heinrich, Frank; Losche, Mathias] Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA.
[Barros, Marilia; Heinrich, Frank; Losche, Mathias] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Datta, Siddartha A. K.; Rein, Alan] NIH, HIV Dynam & Replicat Program, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2849-Pos
BP 577A
EP 577A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000313
ER
PT J
AU Rotella, C
Kilpatrick, JI
Capponi, S
Holmgren, M
Bezanilla, F
Perozo, E
Jarvis, SP
AF Rotella, Chiara
Kilpatrick, Jason I.
Capponi, Simona
Holmgren, Miguel
Bezanilla, Francisco
Perozo, Eduardo
Jarvis, Suzanne P.
TI High Resolution Imaging Atomic Force Microscope Study of Interactions at
the Membrane-Fluid Interface
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Rotella, Chiara; Kilpatrick, Jason I.; Capponi, Simona; Jarvis, Suzanne P.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland.
[Rotella, Chiara; Capponi, Simona; Jarvis, Suzanne P.] Univ Coll Dublin, Sch Phys, Dublin 2, Ireland.
[Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bezanilla, Francisco; Perozo, Eduardo] Univ Chicago, Dept Biochem & Mol Biol, 920 E 58Th St, Chicago, IL 60637 USA.
NR 5
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2867-Pos
BP 580A
EP 581A
PG 7
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000331
ER
PT J
AU Trexler, AJ
Taraska, JW
AF Trexler, Adam J.
Taraska, Justin W.
TI Imaging the Rapid Recruitment of Dynamins at the Exocytic Fusion Pore
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Trexler, Adam J.; Taraska, Justin W.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2929-Pos
BP 593A
EP 593A
PG 1
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000393
ER
PT J
AU Wang, XX
Galletta, BJ
Cooper, JA
Carlsson, AE
AF Wang, Xinxin
Galletta, Brian J.
Cooper, John A.
Carlsson, Anders E.
TI Feedback Interactions between Actin and its Regulators in Endocytic
Protein Patches
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Wang, Xinxin; Carlsson, Anders E.] Washington Univ, Dept Phys, St Louis, MO 63130 USA.
[Galletta, Brian J.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Cooper, John A.] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2934-Pos
BP 594A
EP 595A
PG 6
WC Biophysics
SC Biophysics
GA DK7YL
UT WOS:000375143000398
ER
PT J
AU Landrau, AAD
Holmgren, M
AF Landrau, Angel A. de la Cruz
Holmgren, Miguel
TI Multiple Metal Bridges at the Intracellular Gate of a Voltage Activated
Potassium Channel Prevent Closing
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Landrau, Angel A. de la Cruz; Holmgren, Miguel] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Landrau, Angel A. de la Cruz] Univ Cent Caribe, Cell & Mol Biol, Bayamon, PR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 2970-Pos
BP 601A
EP 601A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200032
ER
PT J
AU Lee, K
Yang, SX
Liu, X
Korn, ED
Sarsoza, F
Bernstein, SI
Pollard, L
Lord, MJ
Trybus, KM
Craig, R
AF Lee, Kyounghwan
Yang, Shixin
Liu, Xiong
Korn, Edward D.
Sarsoza, Floyd
Bernstein, Sanford I.
Pollard, Luther
Lord, Matthew J.
Trybus, Kathleen M.
Craig, Roger
TI Myosin II Head Interaction in Primitive Species
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Lee, Kyounghwan; Yang, Shixin; Craig, Roger] UMass Med Sch, Worcester, MA USA.
[Liu, Xiong; Korn, Edward D.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Sarsoza, Floyd; Bernstein, Sanford I.] San Diego State Univ, San Diego, CA 92182 USA.
[Pollard, Luther; Lord, Matthew J.; Trybus, Kathleen M.] Univ Vermont, Burlington, VT USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3037-Pos
BP 615A
EP 615A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200099
ER
PT J
AU Khelashvili, G
Stanley, N
Sahai, M
Medina, J
LeVine, MV
Shi, L
De Fabritiis, G
Weinstein, H
AF Khelashvili, George
Stanley, Nathaniel
Sahai, Michelle
Medina, Jaime
LeVine, Michael V.
Shi, Lei
De Fabritiis, Gianni
Weinstein, Harel
TI Spontaneous Inward Opening of the Dopamine Transporter is Triggered by
PIP2-Regulated Dynamics of the N-Terminus
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Khelashvili, George; Medina, Jaime; LeVine, Michael V.; Weinstein, Harel] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
[Stanley, Nathaniel; De Fabritiis, Gianni] Univ Pompeu Fabra, Barcelona, Spain.
[Sahai, Michelle] Univ Roehampton, London, England.
[Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3089-Pos
BP 625A
EP 626A
PG 6
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200151
ER
PT J
AU Abramyan, AM
Taro, N
Stolzenberg, S
Shi, L
AF Abramyan, Ara M.
Taro, Nicholas
Stolzenberg, Sebastian
Shi, Lei
TI Towards Identifying Biologically Relevant Intermediate Conformational
States in Dopamine Transporter
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Abramyan, Ara M.; Taro, Nicholas; Shi, Lei] NIDA, Mol Targets & Medicat Discovery Branch, Intramural Res Program, NIH, Baltimore, MD USA.
[Stolzenberg, Sebastian] Free Univ Berlin, Dept Math & Comp Sci, Berlin, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3091-Pos
BP 626A
EP 626A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200153
ER
PT J
AU Fenollar-Ferrer, C
Anselmi, C
Jaque, AV
Karimi-Verzaneh, HA
Poblete-Vilches, H
Mulligan, C
Forster, IC
Mindell, JA
Faraldo-Gomez, JD
Forrest, LR
AF Fenollar-Ferrer, Cristina
Anselmi, Claudio
Jaque, Ariela Vergara
Karimi-Verzaneh, Hossein Ali
Poblete-Vilches, Horacio
Mulligan, Christopher
Forster, Ian C.
Mindell, Joseph A.
Faraldo-Gomez, Jose D.
Forrest, Lucy R.
TI Computational Studies of Elevator-Like Movements in Secondary Transport
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Fenollar-Ferrer, Cristina; Mulligan, Christopher; Mindell, Joseph A.; Forrest, Lucy R.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Anselmi, Claudio; Faraldo-Gomez, Jose D.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Jaque, Ariela Vergara] Kansas State Univ, Kansas City, KS USA.
[Karimi-Verzaneh, Hossein Ali] Continental, Hannover, Germany.
[Poblete-Vilches, Horacio] Kansas State Univ, Inst Computat Comparat Med, Kansas City, KS USA.
[Forster, Ian C.] Univ Zurich, Inst Physiol, Zurich, Switzerland.
[Forster, Ian C.] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3094-Pos
BP 626A
EP 627A
PG 7
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200156
ER
PT J
AU Marinelli, F
Faraldo-Gomez, J
AF Marinelli, Fabrizio
Faraldo-Gomez, Jose
TI Keeping Secondary Transporters under Control: Lessons from a Na+/Ca2+
Exchanger
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Marinelli, Fabrizio; Faraldo-Gomez, Jose] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3092-Pos
BP 626A
EP 626A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200154
ER
PT J
AU Cossio, P
Hummer, G
Szabo, A
AF Cossio, Pilar
Hummer, Gerhard
Szabo, Attila
TI On Artifacts in Single-Molecule Force Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Cossio, Pilar; Hummer, Gerhard] Max Planck Inst Biophys, Theoret Biophys, Frankfurt, Germany.
[Szabo, Attila] NIDDK, NIH, Bethesda, MD 20892 USA.
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3126-Pos
BP 634A
EP 634A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200188
ER
PT J
AU Truex, K
Chung, HS
Louis, JM
Eaton, WA
AF Truex, Katherine
Chung, Hoi Sung
Louis, John M.
Eaton, William A.
TI Single Molecule Fluorescence Studies of Transition Paths in DNA Hairpin
Folding
SO BIOPHYSICAL JOURNAL
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the Biophysical-Society
CY FEB 27-MAR 02, 2016
CL Los Angeles, CA
SP Biophys Soc
C1 [Truex, Katherine; Chung, Hoi Sung; Louis, John M.; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 16
PY 2016
VL 110
IS 3
SU 1
MA 3131-Pos
BP 635A
EP 635A
PG 1
WC Biophysics
SC Biophysics
GA DK7YN
UT WOS:000375143200193
ER
PT J
AU Harly, C
Bhandoola, A
AF Harly, Christelle
Bhandoola, Avinash
TI A doppelganger of T cell development
SO CELL CYCLE
LA English
DT Editorial Material
DE T-cell; development; innate lymphocyte
ID TCF-1; FATE
C1 [Harly, Christelle] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bhandoola, A (reprint author), NCI, Ctr Canc Res, Bldg 37,Room 1108, Bethesda, MD 20892 USA.
EM avinash.bhandoola@nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD FEB 16
PY 2016
VL 15
IS 4
BP 479
EP 480
DI 10.1080/15384101.2015.1125244
PG 2
WC Cell Biology
SC Cell Biology
GA DG5ID
UT WOS:000372110000001
PM 26726938
ER
PT J
AU Sroubek, J
Probst, V
Mazzanti, A
Delise, P
Hevia, JC
Ohkubo, K
Zorzi, A
Champagne, J
Kostopoulou, A
Yin, XY
Napolitano, C
Milan, DJ
Wilde, A
Sacher, F
Borggrefe, M
Ellinor, PT
Theodorakis, G
Nault, I
Corrado, D
Watanabe, I
Antzelevitch, C
Allocca, G
Priori, SG
Lubitz, SA
AF Sroubek, Jakub
Probst, Vincent
Mazzanti, Andrea
Delise, Pietro
Castro Hevia, Jesus
Ohkubo, Kimie
Zorzi, Alessandro
Champagne, Jean
Kostopoulou, Anna
Yin, Xiaoyan
Napolitano, Carlo
Milan, David J.
Wilde, Arthur
Sacher, Frederic
Borggrefe, Martin
Ellinor, Patrick T.
Theodorakis, George
Nault, Isabelle
Corrado, Domenico
Watanabe, Ichiro
Antzelevitch, Charles
Allocca, Giuseppe
Priori, Silvia G.
Lubitz, Steven A.
TI Programmed Ventricular Stimulation for Risk Stratification in the
Brugada Syndrome A Pooled Analysis
SO CIRCULATION
LA English
DT Article
DE death, sudden, cardiac; risk assessment; electrophysiology; arrhythmias,
cardiac; Brugada syndrome
ID WORLDWIDE PUBLISHED DATA; SUDDEN CARDIAC DEATH; ELECTRICAL-STIMULATION;
TYPE-1 ELECTROCARDIOGRAM; CLINICAL CHARACTERISTICS; PROGNOSTIC VALUE;
NATURAL-HISTORY; FIBRILLATION; METAANALYSIS; INDIVIDUALS
AB Background-
The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain.
Methods and Results-
We performed a systematic review and pooled analysis of prospective, observational studies of patients with Brugada syndrome without a history of sudden cardiac arrest who underwent programmed ventricular stimulation. We estimated incidence rates and relative hazards of cardiac arrest or implantable cardioverter-defibrillator shock. We analyzed individual-level data from 8 studies comprising 1312 patients who experienced 65 cardiac events (median follow-up, 38.3 months). A total of 527 patients were induced into arrhythmias with up to triple extrastimuli. Induction was associated with cardiac events during follow-up (hazard ratio, 2.66; 95% confidence interval [CI], 1.44-4.92, P < 0.001), with the greatest risk observed among those induced with single or double extrastimuli. Annual event rates varied substantially by syncope history, presence of spontaneous type 1 ECG pattern, and arrhythmia induction. The lowest risk occurred in individuals without syncope and with drug-induced type 1 patterns (0.23%, 95% CI, 0.05-0.68 for no induced arrhythmia with up to double extrastimuli; 0.45%, 95% CI, 0.01-2.49 for induced arrhythmia), and the highest risk occurred in individuals with syncope and spontaneous type 1 patterns (2.55%, 95% CI, 1.58-3.89 for no induced arrhythmia; 5.60%, 95% CI, 2.98-9.58 for induced arrhythmia).
Conclusions-
In patients with Brugada syndrome, arrhythmias induced with programmed ventricular stimulation are associated with future ventricular arrhythmia risk. Induction with fewer extrastimuli is associated with higher risk. However, clinical risk factors are important determinants of arrhythmia risk, and lack of induction does not necessarily portend low ventricular arrhythmia risk, particularly in patients with high-risk clinical features.
C1 [Sroubek, Jakub] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
[Probst, Vincent] CHU Nantes, Hop Nord, Serv Cardiol, F-44035 Nantes 01, France.
[Mazzanti, Andrea; Napolitano, Carlo; Priori, Silvia G.] IRCCS Fdn Salvatore Maugeri, Mol Cardiol, Pavia, Italy.
[Priori, Silvia G.] Mol Univ Pavia, Dipartimento Med, Pavia, Italy.
[Delise, Pietro] Casa Cura Pederzoli, Div Cardiol, Verona, Italy.
[Castro Hevia, Jesus] Cardiovasc Surg & Cardiol Inst, Arrhythmia Unit, Havana, Cuba.
[Ohkubo, Kimie; Watanabe, Ichiro] Nihon Univ, Sch Med, Dept Med, Div Cardiol, Tokyo, Japan.
[Zorzi, Alessandro; Corrado, Domenico] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy.
[Champagne, Jean; Nault, Isabelle] Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
[Kostopoulou, Anna; Theodorakis, George] Onassis Cardiac Surg Ctr, Dept Electrophysiol & Pacing, Athens, Greece.
[Yin, Xiaoyan] Boston Univ, Framingham, MA USA.
[Yin, Xiaoyan] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Milan, David J.; Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
[Milan, David J.; Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
[Wilde, Arthur] Univ Amsterdam, Acad Med Ctr, Dept Clin & Expt Cardiol, Heart Ctr AMC, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Wilde, Arthur] Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
[Sacher, Frederic] Bordeaux Univ Hosp, LIRYC Inst, INSERM 1045, Bordeaux, France.
[Borggrefe, Martin] Univ Med Ctr Mannheim, Dept Med Cardiol 1, Mannheim, Germany.
[Borggrefe, Martin] DZHK German Ctr Cardiovasc Res, Partner Site Heidelberg Mannheim, Mannheim, Germany.
[Ellinor, Patrick T.; Lubitz, Steven A.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Allocca, Giuseppe] Gen Hosp Conegliano, Dept Cardiol, Treviso, Italy.
[Antzelevitch, Charles] Lankenau Inst Med Res, Wynnewood, PA USA.
RP Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St,GRB 109, Boston, MA 02114 USA.; Lubitz, SA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA.
EM slubitz@mgh.harvard.edu
RI Napolitano, Carlo/K-4760-2016
OI Napolitano, Carlo/0000-0002-7643-4628
FU Doris Duke Charitable Foundation Clinical Scientist Development Award
[2014105]; National Institutes of Health/National Heart, Lung, and Blood
Institute [K23HL114724, HL47678]; CARIPLO [2013-1019]
FX Dr Lubitz is supported by Doris Duke Charitable Foundation Clinical
Scientist Development Award 2014105 and National Institutes of
Health/National Heart, Lung, and Blood Institute K23HL114724 Career
Development Award. Dr Antzelevitch was supported by National Institutes
of Health/National Heart, Lung, and Blood Institute HL47678. Dr Priori
and Napolitano were supported by CARIPLO 2013-1019. None of the funding
sponsors had any role in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; or
preparation, review, or approval of the manuscript.
NR 39
TC 8
Z9 8
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD FEB 16
PY 2016
VL 133
IS 7
BP 622
EP 630
DI 10.1161/CIRCULATIONAHA.115.017885
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DF0DV
UT WOS:000371010100002
PM 26797467
ER
PT J
AU Howard, G
Kissela, BM
Kleindorfer, DO
McClure, LA
Soliman, EZ
Judd, SE
Rhodes, JD
Cushman, M
Moy, CS
Sands, KA
Howard, VJ
AF Howard, George
Kissela, Brett M.
Kleindorfer, Dawn O.
McClure, Leslie A.
Soliman, Elsayed Z.
Judd, Suzanne E.
Rhodes, J. David
Cushman, Mary
Moy, Claudia S.
Sands, Kara A.
Howard, Virginia J.
TI Differences in the role of black race and stroke risk factors for first
vs recurrent stroke
SO NEUROLOGY
LA English
DT Article
ID TRANSIENT ISCHEMIC ATTACK; BLOOD-PRESSURE REDUCTION; SELF-REPORTED
STROKE; SECONDARY PREVENTION; RACIAL-DIFFERENCES; POPULATION; HEALTH;
INFARCTION; VALIDITY; REASONS
AB Objectives:
To assess whether black race and other cerebrovascular risk factors have a differential effect on first vs recurrent stroke events.
Methods:
Estimate the differences in the magnitude of the association of demographic (age, back race, sex) or stroke risk factors (hypertension, diabetes, cigarette smoking, atrial fibrillation, left ventricular hypertrophy, or heart disease) for first vs recurrent stroke from a longitudinal cohort study of 29,682 black or white participants aged 45 years and older.
Results:
Over an average 6.8 years follow-up, 301 of 2,993 participants with a previous stroke at baseline had a recurrent stroke, while 818 of 26,689 participants who were stroke-free at baseline had a first stroke. Among those stroke-free at baseline, there was an age-by-race interaction (p = 0.0002), with a first stroke risk 2.70 (95% confidence interval: 1.86-3.91) times greater for black than white participants at age 45, but no racial disparity at age 85 (hazard ratio = 0.91; 95% confidence interval: 0.70-1.18). In contrast, there was no evidence of a higher risk of recurrent stroke at any age for black participants (p > 0.05). The association of traditional stroke risk factors was generally similar for first and recurrent stroke.
Conclusion:
The association of age and black race differs substantially on first vs recurrent stroke risk, with risk factors playing a similar role.
C1 [Howard, George; McClure, Leslie A.; Judd, Suzanne E.; Rhodes, J. David] UAB, Sch Publ Hlth, Dept Biostat, Birmingham, AL USA.
[Howard, Virginia J.] UAB, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA.
[Kissela, Brett M.; Kleindorfer, Dawn O.] Univ Cincinnati, Sch Med, Dept Neurol, Cincinnati, OH 45221 USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol, Winston Salem, NC USA.
[Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Moy, Claudia S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Sands, Kara A.] UAB, Sch Med, Dept Neurol, Birmingham, AL USA.
RP Howard, G (reprint author), UAB, Sch Publ Hlth, Dept Biostat, Birmingham, AL USA.
EM ghoward@uab.edu
OI Kissela, Brett/0000-0002-9773-4013
FU National Institute of Neurological Disorders and Stroke, NIH
[U01-NS041588]
FX This research project was supported by cooperative agreement
U01-NS041588 from the National Institute of Neurological Disorders and
Stroke, NIH.
NR 23
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 16
PY 2016
VL 86
IS 7
BP 637
EP 642
DI 10.1212/WNL.0000000000002376
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA DE0FF
UT WOS:000370299600008
PM 26791153
ER
PT J
AU Earp, M
Winham, SJ
Larson, N
Permuth, JB
Sicotte, H
Chien, J
Anton-Culver, H
Bandera, EV
Berchuck, A
Cook, LS
Cramer, D
Doherty, JA
Goodman, MT
Levine, DA
Monteiro, ANA
Ness, RB
Pearce, CL
Rossing, MA
Tworoger, SS
Wentzensen, N
Bisogna, M
Brinton, L
Brooks-Wilson, A
Carney, ME
Cunningham, JM
Edwards, RP
Fogarty, ZC
Iversen, ES
Kraft, P
Larson, MC
Le, ND
Lin, HY
Lissowska, J
Modugno, F
Moysich, KB
Olson, SH
Pike, MC
Poole, EM
Rider, DN
Terry, KL
Thompson, PJ
van den Berg, D
Vierkant, RA
Vitonis, AF
Wilkens, LR
Wu, AH
Yang, HP
Ziogas, A
Phelan, CM
Schildkraut, JM
Chen, YA
Sellers, TA
Fridley, BL
Goode, EL
AF Earp, Madalene
Winham, Stacey J.
Larson, Nicholas
Permuth, Jennifer B.
Sicotte, Hugues
Chien, Jeremy
Anton-Culver, Hoda
Bandera, Elisa V.
Berchuck, Andrew
Cook, Linda S.
Cramer, Daniel
Doherty, Jennifer A.
Goodman, Marc T.
Levine, Douglas A.
Monteiro, Alvaro N. A.
Ness, Roberta B.
Pearce, Celeste L.
Rossing, Mary Anne
Tworoger, Shelley S.
Wentzensen, Nicolas
Bisogna, Maria
Brinton, Louise
Brooks-Wilson, Angela
Carney, Michael E.
Cunningham, Julie M.
Edwards, Robert P.
Fogarty, Zachary C.
Iversen, Edwin S.
Kraft, Peter
Larson, Melissa C.
Le, Nhu D.
Lin, Hui-Yi
Lissowska, Jolanta
Modugno, Francesmary
Moysich, Kirsten B.
Olson, Sara H.
Pike, Malcolm C.
Poole, Elizabeth M.
Rider, David N.
Terry, Kathryn L.
Thompson, Pamela J.
van den Berg, David
Vierkant, Robert A.
Vitonis, Allison F.
Wilkens, Lynne R.
Wu, Anna H.
Yang, Hannah P.
Ziogas, Argyrios
Phelan, Catherine M.
Schildkraut, Joellen M.
Chen, Yian Ann
Sellers, Thomas A.
Fridley, Brooke L.
Goode, Ellen L.
TI A targeted genetic association study of epithelial ovarian cancer
susceptibility
SO ONCOTARGET
LA English
DT Article
DE ovarian cancer; high-grade serous carcinoma; genetic association;
susceptibility loci; NF-kappa B
ID GENOME-WIDE ASSOCIATION; HEREDITARY; CARCINOMA; LOCUS; MUTATIONS;
BIOMARKER; VARIANTS; SURVIVAL; 17Q21.31; BREAST
AB Background: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci.
Results: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p < 5x10(-8)), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10-6).
Methods: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure.
Conclusion: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance.
C1 [Earp, Madalene; Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Winham, Stacey J.; Larson, Nicholas; Sicotte, Hugues; Fogarty, Zachary C.; Larson, Melissa C.; Rider, David N.; Vierkant, Robert A.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
[Permuth, Jennifer B.; Monteiro, Alvaro N. A.; Lin, Hui-Yi; Phelan, Catherine M.; Chen, Yian Ann; Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Chien, Jeremy] Univ Kansas, Ctr Canc, Dept Canc Biol, Kansas City, KS USA.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
[Cook, Linda S.] Univ New Mexico, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Cramer, Daniel; Terry, Kathryn L.; Vitonis, Allison F.] Harvard Univ, Sch Med, Boston, MA USA.
[Cramer, Daniel; Tworoger, Shelley S.; Kraft, Peter; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Lebanon, NH USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Levine, Douglas A.; Bisogna, Maria] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Ness, Roberta B.] Univ Texas Sch Publ Hlth, Houston, TX USA.
[Pearce, Celeste L.; Pike, Malcolm C.; van den Berg, David; Wu, Anna H.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Rossing, Mary Anne] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Tworoger, Shelley S.; Poole, Elizabeth M.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA.
[Tworoger, Shelley S.; Poole, Elizabeth M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Wentzensen, Nicolas; Brinton, Louise; Yang, Hannah P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Brooks-Wilson, Angela] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Carney, Michael E.] Univ Hawaii, Ctr Canc, Clin & Translat Res Program, Honolulu, HI 96822 USA.
[Cunningham, Julie M.] Mayo Clin, Div Expt Pathol, Dept Lab Med & Pathol, Rochester, MN USA.
[Edwards, Robert P.; Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Div Gynecol Oncol, Pittsburgh, PA USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Modugno, Francesmary] Magee Womens Res Inst, Canc Res Program, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Moysich, Kirsten B.; Pike, Malcolm C.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Ctr Canc Genet Res & Prevent, Dept Epidemiol, Irvine, CA 92717 USA.
[Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA.
[Fridley, Brooke L.] Univ Kansas, Ctr Canc, Kansas IDeA Network Biomed Res Excellence Bioinfo, Kansas City, KS USA.
RP Goode, EL (reprint author), Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
EM egoode@mayo.edu
RI Brooks-Wilson, Angela/E-9399-2012;
OI Brooks-Wilson, Angela/0000-0003-1009-6408; Chien,
Jeremy/0000-0003-4744-8374
FU National Cancer Institute's Cancer Post-GWAS Initiative; Genetic
Associations and Mechanisms in Oncology (GAMEON) [U19-CA148112];
NIH/National Center for Research Resources/General Clinical Research
Center grant [M01-RR000056]; Canadian Institutes of Health Research
grant [MOP-86727]; Canadian Institutes of Health Research New
Investigator award [MSH-87734]; National Cancer Institute; US Public
Health Service [PSA-042205]; Lon V Smith Foundation grant [LVS-39420];
California Cancer Research Program [00-01389V-20170, 2II0200]; National
Institutes of Health [R01-CA-149429]; NCI CCSG award [P30-CA008748];
[R01-CA058860]; [R01-CA092044]; [P01-CA17054]; [P30-CA14089];
[R01-CA61132]; [N01-PC67010]; [R03-CA113148]; [R03-CA115195];
[N01-CN025403]
FX Funding support for the Follow-up of Ovarian Cancer Genetic Association
and Interaction Studies (FOCI) was provided through the National Cancer
Institute's Cancer Post-GWAS Initiative, Genetic Associations and
Mechanisms in Oncology (GAMEON) (U19-CA148112). In addition, we
acknowledge the following: DOV: National Institutes of Health
R01-CA112523 and R01-CA87538; HAW: National Institutes of Health
(R01-CA58598, N01-CN-55424 and N01-PC-67001); HOP: DOD DAMD17-02-1-0669
and NCI K07-CA080668, R01-CA95023, P50-CA159981; NIH/National Center for
Research Resources/General Clinical Research Center grant M01-RR000056;
MAY: National Institutes of Health (R01-CA122443, P30-CA15083-41,
P50-CA136393); NCO: National Institutes of Health (R01-CA76016) and the
Department of Defense (DAMD17-02-1-0666); NEC: National Institutes of
Health R01-CA54419 and P50-CA105009 and Department of Defense
W81XWH-10-1-02802; NHS: NIH (P01-CA87696 and R01-CA49449): NJO: National
Cancer Institute (K07-CA095666, R01-CA83918, K22-CA138563, and
P30-CA072720) and the Cancer Institute of New Jersey; NCI CCSG award
(P30-CA008748); OVA: This work was supported by Canadian Institutes of
Health Research grant (MOP-86727); LEK is supported by a Canadian
Institutes of Health Research New Investigator award (MSH-87734); POL:
Intramural Research Program of the National Cancer Institute; UCI:
R01-CA058860, R01-CA092044, US Public Health Service PSA-042205, and the
Lon V Smith Foundation grant LVS-39420; USC: P01-CA17054, P30-CA14089,
R01-CA61132, N01-PC67010, R03-CA113148, R03-CA115195, N01-CN025403, and
California Cancer Research Program (00-01389V-20170, 2II0200). CMP is
supported by National Institutes of Health R01-CA-149429.
NR 26
TC 2
Z9 2
U1 1
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 16
PY 2016
VL 7
IS 7
BP 7381
EP 7389
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DE0PD
UT WOS:000370325900004
PM 26848776
ER
PT J
AU Gameiro, SR
Malamas, AS
Tsang, KY
Ferrone, S
Hodge, JW
AF Gameiro, Sofia R.
Malamas, Anthony S.
Tsang, Kwong Y.
Ferrone, Soldano
Hodge, James W.
TI Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype
to enhance T-cell mediated lysis of prostate and breast carcinoma cells
SO ONCOTARGET
LA English
DT Article
DE vorinostat; entinostat; immunogenic modulation; antigen-processing
machinery; histone deacetylases
ID INDUCED IMMUNOGENIC MODULATION; SOLID TUMORS; HDAC INHIBITORS; CANCER
CELLS; ENDOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODIES; EPIGENETIC THERAPY;
AGONIST EPITOPE; DOWN-REGULATION; FLOW-CYTOMETRY
AB The clinical promise of cancer immunotherapy relies on the premise that the immune system can recognize and eliminate tumor cells identified as nonself. However, tumors can evade host immune surveillance through multiple mechanisms, including epigenetic silencing of genes involved in antigen processing and immune recognition. Hence, there is an unmet clinical need to develop effective therapeutic strategies that can restore tumor immune recognition when combined with immunotherapy, such as immune checkpoint blockade and therapeutic cancer vaccines. We sought to examine the potential of clinically relevant exposure of prostate and breast human carcinoma cells to histone deacetylase (HDAC) inhibitors to reverse tumor immune escape to T-cell mediated lysis. Here we demonstrate that prostate (LNCAP) and breast (MDA-MB-231) carcinoma cells are more sensitive to T-cell mediated lysis in vitro after clinically relevant exposure to epigenetic therapy with either the pan-HDAC inhibitor vorinostat or the class I HDAC inhibitor entinostat. This pattern of immunogenic modulation was observed against a broad range of tumor-associated antigens, such as CEA, MUC1, PSA, and brachyury, and associated with augmented expression of multiple proteins involved in antigen processing and tumor immune recognition. Genetic and pharmacological inhibition studies identified HDAC1 as a key determinant in the reversal of carcinoma immune escape. Further, our findings suggest that the observed reversal of tumor immune evasion is driven by a response to cellular stress through activation of the unfolded protein response. This offers the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines.
C1 [Gameiro, Sofia R.; Malamas, Anthony S.; Tsang, Kwong Y.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 50
TC 4
Z9 5
U1 1
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 16
PY 2016
VL 7
IS 7
BP 7390
EP 7402
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DE0PD
UT WOS:000370325900005
PM 26862729
ER
PT J
AU Hsu, CW
Huang, RL
Khuc, T
Shou, D
Bullock, J
Grooby, S
Griffin, S
Zou, CZ
Little, A
Astley, H
Xia, MH
AF Hsu, Chia-Wen
Huang, Ruili
Khuc, Thai
Shou, David
Bullock, Joshua
Grooby, Suzanne
Griffin, Sue
Zou, Chaozhong
Little, Annette
Astley, Holly
Xia, Menghang
TI Identification of approved and investigational drugs that inhibit
hypoxia-inducible factor-1 signaling
SO ONCOTARGET
LA English
DT Article
DE hypoxia inducible factor; cancer; genome editing; drug; high-throughput
screening
ID MYCOPHENOLATE-MOFETIL; TRANSCRIPTIONAL ACTIVITY; TUMOR ANGIOGENESIS;
PROSTATE-CANCER; COLON-CANCER; HIF-1-ALPHA; EXPRESSION; PATHWAY; HIF-1;
GROWTH
AB One of the requirements for tumor development is blood supply, most often driven by hypoxia-induced angiogenesis. Hypoxia induces the stabilization of hypoxiainducible factor-1 alpha (HIF-1 alpha), which induces expression of an angiogenic factor, vascular endothelial growth factor (VEGF). The purpose of this study is to validate a new screening platform combined with orthogonal assays to rapidly identify HIF-1 inhibitors and to evaluate the effectiveness of approved drugs on modulating HIF-1 signaling.
We generated an endogenous HIF-1 alpha-NanoLuc luciferase reporter allele in the human HCT116 colon cancer cell line using genome editing and screened a panel of small interfering RNAs (siRNAs) to 960 druggable targets and approximately 2,500 drugs on a quantitative high-throughput screening (qHTS) platform. Selected compounds were further investigated with secondary assays to confirm their anti-HIF activity and to study their mode of action. The qHTS assay identified over 300 drugs that inhibited HIF-1 alpha-NanoLuc expression. The siRNA screening results supported the effectiveness of several target-specific inhibitors. Moreover, the identified HIF-1 inhibitors, such as mycophenolate mofetil, niclosamide, and trametinib, were able to suppress cancer cell proliferation and angiogenesis. Our study indicates that blocking the mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways effectively inhibits hypoxia-induced HIF-1 alpha accumulation and HIF-1 alpha transactivation and that proteasome inhibitors induce accumulation and decrease transcriptional activity of HIF-1 alpha. These findings underline the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies.
C1 [Hsu, Chia-Wen; Huang, Ruili; Khuc, Thai; Shou, David; Xia, Menghang] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Bullock, Joshua; Grooby, Suzanne; Griffin, Sue; Little, Annette; Astley, Holly] Horizon Discovery Ltd, Cambridge, England.
[Zou, Chaozhong] Amer Type Culture Collect, Gaithersburg, MD USA.
RP Xia, MH (reprint author), NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov
FU Intramural Research Program of the National Center for Advancing
Translational Sciences, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Center for Advancing Translational Sciences, National
Institutes of Health.
NR 39
TC 1
Z9 1
U1 1
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 16
PY 2016
VL 7
IS 7
BP 8172
EP 8183
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DE0PD
UT WOS:000370325900063
PM 26882567
ER
PT J
AU Chumbley, CW
Reyzer, ML
Allen, JL
Marriner, GA
Via, LE
Barry, CE
Caprioli, RM
AF Chumbley, Chad W.
Reyzer, Michelle L.
Allen, Jamie L.
Marriner, Gwendolyn A.
Via, Laura E.
Barry, Clifton E., III
Caprioli, Richard M.
TI Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of
Rifampicin in Liver Tissues
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID ASSISTED-LASER-DESORPTION/IONIZATION; RAT-BRAIN TISSUE; INTERNAL
STANDARD; PHARMACEUTICAL COMPOUNDS; DRUG DISTRIBUTION; QUANTIFICATION;
MS; NORMALIZATION; SECTIONS; LOCALIZATION
AB Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) elucidates molecular distributions in thin tissue sections. Absolute pixel-to-pixel quantitation has remained a challenge, primarily lacking validation of the appropriate analytical methods. In the present work, isotopically labeled internal standards are applied to tissue sections to maximize quantitative reproducibility and yield accurate quantitative results. We have developed a tissue model for rifampicin (RIF), an antibiotic used to treat tuberculosis, and have tested different methods of applying an isotopically labeled internal standard for MALDI IMS analysis. The application of the standard and subsequently the matrix onto tissue sections resulted in quantitation that was not statistically significantly different from results obtained using HPLC-MS/MS of tissue extracts. Quantitative IMS experiments were performed on liver tissue from an animal dosed in vivo. Each microspot in the quantitative images measures the local concentration of RIF in the thin tissue section. Lower concentrations were detected from the blood vessels and around the portal tracts. The quantitative values obtained from these measurements were comparable (>90% similarity) to HPLC-MS/MS results obtained from extracts of the same tissue.
C1 [Chumbley, Chad W.; Caprioli, Richard M.] Vanderbilt Univ, Dept Chem, Box 1583, Nashville, TN 37235 USA.
[Reyzer, Michelle L.; Allen, Jamie L.; Caprioli, Richard M.] Vanderbilt Univ, Mass Spectrometry Res Ctr, Nashville, TN 37240 USA.
[Marriner, Gwendolyn A.; Via, Laura E.; Barry, Clifton E., III] Natl Inst Allergy & Infect Dis, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Dept Clin Lab Sci, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Caprioli, Richard M.] Vanderbilt Univ, Dept Pharmacol, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.
[Caprioli, Richard M.] Vanderbilt Univ, Dept Biochem, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.
[Caprioli, Richard M.] Vanderbilt Univ, Dept Med, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.
RP Caprioli, RM (reprint author), Vanderbilt Univ, Dept Chem, Box 1583, Nashville, TN 37235 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Mass Spectrometry Res Ctr, Nashville, TN 37240 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Dept Pharmacol, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Dept Biochem, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.; Caprioli, RM (reprint author), Vanderbilt Univ, Dept Med, 465 21st Ave South,Med Res Bldg 3, Nashville, TN 37240 USA.
EM r.caprioli@vanderbilt.edu
FU NIH/NIGMS [R01-GM058008, P41-GM103391]; NIAID, NIH; Bill and Melinda
Gates Foundation Accelerator Program [705309]; Aegis Sciences
Corporation
FX The authors would like to thank Tina Tsui for development of the
quantitative imaging software in MATLAB, Dr. Mary Kay Washington for
assisting with the H&E stains, Brian C. Hachey and Philip J. Kingsley
for their assistance with the HPLC-MS/MS experiments, and Danielle
Weiner and Dan Schimel of NIAID, NIH, for assistance with the rabbit
experiments. This work was supported in part by NIH/NIGMS grants
R01-GM058008 and P41-GM103391 to RMC, by the Intramural Research Program
of NIAID, NIH (CEB), and the Bill and Melinda Gates Foundation
Accelerator Program (#705309 to J. Flynn, University of Pittsburgh). CWC
would also like to acknowledge a fellowship from Aegis Sciences
Corporation.
NR 45
TC 18
Z9 18
U1 20
U2 72
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 FEB 16
PY 2016
VL 88
IS 4
BP 2392
EP 2398
DI 10.1021/acs.analchem.5b04409
PG 7
WC Chemistry, Analytical
SC Chemistry
GA DE2JQ
UT WOS:000370454000059
PM 26814665
ER
PT J
AU LeVine, MV
Khelashvili, G
Shi, L
Quick, M
Javitch, JA
Weinstein, H
AF LeVine, Michael V.
Khelashvili, George
Shi, Lei
Quick, Matthias
Javitch, Jonathan A.
Weinstein, Harel
TI Role of Annular Lipids in the Functional Properties of Leucine
Transporter LeuT Proteomicelles
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; MEMBRANE-PROTEINS; NEUROTRANSMITTER
TRANSPORTERS; CRYSTAL-STRUCTURE; SPATIAL-ORGANIZATION;
MOLECULAR-DYNAMICS; STRUCTURAL BASIS; S2 SITE; BINDING; DETERGENTS
AB Recent work has shown that the choice of the type and concentration of detergent used for the solubilization of membrane proteins can strongly influence the results of functional experiments. In particular, the amino acid transporter LeuT can bind two substrate molecules in low concentrations of n-dodecyl beta-D-maltopyranoside (DDM), whereas high concentrations reduce the molar binding stoichiometry to 1:1. Subsequent molecular dynamics (MD) simulations of LeuT in DDM proteomicelles revealed that DDM can penetrate to the extracellular vestibule and make stable contacts in the functionally important secondary substrate binding site (S2), suggesting a potential competitive mechanism for the reduction in binding stoichiometry. Because annular lipids can be retained during solubilization, we performed MD simulations of LeuT proteomicelles at various stages of the solubilization process. We find that at low DDM concentrations, lipids are retained around the protein and penetration of detergent into the S2 site does not occur, whereas at high concentrations, lipids are displaced and the probability of DDM binding in the S2 site is increased. This behavior is dependent on the type of detergent, however, as we find in the simulations that the detergent lauryl maltose-neopentyl glycol, which is approximately twice the size of DDM and structurally more closely resembles lipids, does not penetrate the protein even at very high concentrations. We present functional studies that confirm the computational findings, emphasizing the need for careful consideration of experimental conditions, and for cautious interpretation of data in gathering mechanistic information about membrane proteins.
C1 [LeVine, Michael V.; Khelashvili, George; Shi, Lei; Weinstein, Harel] Cornell Univ WCMC, Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Quick, Matthias; Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
[Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
[Weinstein, Harel] Cornell Univ, Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA.
RP Khelashvili, G (reprint author), WCMC, Dept Physiol & Biophys, 1300 York Ave,Room LC-501A, New York, NY 10065 USA.
EM gek2009@med.cornell.edu
FU National Institutes of Health (NIH) [DA022413, DA17293, P01 DA012408,
U54 GM087519]; NIH, National Institute on Drug Abuse; Ruth L.
Kirschstein National Research Service Award [F31DA035533]
FX This work was supported by National Institutes of Health (NIH) Grants
DA022413, DA17293, P01 DA012408, and U54 GM087519 and by the Intramural
Research Program of the NIH, National Institute on Drug Abuse (L.S.).
M.V.L. is supported by Ruth L. Kirschstein National Research Service
Award F31DA035533.
NR 45
TC 2
Z9 2
U1 2
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 FEB 16
PY 2016
VL 55
IS 6
BP 850
EP 859
DI 10.1021/acs.biochem.5b01268
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DE2JO
UT WOS:000370453800003
PM 26811944
ER
PT J
AU Mills, JL
Dimopoulos, A
AF Mills, James L.
Dimopoulos, Aggeliki
TI FOLIC ACID FORTIFICATION FOR EUROPE? Decision on folic acid
fortification in Europe must consider both risks and benefits Reply
SO BMJ-BRITISH MEDICAL JOURNAL
LA English
DT Letter
ID COGNITIVE IMPAIRMENT; VITAMIN-B-12 STATUS; OLDER AMERICANS; FOLATE;
ANEMIA; DECLINE; AGE
C1 [Mills, James L.; Dimopoulos, Aggeliki] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Mills, JL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM millsj@mail.nih.gov
NR 20
TC 0
Z9 0
U1 3
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1756-1833
J9 BMJ-BRIT MED J
JI BMJ-British Medical Journal
PD FEB 16
PY 2016
VL 352
AR i746
DI 10.1136/bmj.i746
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DE6EW
UT WOS:000370727500003
PM 26882916
ER
PT J
AU de Gonzalez, AB
Salotti, JA
McHugh, K
Little, MP
Harbron, RW
Lee, C
Ntowe, E
Braganza, MZ
Parker, L
Rajaraman, P
Stiller, C
Stewart, DR
Craft, AW
Pearce, MS
AF de Gonzalez, Amy Berrington
Salotti, Jane A.
McHugh, Kieran
Little, Mark P.
Harbron, Richard W.
Lee, Choonsik
Ntowe, Estelle
Braganza, Melissa Z.
Parker, Louise
Rajaraman, Preetha
Stiller, Charles
Stewart, Douglas R.
Craft, Alan W.
Pearce, Mark S.
TI Relationship between paediatric CT scans and subsequent risk of
leukaemia and brain tumours: assessment of the impact of underlying
conditions
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE cancer; computed tomography; ionising radiation
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SERVICE-CENTRAL-REGISTER;
OF-THE-LITERATURE; CANCER-RISK; CHILDHOOD; COHORT; COMPLETENESS;
RADIATION; DIAGNOSIS; NEOPLASMS
AB Background: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings.
Methods: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer-predisposing conditions or previous unreported cancers and compared the dose-response analyses with our original results.
Results: We obtained information from the RIS and death certificates for about 40% of the cohort (n similar to 180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend = 0.02) and by 30% from 0.023 to 0.016 (P-trend < 0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases.
Conclusions: Although there was evidence of some bias in our original risk estimates, re-analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients.
C1 [de Gonzalez, Amy Berrington; Little, Mark P.; Lee, Choonsik; Ntowe, Estelle; Braganza, Melissa Z.; Rajaraman, Preetha; Stewart, Douglas R.] NCI, Radiat Epidemiol Unit, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Salotti, Jane A.; Harbron, Richard W.; Craft, Alan W.; Pearce, Mark S.] Newcastle Univ, Inst Hlth & Soc, Sir James Spence Inst, Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[McHugh, Kieran] Great Ormond St Hosp Sick Children, Great Ormond St, London WC1N 3JH, England.
[Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Med, Halifax, NS, Canada.
[Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Paediat, Halifax, NS, Canada.
[Stiller, Charles] Univ Oxford, New Coll, Oxford, England.
RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Unit, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM Berringtona@mail.nih.gov
FU NIH Intramural Research Program; Cancer Research UK; UK Department of
Health
FX This work was funded by the NIH Intramural Research Program, Cancer
Research UK and the UK Department of Health.
NR 25
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 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 16
PY 2016
VL 114
IS 4
BP 388
EP 394
DI 10.1038/bjc.2015.415
PG 7
WC Oncology
SC Oncology
GA DE2PW
UT WOS:000370470200006
ER
PT J
AU Kolb, JP
Martinez, J
AF Kolb, Joseph P.
Martinez, Jennifer
TI Bon EPOtit! S1P-Mediated EPO Signaling Whets a Macrophage's Appetite for
Apoptotic Cells
SO IMMUNITY
LA English
DT Editorial Material
ID ERYTHROPOIETIN; CLEARANCE
AB Phagocytes clear dying cells within an organism to prevent damaging inflammation and autoimmunity. In this issue of Immunity, Luo et al. (2016) describe how "find-me'' signals from apoptotic cells induce erythropoietin signaling within macrophages to prime them for efferocytosis.
C1 [Kolb, Joseph P.; Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
RP Martinez, J (reprint author), NIEHS, Immun Inflammat & Dis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jennifer.martinez3@nih.gov
NR 9
TC 0
Z9 0
U1 3
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 FEB 16
PY 2016
VL 44
IS 2
BP 209
EP 211
DI 10.1016/j.immuni.2016.01.023
PG 3
WC Immunology
SC Immunology
GA DE0DC
UT WOS:000370294000002
PM 26885850
ER
PT J
AU Mudd, JC
Brenchley, JM
AF Mudd, Joseph C.
Brenchley, Jason M.
TI ILC You Later: Early and Irreparable Loss of Innate Lymphocytes in HIV
Infection
SO IMMUNITY
LA English
DT Editorial Material
ID LYMPHOID-CELLS
AB Loss of IL-17-producing cells in the gut during HIV infection is linked to GI barrier damage. Kloverpris et al. (2016) find that circulating ILCs are lost early and irreversibly during HIV infection. Early ART administration protects against the ILC loss, and this might be clinically beneficial to HIV-infected individuals.
C1 [Mudd, Joseph C.; Brenchley, Jason M.] NIAID, Immunopathogenesis Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20874 USA.
RP Brenchley, JM (reprint author), NIAID, Immunopathogenesis Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20874 USA.
EM jbrenchl@niaid.nih.gov
NR 10
TC 0
Z9 0
U1 3
U2 5
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 FEB 16
PY 2016
VL 44
IS 2
BP 216
EP 218
DI 10.1016/j.immuni.2016.01.022
PG 4
WC Immunology
SC Immunology
GA DE0DC
UT WOS:000370294000005
PM 26885853
ER
PT J
AU Ballesteros-Tato, A
Randall, TD
Lund, FE
Spolski, R
Leonard, WJ
Leon, B
AF Ballesteros-Tato, Andre
Randall, Troy D.
Lund, Frances E.
Spolski, Rosanne
Leonard, Warren J.
Leon, Beatriz
TI T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2
Cell-Mediated Immunity to Inhaled House Dust Mite
SO IMMUNITY
LA English
DT Article
ID DENDRITIC CELLS; B-CELLS; TYPE-2 IMMUNITY; IN-VIVO; DIFFERENTIATION;
INDUCTION; ALLERGEN; ANTIGEN; ASTHMA; INFLAMMATION
AB Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma.
C1 [Ballesteros-Tato, Andre; Randall, Troy D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
[Lund, Frances E.; Leon, Beatriz] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bldg 10, Bethesda, MD 20892 USA.
RP Leon, B (reprint author), Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
EM bleon@uab.edu
FU National Institutes of Health [1R01 AI116584, 1R01 AI110480, 1R01
AI104725, U19 AI109962]; Division of Intramural Research, National
Heart, Lung, and Blood Institute, NIH; UAB
FX The authors would like to thank Uma Mudunuru and Thomas S. Simpler for
animal husbandry. This work was supported by UAB and National Institutes
of Health grants 1R01 AI116584 to B.L., 1R01 AI110480 to A.B.-T., 1R01
AI104725 to F.E.L., and U19 AI109962 to T.D.R. and Division of
Intramural Research, National Heart, Lung, and Blood Institute, NIH.
NR 30
TC 11
Z9 11
U1 1
U2 5
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 FEB 16
PY 2016
VL 44
IS 2
BP 259
EP 273
DI 10.1016/j.immuni.2015.11.017
PG 15
WC Immunology
SC Immunology
GA DE0DC
UT WOS:000370294000010
PM 26825674
ER
PT J
AU Putman, RK
Hatabu, H
Araki, T
Gudmundsson, G
Gao, W
Nishino, M
Okajima, Y
Dupuis, J
Latourelle, JC
Cho, MH
El-Chemaly, S
Coxson, HO
Celli, BR
Fernandez, IE
Zazueta, OE
Ross, JC
Harmouche, R
Estepar, RSJ
Diaz, AA
Sigurdsson, S
Gudmundsson, EF
Eiriksdottir, G
Aspelund, T
Budoff, MJ
Kinney, GL
Hokanson, JE
Williams, MC
Murchison, JT
MacNee, W
Hoffmann, U
O'Donnell, CJ
Launer, LJ
Harrris, TB
Gudnason, V
Silverman, EK
O'Connor, GT
Washko, GR
Rosas, IO
Hunninghake, GM
AF Putman, Rachel K.
Hatabu, Hiroto
Araki, Tetsuro
Gudmundsson, Gunnar
Gao, Wei
Nishino, Mizuki
Okajima, Yuka
Dupuis, Josee
Latourelle, Jeanne C.
Cho, Michael H.
El-Chemaly, Souheil
Coxson, Harvey O.
Celli, Bartolome R.
Fernandez, Isis E.
Zazueta, Oscar E.
Ross, James C.
Harmouche, Rola
Estepar, Raul San Jose
Diaz, Alejandro A.
Sigurdsson, Sigurdur
Gudmundsson, Elias F.
Eiriksdottir, Gudny
Aspelund, Thor
Budoff, Matthew J.
Kinney, Gregory L.
Hokanson, John E.
Williams, Michelle C.
Murchison, John T.
MacNee, William
Hoffmann, Udo
O'Donnell, Christopher J.
Launer, Lenore J.
Harrris, Tamara B.
Gudnason, Vilmundur
Silverman, Edwin K.
O'Connor, George T.
Washko, George R.
Rosas, Ivan O.
Hunninghake, Gary M.
CA ECLIPSE Investigator
COPDGene Investigator
TI Association Between Interstitial Lung Abnormalities and All-Cause
Mortality
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID IDIOPATHIC PULMONARY-FIBROSIS; MUC5B PROMOTER POLYMORPHISM; EXERCISE
CAPACITY; DISEASE; SUSCEPTIBILITY; EPIDEMIOLOGY; PREVALENCE
AB IMPORTANCE Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated.
OBJECTIVE To investigate whether interstitial lung abnormalities are associated with increased mortality.
DESIGN, SETTING, AND POPULATION Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005 -December 2006).
EXPOSURES Interstitial lung abnormality status as determined by chest CT evaluation.
MAIN OUTCOMES AND MEASURES All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort.
RESULTS Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1]to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1]to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis.
CONCLUSIONS AND RELEVANCE In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.
C1 [Putman, Rachel K.; Cho, Michael H.; El-Chemaly, Souheil; Celli, Bartolome R.; Fernandez, Isis E.; Zazueta, Oscar E.; Harmouche, Rola; Diaz, Alejandro A.; Silverman, Edwin K.; Washko, George R.; Rosas, Ivan O.; Hunninghake, Gary M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Pulm & Crit Care Div, Boston, MA 02115 USA.
[Hatabu, Hiroto; Nishino, Mizuki; Okajima, Yuka; Estepar, Raul San Jose] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Hatabu, Hiroto; Araki, Tetsuro; Nishino, Mizuki; Washko, George R.; Hunninghake, Gary M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Pulm Funct Imaging, Boston, MA 02115 USA.
[Gudmundsson, Gunnar] Univ Iceland, Landspital Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland.
[Gao, Wei; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Okajima, Yuka] St Lukes Int Hosp, Dept Radiol, Tokyo, Japan.
[Dupuis, Josee; O'Donnell, Christopher J.; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Latourelle, Jeanne C.; O'Connor, George T.] Boston Univ, Dept Med, Ctr Pulm, Boston, MA 02215 USA.
[Latourelle, Jeanne C.] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Cho, Michael H.; Ross, James C.; Silverman, Edwin K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Coxson, Harvey O.] Univ British Columbia, Dept Radiol, Vancouver, BC, Canada.
[Fernandez, Isis E.] Univ Munich, Univ Hosp Grosshadern, Comprehens Pneumol Ctr, Munich, Germany.
[Fernandez, Isis E.] German Ctr Lung Res, Helmholtz Zentrum Munchen, Munich, Germany.
[Ross, James C.; Harmouche, Rola; Estepar, Raul San Jose] Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA.
[Sigurdsson, Sigurdur; Gudmundsson, Elias F.; Eiriksdottir, Gudny; Aspelund, Thor; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Budoff, Matthew J.] Harbor UCLA, Los Angeles Biomed Res Inst, Dept Med, Torrance, CA USA.
[Kinney, Gregory L.; Hokanson, John E.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Denver, CO USA.
[Williams, Michelle C.] Univ Edinburgh, British Heart Fdn Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland.
[Murchison, John T.] Univ Edinburgh, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland.
[MacNee, William] Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland.
[Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Cardiovasc Epidemiol & Human Genom Branch, Bethesda, MD 20892 USA.
[Launer, Lenore J.; Harrris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Rosas, IO (reprint author), Brigham & Womens Hosp, Pulm & Crit Care Div, 75 Francis St, Boston, MA 02115 USA.
EM irosas@rics.bwh.harvard.edu
RI Coxson, Harvey/A-9861-2017;
OI Coxson, Harvey/0000-0001-5750-9711; MacNee, William/0000-0002-3692-1448
FU National Institutes of Health (NIH) [T32 HL007633]; Icelandic Research
Fund [141513-051]; Landspitali Scientific Fund [A-2015-030]; National
Cancer Institute grant [1K23CA157631]; NIH [K08 HL097029, R01 HL113264,
R21 HL119902, K25 HL104085, R01 HL116931, R01 HL116473, K01 HL118714,
R01 HL089897, R01 HL089856, N01-AG-1-2100, HHSN27120120022C, P01
HL105339, P01 HL114501, R01 HL107246, R01 HL122464, R01 HL111024];
National Heart, Lung, and Blood Institute's Framingham Heart Study
contract [N01-HC-2519.5]; GlaxoSmithKline [NCT00292552, 5C0104960];
National Institute on Aging (NIA) grant [27120120022C]; NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); NIA [27120120022C]
FX Dr Putman is supported by a National Institutes of Health (NIH) grant
(T32 HL007633). Dr Gudmundsson is supported by a project grant from the
Icelandic Research Fund (141513-051) and from the Landspitali Scientific
Fund (A-2015-030). Dr Nishino is supported by a National Cancer
Institute grant (1K23CA157631). Dr Cho is supported by 2 NIH grants (K08
HL097029 and R01 HL113264). Dr EI-Chemaly is supported by an NIH grant
(R21 HL119902). Dr San Jose Estepar is supported by 3 NIH grants (K25
HL104085, R01 HL116931, and R01 HL116473). Dr Diaz is supported by an
NIH grant (K01 HL118714). This work was partially supported by the
National Heart, Lung, and Blood Institute's Framingham Heart Study
contract (N01-HC-2519.5). COPDGene is supported by 2 NIH grants (R01
HL089897 and R01 HL089856). The ECLIPSE study was sponsored by
GlaxoSmithKline (NCT00292552; GSK code 5C0104960). The AGES (Age,
Gene/Environment Susceptibility)-Reykjavik study was supported by a
National Institute on Aging (NIA) grant (27120120022C), 2 NIH contracts
(N01-AG-1-2100 and HHSN27120120022C), the NIA Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). Dr Gudnason is supported by an NIA grant
(27120120022C) and an Icelandic Research Fund project grant
(141513-051). Dr Silverman is supported by 3 NIH grants (R01 HL089856,
P01 HL105339, and P01 HL114501). Dr Washko is supported by 3 NIH grants
(R01 HL107246, R01 HL116473, and R01 HL122464). Dr Rosas is supported by
an NIH grant (P01 HL114501). Dr Hunninghake and this study are supported
by 2 NIH grants (P01 HL114501 and R01 HL111024) and a project grant from
the Icelandic Research Fund (141513-051).
NR 34
TC 13
Z9 13
U1 1
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 FEB 16
PY 2016
VL 315
IS 7
BP 672
EP 681
DI 10.1001/jama.2016.0518
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD8JB
UT WOS:000370171500013
PM 26881370
ER
PT J
AU Menke, A
Casagrande, S
Cowie, CC
AF Menke, Andy
Casagrande, Sarah
Cowie, Catherine C.
TI US Trends for Diabetes Prevalence Among Adults Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Menke, Andy; Casagrande, Sarah] Social & Sci Syst Inc, 8757 Georgia Ave, Silver Spring, MD 20910 USA.
[Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Menke, A (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave, Silver Spring, MD 20910 USA.
EM amenke@s-3.com
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 16
PY 2016
VL 315
IS 7
BP 705
EP 706
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD8JB
UT WOS:000370171500020
PM 26881377
ER
PT J
AU Mandelblatt, JS
Stout, NK
Schechter, CB
van den Broek, JJ
Miglioretti, DL
Krapcho, M
Trentham-Dietz, A
Munoz, D
Lee, SJ
Berry, DA
van Ravesteyn, NT
Alagoz, O
Kerlikowske, K
Tosteson, ANA
Near, AM
Hoeffken, A
Chang, YJ
Heijnsdijk, EA
Chisholm, G
Huang, XL
Huang, H
Ergun, MA
Gangnon, R
Sprague, BL
Plevritis, S
Feuer, E
de Koning, HJ
Cronin, KA
AF Mandelblatt, Jeanne S.
Stout, Natasha K.
Schechter, Clyde B.
van den Broek, Jeroen J.
Miglioretti, Diana L.
Krapcho, Martin
Trentham-Dietz, Amy
Munoz, Diego
Lee, Sandra J.
Berry, Donald A.
van Ravesteyn, Nicolien T.
Alagoz, Oguzhan
Kerlikowske, Karla
Tosteson, Anna N. A.
Near, Aimee M.
Hoeffken, Amanda
Chang, Yaojen
Heijnsdijk, Eveline A.
Chisholm, Gary
Huang, Xuelin
Huang, Hui
Ergun, Mehmet Ali
Gangnon, Ronald
Sprague, Brian L.
Plevritis, Sylvia
Feuer, Eric
de Koning, Harry J.
Cronin, Kathleen A.
TI Collaborative Modeling of the Benefits and Harms Associated With
Different US Breast Cancer Screening Strategies
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID AGE 40 YEARS; RANDOMIZED CONTROLLED-TRIAL; COST-EFFECTIVENESS ANALYSIS;
UNITED-STATES; FOLLOW-UP; COMMUNITY PRACTICE; MENOPAUSAL STATUS; DENSE
BREASTS; MAMMOGRAPHY; RISK
AB Background: Controversy persists about optimal mammography screening strategies.
Objective: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer.
Design: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality.
Setting: United States.
Patients: Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity.
Intervention: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years.
Measurements: Benefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens.
Results: Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2 to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years.
Limitation: Other imaging technologies, polygenic risk, and nonadherence were not considered.
Conclusion: Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening.
C1 [Mandelblatt, Jeanne S.] Lombardi Comprehens Canc Ctr, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA.
[Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA.
[Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA.
[Schechter, Clyde B.] Albert Einstein Coll Med, Dept Family & Social Med, 1300 Morris Pk Ave,Black Bldg 406, Bronx, NY 10461 USA.
[van den Broek, Jeroen J.; van Ravesteyn, Nicolien T.; Heijnsdijk, Eveline A.; de Koning, Harry J.] Univ Med Ctr Rotterdam, Erasmus MC, POB 2040, NL-3000 CA Rotterdam, Netherlands.
[Miglioretti, Diana L.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, One Shields Ave,Med Sci 1C,Room 145, Davis, CA 95616 USA.
[Krapcho, Martin] Information Management Serv Inc, 3901 Calverton Blvd,Suite 200, Calverton, MD 20705 USA.
[Trentham-Dietz, Amy] Univ Wisconsin, Carbone Canc Ctr, 610 Walnut St,WARE Room 307, Madison, WI 53726 USA.
[Munoz, Diego] Stanford Univ, 318 Campus Dr,Room S255, Stanford, CA 94305 USA.
[Lee, Sandra J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Mailstop CLS11007,450 Brookline Ave, Boston, MA 02215 USA.
[Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, 1400 Pressler St,4-5062 Pickens Acad Tower, Houston, TX 77030 USA.
[Alagoz, Oguzhan] Univ Wisconsin, 1513 Univ Ave, Madison, WI 53706 USA.
[Kerlikowske, Karla] Vet Affairs Med Ctr 111A1, 4150 Clement St, San Francisco, CA 94121 USA.
[Tosteson, Anna N. A.] Geisel Sch Med Dartmouth, One Med Ctr Dr HB7505, Lebanon, NH 03756 USA.
[Near, Aimee M.; Chang, Yaojen] Georgetown Univ, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
[Chisholm, Gary] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Unit 1362,POB 301439, Houston, TX 77230 USA.
[Huang, Xuelin] Univ Texas MD Anderson Canc Ctr, 1400 Pressler St,Unit 1411,POB 301402, Houston, TX 77230 USA.
[Huang, Hui] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
[Ergun, Mehmet Ali] Univ Wisconsin, 3233 Mech Engn Bldg,1513 Univ Ave, Madison, WI 53706 USA.
[Gangnon, Ronald] Univ Wisconsin, Dept Populat Hlth Sci, 610 Walnut St, Madison, WI 53726 USA.
[Sprague, Brian L.] Univ Vermont, Off Hlth Promot Res, 1 South Prospect St, Burlington, VT 05401 USA.
[Plevritis, Sylvia] Stanford Univ, James H Clark Ctr, Dept Radiol, Room S255,MC 5442,318 Campus Dr, Stanford, CA 94305 USA.
[Feuer, Eric; Cronin, Kathleen A.] NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,MSC 9765,Room 4E534, Bethesda, MD 20892 USA.
RP Mandelblatt, JS (reprint author), Lombardi Comprehens Canc Ctr, 3300 Whitehaven St,NW,Suite 4100, Washington, DC 20007 USA.
EM mandelbj@georgetown.edu
FU National Institutes of Health
FX National Institutes of Health.
NR 75
TC 14
Z9 14
U1 8
U2 13
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD FEB 16
PY 2016
VL 164
IS 4
BP 215
EP +
DI 10.7326/M15-1536
PG 16
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD7WK
UT WOS:000370135300012
PM 26756606
ER
PT J
AU Nelson, MH
Bowers, JS
Bailey, SR
Diven, MA
Fugle, CW
Kaiser, ADM
Wrzesinski, C
Liu, B
Restifo, NP
Paulos, CM
AF Nelson, Michelle H.
Bowers, Jacob S.
Bailey, Stefanie R.
Diven, Marshall A.
Fugle, Caroline W.
Kaiser, Andrew D. M.
Wrzesinski, Claudia
Liu, Bei
Restifo, Nicholas P.
Paulos, Chrystal M.
TI Toll-like receptor agonist therapy can profoundly augment the antitumor
activity of adoptively transferred CD8(+) T cells without host
preconditioning
SO JOURNAL FOR IMMUNOTHERAPY OF CANCER
LA English
DT Article
DE Total body Irradiation; Adoptive immunotherapy; CD134 T lymphocytes;
Innate immunity
ID INDIGENOUS GASTROINTESTINAL MICROFLORA; METASTATIC MELANOMA; COMBINATION
IMMUNOTHERAPY; MICROBIAL TRANSLOCATION; TUMOR-IMMUNOTHERAPY; BACTERIAL
MUTUALISM; CANCER REGRESSION; DENDRITIC CELLS; CHEMOTHERAPY; DISEASE
AB Background: Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. Microbial components, such as LPS, are key mediators of total body irradiation (TBI) enhancement, but our ability to strategically use these toll-like receptor (TLR) agonists to bolster the potency of T cell-based therapies for cancer remains elusive. Herein, we used TLR4 agonist LPS as a tool to address how and when to use TLR agonists to effectively improve cancer immunotherapy.
Methods: To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmell melanoma mouse model. B16F10-bearing mice were preconditioned with 50y TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD811 T cells, vaccination with fowlpox encoding gpl 00, and IL-2) along with TLR4 agonist LPS. The timing of LPS administration and the requirement of individual components of the tripartite therapy were evaluated based on tumor growth and the phenotype of recovered splenocytes by flow cytometry. We also evaluated the role of non-toxic and clinically used TLR4 and TLR9 agonists monophosphoryl lipid A (MPL) and CpG Oligodeoxynucleotide (CpG ODN), respectively for ACT therapy.
Results: Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8:1T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. Moreover, we found that sequentially administering LPS during or one day prior to ACT therapy compromised tumor regression. In contrast, administering LPS after ACT potentiated the antitumor effectiveness of the regimen, thereby supporting the expansion of transferred tumor-specific CDS' T cells over host CD411T cells. We also found that non-toxic TLR agonists MPL and CpG potentiated the antitumor activity of infused CD8 T cells. Finally, TBI was no longer needed to regress tumors in mice who were depleted of host CD4'1 T cells, given a tripartite ACT regimen and then treated with low dose LPS.
Conclusions: Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. Our findings have clinical implications for the design of next generation immune -based therapies for patients with cancer.
C1 [Nelson, Michelle H.; Bowers, Jacob S.; Bailey, Stefanie R.; Diven, Marshall A.; Fugle, Caroline W.; Liu, Bei; Paulos, Chrystal M.] Med Univ S Carolina, Hollings Canc Ctr, Microbiol & Immunol, Charleston, SC 29425 USA.
[Kaiser, Andrew D. M.; Wrzesinski, Claudia; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nelson, MH (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Microbiol & Immunol, Charleston, SC 29425 USA.
EM nelsonmh@musc.edu; paulos@musc.edu
FU NCATS NIH HHS [KL2 TR000060, TL1 TR001451, UL1 TR000062, UL1 TR001450];
NCI NIH HHS [P30 CA138313, R01 CA175061]; NIGMS NIH HHS [T32 GM008716]
NR 57
TC 3
Z9 4
U1 2
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-1426
J9 J IMMUNOTHER CANCER
JI J. Immunother. Cancer
PD FEB 16
PY 2016
VL 4
AR 6
DI 10.1186/s40425-016-0110-8
PG 14
WC Oncology
SC Oncology
GA DD7YT
UT WOS:000370141600003
PM 26885368
ER
PT J
AU Yeh, CH
Bai, XT
Moles, R
Ratner, L
Waldmann, TA
Toshiki, W
Nicot, C
AF Yeh, Chien-Hung
Bai, Xue Tao
Moles, Ramona
Ratner, Lee
Waldmann, Thomas A.
Toshiki, Watanabe
Nicot, Christophe
TI Mutation of epigenetic regulators TET2 and MLL3 in patients with
HTLV-I-induced acute adult T-cell leukemia
SO MOLECULAR CANCER
LA English
DT Article
DE HTLV-I; Leukemia; ATL; LOH; TET2; MLL3; Epigenetic
ID ACUTE MYELOID-LEUKEMIA; VIRUS TYPE-I; LEUKEMIA/LYMPHOMA; LYMPHOMA;
CANCER; CLASSIFICATION; METHYLATION; NEOPLASMS; ENHANCER; PATHWAY
AB Background: Epigenetic regulators play a critical role in the maintenance of specific chromatin domains in an active or repressed state. Disruption of epigenetic regulatory mechanisms is widespread in cancer cells and largely contributes to the transformation process through active repression of tumor suppressor genes. While mutations of epigenetic regulators have been reported in various lymphoid malignancies and solid cancers, mutation of these genes in HTLV-I-associated T-cell leukemia has not been investigated.
Method: Here we used whole genome next generation sequencing (NGS) of uncultured freshly isolated ATL samples and identified the presence of mutations in SUZ12, DNMT1, DNMT3A, DNMT3B, TET1, TET2, IDH1, IDH2, MLL, MLL2, MLL3 and MLL4.
Results: TET2 was the most frequently mutated gene, occurring in 32 % (10/31) of ATL samples analyzed. Interestingly, NGS revealed nonsense mutations accompanied by loss of heterozygosity (LOH) in TET2 and MLL3, which was further confirmed by cloning and direct sequencing of DNA from uncultured cells. Finally, direct sequencing of matched control and tumor samples revealed that TET2 mutation was present only in ATL tumor cells.
Conclusions: Our results suggest that inactivation of MLL3 and TET2 may play an important role in the tumorigenesis process of HTLV-I-induced ATL.
C1 [Yeh, Chien-Hung; Bai, Xue Tao; Moles, Ramona; Nicot, Christophe] Univ Kansas, Med Ctr, Dept Pathol, Ctr Viral Oncol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
[Ratner, Lee] Washington Univ, Sch Med, Div Mol Oncol, Dept Med, St Louis, MO 63110 USA.
[Waldmann, Thomas A.] NIH, Lymphoid Malignancies Branch, Ctr Canc Res, Bldg 10,Room 4 N-115,10 Ctr Dr, Bethesda, MD 20892 USA.
[Toshiki, Watanabe] Univ Tokyo, Dept Med Genome Sci, Tokyo, Japan.
RP Nicot, C (reprint author), Univ Kansas, Med Ctr, Dept Pathol, Ctr Viral Oncol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM cnicot@kumc.edu
FU Lymphoma & Leukemia Society [LLS 6067-10]; AIDS Malignancy Consortium;
Intramural Research Program of the National Cancer Institute, NIH;
Japanese Ministry of Education, Culture, Sports, Science and Technology
(MEXT) [221S0001]; [CA106258]
FX Authors would like to thank Brandi Miller for editorial assistance. This
work was supported by grant CA106258 to C.N. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. This work was
supported in part by grant LLS 6067-10 from the Lymphoma & Leukemia
Society and AIDS Malignancy Consortium to L.R, the Intramural Research
Program of the National Cancer Institute, NIH (T.A.W.) and by the grant
from the Japanese Ministry of Education, Culture, Sports, Science and
Technology (MEXT) (No. 221S0001) to T.W.
NR 34
TC 14
Z9 14
U1 4
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD FEB 16
PY 2016
VL 15
AR 15
DI 10.1186/s12943-016-0500-z
PG 7
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA DD8AM
UT WOS:000370146100001
PM 26880370
ER
PT J
AU Morens, DM
AF Morens, David M.
TI Richard M. Krause: Avuncular avatar of microbial science
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
C1 [Morens, David M.] NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, Off Director, NIH, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 1
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 FEB 16
PY 2016
VL 113
IS 7
BP 1681
EP 1683
DI 10.1073/pnas.1525722113
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9BF
UT WOS:000370220000021
PM 26831081
ER
PT J
AU Chen, LY
Willis, WD
Eddy, EM
AF Chen, Liang-Yu
Willis, William D.
Eddy, Edward M.
TI Targeting the Gdnf Gene in peritubular myoid cells disrupts
undifferentiated spermatogonial cell development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE spermatogonial stem cell; stem cell niche; male fertility;
spermatogenesis; conditional gene targeting
ID MALE GERM-CELLS; ENTERIC NERVOUS-SYSTEM; MICE LACKING GDNF; STEM-CELLS;
SELF-RENEWAL; SERTOLI-CELLS; NEUROTROPHIC FACTOR; ANDROGEN RECEPTOR;
GROWTH-FACTORS; TYROSINE KINASE
AB Spermatogonial stem cells (SSCs) are a subpopulation of undifferentiated spermatogonia located in a niche at the base of the seminiferous epithelium delimited by Sertoli cells and peritubular myoid (PM) cells. SSCs self-renew or differentiate into spermatogonia that proliferate to give rise to spermatocytes and maintain spermatogenesis. Glial cell line-derived neurotrophic factor (GDNF) is essential for this process. Sertoli cells produce GDNF and other growth factors and are commonly thought to be responsible for regulating SSC development, but limited attention has been paid to the role of PM cells in this process. A conditional knockout (cKO) of the androgen receptor gene in PM cells resulted in male infertility. We found that testosterone (T) induces GDNF expression in mouse PM cells in vitro and neonatal spermatogonia (including SSCs) co-cultured with T-treated PM cells were able to colonize testes of germ cell-depleted mice after transplantation. This strongly suggested that T-regulated production of GDNF by PM cells is required for spermatogonial development, but PM cells might produce other factors in vitro that are responsible. In this study, we tested the hypothesis that production of GDNF by PM cells is essential for spermatogonial development by generating mice with a cKO of the Gdnf gene in PM cells. The cKO males sired up to two litters but became infertile due to collapse of spermatogenesis and loss of undifferentiated spermatogonia. These studies show for the first time, to our knowledge, that the production of GDNF by PM cells is essential for undifferentiated spermatogonial cell development in vivo.
C1 [Chen, Liang-Yu; Willis, William D.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
NR 69
TC 13
Z9 13
U1 2
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 16
PY 2016
VL 113
IS 7
BP 1829
EP 1834
DI 10.1073/pnas.1517994113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9BF
UT WOS:000370220000049
PM 26831079
ER
PT J
AU Patial, S
Curtis, AD
Lai, WS
Stumpo, DJ
Hill, GD
Flake, GP
Mannie, MD
Blackshear, PJ
AF Patial, Sonika
Curtis, Alan D., II
Lai, Wi S.
Stumpo, Deborah J.
Hill, Georgette D.
Flake, Gordon P.
Mannie, Mark D.
Blackshear, Perry J.
TI Enhanced stability of tristetraprolin mRNA protects mice against
immune-mediated inflammatory pathologies
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE AU-rich elements; mRNA stability; inflammation; deadenylation
ID IMIQUIMOD-INDUCED PSORIASIS; ANTIBODY-INDUCED ARTHRITIS;
COLONY-STIMULATING FACTOR; AU-RICH ELEMENTS; NEUTROPHIL PRODUCTION;
RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; G-CSF; DEFICIENCY; ALPHA
AB Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate-rich elements (AREs) in the 3'-untranslated regions (3'UTRs) of specificm RNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTP Delta ARE) in which a 136-base instability motif in the 3'UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS-stimulated macrophages and increased levels of TTP protein in mouse tissues. TTP Delta ARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases.
C1 [Patial, Sonika; Lai, Wi S.; Stumpo, Deborah J.; Blackshear, Perry J.] NIEHS, Signal Transduct Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
[Curtis, Alan D., II; Mannie, Mark D.] E Carolina Univ, Brody Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA.
[Hill, Georgette D.] Integrated Lab Syst, Res Triangle Pk, NC 27709 USA.
[Flake, Gordon P.] NIEHS, Cellular & Mol Pathol Branch, POB 12233, 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.
RP Blackshear, PJ (reprint author), NIEHS, Signal Transduct Lab, POB 12233, Res Triangle Pk, NC 27709 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.; Blackshear, PJ (reprint author), Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
EM black009@niehs.nih.gov
OI Mannie, Mark/0000-0003-0475-8516
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX We thank Dr. Dave Brar for performing the multiplex cytokine assays,
Debra King and Page Myers for technical assistance, Drs. Dori Germolec
and Michael Fessler for useful comments on the manuscript, and the
Histology and Immunohistochemistry Core and the Molecular Genomics Core
for help with histology and NanoString assays, respectively. This
research was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences.
NR 38
TC 7
Z9 7
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 16
PY 2016
VL 113
IS 7
BP 1865
EP 1870
DI 10.1073/pnas.1519906113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9BF
UT WOS:000370220000055
PM 26831084
ER
PT J
AU Simonetti, FR
Sobolewski, MD
Fyne, E
Shao, W
Spindler, J
Hattori, J
Anderson, EM
Watters, SA
Hill, S
Wu, XL
Wells, D
Su, L
Luke, BT
Halvas, EK
Besson, G
Penrose, KJ
Yang, ZM
Kwan, RW
Van Waes, C
Uldrick, T
Citrin, DE
Kovacs, J
Polis, MA
Rehm, CA
Gorelick, R
Piatak, M
Keele, BF
Kearney, MF
Coffin, JM
Hughes, SH
Mellors, JW
Maldarelli, F
AF Simonetti, Francesco R.
Sobolewski, Michele D.
Fyne, Elizabeth
Shao, Wei
Spindler, Jonathan
Hattori, Junko
Anderson, Elizabeth M.
Watters, Sarah A.
Hill, Shawn
Wu, Xiaolin
Wells, David
Su, Li
Luke, Brian T.
Halvas, Elias K.
Besson, Guillaume
Penrose, Kerri J.
Yang, Zhiming
Kwan, Richard W.
Van Waes, Carter
Uldrick, Thomas
Citrin, Deborah E.
Kovacs, Joseph
Polis, Michael A.
Rehm, Catherine A.
Gorelick, Robert
Piatak, Michael
Keele, Brandon F.
Kearney, Mary F.
Coffin, John M.
Hughes, Stephen H.
Mellors, John W.
Maldarelli, Frank
TI Clonally expanded CD4(+) T cells can produce infectious HIV-1 in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV persistence; clonal expansion of infected cells;
replication-competent HIV
ID SUPPRESSIVE ANTIRETROVIRAL THERAPY; NON-AIDS DISEASES; LATENT RESERVOIR;
REPLICATION; INTEGRATION; CANCER; RISK; CURE
AB Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1.
C1 [Simonetti, Francesco R.; Spindler, Jonathan; Hattori, Junko; Anderson, Elizabeth M.; Watters, Sarah A.; Hill, Shawn; Kearney, Mary F.; Hughes, Stephen H.; Maldarelli, Frank] NCI, HIV Dynam & Replicat Program, Frederick, MD 21702 USA.
[Simonetti, Francesco R.] Univ Milan, Dept Biomed & Clin Sci L Sacco, I-20157 Milan, Italy.
[Sobolewski, Michele D.; Fyne, Elizabeth; Halvas, Elias K.; Besson, Guillaume; Penrose, Kerri J.; Mellors, John W.] Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15261 USA.
[Shao, Wei; Wu, Xiaolin; Wells, David; Su, Li; Luke, Brian T.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
[Yang, Zhiming] NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Kwan, Richard W.; Polis, Michael A.; Rehm, Catherine A.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Van Waes, Carter] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
[Van Waes, Carter; Citrin, Deborah E.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Uldrick, Thomas] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Kovacs, Joseph] Natl Inst Hlth Clin Ctr, Crit Care Med Dept, NIH, Bethesda, MD 20892 USA.
[Gorelick, Robert; Piatak, Michael; Keele, Brandon F.] Frederick Natl Lab, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Maldarelli, F (reprint author), NCI, HIV Dynam & Replicat Program, Frederick, MD 21702 USA.; Coffin, JM (reprint author), Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
EM john.coffin@tufts.edu; fmalli@mail.nih.gov
FU National Cancer Institute, NIH [HHSN261200800001E]; NIH Bench to Bedside
Program; Leidos Biomedical Research [12XS547, 13XS110]; F.M. Kirby
Foundation
FX We thank the study participant, his family, and the clinical staff of
the National Institute of Allergy and Infectious Diseases/Critical Care
Medicine Department clinic who cared for him. We thank C. Lane, H.
Masur, and H. Imamichi, for insightful discussions and A. Kane for help
with the figures. This work was supported in part with federal funds
from National Cancer Institute, NIH, Contract HHSN261200800001E (to
R.G., B.F.K., and M.P.), the NIH Bench to Bedside Program (J.W.M. and
F.M.), and Contracts 12XS547 and 13XS110 through Leidos Biomedical
Research (to J.W.M. and J.M.C., respectively). J.M.C. was a Research
Professor of the American Cancer Society, with support from the F.M.
Kirby Foundation.
NR 23
TC 22
Z9 22
U1 2
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 16
PY 2016
VL 113
IS 7
BP 1883
EP 1888
DI 10.1073/pnas.1522675113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9BF
UT WOS:000370220000058
PM 26858442
ER
PT J
AU Gu, Y
Chiu, SL
Liu, B
Wu, PH
Delannoy, M
Lin, DT
Wirtz, D
Huganir, RL
AF Gu, Yi
Chiu, Shu-Ling
Liu, Bian
Wu, Pei-Hsun
Delannoy, Michael
Lin, Da-Ting
Wirtz, Denis
Huganir, Richard L.
TI Differential vesicular sorting of AMPA and GABA(A) receptors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE AMPA receptor; GABA(A) receptor; constitutive exocytosis; TIRFM; SNARE
ID CULTURED HIPPOCAMPAL-NEURONS; INTEGRAL MEMBRANE-PROTEIN; LONG-TERM
POTENTIATION; SYNAPTIC-TRANSMISSION; FLUORESCENT PROTEINS; EXCITATORY
SYNAPSES; NMDA RECEPTORS; CELL BIOLOGY; RAT-BRAIN; TRAFFICKING
AB In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic spines, whereas GABA(A) receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts. The molecular mechanisms underlying the precise sorting of these receptors remain unclear. By directly studying the constitutive exocytic vesicles of AMPA and GABA(A) receptors in vitro and in vivo, we demonstrate that they are initially sorted into different vesicles in the Golgi apparatus and inserted into distinct domains of the plasma membrane. These insertions are dependent on distinct Rab GTPases and SNARE complexes. The insertion of AMPA receptors requires SNAP25-syntaxin1A/B-VAMP2 complexes, whereas insertion of GABA(A) receptors relies on SNAP23-syntaxin1A/B-VAMP2 complexes. These SNARE complexes affect surface targeting of AMPA or GABA(A) receptors and synaptic transmission. Our studies reveal vesicular sortingmechanisms controlling the constitutive exocytosis of AMPA and GABA(A) receptors, which are critical for the regulation of excitatory and inhibitory responses in neurons.
C1 [Gu, Yi; Chiu, Shu-Ling; Liu, Bian; Lin, Da-Ting; Huganir, Richard L.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Wu, Pei-Hsun; Wirtz, Denis] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
[Delannoy, Michael] Johns Hopkins Univ, Sch Med, Microscope Facil, Baltimore, MD 21205 USA.
[Gu, Yi] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
[Lin, Da-Ting] NIDA, Baltimore, MD 21224 USA.
RP Huganir, RL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
EM rhuganir@jhmi.edu
FU NIH [R01 NS036715, R01 MH64856]
FX We thank Dr. Carolyn Machamer for her valuable advice on experiments and
critical reading of the manuscript. We thank members of the R.L.H.
laboratory for constructive comments during the execution of this study,
Benjamin Lin for developing the ImageSplice software for TIRFM imaging
processing, Dr. John Goutsias for advice on TIRFM imaging analysis, Dr.
Jose Esteban for providing cDNAs of Rab dominant negative mutants, Dr.
Ann Hubbard for valuable discussion on experiments, Drs. Victor Anggono,
Gareth M. Thomas, and Lenora Volk for critical reading of the
manuscript, Yingying Wei and Dr. Hongkai Ji for statistical analysis,
and Barbara Smith for the EM experiments. TIRF microscope and relevant
technical assistance were provided by the Johns Hopkins University
School of Medicine Microscope Facility. This research was supported by
NIH Grants R01 NS036715 and R01 MH64856.
NR 58
TC 3
Z9 3
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 FEB 16
PY 2016
VL 113
IS 7
BP E922
EP E931
DI 10.1073/pnas.1525726113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9BF
UT WOS:000370220000016
PM 26839408
ER
PT J
AU Smith, SJ
Pauly, GT
Akram, A
Melody, K
Rai, G
Maloney, DJ
Ambrose, Z
Thomas, CJ
Schneider, JT
Hughes, SH
AF Smith, Steven J.
Pauly, Gary T.
Akram, Aamir
Melody, Kevin
Rai, Ganesha
Maloney, David J.
Ambrose, Zandrea
Thomas, Craig J.
Schneider, Joel T.
Hughes, Stephen H.
TI Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants
SO RETROVIROLOGY
LA English
DT Article
DE HIV-1; Nonnucleoside reverse transcriptase inhibitors; Rilpivirine;
Antiviral activity; Resistance; Analogs; Susceptibility; Binding pocket;
Doravirine
ID REVERSE-TRANSCRIPTASE INHIBITORS; IMMUNODEFICIENCY-VIRUS TYPE-1;
NONNUCLEOSIDE INHIBITORS; POSITIONAL ADAPTABILITY; HIV-1-INFECTED
PATIENTS; CONFORMATIONAL-CHANGES; ANGSTROM RESOLUTION;
CRYSTAL-STRUCTURE; STERIC HINDRANCE; 3TC RESISTANCE
AB Background: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a class of antiretroviral compounds that bind in an allosteric binding pocket in HIV-1 RT, located about 10 angstrom from the polymerase active site. Binding of an NNRTI causes structural changes that perturb the alignment of the primer terminus and polymerase active site, preventing viral DNA synthesis. Rilpivirine (RPV) is the most recent NNRTI approved by the FDA, but like all other HIV-1 drugs, suboptimal treatment can lead to the development of resistance. To generate better compounds that could be added to the current HIV-1 drug armamentarium, we have developed several RPV analogs to combat viral variants that are resistant to the available NNRTIs.
Results: Using a single-round infection assay, we identified several RPV analogs that potently inhibited a broad panel of NNRTI resistant mutants. Additionally, we determined that several resistant mutants selected by either RPV or Doravirine (DOR) caused only a small increase in susceptibility to the most promising RPV analogs.
Conclusions: The antiviral data suggested that there are RPV analogs that could be candidates for further development as NNRTIs, and one of the most promising compounds was modeled in the NNRTI binding pocket. This model can be used to explain why this compound is broadly effective against the panel of NNRTI resistance mutants.
C1 [Smith, Steven J.; Akram, Aamir; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
[Pauly, Gary T.; Schneider, Joel T.] NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
[Melody, Kevin; Ambrose, Zandrea] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Ambrose, Zandrea] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA.
[Rai, Ganesha; Maloney, David J.; Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD USA.
RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
EM hughesst@mail.nih.gov
FU Intramural Research Programs of the National Cancer Institute; National
Human Genome Research Institute; National Center for Advancing
Translational Sciences; Intramural AIDS Targeted Antiviral Program
(IATAP); NIH [R01 AI080290, T32 AI065380]
FX The authors would like to thank Teresa Burdette for help in preparing
the manuscript and Joseph Meyer for help preparing the figures. This
research was supported by the Intramural Research Programs of the
National Cancer Institute, the National Human Genome Research Institute,
the National Center for Advancing Translational Sciences, the Intramural
AIDS Targeted Antiviral Program (IATAP), and NIH Grants R01 AI080290
(ZA) and T32 AI065380 (KM).
NR 33
TC 3
Z9 3
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD FEB 16
PY 2016
VL 13
AR 11
DI 10.1186/s12977-016-0244-2
PG 13
WC Virology
SC Virology
GA DD9FC
UT WOS:000370230100001
PM 26880034
ER
PT J
AU Greer, YE
Lipkowitz, S
AF Greer, Yoshimi Endo
Lipkowitz, Stanley
TI ONC201: Stressing tumors to death
SO SCIENCE SIGNALING
LA English
DT Editorial Material
ID ENDOPLASMIC-RETICULUM STRESS; CELL-DEATH; APOPTOTIC PATHWAY; CANCER;
TRAIL; THERAPY; MECHANISMS
AB The small molecule ONC201 was identified in a screen for compounds that would induce expression of the gene encoding tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in tumors and thus cause an autocrine- or paracrine-induced death in tumor cells. Two Research Articles in this issue of Science Signaling by Ishizawa et al. and Kline et al. describe how ONC201 can also trigger cytotoxicity by inducing a stress response. The mechanisms of the stress response induced differ between hematological malignancies and solid tumors, highlighting the complexity of ONC201-induced toxicity and raising intriguing issues of tissue-specific pathways activated by the drug.
C1 [Greer, Yoshimi Endo; Lipkowitz, Stanley] NCI, Womens Malignancies Branch Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lipkowitz, S (reprint author), NCI, Womens Malignancies Branch Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lipkowis@mail.nih.gov
NR 16
TC 5
Z9 5
U1 1
U2 4
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD FEB 16
PY 2016
VL 9
IS 415
AR fs1
DI 10.1126/scisignal.aad7955
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DD8QM
UT WOS:000370191900002
ER
PT J
AU Avnir, Y
Watson, CT
Glanville, J
Peterson, EC
Tallarico, AS
Bennett, AS
Qin, K
Fu, Y
Huang, CY
Beigel, JH
Breden, F
Zhu, Q
Marasco, WA
AF Avnir, Yuval
Watson, Corey T.
Glanville, Jacob
Peterson, Eric C.
Tallarico, Aimee S.
Bennett, Andrew S.
Qin, Kun
Fu, Ying
Huang, Chiung-Yu
Beigel, John H.
Breden, Felix
Zhu, Quan
Marasco, Wayne A.
TI IGHV1-69 polymorphism modulates anti-influenza antibody repertoires,
correlates with IGHV utilization shifts and varies by ethnicity
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MEMORY B-CELLS; HEMAGGLUTININ-STEM; COPY-NUMBER; INFLUENZA; VACCINE;
H5N1; RECOGNITION; EXPRESSION; DIVERSITY; MULTIPLE
AB IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F-and L-genotypes and CN among the various ethnic groups that may impact HV169-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of "universal" influenza vaccine.
C1 [Avnir, Yuval; Peterson, Eric C.; Tallarico, Aimee S.; Bennett, Andrew S.; Qin, Kun; Fu, Ying; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA.
[Avnir, Yuval; Peterson, Eric C.; Tallarico, Aimee S.; Bennett, Andrew S.; Qin, Kun; Fu, Ying; Zhu, Quan; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, 450 Brookline Ave, Boston, MA 02215 USA.
[Watson, Corey T.; Breden, Felix] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada.
[Watson, Corey T.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Glanville, Jacob] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Program Computat & Syst Immunol, Stanford, CA 94305 USA.
[Huang, Chiung-Yu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Div Biostat & Bioinformat, 550 N Broadway,Room 1103-A, Baltimore, MD 21205 USA.
[Beigel, John H.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 450 Brookline Ave, Boston, MA 02215 USA.; Marasco, WA (reprint author), Harvard Univ, Sch Med, Dept Med, 450 Brookline Ave, Boston, MA 02215 USA.
EM wayne_marasco@dfci.harvard.edu
FU NIH [AI074518, AI109223]; DARPA [W911NF-10-0266]; Intramural Research
Programs of NIAID, National Institutes of Health; NCI, National
Institutes of Health [HHSN261200800001E]
FX MAb G6 was kindly provided by Dr. Roy Jefferis, University of
Birmingham, Medical School, Birmingham, United Kingdom. This work was
supported by the following agencies. WAM - NIH AI074518, AI109223 and
DARPA W911NF-10-0266. FB - Natural Sciences and Engineering Research
Council of Canada. JHB-Intramural Research Programs of NIAID, National
Institutes of Health; NCI, National Institutes of Health Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 39
TC 5
Z9 5
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 16
PY 2016
VL 6
AR 20842
DI 10.1038/srep20842
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD8RT
UT WOS:000370195300001
PM 26880249
ER
PT J
AU Takai, A
Fako, V
Dang, H
Forgues, M
Yu, ZP
Budhu, A
Wang, XW
AF Takai, Atsushi
Fako, Valerie
Dang, Hien
Forgues, Marshonna
Yu, Zhipeng
Budhu, Anuradha
Wang, Xin Wei
TI Three-dimensional Organotypic Culture Models of Human Hepatocellular
Carcinoma
SO SCIENTIFIC REPORTS
LA English
DT Article
ID HEPATOMA-CELL LINES; STEM-CELLS; LIVER-CANCER; IN-VITRO; ORGANOID
CULTURES; MOUSE MODELS; 3D CULTURE; EPCAM; SPHEROIDS; GROWTH
AB Three-dimensional cell culture methods are viable in vitro approaches that facilitate the examination of biological features cancer cells present in vivo. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells in porous alginate scaffolds can generate organoid-like spheroids that mimic numerous features of glandular epithelium in vivo, such as acinar morphogenesis and apical expression patterns of EpCAM, a hepatic stem/progenitor cell marker highly expressed in a subset of HCC with stemness features. We show that the activation of Wnt/beta-catenin signaling, an essential pathway for maintaining HCC stemness, is required for EpCAM(+) HCC spheroid formation as well as the maintenance of the acinous structure. Furthermore, we demonstrate that EpCAM+ HCC cells cultured as spheroids are more sensitive to TGF/beta-induced epithelial-mesenchymal transition with highly tumorigenic and metastatic potential in vivo compared to conventional two-dimensional (2D) culture. In addition, HCC cells in EpCAM+ spheroids are more resistant to chemotherapeutic agents than 2D-cultured cells. The alginate scaffold-based organotypic culture system is a promising, reliable, and easy system that can be configured into a high throughput fashion for the identification of critical signaling pathways and screening of molecular drug targets specific for HCC.
C1 [Takai, Atsushi; Fako, Valerie; Dang, Hien; Forgues, Marshonna; Yu, Zhipeng; Budhu, Anuradha; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, Bethesda, MD [Z01 BC 010877, Z01 BC 010876]; Japan
Society for the Promotion of Science
FX We thank Dominic Esposito of the Protein Expression Laboratory of The
Frederick National Laboratory for Cancer Research for lentiviral
constructs and virus production, and Shelly Lu for the protocol of an
orthotopic liver cancer mouse model. This work was supported by grants
(Z01 BC 010877 and Z01 BC 010876) from the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, Bethesda,
MD. A.T. was also supported by the Japan Society for the Promotion of
Science.
NR 37
TC 2
Z9 2
U1 1
U2 16
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 FEB 16
PY 2016
VL 6
AR 21174
DI 10.1038/srep21174
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD9CS
UT WOS:000370223900001
PM 26880118
ER
PT J
AU Hao, M
Wang, YL
Bryant, SH
AF Hao, Ming
Wang, Yanli
Bryant, Stephen H.
TI Improved prediction of drug-target interactions using regularized least
squares integrating with kernel fusion technique
SO ANALYTICA CHIMICA ACTA
LA English
DT Article
DE Drug-target interactions; Regularized least squares; Kernel fusion;
PubChem BioAssay; Drug repositioning
ID RESOURCE; INFORMATION; DISCOVERY; DATABASE; MACHINE; LIGAND
AB Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision-recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as poly-pharmacology, and may help to accelerate drug discovery by identifying novel drug targets. Published by Elsevier B.V.
C1 [Hao, Ming; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL; Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 37
TC 2
Z9 2
U1 7
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0003-2670
EI 1873-4324
J9 ANAL CHIM ACTA
JI Anal. Chim. Acta
PD FEB 16
PY 2016
VL 909
BP 41
EP 50
DI 10.1016/j.aca.2016.01.014
PG 10
WC Chemistry, Analytical
SC Chemistry
GA DC3BG
UT WOS:000369093600005
PM 26851083
ER
PT J
AU Hong, JS
Romero, R
Lee, DC
Than, NG
Yeo, L
Chaemsaithong, P
Ahn, S
Kim, JS
Kim, CJ
Kim, YM
AF Hong, Joon-Seok
Romero, Roberto
Lee, Deug-Chan
Than, Nandor Gabor
Yeo, Lami
Chaemsaithong, Piya
Ahn, Soyeon
Kim, Jung-Sun
Kim, Chong Jai
Kim, Yeon Mee
TI Umbilical cord prostaglandins in term and preterm parturition
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Chorioamnionitis; eicosanoids; funisitis; intra-amniotic inflammation;
microbial invasion of the amniotic cavity; PGE(2); PGF(2); preeclampsia;
pregnancy
ID HUMAN FETAL MEMBRANES; INFLAMMATORY RESPONSE SYNDROME; AMNIOTIC-FLUID
CONCENTRATIONS; HUMAN GESTATIONAL TISSUES; SPONTANEOUS LABOR ONSET;
HISTOLOGIC CHORIOAMNIONITIS; INTRAAMNIOTIC INFECTION; MICROBIAL
INVASION; INTACT MEMBRANES; PREMATURE RUPTURE
AB Objective: Prostaglandins (PGs) are considered the universal mediators of parturition. Amniotic fluid PGE(2) and PGF(2) concentrations increase before the onset of spontaneous labor at term, as well as during labor. This study was conducted to determine if the concentrations of umbilical cord PGE(2) and PGF(2) change with advancing gestational age, spontaneous labor at term, and preterm labor (with and without funisitis).Methods: Umbilical cord (UC) tissue samples were obtained from women (N=158) with singleton pregnancies in the following groups: (1) term deliveries without labor (TNL; n=20); (2) term deliveries with labor (TIL; n=20); (3) spontaneous preterm deliveries (sPTD) with (n=20) and without acute funisitis (n=20); and (4) preeclampsia without labor (n=78). The concentrations of PGs were determined in different locations of the UC. PGE(2) and PGF(2) were measured by specific immunoassays. Non-parametric statistics were used for analysis.Results: (1) In spontaneous preterm deliveries, the median UC PGE(2) concentration was higher in cases with funisitis than in those without funisitis (233.7pg/mu g versus 87.4pg/mu g of total protein, p=0.001); (2) the median UC PGE(2) concentration in sPTD with funisitis was also higher than that obtained from samples who had undergone labor at term (233.7pg/mu g versus 116.1pg/mu g of total protein, p=0.03); (3) the UC PGE(2) and PGF(2) concentration increased as a function of advancing gestational age before 36 weeks (PGE(2): =0.59, p<0.001; PGF(2): =0.39, p=0.01), but not after 36 weeks (PGE(2): =-0.1, p=0.5; PGF(2): =-0.2, p=0.2); (4) the median UC concentrations of PGE(2) and PGF(2) at term was similar in samples obtained from women with and without labor (PGE(2): TNL 133.7pg/mu g versus TIL 116.1pg/mu g of total protein, p=0.9; PGF(2): TNL 8.4pg/mu g versus TIL 8.1pg/mu g of total protein, p=0.7); and (5) there was no correlation between UC PG concentration and gestational age at term pregnancy (PGE(2): =0.01, p=0.9; PGF(2): =0.07, p=0.7).Conclusions: (1) PGE(2) concentrations in the UC are higher in the presence of acute funisitis than in the absence of this lesion; (2) spontaneous labor at term was not associated with a change in the UC concentration of PGE(2) and PGF(2); and (3) the UC concentrations of PGE(2) and PGF(2) increased as a function of gestational age. We propose that UC PGs act as inflammatory mediators generated in the context of fetal systemic inflammation.
C1 [Hong, Joon-Seok; Romero, Roberto; Lee, Deug-Chan; Than, Nandor Gabor; Yeo, Lami; Chaemsaithong, Piya; Kim, Chong Jai; Kim, Yeon Mee] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
[Hong, Joon-Seok] Seoul Natl Univ, Dept Obstet & Gynecol, Bundang Hosp, Gyeonggi Do, South Korea.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Lee, Deug-Chan] Kangwon Natl Univ, Coll Biomed Sci, Chunchon, South Korea.
[Than, Nandor Gabor; Yeo, Lami; Chaemsaithong, Piya] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Ahn, Soyeon] Seoul Natl Univ, Med Res Collaborating Ctr, Bundang Hosp, Gyeonggi Do, South Korea.
[Kim, Jung-Sun] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med, Seoul, South Korea.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea.
[Kim, Yeon Mee] Inje Univ, Haeundae Paik Hosp, Dept Pathol, Coll Med, Busan, South Korea.
RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS,Hutzel Womens Hosp, 3990 John R St, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov; ykim.haeundae@gmail.com
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, U.S. Department of Health
and Human Services, Bethesda, MD, USA; Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, U.S. Department of Health and Human Services, Detroit, MI, USA
FX This work was supported in part by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, U.S. Department of Health and Human Services, Bethesda, MD, and
Detroit, MI, USA. The authors declare no conflicts of interest.
NR 171
TC 0
Z9 0
U1 1
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD FEB 16
PY 2016
VL 29
IS 4
BP 523
EP 531
DI 10.3109/14767058.2015.1011120
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CY9RI
UT WOS:000366743600002
PM 25758616
ER
PT J
AU Connolly, R
Zhao, F
Miller, K
Tevaarwerk, A
Wagner, L
Lee, M
Murray, J
Gray, R
Piekarz, R
Zujewski, JA
Sparano, J
AF Connolly, R.
Zhao, F.
Miller, K.
Tevaarwerk, A.
Wagner, L.
Lee, M.
Murray, J.
Gray, R.
Piekarz, R.
Zujewski, J. A.
Sparano, J.
TI E2112: Randomized phase III trial of endocrine therapy plus
entinostat/placebo in patients with hormone receptor-positive advanced
breast cancer. A trial of the ECOG-ACRIN cancer research group
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Wake Forest Univ, Hlth Serv, Winston Salem, NC USA.
NCI, Bethesda, MD 20892 USA.
NCI, CTEP, Bethesda, MD 20892 USA.
Montefiore Med Ctr, Albert Einstein Coll Med, New York, NY USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA OT2-01-04
DI 10.1158/1538-7445.SABCS15-OT2-01-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622401234
ER
PT J
AU Glynn, S
Garrrido-Cuesta, P
Wink, D
Ridnour, L
Ambs, S
Keane, M
Walsh, E
Callagy, G
AF Glynn, S.
Garrrido-Cuesta, P.
Wink, D.
Ridnour, L.
Ambs, S.
Keane, M.
Walsh, E.
Callagy, G.
TI NOS2&COX2 activation of TLR4 & EGFR signalling causes poor outcome in
oestrogen receptor-negative breast cancer via pro-survival signals and
immune polarisation
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Natl Univ Ireland Galway, Galway, Ireland.
NCI, Bethesda, MD 20892 USA.
Galway Univ Hosp, Galway, Ireland.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P2-05-15
DI 10.1158/1538-7445.SABCS15-P2-05-15
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622401121
ER
PT J
AU Ma, CX
Suman, VJ
Goetz, M
Northfelt, D
Burkard, M
Ademuyiwa, F
Naughton, M
Margenthaler, J
Aft, R
Gray, R
Tavaarwerk, A
Wilke, L
Haddad, T
Moynihan, T
Loprinzi, C
Hieken, T
Hoog, J
Guo, Z
Han, J
Vij, K
Mardis, E
Sanati, S
Al-Kateb, H
Doyle, L
Erlichman, C
Ellis, MJ
AF Ma, C. X.
Suman, V. J.
Goetz, M.
Northfelt, D.
Burkard, M.
Ademuyiwa, F.
Naughton, M.
Margenthaler, J.
Aft, R.
Gray, R.
Tavaarwerk, A.
Wilke, L.
Haddad, T.
Moynihan, T.
Loprinzi, C.
Hieken, T.
Hoog, J.
Guo, Z.
Han, J.
Vij, K.
Mardis, E.
Sanati, S.
Al-Kateb, H.
Doyle, L.
Erlichman, C.
Ellis, M. J.
TI A phase II neoadjuvant trial of MK-2206, an AKT inhibitor, in
combination with anastrozole for clinical stage 2 or 3 PIK3CA mutant
estrogen receptor positive HER2 negative (ER+HER2-) breast cancer (BC)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Washington Univ, St Louis, MO USA.
Mayo Clin, Rochester, MN USA.
Mayo Clin, Scottsdale, AZ USA.
Univ Wisconsin, Madison, WI USA.
NCI, Bethesda, MD 20892 USA.
Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-13-04
DI 10.1158/1538-7445.SABCS15-P5-13-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400347
ER
PT J
AU Ru, Y
Hu, PT
Kovatich, AJ
Hooke, JA
Liu, J
Kvecher, L
Fantacone-Campbell, JL
Deyarmin, B
Kovatich, AW
Cammarata, F
Rui, H
Davidson-Moncada, J
Shriver, CD
Hu, H
AF Ru, Y.
Hu, P. T.
Kovatich, A. J.
Hooke, J. A.
Liu, J.
Kvecher, L.
Fantacone-Campbell, J. L.
Deyarmin, B.
Kovatich, A. W.
Cammarata, F.
Rui, H.
Davidson-Moncada, J.
Shriver, C. D.
Hu, H.
TI CD163 expression is associated with young age, triple negative subtype,
and poor outcome in breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Windber Res Inst, Windber, PA USA.
Upper Dublin High Sch, Ft Washington, PA USA.
Henry M Jackson Fdn Adv Mil Med, Clin Breast Care Project, Bethesda, MD USA.
MDR Global LLC, Windber, PA USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
NHLBI, Bldg 10, Bethesda, MD 20892 USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P4-09-24
DI 10.1158/1538-7445.SABCS15-P4-09-24
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400152
ER
PT J
AU Yamauchi, T
Imamura, CK
Yamauchi, H
Jinno, H
Takahashi, M
Kitagawa, Y
Nakamura, S
Lim, B
Krishnamurthy, S
Reuben, JM
Liu, D
Tripathy, D
Zujewski, JA
Chen, H
Takebe, N
Saya, H
Ueno, NT
AF Yamauchi, T.
Imamura, C. K.
Yamauchi, H.
Jinno, H.
Takahashi, M.
Kitagawa, Y.
Nakamura, S.
Lim, B.
Krishnamurthy, S.
Reuben, J. M.
Liu, D.
Tripathy, D.
Zujewski, J. A.
Chen, H.
Takebe, N.
Saya, H.
Ueno, N. T.
TI CD44v as a potential predictive biomarker for pathologic complete
response in primary HER2+breast cancer: Utility of adaptive response
biopsy in preoperative therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 St Lukes Int Hosp, Div Med Oncol, Tokyo, Japan.
Keio Univ, Sch Med, Tokyo, Japan.
St Lukes Int Hosp, Tokyo, Japan.
Showa Univ, Sch Med, Tokyo 142, Japan.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
Keio Univ, Sch Med, Div Gene Regulat, Inst Adv Med Res, Tokyo, Japan.
RI Lim, Bora/F-9978-2014
OI Lim, Bora/0000-0002-4182-6058
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P3-07-58
DI 10.1158/1538-7445.SABCS15-P3-07-58
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400122
ER
PT J
AU Yang, HH
Lee, MP
AF Yang, H. H.
Lee, M. P.
TI Breast cancer patient survival prediction based on the signature derived
from DNA methylation and mRNA expression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 [Yang, H. H.; Lee, M. P.] NCI, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-08-20
DI 10.1158/1538-7445.SABCS15-P5-08-20
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400387
ER
PT J
AU Allot, EH
Tse, CK
Carey, L
Anderson, WF
Olshan, AF
Troester, MA
AF Allot, E. H.
Tse, C-K
Carey, L.
Anderson, W. F.
Olshan, A. F.
Troester, M. A.
TI Etiologic heterogeneity in breast cancer across quantitative levels of
estrogen receptor expression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ N Carolina, Chapel Hill, NC USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P1-07-04
DI 10.1158/1538-7445.SABCS15-P1-07-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402301
ER
PT J
AU Anderson, WF
Pfeiffer, RM
Wohlfahrt, J
Ejlertsen, B
Jensen, MB
Kroman, NT
AF Anderson, W. F.
Pfeiffer, R. M.
Wohlfahrt, J.
Ejlertsen, B.
Jensen, M-B
Kroman, N. T.
TI Reproductive factors and subtype specific breast cancer risk
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, Bethesda, MD 20892 USA.
Statens Serum Inst, DK-2300 Copenhagen, Denmark.
Danish Breast Canc Grp, Copenhagen, Denmark.
Rigshosp, DK-2100 Copenhagen, Denmark.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P1-07-03
DI 10.1158/1538-7445.SABCS15-P1-07-03
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402300
ER
PT J
AU Byrd, T
Fousek, K
Pignata, A
Szot, C
Bielamowicz, K
Wakefield, A
Koch, J
Landi, D
Seaman, S
Wels, W
Fletcher, B
Hegde, M
St Croix, B
Ahmed, N
AF Byrd, T.
Fousek, K.
Pignata, A.
Szot, C.
Bielamowicz, K.
Wakefield, A.
Koch, J.
Landi, D.
Seaman, S.
Wels, W.
Fletcher, B.
Hegde, M.
St Croix, B.
Ahmed, N.
TI TEM8 specific CAR T cells serve as a novel targeted therapy for triple
negative breast cancer and its supporting endothelium
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Baylor Coll Med, Houston, TX 77030 USA.
NCI, Frederick, MD 21701 USA.
Georg Speyer Haus, Frankfurt, Germany.
Univ Florida, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA PD3-07
DI 10.1158/1538-7445.SABCS15-PD3-07
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402144
ER
PT J
AU Chumsri, S
Lee, MJ
Tomita, Y
Lee, S
Tomita, S
Cruickshank, S
Ordentlich, P
Trepel, JB
AF Chumsri, S.
Lee, M-J
Tomita, Y.
Lee, S.
Tomita, S.
Cruickshank, S.
Ordentlich, P.
Trepel, J. B.
TI Epigenetic immune modulation by entinostat in breast cancer: Correlative
analysis of ENCORE 301 trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Mayo Clin, Jacksonville, FL 32224 USA.
NCI, Bethesda, MD 20892 USA.
Syndax Pharmaceut Inc, Waltham, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P2-11-10
DI 10.1158/1538-7445.SABCS15-P2-11-10
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400314
ER
PT J
AU Dean-Colomb, W
Tan, M
Tang, W
Ambs, S
Yates, C
AF Dean-Colomb, W.
Tan, M.
Tang, W.
Ambs, S.
Yates, C.
TI Low lactate dehydrogenase B expression correlates with decreased
distant-metastasis free- and recurrence-free survival post-chemotherapy
in basal-like breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ Hosp & Clin, Lafayette, LA USA.
Tuskegee Univ, Tuskegee, AL 36088 USA.
Mitchell Canc Inst, Mobile, AL USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-08-38
DI 10.1158/1538-7445.SABCS15-P5-08-38
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400402
ER
PT J
AU Dowsett, M
Leung, SCY
Zabaglo, L
Arun, I
Badve, SS
Bane, AL
Bartlett, JMS
Borgquist, S
Chang, MC
Dodson, A
Enos, RE
Fineberg, S
Focke, CM
Gao, D
Gown, AM
Grabau, D
Gutierrez, C
Hugh, JC
Kos, Z
Laenkholm, AV
Lin, MG
Mastropasqua, MG
Moriya, T
Nofech-Mozes, S
Osborne, CK
Penault-Llorca, FM
Piper, T
Sakatani, T
Salgado, R
Starczynski, J
Viale, G
Hayes, DF
McShane, LM
Nielsen, TO
AF Dowsett, M.
Leung, S. C. Y.
Zabaglo, L.
Arun, I.
Badve, S. S.
Bane, A. L.
Bartlett, J. M. S.
Borgquist, S.
Chang, M. C.
Dodson, A.
Enos, R. E.
Fineberg, S.
Focke, C. M.
Gao, D.
Gown, A. M.
Grabau, D.
Gutierrez, C.
Hugh, J. C.
Kos, Z.
Laenkholm, A-V
Lin, M-G
Mastropasqua, M. G.
Moriya, T.
Nofech-Mozes, S.
Osborne, C. K.
Penault-Llorca, F. M.
Piper, T.
Sakatani, T.
Salgado, R.
Starczynski, J.
Viale, G.
Hayes, D. F.
McShane, L. M.
Nielsen, T. O.
TI Analytical validation of a standardized scoring protocol for Ki67:
Phase-3 of an international multicenter collaboration
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Inst Canc Res, London SW3 6JB, England.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Tata Med Ctr, New Town, W Bengal, India.
Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
McMaster Univ, Hamilton, ON, Canada.
Ontario Inst Canc Res, Toronto, ON, Canada.
Lund Univ, Lund, Sweden.
Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
EMMES Corp, Rockville, MD USA.
Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA.
Albert Einstein Coll Med, Bronx, NY 10467 USA.
Dietrich Bonhoeffer Med Ctr, Neubrandenburg, Mecklenburg Vor, Germany.
PhenoPath Labs, Seattle, WA USA.
Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
Univ Alberta, Edmonton, AB, Canada.
Ottawa Hosp, Ottawa, ON, Canada.
Slagelse Hosp, Slagelse, Region Sjaellan, Denmark.
Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
European Inst Oncol, Milan, Italy.
Kawasaki Med Univ, Kurashiki, Okayama, Japan.
Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
Univ Allvergne, Clermont Ferrand, France.
Western Gen Hosp, Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
Nippon Med Sch, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 113, Japan.
Inst Jules Bordet, B-1000 Brussels, Belgium.
Birmingham Heart England, Natl Hlth Serv, Birmingham, W Midlands, England.
European Inst Oncol, Milan, Italy.
Univ Milan, Milan, Italy.
Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P1-01-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402249
ER
PT J
AU Gass, HD
May, M
Rojas, P
Abba, M
Sequeira, G
Vazquez, PM
Gonzalez, PL
Elia, A
Alvarez, MM
Molinolo, A
Lanari, CL
AF Gass, H. D.
May, M.
Rojas, P.
Abba, M.
Sequeira, G.
Vazquez, P. Martinez
Gonzalez, P. L.
Elia, A.
Alvarez, M. M.
Molinolo, A.
Lanari, C. L.
TI Breast cancer recurrence risk: A role for the progesterone receptor
isoforms
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Hosp Magdalena V de Martinez Gen Pacheco, Buenos Aires, DF, Argentina.
IBYME CONICET, CABA, Vuelta De Obligado, Argentina.
CINIBA, Buenos Aires, DF, Argentina.
NIDCR, Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P4-09-13
DI 10.1158/1538-7445.SABCS15-P4-09-13
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400142
ER
PT J
AU Gierach, GL
Curtis, RE
Pfeiffer, RM
Mullooly, M
Hoover, RN
Nyante, SJ
Feigelson, HS
Glass, AG
de Gonzalez, AB
AF Gierach, G. L.
Curtis, R. E.
Pfeiffer, R. M.
Mullooly, M.
Hoover, R. N.
Nyante, S. J.
Feigelson, H. S.
Glass, A. G.
de Gonzalez, A. Berrington
TI Adjuvant endocrine therapy and risk of contralateral breast cancer among
a cohort of US women with breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, Bethesda, MD 20892 USA.
Univ N Carolina, Chapel Hill, NC USA.
Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
Kaiser Permanente, Northwest Ctr Hlth Res, Portland, OR USA.
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-12-01
DI 10.1158/1538-7445.SABCS15-P5-12-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400011
ER
PT J
AU Goetz, MP
Suman, VJ
Reid, JM
Northfelt, DW
Mahr, MA
Dockter, T
Kuffel, M
Buhrow, SA
Safgren, SL
McGovern, RM
Collins, JM
Streicher, H
Hawse, JR
Haddad, TC
Erlichman, C
Ames, MM
Ingle, JN
AF Goetz, M. P.
Suman, V. J.
Reid, J. M.
Northfelt, D. W.
Mahr, M. A.
Dockter, T.
Kuffel, M.
Buhrow, S. A.
Safgren, S. L.
McGovern, R. M.
Collins, J. M.
Streicher, H.
Hawse, J. R.
Haddad, T. C.
Erlichman, C.
Ames, M. M.
Ingle, J. N.
TI Final results of a first-in-human phase I study of the tamoxifen (TAM)
metabolite, Z-Endoxifen hydrochloride (Z-Endx) in women with aromatase
inhibitor (AI) refractory metastatic breast cancer (MBC) (NCT01327781)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Mayo Clin, Rochester, MN USA.
NCI, Bethesda, MD 20892 USA.
Mayo Clin, Scottsdale, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA PD2-03
DI 10.1158/1538-7445.SABCS15-PD2-03
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622401243
ER
PT J
AU Goff, SL
Feldman, SA
Somerville, R
Rosenberg, SA
AF Goff, S. L.
Feldman, S. A.
Somerville, R.
Rosenberg, S. A.
TI Adoptive cell transfer (ACT) using tumor infiltrating lymphocytes to
target neoantigens in patients with metastatic breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 [Goff, S. L.; Feldman, S. A.; Somerville, R.; Rosenberg, S. A.] NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA OT1-01-03
DI 10.1158/1538-7445.SABCS15-OT1-01-03
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622401304
ER
PT J
AU Gogineni, ES
Kehrer, JD
Jones, GC
Premo, C
Stinson, S
AF Gogineni, E. S.
Kehrer, J. D.
Jones, G. C.
Premo, C.
Stinson, S.
TI Active breathing control in the management of left-sided breast cancer
with irradiation: A dosimetric analysis of cardiac and lung dose
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 New York Inst Technol, Coll Osteopath Med, Old Westbury, NY 11568 USA.
NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
Suburban Hosp, Johns Hopkins Med, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P3-12-06
DI 10.1158/1538-7445.SABCS15-P3-12-06
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400488
ER
PT J
AU Greer, YE
Tice, D
Lipkowitz, S
AF Greer, Y. E.
Tice, D.
Lipkowitz, S.
TI MEDI3039, a novel highly potent tumor necrosis factor (TNF)-related
apoptosis inducing ligand (TRAIL) receptor agonist, induces apoptotic
cell death in breast cancer cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, Bethesda, MD 20892 USA.
MedImmune LLC, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-03-06
DI 10.1158/1538-7445.SABCS15-P5-03-06
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622404136
ER
PT J
AU Haraldsdottir, A
Torfadottir, JE
Valdimarsdottir, UA
Aspelund, T
Tryggvadottir, L
Launer, LJ
Harris, TB
Gudnason, V
Steingrimsdottir, L
AF Haraldsdottir, A.
Torfadottir, J. E.
Valdimarsdottir, U. A.
Aspelund, T.
Tryggvadottir, L.
Launer, L. J.
Harris, T. B.
Gudnason, V.
Steingrimsdottir, L.
TI Early life residence, fish consumption and risk of breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ Iceland, Fac Food Sci & Nutr, Unit Nutr Res, Reykjavik, Iceland.
Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Reykjavik, Iceland.
Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
Iceland Heart Assoc, Kopavogur, Iceland.
Iceland Canc Registry, Reykjavik, Iceland.
Univ Iceland, Fac Med, Reykjavik, Iceland.
US Natl Inst Aging, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P3-09-02
DI 10.1158/1538-7445.SABCS15-P3-09-02
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402385
ER
PT J
AU Holmberg, C
Bandos, H
Fagerlin, A
Bevers, TB
Battaglia, TA
Wickerham, DL
McCaskill-Stevens, W
AF Holmberg, C.
Bandos, H.
Fagerlin, A.
Bevers, T. B.
Battaglia, T. A.
Wickerham, D. L.
McCaskill-Stevens, W.
TI Results from NRG oncology/NSABP protocol DMP-1: Women's decision-making
in breast cancer risk reduction
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NSABP, Washington, DC USA.
Charite, Berlin Sch Publ Hlth, Berlin, Germany.
Univ Pittsburgh, Pittsburgh, PA 15260 USA.
Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA.
VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
Boston Med Ctr, Boston, MA USA.
Boston Univ, Sch Med, Boston, MA 02215 USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
NCI, Community Oncol & Prevent Trials Res Grp, Breast Canc Prevent, Canc Prevent Div, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P6-10-01
DI 10.1158/1538-7445.SABCS15-P6-10-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402324
ER
PT J
AU Mamounas, EP
Bandos, H
White, JR
Julian, TB
Khan, AJ
Shaitelman, SF
Torres, MA
Vicini, FA
Ganz, PA
McCloskey, SA
Paik, S
Gupta, N
Li, XA
DiCostanzo, DJ
Costantino, JP
Curran, WJ
Wolmark, N
AF Mamounas, E. P.
Bandos, H.
White, J. R.
Julian, T. B.
Khan, A. J.
Shaitelman, S. F.
Torres, M. A.
Vicini, F. A.
Ganz, P. A.
McCloskey, S. A.
Paik, S.
Gupta, N.
Li, X. A.
DiCostanzo, D. J.
Costantino, J. P.
Curran, W. J., Jr.
Wolmark, N.
TI NRG Oncology/NSABP B-51/RTOG 1304: A phase Ill clinical trial to
determine if chest wall and regional nodal radiotherapy (CWRNRT) post
mastectomy (Mx) or the addition of RNRT to breast RT post
breast-conserving surgery (BCS) will reduce invasive cancer events in
patients (pts) with positive axillary (Ax) nodes who are ypNO after
neoadjuvant chemotherapy (NC)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NSABP, NRG Oncol, Pittsburgh, PA USA.
Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA.
NRG Oncol, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
RTOG, NRG Oncol, Philadelphia, PA USA.
Ohio State Univ, Columbus, OH 43210 USA.
Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Emory Healthcare, Emory Winship Canc Inst, Atlanta, GA USA.
21st Century Oncol, Pontiac, MI USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA OT2-02-02
DI 10.1158/1538-7445.SABCS15-OT2-02-02
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622401082
ER
PT J
AU O'Sullivan, CC
Wang, Z
Zhang, Z
Umbricht, C
Jeter, SC
Rosner, GL
Stearns, V
Smith, KL
AF O'Sullivan, C. C.
Wang, Z.
Zhang, Z.
Umbricht, C.
Jeter, S. C.
Rosner, G. L.
Stearns, V.
Smith, K. L.
TI Characteristics, treatment and outcomes of breast cancer diagnosed
during pregnancy and the year after delivery
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, Bethesda, MD 20892 USA.
Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P1-07-01
DI 10.1158/1538-7445.SABCS15-P1-07-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402298
ER
PT J
AU Shaffer, CV
Cai, S
Perez, A
Risinger, AL
Du, L
O'Keefe, BR
Cichewicz, RH
Mooberry, SL
AF Shaffer, C. V.
Cai, S.
Perez, A.
Risinger, A. L.
Du, L.
O'Keefe, B. R.
Cichewicz, R. H.
Mooberry, S. L.
TI Extracts derived from fungi and plants demonstrate specificity for
subtyptes of triple negative breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
Univ Oklahoma, Nat Prod Discovery Grp, Norman, OK 73019 USA.
Univ Oklahoma, Norman, OK 73019 USA.
NCI, Ctr Canc Res, Frederick, MD USA.
NCI, Div Canc Treatment & Diag, Frederick, MD USA.
NR 4
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-04-18
DI 10.1158/1538-7445.SABCS15-P5-04-18
PG 1
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400365
ER
PT J
AU Shak, S
Petkov, VI
Miller, DP
Howlader, N
Gliner, N
Howe, W
Schussler, N
Cronin, K
Baehner, FL
Penberthy, L
AF Shak, S.
Petkov, V. I.
Miller, D. P.
Howlader, N.
Gliner, N.
Howe, W.
Schussler, N.
Cronin, K.
Baehner, F. L.
Penberthy, L.
TI Breast cancer specific survival in 38,568 patients with node negative
hormone receptor positive invasive breast cancer and oncotype DX
recurrence score results in the SEER database
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Genom Hlth Inc, Redwood City, CA USA.
NCI, Bethesda, MD 20892 USA.
IMS Inc, Calverton, MD USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-15-01
DI 10.1158/1538-7445.SABCS15-P5-15-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622403190
ER
PT J
AU Sparano, JA
Gray, RJ
Makower, DF
Pritchard, KI
Albain, KS
Hayes, DF
Geyer, CE
Dees, EC
Perez, EA
Olson, JA
Zujweski, J
Keane, MM
Moreno, HLG
Reddi, RP
Goggins, TF
Mayer, IA
Brufsky, AM
Toppmeyer, DL
Kaklamani, VG
Atkins, JN
Berenberg, JL
Sledge, GW
AF Sparano, J. A.
Gray, R. J.
Makower, D. F.
Pritchard, K. I.
Albain, K. S.
Hayes, D. F.
Geyer, C. E., Jr.
Dees, E. C.
Perez, E. A.
Olson, J. A., Jr.
Zujweski, J.
Keane, M. M.
Moreno, H. L. Gomez
Reddi, R. P.
Goggins, T. F.
Mayer, I. A.
Brufsky, A. M.
Toppmeyer, D. L.
Kaklamani, V. G.
Atkins, J. N.
Berenberg, J. L.
Sledge, G. W., Jr.
TI Prospective trial of endocrine therapy alone in patients with estrogen
receptor positive, HER2-negative, node-negative breast cancer: Results
of the TAILORx low risk registry
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Sunnybrook Res Inst, Toronto, ON, Canada.
Loyola Univ, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA.
Univ N Carolina, Chapel Hill, NC USA.
Mayo Clin, Jacksonville, FL 32224 USA.
Duke Univ, Med Ctr, Durham, NC USA.
NCI, Bethesda, MD 20892 USA.
Univ Coll Hosp, Galway, Ireland.
Oncosalud SAC, Lima, Peru.
Via Christi Reg Med Ctr, Wichita, KS USA.
Fox Valley Hematol & Oncol, Appleton, WI USA.
Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
Northwestern Univ, Chicago, IL 60611 USA.
Southeast Clin Oncol Res Consortium, Goldsboro, NC USA.
Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
Stanford Univ, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P2-08-01
DI 10.1158/1538-7445.SABCS15-P2-08-01
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622400420
ER
PT J
AU Sun, Y
Carlson, JH
Lin, X
De, PK
Williams, C
Hausman, S
Dey, N
Leyland-Jones, BR
AF Sun, Y.
Carlson, J. H.
Lin, X.
De, P. K.
Williams, C.
Hausman, S.
Dey, N.
Leyland-Jones, B. R.
TI Preclinical efficacy of targeting c-MET by ARQ197 in combination with
PARP inhibitor plus standard cytotoxic agent in triple-negative breast
cancer cell lines
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Avera Canc Inst, Sioux Falls, SD USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P3-14-08
DI 10.1158/1538-7445.SABCS15-P3-14-08
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402136
ER
PT J
AU Tang, SC
Bates, S
Kesari, S
Brenner, AJ
Anders, CK
Garcia, A
Ibrahim, NK
Tkaczuk, KHR
Kumthekar, P
AF Tang, S-C
Bates, S.
Kesari, S.
Brenner, A. J.
Anders, C. K.
Garcia, A.
Ibrahim, N. K.
Tkaczuk, K. H. R.
Kumthekar, P.
TI A phase II, open-label, multi-center study of ANG1005, a novel brain
penetrant taxane derivative, in breast cancer patients with recurrent
CNS metastases
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Georgia Regents Univ, Ctr Canc, Augusta, GA USA.
NCI, NIH, Bethesda, MD 20892 USA.
UC San Diego Moores Canc Ctr, La Jolla, CA USA.
UTHSCSA, Canc Therapy & Res Ctr, San Antonio, TX USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
Northwestern Univ, Chicago, IL 60611 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P6-17-04
DI 10.1158/1538-7445.SABCS15-P6-17-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622403250
ER
PT J
AU Thompson, MD
Grubbs, CJ
Moeinpour, F
Steele, VE
Miller, MS
Lubet, RA
AF Thompson, M. D.
Grubbs, C. J.
Moeinpour, F.
Steele, V. E.
Miller, M. S.
Lubet, R. A.
TI Metabolic profiles in female Sprague-Dawley rats receiving either a
standard (4% fat) or Western (20% fat) diet and changes in rats bearing
mammary cancers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, NIH, Rockville, MD USA.
Univ Alabama Birmingham, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P3-11-04
DI 10.1158/1538-7445.SABCS15-P3-11-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402390
ER
PT J
AU Wang, J
Figueroa, JD
Wallstrom, G
Barker, K
Park, JG
Demirkan, G
Lissowska, J
Anderson, K
Qiu, J
LaBaer, J
AF Wang, J.
Figueroa, J. D.
Wallstrom, G.
Barker, K.
Park, J. G.
Demirkan, G.
Lissowska, J.
Anderson, K.
Qiu, J.
LaBaer, J.
TI Plasma autoantibodies associated with basal-like breast cancers
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Arizona State Univ, Tempe, AR USA.
NCI, Bethesda, MD 20892 USA.
M Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P5-02-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402245
ER
PT J
AU White, AJ
Bradshaw, PT
Herring, AH
Teitelbaum, SL
Beyea, J
Stelman, SD
Steck, SE
Mordukhovich, I
Eng, SM
Engel, LS
Conway, K
Hatch, M
Neugut, AL
Santella, RM
Gammon, MD
AF White, A. J.
Bradshaw, P. T.
Herring, A. H.
Teitelbaum, S. L.
Beyea, J.
Stelman, S. D.
Steck, S. E.
Mordukhovich, I.
Eng, S. M.
Engel, L. S.
Conway, K.
Hatch, M.
Neugut, A. L.
Santella, R. M.
Gammon, M. D.
TI Exposure to multiple sources of polycyclic aromatic hydrocarbon and
breast cancer incidence
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ N Carolina, Chapel Hill, NC USA.
Ichan Sch Med Mt Sinai, New York, NY 10029 USA.
Columbia Univ, New York, NY 10027 USA.
Univ S Carolina, Columbia, SC 29208 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P6-09-08
DI 10.1158/1538-7445.SABCS15-P6-09-08
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402397
ER
PT J
AU White, AJ
Chen, J
McCullough, LE
Xu, X
Cho, YH
Conway, K
Beyea, J
Stellman, SD
Steck, SE
Mordukhovich, I
Eng, SM
Terry, MB
Engel, LS
Hatch, M
Neugut, AI
Hibshoosh, H
Santella, RM
Gammon, MD
AF White, A. J.
Chen, J.
McCullough, L. E.
Xu, X.
Cho, Y. H.
Conway, K.
Beyea, J.
Stellman, S. D.
Steck, S. E.
Mordukhovich, I.
Eng, S. M.
Terry, M. B.
Engel, L. S.
Hatch, M.
Neugut, A. I.
Hibshoosh, H.
Santella, R. M.
Gammon, M. D.
TI Sources of polycyclic aromatic hydrocarbons associated with
gene-specific promoter methylation in women with breast cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 Univ N Carolina, Chapel Hill, NC USA.
Ichan Sch Med Mt Sinai, New York, NY 10029 USA.
Univ Montana, Missoula, MT 59812 USA.
Columbia Univ, New York, NY 10027 USA.
Univ S Carolina, Columbia, SC 29208 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P1-08-04
DI 10.1158/1538-7445.SABCS15-P1-08-04
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402290
ER
PT J
AU Yang, XR
Li, J
Li, EN
Guida, JL
Li, M
Sung, H
Lu, N
Hu, N
Gierach, GL
AF Yang, X. R.
Li, J.
Li, E-N
Guida, J. L.
Li, M.
Sung, H.
Lu, N.
Hu, N.
Gierach, G. L.
TI Association between mammographic density and breast cancer subtypes
among Chinese women
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 38th Annual CTRC-AACR San Antonio Breast Cancer Symposium
CY DEC 08-12, 2015
CL San Antonio, TX
SP Canc Therapy Res Ctr, Amer Assoc Canc Res
C1 NCI, Bethesda, MD 20892 USA.
Chinese Acad Med Sci, Canc Hosp, Beijing 100730, Peoples R China.
Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China.
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
SU 4
MA P6-10-10
DI 10.1158/1538-7445.SABCS15-P6-10-10
PG 2
WC Oncology
SC Oncology
GA DL4QN
UT WOS:000375622402332
ER
PT J
AU Shears, SB
AF Shears, Stephen B.
TI Towards pharmacological intervention in inositol pyrophosphate
signalling
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE inositol phosphate; cell-signalling; drug; pharmacology; structure
ID HEXAKISPHOSPHATE KINASE 1; DRUG DISCOVERY; CELL-DEATH; DIPHOSPHOINOSITOL
PENTAKISPHOSPHATE; INSULIN SENSITIVITY; PP-INSP(5) KINASE; CHEMICAL
BIOLOGY; TELOMERE LENGTH; PYROPHOSPHORYLATION; BINDING
AB To help define the molecular basis of cellular signalling cascades, and their biological functions, there is considerable value in utilizing a high-quality chemical 'probe' that has a well-defined interaction with a specific cellular protein. Such reagents include inhibitors of protein kinases and small molecule kinases, as well as mimics or antagonists of intracellular signals. The purpose of this review is to consider recent progress and promising future directions for the development of novel molecules that can interrogate and manipulate the cellular actions of inositol pyrophosphates (PP-IPs) - a specialized, 'energetic' group of cell-signalling molecules in which multiple phosphate and diphosphate groups are crammed around a cyclohexane polyol scaffold.
C1 [Shears, Stephen B.] NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA.
RP Shears, SB (reprint author), NIEHS, Inositol Signaling Sect, Lab Signal Transduct, NIH,DHSS, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov
FU Intramural Research Program of the NIH/National Institute of
Environmental Health Sciences
FX This work was supported by the Intramural Research Program of the
NIH/National Institute of Environmental Health Sciences.
NR 76
TC 3
Z9 3
U1 5
U2 8
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0300-5127
EI 1470-8752
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD FEB 15
PY 2016
VL 44
BP 191
EP 196
DI 10.1042/BST20150184
PN 1
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ3QD
UT WOS:000374119800026
PM 26862205
ER
PT J
AU Kim, YJ
Guzman-Hernandez, ML
Wisniewski, E
Echeverria, N
Balla, T
AF Kim, Yeun Ju
Guzman-Hernandez, Maria Luisa
Wisniewski, Eva
Echeverria, Nicolas
Balla, Tamas
TI Phosphatidylinositol and phosphatidic acid transport between the ER and
plasma membrane during PLC activation requires the Nir2 protein
SO BIOCHEMICAL SOCIETY TRANSACTIONS
LA English
DT Article
DE amyotrophic lateral sclerosis; endoplasmic reticulum; lipid transfer;
phosphatidylinositol; phospholipase C
ID RETINAL-DEGENERATION-B; AMYOTROPHIC-LATERAL-SCLEROSIS; PM CONTACT SITES;
ENDOPLASMIC-RETICULUM; LIPID-TRANSFER; PHOSPHOLIPID TRANSFER;
GOLGI-COMPLEX; RDGB; HOMEOSTASIS; GENE
AB Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases. Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P-2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function. Recent studies identified the large PITP protein, Nir2 as important for PtdIns transfer from the ER to the PM. It was also found that Nir2 was required for the transfer of phosphatidic acid (PtdOH) from the PM to the ER. In Nir2-depleted cells, activation of PLC leads to PtdOH accumulation in the PM and PtdIns synthesis becomes severely impaired. In quiescent cells, Nir2 is localized to the ER via interaction of its FFAT domain with ER-bound VAMP-associated proteins VAP-A and -B. After PLC activation, Nir2 also binds to the PM via interaction of its C-terminal domains with diacylglycerol (DAG) and PtdOH. Through these interactions, Nir2 functions in ER-PM contact zones. Mutations in VAP-B that have been identified in familial forms of amyotrophic lateral sclerosis (ALS or Lou-Gehrig's disease) cause aggregation of the VAP-B protein, which then impairs its binding to several proteins, including Nir2. These findings have shed new lights on the importance of non-vesicular lipid transfer of PtdIns and PtdOH in ER-PM contact zones with a possible link to a devastating human disease.
C1 [Kim, Yeun Ju; Guzman-Hernandez, Maria Luisa; Wisniewski, Eva; Echeverria, Nicolas; Balla, Tamas] Eunice Kennedy Shriver NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Balla, T (reprint author), Eunice Kennedy Shriver NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
OI Balla, Tamas/0000-0002-9077-3335
FU intramural research program of the NICHD of the National Institutes of
Health; Hungarian American Enterprise Scholarship Fund
FX This work was supported by the intramural research program of the NICHD
of the National Institutes of Health; and the Hungarian American
Enterprise Scholarship Fund.
NR 43
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U1 2
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PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0300-5127
EI 1470-8752
J9 BIOCHEM SOC T
JI Biochem. Soc. Trans.
PD FEB 15
PY 2016
VL 44
BP 197
EP 201
DI 10.1042/BST20150187
PN 1
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DJ3QD
UT WOS:000374119800027
PM 26862206
ER
PT J
AU Walsh, SR
Moodie, Z
Fiore-Gartland, AJ
Morgan, C
Wilck, MB
Hammer, SM
Buchbinder, SP
Kalams, SA
Goepfert, PA
Mulligan, MJ
Keefer, MC
Baden, LR
Swann, EM
Grant, S
Ahmed, H
Li, F
Hertz, T
Self, SG
Friedrich, D
Frahm, N
Liao, HX
Montefiori, DC
Tomaras, GD
McElrath, MJ
Hural, J
Graham, BS
Jin, X
AF Walsh, Stephen R.
Moodie, Zoe
Fiore-Gartland, Andrew J.
Morgan, Cecilia
Wilck, Marissa B.
Hammer, Scott M.
Buchbinder, Susan P.
Kalams, Spyros A.
Goepfert, Paul A.
Mulligan, Mark J.
Keefer, Michael C.
Baden, Lindsey R.
Swann, Edith M.
Grant, Shannon
Ahmed, Hasan
Li, Fusheng
Hertz, Tomer
Self, Steven G.
Friedrich, David
Frahm, Nicole
Liao, Hua-Xin
Montefiori, David C.
Tomaras, Georgia D.
McElrath, M. Juliana
Hural, John
Graham, Barney S.
Jin, Xia
CA HVTN 083 Study Grp
NIAID HVTN
TI Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous
Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN
083
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE immunogenicity; prime-boost; HIV-1; adenovirus; vaccines; epitope
mapping; clinical trial
ID IMMUNODEFICIENCY-VIRUS TYPE-1; EFFICACY TRIAL; VIRAL LOAD; FOLLOW-UP;
VACCINES; STEP; IMMUNODOMINANCE; IMMUNITY; GAG; NEUTRALIZATION
AB Background. Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both.
Methods. A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen.
Results. T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI],.6-1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2-5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [+/- SD], 0.32 +/- 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively).
Conclusions. These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized.
C1 [Walsh, Stephen R.; Wilck, Marissa B.; Baden, Lindsey R.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
[Walsh, Stephen R.] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 3 Blackfan Cir, Boston, MA 02215 USA.
[Walsh, Stephen R.; Wilck, Marissa B.; Baden, Lindsey R.] Harvard Univ, Sch Med, Boston, MA USA.
[Moodie, Zoe; Fiore-Gartland, Andrew J.; Morgan, Cecilia; Grant, Shannon; Ahmed, Hasan; Li, Fusheng; Hertz, Tomer; Self, Steven G.; Friedrich, David; Frahm, Nicole; McElrath, M. Juliana; Hural, John] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Frahm, Nicole; McElrath, M. Juliana] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Hammer, Scott M.] Columbia Univ, New York, NY USA.
[Hammer, Scott M.] Univ Rochester, New York, NY USA.
[Buchbinder, Susan P.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Kalams, Spyros A.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Goepfert, Paul A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Mulligan, Mark J.] Emory Univ, Decatur, GA USA.
[Swann, Edith M.] NIAID, Div AIDS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Graham, Barney S.] NIAID, Dale & Betty Bumpers Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Liao, Hua-Xin; Montefiori, David C.; Tomaras, Georgia D.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA.
[Wilck, Marissa B.] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA.
[Li, Fusheng] Chinese Inst Canc & Infect Dis, Shenzhen, Peoples R China.
[Hertz, Tomer] Ben Gurion Univ Negev, Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel.
[Jin, Xia] Chinese Acad Sci, Vaccine Translat Res Unit, Inst Pasteur Shanghai, Shanghai, Peoples R China.
RP Walsh, SR (reprint author), Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, 3 Blackfan Cir, Boston, MA 02215 USA.
EM srwalsh@bidmc.harvard.edu
RI Tomaras, Georgia/J-5041-2016; Hertz, Tomer/S-5744-2016
OI Hertz, Tomer/0000-0002-0561-1578
FU National Institute of Allergy and Infectious Diseases; National Center
for Advancing Translational Sciences (US Public Health Service) [UM1
AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069452, UM1AI069418, UM1
AI069511, UM 1AI069412, UL 1RR025758, UM1 AI069470, UM1 AI069439, UL1
TR000445, UM1 AI069496]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases and the National Center for Advancing Translational
Sciences (US Public Health Service grants UM1 AI068614 [to HVTN Core
FHCRC], UM1 AI068635 [to SCHARP], UM1 AI068618 [to HVTN Laboratory
program FHCRC], UM1 AI069452 [to UAB], UM1AI069418 [to Emory], UM1
AI069511 [to Rochester], UM 1AI069412 and UL 1RR025758 [to Harvard], UM1
AI069470 [to Columbia], UM1 AI069439 and UL1 TR000445 [to Vanderbilt],
and UM1 AI069496 [to SFDPH]).
NR 45
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2016
VL 213
IS 4
BP 541
EP 550
DI 10.1093/infdis/jiv496
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XS
UT WOS:000372437700007
PM 26475930
ER
PT J
AU Markowitz, N
Davey, RT
Markowitz, N
Beigel, J
Wentworth, D
Babiker, A
Rehman, T
Dewar, R
Metcalf, J
Uyeki, TM
Finley, EB
Standridge, B
Riska, P
Lane, HC
Gordin, F
Neaton, JD
Denning, E
DuChene, A
Engen, N
Harrison, M
Quan, K
Thompson, G
Sanchez, A
Hoover, M
Natarajan, V
Holley, HP
Tierney, J
Voell, J
Baxter, J
Bigley, D
Coburn, P
Faber, L
Gardner, E
Harlow, L
Jain, M
Makohon, L
McConnell, R
Moghe, J
Nahra, R
Omotosho, B
Petersen, T
Polenakovik, H
Rizza, S
Scott, J
Shoen, A
Solorzano, C
Temesgen, Z
Whitaker, J
AF Markowitz, N.
Davey, Richard T., Jr.
Markowitz, Norman
Beigel, John
Wentworth, Deborah
Babiker, Abdel
Rehman, Tauseef
Dewar, Robin
Metcalf, Julia
Uyeki, Timothy M.
Finley, Elizabeth B.
Standridge, Barbara
Riska, Paul
Lane, H. Clifford
Gordin, Fred
Neaton, James D.
Denning, E.
DuChene, A.
Engen, N.
Harrison, M.
Quan, K.
Thompson, G.
Sanchez, Adriana
Hoover, Marie
Natarajan, Venn
Holley, H. Preston
Tierney, John
Voell, Jocelyn
Baxter, J.
Bigley, D.
Coburn, P.
Faber, L.
Gardner, E.
Harlow, L.
Jain, M.
Makohon, L.
McConnell, R.
Moghe, J.
Nahra, R.
Omotosho, B.
Petersen, T.
Polenakovik, H.
Rizza, S.
Scott, J.
Shoen, A.
Solorzano, C.
Temesgen, Z.
Whitaker, J.
CA INSIGHT FLU005 IVIG Pilot Study
TI INSIGHT FLU005: An Anti-Influenza Virus Hyperimmune Intravenous
Immunoglobulin Pilot Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE anti-influenza virus hIVIG; influenza; antibody titers; randomized trial
ID INFLUENZA A(H1N1) INFECTION; CONVALESCENT PLASMA; UNITED-STATES; A H1N1;
PROTECTION; PNEUMONIA; ANTIBODY
AB Hemagglutination inhibition (HAI) antibody responses to anti-influenza virus hyperimmune intravenous immunoglobulin (hIVIG) were characterized. Thirty-one patients with influenza during the 2013-2014 season were randomly assigned to receive 0.25 g/kg of hIVIG (n = 16) or placebo (n = 15). For hIVIG recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [CI], 2.61-6.13) for 2009 pandemic influenza A(H1N1) and 1.76 (95% CI, 1.33-2.32) for influenza A(H3N2) and influenza B. Among patients with 2009 pandemic influenza A(H1N1), ratios for hIVIG (n = 9) versus placebo (n = 8) were higher 1 hour after infusion (3.9 [95% CI, 2.3-6.7]) and sustained through day 3 (2.0 [95% CI, 1.0-4.0]). hIVIG administration significantly increases HAI titer levels among patients with influenza, supporting the need to perform a clinical outcomes study.
C1 [Markowitz, N.] Henry Ford Hosp, 2799 W Grand Blvd,CFP 306, Detroit, MI 48202 USA.
[Holley, H. Preston; Tierney, John; Voell, Jocelyn] Natl Inst Allergy & Infect Dis, Bethesda, MD USA.
RP Markowitz, N (reprint author), Henry Ford Hosp, 2799 W Grand Blvd,CFP 306, Detroit, MI 48202 USA.
FU NIAID Intramural Research Program; NIAID Division of Clinical Research
[HHSN261200800001E]
FX This work was supported by the NIAID Intramural Research Program and the
NIAID Division of Clinical Research, through a contract with the
University of Minnesota (Leidos prime contract HHSN261200800001E).
NR 14
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2016
VL 213
IS 4
BP 574
EP 578
DI 10.1093/infdis/jiv453
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XS
UT WOS:000372437700012
ER
PT J
AU Kubler, A
Larsson, C
Luna, B
Andrade, BB
Amaral, EP
Urbanowski, M
Orandle, M
Bock, K
Ammerman, NC
Cheung, LS
Winglee, K
Halushka, M
Park, JK
Sher, A
Friedland, JS
Elkington, PT
Bishai, WR
AF Kubler, Andre
Larsson, Christer
Luna, Brian
Andrade, Bruno B.
Amaral, Eduardo P.
Urbanowski, Michael
Orandle, Marlene
Bock, Kevin
Ammerman, Nicole C.
Cheung, Laurene S.
Winglee, Kathryn
Halushka, Marc
Park, Jin Kyun
Sher, Alan
Friedland, Jon S.
Elkington, Paul T.
Bishai, William R.
TI Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary
Tuberculosis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE tuberculosis; cathepsin K; rabbit; collagen; collagenolysis; RNAseq
ID MATRIX METALLOPROTEINASES; MYCOBACTERIUM-TUBERCULOSIS; RESISTANT
TUBERCULOSIS; MULTIDRUG-RESISTANT; LUNG; FIBROSIS; OSTEOCLASTS;
EXPRESSION; ODANACATIB; PATHOLOGY
AB Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).
C1 [Kubler, Andre; Friedland, Jon S.; Elkington, Paul T.] Univ London Imperial Coll Sci Technol & Med, Infect Dis & Immun, London SW7 2AZ, England.
[Elkington, Paul T.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England.
[Kubler, Andre; Luna, Brian; Urbanowski, Michael; Ammerman, Nicole C.; Cheung, Laurene S.; Winglee, Kathryn; Bishai, William R.] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA.
[Halushka, Marc] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Andrade, Bruno B.; Amaral, Eduardo P.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Orandle, Marlene; Bock, Kevin] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Larsson, Christer] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden.
[Park, Jin Kyun; Bishai, William R.] Seoul Natl Univ Hosp, Div Rheumatol, Dept Internal Med, Seoul, South Korea.
RP Bishai, WR (reprint author), Johns Hopkins Sch Med, 1550 Orleans St CRB2,Rm 108, Baltimore, MD 21287 USA.
EM wbishai@jhmi.edu
OI Luna, PhD, Brian/0000-0001-6718-4551; Halushka,
Marc/0000-0002-7112-7389; Elkington, Paul/0000-0003-0390-0613
FU Howard Hughes Medical Institute; National Institutes of Health (NIH)
[R01 AI 079590, R01 AI037856, R01 AI036973, R33 A1102239]; NIH
Intramural Research Program; Imperial College London; Swedish Research
Council; Swedish Society for Medical Research
FX This work was supported by the Howard Hughes Medical Institute (to W. R.
B.), the National Institutes of Health (NIH; R01 AI 079590, R01
AI037856, and R01 AI036973 to W. R. B. and R33 A1102239 to P. E.), the
NIH Intramural Research Program (to A. S., B. B. A., and E. P. A.),
Imperial College London (to A. K. and J. S. F.), the Swedish Research
Council (to C. L.), and the Swedish Society for Medical Research (to C.
L.).
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 15
PY 2016
VL 213
IS 4
BP 618
EP 627
DI 10.1093/infdis/jiv458
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XS
UT WOS:000372437700019
PM 26416658
ER
PT J
AU Morrison, J
Laurie, CC
Marazita, ML
Sanders, AE
Offenbacher, S
Salazar, CR
Conomos, MP
Thornton, T
Jain, D
Laurie, CA
Kerr, KF
Papanicolaou, G
Taylor, K
Kaste, LM
Beck, JD
Shaffer, JR
AF Morrison, Jean
Laurie, Cathy C.
Marazita, Mary L.
Sanders, Anne E.
Offenbacher, Steven
Salazar, Christian R.
Conomos, Matthew P.
Thornton, Timothy
Jain, Deepti
Laurie, Cecelia A.
Kerr, Kathleen F.
Papanicolaou, George
Taylor, Kent
Kaste, Linda M.
Beck, James D.
Shaffer, John R.
TI Genome-wide association study of dental caries in the Hispanic
Communities Health Study/Study of Latinos (HCHS/SOL)
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SMOOTH-SURFACE CARIES; PIT-AND-FISSURE; PERMANENT DENTITION; TOOTH GERM;
SCAN; PREVALENCE; INFERENCE; VISFATIN; PATTERNS; DISORDER
AB Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18-74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20-53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 x 10(-10)), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 x 10(-8)) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata.
C1 [Morrison, Jean; Laurie, Cathy C.; Conomos, Matthew P.; Thornton, Timothy; Jain, Deepti; Laurie, Cecelia A.; Kerr, Kathleen F.] Univ Washington, Dept Biostat, Seattle, WA 98077 USA.
[Marazita, Mary L.; Shaffer, John R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, 130 De Soto St, Pittsburgh, PA 15261 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial & Dent Genet, Pittsburgh, PA 15261 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Clin & Translat Sci Inst, Pittsburgh, PA 15261 USA.
[Sanders, Anne E.; Beck, James D.] Univ N Carolina, Sch Dent, Dept Dent Ecol, Ctr Oral & System Dis, Chapel Hill, NC 27599 USA.
[Offenbacher, Steven] Univ N Carolina, Sch Dent, Dept Periodontol, Ctr Oral & Syst Dis, Chapel Hill, NC 27599 USA.
[Salazar, Christian R.] Albert Einstein Coll Med, Dept Epidemiol, New York, NY 10461 USA.
[Salazar, Christian R.] Albert Einstein Coll Med, Dept Populat Hlth, New York, NY 10461 USA.
Montefiore Med Ctr, New York, NY 10461 USA.
[Papanicolaou, George] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Taylor, Kent] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Kaste, Linda M.] Univ Illinois, Coll Dent, Chicago, IL 60162 USA.
[Kaste, Linda M.] Univ Illinois, Sch Publ Hlth, Chicago, IL 60162 USA.
RP Shaffer, JR (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, 130 De Soto St, Pittsburgh, PA 15261 USA.
EM john.r.shaffer@pitt.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233,
N01-HC65234, N01-HC65235, N01-HC65236, N01-HC65237]; NHLBI; NIDCR
[HHSN268201300005C AM03, MOD03]
FX The baseline examination of the Hispanic Community Health Study/Study of
Latinos was carried out as a collaborative study supported by contracts
from the National Heart, Lung, and Blood Institute (NHLBI) to the
University of North Carolina (N01-HC65233), University of Miami
(N01-HC65234), Albert Einstein College of Medicine (N01-HC65235),
Northwestern University (N01-HC65236) and San Diego State University
(N01-HC65237). The following Institutes/Centers/Offices contribute to
the HCHS/SOL through a transfer of funds to the NHLBI: National
Institute on Minority Health and Health Disparities, National Institute
on Deafness and Other Communication Disorders, National Institute of
Dental and Craniofacial Research, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institute of Neurological
Disorders and Stroke, NIH Institution-Office of Dietary Supplements. The
Genetic Analysis Center at the University of Washington was supported by
NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03).
Investigators website: http://www.cscc.unc.edu/hchs/
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD FEB 15
PY 2016
VL 25
IS 4
BP 807
EP 816
DI 10.1093/hmg/ddv506
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DG5WS
UT WOS:000372151000016
PM 26662797
ER
PT J
AU Capitani, G
Duarte, JM
Baskaran, K
Bliven, S
Somody, JC
AF Capitani, Guido
Duarte, Jose M.
Baskaran, Kumaran
Bliven, Spencer
Somody, Joseph C.
TI Understanding the fabric of protein crystals: computational
classification of biological interfaces and crystal contacts
SO BIOINFORMATICS
LA English
DT Review
ID PLANT GLUTAMATE-DECARBOXYLASE; QUATERNARY STRUCTURE; PACKING CONTACTS;
CORRELATED MUTATIONS; CYTOSOLIC SULFOTRANSFERASES; EVOLUTIONARY
CONSERVATION; SHAPE COMPLEMENTARITY; HOMOLOGOUS PROTEINS; DOCKING
SOLUTIONS; STRUCTURAL BASIS
AB Modern structural biology still draws the vast majority of information from crystallography, a technique where the objects being investigated are embedded in a crystal lattice. Given the complexity and variety of those objects, it becomes fundamental to computationally assess which of the interfaces in the lattice are biologically relevant and which are simply crystal contacts. Since the mid-1990s, several approaches have been applied to obtain high-accuracy classification of crystal contacts and biological protein-protein interfaces. This review provides an overview of the concepts and main approaches to protein interface classification: thermodynamic estimation of interface stability, evolutionary approaches based on conservation of interface residues, and co-occurrence of the interface across different crystal forms. Among the three categories, evolutionary approaches offer the strongest promise for improvement, thanks to the incessant growth in sequence knowledge. Importantly, protein interface classification algorithms can also be used on multimeric structures obtained using other high-resolution techniques or for protein assembly design or validation purposes. A key issue linked to protein interface classification is the identification of the biological assembly of a crystal structure and the analysis of its symmetry. Here, we highlight the most important concepts and problems to be overcome in assembly prediction. Over the next few years, tools and concepts of interface classification will probably become more frequently used and integrated in several areas of structural biology and structural bioinformatics. Among the main challenges for the future are better addressing of weak interfaces and the application of interface classification concepts to prediction problems like protein-protein docking.
C1 [Capitani, Guido; Duarte, Jose M.; Baskaran, Kumaran; Bliven, Spencer; Somody, Joseph C.] Paul Scherrer Inst, Lab Biomol Res, OFLC 110, CH-5232 Villigen, Switzerland.
[Capitani, Guido; Duarte, Jose M.] ETH, Dept Biol, CH-8093 Zurich, Switzerland.
[Bliven, Spencer] Univ Calif San Diego, Bioinformat & Syst Biol Program, La Jolla, CA 92093 USA.
[Bliven, Spencer] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Somody, Joseph C.] ETH, Dept Comp Sci, CH-8092 Zurich, Switzerland.
RP Capitani, G (reprint author), Paul Scherrer Inst, Lab Biomol Res, OFLC 110, CH-5232 Villigen, Switzerland.; Capitani, G (reprint author), ETH, Dept Biol, CH-8093 Zurich, Switzerland.
EM guido.capitani@psi.ch
OI Somody, Joseph C./0000-0002-3513-3765; Duarte, Jose
Manuel/0000-0002-9544-5621; Bliven, Spencer/0000-0002-1200-1698
FU Swiss National Science Foundation [31003A_140879]; Research Committee of
the Paul Scherrer Institute [FK-05.08.1, FK-04.09.1]; Intramural
Research Program of the National Center for Biotechnology Information,
National Library of Medicine, National Institutes of Health
FX Financial support to G.C. from the Swiss National Science Foundation
(grant 31003A_140879) and the Research Committee of the Paul Scherrer
Institute (grants FK-05.08.1, FK-04.09.1) is gratefully acknowledged, as
is IT support from SyBIT/SIS. This research was supported in part by the
Intramural Research Program of the National Center for Biotechnology
Information, National Library of Medicine, National Institutes of Health
(support to S.B.).
NR 96
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U1 2
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD FEB 15
PY 2016
VL 32
IS 4
BP 481
EP 489
DI 10.1093/bioinformatics/btv622
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DF9PO
UT WOS:000371693700001
PM 26508758
ER
PT J
AU Chen, MH
Yang, Q
AF Chen, Ming-Huei
Yang, Qiong
TI RVFam: an R package for rare variant association analysis with family
data
SO BIOINFORMATICS
LA English
DT Article
ID GENERAL PEDIGREES
AB Family-based designs offer unique advantage for identifying rare risk variants in genetic association studies. There are existing tools for analyzing rare variants in families but lacking components to handle binary traits properly and survival traits. In this report, we introduce an R software package RVFam (Rare Variant association analysis with Family data) designed to analyze continuous, binary and survival traits against rare and common sequencing variants in genome-wide association studies (GWAS) involving family data. Single and multiple variant association tests were implemented while accounting for arbitrary family structures. Extensive simulation studies were performed to evaluate all the approaches implemented in RVFam.
C1 [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Chen, Ming-Huei; Yang, Qiong] NHLBI, Framingham Heart Study, Populat Sci Branch, Div Intramural Res,NIH, Framingham, MA 01702 USA.
RP Yang, Q (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
EM qyang@bu.edu
FU National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute (NHLBI)'s Framingham Heart Study [N01 HC25195, N01
HHSN-268201500001]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center
FX This work was partially supported by the National Institutes of Health
(NIH)/National Heart, Lung, and Blood Institute (NHLBI)'s Framingham
Heart Study contract (N01 HC25195 and N01 HHSN-268201500001). A portion
of this research utilized the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center.
NR 8
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U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD FEB 15
PY 2016
VL 32
IS 4
BP 624
EP 626
DI 10.1093/bioinformatics/btv609
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DF9PO
UT WOS:000371693700027
PM 26508760
ER
PT J
AU Barr, RG
Aviles-Santa, L
Davis, SM
Aldrich, TK
Gonzalez, F
Henderson, AG
Kaplan, RC
LaVange, L
Liu, K
Loredo, JS
Mendes, ES
Ni, A
Ries, A
Salathe, M
Smith, LJ
AF Barr, R. Graham
Aviles-Santa, Larissa
Davis, Sonia M.
Aldrich, Tom K.
Gonzalez, Franklyn, II
Henderson, Ashley G.
Kaplan, Robert C.
LaVange, Lisa
Liu, Kiang
Loredo, Jose S.
Mendes, Eliana S.
Ni, Ai
Ries, Andrew
Salathe, Matthias
Smith, Lewis J.
TI Pulmonary Disease and Age at Immigration among Hispanics Results from
the Hispanic Community Health Study/Study of Latinos
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE asthma; chronic obstructive pulmonary disease; race/ethnicity; social
determinants of health
ID EXAMINATION SURVEY NHANES; PUERTO-RICAN CHILDREN; NATIONAL-HEALTH;
UNITED-STATES; LUNG-FUNCTION; ASTHMA PREVALENCE; CHILDHOOD ASTHMA; GALA
II; REFERENCE VALUES; US POPULATION
AB Rationale: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking.
Objectives: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether-chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States.
Methods: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation.
Measurements and Main Results: The prevalence of physician diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking andprior asthma (P = 0.22), by country of birth, or by age at immigration.
Conclusions: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.
C1 [Barr, R. Graham] Columbia Univ, Dept Med, Med Ctr, 630 West 168th St,PH 9 East,Room 105, New York, NY USA.
[Barr, R. Graham] Columbia Univ, Med Ctr, Dept Epidemiol, 630 West 168th St,PH 9 East,Room 105, New York, NY 10032 USA.
[Aviles-Santa, Larissa] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Davis, Sonia M.; Gonzalez, Franklyn, II; LaVange, Lisa; Ni, Ai] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Henderson, Ashley G.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Aldrich, Tom K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA.
[Liu, Kiang] Northwestern Univ, Dept Preventat Med, Chicago, IL 60611 USA.
[Smith, Lewis J.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Loredo, Jose S.; Ries, Andrew] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Mendes, Eliana S.; Salathe, Matthias] Univ Miami, Dept Med, Miami, FL USA.
RP Barr, RG (reprint author), Columbia Univ, Dept Med, Med Ctr, 630 West 168th St,PH 9 East,Room 105, New York, NY USA.; Barr, RG (reprint author), Columbia Univ, Med Ctr, Dept Epidemiol, 630 West 168th St,PH 9 East,Room 105, New York, NY 10032 USA.
EM rgb9@columbia.edu
OI Salathe, Matthias/0000-0001-9092-4861
FU NHLBI [N01-HC65233, R01-HL077612, RC1-HL100543, R01-HL083091,
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168,
N01-HC-95169]; University of Miami [N01-HC65234]; Albert Einstein
College of Medicine [N01-HC65235]; Northwestern University
[N01-HC65236]; San Diego State University [N01-HC65237]; National Center
on Minority Health and Health Disparities; National Institute on
Deafness and Other Communication Disorders; National Institute of Dental
and Craniofacial Research; National Institute of Diabetes and Digestive
and Kidney Diseases; National Institute of Neurological Disorders and
Stroke; Office of Dietary Supplements; National Center for Research
Resources [UL1-TR-000040, UL1-TR-001079]
FX The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) was
performed as a collaborative study supported by contracts from the NHLBI
to the University of North Carolina (N01-HC65233), the University of
Miami (N01-HC65234), the Albert Einstein College of Medicine
(N01-HC65235), Northwestern University (N01-HC65236), and San Diego
State University (N01-HC65237). The following institutes, centers, or
offices contribute to the HCHS/SOL through a transfer of funds to the
NHLBI: the National Center on Minority Health and Health Disparities,
the National Institute on Deafness and Other Communication Disorders,
the National Institute of Dental and Craniofacial Research, the National
Institute of Diabetes and Digestive and Kidney Diseases, the National
Institute of Neurological Disorders and Stroke, and the Office of
Dietary Supplements. MESA (Multi-Ethnic Study of Atherosclerosis) and
the MESA Lung Study were supported by NHLBI grants R01-HL077612,
RC1-HL100543, and R01-HL083091 and contracts N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. They were
also supported by National Center for Research Resources grants
UL1-TR-000040 and UL1-TR-001079. The funding agency had a role in the
design and conduct of the study; in the collection, analysis, and
interpretation of the data; and in the review and approval of the
manuscript.
NR 50
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U1 1
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PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD FEB 15
PY 2016
VL 193
IS 4
BP 386
EP 395
DI 10.1164/rccm.201506-1211OC
PG 10
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DE1MW
UT WOS:000370392100011
PM 26451874
ER
PT J
AU Srivastava, AK
Jaganathan, S
Stephen, L
Hollingshead, MG
Layhee, A
Damour, E
Govindharajulu, JP
Donohue, J
Esposito, D
Mapes, JP
Kinders, RJ
Takebe, N
Tomaszewski, JE
Kummar, S
Doroshow, JH
Parchment, RE
AF Srivastava, Apurva K.
Jaganathan, Soumya
Stephen, Laurie
Hollingshead, Melinda G.
Layhee, Adam
Damour, Eric
Govindharajulu, Jeevan Prasaad
Donohue, Jennifer
Esposito, Dominic
Mapes, James P.
Kinders, Robert J.
Takebe, Naoko
Tomaszewski, Joseph E.
Kummar, Shivaani
Doroshow, James H.
Parchment, Ralph E.
TI Effect of a Smac Mimetic (TL32711, Birinapant) on the Apoptotic Program
and Apoptosis Biomarkers Examined with Validated Multiplex Immunoassays
Fit for Clinical Use
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID BCL-2 PROTEIN FAMILY; CELL-DEATH; BREAST-CANCER; XENOGRAFTS; MODULATION;
GENERATION; INHIBITOR; MECHANISM; PATHWAYS; LEUKEMIA
AB Purpose: To support clinical pharmacodynamic evaluation of the Smac mimetic TL32711 (birinapant) and other apoptosistargeting drugs, we describe the development, validation, and application of novel immunoassays for 15 cytosolic and membrane-associated proteins indicative of the induction, onset, and commitment to apoptosis in human tumors.
Experimental Design: The multiplex immunoassays were constructed on the Luminex platform with apoptosis biomarkers grouped into three panels. Panel 1 contains Bak, Bax, total caspase-3, total lamin-B (intact and 45 kDa fragment), and Smac; panel 2 contains Bad, Bax-Bcl-2 heterodimer, Bcl-xL, Bim, and Mcl1; and panel 3 contains active (cleaved) caspase-3, Bcl-xL-Bak heterodimer, Mcl1-Bak heterodimer, pS99-Bad, and survivin. Antibody specificity was confirmed by immunoprecipitation and Western blot analysis.
Results: Two laboratories analytically validated the multiplex immunoassays for application with core-needle biopsy samples processed to control preanalytical variables; the biologic variability for each biomarker was estimated from xenograft measurements. Studies of TL32711 in xenograft models confirmed a dose-dependent increase in activated caspase-3 6 hours after dosing and provided assay fit-for-purpose confirmation. Coincident changes in cytosolic lamin-B and subsequent changes in Bcl-xL provided correlative evidence of caspase-3 activation. The validated assay is suitable for use with clinical specimens; 14 of 15 biomarkers were quantifiable in patient core-needle biopsies.
Conclusions: The validated multiplex immunoassays developed for this study provided proof of mechanism data for TL32711 and are suitable for quantifying apoptotic biomarkers in clinical trials. (C) 2015 AACR.
C1 [Srivastava, Apurva K.; Jaganathan, Soumya; Govindharajulu, Jeevan Prasaad; Kinders, Robert J.; Parchment, Ralph E.] Leidos Biomed Res Inc, Lab Human Toxicol & Pharmacol, Appl Dev Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Stephen, Laurie; Layhee, Adam; Damour, Eric; Donohue, Jennifer; Mapes, James P.] Myriad RBM, Austin, TX USA.
[Hollingshead, Melinda G.] Frederick Natl Lab Canc Res, Biol Testing Branch, Dev Therapeut Program, Frederick, MD USA.
[Esposito, Dominic] Leidos Biomed Res Inc, Prot Express Lab, Canc Res Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Takebe, Naoko] NCI, Invest Drug Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Tomaszewski, Joseph E.; Kummar, Shivaani; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Srivastava, AK (reprint author), Frederick Natl Lab Canc Res, 1050 Boyles St, Frederick, MD 21702 USA.
EM srivastavaa4@mail.nih.gov
FU NCI; NIH [HHSN261200800001E]; American Recovery and Reinvestment Act
funds
FX This project has been funded in whole or in part with federal funds from
the NCI, NIH, under Contract No. HHSN261200800001E, including a
subcontract with Myriad RBM. This research was supported (in part) by
American Recovery and Reinvestment Act funds.
NR 36
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U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD FEB 15
PY 2016
VL 22
IS 4
BP 1000
EP 1010
DI 10.1158/1078-0432.CCR-14-3156
PG 11
WC Oncology
SC Oncology
GA DD7TY
UT WOS:000370128500025
PM 26446940
ER
PT J
AU Cegielski, JP
Kurbatova, E
van der Walt, M
Brand, J
Ershova, J
Tupasi, T
Caoili, JC
Dalton, T
Contreras, C
Yagui, M
Bayona, J
Kvasnovsky, C
Leimane, V
Kuksa, L
Chen, MP
Via, LE
Hwang, SH
Wolfgang, M
Volchenkov, GV
Somova, T
Smith, SE
Akksilp, S
Wattanaamornkiet, W
Kim, HJ
Kim, CK
Kazennyy, BY
Khorosheva, T
Kliiman, K
Viiklepp, P
Jou, R
Huang, ASE
Vasilyeva, IA
Demikhova, OV
AF Cegielski, J. Peter
Kurbatova, Ekaterina
van der Walt, Martie
Brand, Jeannette
Ershova, Julia
Tupasi, Thelma
Caoili, Janice Campos
Dalton, Tracy
Contreras, Carmen
Yagui, Martin
Bayona, Jaime
Kvasnovsky, Charlotte
Leimane, Vaira
Kuksa, Liga
Chen, Michael P.
Via, Laura E.
Hwang, Soo Hee
Wolfgang, Melanie
Volchenkov, Grigory V.
Somova, Tatiana
Smith, Sarah E.
Akksilp, Somsak
Wattanaamornkiet, Wanpen
Kim, Hee Jin
Kim, Chang-Ki
Kazennyy, Boris Y.
Khorosheva, Tatiana
Kliiman, Kai
Viiklepp, Piret
Jou, Ruwen
Huang, Angela Song-En
Vasilyeva, Irina A.
Demikhova, Olga V.
CA Global PETTS Investigators
TI Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to
Treatment and Initial Versus Acquired Second-Line Drug Resistance
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE multidrug-resistant tuberculosis; extensively drug-resistant
tuberculosis; second-line drugs; treatment outcome; acquired drug
resistance
ID MYCOBACTERIUM-TUBERCULOSIS; AGGRESSIVE REGIMENS; UNITED-STATES
AB Background. Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.
Methods. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.
Results. Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P<.001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from <= 1 to >= 5 (P<.001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P<.001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval,.56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.
Conclusions. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.
C1 [Cegielski, J. Peter; Kurbatova, Ekaterina; Ershova, Julia; Dalton, Tracy; Kvasnovsky, Charlotte; Chen, Michael P.; Wolfgang, Melanie] US Ctr Dis Control & Prevent, Atlanta, GA USA.
[van der Walt, Martie; Via, Laura E.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[van der Walt, Martie; Brand, Jeannette] MRC, Pretoria, South Africa.
[Tupasi, Thelma; Caoili, Janice Campos] Trop Dis Fdn, Manila, Philippines.
[Contreras, Carmen; Bayona, Jaime] Socios Salud Sucursal, Lima, Peru.
[Yagui, Martin] Natl Inst Hlth, Lima, Peru.
[Leimane, Vaira; Kuksa, Liga] Riga East Univ Hosp, Ctr TB & Lung Dis, Riga, Latvia.
[Hwang, Soo Hee] Natl Masan Hosp, Chang Won, South Korea.
[Kim, Hee Jin; Kim, Chang-Ki] Korean Inst TB, Seoul, South Korea.
[Volchenkov, Grigory V.; Somova, Tatiana] Vladimir Oblast TB Dispensary, Moscow, Russia.
[Kazennyy, Boris Y.; Khorosheva, Tatiana] Orel Oblast TB Dispensary, Moscow, Russia.
[Vasilyeva, Irina A.; Demikhova, Olga V.] Russian Acad Med Sci, Cent TB Res Inst, Moscow, Russia.
[Akksilp, Somsak] Minist Hlth, Bangkok, Thailand.
[Wattanaamornkiet, Wanpen] Office Dis Prevent & Control Reg 7, Ubon Ratchathani, Thailand.
[Kliiman, Kai] Tartu Univ Hosp, Tallinn, Estonia.
[Viiklepp, Piret] Natl Inst Hlth Dev, Natl TB Registry, Tallinn, Estonia.
[Jou, Ruwen; Huang, Angela Song-En] Taiwan Ctr Dis Control, Taipei, Taiwan.
RP Cegielski, JP (reprint author), Ctr Dis Control & Prevent, Global TB Branch, Div Global HIV & TB, Mail Stop E 04,1600 Clifton Rd,NE, Atlanta, GA 30329 USA.
EM pcegielski@cdc.gov
FU US Agency for International Development; CDC; US National Institute of
Allergy and Infectious Diseases Division of Intramural Research
FX This work was supported by the US Agency for International Development,
the CDC, and, for one of the South Korean sites, by the US National
Institute of Allergy and Infectious Diseases Division of Intramural
Research.
NR 23
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U1 3
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 15
PY 2016
VL 62
IS 4
BP 418
EP 430
DI 10.1093/cid/civ910
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DD9VX
UT WOS:000370274900007
PM 26508515
ER
PT J
AU Kattakuzhy, S
Wilson, E
Sidharthan, S
Sims, Z
McLaughlin, M
Price, A
Silk, R
Gross, C
Akoth, E
McManus, M
Emmanuel, B
Shrivastava, S
Tang, L
Nelson, A
Teferi, G
Chavez, J
Lam, B
Mo, H
Osinusi, A
Polis, MA
Masur, H
Kohli, A
Kottilil, S
AF Kattakuzhy, Sarah
Wilson, Eleanor
Sidharthan, Sreetha
Sims, Zayani
McLaughlin, Mary
Price, Angie
Silk, Rachel
Gross, Chloe
Akoth, Elizabeth
McManus, Maryellen
Emmanuel, Benjamin
Shrivastava, Shikha
Tang, Lydia
Nelson, Amy
Teferi, Gebeyehu
Chavez, Jose
Lam, Brian
Mo, Hongmei
Osinusi, Anuoluwapo
Polis, Michael A.
Masur, Henry
Kohli, Anita
Kottilil, Shyamasundaran
TI Moderate Sustained Virologic Response Rates With 6-Week Combination
Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced
Liver Disease
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE hepatitis C; advanced fibrosis; short-duration
ID GENOTYPE 1 INFECTION; PLUS RIBAVIRIN; CHRONIC HCV; SOFOSBUVIR;
LEDIPASVIR; CIRRHOSIS; ABT-450/R-OMBITASVIR; DASABUVIR; TRIAL; DRUG
AB Background. Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis.
Methods. Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged >= 18 years, had chronic HCV genotype 1 infection (serum HCV RNA >= 2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay.
Results. Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P=.51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen.
Conclusions. Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy.
C1 [Kattakuzhy, Sarah; Wilson, Eleanor; Price, Angie; Silk, Rachel; Gross, Chloe; Akoth, Elizabeth; Emmanuel, Benjamin; Shrivastava, Shikha; Tang, Lydia; Nelson, Amy; Kottilil, Shyamasundaran] Univ Maryland, Div Clin Care & Res, Inst Human Virol, Baltimore, MD 21201 USA.
[Sidharthan, Sreetha; Sims, Zayani; Masur, Henry] NIAID, Dept Crit Care Med, NIH Clin Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[McLaughlin, Mary] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Polis, Michael A.] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[McManus, Maryellen] ParkerTide, Washington, DC USA.
[Teferi, Gebeyehu; Chavez, Jose] Unity Hlth Care, Washington, DC USA.
[Lam, Brian] INOVA Fairfax Hosp, Dept Hepatol, Fairfax, VA USA.
[Mo, Hongmei; Osinusi, Anuoluwapo] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
[Kohli, Anita] Creighton Univ, St Josephs Hosp, Dept Hepatol, Phoenix, AZ USA.
[Kohli, Anita] Creighton Univ, Med Ctr, Phoenix, AZ USA.
RP Kottilil, S (reprint author), Univ Maryland, Sch Med, Div Clin Care & Res, Inst Human Virol, Rm S222,725 W Lombard St, Baltimore, MD 21201 USA.
EM skottilil@ihv.umaryland.edu
OI Wilson, Eleanor/0000-0002-4855-514X
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; NIAID; German Research Foundation; clinical
research unit KFO 129; NIH; Gilead Sciences
FX This project has been funded in whole or in part with funds from the
National Cancer Institute, National Institutes of Health (NIH) (contract
HHSN261200800001E) and the NIAID. It was also supported in part by the
German Research Foundation and by the clinical research unit KFO 129.
Study medications were provided by Gilead Sciences, and the study was
partially funded by a collaborative research and development agreement
between NIH and Gilead Sciences.
NR 21
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 15
PY 2016
VL 62
IS 4
BP 440
EP 447
DI 10.1093/cid/civ897
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DD9VX
UT WOS:000370274900010
PM 26503379
ER
PT J
AU Ferrari, LL
Agostinelli, LJ
Krashes, MJ
Lowell, BB
Scammell, TE
Arrigoni, E
AF Ferrari, L. L.
Agostinelli, L. J.
Krashes, M. J.
Lowell, B. B.
Scammell, T. E.
Arrigoni, E.
TI Dynorphin inhibits basal forebrain cholinergic neurons by pre- and
postsynaptic mechanisms
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID RECEPTOR MESSENGER-RNA; KAPPA-OPIOID RECEPTOR; IN-SITU HYBRIDIZATION;
CORTICAL ACETYLCHOLINE-RELEASE; OREXIN/HYPOCRETIN NEURONS;
NOCICEPTIN/ORPHANIN FQ; HYPOCRETIN NEURONS; PARADOXICAL SLEEP; GLUTAMATE
RELEASE; LOCUS-COERULEUS
AB The basal forebrain (BF) is an essential component of the ascending arousal systems and may be a key site through which the orexin (also known as hypocretin) neurons drive arousal and promote the maintenance of normal wakefulness. All orexin neurons also make dynorphin, and nearly all brain regions innervated by the orexin neurons express kappa opiate receptors, the main receptor for dynorphin. This is remarkable because orexin excites target neurons including BF neurons, but dynorphin has inhibitory effects. We identified the sources of dynorphin input to the magnocellular preoptic nucleus and substantia innominata (MCPO/SI) in mice and determined the effects of dynorphin-A on MCPO/SI cholinergic neurons using patch-clamp recordings in brain slices. We found that the orexin neurons are the main source of dynorphin input to the MCPO/SI region, and dynorphin-A inhibits MCPO/SI cholinergic neurons through -opioid receptors by (1) activation of a G protein-coupled inwardly rectifying potassium current, (2) inhibition of a voltage-gated Ca2+ current and (3) presynaptic depression of the glutamatergic input to these neurons. The responses both to dynorphin-A and to orexin-A desensitize, but co-application of dynorphin-A and orexin-A produces a sustained response. In addition, the polarity of the response to the co-application depends on the membrane potential of BF neurons; at -40mV the net effect of the co-application is inhibition by dynorphin-A, whereas at -70mV the excitatory response to orexin-A prevails. This suggests that depending on their state of activation, BF cholinergic neurons can be excited or inhibited by signals from the orexin neurons.
C1 [Ferrari, L. L.; Agostinelli, L. J.; Scammell, T. E.; Arrigoni, E.] Beth Israel Deaconess Med Ctr, Dept Neurol, 3 Blackfan Circle,Ctr Life Sci Rm 713, Boston, MA 02215 USA.
[Krashes, M. J.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Lowell, B. B.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Arrigoni, E (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 3 Blackfan Circle,Ctr Life Sci Rm 713, Boston, MA 02215 USA.
EM earrigon@bidmc.harvard.edu
FU NIH [RO1NS061863]; Administrative Supplement Utilizing Recovery Act
Funds [RO1NS061863, R21NS082854, P01HL095491, R01NS091126]
FX This study was supported by NIH grants: RO1NS061863, the Administrative
Supplement Utilizing Recovery Act Funds RO1NS061863, R21NS082854,
P01HL095491 and R01NS091126.
NR 57
TC 1
Z9 1
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
EI 1469-7793
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD FEB 15
PY 2016
VL 594
IS 4
BP 1069
EP 1085
DI 10.1113/JP271657
PG 17
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA DE4ZT
UT WOS:000370640300018
PM 26613645
ER
PT J
AU Xiao, L
Rao, JN
Cao, S
Liu, L
Chung, HK
Zhang, Y
Zhang, J
Liu, YL
Gorospe, M
Wang, JY
AF Xiao, Lan
Rao, Jaladanki N.
Cao, Shan
Liu, Lan
Chung, Hee Kyoung
Zhang, Yun
Zhang, Jennifer
Liu, Yulan
Gorospe, Myriam
Wang, Jian-Ying
TI Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier
function by modulating the expression levels of tight junction proteins
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID MESSENGER-RNA; COMPETITIVE-BINDING; HUMAN-DISEASE; CANCER CELLS; HUR;
TRANSLATION; STABILITY; MICRORNAS; PROLIFERATION; PERMEABILITY
AB Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation. In contrast, increasing the levels of SPRY4-IT1 in the intestinal mucosa protected the gut barrier in mice exposed to septic stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted with TJ mRNAs, and this process was enhanced through the association with the RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These findings highlight a novel role for SPRY4-IT1 in controlling the intestinal epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ expression by altering the stability and translation of TJ mRNAs.
C1 [Xiao, Lan; Rao, Jaladanki N.; Liu, Lan; Chung, Hee Kyoung; Zhang, Yun; Zhang, Jennifer; Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.
[Wang, Jian-Ying] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Xiao, Lan; Rao, Jaladanki N.; Liu, Lan; Chung, Hee Kyoung; Zhang, Yun; Zhang, Jennifer; Wang, Jian-Ying] Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
[Cao, Shan; Liu, Yulan] Peking Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100044, Peoples R China.
[Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Surg, Cell Biol Grp, Baltimore, MD 21201 USA.; Wang, JY (reprint author), Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.; Wang, JY (reprint author), Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA.
EM jwang@smail.umaryland.edu
FU U.S. Department of Veterans Affairs; National Institutes of Health
[DK57819, DK61972, DK68491]; National Institute on Aging-Intramural
Research Program, National Institutes of Health
FX This work is supported by Merit Review Awards (to J.Y.W. and J.N.R.)
from the U.S. Department of Veterans Affairs, grants from the National
Institutes of Health (DK57819, DK61972, and DK68491 to J.Y.W.), and
funding from the National Institute on Aging-Intramural Research
Program, National Institutes of Health (to M.G.). J.Y.W. is a Senior
Research Career Scientist, Biomedical Laboratory Research and
Development Service, U.S. Department of Veterans Affairs.
NR 55
TC 5
Z9 5
U1 0
U2 7
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD FEB 15
PY 2016
VL 27
IS 4
BP 617
EP 626
DI 10.1091/mbc.E15-10-0703
PG 10
WC Cell Biology
SC Cell Biology
GA DD5KL
UT WOS:000369962500003
PM 26680741
ER
PT J
AU Shao, Q
Fallica, J
Casin, KM
Murphy, E
Steenbergen, C
Kohr, MJ
AF Shao, Qin
Fallica, Jonathan
Casin, Kevin M.
Murphy, Elizabeth
Steenbergen, Charles
Kohr, Mark J.
TI Characterization of the sex-dependent myocardial S-nitrosothiol proteome
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE sex differences; ischemia-reperfusion injury; cardioprotection;
S-nitrosylation; endothelial nitric oxide synthase; S-nitrosoglutathione
reductase
ID ISCHEMIA-REPERFUSION INJURY; ESTROGEN-RECEPTOR-BETA; RAT CARDIAC
MYOCYTES; NITRIC-OXIDE; GENDER-DIFFERENCES; INFARCT SIZE;
ISCHEMIA/REPERFUSION INJURY; INTRACELLULAR CA2+; HEART-DISEASE; RABBIT
HEART
AB Premenopausal women exhibit endogenous cardioprotective signaling mechanisms that are thought to result from the beneficial effects of estrogen, which we have shown to increase protein S-nitrosylation in the heart. S-nitrosylation is a labile protein modification that increases with a number of different forms of cardioprotection, including ischemic preconditioning. Herein, we sought to identify a potential role for protein S-nitrosylation in sex-dependent cardioprotection. We utilized a Langen-dorff-perfused mouse heart model of ischemia-reperfusion injury with male and female hearts, and S-nitrosylation-resin-assisted capture with liquid chromatography tandem mass spectrometry to identify S-nitrosylated proteins and modification sites. Consistent with previous studies, female hearts exhibited resilience to injury with a significant increase in functional recovery compared with male hearts. In a separate set of hearts, we identified a total of 177 S-nitrosylated proteins in female hearts at baseline compared with 109 S-nitrosylated proteins in male hearts. Unique S-nitrosylated proteins in the female group included the F1FO-ATPase and cyclophilin D. We also utilized label-free peptide analysis to quantify levels of common S-nitrosylated identifications and noted that the S-nitrosylation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2a was nearly 70% lower in male hearts compared with female, with no difference in expression. Furthermore, we found a significant increase in endothelial nitric oxide synthase expression, phosphorylation, and total nitric oxide production in female hearts compared with males, likely accounting for the enhanced S-nitrosylation protein levels in female hearts. In conclusion, we identified a number of novel S-nitrosylated proteins in female hearts that are likely to contribute to sex-dependent cardioprotection.
C1 [Shao, Qin] Shandong Jiaotong Univ, Sch Med, Renji Hosp, Dept Cardiol, Shanghai, Peoples R China.
[Shao, Qin; Steenbergen, Charles; Kohr, Mark J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Fallica, Jonathan; Casin, Kevin M.; Kohr, Mark J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Murphy, Elizabeth] Natl Heart Lung & Blood Inst, Syst Biol Ctr, Bethesda, MD USA.
RP Kohr, MJ (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Rm E7616, Baltimore, MD 21205 USA.
EM mkohr1@jhu.edu
FU National Natural Science Foundation of China [81270374, 81570390]; China
Scholarship Council; NHLBI/National Institutes of Health (NIH)
Intramural Program [ZIA-HL-002065]; NIH [T32-ES-0741, R01-HL-039752,
R00-HL-114721]; American Heart Association [12BGIA11780030]
FX This work was supported by the National Natural Science Foundation of
China (81270374, 81570390; Q. Shao), the China Scholarship Council (Q.
Shao), the NHLBI/National Institutes of Health (NIH) Intramural Program
(ZIA-HL-002065; E. Murphy), the NIH (T32-ES-0741, K. M. Casin;
R01-HL-039752, C. Steenbergen; R00-HL-114721, M. J. Kohr), and the
American Heart Association (12BGIA11780030, M. J. Kohr).
NR 53
TC 1
Z9 1
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD FEB 15
PY 2016
VL 310
IS 4
BP H505
EP H515
DI 10.1152/ajpheart.00681.2015
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA DD8QE
UT WOS:000370191000005
PM 26702143
ER
PT J
AU Hon, YY
Lin, EE
Tian, X
Yang, Y
Sun, H
Swenson, ER
Taveira-Dasilva, AM
Gladwin, MT
Machado, RF
AF Hon, Yuen Yi
Lin, Elaina E.
Tian, Xin
Yang, Yang
Sun, He
Swenson, Erik R.
Taveira-Dasilva, Angelo M.
Gladwin, Mark T.
Machado, Roberto F.
TI Increased consumption and vasodilatory effect of nitrite during exercise
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE nitrite store; incremental exercise test; pharmacokinetics;
hemodynamics; vasodilation
ID DIETARY NITRATE SUPPLEMENTATION; OXIDE PRODUCTION; BLOOD-FLOW;
MITOCHONDRIAL RESPIRATION; XANTHINE-OXIDASE; OXYGEN-UPTAKE; O-2 COST;
L-NAME; CAPACITY; HUMANS
AB This study investigated the effects of aerobic-to-anaerobic exercise on nitrite stores in the human circulation and evaluated the effects of systemic nitrite infusion on aerobic and anaerobic exercise capacity and hemodynamics. Six healthy volunteers were randomized to receive sodium nitrite or saline for 70 min in two separate occasions in an exercise study. Subjects cycled on an upright electronically braked cycle ergometer 30 min into the infusion according to a ramp protocol designed to attain exhaustion in 10 min. They were allowed to recover for 30 min thereafter. The changes of whole blood nitrite concentrations over the 70-min study period were analyzed by pharmacokinetic modeling. Longitudinal measurements of hemodynamic and clinical variables were analyzed by fitting nonparametric regression spline models. During exercise, nitrite consumption/elimination rate was increased by similar to 137%. Cardiac output (CO), mean arterial pressure (MAP), and pulmonary artery pressure (PAP) were increased, but smaller elevation of MAP and larger increases of CO and PAP were found during nitrite infusion compared with placebo control. The higher CO and lower MAP during nitrite infusion were likely attributed to vasodilation and a trend toward decrease in systemic vascular resistance. In contrast, there were no significant changes in mean pulmonary artery pressures and pulmonary vascular resistance. These findings, together with the increased consumption of nitrite and production of iron-nitrosyl-hemoglobin during exercise, support the notion of nitrite conversion to release NO resulting in systemic vasodilatation. However, at the dosing used in this protocol achieving micromolar plasma concentrations of nitrite, exercise capacity was not enhanced, as opposed to other reports using lower dosing.
C1 [Hon, Yuen Yi] Clin Ctr Pharm Dept, NIH, Bethesda, MD USA.
[Lin, Elaina E.; Gladwin, Mark T.; Machado, Roberto F.] NHLBI, Vasc Med Branch, Bldg 10, Bethesda, MD 20892 USA.
[Tian, Xin; Yang, Yang] NHLBI, Off Biostat Res, Bldg 10, Bethesda, MD 20892 USA.
[Sun, He] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China.
[Swenson, Erik R.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Taveira-Dasilva, Angelo M.] NHLBI, Cardiovasc & Pulm Branch, Bldg 10, Bethesda, MD 20892 USA.
RP Machado, RF (reprint author), Univ Illinois, Sect Pulm Crit Care Med Sleep & Allergy, 840 S Wood St,Rm 920-N,Clin Sci Bldg,MC 719, Chicago, IL 60612 USA.
EM machador@uic.edu
FU Intramural Research Program of Clinical Center Pharmacy Department;
National Heart, Lung, and Blood Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of Clinical
Center Pharmacy Department and the National Heart, Lung, and Blood
Institute, National Institutes of Health. There was no commercial
sponsorship.
NR 43
TC 2
Z9 2
U1 5
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD FEB 15
PY 2016
VL 310
IS 4
BP 1354
EP 1364
DI 10.1152/ajplung.00081.2015
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA DD7DU
UT WOS:000370084700006
ER
PT J
AU Noonan, AM
Bunch, KP
Chen, JQ
Herrmann, MA
Lee, JM
Kohn, EC
O'Sullivan, CC
Jordan, E
Houston, N
Takebe, N
Kinders, RJ
Cao, L
Peer, CJ
Figg, WD
Annunziata, CM
AF Noonan, Anne M.
Bunch, Kristen P.
Chen, Jin-Qiu
Herrmann, Michelle A.
Lee, Jung-Min
Kohn, Elise C.
O'Sullivan, Ciara C.
Jordan, Elizabeth
Houston, Nicole
Takebe, Naoko
Kinders, Robert J.
Cao, Liang
Peer, Cody J.
Figg, W. Douglas
Annunziata, Christina M.
TI Pharmacodynamic markers and clinical results from the phase 2 study of
the SMAC mimetic birinapant in women with relapsed platinum-resistant or
-refractory epithelial ovarian cancer
SO CANCER
LA English
DT Article
DE birinapant; inhibitors of apoptosis proteins (IAP); ovarian cancer;
pharmacodynamics; second mitochondria-derived activator of caspases
(SMAC) mimetic
ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; TNF-ALPHA; ACTIVATION; CARCINOMA;
APOPTOSIS; PROTEINS; INHIBITOR; CELLS; CHEMORESISTANCE
AB BACKGROUNDInhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. It was hypothesized that blocking IAPs with birinapant would increase tumor cell death and result in objective responses for women with platinum-refractory and -resistant ovarian cancer.
METHODSIn this phase 2, Cancer Therapy Evaluation Program-sponsored study, patients received birinapant at 47mg/m(2) on days 1, 8, and 15 of 28-day cycles. Pharmacokinetics were obtained during cycle 1. Plasma, peripheral blood mononuclear cells (PBMCs), and percutaneous tumor biopsy samples were collected before cycle 1 and after 6 weeks. The primary endpoint was an objective response or progression-free survival lasting greater than 6 months in a mini-max design.
RESULTSEleven patients received birinapant; after this, accrual was terminated for lack of a clinical benefit. Birinapant was well tolerated, with predominantly grade 2 adverse events and 1 case of grade 3 lymphopenia. Pretreatment biopsy samples and PBMCs were collected; paired posttreatment biopsy samples and PBMCs were collected from 7 and 10 patients, respectively. There was consistent downregulation of cellular inhibitor of apoptosis protein 1 in tumors (P=.016) and PBMCs (P<.01). Procaspase 3 also decreased in tumors (P=.031) and PBMCs (P<.01); cleaved caspase 3 colocalized with H2A histone family member X (-H2AX) in tumors after birinapant exposure. Peripheral T and B cells decreased significantly after treatment, but natural killer cells did not (P=.04, P=.05, and P=.43, respectively).
CONCLUSIONSBirinapant shows consistent target suppression in vivo without single-agent antitumor activity in this small population. Single-agent pharmacodynamics are necessary to understand the drug's mechanism of action and set the stage for rational combination therapy. Preclinical studies are ongoing to identify optimal synergistic combinations for future clinical trials. (c) 2015 American Cancer Society.
C1 [Noonan, Anne M.; Bunch, Kristen P.; Lee, Jung-Min; Kohn, Elise C.; O'Sullivan, Ciara C.; Jordan, Elizabeth; Houston, Nicole; Annunziata, Christina M.] NCI, Womens Malignancies Branch, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
[Bunch, Kristen P.] Walter Reed Natl Mil Med Ctr, Dept Gynecol Oncol, Bethesda, MD USA.
[Chen, Jin-Qiu; Herrmann, Michelle A.] NCI, Collaborat Prot Technol Resource, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
[Takebe, Naoko] NCI, Canc Therapy Evaluat Program, Shady Grove, MD USA.
[Kinders, Robert J.] NCI, Pharmacodynam Assay Dev & Implementat Sect, Div Canc Treatment & Diag, Frederick, MD 21701 USA.
[Cao, Liang] NCI, Canc Genet Branch, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
[Peer, Cody J.; Figg, W. Douglas] NCI, Clin Pharmacol Program, Off Clin Director, Ctr Canc Res, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
RP Annunziata, CM (reprint author), NCI, Womens Malignancies Branch, 10 Ctr Dr,Room 4B54, Bethesda, MD 20892 USA.
EM annunzic@mail.nih.gov
RI Annunziata, Christina/L-3219-2016; Figg Sr, William/M-2411-2016
OI Annunziata, Christina/0000-0003-2033-6532;
FU Intramural Research Program of National Cancer Institute; Division of
Cancer Treatment and Diagnosis of National Cancer Institute; Cancer
Therapy Evaluation Program of National Cancer Institute
FX This work was supported by the Intramural Research Program of the
National Cancer Institute (to Christina M. Annunziata, W. Douglas Figg,
and Liang Cao), the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute (to Robert J. Kinders), and the Cancer Therapy
Evaluation Program of the National Cancer Institute (to Naoko Takebe).
NR 35
TC 4
Z9 5
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD FEB 15
PY 2016
VL 122
IS 4
BP 588
EP 597
DI 10.1002/cncr.29783
PG 10
WC Oncology
SC Oncology
GA DD5YA
UT WOS:000369999600014
PM 26566079
ER
PT J
AU Lee, HS
Lee, NCO
Kouprina, N
Kim, JH
Kagansky, A
Bates, S
Trepel, JB
Pommier, Y
Sackett, D
Larionov, V
AF Lee, Hee-Sheung
Lee, Nicholas C. O.
Kouprina, Natalay
Kim, Jung-Hyun
Kagansky, Alex
Bates, Susan
Trepel, Jane B.
Pommier, Yves
Sackett, Dan
Larionov, Vladimir
TI Effects of Anticancer Drugs on Chromosome Instability and New Clinical
Implications for Tumor-Suppressing Therapies
SO CANCER RESEARCH
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITORS; HUMAN ARTIFICIAL CHROMOSOME; VITRO
MICRONUCLEUS TEST; PARP INHIBITORS; SACCHAROMYCES-CEREVISIAE;
CONDITIONAL CENTROMERE; NAB-PACLITAXEL; MITOTIC DELAY; CANCER-CELLS;
DNA-DAMAGE
AB Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this attribute is appealing for therapeutic exploitation, drugs that increase CIN beyond this therapeutic threshold are currently limited. In our previous work, we developed a quantitative assay for measuring CIN based on the use of a nonessential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Here, we used this assay to rank 62 different anticancer drugs with respect to their effects on chromosome transmission fidelity. Drugs with various mechanisms of action, such as antimicrotubule activity, histone deacetylase inhibition, mitotic checkpoint inhibition, and targeting of DNA replication and damage responses, were included in the analysis. Ranking of the drugs based on their ability to induce HAC loss revealed that paclitaxel, gemcitabine, dactylolide, LMP400, talazoparib, olaparib, peloruside A, GW843682, VX-680, and cisplatin were the top 10 drugs demonstrating HAC loss at a high frequency. Therefore, identification of currently used compounds that greatly increase chromosome mis-segregation rates should expedite the development of new therapeutic strategies to target and leverage the CIN phenotype in cancer cells. (C) 2016 AACR.
C1 [Lee, Hee-Sheung; Lee, Nicholas C. O.; Kouprina, Natalay; Kim, Jung-Hyun; Bates, Susan; Trepel, Jane B.; Pommier, Yves; Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Kagansky, Alex] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Sackett, Dan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Larionov, V (reprint author), NCI, 37 Convent Dr,Bldg 37,Room 5032A, Bethesda, MD 20892 USA.
EM sackettd@mail.nih.gov
RI Kagansky, Alexander/B-3137-2011; Lee, Nicholas/F-3668-2015
OI Kagansky, Alexander/0000-0002-6219-6892;
FU Intramural Research Program of the NIH, NCI, Center for Cancer Research;
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH; Wellcome Trust
Principal Research Fellowship [073915]
FX This work was supported by the Intramural Research Program of the NIH,
NCI, Center for Cancer Research (V. Larionov, S. Bates, J.B. Trepel, and
Y. Pommier), by funds from the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH (D. Sackett), and a Wellcome Trust Principal Research
Fellowship (grant number 073915 to A. Kagansky).
NR 57
TC 3
Z9 3
U1 3
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 15
PY 2016
VL 76
IS 4
BP 902
EP 911
DI 10.1158/0008-5472.CAN-15-1617
PG 10
WC Oncology
SC Oncology
GA DD7UI
UT WOS:000370129600015
PM 26837770
ER
PT J
AU Chitnis, A
Balle-Cuif, L
AF Chitnis, Ajay
Balle-Cuif, Laure
TI The Notch meeting: an odyssey from structure to function
SO DEVELOPMENT
LA English
DT Review
DE Molecular characterization; Structure-function; Systems biology
ID ACTIVATION; ENHANCERS; LEUKEMIA; LIGANDS; CELLS
AB The Notch signaling pathway plays fundamental roles in diverse developmental processes. Studies of the basic biology of Notch function have provided insights into how its dysfunction contributes to multi-systemic diseases and cancer. In addition, our understanding of Notch signaling in maintaining stem/progenitor cell populations is revealing new avenues for rekindling regeneration. The Notch IX meeting, which was held in Athens, Greece in October 2015, brought together scientists working on different model systems and studying Notch signaling in various contexts. Here, we provide a summary of the key points that were presented at the meeting. Although we focus on the molecular mechanisms that determine Notch signaling and its role in development, we also cover talks describing roles for Notch in adulthood. Together, the talks revealed how interactions between adjacent cells mediated by Notch regulate development and physiology at multiple levels.
C1 [Chitnis, Ajay] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, Sect Neural Dev Dynam, Bldg 6B,Room 3B 315, Bethesda, MD 20892 USA.
[Balle-Cuif, Laure] Univ Paris 11, Paris Saclay Inst Neurosci NeuroPSI, CNRS, UMR 9197, Ave Terrasse,Bldg 5, F-91190 Gif Sur Yvette, France.
RP Chitnis, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Dev Biol, Sect Neural Dev Dynam, Bldg 6B,Room 3B 315, Bethesda, MD 20892 USA.
EM chitnisa@mail.nih.gov
FU Eunice Kennedy Shriver National Institutes of Child Health and Human
Development, National Institutes of Health; Centre National de la
Recherche Scientifique; European Research Council advanced grant
FX A.B.C. is supported by the Eunice Kennedy Shriver National Institutes of
Child Health and Human Development, National Institutes of Health.
L.B.C. is supported by Centre National de la Recherche Scientifique and
a European Research Council advanced grant.
NR 17
TC 1
Z9 1
U1 5
U2 14
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD FEB 15
PY 2016
VL 143
IS 4
BP 547
EP 553
DI 10.1242/dev.131086
PG 7
WC Developmental Biology
SC Developmental Biology
GA DD7VQ
UT WOS:000370133200001
PM 26884393
ER
PT J
AU Liu, LY
Alexa, K
Cortes, M
Schatzman-Bone, S
Kim, AJ
Mukhopadhyay, B
Cinar, R
Kunos, G
North, TE
Goessling, W
AF Liu, Leah Y.
Alexa, Kristen
Cortes, Mauricio
Schatzman-Bone, Stephanie
Kim, Andrew J.
Mukhopadhyay, Bani
Cinar, Resat
Kunos, George
North, Trista E.
Goessling, Wolfram
TI Cannabinoid receptor signaling regulates liver development and
metabolism
SO DEVELOPMENT
LA English
DT Article
DE Cannabinoid receptor; Liver development; Methionine; Zebrafish; Mouse
ID S-ADENOSYLHOMOCYSTEINE-HYDROLASE; ENDOCANNABINOID SYSTEM; METHIONINE
METABOLISM; TARGETED DISRUPTION; HEPATIC STEATOSIS; LIPID-METABOLISM;
CB1 RECEPTORS; ZEBRAFISH; MICE; EXPRESSION
AB Endocannabinoid (EC) signaling mediates psychotropic effects and regulates appetite. By contrast, potential roles in organ development and embryonic energy consumption remain unknown. Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor (Cnr) activity disrupts liver development and metabolic function in zebrafish (Danio rerio), impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 (cnr1) and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation. Functional assays reveal abnormal biliary anatomy and lipid handling. Adult cnr2 mutants are susceptible to hepatic steatosis. Metabolomic analysis reveals reduced methionine content in Cnr mutants. Methionine supplementation rescues developmental and metabolic defects in Cnr mutant livers, suggesting a causal relationship between EC signaling, methionine deficiency and impaired liver development. The effect of Cnr on methionine metabolism is regulated by sterol regulatory element-binding transcription factors (Srebfs), as their overexpression rescues Cnr mutant liver phenotypes in a methionine-dependent manner. Our work describes a novel developmental role for EC signaling, whereby Cnr-mediated regulation of Srebfs and methionine metabolism impacts liver development and function.
C1 [Liu, Leah Y.; Alexa, Kristen; Schatzman-Bone, Stephanie; Kim, Andrew J.; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[Cortes, Mauricio; North, Trista E.] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Mukhopadhyay, Bani; Cinar, Resat; Kunos, George] NIAAA, Lab Physiol Studies, Bethesda, MD 20982 USA.
[North, Trista E.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Goessling, Wolfram] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Goessling, Wolfram] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Goessling, W (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.; Goessling, W (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Goessling, W (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.; Goessling, W (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.; Goessling, W (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM wgoessling@partners.org
OI Goessling, Wolfram/0000-0001-9972-1569; CINAR, RESAT/0000-0002-8597-7253
FU National Institutes of Health NIAAA [F31AA022548]; NIDDK [R03096156,
R01DK090311]; Harvard Stem Cell Institute; Biomedical Sciences
FX This work was supported by National Institutes of Health NIAAA
[F31AA022548 to L.Y.L.] and NIDDK [R03096156 to T.E.N. and R01DK090311
to W.G.], and by the Harvard Stem Cell Institute [to T.E.N. and W.G.].
W.G. is a Pew Scholar in the Biomedical Sciences. Deposited in PMC for
release after 12 months.
NR 60
TC 1
Z9 1
U1 2
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
EI 1477-9129
J9 DEVELOPMENT
JI Development
PD FEB 15
PY 2016
VL 143
IS 4
BP 609
EP 622
DI 10.1242/dev.121731
PG 14
WC Developmental Biology
SC Developmental Biology
GA DD7VQ
UT WOS:000370133200008
PM 26884397
ER
PT J
AU Bola, RA
Kiyatkin, EA
AF Bola, R. Aaron
Kiyatkin, Eugene A.
TI Robust Brain Hyperglycemia during General Anesthesia: Relationships with
Metabolic Brain Inhibition and Vasodilation
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE brain and body hypothermia; metabolic brain inhibition; anesthesia;
vasoconstriction; vasodilation; nucleus accumbens; rats
ID EXTRACELLULAR GLUCOSE-CONCENTRATIONS; FREELY MOVING RATS;
NUCLEUS-ACCUMBENS; INTRAVENOUS COCAINE; UNRESTRAINED RATS;
NEURONAL-ACTIVITY; BLOOD-FLOW; PHYSIOLOGICAL FLUCTUATIONS; TEMPERATURE
HOMEOSTASIS; RETICULATA NEURONS
AB Glucose is the main energetic substrate for the metabolic activity of brain cells and its proper delivery into the extracellular space is essential for maintaining normal neural functions. Under physiological conditions, glucose continuously enters the extracellular space from arterial blood via gradient-dependent facilitated diffusion governed by the GLUT-1 transporters. Due to this gradient-dependent mechanism, glucose levels rise in the brain after consumption of glucose-containing foods and drinks. Glucose entry is also accelerated due to local neuronal activation and neuro-vascular coupling, resulting in transient hyperglycemia to prevent any metabolic deficit. Here, we explored another mechanism that is activated during general anesthesia and results in significant brain hyperglycemia. By using enzyme-based glucose biosensors we demonstrate that glucose levels in the nucleus accumbens (NAc) strongly increase after iv injection of Equthesin, a mixture of chloral hydrate and sodium pentobarbital, which is often used for general anesthesia in rats. By combining electrochemical recordings with brain, muscle, and skin temperature monitoring, we show that the gradual increase in brain glucose occurring during the development of general anesthesia tightly correlate with decreases in brain-muscle temperature differentials, suggesting that this rise in glucose is related to metabolic inhibition. While the decreased consumption of glucose by brain cells could contribute to the development of hyperglycemia, an exceptionally strong positive correlation (r = 0.99) between glucose rise and increases in skin-muscle temperature differentials was also found, suggesting the strong vasodilation of cerebral vessels as the primary mechanism for accelerated entry of glucose into brain tissue. Our present data could explain drastic differences in basal glucose levels found in awake and anesthetized animal preparations. They also suggest that glucose entry into brain tissue could be strongly modulated by pharmacological drugs via drug-induced changes in metabolic activity and the tone of cerebral vessels.
C1 [Bola, R. Aaron; Kiyatkin, Eugene A.] NIDA, In Vivo Electrophsiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophsiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH, Baltimore, MD USA.
EM ekiyatki@intra.nida.nih.gov
FU National Institute on Drug Abuse - Intramural Research Program, NIH
[1ZIADA000566-05]
FX Supported by the National Institute on Drug Abuse - Intramural Research
Program, NIH (1ZIADA000566-05).
NR 51
TC 1
Z9 1
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PD FEB 15
PY 2016
VL 7
AR 39
DI 10.3389/fphys.2016.00039
PG 13
WC Physiology
SC Physiology
GA DD6NW
UT WOS:000370041900003
PM 26913008
ER
PT J
AU Lee, SH
Baker, CI
AF Lee, Sue-Hyun
Baker, Chris I.
TI Multi-Voxel Decoding and the Topography of Maintained Information During
Visual Working Memory
SO FRONTIERS IN SYSTEMS NEUROSCIENCE
LA English
DT Review
DE working memory; short term memory; multivoxel pattern analysis (MVPA);
visual imagery; visual working memory; fMRI
ID SHORT-TERM-MEMORY; POSTERIOR PARIETAL CORTEX; PREDICTS
INDIVIDUAL-DIFFERENCES; PREFRONTAL CORTEX; SUSTAINED ACTIVITY; NEURAL
MECHANISMS; PATTERN-ANALYSIS; FRONTAL-CORTEX; MENTAL-IMAGERY; MOTION
TASK
AB The ability to maintain representations in the absence of external sensory stimulation, such as in working memory, is critical for guiding human behavior. Human functional brain imaging studies suggest that visual working memory can recruit a network of brain regions from visual to parietal to prefrontal cortex. In this review, we focus on the maintenance of representations during visual working memory and discuss factors determining the topography of those representations. In particular, we review recent studies employing multi-voxel pattern analysis (MVPA) that demonstrate decoding of the maintained content in visual cortex, providing support for a "sensory recruitment" model of visual working memory. However, there is some evidence that maintained content can also be decoded in areas outside of visual cortex, including parietal and frontal cortex. We suggest that the ability to maintain representations during working memory is a general property of cortex, not restricted to specific areas, and argue that it is important to consider the nature of the information that must be maintained. Such information-content is critically determined by the task and the recruitment of specific regions during visual working memory will be both task- and stimulus-dependent. Thus, the common finding of maintained information in visual, but not parietal or prefrontal, cortex may be more of a reflection of the need to maintain specific types of visual information and not of a privileged role of visual cortex in maintenance.
C1 [Lee, Sue-Hyun] Korea Adv Inst Sci & Technol, Coll Engn, Dept Bio & Brain Engn, Daejeon, South Korea.
[Lee, Sue-Hyun; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Baker, CI (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM bakerchris@mail.nih.gov
RI Lee, Sue Hyun/F-5490-2015
NR 90
TC 3
Z9 3
U1 12
U2 18
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5137
J9 FRONT SYST NEUROSCI
JI Front. Syst. Neurosci.
PD FEB 15
PY 2016
VL 10
AR 2
DI 10.3380/fnsys.2016.00002
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DD7YN
UT WOS:000370141000001
PM 26912997
ER
PT J
AU Meier, TB
Bellgowan, PSF
Bergamino, M
Ling, JM
Mayer, AR
AF Meier, Timothy B.
Bellgowan, Patrick S. F.
Bergamino, Maurizio
Ling, Josef M.
Mayer, Andrew R.
TI Thinner Cortex in Collegiate Football Players With, but not Without, a
Self-Reported History of Concussion
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE anterior cingulate; concussion; cortical thickness; football; fractional
anisotropy
ID TRAUMATIC BRAIN-INJURY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
RETIRED NFL PLAYERS; CORTICAL THICKNESS; NEUROCOGNITIVE PERFORMANCE;
DEPRESSIVE SYMPTOMS; METRICS ANAM; ABNORMALITIES; SPORT; MORPHOMETRY
AB Emerging evidence suggests that a history of sports-related concussions can lead to long-term neuroanatomical changes. The extent to which similar changes are present in young athletes is undetermined at this time. Here, we tested the hypothesis that collegiate football athletes with (n=25) and without (n=24) a self-reported history of concussion would have cortical thickness differences and altered white matter integrity relative to healthy controls (n=27) in fronto-temporal regions that appear particularly susceptible to traumatic brain injury. Freesurfer software was used to estimate cortical thickness, fractional anisotropy was calculated in a priori white matter tracts, and behavior was assessed using a concussion behavioral battery. Groups did not differ in self-reported symptoms (p>0.10) or cognitive performance (p>0.10). Healthy controls reported significantly higher happiness levels than both football groups (all p<0.01). Contrary to our hypothesis, no differences in fractional anisotropy were observed between our groups (p>0.10). However, football athletes with a history of concussion had significantly thinner cortex in the left anterior cingulate cortex, orbital frontal cortex, and medial superior frontal cortex relative to healthy controls (p=0.02, d= -0.69). Further, football athletes with a history of concussion had significantly thinner cortex in the right central sulcus and precentral gyrus relative to football athletes without a history of concussion (p=0.03, d= -0.71). No differences were observed between football athletes without a history of concussion and healthy controls. These results suggest that previous concussions, but not necessarily football exposure, may be associated with cortical thickness differences in collegiate football athletes.
C1 [Meier, Timothy B.; Ling, Josef M.; Mayer, Andrew R.] Mind Res Network, Lovelace Biomed & Environm Res Inst, Pete & Nancy Domenici Hall,1101 Yale Blvd NE, Albuquerque, NM 87106 USA.
[Meier, Timothy B.; Bergamino, Maurizio] Laureate Inst Brain Res, Tulsa, OK USA.
[Bellgowan, Patrick S. F.] NINDS, NIH, North Bethesda, MD USA.
[Mayer, Andrew R.] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA.
[Mayer, Andrew R.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
RP Meier, TB (reprint author), Mind Res Network, Lovelace Biomed & Environm Res Inst, Pete & Nancy Domenici Hall,1101 Yale Blvd NE, Albuquerque, NM 87106 USA.
EM tmeier@mrn.org
RI Meijer, Anna/K-5118-2016
NR 57
TC 2
Z9 2
U1 5
U2 13
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD FEB 15
PY 2016
VL 33
IS 4
BP 330
EP 338
DI 10.1089/neu.2015.3919
PG 9
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DD2NH
UT WOS:000369758800002
PM 26061068
ER
PT J
AU Doshi, J
Erus, G
Ou, YM
Resnick, SM
Gur, RC
Gur, RE
Satterthwaite, TD
Furth, S
Davatzikos, C
AF Doshi, Jimit
Erus, Guray
Ou, Yangming
Resnick, Susan M.
Gur, Ruben C.
Gur, Raquel E.
Satterthwaite, Theodore D.
Furth, Susan
Davatzikos, Christos
CA Alzheimer's Neuroimaging
TI MUSE: MUlti-atlas region Segmentation utilizing Ensembles of
registration algorithms and parameters, and locally optimal atlas
selection
SO NEUROIMAGE
LA English
DT Article
DE MRI; Multi-atlas segmentation; Registration; Label fusion; ROI
ID IMAGE SEGMENTATION; LABEL FUSION; OLDER-ADULTS; DEFORMABLE REGISTRATION;
ALZHEIMERS-DISEASE; HUMAN BRAIN; MRI; HIPPOCAMPUS; VALIDATION; CHILDREN
AB Atlas-based automated anatomical labeling is a fundamental tool in medical image segmentation, as it defines regions of interest for subsequent analysis of structural and functional image data. The extensive investigation of multi-atlas warping and fusion techniques over the past 5 or more years has clearly demonstrated the advantages of consensus-based segmentation. However, the common approach is to use multiple atlases with a single registration method and parameter set, which is not necessarily optimal for every individual scan, anatomical region, and problem/data-type. Different registration criteria and parameter sets yield different solutions, each providing complementary information. Herein, we present a consensus labeling framework that generates a broad ensemble of labeled atlases in target image space via the use of several warping algorithms, regularization parameters, and atlases. The label fusion integrates two complementary sources of information: a local similarity ranking to select locally optimal atlases and a boundary modulation term to refine the segmentation consistently with the target image's intensity profile. The ensemble approach consistently outperforms segmentations using individual warping methods alone, achieving high accuracy on several benchmark datasets. The MUSE methodology has been used for processing thousands of scans from various datasets, producing robust and consistent results. MUSE is publicly available both as a downloadable software package, and as an application that can be run on the CBICA Image Processing Portal (https://ipp.cbica.upenn.edu), a web based platform for remote processing of medical images. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Doshi, Jimit; Erus, Guray; Ou, Yangming; Davatzikos, Christos] Univ Penn, Ctr Biomed Image Comp & Analyt CBICA, Philadelphia, PA 19104 USA.
[Ou, Yangming] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Biomed Imaging Ctr, Boston, MA 02129 USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA.
[Gur, Ruben C.; Gur, Raquel E.; Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Furth, Susan] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA.
RP Erus, G (reprint author), Univ Penn, Ctr Biomed Image Comp & Analyt CBICA, Philadelphia, PA 19104 USA.; Erus, G (reprint author), Univ Penn, Richards Bldg,3700 Hamilton Walk,7th Floor, Philadelphia, PA 19104 USA.
EM jimit.doshi@uphs.upenn.edu
FU Intramural Research Program, National Institute on Aging, NIH; National
Institutes of Health [R01-AG014971]; [HHSN271201300284]
FX This work was partially supported by the Intramural Research Program,
National Institute on Aging, NIH. This work is also supported in part by
the National Institutes of Health grant number R01-AG014971, and by
contract HHSN271201300284.
NR 52
TC 8
Z9 8
U1 1
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2016
VL 127
BP 186
EP 195
DI 10.1016/j.neuroimage.2015.11.073
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DD5HE
UT WOS:000369952900017
PM 26679328
ER
PT J
AU Avram, AV
Sarlls, JE
Barnett, AS
Ozarslan, E
Thomas, C
Irfanoglu, MO
Hutchinson, E
Pierpaoli, C
Basser, PJ
AF Avram, Alexandru V.
Sarlls, Joelle E.
Barnett, Alan S.
Ozarslan, Evren
Thomas, Cibu
Irfanoglu, M. Okan
Hutchinson, Elizabeth
Pierpaoli, Carlo
Basser, Peter J.
TI Clinical feasibility of using mean apparent propagator (MAP) MRI to
characterize brain tissue microstructure
SO NEUROIMAGE
LA English
DT Article
DE Mean apparent propagator (MAP); Diffusion propagator; Tissue
microstructure; Non-Gaussianity; Anisotropy; Diffusion tensor imaging
(DTI)
ID TENSOR IMAGING GDTI; DIFFUSION MRI; GENERALIZED DIFFUSION; ANISOTROPY;
SPECTROSCOPY; ORIENTATION; SIGNAL
AB Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our ability to perform whole-brain fiber tractography. Reconstructions from subsampled data sets suggest that MAP MRI parameters can be computed from a relatively small number of DWIs acquired with high b-value and good signal-to-noise ratio in clinically achievable scan durations of less than 10 min. The neuroanatomical consistency across healthy subjects and reproducibility in test-retest experiments of MAP MRI microstructural parameters further substantiate the robustness and clinical feasibility of this technique. The MAP MRI metrics could potentially provide more sensitive clinical biomarkers with increased pathophysiological specificity compared to microstructural measures derived using conventional diffusion MRI techniques. Published by Elsevier Inc.
C1 [Avram, Alexandru V.; Barnett, Alan S.; Thomas, Cibu; Irfanoglu, M. Okan; Hutchinson, Elizabeth; Pierpaoli, Carlo; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20814 USA.
[Sarlls, Joelle E.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Barnett, Alan S.; Thomas, Cibu; Irfanoglu, M. Okan; Hutchinson, Elizabeth; Pierpaoli, Carlo] Henry Jackson Fdn Mil Med, Bethesda, MD USA.
[Ozarslan, Evren] Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Ozarslan, Evren] Bogazici Univ, Dept Phys, Istanbul, Turkey.
RP Avram, AV (reprint author), NICHD, NIH, Bldg 13,Room 3 W16,13 South Dr, Bethesda, MD 20814 USA.
EM alexandru.avram@nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institute of Neurological Disorders and Stroke (NINDS) at the National
Institutes of Health (NIH); Department of Defense in the Center of
Neuroscience and Regenerative Medicine (CNRM); TUBITAK-EU COFUND project
[114C015]; TUBITAK [114E053]; Bogazici University [BAP 8521]; NIH
[R01MH074794]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) and the National Institute of Neurological Disorders and Stroke
(NINDS) at the National Institutes of Health (NIH), and the Department
of Defense in the Center of Neuroscience and Regenerative Medicine
(CNRM). EO was supported by TUBITAK-EU COFUND project no. 114C015,
TUBITAK project no. 114E053, Bogazici University research funding BAP
8521, and NIH R01MH074794. We thank Dr. Jian Cheng for helpful
discussions. In vivo MRI experiments were performed at the NIH MRI
Research Facility (NMRF). This study utilized the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, MD (http://biowulf.nih.gov).
NR 37
TC 1
Z9 1
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2016
VL 127
BP 422
EP 434
DI 10.1016/j.neuroimage.2015.11.027
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DD5HE
UT WOS:000369952900036
PM 26584864
ER
PT J
AU Bouhrara, M
Spencer, RG
AF Bouhrara, Mustapha
Spencer, Richard G.
TI Improved determination of the myelin water fraction in human brain using
magnetic resonance imaging through Bayesian analysis of mcDESPOT
SO NEUROIMAGE
LA English
DT Article
DE mcDESPOT; Myelin water fraction; Bayesian analysis; Stochastic region
contraction algorithm; Nonlinear least squares; Brain
ID STOCHASTIC REGION CONTRACTION; MULTICOMPONENT T2 ANALYSIS; APPEARING
WHITE-MATTER; HUMAN KNEE-JOINT; IN-VIVO; MULTIPLE-SCLEROSIS; TRANSVERSE
RELAXATION; ARTICULAR-CARTILAGE; T-2-ASTERISK DECAY; PROBABILITY-THEORY
AB Myelin water fraction (MWF) mapping with magnetic resonance imaging has led to the ability to directly observe myelination and demyelination in both the developing brain and in disease. Multicomponent driven equilibrium single pulse observation of T-1 and T-2 (mcDESPOT) has been proposed as a rapid approach for multicomponent relaxometry and has been applied to map MWF in the human brain. However, even for the simplest two-pool signal model consisting of myelin-associated and non-myelin-associated water, the dimensionality of the parameter space for obtaining MWF estimates remains high. This renders parameter estimation difficult, especially at low-to-moderate signal-to-noise ratios (SNRs), due to the presence of local minima and the flatness of the fit residual energy surface used for parameter determination using conventional nonlinear least squares (NLLS)-based algorithms. In this study, we introduce three Bayesian approaches for analysis of the mcDESPOT signal model to determine MWF. Given the high-dimensional nature of the mcDESPOT signal model, and, therefore the high-dimensional marginalizations over nuisance parameters needed to derive the posterior probability distribution of the MWF, the Bayesian analyses introduced here use different approaches to reduce the dimensionality of the parameter space. The first approach uses normalization by average signal amplitude, and assumes that noise can be accurately estimated from signal-free regions of the image. The second approach likewise uses average amplitude normalization, but incorporates a full treatment of noise as an unknown variable through marginalization. The third approach does not use amplitude normalization and incorporates marginalization over both noise and signal amplitude. Through extensive Monte Carlo numerical simulations and analysis of in vivo human brain datasets exhibiting a range of SNR and spatial resolution, we demonstrated markedly improved accuracy and precision in the estimation of MWF using these Bayesian methods as compared to the stochastic region contraction (SRC) implementation of NLLS. Published by Elsevier Inc.
C1 [Bouhrara, Mustapha; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
RP Bouhrara, M; Spencer, RG (reprint author), NIA, NIH, Intramural Res Program, BRC 04B-116,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bouhraram@mail.nih.gov; spencer@helix.nih.gov
FU NIH, National Institute on Aging
FX This work was supported by the Intramural Research Program of the NIH,
National Institute on Aging. We thank David A. Reiter, Donnie Cameron
and Christopher Bergeron for their assistance with data acquisition.
NR 60
TC 3
Z9 3
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD FEB 15
PY 2016
VL 127
BP 456
EP 471
DI 10.1016/j.neuroimage.2015.10.034
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DD5HE
UT WOS:000369952900039
PM 26499810
ER
PT J
AU Gistelinck, C
Gioia, R
Gagliardi, A
Tonelli, F
Marchese, L
Bianchi, L
Landi, C
Bini, L
Huysseune, A
Witten, PE
Staes, A
Gevaert, K
De Rocker, N
Menten, B
Malfait, F
Leikin, S
Carra, S
Tenni, R
Rossi, A
De Paepe, A
Coucke, P
Willaert, A
Forlino, A
AF Gistelinck, C.
Gioia, R.
Gagliardi, A.
Tonelli, F.
Marchese, L.
Bianchi, L.
Landi, C.
Bini, L.
Huysseune, A.
Witten, P. E.
Staes, A.
Gevaert, K.
De Rocker, N.
Menten, B.
Malfait, F.
Leikin, S.
Carra, S.
Tenni, R.
Rossi, A.
De Paepe, A.
Coucke, P.
Willaert, A.
Forlino, A.
TI Zebrafish Collagen Type I: Molecular and Biochemical Characterization of
the Major Structural Protein in Bone and Skin
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OSTEOGENESIS IMPERFECTA; DANIO-RERIO; 2-DIMENSIONAL ELECTROPHORESIS;
WIDE DISTRIBUTION; ALPHA-CHAINS; FISH; PROCOLLAGEN; STABILITY;
IDENTIFICATION; PERSPECTIVES
AB Over the last years the zebrafish imposed itself as a powerful model to study skeletal diseases, but a limit to its use is the poor characterization of collagen type I, the most abundant protein in bone and skin. In tetrapods collagen type I is a trimer mainly composed of two alpha 1 chains and one alpha 2 chain, encoded by COL1A1 and COL1A2 genes, respectively. In contrast, in zebrafish three type I collagen genes exist, col1a1a, col1a1b and col1a2 coding for alpha 1(I), alpha 3(I) and alpha 2(I) chains. During embryonic and larval development the three collagen type I genes showed a similar spatio-temporal expression pattern, indicating their co-regulation and interdependence at these stages. In both embryonic and adult tissues, the presence of the three a(I) chains was demonstrated, although in embryos alpha 1(I) was present in two distinct glycosylated states, suggesting a developmental-specific collagen composition. Even though in adult bone, skin and scales equal amounts of alpha 1(I), alpha 3(I) and alpha 2(I) chains are present, the presented data suggest a tissue-specific stoichiometry and/or post-translational modification status for collagen type I. In conclusion, this data will be useful to properly interpret results and insights gained from zebrafish models of skeletal diseases.
C1 [Gistelinck, C.; De Rocker, N.; Menten, B.; Malfait, F.; De Paepe, A.; Coucke, P.; Willaert, A.] Univ Ghent, Ctr Med Genet Ghent, B-9000 Ghent, Belgium.
[Gioia, R.; Tonelli, F.; Marchese, L.; Tenni, R.; Rossi, A.; Forlino, A.] Univ Pavia, Dept Mol Med, Biochem Unit, Via Palestro 3, I-27100 Pavia, Italy.
[Gagliardi, A.; Bianchi, L.; Landi, C.; Bini, L.] Univ Siena, Dept Life Sci, Funct Prote Lab, Via Laterina 8, I-53100 Siena, Italy.
[Huysseune, A.; Witten, P. E.] Univ Ghent, Dept Biol, B-9000 Ghent, Belgium.
[Staes, A.; Gevaert, K.] VIB, Dept Med Prot Res, Ghent, Belgium.
[Staes, A.; Gevaert, K.] Univ Ghent, Dept Biochem, B-9000 Ghent, Belgium.
[Leikin, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Carra, S.] Univ Milan, Dept Biosci, Milan, Italy.
RP Forlino, A (reprint author), Univ Pavia, Dept Mol Med, Biochem Unit, Via Palestro 3, I-27100 Pavia, Italy.
EM aforlino@unipv.it
RI Leikin, Sergey/A-5518-2008; Carra, Silvia/K-4643-2016; Gevaert,
Kris/D-6489-2017;
OI Leikin, Sergey/0000-0001-7095-0739; Carra, Silvia/0000-0002-9321-9508;
Gevaert, Kris/0000-0002-4237-0283; Staes, An/0000-0001-8767-8508; landi,
claudia/0000-0003-0410-8038
FU Consorzio Interuniversitario Biotecnologie (CIB); Fondazione Cariplo
[2013-0612]; Telethon [GGP13098]; European Community, FP7, "Sybil"
project [602300]; Ghent University Methusalem [BOF08/01M01108]; Belgian
Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP)
program [IAP P7/43-BeMGI]
FX We thank Prof. Franco Cotelli, Department of Biosciences, University of
Milano, Milan, Italy for data discussion, Dr Velia Penza, Department of
Molecular Medicine, Biochemistry Unit, University of Pavia, Italy for
initial collagen preparation from embryos and adult zebrafish, Dr
Patrizia Arcidiaco, Centro Grandi Strumenti, University of Pavia, Italy
for support with amino acid analysis and the animal facility "Centro di
servizio per la gestione unificata delle attivita di stabulazione e di
radiobiologia" of the University of Pavia. We thank the Consorzio
Interuniversitario Biotecnologie (CIB) who provided one year fellowship
for RG. This work was supported by Fondazione Cariplo [grant n.
2013-0612] to AF, Telethon [grant n. GGP13098] to AF, the European
Community, FP7, "Sybil" project [grant n. 602300] to AR and AF, the
Ghent University Methusalem grant BOF08/01M01108 to ADP and by funding
from the Belgian Science Policy Office Interuniversity Attraction Poles
(BELSPO-IAP) program through the project IAP P7/43-BeMGI.
NR 60
TC 2
Z9 2
U1 7
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 15
PY 2016
VL 6
AR 21540
DI 10.1038/srep21540
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6NR
UT WOS:000370041400001
PM 26876635
ER
PT J
AU Guo, SR
Lv, L
Shen, YY
Hu, ZL
He, QJ
Chen, XY
AF Guo, Shengrong
Lv, Li
Shen, Yuanyuan
Hu, Zhongliang
He, Qianjun
Chen, Xiaoyuan
TI A nanoparticulate pre-chemosensitizer for efficacious chemotherapy of
multidrug resistant breast cancer
SO SCIENTIFIC REPORTS
LA English
DT Article
ID DRUG-DELIVERY; ANTITUMOR EFFICACY; RECENT PROGRESS; P-GLYCOPROTEIN; GENE
DELIVERY; IN-VITRO; CURCUMIN; THERAPY; CELLS; MICELLES
AB Small-molecule chemosensitizers can reverse cancer multidrug resistance (MDR), thus significantly improving the in vitro effect of chemotherapy drugs for MDR cancer cells, however, their in vivo effects are not always very good, because they are difficult to effectively accumulate in tumor and enter the same cancer with chemotherapy drugs after systemic administration due to individual biopharmaceutical properties. To overcome these limitations, here we study a novel nanoparticular pre-chemosensitizer which can be also used as nanocarrier of chemotherapy drugs. We take an 'all in one' approach to develop a self-assembled nanoparticle formula of amphiphilic poly(curcumin-dithiodipropionic acid)-b-poly(ethylene glycol)-biotin. The nanoparticle is capable of tumor-targeted delivery, responsive degradation at the intracellular level of glutathione and subsequent intracellular co-release of the chemosensitizer curcumin and the encapsulated chemotherapeutic drug doxorubicin to maximize a synergistic effect of chemosensitization and chemotherapy. We demonstrate that the antitumor efficacy of nanoparticle is much superior to that of doxorubicin in the multidrug resistant MCF-7/ADR xenografted nude mice.
C1 [Guo, Shengrong; Lv, Li; Shen, Yuanyuan] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China.
[Hu, Zhongliang] Univ Leeds, Sch Chem & Proc Engn, Leeds LS3 9BD, W Yorkshire, England.
[He, Qianjun] Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen, Guangdong, Peoples R China.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Guo, SR (reprint author), Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China.; He, QJ (reprint author), Shenzhen Univ, Sch Med, Dept Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasoun, Shenzhen, Guangdong, Peoples R China.; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
EM srguo@sjtu.edu.cn; nanoflower@126.com; shawn.chen@nih.gov
RI HE, QIANJUN/M-2642-2013
OI HE, QIANJUN/0000-0003-0689-8838
FU National Natural Science Foundation of China (NSFC) [81171439]; National
Key Technology R & D Program of the Ministry of Science and Technology
[2012BAI18B01]; European Union FP7 via a Marie Curie International
Incoming Fellowship [PIIF-GA-2012-331281]; Intramural Research Program,
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health
FX This work was supported by National Natural Science Foundation of China
(NSFC, Grant No. 81171439), the National Key Technology R & D Program of
the Ministry of Science and Technology (2012BAI18B01), the European
Union FP7 via a Marie Curie International Incoming Fellowship to S. G.
(Grant No. PIIF-GA-2012-331281), and the Intramural Research Program,
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health. We also thank the Instrumental Analysis Center of
Shanghai Jiao Tong University for technical support in TEM and LC-HRMS
analysis.
NR 35
TC 6
Z9 6
U1 10
U2 47
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 FEB 15
PY 2016
VL 6
AR 21459
DI 10.1038/srep21459
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6NJ
UT WOS:000370040600001
PM 26875787
ER
PT J
AU Marzi, A
Murphy, AA
Feldmann, F
Parkins, CJ
Haddock, E
Hanley, PW
Emery, MJ
Engelmann, F
Messaoudi, I
Feldmann, H
Jarvis, MA
AF Marzi, Andrea
Murphy, Aisling A.
Feldmann, Friederike
Parkins, Christopher J.
Haddock, Elaine
Hanley, Patrick W.
Emery, Matthew J.
Engelmann, Flora
Messaoudi, Ilhem
Feldmann, Heinz
Jarvis, Michael A.
TI Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein
protects nonhuman primates from Ebola virus infection
SO SCIENTIFIC REPORTS
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; HIGHLY PATHOGENIC SIV; RHESUS
CYTOMEGALOVIRUS; MURINE CYTOMEGALOVIRUS; IMMUNE-RESPONSES; HOUSE MICE;
CHALLENGE; TRANSMISSION; EFFECTOR; HERPESVIRUS
AB Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.
C1 [Marzi, Andrea; Haddock, Elaine; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Murphy, Aisling A.; Jarvis, Michael A.] Univ Plymouth, Sch Biomed & Healthcare Sci, Plymouth PL4 8AA, Devon, England.
[Feldmann, Friederike; Hanley, Patrick W.] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA.
[Parkins, Christopher J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97201 USA.
[Emery, Matthew J.] Univ Plymouth, Sch Biol Sci, Plymouth PL4 8AA, Devon, England.
[Engelmann, Flora; Messaoudi, Ilhem] Univ Calif Riverside, Sch Med, Riverside, CA 92521 USA.
RP Jarvis, MA (reprint author), Univ Plymouth, Sch Biomed & Healthcare Sci, Plymouth PL4 8AA, Devon, England.
EM michael.jarvis@plymouth.ac.uk
FU Plymouth University, School of Biomedical and Healthcare Sciences;
Division of Intramural Research, NIAID, NIH
FX We thank Drs P. Barry and W. Chang (University of California at Davis,
CA, USA) for providing the pRhCMV (68.1) RhCMV BAC, and Dr. D. Court
(NCI-Frederick, MD) for providing the E/T-based recombination system. We
are grateful to Drs T. Shenk (Princeton University, NJ, USA) and P.
Barry for providing anti-CMV antibodies, Dr. A. Takada (Hokkaido
University, Sapporo, Japan) for providing the monoclonal anti-EBOV GP1
antibody, Dr. Y. Kawaoka (University of Wisconsin-Madison, WI, USA) for
providing the anti-EBOV VP40 polyclonal rabbit serum, and Dr. T.
Geisbert (University of Texas Medical Branch, TX, USA) for the positive
control NHP sera used in neutralization assays. We would also like to
thank the Rocky Mountain Veterinary Branch (NIH, NIAID) for their
technical support. This work was partly funded by Plymouth University,
School of Biomedical and Healthcare Sciences internal funding, and the
Division of Intramural Research, NIAID, NIH.
NR 59
TC 2
Z9 2
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 FEB 15
PY 2016
VL 6
AR 21674
DI 10.1038/srep21674
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6OV
UT WOS:000370044400001
PM 26876974
ER
PT J
AU Ujiie, H
Shevach, EM
AF Ujiie, Hideyuki
Shevach, Ethan M.
TI gamma delta T Cells Protect the Liver and Lungs of Mice from
Autoimmunity Induced by Scurfy Lymphocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID REGULATORY ROLE; IMMUNE SUPPRESSION; TUMOR-IMMUNITY; NK CELLS;
EXPRESSION; INFLAMMATION; MOUSE; CD39; BETA; ENTEROPATHY
AB gamma delta T cells have been shown to have immunoregulatory functions in several experimental autoimmune models. A mutation of the Foxp3 gene leads to the absence of regulatory T cells (Tregs) and a fatal systemic autoimmune disease in scurfy mice. Transfer of scurfy lymphocytes to RAG deficient (RAG(-/-)) recipients reproduces the inflammatory phenotype of the scurfy donor, including hepatitis and pneumonitis. In this study, we show that TCR alpha(-/-) recipients, which lack alpha beta T cells but have gamma delta T cells and B cells, are significantly protected from the hepatitis and pneumonitis, but not the dermatitis, induced by adoptive transfer of scurfy lymphocytes. Cotransfer of gamma delta T cells, but not B cells, prevented hepatitis and pneumonitis in RAG(-/-) recipients of scurfy lymphocytes. gamma delta T cells in the TCR alpha(-/-) recipients of scurfy cells markedly expanded and expressed a highly activated (CD62L(lo)CD44(hi)) phenotype. The activated gamma delta T cells expressed high levels of CD39 and NKG2D on their cell surface. A high frequency of scurfy T cells in TCR alpha(-/-) recipients produced IL-10, suggesting that gamma delta T cells may enhance suppressor cytokine production from scurfy T cells in TCR alpha(-/-) recipients. This study indicates that gamma delta T cells may contribute to the maintenance of immunological homeostasis by suppressing autoreactive T cells in liver and lung.
C1 [Ujiie, Hideyuki; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, 10 Ctr Dr,MSC 1892,Bldg 10,Room 11N315, Bethesda, MD 20892 USA.
[Ujiie, Hideyuki] Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido, Japan.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,MSC 1892,Bldg 10,Room 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU intramural program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health; Japan Society for the Promotion
of Science Postdoctoral Fellowships; Nakatomi Foundation; Sumitomo Life
Welfare and Culture Foundation
FX This work was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. H.U. was also supported by the Japan Society for the Promotion
of Science Postdoctoral Fellowships for Research Abroad program, the
Nakatomi Foundation, and by the Sumitomo Life Welfare and Culture
Foundation.
NR 39
TC 1
Z9 1
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2016
VL 196
IS 4
BP 1517
EP 1528
DI 10.4049/jimmunol.1501774
PG 12
WC Immunology
SC Immunology
GA DD0TJ
UT WOS:000369632300011
PM 26773142
ER
PT J
AU Hosokawa, K
Muranski, P
Feng, XM
Townsley, DM
Liu, BY
Knickelbein, J
Keyvanfar, K
Dumitriu, B
Ito, S
Kajigaya, S
Taylor, JG
Kaplan, MJ
Nussenblatt, RB
Barrett, AJ
O'Shea, J
Young, NS
AF Hosokawa, Kohei
Muranski, Pawel
Feng, Xingmin
Townsley, Danielle M.
Liu, Baoying
Knickelbein, Jared
Keyvanfar, Keyvan
Dumitriu, Bogdan
Ito, Sawa
Kajigaya, Sachiko
Taylor, James G.
Kaplan, Mariana J.
Nussenblatt, Robert B.
Barrett, A. John
O'Shea, John
Young, Neal S.
TI Memory Stem T Cells in Autoimmune Disease: High Frequency of Circulating
CD8(+) Memory Stem Cells in Acquired Aplastic Anemia
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA;
IMMUNOSUPPRESSIVE THERAPY; IMMUNE-RESPONSES; REGULATORY CELLS;
FLOW-CYTOMETRY; CD4(+); PD-1; LYMPHOCYTES; TRANSPLANTATION
AB Memory stem T cells (TSCMs) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. Hallmarks of autoimmune disease pathogenesis are abnormal CD4(+) and CD8(+) T cell activation. We investigated the TSCM subset in 55, 34, 43, and 5 patients with acquired aplastic anemia (AA), autoimmune uveitis, systemic lupus erythematosus, and sickle cell disease, respectively, as well as in 41 age-matched healthy controls. CD8(+) TSCM frequency was significantly increased in AA compared with healthy controls. An increased CD8(+) TSCM frequency at diagnosis was associated with responsiveness to immunosuppressive therapy, and an elevated CD8(+) TSCM population after immunosuppressive therapy correlated with treatment failure or relapse in AA patients. IFN-gamma and IL-2 production was significantly increased in various CD8(+) and CD4(+) T cell subsets in AA patients, including CD8(+) and CD4(+) TSCMs. CD8(+) TSCM frequency was also increased in patients with autoimmune uveitis or sickle cell disease. A positive correlation between CD4(+) and CD8(+) TSCM frequencies was found in AA, autoimmune uveitis, and systemic lupus erythematosus. Evaluation of PD-1, CD160, and CD244 expression revealed that TSCMs were less exhausted compared with other types of memory T cells. Our results suggest that the CD8(+) TSCM subset is a novel biomarker and a potential therapeutic target for AA.
C1 [Hosokawa, Kohei; Muranski, Pawel; Feng, Xingmin; Townsley, Danielle M.; Keyvanfar, Keyvan; Dumitriu, Bogdan; Ito, Sawa; Kajigaya, Sachiko; Taylor, James G.; Barrett, A. John; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Liu, Baoying; Knickelbein, Jared; Nussenblatt, Robert B.] NEI, Clin Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[O'Shea, John] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Hosokawa, K (reprint author), NHLBI, Cell Biol Sect, Hematol Branch, NIH, Bldg 10-CRC,Room 3E-5140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kohei.hosokawa@nih.gov
OI Taylor, James/0000-0002-4421-1809
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood
Institute.
NR 59
TC 8
Z9 8
U1 3
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2016
VL 196
IS 4
BP 1568
EP 1578
DI 10.4049/jimmunol.1501739
PG 11
WC Immunology
SC Immunology
GA DD0TJ
UT WOS:000369632300016
PM 26764034
ER
PT J
AU Vargas-Inchaustegui, DA
Demers, A
Shaw, JM
Kang, GB
Ball, D
Tuero, I
Musich, T
Mohanram, V
Demberg, T
Karpova, TS
Li, QS
Robert-Guroff, M
AF Vargas-Inchaustegui, Diego A.
Demers, Andrew
Shaw, Julia M.
Kang, Guobin
Ball, David
Tuero, Iskra
Musich, Thomas
Mohanram, Venkatramanan
Demberg, Thorsten
Karpova, Tatiana S.
Li, Qingsheng
Robert-Guroff, Marjorie
TI Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus
Env-Specific T Follicular Helper Cells in Rhesus Macaques
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GERMINAL CENTER B; IMMUNE-RESPONSES; SIV INFECTION; TFH CELLS; FH CELLS;
REPLICATION; PHENOTYPE; ANTIGEN; DIFFERENTIATION; PERSISTENCE
AB Measurement of Ag-specific T follicular helper (T-FH) cell activity in rhesus macaques has not previously been reported. Given that rhesus macaques are the animal model of choice for evaluating protective efficacy of HIV/SIV vaccine candidates and that T-FH cells play a pivotal role in aiding B cell maturation, quantifying vaccine induction of HIV/SIV-specific T-FH cells would greatly benefit vaccine development. In this study, we quantified SIV Env-specific IL-21-producing T-FH cells for the first time, to our knowledge, in a nonhuman primate vaccine study. Macaques were primed twice mucosally with adenovirus 5 host range mutant recombinants encoding SIV Env, Rev, Gag, and Nef followed by two i.m. boosts with monomeric SIV gp120 or oligomeric SIV gp140 proteins. At 2 wk after the second protein boost, we obtained lymph node biopsy specimens and quantified the frequency of total and SIV Env-specific IL-21(+) T-FH cells and total germinal center B cells, the size and number of germinal centers, and the frequency of SIV-specific Ab-secreting cells in B cell zones. Multiple correlation analyses established the importance of T-FH for development of B cell responses in systemic and mucosally localized compartments, including blood, bone marrow, and rectum. Our results suggest that the SIV-specific T-FH cells, initially induced by replicating adenovirus-recombinant priming, are long lived. The multiple correlations of SIV Env-specific T-FH cells with systemic and mucosal SIV-specific B cell responses indicate that this cell population should be further investigated in HIV vaccine development as a novel correlate of immunity.
C1 [Vargas-Inchaustegui, Diego A.; Shaw, Julia M.; Tuero, Iskra; Musich, Thomas; Mohanram, Venkatramanan; Demberg, Thorsten; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Demers, Andrew; Kang, Guobin; Li, Qingsheng] Univ Nebraska, Nebraska Ctr Virol, Sch Biol Sci, Lincoln, NE 68583 USA.
[Ball, David; Karpova, Tatiana S.] NCI, Ctr Canc Res Core Fluorescence Imaging Facil, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Vargas-Inchaustegui, DA; Robert-Guroff, M (reprint author), NCI, NIH, Bldg 41,Rooms D804 & D310, Bethesda, MD 20892 USA.
EM vargasinchausda@mail.nih.gov; guroffm@mail.nih.gov
RI Mohanram, Venkatramanan/I-3652-2016
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute [R01 DK087625-01]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute and by
Grant R01 DK087625-01 (to Q.L.).
NR 48
TC 7
Z9 7
U1 1
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2016
VL 196
IS 4
BP 1700
EP 1710
DI 10.4049/jimmunol.1502137
PG 11
WC Immunology
SC Immunology
GA DD0TJ
UT WOS:000369632300028
PM 26773147
ER
PT J
AU Zhang, L
Wu, WKK
Gallo, RL
Fang, EF
Hu, W
Ling, TKW
Shen, J
Chan, RLY
Lu, L
Luo, XM
Li, MX
Chan, KM
Yu, J
Wong, VWS
Ng, SC
Wong, SH
Chan, FKL
Sung, JJY
Chan, MTV
Cho, CH
AF Zhang, Lin
Wu, William K. K.
Gallo, Richard L.
Fang, Evandro F.
Hu, Wei
Ling, Thomas K. W.
Shen, Jing
Chan, Ruby L. Y.
Lu, Lan
Luo, Xiao M.
Li, Ming X.
Chan, Kam M.
Yu, Jun
Wong, Vincent W. S.
Ng, Siew C.
Wong, Sunny H.
Chan, Francis K. L.
Sung, Joseph J. Y.
Chan, Matthew T. V.
Cho, Chi H.
TI Critical Role of Antimicrobial Peptide Cathelicidin for Controlling
Helicobacter pylori Survival and Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN GASTRIC-MUCOSA; BIOFILM FORMATION; LACTOCOCCUS-LACTIS; IN-VITRO;
PSEUDOMONAS-AERUGINOSA; ULCERATIVE-COLITIS; TRUNCATED VARIANTS;
CELL-SURFACE; LL-37; CANCER
AB The antimicrobial peptide cathelicidin is critical for protection against different kinds of microbial infection. This study sought to elucidate the protective action of cathelicidin against Helicobacter pylori infection and its associated gastritis. Exogenous cathelicidin was found to inhibit H. pylori growth, destroy the bacteria biofilm, and induce morphological alterations in H. pylori membrane. Additionally, knockdown of endogenous cathelicidin in human gastric epithelial HFE-145 cells markedly increased the intracellular survival of H. pylori. Consistently, cathelicidin knockout mice exhibited stronger H. pylori colonization, higher expression of proinflammatory cytokines IL-6, IL-1 beta, and ICAM1, and lower expression of the anti-inflammatory cytokine IL-10 in the gastric mucosa upon H. pylori infection. In wild-type mice, H. pylori infection also stimulated gastric epithelium-derived cathelicidin production. Importantly, pretreatment with bioengineered Lactococcus lactis that actively secretes cathelicidin significantly increased mucosal cathelicidin levels and reduced H. pylori infection and the associated inflammation. Moreover, cathelicidin strengthened the barrier function of gastric mucosa by stimulating mucus synthesis. Collectively, these findings indicate that cathelicidin plays a significant role as a potential natural antibiotic for H. pylori clearance and a therapeutic agent for chronic gastritis.
C1 [Zhang, Lin; Wu, William K. K.; Yu, Jun; Wong, Vincent W. S.; Ng, Siew C.; Wong, Sunny H.; Chan, Francis K. L.; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Inst Digest Dis, Li Ka Shing Inst Hlth Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Zhang, Lin; Wu, William K. K.; Yu, Jun; Wong, Vincent W. S.; Ng, Siew C.; Wong, Sunny H.; Chan, Francis K. L.; Sung, Joseph J. Y.] Chinese Univ Hong Kong, State Key Lab Digest Dis, Li Ka Shing Inst Hlth Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China.
[Zhang, Lin; Yu, Jun; Wong, Vincent W. S.; Ng, Siew C.; Wong, Sunny H.; Chan, Francis K. L.; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Fac Med, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.
[Zhang, Lin; Wu, William K. K.; Yu, Jun; Wong, Sunny H.; Chan, Francis K. L.; Sung, Joseph J. Y.] CUHK Shenzhen Res Inst, Shenzhen 518057, Peoples R China.
[Wu, William K. K.; Chan, Matthew T. V.] Chinese Univ Hong Kong, Dept Anesthesia & Intens Care, Hong Kong, Hong Kong, Peoples R China.
[Gallo, Richard L.] Univ Calif San Diego, Div Dermatol, La Jolla, CA 92093 USA.
[Fang, Evandro F.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Hu, Wei; Shen, Jing; Chan, Ruby L. Y.; Lu, Lan; Luo, Xiao M.; Li, Ming X.; Chan, Kam M.; Cho, Chi H.] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Ling, Thomas K. W.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China.
RP Wu, WKK (reprint author), Chinese Univ Hong Kong, Dept Anesthesia & Intens Care, CUHK Shenzhen Res Inst, 2 Yuexing Rd, Shenzhen 518057, Peoples R China.; Zhang, L (reprint author), Chinese Univ Hong Kong, Dept Med & Therapeut, CUHK Shenzhen Res Inst, 2 Yuexing Rd, Shenzhen 518057, Peoples R China.
EM linzhang@cuhk.edu.hk; wukakei@cuhk.edu.hk
RI Wu, William K.K./A-3277-2009; Wong, Vincent/K-3864-2014; Wong,
Sunny/N-3754-2015; Ng, Siew Chien/N-4733-2015; Chan, Matthew
/J-2884-2013; Yu, Jun /D-8569-2015; ZHANG , Lin/O-9109-2015; Cho, Chi
Hin/C-6543-2014; Chan, Francis K. L./F-4851-2010
OI Wu, William K.K./0000-0002-5662-5240; Wong, Sunny/0000-0002-3354-9310;
Ng, Siew Chien/0000-0002-6850-4454; Cho, Chi Hin/0000-0002-7658-3260;
Chan, Francis K. L./0000-0001-7388-2436
FU Research Fund for the Control of Infectious Diseases Grant from the Food
and Health Bureau of Hong Kong, National Natural Science Foundation of
China [08070402, 81402014]; Shenzhen Science and Technology Program
[JCYC20140905151710921]
FX This work was supported by Research Fund for the Control of Infectious
Diseases Grant 08070402 from the Food and Health Bureau of Hong Kong,
National Natural Science Foundation of China Grant 81402014 and by
Shenzhen Science and Technology Program JCYC20140905151710921.
NR 61
TC 2
Z9 2
U1 7
U2 23
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD FEB 15
PY 2016
VL 196
IS 4
BP 1799
EP 1809
DI 10.4049/jimmunol.1500021
PG 11
WC Immunology
SC Immunology
GA DD0TJ
UT WOS:000369632300037
PM 26800870
ER
PT J
AU Kines, RC
Cerio, RJ
Roberts, JN
Thompson, CD
de Los Pinos, E
Lowy, DR
Schiller, JT
AF Kines, Rhonda C.
Cerio, Rebecca J.
Roberts, Jeffrey N.
Thompson, Cynthia D.
de Los Pinos, Elisabet
Lowy, Douglas R.
Schiller, John T.
TI Human papillomavirus capsids preferentially bind and infect tumor cells
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; heparan sulfate proteoglycans; tumor tropism
ID SURFACE HEPARAN-SULFATE; VIRUS-LIKE PARTICLES; LUNG-CANCER;
COLORECTAL-CANCER; GLYCOSAMINOGLYCANS; GROWTH; HPV; IDENTIFICATION;
PROTEOGLYCANS; METASTASIS
AB We previously determined that human papillomavirus (HPV) virus-like particles (VLPs) and pseudovirions (PsV) did not, respectively, bind to or infect intact epithelium of the cervicovaginal tract. However, they strongly bound heparan sulfate proteoglycans (HSPG) on the basement membrane of disrupted epithelium and infected the keratinocytes that subsequently entered the disrupted site. We here report that HPV capsids (VLP and PsV) have the same restricted tropism for a wide variety of disrupted epithelial and mesothelial tissues, whereas intact tissues remain resistant to binding. However, the HPV capsids directly bind and infect most tumor-derived cell lines in vitro and have analogous tumor-specific properties in vivo, after local or intravenous injection, using orthotopic models for human ovarian and lung cancer, respectively. The pseudovirions also specifically infected implanted primary human ovarian tumors. Heparin and i-carrageenan blocked binding and infection of all tumor lines tested, implying that tumor cell binding is HSPG-dependent. A survey using a panel of modified heparins indicates that N-sulfation and, to a lesser degree, O-6 sulfation of the surface HSPG on the tumors are important for HPV binding. Therefore, it appears that tumor cells consistently evolve HSPG modification patterns that mimic the pattern normally found on the basement membrane but not on the apical surfaces of normal epithelial or mesothelial cells. Consequently, appropriately modified HPV VLPs and/or PsV could be useful reagents to detect and potentially treat a remarkably broad spectrum of cancers.
C1 [Kines, Rhonda C.; de Los Pinos, Elisabet] Aura Biosci, Cambridge, MA USA.
[Cerio, Rebecca J.; Roberts, Jeffrey N.; Thompson, Cynthia D.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, 9000 Rockville Pike,Bldg 37,Room 4106, Bethesda, MD 20892 USA.
EM schillej@dc37a.nci.nih.gov
FU NIH Intramural Program and Aura Biosciences
FX Grant sponsors: NIH Intramural Program and Aura Biosciences
NR 44
TC 3
Z9 3
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD FEB 15
PY 2016
VL 138
IS 4
BP 901
EP 911
DI 10.1002/ijc.29823
PG 11
WC Oncology
SC Oncology
GA DC4BH
UT WOS:000369164200012
PM 26317490
ER
PT J
AU Barone, FC
Gustafson, D
Crystal, HA
Moreno, H
Adamski, MG
Arai, K
Baird, AE
Balucani, C
Brickman, AM
Cechetto, D
Gorelick, P
Biessels, GJ
Kiliaan, A
Launer, L
Schneider, J
Sorond, FA
Whitmer, R
Wright, C
Zhang, ZG
AF Barone, Frank C.
Gustafson, Deborah
Crystal, Howard A.
Moreno, Herman
Adamski, Mateusz G.
Arai, Ken
Baird, Alison E.
Balucani, Clotilde
Brickman, Adam M.
Cechetto, David
Gorelick, Philip
Biessels, Geert Jan
Kiliaan, Amanda
Launer, Lenore
Schneider, Julie
Sorond, Farzaneh A.
Whitmer, Rachel
Wright, Clinton
Zhang, Zheng Gang
TI First translational 'Think Tank' on cerebrovascular disease, cognitive
impairment and dementia
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID LATE-ONSET DEMENTIA; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; MEDITERRANEAN
DIET; VASCULAR DEMENTIA; GENE-EXPRESSION; DIAGNOSTIC-CRITERIA; METABOLIC
SYNDROME; BRAIN-INJURY; T-CELLS
AB As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/ debated the potential utility of diagnostic/ prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our " First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop".
C1 [Barone, Frank C.; Gustafson, Deborah; Crystal, Howard A.; Moreno, Herman; Baird, Alison E.; Balucani, Clotilde] Suny Downstate Med Ctr, Neurol, Brooklyn, NY 11203 USA.
[Barone, Frank C.; Moreno, Herman; Baird, Alison E.] Suny Downstate Med Ctr, Physiol & Pharmacol, Brooklyn, NY 11203 USA.
[Gustafson, Deborah] Suny Downstate Med Ctr, Sect Neuroepidemiol, Brooklyn, NY 11203 USA.
[Crystal, Howard A.] Suny Downstate Med Ctr, Pathol, Brooklyn, NY 11203 USA.
[Adamski, Mateusz G.] Jagiellonian Univ, Jagiellonian Ctr Expt Therapeut, Krakow, Poland.
[Arai, Ken] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Boston, MA 02115 USA.
[Arai, Ken] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Neuroprotect Res Lab, Boston, MA 02115 USA.
[Brickman, Adam M.] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA.
[Cechetto, David] Univ Western Ontario, Dept Anat & Cell Biol, Schulich Sch Med & Dent, London, ON, Canada.
[Gorelick, Philip] Michigan State Univ, Mercy Hlth Hauenstein Neurosci, Translat Sci & Mol Med, Coll Human Med, Grand Rapids, MI USA.
[Biessels, Geert Jan] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol, Utrecht, Netherlands.
[Kiliaan, Amanda] Radboud Univ Nijmegen, Dept Anat, Preclin Imaging Ctr, Donders Inst Brain Cognit & Behav,Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Launer, Lenore] NIA, Neuroepidemiol Sect, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Schneider, Julie] Rush Univ, Med Ctr, Pathol Neuropathol & Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Sorond, Farzaneh A.] Brigham & Womens Hosp, Dept Neurol, Stroke Div, 75 Francis St, Boston, MA 02115 USA.
[Whitmer, Rachel] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Wright, Clinton] Univ Miami, McKnight Brain Inst, Div Cognit Disorders Neurol Publ Hlth Sci & Neuro, Miami, FL USA.
[Zhang, Zheng Gang] Henry Ford Hosp, Neurol, Detroit, MI 48202 USA.
RP Barone, FC (reprint author), Suny Downstate Med Ctr, Neurol, Brooklyn, NY 11203 USA.
EM frank.barone@downstate.edu
RI Adamski, Mateusz/K-7634-2016; Kiliaan, Amanda/D-8778-2012; Adamski,
Mateusz G/F-6274-2015;
OI Adamski, Mateusz G/0000-0002-8340-2181; barone, Frank
C/0000-0001-8509-3936
FU Leo and Anne Albert Charitable Trust; American Heart Association
[13GRNT14770012]
FX "The Leo and Anne Albert Charitable Trust" fully supported this
inaugural international workshop and also fully supported the
publication of this summary of the meeting. The American Heart
Association provided "Grant in Aid" (13GRNT14770012; Founders Affiliate)
support to the primary organizer (FCB).
NR 74
TC 0
Z9 0
U1 6
U2 12
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 FEB 13
PY 2016
VL 14
AR 50
DI 10.1186/s12967-016-0806-z
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DD5BV
UT WOS:000369938300001
PM 26873444
ER
PT J
AU Jara-Oseguera, A
Bae, C
Swartz, KJ
AF Jara-Oseguera, Andres
Bae, Chanhyung
Swartz, Kenton J.
TI An external sodium ion binding site controls allosteric gating in TRPV1
channels
SO ELIFE
LA English
DT Article
ID DEPENDENT K+ CHANNEL; CAPSAICIN RECEPTOR; VANILLOID RECEPTOR; PORE
TURRET; HEAT ACTIVATION; DOMAIN; VOLTAGE; VR1; THERMODYNAMICS;
SENSITIVITY
AB TRPV1 channels in sensory neurons are integrators of painful stimuli and heat, yet how they integrate diverse stimuli and sense temperature remains elusive. Here, we show that external sodium ions stabilize the TRPV1 channel in a closed state, such that removing the external ion leads to channel activation. In studying the underlying mechanism, we find that the temperature sensors in TRPV1 activate in two steps to favor opening, and that the binding of sodium to an extracellular site exerts allosteric control over temperature-sensor activation and opening of the pore. The binding of a tarantula toxin to the external pore also exerts control over temperature-sensor activation, whereas binding of vanilloids influences temperature-sensitivity by largely affecting the open/closed equilibrium. Our results reveal a fundamental role of the external pore in the allosteric control of TRPV1 channel gating and provide essential constraints for understanding how these channels can be tuned by diverse stimuli.
C1 [Jara-Oseguera, Andres; Bae, Chanhyung; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM swartzk@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke [NS002945]
FX National Institute of Neurological Disorders and Stroke NS002945 Kenton
J Swartz
NR 54
TC 4
Z9 4
U1 2
U2 5
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 12
PY 2016
VL 5
AR e13356
DI 10.7554/eLife.13356
PG 33
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DG2AC
UT WOS:000371867600001
ER
PT J
AU Smith, SH
Peredo, CE
Takeda, Y
Bui, T
Neil, J
Rickard, D
Millerman, E
Therrien, JP
Nicodeme, E
Brusq, JM
Birault, V
Viviani, F
Hofland, H
Jetten, AM
Cote-Sierra, J
AF Smith, Susan H.
Peredo, Carlos E.
Takeda, Yukimasa
Thi Bui
Neil, Jessica
Rickard, David
Millerman, Elizabeth
Therrien, Jean-Philippe
Nicodeme, Edwige
Brusq, Jean-Marie
Birault, Veronique
Viviani, Fabrice
Hofland, Hans
Jetten, Anton M.
Cote-Sierra, Javier
TI Development of a Topical Treatment for Psoriasis Targeting ROR gamma:
From Bench to Skin
SO PLOS ONE
LA English
DT Article
ID T(H)17 CELL-DIFFERENTIATION; NUCLEAR RECEPTORS; T-CELLS; IN-VIVO;
INFLAMMATION; POTENT; IDENTIFICATION; ACTIVATION; MECHANISMS; EXPRESSION
AB Background
Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies. Thus, for the majority of psoriasis patients ineligible for systemic treatments, a small molecule targeting ROR gamma t, the master regulator of IL-17 family cytokines, may represent an alternative topical medicine with biologic-like efficacy.
Methods and Findings
The preclinical studies described in this manuscript bridge the gap from bench to bedside to provide the scientific foundation for a compound entering clinical trials for patients with mild to moderate psoriasis. In addition to several ex vivo reporter assays, primary T cell cultures, and the imiquimod mouse model, we demonstrate efficacy in a newly developed human ex vivo skin assay, where Th17-skewed cytokine expression is induced from skin-resident immune cells. Importantly, the skin barrier remains intact allowing for the demonstration of topical drug delivery. With the development of this novel assay, we demonstrate potent compound activity in the target tissue: human skin. Finally, target engagement by this small molecule was confirmed in ex vivo lesional psoriatic skin.
Conclusions
Our work describes a progressive series of assays to demonstrate the potential clinical value of a novel ROR gamma inverse agonist small molecule with high potency and selectivity, which will enter clinical trials in late 2015 for psoriasis patients.
C1 [Smith, Susan H.; Peredo, Carlos E.; Thi Bui; Neil, Jessica; Millerman, Elizabeth; Therrien, Jean-Philippe; Hofland, Hans; Cote-Sierra, Javier] Stiefel, Discovery & Preclin Dev, Res Triangle Pk, NC USA.
[Takeda, Yukimasa; Jetten, Anton M.] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Nicodeme, Edwige; Brusq, Jean-Marie; Viviani, Fabrice] GlaxoSmithKline, Flexible Discovery Unit, Les Ulis, France.
[Rickard, David] GlaxoSmithKline, MDR PTS, Res Triangle Pk, NC USA.
[Birault, Veronique] GlaxoSmithKline, Med Res Ctr, Resp Therapeut Area, Gunnels Wood Rd, Stevenage, Herts, England.
[Hofland, Hans] Dermira Inc, Redwood City, CA USA.
[Cote-Sierra, Javier] Pfizer Inc, External R&D Innovat Inflammat & Immunol, Cambridge, MA USA.
RP Smith, SH (reprint author), Stiefel, Discovery & Preclin Dev, Res Triangle Pk, NC USA.
EM susan.h.smith@stiefel.com
FU GlaxoSmithKline, plc.; Intramural Research Program of the NIEHS, NIH
[Z01-ES-100485]
FX The funder (GlaxoSmithKline, plc.) provided support in the form of
salaries for authors (SHS, CEP, TB, JN, DR, EM, JPT, EN, JMB, VB, HH,
JCS). The specific roles these authors are articulated in the "author
contributions" section. This work was also in part funded by the
Intramural Research Program of the NIEHS, NIH (Z01-ES-100485) in the
form of salaries for authors (YT and AMJ), but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific
roles of these authors are articulated in the "author contributions"
section.
NR 38
TC 5
Z9 5
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 FEB 12
PY 2016
VL 11
IS 2
AR e0147979
DI 10.1371/journal.pone.0147979
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6SI
UT WOS:000370054100014
PM 26870941
ER
PT J
AU Gehlot, P
Shukla, V
Gupta, S
Makidon, PE
AF Gehlot, Prashasnika
Shukla, Vivek
Gupta, Sanjay
Makidon, Paul E.
TI Detection of ALDH1 activity in rabbit hepatic VX2 tumors and isolation
of ALDH1 positive cancer stem cells
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Hepatocellular carcinoma; Aldehyde dehydrogenase; Cancer stem cells;
Rabbit VX2
ID ALDEHYDE DEHYDROGENASE-ACTIVITY; ACUTE MYELOID-LEUKEMIA;
HEPATOCELLULAR-CARCINOMA; LUNG-CANCER; LIVER-CANCER; THERAPY; MARKER;
EXPRESSION; RESISTANCE; MANAGEMENT
AB Background: Aldehyde dehydrogenase 1 (ALDH1) activity has been implicated in the therapeutic drug resistance of many malignancies and has been widely used as a marker to identify stem-like cells, including in primary liver cancer. Cancer stem cells (CSCs) are thought to play a crucial role in cancer progression and metastasis. In order to clarify the validity of the rabbit VX2 liver cancer model, we questioned if it expresses ALDH1 as a potential marker of CSCs. Hepatocellular carcinoma is a common malignancy worldwide and has poor prognosis. Most of the animal models used to study hepatocellular carcinoma are rodent models which lack clinical relevance. The rabbit VX2 model is a large animal model useful for preclinical and for developing drugs targeting cancer stem cells.
Materials and methods: We used flow cytometry to identify rabbit VX2 liver tumor cells that express ALDH1A1 activity at a high level and confirmed the results with RT-PCR, immunohistochemical and western blot analyses. Further, mRNA and protein expression analysis of tumor samples also express the markers for stemness like klf4, oct3/4, CD44 and nanog as well as the differentiation marker alpha-fetoprotein.
Results: We used Aldefluor flow cytometry-based assay to identify cells with high ALDH1 activity in the rabbit VX2 liver cancer model. We used the brightest 4.39 % of the total cancer cell population in our study. We performed semi-quantitative as well as real time PCR to characterize the stemness derived from VX2 tumors and tissues from normal rabbit liver. We demonstrated that VX2 tumors have higher expression of cancer stem cell markers such as AlDH1A1 and CD44 in comparison to normal rabbit liver cells. Additionally, real time PCR analysis of the same samples using syber-green demonstrated the significant change (p > 0.05) in the expression of genes. We validated the gene expression of the stemness markers by performing western blot and immunofluorescence. We showed that cancer stem cell markers (AlDH1A1, CD44) and the differentiation marker alpha-fetoprotein were upregulated in VX2 tumor cells. The same extent of upregulation was observed in stemness markers (klf4, oct3/4 and nanog) in VX2 tumors in comparison to normal rabbit liver.
Conclusion: The overall results of this study indicate that ALDH1 is a valid CSC marker for VX2 cancer. This finding suggests that the rabbit VX2 liver cancer model is useful in studying drug resistance in hepatocellular carcinoma and may be useful for basic and preclinical studies of other types of human cancer.
C1 [Gehlot, Prashasnika] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Shukla, Vivek] NCI, TGIB Branch, Betehsda, MD USA.
[Gupta, Sanjay] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol Imaging, Houston, TX 77030 USA.
[Makidon, Paul E.] Univ Michigan, Unit Lab Anim Med, Sch Med, Ann Arbor, MI 48109 USA.
RP Gehlot, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
EM pgehlot@med.umich.edu
FU Unit for Laboratory Animal Medicine, University of Michigan Medical
School
FX This work was funded in part by funding from the Unit for Laboratory
Animal Medicine, University of Michigan Medical School. The authors
would like to thank Karen Ramirez and Kathryn E Ruisaard (flowcytometry)
at MD Anderson Cancer Center.
NR 38
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U1 1
U2 8
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 FEB 12
PY 2016
VL 14
AR 49
DI 10.1186/s12967-016-0785-0
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DD5BP
UT WOS:000369937600002
PM 26873175
ER
PT J
AU Simonti, CN
Vernot, B
Bastarache, L
Bottinger, E
Carrell, DS
Chisholm, RL
Crosslin, DR
Hebbring, SJ
Jarvik, GP
Kullo, IJ
Li, RL
Pathak, J
Ritchie, MD
Roden, DM
Verma, SS
Tromp, G
Prato, JD
Bush, WS
Akey, JM
Denny, JC
Capra, JA
AF Simonti, Corinne N.
Vernot, Benjamin
Bastarache, Lisa
Bottinger, Erwin
Carrell, David S.
Chisholm, Rex L.
Crosslin, David R.
Hebbring, Scott J.
Jarvik, Gail P.
Kullo, Iftikhar J.
Li, Rongling
Pathak, Jyotishman
Ritchie, Marylyn D.
Roden, Dan M.
Verma, Shefali S.
Tromp, Gerard
Prato, Jeffrey D.
Bush, William S.
Akey, Joshua M.
Denny, Joshua C.
Capra, John A.
TI The phenotypic legacy of admixture between modern humans and Neandertals
SO SCIENCE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ANCESTRY; EXPRESSION; DENISOVAN; EVOLUTION;
EUROPEANS; SEQUENCE; DISEASE; DNA
AB Many modern human genomes retain DNA inherited from interbreeding with archaic hominins, such as Neandertals, yet the influence of this admixture on human traits is largely unknown. We analyzed the contribution of common Neandertal variants to over 1000 electronic health record (EHR)-derived phenotypes in similar to 28,000 adults of European ancestry. We discovered and replicated associations of Neandertal alleles with neurological, psychiatric, immunological, and dermatological phenotypes. Neandertal alleles together explained a significant fraction of the variation in risk for depression and skin lesions resulting from sun exposure (actinic keratosis), and individual Neandertal alleles were significantly associated with specific human phenotypes, including hypercoagulation and tobacco use. Our results establish that archaic admixture influences disease risk in modern humans, provide hypotheses about the effects of hundreds of Neandertal haplotypes, and demonstrate the utility of EHR data in evolutionary analyses.
C1 [Simonti, Corinne N.; Roden, Dan M.; Denny, Joshua C.; Capra, John A.] Vanderbilt Univ, Vanderbilt Genet Inst, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Vernot, Benjamin; Crosslin, David R.; Jarvik, Gail P.; Akey, Joshua M.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Bastarache, Lisa; Roden, Dan M.; Prato, Jeffrey D.; Denny, Joshua C.; Capra, John A.] Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Bottinger, Erwin] Mt Sinai Sch Med, New York, NY USA.
[Carrell, David S.; Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Med Ctr, Dept Med Med Genet, Seattle, WA 98195 USA.
[Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA.
[Hebbring, Scott J.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI USA.
[Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Li, Rongling] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Pathak, Jyotishman] Mayo Clin, Div Hlth Sci Res, Rochester, MN USA.
[Ritchie, Marylyn D.; Verma, Shefali S.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Ritchie, Marylyn D.] Geisinger Hlth Syst, Biomed & Translat Informat, Danville, PA USA.
[Roden, Dan M.; Denny, Joshua C.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Roden, Dan M.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA.
[Tromp, Gerard] Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.
[Tromp, Gerard] Univ Stellenbosch, Dept Biomed Sci, Div Mol Biol & Human Genet, Fac Hlth Sci, ZA-7505 Tygerberg, South Africa.
[Bush, William S.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Capra, John A.] Vanderbilt Univ, Dept Biol Sci, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Capra, John A.] Vanderbilt Univ, Ctr Quantitat Sci, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Pathak, Jyotishman] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA.
RP Capra, JA (reprint author), Vanderbilt Univ, Vanderbilt Genet Inst, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM tony.capra@vanderbilt.edu
FU NIH [5T32EY021453, R01GM110068, 1R01GM114128]; Vanderbilt Center for
Quantitative Sciences; National Human Genome Research Institute
[U01HG004438, U01HG004610, U01HG008657, U01HG004608, 1K22LM011938,
U01HG006389, U01HG04599, U01HG006379, U01HG004609, U01HG006388,
U01HG04603, U01HG006378, U01HG006385, U01HG006382, U01HG006380];
Glenview Capital; [R01LM010685]
FX The data reported in this paper are available in the supplementary
materials and in the Neandertal PheWAS Catalog
(https://phewas.mc.vanderbilt.edu/neanderthal). The raw genotype and
phenotype data used in this study are subject to the data use and
availability requirements of the eMERGE network outlined at
https://emerge.mc.vanderbilt.edu/collaborate. We thank A. Fish, J. Hall,
D. Mortlock, D. Samuels, M. Sivley, and P. Wu for helpful discussions.
C.N.S. was supported by NIH grant 5T32EY021453 to Vanderbilt University
and a pilot project award from the Vanderbilt Center for Quantitative
Sciences. The eMERGE Network was initiated and funded by the National
Human Genome Research Institute through the following grants:
U01HG004438 to Johns Hopkins University; U01HG004610 and U01HG008657 to
Group Health Cooperative and University of Washington, Seattle;
U01HG004608 and 1K22LM011938 to the Marshfield Clinic; U01HG006389 to
the Essentia Institute of Rural Health; U01HG04599 and U01HG006379 to
the Mayo Clinic; U01HG004609 and U01HG006388 to Northwestern University;
U01HG04603 and U01HG006378 to Vanderbilt University; U01HG006385 to the
Coordinating Center of the eMERGE Network; U01HG006382 to the Geisinger
Clinic; and U01HG006380 to the Mount Sinai School of Medicine. J. M. A.
is a paid consultant for Glenview Capital and provides advice on
next-generation sequencing technologies. PheWAS method development was
supported by grant R01LM010685. J. M. A. was supported in part by NIH
grant R01GM110068. S.J.H was supported in part by NIH grant
1R01GM114128. The authors report no conflicts of interest.
NR 25
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Z9 20
U1 43
U2 91
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD FEB 12
PY 2016
VL 351
IS 6274
BP 737
EP 741
DI 10.1126/science.aad2149
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD3GL
UT WOS:000369810000047
PM 26912863
ER
PT J
AU Nemeth, K
Mezey, E
AF Nemeth, Krisztian
Mezey, Eva
TI Origin of stem cells in the BM niche: new clues from mastocytosis
SO BLOOD
LA English
DT Editorial Material
C1 [Nemeth, Krisztian; Mezey, Eva] NIH, Bethesda, MD 20892 USA.
[Nemeth, Krisztian] Med Coll Wisconsin, Madison, WI USA.
RP Nemeth, K (reprint author), NIH, Bethesda, MD 20892 USA.
FU NIDDK NIH HHS [P30 DK089502]
NR 10
TC 0
Z9 0
U1 2
U2 2
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 FEB 11
PY 2016
VL 127
IS 6
BP 670
EP +
DI 10.1182/blood-2015-12-686626
PG 3
WC Hematology
SC Hematology
GA DI3JJ
UT WOS:000373394600006
PM 26869307
ER
PT J
AU Zerze, GH
Mittal, J
Best, RB
AF Zerze, Guel H.
Mittal, Jeetain
Best, Robert B.
TI Diffusive Dynamics of Contact Formation in Disordered Polypeptides
SO PHYSICAL REVIEW LETTERS
LA English
DT Article
ID SINGLE-MOLECULE SPECTROSCOPY; LOOP FORMATION; UNFOLDED PROTEINS; SPEED
LIMIT; SIMULATIONS; WATER; COLLAPSE; PEPTIDE; MODEL; EFFICIENT
AB Experiments measuring contact formation between probes in disordered chains provide information on the fundamental time scales relevant to protein folding. However, their interpretation usually relies on one-dimensional (1D) diffusion models, as do many experiments probing a single distance. Here, we use all-atom molecular simulations to capture both the time scales of contact formation, as well as the scaling with peptide length for tryptophan triplet quenching experiments, revealing the sensitivity of the experimental quenching times to the configurational space explored by the chain. We find a remarkable consistency between the results of the full calculation and from Szabo-Schulten-Schulten theory applied to a 1D diffusion model, supporting the validity of such models. The significant reduction in diffusion coefficient at the small probe separations which most influence quenching rate, suggests that contact formation and Forster resonance energy transfer correlation experiments provide complementary information on diffusivity.
C1 [Zerze, Guel H.; Mittal, Jeetain] Lehigh Univ, Dept Chem & Biomol Engn, Bethlehem, PA 18015 USA.
[Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
RP Mittal, J (reprint author), Lehigh Univ, Dept Chem & Biomol Engn, Bethlehem, PA 18015 USA.; Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM jeetain@lehigh.edu; robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU U.S. Department of Energy (DOE), Office of Science, Basic Energy
Sciences (BES) [DESC0013979]; Intramural Research Program of the NIDDK,
NIH; National Science Foundation (NSF) [TG-MCB-120014]
FX We thank Marco Buscaglia, Bill Eaton, Gerhard Hummer, and Ben Schuler
for helpful comments on the Letter. Work at Lehigh University was
supported by the U.S. Department of Energy (DOE), Office of Science,
Basic Energy Sciences (BES) under Award No. DESC0013979 and the
Intramural Research Program of the NIDDK, NIH (R. B. B.). Use of the
high-performance computing capabilities of the Extreme Science and
Engineering Discovery Environment (XSEDE), which is supported by the
National Science Foundation (NSF) Grant No. TG-MCB-120014, is gratefully
acknowledged. This work utilized the high-performance computational
capabilities of the Biowulf Linux cluster at the NIH, Bethesda, MD.
NR 38
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U1 5
U2 14
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 0031-9007
EI 1079-7114
J9 PHYS REV LETT
JI Phys. Rev. Lett.
PD FEB 11
PY 2016
VL 116
IS 6
AR 068102
DI 10.1103/PhysRevLett.116.068102
PG 5
WC Physics, Multidisciplinary
SC Physics
GA DD6JJ
UT WOS:000370030200006
PM 26919016
ER
PT J
AU Matthies, D
Dalmas, O
Borgnia, MJ
Dominik, PK
Merk, A
Rao, P
Reddy, BG
Islam, S
Bartesaghi, A
Perozo, E
Subramaniam, S
AF Matthies, Doreen
Dalmas, Olivier
Borgnia, Mario J.
Dominik, Pawel K.
Merk, Alan
Rao, Prashant
Reddy, Bharat G.
Islam, Shahidul
Bartesaghi, Alberto
Perozo, Eduardo
Subramaniam, Sriram
TI Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break
upon Gating
SO CELL
LA English
DT Article
ID ACETYLCHOLINE-RECEPTOR; ANGSTROM RESOLUTION; MOLECULAR-MECHANISM;
BETA-GALACTOSIDASE; CRYSTAL-STRUCTURE; P2X RECEPTORS; ION CHANNELS;
TRANSPORT; SYSTEM; VISUALIZATION
AB CorA, the major Mg2+ uptake system in prokaryotes, is gated by intracellular Mg2+ (K-D similar to 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg2+-bound and Mg2+-free conditions, but EPR spectroscopic studies reveal large Mg2+-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg2+-bound closed conformation and in two open Mg2+-free states at resolutions of 3.8, 7.1, and 7.1 angstrom, respectively. In the absence of bound Mg2+, four of the five subunits are displaced to variable extents (similar to 10-25 angstrom) by hinge-like motions as large as similar to 35 degrees at the stalk helix. The transition between a single 5-fold symmetric closed state and an ensemble of low Mg2+, open, asymmetric conformational states is, thus, the key structural signature of CorA gating. This mechanism is likely to apply to other structurally similar divalent ion channels.
C1 [Matthies, Doreen; Borgnia, Mario J.; Merk, Alan; Rao, Prashant; Bartesaghi, Alberto; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dalmas, Olivier; Dominik, Pawel K.; Reddy, Bharat G.; Islam, Shahidul; Perozo, Eduardo] Univ Chicago, Dept Biochem & Mol Biol, Inst Biophys Dynam, Chicago, IL 60637 USA.
RP Subramaniam, S (reprint author), Univ Chicago, Dept Biochem & Mol Biol, Inst Biophys Dynam, 920 E 58Th St, Chicago, IL 60637 USA.
EM eperozo@uchicago.edu; ss1@nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH; NIH
[GM088406]
FX This research was supported by funds from the Center for Cancer
Research, National Cancer Institute, NIH, and NIH grant GM088406. We
thank Jason Pierson and Lingbo Yu for assistance with data collection;
Robert Mueller for technical assistance with electron microscopy; and
Soojay Banerjee, Lesley A. Earl, Benoit Roux, and Anthony Kossiakoff for
helpful discussions. We also thank Veronica Falconieri for assistance in
preparation of the graphical abstract. This work utilized the
computational resources of the NIH High-Performance Computing (HPC)
Biowulf cluster (http://hpc.nih.gov) and the Gordon cluster at the
Extreme Science and Engineering Discovery Environment (XSEDE).
NR 52
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Z9 15
U1 8
U2 23
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD FEB 11
PY 2016
VL 164
IS 4
BP 747
EP 756
DI 10.1016/j.cell.2015.12.055
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DD5XN
UT WOS:000369998300019
PM 26871634
ER
PT J
AU He, SS
Xiao, JB
Dulcey, AE
Lin, B
Rolt, A
Hu, ZY
Hu, X
Wang, AQ
Xu, X
Southall, N
Ferrer, M
Zheng, W
Liang, TJ
Marugan, JJ
AF He, Shanshan
Xiao, Jingbo
Dulcey, Andres E.
Lin, Billy
Rolt, Adam
Hu, Zongyi
Hu, Xin
Wang, Amy Q.
Xu, Xin
Southall, Noel
Ferrer, Marc
Zheng, Wei
Liang, T. Jake
Marugan, Juan J.
TI Discovery, Optimization, and Characterization of Novel Chlorcyclizine
Derivatives for the Treatment of Hepatitis C Virus Infection
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID GENOTYPE 1 INFECTION; ENTRY; IDENTIFICATION; ANTAGONISTS; LEDIPASVIR;
SOFOSBUVIR; THERAPIES; HISTAMINE; BINDING; DRUGS
AB Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improved in vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host virus interaction.
C1 [He, Shanshan; Lin, Billy; Hu, Zongyi; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Xiao, Jingbo; Dulcey, Andres E.; Rolt, Adam; Hu, Xin; Wang, Amy Q.; Xu, Xin; Southall, Noel; Ferrer, Marc; Zheng, Wei; Marugan, Juan J.] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.; Marugan, JJ (reprint author), NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM jliang@nih.gov; maruganj@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Molecular Libraries; NIH
[N01-DK-7-0004/HHSN26700700004C]
FX We thank S. Michael and M. Balcom for assistance with the robotic
control in qHTS; P. Shinn, M. Itkin, and D. van Leer for help with
compound management; and B. Zhang for technical assistance. We are
grateful for the financial support from the Intramural Research Program
of the National Institute of Diabetes and Digestive and Kidney Diseases
and Molecular Libraries. Primary human hepatocytes were provided by the
NIH-funded Liver Tissue Procurement and Cell Distribution System
(N01-DK-7-0004/HHSN26700700004C, principal investigator, D. Geller,
University of Pittsburgh).
NR 35
TC 4
Z9 4
U1 4
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 11
PY 2016
VL 59
IS 3
BP 841
EP 853
DI 10.1021/acs.jmedchem.5b00752
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DD8YL
UT WOS:000370212700004
PM 26599718
ER
PT J
AU Davies, B
Hatton, E
Altemose, N
Hussin, JG
Pratto, F
Zhang, G
Hinch, AG
Moralli, D
Biggs, D
Diaz, R
Preece, C
Li, R
Bitoun, E
Brick, K
Green, CM
Amerini-Otero, RDC
Myers, SR
Donnelly, P
AF Davies, Benjamin
Hatton, Edouard
Altemose, Nicolas
Hussin, Julie G.
Pratto, Florencia
Zhang, Gang
Hinch, Anjali Gupta
Moralli, Daniela
Biggs, Daniel
Diaz, Rebeca
Preece, Chris
Li, Ran
Bitoun, Emmanuelle
Brick, Kevin
Green, Catherine M.
Amerini-Otero, R. Daniel C.
Myers, Simon R.
Donnelly, Peter
TI Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in
mice
SO NATURE
LA English
DT Article
ID HISTONE H3 METHYLTRANSFERASE; RECOMBINATION HOT-SPOT; MEIOTIC
RECOMBINATION; HOMOLOGY SEARCH; ALIGNMENT; COMPLEX; DRIVE; GENE
AB The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such ` symmetric' PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation.
C1 [Davies, Benjamin; Hatton, Edouard; Altemose, Nicolas; Hussin, Julie G.; Zhang, Gang; Hinch, Anjali Gupta; Moralli, Daniela; Biggs, Daniel; Diaz, Rebeca; Preece, Chris; Li, Ran; Bitoun, Emmanuelle; Green, Catherine M.; Myers, Simon R.; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Altemose, Nicolas; Li, Ran; Myers, Simon R.; Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3LB, England.
[Pratto, Florencia; Brick, Kevin; Amerini-Otero, R. Daniel C.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Donnelly, P (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
EM myers@stats.ox.ac.uk; donnelly@well.ox.ac.uk
OI Diaz, Rebeca/0000-0003-0937-5928
FU Wellcome Trust [090532/Z/09/Z, 095552/Z/11/Z, 098387/Z/12/Z]; NIDDK
Intramural Research Program; Nuffield Department of Medicine Prize
Studentship; Human Frontiers Postdoctoral Program [LT-001017/2013-L]
FX We thank N. Hortin, S. Chen and R. Davies for technical assistance, the
High-Throughput Genomics Group at the Wellcome Trust Centre for Human
Genetics for the generation of the sequencing data and R. Esnouf and J.
Diprose for assistance with computing facilities. PWD/PhJ mice were a
gift from J. Forejt. This work was supported by the Wellcome Trust Core
Award Grant 090532/Z/09/Z, Senior Investigator Award 095552/Z/11/Z (to
P.D.), Investigator Award 098387/Z/12/Z (to S.R.M.) and the NIDDK
Intramural Research Program (R.D.C.O.). E.H. is funded by a Nuffield
Department of Medicine Prize Studentship. J.G.H. is an EPAC/Linacre
Junior Research Fellow funded by the Human Frontiers Postdoctoral
Program (LT-001017/2013-L).
NR 40
TC 18
Z9 19
U1 13
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 171
EP +
DI 10.1038/nature16931
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700029
PM 26840484
ER
PT J
AU Quick, J
Loman, NJ
Duraffour, S
Simpson, JT
Ettore, S
Cowley, L
Bore, JA
Koundouno, R
Dudas, G
Mikhail, A
Ouedraogo, N
Afrough, B
Bah, A
Baum, JHJ
Becker-Ziaja, B
Boettcher, JP
Cabeza-Cabrerizo, M
Camino-Sanchez, A
Carter, LL
Doerrbecker, J
Enkirch, T
Garcia-Dorival, I
Hetzelt, N
Hinzmann, J
Holm, T
Kafetzopoulou, LE
Koropogui, M
Kosgey, A
Kuisma, E
Logue, CH
Mazzarelli, A
Meisel, S
Mertens, M
Michel, J
Ngabo, D
Nitzsche, K
Pallasch, E
Patrono, LV
Portmann, J
Repits, JG
Rickett, NY
Sachse, A
Singethan, K
Vitoriano, I
Emanaberhan, RLY
Zekeng, EG
Racine, T
Bello, A
Sall, AA
Faye, O
Faye, O
Magassouba, N
Williams, CV
Amburgey, V
Winona, L
Davis, E
Gerlach, J
Washington, F
Monteil, V
Jourdain, M
Bererd, M
Camara, A
Somlare, H
Camara, A
Gerard, M
Bado, G
Baillet, B
Delaune, D
Nebie, KY
Diarra, A
Savane, Y
Pallawo, RB
Gutierrez, GJ
Milhano, N
Roger, I
Williams, CJ
Yattara, F
Lewandowski, K
Taylor, J
Rachwal, P
Turner, DJ
Pollakis, G
Hiscox, JA
Matthews, DA
O'Shea, MK
Johnston, AM
Wilson, D
Hutley, E
Smit, E
DiCaro, A
Wolfel, R
Stoecker, K
Fleischmann, E
Gabriel, M
Weller, SA
Koivogui, L
Diallo, B
Keita, S
Rambaut, A
Formenty, P
Gunther, S
Carroll, MW
AF Quick, Joshua
Loman, Nicholas J.
Duraffour, Sophie
Simpson, Jared T.
Severi, Ettore
Cowley, Lauren
Bore, Joseph Akoi
Koundouno, Raymond
Dudas, Gytis
Mikhail, Amy
Ouedraogo, Nobila
Afrough, Babak
Bah, Amadou
Baum, Jonathan H. J.
Becker-Ziaja, Beate
Boettcher, Jan Peter
Cabeza-Cabrerizo, Mar
Camino-Sanchez, Alvaro
Carter, Lisa L.
Doerrbecker, Juliane
Enkirch, Theresa
Garcia-Dorival, Isabel
Hetzelt, Nicole
Hinzmann, Julia
Holm, Tobias
Kafetzopoulou, Liana Eleni
Koropogui, Michel
Kosgey, Abigael
Kuisma, Eeva
Logue, Christopher H.
Mazzarelli, Antonio
Meisel, Sarah
Mertens, Marc
Michel, Janine
Ngabo, Didier
Nitzsche, Katja
Pallasch, Elisa
Patrono, Livia Victoria
Portmann, Jasmine
Repits, Johanna Gabriella
Rickett, Natasha Y.
Sachse, Andreas
Singethan, Katrin
Vitoriano, Ines
Emanaberhan, Rahel L. Y.
Zekeng, Elsa G.
Racine, Trina
Bello, Alexander
Sall, Amadou Alpha
Faye, Ousmane
Faye, Oumar
Magassouba, N'Faly
Williams, Cecelia V.
Amburgey, Victoria
Winona, Linda
Davis, Emily
Gerlach, Jon
Washington, Frank
Monteil, Vanessa
Jourdain, Marine
Bererd, Marion
Camara, Alimou
Somlare, Hermann
Camara, Abdoulaye
Gerard, Marianne
Bado, Guillaume
Baillet, Bernard
Delaune, Deborah
Nebie, Koumpingnin Yacouba
Diarra, Abdoulaye
Savane, Yacouba
Pallawo, Raymond Bernard
Gutierrez, Giovanna Jaramillo
Milhano, Natacha
Roger, Isabelle
Williams, Christopher J.
Yattara, Facinet
Lewandowski, Kuiama
Taylor, James
Rachwal, Phillip
Turner, Daniel J.
Pollakis, Georgios
Hiscox, Julian A.
Matthews, David A.
O'Shea, Matthew K.
Johnston, Andrew McD
Wilson, Duncan
Hutley, Emma
Smit, Erasmus
DiCaro, Antonino
Woelfel, Roman
Stoecker, Kilian
Fleischmann, Erna
Gabriel, Martin
Weller, Simon A.
Koivogui, Lamine
Diallo, Boubacar
Keita, Sakoba
Rambaut, Andrew
Formenty, Pierre
Guenther, Stephan
Carroll, Miles W.
TI Real-time, portable genome sequencing for Ebola surveillance
SO NATURE
LA English
DT Article
ID NANOPORE SEQUENCER; SIERRA-LEONE; VIRUS; OUTBREAK; TRANSMISSION; DNA;
EVOLUTION; DYNAMICS
AB The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths(1). Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 x 10(-3) and 1.42 x 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic(2-7). Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions(8). Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities(9). To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.
C1 [Quick, Joshua; Loman, Nicholas J.; Boettcher, Jan Peter; Garcia-Dorival, Isabel] Univ Birmingham, Inst Microbiol & Infect, Birmingham B15 2TT, W Midlands, England.
[Duraffour, Sophie; Bore, Joseph Akoi; Koundouno, Raymond; Afrough, Babak; Bah, Amadou; Baum, Jonathan H. J.; Becker-Ziaja, Beate; Boettcher, Jan Peter; Cabeza-Cabrerizo, Mar; Camino-Sanchez, Alvaro; Carter, Lisa L.; Doerrbecker, Juliane; Enkirch, Theresa; Garcia-Dorival, Isabel; Hetzelt, Nicole; Hinzmann, Julia; Holm, Tobias; Kafetzopoulou, Liana Eleni; Koropogui, Michel; Kosgey, Abigael; Kuisma, Eeva; Logue, Christopher H.; Mazzarelli, Antonio; Meisel, Sarah; Mertens, Marc; Michel, Janine; Ngabo, Didier; Nitzsche, Katja; Pallasch, Elisa; Patrono, Livia Victoria; Portmann, Jasmine; Repits, Johanna Gabriella; Rickett, Natasha Y.; Sachse, Andreas; Singethan, Katrin; Vitoriano, Ines; Emanaberhan, Rahel L. Y.; Zekeng, Elsa G.; DiCaro, Antonino; Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna; Gabriel, Martin; Guenther, Stephan; Carroll, Miles W.] Bernhard Nocht Inst Trop Med, European Mobile Lab Consortium, D-20359 Hamburg, Germany.
[Duraffour, Sophie; Baum, Jonathan H. J.; Becker-Ziaja, Beate; Cabeza-Cabrerizo, Mar; Doerrbecker, Juliane; Holm, Tobias; Meisel, Sarah; Nitzsche, Katja; Pallasch, Elisa; Patrono, Livia Victoria; Emanaberhan, Rahel L. Y.; Gabriel, Martin; Guenther, Stephan] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany.
[Simpson, Jared T.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Simpson, Jared T.] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada.
[Severi, Ettore; Milhano, Natacha; Williams, Christopher J.] European Ctr Dis Prevent & Control ECDC, S-17165 Solna, Sweden.
[Cowley, Lauren; Mikhail, Amy] Publ Hlth England, Natl Infect Serv, London NW9 5EQ, England.
[Dudas, Gytis; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 2FL, Midlothian, Scotland.
[Ouedraogo, Nobila] Robert Koch Inst, PAE, German FETP, D-13302 Berlin, Germany.
[Afrough, Babak; Kuisma, Eeva; Logue, Christopher H.; Ngabo, Didier; Vitoriano, Ines; Lewandowski, Kuiama; Carroll, Miles W.] Publ Hlth England, Natl Infect Serv, Porton Down SP4 0JG, Wilts, England.
[Bah, Amadou] Swiss Trop & Publ Hlth Inst, CH-4002 Basel, Switzerland.
[Boettcher, Jan Peter; Hetzelt, Nicole; Hinzmann, Julia; Michel, Janine; Sachse, Andreas] Robert Koch Inst, D-13302 Berlin, Germany.
[Carter, Lisa L.] UCL, London WC1E 6BT, England.
[Enkirch, Theresa] Paul Ehrlich Inst, Div Vet Med, D-63225 Langen, Germany.
[Garcia-Dorival, Isabel; Rickett, Natasha Y.; Zekeng, Elsa G.; Pollakis, Georgios; Hiscox, Julian A.] Univ Liverpool, Inst Infect & Global Hlth, Liverpool L69 7BE, Merseyside, England.
[Kafetzopoulou, Liana Eleni] Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, B-3000 Louvain, Belgium.
[Koropogui, Michel; Yattara, Facinet; Keita, Sakoba] Minist Hlth Guinea, Conakry, Guinea.
[Kosgey, Abigael] Kenya Govt Med Res Ctr, Nairobi 00200, Kenya.
[Mazzarelli, Antonio; DiCaro, Antonino] Natl Inst Infect Dis L Spallanzani, I-00149 Rome, Italy.
[Mertens, Marc] Friedrich Loeffler Inst, D-17493 Greifswald, Germany.
[Portmann, Jasmine] Fed Off Civil Protect, Spiez Lab, CH-3700 Spiez, Switzerland.
[Repits, Johanna Gabriella] Janssen Cilag, S-19207 Stockholm, Sweden.
[Rickett, Natasha Y.; Zekeng, Elsa G.; Pollakis, Georgios; Hiscox, Julian A.] Univ Liverpool, NIHR Hlth Protect Res Unit Emerging & Zoonot Infe, Liverpool L69 7BE, Merseyside, England.
[Singethan, Katrin] Tech Univ Munich, Inst Virol, D-81675 Munich, Germany.
[Racine, Trina; Bello, Alexander] Publ Hlth Agcy Canada, Winnipeg, MB R3E 3R2, Canada.
[Sall, Amadou Alpha; Faye, Ousmane] Inst Pasteur, Dakar, Senegal.
[Magassouba, N'Faly] Lab Fievres Hemorrag Guinee, Conakry, Guinea.
[Williams, Cecelia V.; Amburgey, Victoria; Winona, Linda] Sandia Natl Labs, Albuquerque, NM 87185 USA.
[Williams, Cecelia V.; Amburgey, Victoria; Winona, Linda; Davis, Emily; Gerlach, Jon; Washington, Frank] Ratoma Ebola Diagnost Ctr, Conakry, Guinea.
[Davis, Emily; Gerlach, Jon; Washington, Frank] MRIGlobal, Kansas City, MO 64110 USA.
[Monteil, Vanessa; Jourdain, Marine; Bererd, Marion; Camara, Alimou; Somlare, Hermann; Camara, Abdoulaye; Gerard, Marianne; Bado, Guillaume; Baillet, Bernard] Expertise France, Lab Kplan Forecariah Guinee, F-75006 Paris, France.
[Delaune, Deborah] Federat Lab HIA Begin, F-94163 St Mande, France.
[Delaune, Deborah] Ctr Traitement Soignants, Biol Lab, Conakry, Guinea.
[Nebie, Koumpingnin Yacouba; Diarra, Abdoulaye; Savane, Yacouba; Pallawo, Raymond Bernard; Roger, Isabelle; Diallo, Boubacar; Formenty, Pierre] World Hlth Org, Conakry, Guinea.
[Gutierrez, Giovanna Jaramillo] London Sch Hyg & Trop Med, London EC1E 7HT, England.
[Milhano, Natacha] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
[Williams, Christopher J.] Publ Hlth Wales, Cardiff CF11 9LJ, S Glam, Wales.
[Taylor, James; Rachwal, Phillip; Weller, Simon A.] Dstl Porton Down, Salisbury SP4 0JQ, Wilts, England.
[Turner, Daniel J.] Oxford Nanopore Technol, Oxford OX4 4GA, England.
[Matthews, David A.] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England.
[O'Shea, Matthew K.; Johnston, Andrew McD; Wilson, Duncan] Royal Ctr Def Med, Acad Dept Mil Med, Birmingham B15 2TH, W Midlands, England.
[Hutley, Emma] Royal Ctr Def Med, Ctr Def Pathol, Birmingham B15 2TH, W Midlands, England.
[Smit, Erasmus] Queen Elizabeth Hosp, Birmingham B12 2TH, W Midlands, England.
[Woelfel, Roman; Stoecker, Kilian; Fleischmann, Erna] Bundeswehr Inst Microbiol, D-80937 Munich, Germany.
[Koivogui, Lamine] Inst Natl St Publ, Conakry, Guinea.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Rambaut, Andrew] Univ Edinburgh, Ctr Immunol Infect & Evolut, Edinburgh EH9 2FL, Midlothian, Scotland.
[Carroll, Miles W.] Univ Southampton, South Gen Hosp, Southampton SO16 6YD, Hants, England.
[Carroll, Miles W.] NIHR Hlth Protect Res, Res Unit Emerging & Zoonot Infect, PHE Porton Down, London, England.
RP Loman, NJ (reprint author), Univ Birmingham, Inst Microbiol & Infect, Birmingham B15 2TT, W Midlands, England.
EM n.j.loman@bham.ac.uk
RI Di Caro, Antonino/K-6854-2016;
OI Johnston, Andrew McDonald/0000-0002-0220-0589; Hiscox,
Julian/0000-0002-6582-0275; Matthews, David/0000-0003-4611-8795; Di
Caro, Antonino/0000-0001-6027-3009; Loman, Nicholas/0000-0002-9843-8988;
Ngabo, Didier/0000-0003-1818-1439; Dudas, Gytis/0000-0002-0227-4158;
Mazzarelli, Antonio/0000-0001-6285-4368
FU European Union [666100]; Directorate-General for International
Cooperation and Development [IFS/2011/272-372]; NIHR Surgical
Reconstruction and Microbiology Research Centre (SRMRC); Medical
Research Council; Ontario Institute for Cancer Research through
Government of Ontario; UK Ministry of Defence (MOD); EU
[278433-PREDEMICS]; ERC [260864]
FX The EMLab is a technical partner in the WHO Emerging and Dangerous
Pathogens Laboratory Network (EDPLN), and the Global Outbreak Alert and
Response Network (GOARN) and the deployments in West Africa have been
coordinated and supported by the GOARN Operational Support Team at
WHO/HQ and the African Union. This work was carried out in the context
of the project EVIDENT (Ebola virus disease: correlates of protection,
determinants of outcome, and clinical management) that received funding
from the European Union's Horizon 2020 research and innovation program
under grant agreement No 666100 and in the context of service contract
IFS/2011/272-372 funded by Directorate-General for International
Cooperation and Development. J.Q. is funded by the NIHR Surgical
Reconstruction and Microbiology Research Centre (SRMRC). N.J.L. is
funded by a Medical Research Council Special Training Fellowship in
Biomedical Informatics (to September 2015) and a Medical Research
Council Bioinformatics Fellowship. J.T.S. is supported by the Ontario
Institute for Cancer Research through funding provided by the Government
of Ontario. Dstl support was funded by the UK Ministry of Defence (MOD).
Dstl authors thank S. Lonsdale, C. Lonsdale and C. Mayers for supply of
RNA, previous assistance, and review of the manuscript. The views
expressed in this paper are not necessarily endorsed by the UK MOD. A.R.
was supported by EU Seventh Framework Programme [FP7/2007-2013] under
Grant Agreement no. 278433-PREDEMICS and ERC Grant agreement no. 260864.
We are grateful for the generous support of University of Birmingham
alumni for donations in support of the pilot work. The MRC Cloud
Infrastructure for Microbial Bioinformatics (CLIMB) cyberinfrastructure
was used to conduct bioinformatics analysis. The authors would like to
thank B. Oppenheim and C. Wardius for help with logistics and the staff
of Alta Biosciences, University of Birmingham and Sigma-Aldrich for
generating PCR primers especially rapidly for this project. The authors
would like to thank scientists deployed from the Special Pathogens
Program from the National Microbiology Laboratory, Public Health Agency
of Canada, who worked on EBOV diagnostics in Guinea. We are grateful to
I. Goodfellow, M. Cotten and P. Kellam for permission to include
sequences from Sierra Leone in this analysis. We thank R. Vipond for
assistance with validation experiments. We thank H. Eno and B. Myers for
help with proofreading. We are thankful for the generous support of
reagents and technical support from Oxford Nanopore. We thank the staff
at Oxford Nanopore for technical and logistical support during this
project with special thanks to S. Brooking, O. Hartwell, R. Pettett, C.
Brown, G. Sanghera and R. Ronan. We thank T. Bedford and R. Neher for
developing the Nextstrain website.
NR 33
TC 72
Z9 73
U1 19
U2 83
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 11
PY 2016
VL 530
IS 7589
BP 228
EP +
DI 10.1038/nature16996
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD4TX
UT WOS:000369916700041
PM 26840485
ER
PT J
AU Blech-Hermoni, Y
Dasgupta, T
Coram, RJ
Ladd, AN
AF Blech-Hermoni, Yotam
Dasgupta, Twishasri
Coram, Ryan J.
Ladd, Andrea N.
TI Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1)
Regulation in Embryonic Heart Muscle
SO PLOS ONE
LA English
DT Article
ID MESSENGER-RNA DECAY; BINDING PROTEIN CUGBP1; SERUM RESPONSE FACTOR;
GU-RICH ELEMENTS; MYOTONIC-DYSTROPHY; GENE-EXPRESSION; ALTERNATIVE
POLYADENYLATION; DEVELOPMENTAL EXPRESSION; INCREASES TRANSLATION;
SPLICING EVENTS
AB CUG-BP, Elav-like family member 1 (CELF1) is a highly conserved RNA binding protein that regulates pre-mRNA alternative splicing, polyadenylation, mRNA stability, and translation. In the heart, CELF1 is expressed in the myocardium, where its levels are tightly regulated during development. CELF1 levels peak in the heart during embryogenesis, and aberrant up-regulation of CELF1 in the adult heart has been implicated in cardiac pathogenesis in myotonic dystrophy type 1, as well as in diabetic cardiomyopathy. Either inhibition of CELF activity or over-expression of CELF1 in heart muscle causes cardiomyopathy in transgenic mice. Nonetheless, many of the cardiac targets of CELF1 regulation remain unknown. In this study, to identify cardiac targets of CELF1 we performed cross-linking immunoprecipitation (CLIP) for CELF1 from embryonic day 8 chicken hearts. We identified a previously unannotated exon in MYH7B as a novel target of CELF1-mediated regulation. We demonstrated that knockdown of CELF1 in primary chicken embryonic cardiomyocytes leads to increased inclusion of this exon and decreased MYH7B levels. We also investigated global changes in the transcriptome of primary embryonic cardiomyocytes following CELF1 knockdown in a published RNA-seq dataset. Pathway and network analyses identified strong associations between CELF1 and regulation of cell cycle and translation. Important regulatory proteins, including both RNA binding proteins and a cardiac transcription factor, were affected by loss of CELF1. Together, these data suggest that CELF1 is a key regulator of cardiomyocyte gene expression.
C1 [Blech-Hermoni, Yotam; Dasgupta, Twishasri; Coram, Ryan J.; Ladd, Andrea N.] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Blech-Hermoni, Yotam; Ladd, Andrea N.] Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cell Biol Program, Cleveland, OH 44106 USA.
[Blech-Hermoni, Yotam] NINDS, Hereditary Muscle Dis Unit, Neurogenet Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Dasgupta, Twishasri] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
[Coram, Ryan J.] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 USA.
RP Ladd, AN (reprint author), Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.; Ladd, AN (reprint author), Case Western Reserve Univ, Sch Med, Dept Mol Biol & Microbiol, Cell Biol Program, Cleveland, OH 44106 USA.
EM ladda@ccf.org
FU National Institutes of Health [R01HL089376, 5T32GM008056]
FX This work was supported by a grant to ANL from the National Institutes
of Health (R01HL089376). YB-H was supported in part by a National
Institutes of Health training grant (5T32GM008056). The National
Institutes of Health had no involvement in the study design, collection,
analysis, or interpretation of the data, or the writing or submission of
this article for publication.
NR 84
TC 2
Z9 2
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 FEB 11
PY 2016
VL 11
IS 2
AR e0149061
DI 10.1371/journal.pone.0149061
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6RE
UT WOS:000370050700058
PM 26866591
ER
PT J
AU Pain, M
Fuller, AW
Basore, K
Pillai, AD
Solomon, T
Bokhari, AAB
Desai, SA
AF Pain, Margaret
Fuller, Alexandra W.
Basore, Katherine
Pillai, Ajay D.
Solomon, Tsione
Bokhari, Abdullah A. B.
Desai, Sanjay A.
TI Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface
Anion Channel Inhibitors
SO PLOS ONE
LA English
DT Article
ID FALCIPARUM IN-VITRO; RED-BLOOD-CELLS; INFECTED ERYTHROCYTES;
NUTRIENT-UPTAKE; CLAG3 GENES; ANTIMALARIAL-DRUGS; MULTIGENE FAMILY;
PERMEATION; MECHANISMS; RESISTANCE
AB Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC) mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel's structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing.
C1 [Pain, Margaret; Fuller, Alexandra W.; Basore, Katherine; Pillai, Ajay D.; Solomon, Tsione; Bokhari, Abdullah A. B.; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM sdesai@niaid.nih.gov
OI Basore, Katherine/0000-0001-5974-0968
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; Medicines for
Malaria Venture
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases and by the Medicines for Malaria Venture. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
TC 0
Z9 0
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 11
PY 2016
VL 11
IS 2
AR e0149214
DI 10.1371/journal.pone.0149214
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6RE
UT WOS:000370050700078
PM 26866812
ER
PT J
AU Saba, C
Paoloni, M
Mazcko, C
Kisseberth, W
Burton, JH
Smith, A
Wilson-Robles, H
Allstadt, S
Vail, D
Henry, C
Lana, S
Ehrhart, EJ
Charles, B
Kent, M
Lawrence, J
Burgess, K
Borgatti, A
Suter, S
Woods, P
Gordon, I
Vrignaud, P
Khanna, C
LeBlanc, AK
AF Saba, Corey
Paoloni, Melissa
Mazcko, Christina
Kisseberth, William
Burton, Jenna H.
Smith, Annette
Wilson-Robles, Heather
Allstadt, Sara
Vail, David
Henry, Carolyn
Lana, Susan
Ehrhart, E. J.
Charles, Brad
Kent, Michael
Lawrence, Jessica
Burgess, Kristine
Borgatti, Antonella
Suter, Steve
Woods, Paul
Gordon, Ira
Vrignaud, Patricia
Khanna, Chand
LeBlanc, Amy K.
TI A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic
Profile and Biological Activity in a Naturally-Occurring Canine Cancer
Model
SO PLOS ONE
LA English
DT Article
ID TRANSLATION; TRIALS
AB Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and < 1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.
C1 [Saba, Corey; Lawrence, Jessica] Univ Georgia, Coll Vet Med, Athens, GA USA.
[Paoloni, Melissa; Mazcko, Christina; Gordon, Ira; Khanna, Chand; LeBlanc, Amy K.] NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kisseberth, William] Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA.
[Burton, Jenna H.; Lana, Susan; Ehrhart, E. J.; Charles, Brad] Colorado State Univ, Coll Vet Med & Biol Sci, Ft Collins, CO 80523 USA.
[Smith, Annette] Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA.
[Wilson-Robles, Heather] Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA.
[Allstadt, Sara; Kent, Michael] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA.
[Vail, David] Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA.
[Henry, Carolyn] Univ Missouri, Coll Vet Med, Columbia, MO USA.
[Burgess, Kristine] Tufts Univ, Sch Vet Med, 200 Westboro Rd, North Grafton, MA 01536 USA.
[Borgatti, Antonella] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA.
[Suter, Steve] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA.
[Woods, Paul] Univ Guelph, Ontario Vet Coll, Guelph, ON N1G 2W1, Canada.
[Vrignaud, Patricia] Sanofi Aventis, F-94403 Vitry Sur Seine, France.
RP LeBlanc, AK (reprint author), NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM amy.leblanc@nih.gov
OI , Carolyn/0000-0002-2761-5203
FU Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), NCI, Center for Cancer
Research. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.; This
research was supported in part by the Intramural Research Program of the
National Institutes of Health (NIH), NCI, Center for Cancer Research.
The results and interpretations presented herein do not reflect the
views of the US Government. We wish to thank the clinical staff at each
participating COTC site, and the pets and their owners for
participation.
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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 FEB 11
PY 2016
VL 11
IS 2
AR e0149194
DI 10.1371/journal.pone.0149194
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6RE
UT WOS:000370050700077
PM 26866698
ER
PT J
AU Metcalfe, DD
Pawankar, R
Ackerman, SJ
Akin, C
Clayton, F
Falcone, FH
Gleich, GJ
Irani, AM
Johansson, MW
Klion, AD
Leiferman, KM
Levi-Schaffer, F
Nilsson, G
Okayama, Y
Prussin, C
Schroeder, JT
Schwartz, LB
Simon, HU
Walls, AF
Triggiani, M
AF Metcalfe, Dean D.
Pawankar, Ruby
Ackerman, Steven J.
Akin, Cem
Clayton, Frederic
Falcone, Franco H.
Gleich, Gerald J.
Irani, Anne-Marie
Johansson, Mats W.
Klion, Amy D.
Leiferman, Kristin M.
Levi-Schaffer, Francesca
Nilsson, Gunnar
Okayama, Yoshimichi
Prussin, Calman
Schroeder, John T.
Schwartz, Lawrence B.
Simon, Hans-Uwe
Walls, Andrew F.
Triggiani, Massimo
TI Biomarkers of the involvement of mast cells, basophils and eosinophils
in asthma and allergic diseases
SO WORLD ALLERGY ORGANIZATION JOURNAL
LA English
DT Review
ID LEYDEN CRYSTAL PROTEIN; FC-EPSILON-RI; MAJOR BASIC-PROTEIN; RESPIRATORY
SYNCYTIAL VIRUS; FLUID HISTAMINE LEVELS; SYSTEMIC MASTOCYTOSIS; CATIONIC
PROTEIN; SERUM TRYPTASE; ATOPIC ASTHMA; HUMAN-LUNG
AB Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology.
C1 [Metcalfe, Dean D.; Prussin, Calman] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Pawankar, Ruby] Nippon Med Sch, Dept Pediat, Div Allergy, 1-1-5 Sendagi, Tokyo 113, Japan.
[Ackerman, Steven J.] Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL USA.
[Akin, Cem] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Clayton, Frederic] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA.
[Falcone, Franco H.] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England.
[Gleich, Gerald J.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[Irani, Anne-Marie] Virginia Commonwealth Univ, Childrens Hosp Richmond, Richmond, VA USA.
[Johansson, Mats W.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA.
[Klion, Amy D.] NIAID, Human Eosinophil Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Leiferman, Kristin M.] Univ Utah, Salt Lake City, UT USA.
[Levi-Schaffer, Francesca] Hebrew Univ Jerusalem, Jerusalem, Israel.
[Nilsson, Gunnar] Karolinska Inst, Dept Med, Clin Immunol & Allergy, Stockholm, Sweden.
[Nilsson, Gunnar] Karolinska Univ Hosp, Stockholm, Sweden.
[Okayama, Yoshimichi] Nihon Univ, Allergy & Immunol Grp, Res Inst Med Sci, Grad Sch Med, Tokyo, Japan.
[Schroeder, John T.] Johns Hopkins Univ, Sch Med, Dept Med, Div Clin Immunol & Allergy, Baltimore, MD 21205 USA.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Richmond, VA USA.
[Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, Bern, Switzerland.
[Walls, Andrew F.] Southampton Gen Hosp, Immunopharmacol Grp, Southampton SO9 4XY, Hants, England.
[Triggiani, Massimo] Univ Salerno, Div Clin Immunol & Allergy, I-84100 Salerno, Italy.
RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dmetcalfe@niaid.nih.gov
OI Akin, Cem/0000-0001-6301-4520
FU Department of Health [H039]; FDA HHS [R01 FD004086]; Medical Research
Council [G0500729]; NHLBI NIH HHS [P01 HL088594, R21 HL118588, U10
HL109168]; NIAID NIH HHS [R01 AI115703]
NR 135
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Z9 6
U1 2
U2 15
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1939-4551
J9 WORLD ALLERGY ORGAN
JI World Allergy Organ. J.
PD FEB 11
PY 2016
VL 9
DI 10.1186/s40413-016-0094-3
PG 15
WC Allergy
SC Allergy
GA DD6HI
UT WOS:000370024900001
PM 26904159
ER
PT J
AU Fiore-Gartland, A
Manso, BA
Friedrich, DP
Gabriel, EE
Finak, G
Moodie, Z
Hertz, T
De Rosa, SC
Frahm, N
Gilbert, PB
McElrath, MJ
AF Fiore-Gartland, Andrew
Manso, Bryce A.
Friedrich, David P.
Gabriel, Erin E.
Finak, Greg
Moodie, Zoe
Hertz, Tomer
De Rosa, Stephen C.
Frahm, Nicole
Gilbert, Peter B.
McElrath, M. Juliana
TI Pooled-Peptide Epitope Mapping Strategies Are Efficient and Highly
Sensitive: An Evaluation of Methods for Identifying Human T Cell Epitope
Specificities in Large-Scale HIV Vaccine Efficacy Trials
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE CONTROL; ELISPOT-ASSAY; OF-CONCEPT;
CLINICAL-TRIALS; HLA RESTRICTION; AIDS VACCINE; DOUBLE-BLIND; RESPONSES;
TYPE-1
AB The interferon gamma, enzyme-linked immunospot (IFN-gamma ELISpot) assay is widely used to identify viral antigen-specific T cells is frequently employed to quantify T cell responses in HIV vaccine studies. It can be used to define T cell epitope specificities using panels of peptide antigens, but with sample and cost constraints there is a critical need to improve the efficiency of epitope mapping for large and variable pathogens. We evaluated two epitope mapping strategies, based on group testing, for their ability to identify vaccine-induced T-cells from participants in the Step HIV-1 vaccine efficacy trial, and compared the findings to an approach of assaying each peptide individually. The group testing strategies reduced the number of assays required by >7-fold without significantly altering the accuracy of T-cell breadth estimates. Assays of small pools containing 7-30 peptides were highly sensitive and effective at detecting single positive peptides as well as summating responses to multiple peptides. Also, assays with a single 15-mer peptide, containing an identified epitope, did not always elicit a response providing validation that 15-mer peptides are not optimal antigens for detecting CD8+ T cells. Our findings further validate pooling-based epitope mapping strategies, which are critical for characterizing vaccineinduced T-cell responses and more broadly for informing iterative vaccine design. We also show ways to improve their application with computational peptide: MHC binding predictors that can accurately identify the optimal epitope within a 15-mer peptide and within a pool of 15-mer peptides.
C1 [Fiore-Gartland, Andrew; Manso, Bryce A.; Friedrich, David P.; Finak, Greg; Moodie, Zoe; De Rosa, Stephen C.; Frahm, Nicole; Gilbert, Peter B.; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Gabriel, Erin E.] NIAID, Biostat Res Branch, Rockville, MD 20852 USA.
[Hertz, Tomer] Ben Gurion Univ Negev, Shraga Segal Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel.
RP Fiore-Gartland, A (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
EM agartlan@fredhutch.org
RI Hertz, Tomer/S-5744-2016;
OI Hertz, Tomer/0000-0002-0561-1578; Gabriel, Erin/0000-0002-0504-8404
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [UM1AI068635, UM1AI068618]
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 UM1AI068635 and UM1AI068618. GF is an ISAC
scholar. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 62
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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 FEB 10
PY 2016
VL 11
IS 2
AR e0147812
DI 10.1371/journal.pone.0147812
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600039
PM 26863315
ER
PT J
AU Ho, JE
Larson, MG
Ghorbani, A
Cheng, S
Chen, MH
Keyes, M
Rhee, EP
Clish, CB
Vasan, RS
Gerszten, RE
Wang, TJ
AF Ho, Jennifer E.
Larson, Martin G.
Ghorbani, Anahita
Cheng, Susan
Chen, Ming-Huei
Keyes, Michelle
Rhee, Eugene P.
Clish, Clary B.
Vasan, Ramachandran S.
Gerszten, Robert E.
Wang, Thomas J.
TI Metabolomic Profiles of Body Mass Index in the Framingham Heart Study
Reveal Distinct Cardiometabolic Phenotypes
SO PLOS ONE
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; AMINO-ACIDS;
GLUCOSE-TOLERANCE; BRANCHED-CHAIN; YOUNG-ADULTS; RISK-FACTORS; FINNISH
MEN; DISEASE; HUMANS
AB Background
Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling.
Methods and Results
We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha-ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to "modify" the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals.
Conclusions
In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits.
C1 [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Chen, Ming-Huei; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Chen, Ming-Huei; Vasan, Ramachandran S.] Boston Univ, Sch Med, Framingham, MA USA.
[Ho, Jennifer E.; Keyes, Michelle; Rhee, Eugene P.; Gerszten, Robert E.] Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusetts Gen Hosp, Boston, MA USA.
[Ho, Jennifer E.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Ghorbani, Anahita] Mt Auburn Hosp, Cambridge, MA USA.
[Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Div Cardiol, Sch Med, Boston, MA 02115 USA.
[Rhee, Eugene P.] Harvard Univ, Sch Med, Dept Med, Renal Div,Massachusetts Gen Hosp, Boston, MA USA.
[Rhee, Eugene P.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Vasan, Ramachandran S.] Boston Univ, Div Cardiol & Prevent Med, Dept Med, Boston, MA 02215 USA.
[Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA.
RP Ho, JE (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.; Ho, JE (reprint author), Boston Univ, Sch Med, Framingham, MA USA.; Ho, JE (reprint author), Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Massachusetts Gen Hosp, Boston, MA USA.; Ho, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
EM jho1@mgh.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195, HHSN268201500001I]; National Institutes of Health
[K23-HL116780, 2R01-DK081572]; Boston University School of Medicine
Department of Medicine Career Investment Award; Ellison Foundation
FX This work was partially supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195 and
HHSN268201500001I), National Institutes of Health grants K23-HL116780
(JEH), 2R01-DK081572 (MGL, REG, TJW), a Boston University School of
Medicine Department of Medicine Career Investment Award (JEH), and the
Ellison Foundation (SC). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
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U1 3
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 FEB 10
PY 2016
VL 11
IS 2
AR e0148361
DI 10.1371/journal.pone.0148361
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600059
PM 26863521
ER
PT J
AU Prothmann, M
von Knobelsdorff-Brenkenhoff, F
Topper, A
Dieringer, MA
Shahid, E
Graessl, A
Rieger, J
Lysiak, D
Thalhammer, C
Huelnhagen, T
Kellman, P
Niendorf, T
Schulz-Menger, J
AF Prothmann, Marcel
von Knobelsdorff-Brenkenhoff, Florian
Toepper, Agnieszka
Dieringer, Matthias A.
Shahid, Etham
Graessl, Andreas
Rieger, Jan
Lysiak, Darius
Thalhammer, C.
Huelnhagen, Till
Kellman, Peter
Niendorf, Thoralf
Schulz-Menger, Jeanette
TI High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla
in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson
Learned from 7.0 Tesla
SO PLOS ONE
LA English
DT Article
ID MYOCARDIAL CRYPTS; HEART-ASSOCIATION; TASK-FORCE; PREVALENCE; DIAGNOSIS;
FIBROSIS; DISEASE; DESIGN; MRI
AB Background
Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details.
Methods
We screened 131 patients with HCM. 13 patients (9 males, 56 +/- 31 years) and 13 healthy age-and gender-matched subjects (9 males, 55 +/- 31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm(3) and (1.4x1.4x4.0) mm(3); at 3.0T: (1.8x1.8x6.0) mm(3)). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis.
Results
All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (p(LVEDV) = 0.110; p(LVESV) = 0.091; p(LVMASS) = 0.131; p(LVEF) = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol.
Conclusions
CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE.
C1 [Prothmann, Marcel; von Knobelsdorff-Brenkenhoff, Florian; Toepper, Agnieszka; Dieringer, Matthias A.; Shahid, Etham; Graessl, Andreas; Lysiak, Darius; Thalhammer, C.; Huelnhagen, Till; Niendorf, Thoralf; Schulz-Menger, Jeanette] Max Delbruck Ctr Mol Med, BUFF, Berlin, Germany.
[Prothmann, Marcel; von Knobelsdorff-Brenkenhoff, Florian; Toepper, Agnieszka; Dieringer, Matthias A.; Shahid, Etham; Schulz-Menger, Jeanette] Expt & Clin Res Ctr, Working Grp Cardiovasc Magnet Resonance, Berlin, Germany.
[Prothmann, Marcel; von Knobelsdorff-Brenkenhoff, Florian; Toepper, Agnieszka; Dieringer, Matthias A.; Shahid, Etham; Schulz-Menger, Jeanette] HELIOS Klinikum Berlin Buch, Dept Cardiol & Nephrol, Berlin, Germany.
[Rieger, Jan; Lysiak, Darius; Niendorf, Thoralf] MRI TOOLS GmbH, Berlin, Germany.
[Kellman, Peter] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Niendorf, Thoralf; Schulz-Menger, Jeanette] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany.
RP Schulz-Menger, J (reprint author), Max Delbruck Ctr Mol Med, BUFF, Berlin, Germany.; Schulz-Menger, J (reprint author), Expt & Clin Res Ctr, Working Grp Cardiovasc Magnet Resonance, Berlin, Germany.; Schulz-Menger, J (reprint author), HELIOS Klinikum Berlin Buch, Dept Cardiol & Nephrol, Berlin, Germany.; Schulz-Menger, J (reprint author), DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany.
EM Jeanette.Schulz-Menger@charite.de
FU Charite
FX The study was supported by university funds (Charite) hold by Prof. Dr.
med. Jeanette Schulz Menger. Thoralf Niendorf is founder and CEO of MRI.
TOOLS GmbH, Berlin, Germany. Jan Rieger is founder and CTO of MRI. TOOLS
GmbH, Berlin, Germany. Darius Lysiak is currently employee of MRI. TOOLS
GmbH, Berlin, Germany. MRI. TOOLS GmbH provided support in the form of
salaries for authors Jan Rieger and Darius Lysiak, but did not have any
additional role in the study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The specific
roles of these authors are articulated in the 'author contributions'
section.
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U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 10
PY 2016
VL 11
IS 2
AR e0148066
DI 10.1371/journal.pone.0148066
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6PR
UT WOS:000370046600042
PM 26863618
ER
PT J
AU Lu, N
Tian, Y
Tian, W
Huang, P
Liu, Y
Tang, YX
Wang, CY
Wang, SJ
Su, YY
Zhang, YL
Pan, J
Teng, ZG
Lu, GM
AF Lu, Nan
Tian, Ying
Tian, Wei
Huang, Peng
Liu, Ying
Tang, Yuxia
Wang, Chunyan
Wang, Shouju
Su, Yunyan
Zhang, Yunlei
Pan, Jing
Teng, Zhaogang
Lu, Guangming
TI Smart Cancer Cell Targeting Imaging and Drug Delivery System by
Systematically Engineering Periodic Mesoporous Organosilica
Nanoparticles
SO ACS APPLIED MATERIALS & INTERFACES
LA English
DT Article
DE HER2 positive cancer; periodic mesoporous organosilica; cancer cell
targeting near-infrared fluorescence imaging; drug delivery
ID IRON-OXIDE; THERANOSTIC APPLICATIONS; TOPOLOGICAL TRANSFORMATION;
POLYPYRROLE NANOPARTICLES; PHOTODYNAMIC THERAPY; PHOTOTHERMAL THERAPY;
RENAL CLEARANCE; TUMOR; NANOCOMPOSITES; RELEASE
AB The integration of diagnosis and therapy into one nanoplatform, known as theranostics, has attracted increasing attention in the biomedical areas. Herein, we first present a cancer cell targeting imaging and drug delivery system based on engineered thioether-bridged periodic mesoporous organosilica nanoparticles (PMOs). The PMOs are stably and selectively conjugated with near infrared fluorescence (NIRF) dye Cyanine 5.5 (Cy5.5) and anti-Her2 affibody on the outer surfaces to endow them with excellent NIRF imaging, and cancer targeting properties. Also, taking the advantage of the thioether-group-incorporated mesopores, the release of chemotherapy drug doxorubicin (DOX) loaded in the PMOs is responsive to the tumor-related molecule glutathione (GSH). The drug release percentage reaches 84.8% in 10 mM of GSH solution within 24h, which is more than 2-fold higher than that without GSH. In addition, the drug release also exhibits pH-responsive, which reaches 53.6% at pH 5 and 31.7% at pH 7.4 within 24 h. Confocal laser scanning, microscopy and flow cytometry analysis demonstrate that the PMOs-based theranostic platforms can efficiently target to and enter Her2 positive tumor cells. Thus, the smart imaging and drug delivery nanoplatforms induce high tumor cell growth inhibition. Meanwhile, the Cy5.5 conjugated PMOs perform great NIRF imaging ability, which could monitor the intracellular distribution, delivery and release of the chemotherapy drug. In addition, cell viability and histological assessments show the engineered PMOs have good biocompatibility, further encouraging the following biomedical applications. Over all, the systemically engineered PMOs can serve as a riovel cancer cell targeting imaging and drug delivery platform with NIRF imaging, GSH and pH dual-responsive drug. release, and high tumor cell targeting ability.
C1 [Lu, Nan; Tian, Ying; Tian, Wei; Liu, Ying; Tang, Yuxia; Wang, Chunyan; Wang, Shouju; Su, Yunyan; Zhang, Yunlei; Pan, Jing; Teng, Zhaogang; Lu, Guangming] Nanjing Univ, Jinling Hosp, Dept Med Imaging, Sch Med, Nanjing 210002, Jiangsu, Peoples R China.
[Teng, Zhaogang; Lu, Guangming] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210093, Jiangsu, Peoples R China.
[Lu, Nan; Huang, Peng] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, Bethesda, MD 20892 USA.
[Huang, Peng] Shenzhen Univ, Guangdong Key Lab Biomed Measurements & Ultrasoun, Dept Biomed Engn, Sch Med, Shenzhen 518060, Guangdong, Peoples R China.
RP Teng, ZG; Lu, GM (reprint author), Nanjing Univ, Jinling Hosp, Dept Med Imaging, Sch Med, Nanjing 210002, Jiangsu, Peoples R China.; Teng, ZG; Lu, GM (reprint author), Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210093, Jiangsu, Peoples R China.
EM tzg@fudan.edu.cn; cjr.luguangming@vip.163.com
RI Huang, Peng/R-2480-2016
OI Huang, Peng/0000-0003-3651-7813
FU National Key Basic Research Program of the PRC [2014CB744504,
2011CB707700]; Major International (Regional) Joint Research Program of
China [81120108013]; National Natural Science Foundation of China
[81201175]; Natural Science Foundation of Jiangsu Province [BK20130863];
National Science Foundation for Postdoctoral Scientists of China
[2013T60939, 2012M521934]; Science Foundation of Nanjing University of
Posts and Telecommunications [NY213045, 214096]
FX We greatly appreciate financial support from the National Key Basic
Research Program of the PRC (2014CB744504 and 2011CB707700), the Major
International (Regional) Joint Research Program of China (81120108013),
the National Natural Science Foundation of China (81201175), the Natural
Science Foundation of Jiangsu Province (BK20130863), the National
Science Foundation for Postdoctoral Scientists of China (2013T60939 and
2012M521934), and the Science Foundation of Nanjing University of Posts
and Telecommunications (NY213045 and 214096).
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PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1944-8244
J9 ACS APPL MATER INTER
JI ACS Appl. Mater. Interfaces
PD FEB 10
PY 2016
VL 8
IS 5
BP 2985
EP 2993
DI 10.1021/acsami.5b09585
PG 9
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA DD8XY
UT WOS:000370211400013
PM 26767305
ER
PT J
AU Finak, G
Langweiler, M
Jaimes, M
Malek, M
Taghiyar, J
Korin, Y
Raddassi, K
Devine, L
Obermoser, G
Pekalski, ML
Pontikos, N
Diaz, A
Heck, S
Villanova, F
Terrazzini, N
Kern, F
Qian, Y
Stanton, R
Wang, K
Brandes, A
Ramey, J
Aghaeepour, N
Mosmann, T
Scheuermann, RH
Reed, E
Palucka, K
Pascual, V
Blomberg, BB
Nestle, F
Nussenblatt, RB
Brinkman, RR
Gottardo, R
Maecker, H
Mccoy, JP
AF Finak, Greg
Langweiler, Marc
Jaimes, Maria
Malek, Mehrnoush
Taghiyar, Jafar
Korin, Yael
Raddassi, Khadir
Devine, Lesley
Obermoser, Gerlinde
Pekalski, Marcin L.
Pontikos, Nikolas
Diaz, Alain
Heck, Susanne
Villanova, Federica
Terrazzini, Nadia
Kern, Florian
Qian, Yu
Stanton, Rick
Wang, Kui
Brandes, Aaron
Ramey, John
Aghaeepour, Nima
Mosmann, Tim
Scheuermann, Richard H.
Reed, Elaine
Palucka, Karolina
Pascual, Virginia
Blomberg, Bonnie B.
Nestle, Frank
Nussenblatt, Robert B.
Brinkman, Ryan Remy
Gottardo, Raphael
Maecker, Holden
Mccoy, J. Philip
TI Standardizing Flow Cytometry Immunophenotyping Analysis from the Human
ImmunoPhenotyping Consortium
SO SCIENTIFIC REPORTS
LA English
DT Article
ID QUALITY-ASSURANCE; ASSAYS
AB Standardization of immunophenotyping requires careful attention to reagents, sample handling, instrument setup, and data analysis, and is essential for successful cross-study and cross-center comparison of data. Experts developed five standardized, eight-color panels for identification of major immune cell subsets in peripheral blood. These were produced as pre-configured, lyophilized, reagents in 96-well plates. We present the results of a coordinated analysis of samples across nine laboratories using these panels with standardized operating procedures (SOPs). Manual gating was performed by each site and by a central site. Automated gating algorithms were developed and tested by the FlowCAP consortium. Centralized manual gating can reduce cross-center variability, and we sought to determine whether automated methods could streamline and standardize the analysis. Within-site variability was low in all experiments, but cross-site variability was lower when central analysis was performed in comparison with site-specific analysis. It was also lower for clearly defined cell subsets than those based on dim markers and for rare populations. Automated gating was able to match the performance of central manual analysis for all tested panels, exhibiting little to no bias and comparable variability. Standardized staining, data collection, and automated gating can increase power, reduce variability, and streamline analysis for immunophenotyping.
C1 [Finak, Greg; Ramey, John; Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Langweiler, Marc] NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA.
[Jaimes, Maria] BD Biosci, San Jose, CA USA.
[Malek, Mehrnoush; Taghiyar, Jafar; Aghaeepour, Nima; Brinkman, Ryan Remy] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V3J 4W6, Canada.
[Korin, Yael; Reed, Elaine] UCLA Pathol & Lab Med, Los Angeles, CA USA.
[Raddassi, Khadir; Devine, Lesley] Yale Univ, Sch Med, Dept Neurol, New Haven, CT USA.
[Obermoser, Gerlinde; Palucka, Karolina; Pascual, Virginia] Baylor Inst Immunol Res, Dallas, TX USA.
[Pekalski, Marcin L.; Pontikos, Nikolas] Univ Cambridge, Cambridge Inst Med Res, JDRF Wellcome Trust Diabet & Inflammat Lab, Cambridge, England.
[Diaz, Alain; Blomberg, Bonnie B.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Heck, Susanne; Villanova, Federica; Nestle, Frank] Guys Hosp, Guys & St Thomas Hosp, London SE1 9RT, England.
[Terrazzini, Nadia] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England.
[Kern, Florian] Brighton & Sussex Med Sch, Div Med, Brighton BN1 9PS, E Sussex, England.
[Qian, Yu; Stanton, Rick; Scheuermann, Richard H.] J Craig Venter Inst, Dept Informat, La Jolla, CA 92037 USA.
[Wang, Kui] Univ Queensland, Sch Math & Phys, Brisbane, Qld, Australia.
[Brandes, Aaron] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Aghaeepour, Nima] Stanford Univ, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA.
[Mosmann, Tim] Univ Rochester, Med Ctr, Sch Med & Dent, Rochester, NY 14642 USA.
[Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brinkman, Ryan Remy] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada.
[Maecker, Holden] Stanford Univ, Sch Med, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
[Mccoy, J. Philip] NHLBI Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
RP Mccoy, JP (reprint author), NHLBI Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
EM mccoyjp@mail.nih.gov
RI Brinkman, Ryan/B-1108-2008
OI Brinkman, Ryan/0000-0002-9765-2990
FU National Institutes of Health [R01 EB008400]; Human Immunology Project
Consortium (HIPC) [U19 AI089986]; Wellcome Trust Strategic Award
[100140]; intramural research program of NHLBI, NIH; [5U19AI090019]
FX This work was supported by grant 5U19AI090019, and [R01 EB008400] from
the National Institutes of Health, and the Human Immunology Project
Consortium (HIPC) [U19 AI089986], a Wellcome Trust Strategic Award
(100140) to the Cambridge Institute for Medical Research (CIMR) and from
the intramural research program of NHLBI, NIH. The authors thank Meena
Malipatlolla, Shannon Opiela, PhD, and Kay Kayembe for technical
assistance. GF is an ISAC scholar. The authors would like to acknowledge
all of the member of the FlowCAP consortium and extend our thanks for
their participation.
NR 26
TC 11
Z9 11
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 10
PY 2016
VL 6
AR 20686
DI 10.1038/srep20686
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD3ME
UT WOS:000369825500001
PM 26861911
ER
PT J
AU Bae, C
Anselmi, C
Kalia, J
Jara-Oseguera, A
Schwieters, CD
Krepkiy, D
Lee, CW
Kim, EH
Kim, JI
Faraldo-Gomez, JD
Swartz, KJ
AF Bae, Chanhyung
Anselmi, Claudio
Kalia, Jeet
Jara-Oseguera, Andres
Schwieters, Charles D.
Krepkiy, Dmitriy
Lee, Chul Won
Kim, Eun-Hee
Kim, Jae Il
Faraldo-Gomez, Jose D.
Swartz, Kenton J.
TI Structural insights into the mechanism of activation of the TRPV1
channel by a membrane-bound tarantula toxin
SO ELIFE
LA English
DT Article
ID MOLECULAR-STRUCTURE DETERMINATION; ION-CHANNEL; PROTEIN STRUCTURES;
VOLTAGE SENSORS; K+ CHANNEL; CRYSTAL-STRUCTURE; LIPID-MEMBRANES; DENSITY
MAPS; CYSTINE KNOT; PORE DOMAIN
AB Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation.
C1 [Bae, Chanhyung; Kalia, Jeet; Jara-Oseguera, Andres; Krepkiy, Dmitriy; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bae, Chanhyung; Kim, Jae Il] Gwangju Inst Sci & Technol, Dept Life Sci, Gwangju, South Korea.
[Anselmi, Claudio; Faraldo-Gomez, Jose D.] NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Kalia, Jeet] Indian Inst Sci Educ & Res, Pune, Maharashtra, India.
[Schwieters, Charles D.] NIH, Ctr Informat Technol, Div Computat Biosci, Bldg 10, Bethesda, MD 20892 USA.
[Lee, Chul Won] Chonnam Natl Univ, Dept Chem, Gwanju, South Korea.
[Kim, Eun-Hee] Korea Basic Sci Inst, Prot Struct Res Grp, Ochang, South Korea.
RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.; Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Gwangju, South Korea.; Faraldo-Gomez, JD (reprint author), NHLBI, Theoret Mol Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jikim@gist.ac.kr; jose.faraldo@nih.gov; swartzk@ninds.nih.gov
RI Faraldo-Gomez, Jose/H-7127-2016;
OI Anselmi, Claudio/0000-0002-3017-5085
FU National Institute of Neurological Disorders and Stroke; National Heart,
Lung, and Blood Institute; Center for Information Technology; National
Research Foundation of Korea; Korea Research Institute of Bioscience and
Biotechnology
FX National Institute of Neurological Disorders and Stroke Kenton J Swartz;
National Heart, Lung, and Blood Institute Jose D Faraldo-Gomez; Center
for Information Technology Charles D Schwieters; National Research
Foundation of Korea Jae II Kim; Korea Research Institute of Bioscience
and Biotechnology Chanhyung Bae B
NR 74
TC 10
Z9 10
U1 7
U2 20
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 10
PY 2016
VL 5
AR e11273
DI 10.7554/eLife.11273
PG 30
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DD3BJ
UT WOS:000369795700001
ER
PT J
AU Newhauser, WD
de Gonzalez, AB
Schulte, R
Lee, C
AF Newhauser, Wayne D.
de Gonzalez, Amy Berrington
Schulte, Reinhard
Lee, Choonsik
TI A Review of Radiotherapy-Induced Late Effects Research after Advanced
Technology Treatments
SO FRONTIERS IN ONCOLOGY
LA English
DT Review
DE late effects; dose; risk; measurement; calculation; proton; photon
ID PROTON CRANIOSPINAL IRRADIATION; MONTE-CARLO SIMULATIONS; NEUTRON
DOSE-EQUIVALENT; PASSIVELY SCATTERED PROTON; CHILDHOOD-CANCER SURVIVOR;
RADIOGENIC 2ND CANCERS; TREATMENT PLANNING SYSTEM; RADIATION-THERAPY;
SECONDARY NEUTRON; ADULT SURVIVORS
AB The number of incident cancers and long-term cancer survivors is expected to increase substantially for at least a decade. Advanced technology radiotherapies, e.g., using beams of protons and photons, offer dosimetric advantages that theoretically yield better outcomes. In general, evidence from controlled clinical trials and epidemiology studies are lacking. To conduct these studies, new research methods and infrastructure will be needed. In the paper, we review several key research methods of relevance to late effects after advanced technology proton-beam and photon-beam radiotherapies. In particular, we focus on the determination of exposures to therapeutic and stray radiation and related uncertainties, with discussion of recent advances in exposure calculation methods, uncertainties, in silico studies, computing infrastructure, electronic medical records, and risk visualization. We identify six key areas of methodology and infrastructure that will be needed to conduct future outcome studies of radiation late effects.
C1 [Newhauser, Wayne D.] Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.
[Newhauser, Wayne D.] Mary Bird Perkins Canc Ctr, Dept Phys, Baton Rouge, LA USA.
[de Gonzalez, Amy Berrington; Lee, Choonsik] NIH, Radiat Epidemiol Branch, Rockville, MD USA.
[Schulte, Reinhard] Loma Linda Univ, Med Ctr, Dept Basic Sci, Loma Linda, CA USA.
RP Newhauser, WD (reprint author), Louisiana State Univ, Dept Phys & Astron, Baton Rouge, LA 70803 USA.; Newhauser, WD (reprint author), Mary Bird Perkins Canc Ctr, Dept Phys, Baton Rouge, LA USA.
EM newhauser@lsu.edu
FU Bella Bowman Foundation
FX This work was supported in part by the Bella Bowman Foundation.
NR 123
TC 0
Z9 0
U1 3
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD FEB 10
PY 2016
VL 6
AR 13
DI 10.3389/fonc.2016.00013
PG 11
WC Oncology
SC Oncology
GA DD3DI
UT WOS:000369801100001
PM 26904500
ER
PT J
AU Hartz, AMS
Zhong, Y
Wolf, A
LeVine, H
Miller, DS
Bauer, B
AF Hartz, Anika M. S.
Zhong, Yu
Wolf, Andrea
LeVine, Harry, III
Miller, David S.
Bauer, Bjoern
TI A beta 40 Reduces P-Glycoprotein at the Blood-Brain Barrier through the
Ubiquitin-Proteasome Pathway
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Alzheimer's disease; blood-brain barrier; P-glycoprotein; transporter;
ubiquitin-proteasome system
ID CEREBRAL AMYLOID ANGIOPATHY; ALZHEIMERS-DISEASE; MOUSE MODEL; A-BETA;
UP-REGULATION; CELL-SURFACE; CANCER-CELLS; RESISTANCE; MECHANISMS;
EXPRESSION
AB Failure to clear amyloid-beta (A beta) from the brain is in part responsible for A beta brain accumulation in Alzheimer's disease (AD). A critical protein for clearing A beta across the blood-brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood-brain barrier in AD, which has been shown to be associated with A beta brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We exposed isolated rat brain capillaries to 100 nM A beta 40, A beta 40, aggregated A beta 40, and A beta 42. We observed that only A beta 40 triggered reduction of P-gp protein expression and transport activity levels; this occurred in a dose-and time-dependent manner. To identify the steps involved in A beta-mediated P-gp reduction, we inhibited protein ubiquitination, protein trafficking, and the ubiquitin-proteasome system, and monitored P-gp protein expression, transport activity, and P-gp-ubiquitin levels. Thus, exposing brain capillaries to A beta 40 triggers ubiquitination, internalization, and proteasomal degradation of P-gp. These findings may provide potential therapeutic targets within the blood-brain barrier to limit P-gp degradation in AD and improve A beta brain clearance.
C1 [Hartz, Anika M. S.; Zhong, Yu; LeVine, Harry, III] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA.
[Hartz, Anika M. S.] Univ Kentucky, Dept Pharmacol & Nutr Sci, Lexington, KY 40536 USA.
[Hartz, Anika M. S.; Wolf, Andrea; Bauer, Bjoern] Univ Minnesota, Dept Pharm Practice & Pharmaceut Sci, Coll Pharm, Duluth, MN 55812 USA.
[Miller, David S.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Bauer, Bjoern] Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA.
RP Hartz, AMS (reprint author), Univ Kentucky, Dept Pharmacol & Nutr Sci, Sanders Brown Ctr Aging 329, 800 South Limestone, Lexington, KY 40536 USA.
EM anika.hartz@uky.edu
FU National Institute on Aging Grant [1R01AG039621]; 3M Science and
Technology Doctoral Fellowship; 3M Grant [P01-AG005119-20]; Division of
Intramural Research at National Institute of Environmental Health
Sciences/National Institutes of Health
FX This work was supported by National Institute on Aging Grant
1R01AG039621 to A.M.S.H., 3M Science and Technology Doctoral Fellowship
to A.W., 3M Grant P01-AG005119-20 to H.L., and the Division of
Intramural Research at National Institute of Environmental Health
Sciences/National Institutes of Health to D.S.M. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institute on Aging or the National
Institutes of Health. We thank Stephanie Edelmann, Ralf Rempe, Yu Zhong,
and Tal Ashkenazi-Frolinger for proofreading the manuscript and
editorial assistance; Britt Johnson, Kevin Viken, and Emma Soldner for
technical assistance; and Lynne Bemis and Evan Odean for the NanoSight
analysis.
NR 44
TC 9
Z9 9
U1 5
U2 12
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 FEB 10
PY 2016
VL 36
IS 6
BP 1930
EP 1941
DI 10.1523/JNEUROSCI.0350-15.2016
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DD5LF
UT WOS:000369964500013
PM 26865616
ER
PT J
AU Labandeira, CC
Yang, Q
Santiago-Blay, JA
Hotton, CL
Monteiro, A
Wang, YJ
Goreva, Y
Shih, CK
Siljestrom, S
Rose, TR
Dilcher, DL
Ren, D
AF Labandeira, Conrad C.
Yang, Qiang
Santiago-Blay, Jorge A.
Hotton, Carol L.
Monteiro, Antonia
Wang, Yong-Jie
Goreva, Yulia
Shih, ChungKun
Siljestrom, Sandra
Rose, Tim R.
Dilcher, David L.
Ren, Dong
TI The evolutionary convergence of mid-Mesozoic lacewings and Cenozoic
butterflies
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE angiosperms; gymnosperms; Kalligrammatidae; Papilionoidea; tubular
proboscis; wing eyespots
ID YIXIAN FORMATION; NEUROPTERIDA INSECTA; POLLINATION; KALLIGRAMMATIDAE;
GYMNOSPERMS; CHINA; EYESPOTS; AMERICA; MIMICRY; MELANIN
AB Mid-Mesozoic kalligrammatid lacewings (Neuroptera) entered the fossil record 165 million years ago (Ma) and disappeared 45 Ma later. Extant papilionoid butterflies (Lepidoptera) probably originated 80-70 Ma, long after kalligrammatids became extinct. Although poor preservation of kalligrammatid fossils previously prevented their detailed morphological and ecological characterization, we examine new, well-preserved, kalligrammatid fossils from Middle Jurassic and Early Cretaceous sites in northeastern China to unravel a surprising array of similar morphological and ecological features in these two, unrelated clades. We used polarized light and epifluorescence photography, SEM imaging, energy dispersive spectrometry and time-of-flight secondary ion mass spectrometry to examine kalligrammatid fossils and their environment. We mapped the evolution of specific traits onto a kalligrammatid phylogeny and discovered that these extinct lacewings convergently evolved wing eyespots that possibly contained melanin, and wing scales, elongate tubular proboscides, similar feeding styles, and seed-plant associations, similar to butterflies. Long-proboscid kalligrammatid lacewings lived in ecosystems with gymnosperm-insect relationships and likely accessed bennettitalean pollination drops and pollen. This system later was replaced by mid-Cretaceous angiosperms and their insect pollinators.
C1 [Labandeira, Conrad C.; Yang, Qiang; Wang, Yong-Jie; Shih, ChungKun; Ren, Dong] Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China.
[Labandeira, Conrad C.; Santiago-Blay, Jorge A.; Hotton, Carol L.; Shih, ChungKun] Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA.
[Goreva, Yulia; Siljestrom, Sandra; Rose, Tim R.] Smithsonian Inst, Natl Museum Nat Hist, Dept Mineral Sci, Washington, DC 20013 USA.
[Labandeira, Conrad C.] Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.
[Labandeira, Conrad C.] Univ Maryland, BEES Program, College Pk, MD 20742 USA.
[Yang, Qiang] Sun Yat Sen Univ, Sch Life Sci, Coll Ecol & Evolut,Guangdong Higher Educ Inst, State Key Lab Biocontrol,Key Lab Biodivers Dynam, Guangzhou 510275, Guangdong, Peoples R China.
[Yang, Qiang] Shijiazhuang Univ Econ, Geosci Museum, Shijiazhuang 050031, Peoples R China.
[Santiago-Blay, Jorge A.] Univ Puerto Rico, Dept Crop & Agroenvironm Sci, Mayaguez, PR 00681 USA.
[Hotton, Carol L.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Monteiro, Antonia] Yale Univ, Dept Ecol & Evolutionary Biol, New Haven, CT 06511 USA.
[Monteiro, Antonia] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
[Monteiro, Antonia] Yale NUS Coll, Singapore 138614, Singapore.
[Goreva, Yulia] CALTECH, Jet Prop Lab, Natl Aeronaut & Space Adm, 4800 Oak Grove Dr, Pasadena, CA 91125 USA.
[Siljestrom, Sandra] SP Tech Res Inst Sweden, Dept Chem Mat & Surfaces, S-51115 Boras, Sweden.
[Siljestrom, Sandra] Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA.
[Dilcher, David L.] Indiana Univ, Dept Geol, Bloomington, IN 47405 USA.
[Dilcher, David L.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
RP Labandeira, CC; Ren, D (reprint author), Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China.; Labandeira, CC (reprint author), Smithsonian Inst, Natl Museum Nat Hist, Dept Paleobiol, Washington, DC 20013 USA.; Labandeira, CC (reprint author), Univ Maryland, Dept Entomol, College Pk, MD 20742 USA.; Labandeira, CC (reprint author), Univ Maryland, BEES Program, College Pk, MD 20742 USA.
EM labandec@si.edu; rendong@mail.cnu.edu.cn
OI Monteiro, Antonia/0000-0001-9696-459X
FU National Basic Research Program of China (973 Program) [2012CB821906];
National Science Foundation of China [31230065, 31309105, 31372243,
41272006, 41372013]; Beijing Municipal Commission of Education Project
[201207120]; China Postdoctoral Science Foundation [2012T50113];
Doctoral Program of Higher Education of China [20131108120005]; Beijing
Natural Science Foundation [5132008]; Great Wall Scholar Project of the
Beijing Municipal Commission of Education [KZ201310028033]; Program for
Changjiang Scholars and Innovative Research Teams at University
[IRT13081]; Natural Science Foundation of Hebei Province [C2015403012];
Intramural Research Program of the National Institutes of Health,
Library of Medicine; Deep Carbon Observatory; Postdoctoral Fellowship
Program of the Geophysical Laboratory, Carnegie Institution of
Washington; Swedish National Space Board [121/11]
FX This work was supported by the National Basic Research Program of China
(973 Program) (grant 2012CB821906), National Science Foundation of China
(grant nos. 31230065, 31309105, 31372243, 41272006 and 41372013),
Beijing Municipal Commission of Education Project (grant no. 201207120),
China Postdoctoral Science Foundation (grant no. 2012T50113), Doctoral
Program of Higher Education of China (grant no. 20131108120005), Beijing
Natural Science Foundation (grant 5132008), Great Wall Scholar Project
of the Beijing Municipal Commission of Education (grant no.
KZ201310028033), Program for Changjiang Scholars and Innovative Research
Teams at University (IRT13081), Natural Science Foundation of Hebei
Province (grant no. C2015403012), Intramural Research Program of the
National Institutes of Health, Library of Medicine, to C.L.H. and the
Deep Carbon Observatory to Y.G. and S.S. S.S. also was supported through
the Postdoctoral Fellowship Program of the Geophysical Laboratory,
Carnegie Institution of Washington and the Swedish National Space Board
(contract 121/11).
NR 65
TC 6
Z9 7
U1 6
U2 22
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD FEB 10
PY 2016
VL 283
IS 1824
AR 20152893
DI 10.1098/rspb.2015.2893
PG 9
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA DD5PE
UT WOS:000369975500024
ER
PT J
AU Furuyama, W
Marzi, A
Nanbo, A
Haddock, E
Maruyama, J
Miyamoto, H
Igarashi, M
Yoshida, R
Noyori, O
Feldmann, H
Takada, A
AF Furuyama, Wakako
Marzi, Andrea
Nanbo, Asuka
Haddock, Elaine
Maruyama, Junki
Miyamoto, Hiroko
Igarashi, Manabu
Yoshida, Reiko
Noyori, Osamu
Feldmann, Heinz
Takada, Ayato
TI Discovery of an antibody for pan-ebolavirus therapy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID VIRUS GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES;
HEMORRHAGIC-FEVER; INFECTION; ENTRY; PROTECTION; EPITOPES; DISEASE; ZMAB
AB During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad-acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses.
C1 [Furuyama, Wakako; Maruyama, Junki; Miyamoto, Hiroko; Igarashi, Manabu; Yoshida, Reiko; Noyori, Osamu; Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Marzi, Andrea; Haddock, Elaine; Feldmann, Heinz] NIAID, Lab Virol, Div Intramural Res, Natl Inst Hlth,Rocky Mt Labs, Hamilton, MT USA.
[Nanbo, Asuka] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido, Japan.
[Nanbo, Asuka] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan.
RP Takada, A (reprint author), Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
EM atakada@czc.hokudai.ac.jp
RI Nanbo, Asuka/C-6630-2012; YOSHIDA, Reiko/F-6883-2012; Maruyama,
Junki/H-7993-2013
OI Nanbo, Asuka/0000-0001-8764-1350;
FU Rocky Mountain Veterinary Branch (NIAID, NIH); Research Program on
Emerging and Re-emerging Infectious Diseases from Japan Agency for
Medical Research and development (AMED); Japan Initiative for Global
Research Network on Infectious Diseases (J-GRID); Ministry of Education,
Culture, Sports, Science and Technology (MEXT); Science and Technology
Research Partnership for Sustainable Development (SATREPS); Health and
Labor Sciences Research Grant, Japan; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA
FX We thank M. Ishijima for technical assistance and K. Barrymore for
editing the manuscript. We are grateful to the Rocky Mountain Veterinary
Branch (NIAID, NIH) for their support of the animal work. This work was
supported by the Research Program on Emerging and Re-emerging Infectious
Diseases from Japan Agency for Medical Research and development (AMED)
and the Japan Initiative for Global Research Network on Infectious
Diseases (J-GRID). It was partly supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), the Science and Technology Research
Partnership for Sustainable Development (SATREPS), the Health and Labor
Sciences Research Grant, Japan and the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA.
NR 47
TC 16
Z9 16
U1 11
U2 24
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 FEB 10
PY 2016
VL 6
AR 20514
DI 10.1038/srep20514
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD2GQ
UT WOS:000369741100001
PM 26861827
ER
PT J
AU Charnaud, SC
McGready, R
Herten-Crabb, A
Powell, R
Guy, A
Langer, C
Richards, JS
Gilson, PR
Chotivanich, K
Tsuboi, T
Narum, DL
Pimanpanarak, M
Simpson, JA
Beeson, JG
Nosten, F
Fowkes, FJI
AF Charnaud, Sarah C.
McGready, Rose
Herten-Crabb, Asha
Powell, Rosanna
Guy, Andrew
Langer, Christine
Richards, Jack S.
Gilson, Paul R.
Chotivanich, Kesinee
Tsuboi, Takafumi
Narum, David L.
Pimanpanarak, Mupawjay
Simpson, Julie A.
Beeson, James G.
Nosten, Francois
Fowkes, Freya J. I.
TI Maternal-foetal transfer of Plasmodium falciparum and Plasmodium vivax
antibodies in a low transmission setting
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PLACENTAL MALARIA INFECTION; CELL-FREE SYSTEM; IMMUNE-RESPONSES;
PREGNANT-WOMEN; MEROZOITE ANTIGENS; IMMUNOGLOBULIN-G; TRANSPLACENTAL
TRANSFER; VACCINE CANDIDATES; CLINICAL MALARIA; IGG SUBCLASSES
AB During pregnancy immunolglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both P. falciparum and P. vivax are unknown. Pregnant women were screened weekly for Plasmodium infection. Mother-neonate paired serum samples at delivery were tested for IgG to antigens from P. falciparum, P. vivax and other infectious diseases. Antibodies to malarial and non-malarial antigens were highly correlated between maternal and neonatal samples (median [range] spearman rho = 0.78 [0.57-0.93]), although Plasmodium spp. antibodies tended to be lower in neonates than mothers. Estimated gestational age at last P. falciparum infection, but not P. vivax infection, was positively associated with antibody levels in the neonate (P. falciparum merozoite, spearman. median [range] 0.42 [0.33-0.66], PfVAR2CSA 0.69; P. vivax rho = 0.19 [0.09-0.3]). Maternal-foetal transfer of antimalarial IgG to Plasmodium spp. antigens occurs in low transmission settings. P. vivax IgG acquisition is not associated with recent exposure unlike P. falciparum IgG, suggesting a difference in acquisition of antibodies. IgG transfer is greatest in the final weeks of pregnancy which has implications for the timing of future malaria vaccination strategies in pregnant women.
C1 [Charnaud, Sarah C.; Herten-Crabb, Asha; Powell, Rosanna; Guy, Andrew; Langer, Christine; Richards, Jack S.; Gilson, Paul R.; Beeson, James G.; Fowkes, Freya J. I.] Macfarlane Burnet Inst Med Res, Melbourne, Vic, Australia.
[McGready, Rose; Pimanpanarak, Mupawjay; Nosten, Francois] Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand.
[McGready, Rose; Nosten, Francois] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
[McGready, Rose; Nosten, Francois] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England.
[Herten-Crabb, Asha; Richards, Jack S.; Beeson, James G.] Univ Melbourne, Dept Med, Melbourne, Vic 3010, Australia.
[Guy, Andrew] Monash Univ, Alfred Med Res & Educ Precinct, Dept Immunol, Melbourne, Vic 3004, Australia.
[Chotivanich, Kesinee] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok 10700, Thailand.
[Tsuboi, Takafumi] Ehime Univ, Proteosci Ctr, Div Malaria Res, Matsuyama, Ehime, Japan.
[Narum, David L.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Simpson, Julie A.; Fowkes, Freya J. I.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Fowkes, Freya J. I.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Fowkes, Freya J. I.] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia.
RP Fowkes, FJI (reprint author), Macfarlane Burnet Inst Med Res, Melbourne, Vic, Australia.
EM fowkes@burnet.edu.au
FU National Health and Medical Research Council of Australia [1049213];
Australian Research Council; Victorian State Government Operational
Infrastructure Support grant; Intramural Research Program of the NIH
FX We thank Julia McGuire for initial analyses. We thank Joe Smith for DBL5
and DBL-alpha antigens, Robin Anders for MSP2 antigen and Annie Mo for
EBA175 antigen. This work was supported by the National Health and
Medical Research Council of Australia (project grant 1049213,
fellowships to FJIF and JGB, Infrastructure for Research Institutes
Support Scheme Grant), Australian Research Council (Future Fellowship to
FJIF and JGB), and Victorian State Government Operational Infrastructure
Support grant. This research was supported in part by the Intramural
Research Program of the NIH. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 70
TC 2
Z9 2
U1 0
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 FEB 10
PY 2016
VL 6
AR 20859
DI 10.1038/srep20859
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD3MV
UT WOS:000369827200001
PM 26861682
ER
PT J
AU Kwon, D
Hoffman, FO
Moroz, BE
Simon, SL
AF Kwon, Deukwoo
Hoffman, F. Owen
Moroz, Brian E.
Simon, Steven L.
TI Bayesian dose-response analysis for epidemiological studies with complex
uncertainty in dose estimation
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Bayesian model averaging; cancer risk estimation; dose-response model;
radiation epidemiology
ID HANFORD THYROID-DISEASE; NUCLEAR TEST-SITE; NEVADA TEST-SITE;
MEASUREMENT ERROR; LUNG-CANCER; RESIDENTIAL RADON; MONTE-CARLO; LOCAL
FALLOUT; RADIATION; EXPOSURE
AB Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Hoffman, F. Owen] Oak Ridge Ctr Risk Anal, Oak Ridge, TN USA.
[Moroz, Brian E.; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kwon, D (reprint author), Univ Miami, Sylvester Comprehens Canc Ctr, 1120 NW 14 St,Clin Res Bldg Rm 1054, Miami, FL 33136 USA.
EM DKwon@med.miami.edu
FU National Cancer Institute Intramural Research Program; National
Institute of Allergy and Infectious Diseases; National Cancer Institute;
NIAID [Y2-Al-5077]; NCI [Y3-CO-5117]
FX This work was supported by the National Cancer Institute Intramural
Research Program and by the Intra-Agency agreement between the National
Institute of Allergy and Infectious Diseases and the National Cancer
Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117.
This research utilized the high-performance computational capabilities
of the Biowulf cluster at the National Institutes of Health, Bethesda,
Maryland, USA (). The authors are grateful to the Editor, two Referees,
and an Associate Editor for their constructive comments that improved
the quality of this article. We would like to acknowledge, in
particular, the important conceptual and practical contributions to this
work from our colleagues Robert M. Weinstock (deceased), Eduard Hofer
and, especially, Dr. Ruth Pfeiffer. In addition, we thank our
colleagues, Drs. Charles Land, Andre Bouville, Nicholas Luckyanov,
Vladimir Drozdovitch, and Harold Beck for their assistance with the
Kazakhstan dose reconstruction. We also acknowledge Brian A Thomas of
the Oak Ridge Center for Risk Analysis for his assistance in making the
plots in log-scale included in the figures to this paper.
NR 37
TC 1
Z9 1
U1 3
U2 11
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 FEB 10
PY 2016
VL 35
IS 3
BP 399
EP 423
DI 10.1002/sim.6635
PG 25
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 DA7GP
UT WOS:000367972900009
PM 26365692
ER
PT J
AU Maio, N
Ghezzi, D
Verrigni, D
Rizza, T
Bertini, E
Martinelli, D
Zeviani, M
Singh, A
Carrozzo, R
Rouault, TA
AF Maio, Nunziata
Ghezzi, Daniele
Verrigni, Daniela
Rizza, Teresa
Bertini, Enrico
Martinelli, Diego
Zeviani, Massimo
Singh, Anamika
Carrozzo, Rosalba
Rouault, Tracey A.
TI Disease-Causing SDHAF1 Mutations Impair Transfer of Fe-S Clusters to
SDHB
SO CELL METABOLISM
LA English
DT Article
ID COMPLEX-II DEFICIENCY; SUCCINATE-DEHYDROGENASE; ENERGY-METABOLISM;
HYPOXIA; PROTEIN; SUBUNIT; LEUKOENCEPHALOPATHY; FLAVINYLATION;
DYSFUNCTION; MATURATION
AB SDHAF1 mutations cause a rare mitochondrial complex II (CII) deficiency, which manifests as infantile leukoencephalopathy with elevated levels of serum and white matter succinate and lactate. Here, we demonstrate that SDHAF1 contributes to iron-sulfur (Fe-S) cluster incorporation into the Fe-S subunit of CII, SDHB. SDHAF1 transiently binds to aromatic peptides of SDHB through an arginine-rich region in its C terminus and specifically engages a Fe-S donor complex, consisting of the scaffold, holo-ISCU, and the co-chaperone-chaperone pair, HSC20-HSPA9, through an LYR motif near its N-terminal domain. Pathogenic mutations of SDHAF1 abrogate binding to SDHB, which impairs biogenesis of holo-SDHB and results in LONP1-mediated degradation of SDHB. Riboflavin treatment was found to ameliorate the neurologic condition of patients. We demonstrate that riboflavin enhances flavinylation of SDHA and reduces levels of succinate and Hypoxia-Inducible Factor (HIF)-1 alpha and -2 alpha, explaining the favorable response of patients to riboflavin.
C1 [Maio, Nunziata; Singh, Anamika; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Med Program, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Ghezzi, Daniele] Ist Ricovero & Cura Carattere Sci, Fdn Carlo Besta Neurol Inst, Unit Mol Neurogenet, I-20126 Milan, Italy.
[Verrigni, Daniela; Rizza, Teresa; Bertini, Enrico; Carrozzo, Rosalba] Bambino Gesu Pediat Hosp, Mol Med Lab, Unit Muscular & Neurodegenerat Disorders, Ist Ricovero & Cura Carattere Sci, I-00165 Rome, Italy.
[Martinelli, Diego] Bambino Gesu Pediat Hosp, Unit Metab, Ist Ricovero & Cura Carattere Sci, I-00165 Rome, Italy.
[Zeviani, Massimo] MRC, Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Med Program, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
RI Ghezzi, Daniele/J-7873-2016; Carrozzo, Rosalba/A-2808-2014;
OI Carrozzo, Rosalba/0000-0002-3327-4054; Ghezzi,
Daniele/0000-0002-6564-3766
FU Eunice Kennedy Shriver NICHD Intramural Research Program; Cell lines and
DNA Bank of Paediatric Movement Disorders and Neurodegenerative Diseases
of the Telethon Network of Genetic Biobanks [GTB12001J]; EurobiobanK
Network; Pierfranco and Luisa Mariani Foundation; Telethon [GGP11011];
ERC [FP7-322424]
FX We thank our colleagues, support by the Eunice Kennedy Shriver NICHD
Intramural Research Program, the Cell lines and DNA Bank of Paediatric
Movement Disorders and Neurodegenerative Diseases of the Telethon
Network of Genetic Biobanks (grant GTB12001J), and the EurobiobanK
Network. Supported by the Pierfranco and Luisa Mariani Foundation,
Telethon Grant GGP11011, and ERC Advanced Grant FP7-322424. We thank Dr.
Ross Tomaino for the mass spectrometric analyses.
NR 41
TC 6
Z9 7
U1 4
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD FEB 9
PY 2016
VL 23
IS 2
BP 292
EP 302
DI 10.1016/j.cmet.2015.12.005
PG 11
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DI6MR
UT WOS:000373613800008
PM 26749241
ER
PT J
AU Roche, J
Shen, Y
Lee, JH
Ying, JF
Bax, A
AF Roche, Julien
Shen, Yang
Lee, Jung Ho
Ying, Jinfa
Bax, Ad
TI Monomeric A beta(1-40) and A beta(1-42) Peptides in Solution Adopt Very
Similar Ramachandran Map Distributions That Closely Resemble Random Coil
SO BIOCHEMISTRY
LA English
DT Article
ID AMYLOID-BETA-PEPTIDE; NUCLEATION-DEPENDENT POLYMERIZATION; INTRINSICALLY
DISORDERED PROTEIN; MOLECULAR-DYNAMICS SIMULATIONS; ALZHEIMERS-DISEASE;
COUPLING-CONSTANTS; ALPHA-SYNUCLEIN; ANGLE DISTRIBUTIONS; SPECTRAL
RESOLUTION; A-BETA-42 PEPTIDES
AB The pathogenesis of Alzheimer's disease is characterized by the aggregation and fibrillation of amyloid peptides A beta(1-40) and A beta(1-42) into amyloid plaques. Despite strong potential therapeutic interest, the structural pathways associated with the conversion of monomeric A beta peptides into oligomeric species remain largely unknown. In particular, the higher aggregation propensity and associated toxicity of A beta(1-42) compared to that of A beta(1-40) are poorly understood. To explore in detail the structural propensity of the monomeric A beta(1-40) and A beta(1-42) peptides in solution, we recorded a large set of nuclear magnetic resonance (NMR) parameters, including chemical shifts, nuclear Overhauser effects (NOEs), and J couplings. Systematic comparisons show that at neutral pH the A beta(1-40) and A beta(1-42) peptides populate almost indistinguishable coil-like conformations. Nuclear Overhauser effect spectra collected at very high resolution remove assignment ambiguities and show no long-range NOE contacts. Six sets of backbone J couplings ((3)J(HNH alpha), (3)J(C'C'), (3)J(C'H alpha), (1)J(H alpha C alpha), (2)J(NC alpha), and (1)J(NC alpha)) recorded for A beta(1-40) were used as input for the recently developed MERA Ramachandran map analysis, yielding residue-specific backbone phi/psi torsion angle distributions that closely resemble random coil distributions, the absence of a significantly elevated propensity for beta-conformations in the C-terminal region of the peptide, and a small but distinct propensity for alpha(L), at K28. Our results suggest that the self-association of A beta peptides into toxic oligomers is not driven by elevated propensities of the monomeric species to adopt beta-strand-like conformations. Instead, the accelerated disappearance of A beta NMR signals in D2O over H2O, particularly pronounced for A beta(1-42), suggests that intermolecular interactions between the hydrophobic regions of the peptide dominate the aggregation process.
C1 [Roche, Julien; Shen, Yang; Lee, Jung Ho; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Shen, Yang/C-3064-2008
OI Shen, Yang/0000-0003-1408-8034
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (NIH); Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH
FX This work was funded by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (NIH), and the Intramural AIDS-Targeted Antiviral
Program of the Office of the Director, NIH.
NR 95
TC 7
Z9 7
U1 11
U2 31
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 9
PY 2016
VL 55
IS 5
BP 762
EP 775
DI 10.1021/acs.biochem.5b01259
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DD7OW
UT WOS:000370115000003
PM 26780756
ER
PT J
AU Masaoka, T
Zhao, HY
Hirsch, DR
D'Erasmo, MP
Meck, C
Varnado, B
Gupta, A
Meyers, MJ
Baines, J
Beutler, JA
Murelli, RP
Tang, L
Le Grice, SFJ
AF Masaoka, Takashi
Zhao, Haiyan
Hirsch, Danielle R.
D'Erasmo, Michael P.
Meck, Christine
Varnado, Brittany
Gupta, Ankit
Meyers, Marvin J.
Baines, Joel
Beutler, John A.
Murelli, Ryan P.
Tang, Liang
Le Grice, Stuart F. J.
TI Characterization of the C-Terminal Nuclease Domain of Herpes Simplex
Virus pUL15 as a Target of Nucleotidyltransferase Inhibitors
SO BIOCHEMISTRY
LA English
DT Article
ID HIV-1 REVERSE-TRANSCRIPTASE; RIBONUCLEASE-H ACTIVITY; INTEGRASE
INHIBITORS; HYDROXYLATED TROPOLONES; ALPHA-HYDROXYTROPOLONES; RNA/DNA
HYBRIDS; ACTIVE-SITE; INFECTION; REPLICATION; ENZYME
AB The natural product alpha-hydroxytropolones manicol and beta-thujaplicinol inhibit replication of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2, respectively) at nontoxic concentrations. Because these were originally developed as divalent metal-sequestering inhibitors of the ribonuclease H activity of HIV-1 reverse transcriptase, alpha-hydroxytropolones likely target related HSV proteins of the nucleotidyltransferase (NTase) superfamily, which share an "RNase H-like" fold. One potential candidate is pUL15, a component of the viral terminase molecular motor complex, whose C-terminal nuclease domain, pUL15C, has recently been crystallized. Crystallography also provided a working model for DNA occupancy of the nuclease active site, suggesting potential protein-nucleic acid contacts over a region of similar to 14 bp. In this work, we extend crystallographic analysis-by examining pUL15C-mediated hydrolysis of short, closely related DNA duplexes. In addition to defining a minimal substrate length, this strategy facilitated construction of a dual-probe fluorescence assay for rapid kinetic analysis of wild-type and mutant nucleases. On the basis of its proposed role in binding the phosphate backbone, studies with pUL15C variant Lys700Ala showed that this mutation affected neither binding of. duplex DNA nor binding of small molecule to the active site but caused a 17-fold reduction in the turnover rate (k(cat)), possibly by slowing-conversion of the enzyme-substrate complex to the, enzyme product complex and/or inhibiting dissociation from the hydrolysis product. Finally, with a view of pUL15-associated nuclease activity as an antiviral target, the dual-probe fluorescence assay, in combination with differential scanning fluorimetry, was used to demonstrate inhibition by several classes of small Molecules that target divalent metal at the active site.
C1 [Masaoka, Takashi; Le Grice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21702 USA.
[Zhao, Haiyan; Varnado, Brittany; Tang, Liang] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
[Hirsch, Danielle R.; D'Erasmo, Michael P.; Meck, Christine; Murelli, Ryan P.] CUNY Brooklyn Coll, Dept Chem, Brooklyn, NY 11210 USA.
[Hirsch, Danielle R.; D'Erasmo, Michael P.; Meck, Christine; Murelli, Ryan P.] CUNY, Grad Ctr, PhD Program Chem, New York, NY 10016 USA.
[Gupta, Ankit] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO 63104 USA.
[Meyers, Marvin J.] St Louis Univ, Dept Chem, St Louis, MO 63103 USA.
[Baines, Joel] Louisiana State Univ, Sch Vet Med, Baton Rouge, LA 70803 USA.
[Beutler, John A.] NCI, Mol Targets Lab, Frederick, MD 21702 USA.
RP Le Grice, SFJ (reprint author), NCI, Basic Res Lab, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services; National Institutes of Health [SC1GM111158,
R01GM090010, R01AI507421]; St. Louis University Department of Molecular
Microbiology and Immunology
FX S.F.J.L.G., T.M., and J.A.B. are supported by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health,
Department of Health and Human Services. D.R.H., M.P.D., and C.M. are
supported by National Institutes of Health Grant SC1GM111158 to R.P.M.
H.Z. is supported by National Institutes of Health Grant R01GM090010 to
L.T. J.B. is supported in part by National Institutes of Health Grant
R01AI507421. A.G. was a recipient of a seed grant from the St. Louis
University Department of Molecular Microbiology and Immunology.
NR 39
TC 4
Z9 4
U1 3
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 9
PY 2016
VL 55
IS 5
BP 809
EP 819
DI 10.1021/acs.biochem.5b01254
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DD7OW
UT WOS:000370115000007
PM 26829613
ER
PT J
AU Silvestri, V
Barrowdale, D
Mulligan, AM
Neuhausen, SL
Fox, S
Karlan, BY
Mitchell, G
James, P
Thull, DL
Zorn, KK
Carter, NJ
Nathanson, KL
Dornchek, SM
Rebbeck, TR
Ramus, SJ
Nussbaum, RL
Olopade, OI
Rantala, J
Yoon, SY
Caligo, MA
Spugnesi, L
Bojesen, A
Pedersen, IS
Thomassen, M
Jensen, UB
Toland, AE
Senter, L
Andrulis, IL
Glendon, G
Hulick, PJ
Irnyanitov, EN
Greene, MH
Mai, PL
Singer, CF
Rappaport-Fuerhauser, C
Kramer, G
Vijai, J
Offit, K
Robson, M
Lincoln, A
Jacobs, L
Machackova, E
Foretova, L
Navratilova, M
Vasickova, P
Couch, FJ
Hallberg, E
Ruddy, KJ
Sharma, P
Kim, SW
Teixeira, MR
Pinte, P
Montagna, M
Matricardi, L
Arason, A
Johannsson, OT
Barkardottir, RB
Jakubowska, A
Lubinski, J
Izquierdo, A
Pujana, MA
Balmana, J
Diez, O
Ivady, G
Papp, J
Olah, E
Kwong, A
Nevanlinna, H
Aittomaki, K
Segura, PP
Caldes, T
Van Maerken, T
Poppe, B
Claes, KBM
Isaacs, C
Elan, C
Lasset, C
Stoppa-Lyonnet, D
Barjhoux, L
Belotti, M
Meindl, A
Gehrig, A
Sutter, C
Enger, C
Niederacher, D
Steinemann, D
Hahnen, E
Kast, K
Arnold, N
Varon-Mateeva, R
Wand, D
Godwin, AK
Evans, DG
Frost, D
Perkins, J
Adlard, J
Izatt, L
Platte, R
Eeles, R
Ellis, S
Hamann, U
Garber, J
Fostira, F
Fountzilas, G
Pasini, B
Giannini, G
Rizzolo, P
Russo, A
Cortesi, L
Papi, L
Varesco, L
Palli, D
Zanna, I
Savarese, A
Radice, P
Manoukian, S
Peissel, B
Barile, M
Bonanni, B
Viel, A
Pensotti, V
Tommasi, S
Peterlongo, P
Weitzel, JN
Osorio, A
Benitez, J
McGuffog, L
Healey, S
Gerdes, AM
Ejlertsen, B
Hansen, TVO
Steele, L
Ding, YC
Tung, N
Janavicius, R
Goldgar, DE
Buys, SS
Daly, MB
Bane, A
Terry, MB
John, EM
Southey, M
Easton, DF
Chenevix-Trench, G
Antoniou, AC
Ottini, L
AF Silvestri, Valentina
Barrowdale, Daniel
Mulligan, Anna Marie
Neuhausen, Susan L.
Fox, Stephen
Karlan, Beth Y.
Mitchell, Gillian
James, Paul
Thull, Darcy L.
Zorn, Kristin K.
Carter, Natalie J.
Nathanson, Katherine L.
Dornchek, Susan M.
Rebbeck, Timothy R.
Ramus, Susan J.
Nussbaum, Robert L.
Olopade, Olufunrnilayo I.
Rantala, Johanna
Yoon, Sook-Yee
Caligo, Maria A.
Spugnesi, Laura
Bojesen, Anders
Pedersen, Inge Sokilde
Thomassen, Muds
Jensen, Uffe Birk
Toland, Amanda Ewart
Senter, Leigha
Andrulis, Irene L.
Glendon, Gord
Hulick, Peter J.
Irnyanitov, Evgeny N.
Greene, Mark H.
Mai, Phuong L.
Singer, Christian F.
Rappaport-Fuerhauser, Christine
Kramer, Gero
Vijai, Joseph
Offit, Kenneth
Robson, Mark
Lincoln, Anne
Jacobs, Lauren
Machackova, Eva
Foretova, Lenka
Navratilova, Marie
Vasickova, Petra
Couch, Fergus J.
Hallberg, Emily
Ruddy, Kathryn J.
Sharma, Priyanka
Kim, Sung-Won
Teixeira, Manuel R.
Pinte, Pedro
Montagna, Marco
Matricardi, Laura
Arason, Adalgeir
Johannsson, Oskar Th
Barkardottir, Rosa B.
Jakubowska, Anna
Lubinski, Jan
Izquierdo, Angel
Angel Pujana, Miguel
Balmana, Judith
Diez, Orland
Ivady, Gabriella
Papp, Janos
Olah, Edith
Kwong, Ava
Nevanlinna, Heli
Aittomaki, Kristiina
Perez Segura, Pedro
Caldes, Trinidad
Van Maerken, Tom
Poppe, Bruce
Claes, Kathleen B. M.
Isaacs, Claudine
Elan, Camille
Lasset, Christine
Stoppa-Lyonnet, Dominique
Barjhoux, Laure
Belotti, Muriel
Meindl, Alfons
Gehrig, Andrea
Sutter, Christian
Enger, Christoph
Niederacher, Dieter
Steinemann, Doris
Hahnen, Eric
Kast, Karin
Arnold, Norbert
Varon-Mateeva, Raymonda
Wand, Dorothea
Godwin, Andrew K.
Evans, D. Gareth
Frost, Debra
Perkins, Jo
Adlard, Julian
Izatt, Louise
Platte, Radka
Eeles, Ros
Ellis, Steve
Hamann, Ute
Garber, Judy
Fostira, Florentia
Fountzilas, George
Pasini, Barbara
Giannini, Giuseppe
Rizzolo, Piera
Russo, Antonio
Cortesi, Laura
Papi, Laura
Varesco, Liliana
Palli, Domenico
Zanna, Ines
Savarese, Antonella
Radice, Paolo
Manoukian, Siranoush
Peissel, Bernard
Barile, Monica
Bonanni, Bernardo
Viel, Alessandra
Pensotti, Valeria
Tommasi, Stefania
Peterlongo, Paolo
Weitzel, Jeffrey N.
Osorio, Ana
Benitez, Javier
McGuffog, Lesley
Healey, Sue
Gerdes, Anne-Marie
Ejlertsen, Bent
Hansen, Thomas V. O.
Steele, Linda
Ding, Yuan Chun
Tung, Nadine
Janavicius, Ramunas
Goldgar, David E.
Buys, Saundra S.
Daly, Mary B.
Bane, Anita
Terry, Mary Beth
John, Esther M.
Southey, Melissa
Easton, Douglas F.
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Ottini, Laura
CA kConFab Investigators
Hereditary Breast Ovarian Canc Res
EMBRACE
TI Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data
from the Consortium of Investigators of Modifiers of BRCA1/2
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Male breast cancer; BRCA1/2; Pathology; Histologic grade;
Genotype-phenotype correlations
ID POPULATION; RISK; CARCINOMA; FEATURES; GRADE
AB Background: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).
Methods: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.
Results: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 x 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 x 10(-12)).
Conclusions: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
C1 [Silvestri, Valentina; Giannini, Giuseppe; Rizzolo, Piera; Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Viale Regina Elena 324, I-00161 Rome, Italy.
[Barrowdale, Daniel; Frost, Debra; Perkins, Jo; Ellis, Steve; McGuffog, Lesley; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Mulligan, Anna Marie; Andrulis, Irene L.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Neuhausen, Susan L.; Steele, Linda; Ding, Yuan Chun] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA.
[Fox, Stephen] Peter MacCallum Canc Inst, East Melbourne, Australia.
[Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Mitchell, Gillian; James, Paul] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia.
[Mitchell, Gillian; James, Paul] Univ Melbourne, Dept Oncol, Melbourne, Vic, Australia.
[Thull, Darcy L.; Zorn, Kristin K.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Carter, Natalie J.] UPMC Canc Ctr, Pittsburgh, PA USA.
[Nathanson, Katherine L.; Dornchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Ramus, Susan J.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA.
[Olopade, Olufunrnilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
[Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[Yoon, Sook-Yee] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia.
[Yoon, Sook-Yee] Univ Malaya, Med Ctr, Fac Med, Canc Res Inst, Kuala Lumpur, Malaysia.
[Caligo, Maria A.; Spugnesi, Laura] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy.
[Caligo, Maria A.; Spugnesi, Laura] Univ Hosp Pisa, Pisa, Italy.
[Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark.
[Thomassen, Muds] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark.
[Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus N, Denmark.
[Toland, Amanda Ewart] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Senter, Leigha] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Dept Human Genet, Columbus, OH 43210 USA.
[Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Hulick, Peter J.] North Shore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA.
[Irnyanitov, Evgeny N.] NN Petrov Oncol Res Inst, St Petersburg, Russia.
[Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Singer, Christian F.; Rappaport-Fuerhauser, Christine] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria.
[Kramer, Gero] Med Univ Vienna, Dept Urol, Vienna, Austria.
[Vijai, Joseph; Offit, Kenneth; Lincoln, Anne; Jacobs, Lauren] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Robson, Mark] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA.
[Machackova, Eva; Navratilova, Marie; Vasickova, Petra] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Foretova, Lenka] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic.
[Foretova, Lenka] Masaryk Univ, Fac Med, Brno, Czech Republic.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Couch, Fergus J.; Hallberg, Emily] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Ruddy, Kathryn J.] Mayo Clin, Dept Oncol, Rochester, MN USA.
[Sharma, Priyanka] Univ Kansas, Med Ctr, Dept Hematol & Oncol, Kansas City, KS 66103 USA.
[Kim, Sung-Won] Daerim St Marys Hosp, Dept Surg, Seoul, South Korea.
[Teixeira, Manuel R.; Pinte, Pedro] Portuguese Inst Oncol, Dept Genet, Oporto, Portugal.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Montagna, Marco; Matricardi, Laura] IRCCS Sci Inst Hospitalizat & Care, IOV, Immunol & Mol Oncol Unit, Padua, Italy.
[Arason, Adalgeir; Barkardottir, Rosa B.] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Arason, Adalgeir; Barkardottir, Rosa B.] Univ Iceland, Fac Med, Biomed Ctr BMC, Reykjavik, Iceland.
[Johannsson, Oskar Th] Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland.
[Johannsson, Oskar Th] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Izquierdo, Angel] Catalan Inst Oncol, Biomed Res Inst Girona IDIBGI, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain.
[Angel Pujana, Miguel] Catalan Inst Oncol, Bellvitge Biomed Res Inst IDIBELL, Breast Canc & Syst Biol Unit, Barcelona, Spain.
[Balmana, Judith] Vall dHebron Univ Hosp, Dept Med Oncol, Barcelona, Spain.
[Diez, Orland] Vall dHebron Univ Hosp, Oncogenet Grp, VHIO, Barcelona, Spain.
[Diez, Orland] Univ Autonoma Barcelona, E-08193 Barcelona, Spain.
[Ivady, Gabriella] Natl Inst Oncol, Dept Pathol, Budapest, Hungary.
[Papp, Janos; Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Nevanlinna, Heli; Aittomaki, Kristiina] Helsinki Univ Hosp, Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland.
[Perez Segura, Pedro] San Carlos Clin Hosp, Hlth Res Inst IdISSC, Dept Oncol, Madrid, Spain.
[Caldes, Trinidad] San Carlos Clin Hosp, Hlth Res Inst IdISSC, Mol Oncol Lab, Madrid, Spain.
[Van Maerken, Tom; Poppe, Bruce; Claes, Kathleen B. M.] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Elan, Camille; Stoppa-Lyonnet, Dominique; Belotti, Muriel] Inst Curie, Dept Tumor Biol, Paris, France.
[Lasset, Christine] Univ Lyon 1, CNRS UMR5558, F-69365 Lyon, France.
[Lasset, Christine] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, F-69373 Lyon, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Barjhoux, Laure] Univ Lyon, Ctr Rech Cancerol Lyon, CNRS UMR5286, INSERM U1052, Lyon, France.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, D-80290 Munich, Germany.
[Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Wurzburg, Germany.
[Sutter, Christian] Univ Heidelberg Hosp, Inst Human Genet, Heidelberg, Germany.
[Enger, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dusseldorf, Germany.
[Steinemann, Doris] Hannover Med Sch, Hannover, Germany.
[Hahnen, Eric] Univ Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, D-50931 Cologne, Germany.
[Hahnen, Eric] Univ Cologne, Fac Med, CIO, D-50931 Cologne, Germany.
[Hahnen, Eric] Univ Cologne, Fac Med, CMMC, D-50931 Cologne, Germany.
[Hahnen, Eric] Univ Hosp Cologne, Cologne, Germany.
[Kast, Karin] Tech Univ Dresden, Dept Obstet & Gynecol, D-01062 Dresden, Germany.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecolgy & Obstet, Kiel, Germany.
[Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Berlin, Germany.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Genet Med, Manchester, Lancs, England.
[Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England.
[Izatt, Louise] Guys & St Thomas NHS Fdn Trust, Clin Genet, London, England.
[Platte, Radka] Inst Canc Res, Oncogenet Team, Sutton, Surrey, England.
[Platte, Radka] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England.
[Eeles, Ros; Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA.
[Fostira, Florentia] Natl Ctr Sci Res Demokritos, Inst Nucl & Radiol Sci & Technol INRASTES, Mol Diagnost Lab, Athens, Greece.
[Fountzilas, George] Aristotle Univ Thessaloniki, Dept Med Oncol, Papageorgiou Hosp, Sch Med, GR-54006 Thessaloniki, Greece.
[Pasini, Barbara] Univ Turin, Dept Med Sci, Turin, Italy.
[Pasini, Barbara] AO Citta Salute & Sci, Turin, Italy.
[Russo, Antonio] Univ Palermo, Dept Surg & Ontol Sci, Sect Med Oncol, Palermo, Italy.
[Cortesi, Laura] Univ Modena & Reggio Emilia, Dept Haematol & Oncol, Modena, Italy.
[Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy.
[Varesco, Liliana] Natl Inst Canc Res, AOU San Martino IST, IRCCS Sci Inst Hospitalizat & Care, Unit Hereditary Canc,Dept Epidemiol Prevent & Spe, Genoa, Italy.
[Palli, Domenico; Zanna, Ines] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Savarese, Antonella] Regina Elena Inst Canc Res, Dept Med Oncol, Unit Genet Counselling, Rome, Italy.
[Radice, Paolo] Natl Canc Inst INT, IRCCS Sci Inst Hospitalizat & Care, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, I-20133 Milan, Italy.
[Manoukian, Siranoush; Peissel, Bernard] Natl Canc Inst INT, IRCCS Sci Inst Hospitalizat & Care, Dept Prevent & Predict Med, Unit Med Genet, I-20133 Milan, Italy.
[Barile, Monica; Bonanni, Bernardo] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Viel, Alessandra] CRO Avian Natl Canc Inst, Div Expt Oncol, Avian, PN, Italy.
[Pensotti, Valeria; Peterlongo, Paolo] FIRC, IFOM, Inst Mol Oncol, Milan, Italy.
[Pensotti, Valeria] Cogentech Canc Genet Test Lab, Milan, Italy.
[Tommasi, Stefania] Natl Canc Inst Giovanni Paolo II, Bari, Italy.
[Weitzel, Jeffrey N.] City Hope Clin Canc Genet Community Res Network, Clin Canc Genet, Duarte, CA USA.
[Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Human Canc Genet Program, Madrid, Spain.
[Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain.
[Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
[Gerdes, Anne-Marie] Copenhagen Univ Hosp, Rigshosp, Dept Clin Genet, Copenhagen, Denmark.
[Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark.
[Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
[Janavicius, Ramunas] State Res Inst, Ctr Innovat Med, Vilnius, Lithuania.
[Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT USA.
[Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Bane, Anita] McMaster Univ, Dept Pathol & Mol Med, Juravinski Hosp & Canc Ctr, Hamilton, ON, Canada.
[Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA.
[Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
RP Ottini, L (reprint author), Univ Roma La Sapienza, Dept Mol Med, Viale Regina Elena 324, I-00161 Rome, Italy.
EM laura.ottini@uniroma1.it
RI montagna, marco/E-2225-2012; Teixeira, Manuel/E-4885-2011; Osorio,
Ana/I-4324-2014; Andrulis, Irene/E-7267-2013; Arnold,
Norbert/E-3012-2010; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017;
OI Fox, Stephen/0000-0002-7648-8896; Evans, Gareth/0000-0002-8482-5784;
montagna, marco/0000-0002-4929-2150; Barrowdale,
Daniel/0000-0003-1661-3939; Teixeira, Manuel/0000-0002-4896-5982;
Osorio, Ana/0000-0001-8124-3984; Arnold, Norbert/0000-0003-4523-8808;
Eeles, Rosalind/0000-0002-3698-6241; Ramus, Susan/0000-0003-0005-7798;
PALLI, Domenico/0000-0002-5558-2437; Joseph, Vijai/0000-0002-7933-151X;
manoukian, siranoush/0000-0002-6034-7562; Peissel,
Bernard/0000-0001-9233-3571; Robson, Mark/0000-0002-3109-1692; Tommasi,
Stefania/0000-0002-2157-2978
FU National Cancer Institute [UM1 CA164920, RC4CA153828]; Research Council
of Lithuania [LIG-07/2012]; Breast Cancer Research Foundation; Morris
and Horowitz Families Endowed Professorship; NEYE Foundation; Spanish
Association against Cancer [AECC08]; Mutua Madrilena Foundation (FMMA);
RTICC [06/0020/1060]; Office of the Director, National Institutes of
Health; Fondazione IRCCS Istituto Nazionale Tumori; FiorGen Foundation
for Pharmacogenomics; AIRC [IG12780]; FIRC; Cancer Research UK
[C1287/A10118, C1287/A11990, C5047/A8385, C1287/A10710, C12292/A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565];
NHMRC; European Union [European Social Fund (ESF)]; Greek national funds
through the Operational Program "Education and Lifelong Learning" of the
National Strategic Reference Framework (NSRF)-Research Funding Program
of the General Secretariat for Research & Technology: ARISTEIA; European
Social Fund; DKFZ. EMBRACE; NIHR grant to the Biomedical Research
Centre, Manchester, UK; Royal Marsden NHS Foundation Trust; NIHR;
Biomedical Research Centre; University of Kansas Cancer Center [P30
CA168524]; Kansas Bioscience Authority Eminent Scholar Program;
Chancellors Distinguished Chair in Biomedical Sciences Professorship;
German Cancer Aid [110837]; Center for Molecular Medicine Cologne
(CMMC); Ligue Nationale Contre le Cancer; Association "Le cancer du
sein, parlors-enl" Award; Canadian Institutes of Health Research for the
"CIHR Team in Familial Risks of Breast Cancer; National Institute of
Cancer (INCa); Non-Therapeutic Subject Registry Shared Resource at
Georgetown University (NIH/NCI) [P30-CA051008]; Fisher Center for
Familial Cancer Research; GOA [BOF10/GOA/019]; ISCIII (Spain)
[RD12/00369/0006, 12/00539]; European Regional Development FEDER funds;
Helsinki University Hospital Research Fund, Academy of Finland [266528];
Finnish Cancer Society and the Sigrid Juselius Foundation; Dutch Cancel
Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands
Organization of Scientific Research [NWO 91109024]; Pink Ribbon [110005,
2014-187.WO76]; BBMRI [NWO 184.021.007/CP46]; Dutch Cancer Society
[NKI1998-1854, NKI2004-3088, NKI2007-3756]; Transcan [JTC 2012]; Cancer
[12-054]; Hong Kong Hereditary Breast Cancer Family Registry; Dr. Ellen
Li Charitable Foundation, Hong Kong; Hungarian research [KTA-OTKA
CK-80745, OTPA K-112228]; Norwegian EEA Financial Mechanism
[Hu0115/NA/2008-3/OP-9]; Asociacion Espanola Contra el Cancer, Spanish
Health Research Fund; Carlos III Health Institute; Catalan Health
Institute and Autonomous Government of Catalonia; ISCIIRETIC
[RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285,
PIE13/00022, 2009SGR290, 2014SGR364]; IHCC [PBZ_KBN_122/P05/2004];
Icelandic Association "Walking for Breast Cancer Research"; Landspitali
University Hospital Research Fund; Liga Portuguesa Contra o Cancro;
National Breast Cancer Foundation, and previously; National Health and
Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia;
Cancer Foundation of Western Australia; National Breast Cancer
Foundation, Cancer Australia; National Institutes of Health (USA);
National R&D Program for Cancer Control, Ministry for Health, Welfare
and Family Affairs, Republic of Korea [1020350]; NIH, an NCI Specialized
Program of Research Excellence (SPORE) in Breast Cancer [CA116167,
CA128978, CA176785, CA116201]; U.S. Department of Defense Ovarian Cancer
Idea award [W81XWH-10-1-0341]; David F. and Margaret rein Family
Foundation; Ting Tsung and We Fong Chao Foundation; MH CZ - DRO [MMCI,
00209805]; European Regional Development Fund; State Budget of the Czech
Republic [RECAMO,CZ.1.05./21.00/03.0101]; Charles University in Prague
[UNCE204024]; Robert. and Kate Niehaus Clinical Cancer Genetics
Initiative; Andrew Sabin Reserch Fund; Intramural Research Program of
the National Cancer Institute, [711]; Russian Federation for Basic
Research [13-04-92613, 14-04-93959, 15-04-01744]; Ohio State University
Comprehensive Cancer Center; ITT (Istituto Toscano Tumori); SEABASS:
Ministry of Science, Technology and Innovation Ministry of Higher
Education and Cancer Research Initiatives Foundation [UMC/HIR/MOHE/06];
Malaysia Ministry of Science, Technology and Innovation, Ministry of
Higher Education [UM.C/HIR/MOHE/06]; Cancer Research Initiatives
Foundation; Swedish, Cancer Society; NCI Specialized Program of Research
Excellence (SPORE) in Breast Cancer [CA125183, R01 CA142996,
1U01CA161032]; Ralph and Marion Falk Medical Research Trust;
Entertainment Industry Fund National Womens Can Research Alliance and
the Breast Cancer research Foundation; CRUK; University Pennsylvania
National Instiutes of Health (NIH) [R01-CA102776, R01-CA083855]; Susan
G. Komen Foundation forte Cure, Basser Research Center; UPITT/MWH:
Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program;
VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer
Foundation Geoffrey Lindeman, Marion Harris, Martin Delatyki of the
Victorian Familial Cancer Trials Group; American Cancer Society Early
Detection Professorship [SIOP-06-258-01-COUN]; National Center for
Advancing Translational Sciences (NCATS) [UL1TR000124]; European
Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175];
National Institutes of Health [CA128978]; Post-Cancer GWAS initiative
[1U19 CA148537, 1U19 CA148065, 1U19 CA146112]; U.S. Department of
Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research
(CIHR); CIHR Team in Familial Risks of Breast Cancer, Komen Foundation;
Ovarian Cancer Research Fund; [SAF2010-20493]; [FISPI08/1120];
[5U01CA113916]; [R01CA140323]; [NO2-CP-11019-50]; [N02-CP-65504]
FX BCFR: This work was supported by grant UM1 CA164920 from the National
Cancer Institute. The content of this manuscript does not necessarily
reflect the views or policies of the National Cancer Institute or any of
the collaborating centres in the Breast Cancer Family Registry (BCFR),
nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. government or the BCFR. BCFR-AU:
Acknowledge Maggie Angelakos, Judi Maskiell, Gillian Dite and Helen
Tsimiklis. BCFR-NY: We thank members and participants in the New York
site of the Breast Cancer Family Registry for their contributions to the
study. BCFR-ON: We thank members and participants in the Ontario
Familial Breast Cancer Registry for their contributions to the study.
BFBOCC-LT is partly supported by Research Council of Lithuania grant
LIG-07/2012. We acknowledge Vilius Rudaitis and Laimonas Griskevicius.
BIDMC is supported by the Breast Cancer Research Foundation. BRICOH: SLN
was partially supported by the Morris and Horowitz Families Endowed
Professorship. CBCS: This work was supported by the NEYE Foundation.
CNIO: This work was partially supported by Spanish Association against
Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena
Foundation (FMMA) and SAF2010-20493. We thank Alicia Barroso, Rosario
Alonso and Guillermo Pita for their assistance. COH-CCGCRN: City of Hope
Clinical Cancer Genetics Community Network and the Hereditary Cancer
Research Registry, supported in part by award number RC4CA153828 (JNW,
principal investigator) from the National Cancer Institute and the
Office of the Director, National Institutes of Health. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
CONSIT TEAM: Funds from Italian citizens who allocated the 5 x 1000
share of their tax payment in support of the Fondazione IRCCS Istituto
Nazionale Tumori, according to Italian laws (INT institutional strategic
projects '5 x 1000') to SM and from FiorGen Foundation for
Pharmacogenomics to LP. LO is supported by AIRC (IG12780). VS is
supported by FIRC (triennial fellowship "Mario e Valeria Rindi"). We
acknowledge Maria Grazia Tibiletti of the Ospedale di Circolo-Universita
dell'Insubria, Varese, Italy. CORE: The CIMBA data management and data
analysis were supported by Cancer Research UK grants C12292/A11174 and
C1287/A10118. SH is supported by an NHMRC program grant (to GCT). ACA is
a Cancer Research UK senior cancer research fellow. GCT is an NHMRC
senior principal research fellow. DEMOKRITOS: This research has been
co-financed by the European Union [European Social Fund (ESF)] and Greek
national funds through the Operational Program "Education and Lifelong
Learning" of the National Strategic Reference Framework (NSRF)-Research
Funding Program of the General Secretariat for Research & Technology:
ARISTEIA. Investing in knowledge society through the European Social
Fund. DKFZ: The DKFZ study was supported by the DKFZ. EMBRACE is
supported by Cancer Research UK grants C1287/A10118 and C1287/A11990.
DGE and Fiona Lalloo are supported by an NIHR grant to the Biomedical
Research Centre, Manchester, UK. The investigators at The Institute of
Cancer Research and The Royal Marsden NHS Foundation Trust are supported
by an NIHR grant to the Biomedical Research Centre at The Institute of
Cancer Research and The Royal Marsden NHS Foundation Trust. RE and
Elizabeth Bancroft are supported by Cancer Research UK grant
C5047/A8385.; RE is also supported by NIHR support of the Biomedical
Research Centre at The Institute of Cancer Research and The Royal
Marsden NHS Foundation Trust. RE is supported by NIHR support to the
Biomedical Research Centre at The Institute of Cancer Research and The
Royal Marsden NHS Foundation Trust. FCCC: The authors acknowledge
support from The University of Kansas Cancer Center (P30 CA168524) and
the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded
by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair
in Biomedical Sciences Professorship. We thank Ms. Jo Ellen Weaver and
Dr. Betsy Bove for their technical support. GC-HBOC: The German
Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is
supported by the German Cancer Aid (grant 110837 to Rita K. Schmutgler)
and by the Center for Molecular Medicine Cologne (CMMC). GEMo: The study
was supported by the Ligue Nationale Contre le Cancer; the Association
"Le cancer du sein, parlors-enl" Award; the Canadian Institutes of
Health Research for the "CIHR Team in Familial Risks of Breast Cancer
program and the trench National Institute of Cancer (INCa). Genetic
Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study:
National Cancer Genetics Network "UNICANCER Genetic Group", France. We
thank all the GEMO collaborating groups for their contribution to this
study. DEMO Collaborating Centers are Coordinating Centres: Unite Mixte
de Genetique Constitutionnelle des Cancers Frequents, Hospices Gyms de
Lyon - Centre Leon Berard, & Equipe Genetique du cancer du sein", Centre
de Recherche en Cancerologie de Lyon: Olga Sinilnikova dagger, Sylvie
Nlazoyer, Francesca Damiola, Laure Barjhoux, Carole Verny-Pierre,
Melanie Leone, Nadia Boutry-Kryza, Alain Calender, Sophie Grand; and
Service de Genetique Oncologique, Institut Curie, Paris: Dominique
Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer,
Etienne Rouleau, Lisa Golmard, Agnes Collet Virginie Moncoutier, Cedrick
Lefol, Muriel Belotti, Antoine de Pauw, Camille Elan, Catherine Nogues,
Emmanuelle Fourme Anne-Marie Birot. Institut Gustave Roussy,Villejuif
Brigitte Bressac-de-Paillerets, Olivier Caron, Marine Guillaud-Batasille
Centre Jean Perrin, Clerrnont-Ferrand: Yves-Jean Bignon, Nancy
Uhrhammer. centre Leon Berard, Lyon: Christine Lasset, Valerie Bonadona,
Sandrine Handallou. Centre Francois Baclesse, Caen: Agnes Hardouin,
Pascaline Berthet, Dominique Vaur, Laurent Castera. Institut Paoli
Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi
Audrey Remenieras, Francois Eisinger. CHU Arnaud-de-Villeneuve,
Montpellier: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret,
Lille: Jean-Philippe Peyrat, Joelle Fournier, Francoise Revillion
PhilippeVennint dagger, Claude Adenis. Centre Paul Strauss, Strasbourg:
Daniele Muller, Jean-Pierre Fricker. Institut Bergonie, Bordeaux:
Emmanuelle Barouk-Simonet, Francoisc Bonn I, Bubien, Nicolas Sevenet,
Michel Longy. Institut Claudius Regaud, Toulousee: Christine Tor la
Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU Grenoble:
Dominique Leroux Helene Dreyfus, Christine Rebischung, Magalie
Peysselon. CHU Dijon: Fanny Coron, Laurence Faivre. CHU St-Etienne:
Fabienne Prieur, Marine Lebrun, Caroline Kientz. Hotel Dieu Centre
Hospitalier, Chambery: Sandra Fert Ferrer. Centre Antoine Lacassagne,
Nice: Marc Frenay CHU Limoges: Laurence Venat-Bouvet. CHU Nantes:
Capucine Delnatte. CHU Bretonncau, Tours: Isabelle Mortemonsque.; Groupe
Hospitalier Pitie-Salpetriere, Pals: Florence Coulet, Chrystelle Cobs,
Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les-Nancy Johanna
Sokolowska, Myriam Bronner CHU Besancon: Marie-Agnes Collonge-Rame,
Alexandre Damette. Creighton University, On NE, USA Henry T. Lynch,
Carrie L. Snyder. Georgetown University: CI received support from the
Non-Therapeutic Subject Registry Shared Resource at Georgetown
University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial
Cancer Research, and Swing for the Cure. G-FAST: Kim De Leeneer is
supported by GOA glaint BOF10/GOA/019 (Ghent University) and spearhead
financing of Ghent University Hospital. We thank the technical support
of IIse Coene en Brecht Crombez. was supported by a grant
RD12/00369/0006 and 12/00539 from ISCIII (Spain), partially supported by
European Regional Development FEDER funds. We acknowledge Alicia Tosar
for her technical assistance. HEBCS was financially supported by the
Helsinki University Hospital Research Fund, Academy of Finland (266528),
the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBCS
thanks Taru A. Mu amen, Drs. Carl Blomqvist and Kirsimari Aaltonen and
RNs Irja Erkkila and Virpi Palola for their help with the HEBCS data and
samples. HERON is supported by the Dutch Cancel Society grants
NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization
of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005
and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration
teams of the Comprehensive Cancer Centre Netherlands and Comprehensive
Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch
Pathology Registry) for part of the data collection. The Hereditary
Breast and Ovarian Cancer Research Group Netherlands (HERON) consists of
the following collaborating centres: coordinating centre: Netherlands
Cancer Institute, Amsterdam, the Netherlands: M. A. Rookus, F. B. L.
Hogervorst F. E. van Leeuwen, S. Verhoef, M. K Schmidt, N. S. Russell,
J. L. de Lange, R. Wijnands; Erasmus Medical Center, Rotterdam, the
Netherlands:1 M. Collee A. M. W. van den Ouweland, M. J. Floc ning, C.
Seynaeve, C. H. M. van Deurzen, I. M. Obdeijn; Leiden University Medical
Center, the Netherlands: C. J. van Asperen, J. T. Wijnen, R. A. E. M.
Tollenaar, P. Devilee, T. C T. E. F. van Cronenburg; Radboud University
Nijmegen Medical Center, the Netherlands: C. M. Kets, A. R. Mensenkamp;
University Medical Center Utrecht, the Netherlands: M. G. E. M. Ausems,
R. B. van der Luijt, C. C. van der Pol; Amsterdam Medical Center,
Amsterdam, the Netherlands: C. M. Aalfs, T. A. M. van Os; VU University
Medical Center, Amsterdam, Amsterdam, the Netherlands: j. J. P. Gille,
Q. Waisfisz, H University Hospital Maastricht, the Netherlands: E. B.
Gomez-Garcia M. J Blok; University Medical Center (Groningen, the
Netherlands: J.C Oosterwijk, A. H. van der Hout, M. J. Mourits, G. H. de
Bock; -File Netherlands Foundation for the detection of hereditary
tumours, Leiden, the Netherlands: H. F. Vasen; The Netherlands
Comprehensive Cancer Organization (IKNL): S. Siesling, J. Verloop; The
Dutch Pathology Registy (PALGA): L. I. H. Overbeek. The HEBON study is
supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088
NKI2007-3756, the Netherlands Organization of Scientific Research grant
NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI
grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer
12-054. HEBON thanks the registration teams of IKNL. and PALGA for part
of the data collection.; HRBCP is supported by The Hong Kong Hereditary
Breast Cancer Family Registry and the Dr. Ellen Li Charitable
Foundation, Hong Kong. We, the thank Hong Kong Sanatorium and Hospital
for their continual support HUNBOCS: Hungarian Breast and Ovarian Cancer
Study was supported by Hungarian research grants KTA-OTKA CK-80745, OTPA
K-112228 and the Norwegian EEA Financial Mechanism
Hu0115/NA/2008-3/OP-9. We thank the ilungarian Breast and Ovarian Cancer
Study Group members Gangs Papp, Tibor Vaszko Aniko Bozsik, Timea Pocza,
Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi,
Department of Molecular Genetics, National Institute of Oncology,
Budapest Hungary) and the clinicians and patients for their
contributions to this study. HVH: We, thank the Oncogcnetics Group
(VHIO), and the High Risk and Cancer Prevention Unit of the University
Hospital Vall d'Hebron. ICO: Contract grant sponsor: Asociacion Espanola
Contra el Cancer, Spanish Health Research Fund; Carlos III Health
Institute; Catalan Health Institute and Autonomous Government of
Catalonia. contract grant numbers: ISCIIRETIC RD06/0020/1051,
RD12/0036/008 PI10/01422, PI10/00748, PI13/00285, PIE13/00022,
2009SGR290 and 2014SGR364. We thank the ICO Hereditary Cancer Program
team led by Dr. Gabriel Capella. The IHCC was supported by Grant
PBZ_KBN_122/P05/2004. The ILUH group was supported by the Icelandic
Association "Walking for Breast Cancer Research" and by the Landspitali
University Hospital Research Fund. IOVHBOCS is supported by Minister()
della Salute and "5x1000" Istituto Oncologico Veneto grant. IPOBCS: This
study was part supported by Liga Portuguesa Contra o Cancro. We thank
Drs. Ana Peixoto, Catarina Santos, Patricia Rocha and Pedro Pinto for
their skilful contribution to the study. kConFab is supported by a grant
from the National Breast Cancer Foundation, and previously by the
National Health and Medical Research Council (NHMRC), the Queensland
Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania
and South Australia, and the Cancer Foundation of Western Australia; We,
thank Heather Thorne, Eveline Niedermayr, all the kConFab research
nurses and. staff, the heads and staff of the Family Cancer Clinics, and
the Clinical Follow Up Study [which has received funding from the NHMRC,
the National Breast Cancer Foundation, Cancer Australia, and the
National Institutes of Health (USA)] for their contributions to this
resource, and the many familles who contribute to kConFab. KOIIBRA is
supported by a grant from the National R&D Program for Cancer Control,
Ministry for Health, Welfare and Family Affairs, Republic of Korea
(1020350). MAYO is supported by NIH grants CA116167, CA128978 and
CA176785, an NCI Specialized Program of Research Excellence (SPORE) in
Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer
Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research
Foundation, a generous gift from the David F. and Margaret rein Family
Foundation and the Ting Tsung and We Fong Chao Foundation. MODSQUAD was
supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional
Development Fund and the State Budget of the Czech Republic
(RECAMO,CZ.1.05./21.00/03.0101) to LF, and by Charles University in
Prague project UNCE204024 (to MZ).; MODSQUAD acknowledges ModSQuaD
members Csilla Szabo (National Human Genome Research Institute, National
Institutes of Health, Bethesda, MD, USA) and Michal Zikan, Petr
Pohlreich and Zdenek Kleibl (Oncogynecologic Center and Department of
Biochemistry and Experimental Oncology, First Faculty of Medicine,
Charles University, Prague, Czech Republic). MSKCC is supported by
grants from the Breast Cancer Research Foundation, the Robert. and Kate
Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin
Reserch Fund. NCI: The research of MHG and PLM was supported by the
Intramural Research Program of the National Cancer Institute, 711, and
by support services contracts NO2-CP-11019-50 and N02-CP-65504 with
Westat, Inc., Rockville, MD, USA. NNPIO: This work has been supported by
the Russian Federation for Basic Research (grants 13-04-92613,
14-04-93959 and 15-04-01744). OCGN: We thank members and participants in
the Ontario Cancer Genetics Network for their contributions to the
study. OSUCCG is supported by The Ohio State University Comprehensive
Cancer Center. Leigha Senter, Kevin Sweet, Caroline Craven and Michelle
O'Conor were in in accrual of study participants, ascertainment of
medical records and database management. Samples were processed by the
OSU Human Genetics Sample Bank. PBCS: This work was supported by the ITT
(Istituto Toscano Tumori) grants 2011-2013. SEABASS: Ministry of
Science, Technology and Innovation Ministry of Higher Education
(UMC/HIR/MOHE/06) and Cancer Research Initiatives Foundation. We thank
Yip Cheng Har, Nur Aishah Mohd Talb, Phuah Sze Yee, Norhashimah Hassan
and all the research nurses, research assistants and doctors involved in
the MyBrCa Study for assistance in patient recruitment, data collet on
and sample preparation. In addition, we thank Philip lau, Sng Jen-Hwei
and Sharifah Nor Akmal for contributing samples from the Singapore
Breast Cancer Study and the HUKM-HKL Study, respectively. The Malaysian
Breast Cancer Genetic Study is funded by resarch grants from the
Malaysia Ministry of Science, Technology and Innovation, Ministry of
Higher Education (UM.C/HIR/MOHE/06) and charitable funding from Cancer
Research Initiatives Foundation. SWE-BRCA collaborators are supported by
the Swedish, Cancer Society. Swedish, scientists participating as
SWE-BRCA collaborators are as follows: from Lund University and
University Hospital: angstrom ke Borg, Hakan Olsson, Helena Jemstrom,
Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from
Gothenburg Sahlgrenska University Hospital: Anna Ofverholm, Margareta
Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska
University Hospital: Anna von Wachenfeldt, Annelle Liljegren, Annika
Lindblom, Brita Arver, Gisela Barbany Bustinza, Johanna Rantala; from
Umea University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor,
Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta
Hellstrom Pigg, Richard Rosenquist; from Linkoping University Hospital:
Marie Stenmark-Askmalm, Sigrun Liedgren. The University of Chicago is
supported by NCI Specialized Program of Research Excellence (SPORE) in
Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph
and Marion Falk Medical Research Trust, the Entertainment Industry Fund
National Womens Can Research Alliance and the Breast Cancer research
Foundation. OIO is an American Cancer Society clinical research
professor.; We thank Cecilla Zvocec, Qun Niu, physicians, genetic
counsellors, research nurses anti staff of the Cancer Risk Clinic for
their contributions to this resource, and the many families who
contribute to Our program. UCSF Cancer Risk Program and Helen Diller
Family Comprehensive Cancer Center. We thank the following genetic
counsellors for participant recruitment: Beth Crawford, Kate Loranger,
Julie Mak, Nicola Stewart Robin Lee, Amie Blanco and Peggy Conrad.
Thanks are also extended to Ms. Salina Chan for her data management.
UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We
thank Paul Pharoah, Simon Gayther Susan Ramus, Carole Pye, Patricia
Harrington and Eva Wozniak for their contributions to the UKFOCR.
University Pennsylvania National Instiutes of Health (NIH) (grants
R01-CA102776 and R01-CA083855); Breast Cancer Research Foundation; Susan
G. Komen Foundation forte Cure, Basser Research Center for BRCA.
UPITT/MWH: Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research
Program; Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency,
Cancer Australia, National Breast Cancer Foundation Geoffrey Lindeman,
Marion Harris, Martin Delatyki of the Victorian Familial Cancer Trials
Group.;Ale thank Sarah Sawyer and Rebecca Driessen for assembling this
data and Ella Thompson for performing all DNA amplification. WCP: BYK is
funded by the American Cancer Society Early Detection Professorship
(SIOP-06-258-01-COUN) and National Center for Advancing Translational
Sciences (NCATS) grant UL1TR000124. Funding for the ICOGS infrastructure
came from: the European Community's Seventh Framework Programme under
grant agreement number 223175 (HEALTH-F2-2009-223175) (COGS), Cancer
Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National
Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19
CA148537, 1U19 CA148065 and 1U19 CA146112 - the GAME-ON Initiative), the
U.S. Department of Defense (W81XWH-10-1-0341), the Canadian Institutes
of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer, Komen Foundation for the Cure, the Breast Cancer Research
Foundation and the Ovarian Cancer Research Fund.
NR 30
TC 1
Z9 1
U1 11
U2 26
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD FEB 9
PY 2016
VL 18
AR 15
DI 10.1186/s13058-016-0671-y
PG 13
WC Oncology
SC Oncology
GA DD0DQ
UT WOS:000369590900001
PM 26857456
ER
PT J
AU Cowan, JE
McCarthy, NI
Anderson, G
AF Cowan, Jennifer E.
McCarthy, Nicholas I.
Anderson, Graham
TI CCR7 Controls Thymus Recirculation, but Not Production and Emigration,
of Foxp3(+) T Cells
SO CELL REPORTS
LA English
DT Article
ID DEVELOPING THYMOCYTES; NEGATIVE SELECTION; MEDULLA MIGRATION;
DIFFERENTIATION; CORTEX; LYMPHOCYTES; HOMEOSTASIS; EXPRESSION; SIGNALS;
MICE
AB Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7-mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-) Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation.
C1 [Cowan, Jennifer E.; McCarthy, Nicholas I.; Anderson, Graham] Univ Birmingham, Inst Immunol & Immunotherapy, Ctr Immune Regulat, MRC, Birmingham B15 2TT, W Midlands, England.
[Cowan, Jennifer E.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Anderson, G (reprint author), Univ Birmingham, Inst Immunol & Immunotherapy, Ctr Immune Regulat, MRC, Birmingham B15 2TT, W Midlands, England.
EM g.anderson@bham.ac.uk
FU MRC Programme grant [MR/N000919/1]
FX The authors thank Dr. Andrea Bacon and BMSU staff for animal husbandry.
This work was supported by an MRC Programme grant to G.A.
(MR/N000919/1).
NR 29
TC 1
Z9 1
U1 2
U2 5
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 FEB 9
PY 2016
VL 14
IS 5
BP 1041
EP 1048
DI 10.1016/j.celrep.2016.01.003
PG 8
WC Cell Biology
SC Cell Biology
GA DD0NG
UT WOS:000369616100008
PM 26832402
ER
PT J
AU Dell'Orso, S
Wang, AHJ
Shih, HY
Saso, K
Berghella, L
Gutierrez-Cruz, G
Ladurner, AG
O'Shea, JJ
Sartorelli, V
Zare, H
AF Dell'Orso, Stefania
Wang, A. Hongjun
Shih, Han-Yu
Saso, Kayoko
Berghella, Libera
Gutierrez-Cruz, Gustavo
Ladurner, Andreas G.
O'Shea, John J.
Sartorelli, Vittorio
Zare, Hossein
TI The Histone Variant MacroH2A1.2 Is Necessary for the Activation of
Muscle Enhancers and Recruitment of the Transcription Factor Pbx1
SO CELL REPORTS
LA English
DT Article
ID INACTIVE X-CHROMOSOME; DNA-BINDING PROTEINS; GENE-EXPRESSION;
CRYSTAL-STRUCTURE; CELL IDENTITY; CORE HISTONE; CHROMATIN; MYOD;
DIFFERENTIATION; PLURIPOTENCY
AB Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an similar to 25 kDa evolutionarily conserved non-histonemacro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation.
C1 [Dell'Orso, Stefania; Wang, A. Hongjun; Saso, Kayoko; Gutierrez-Cruz, Gustavo; Sartorelli, Vittorio; Zare, Hossein] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Shih, Han-Yu; O'Shea, John J.] NIAMS, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Berghella, Libera] IRCCS Fdn Santa Lucia, Epigenet & Regenerat Med, I-00143 Rome, Italy.
[Ladurner, Andreas G.] Univ Munich, Dept Physiol Chem, LMU Biomed Ctr, Butenandt Inst, Marchioninistr 15, D-81377 Munich, Germany.
RP Sartorelli, V (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
EM sartorev@mail.nih.gov
FU NIAMS
FX We thank members of the V.S. laboratory for helpful discussion and
technical advice. This work was supported in part by the Intramural
Research Program of NIAMS.
NR 68
TC 0
Z9 0
U1 1
U2 5
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 FEB 9
PY 2016
VL 14
IS 5
BP 1156
EP 1168
DI 10.1016/j.celrep.2015.12.103
PG 13
WC Cell Biology
SC Cell Biology
GA DD0NG
UT WOS:000369616100017
PM 26832413
ER
PT J
AU Ali, JM
Negus, MC
Conlon, TM
Harper, IG
Qureshi, MS
Motallebzadeh, R
Willis, R
Saeb-Parsy, K
Bolton, EM
Bradley, JA
Pettigrew, GJ
AF Ali, Jason M.
Negus, Margaret C.
Conlon, Thomas M.
Harper, Ines G.
Qureshi, M. Saeed
Motallebzadeh, Reza
Willis, Richard
Saeb-Parsy, Kourosh
Bolton, Eleanor M.
Bradley, J. Andrew
Pettigrew, Gavin J.
TI Diversity of the CD4 T Cell Alloresponse: The Short and the Long of It
SO CELL REPORTS
LA English
DT Article
ID HUMAN ENDOTHELIAL-CELLS; TRANSPLANT REJECTION; CARDIAC ALLOGRAFTS;
GRAFT-REJECTION; ALLORECOGNITION PATHWAYS; POSITIVE SELECTION;
REGULATORY CELLS; IMMUNE-RESPONSE; INFECTION; TOLERANCE
AB MHC alloantigen is recognized by two pathways: "directly,'' intact on donor cells, or "indirectly,'' as self-restricted allopeptide. The duration of each pathway, and its relative contribution to allograft vasculopathy, remain unclear. Using a murine model of chronic allograft rejection, we report that direct-pathway CD4 T cell alloresponses, as well as indirect-pathway responses against MHC class II alloantigen, are curtailed by rapid elimination of donor hematopoietic antigen-presenting cells. In contrast, persistent presentation of epitope resulted in continual division and less-profound contraction of the class I allopeptide-specific CD4 T cell population, with approximately 10,000-fold more cells persisting than following acute allograft rejection. This expanded population nevertheless displayed sub-optimal anamnestic responses and was unable to provide co-stimulation-independent help for generating alloantibody. Indirect-pathway CD4 T cell responses are heterogeneous. Appreciation that responses against particular alloantigens dominate at late time points will likely inform development of strategies aimed at improving transplant outcomes.
C1 [Ali, Jason M.; Negus, Margaret C.; Conlon, Thomas M.; Harper, Ines G.; Qureshi, M. Saeed; Motallebzadeh, Reza; Saeb-Parsy, Kourosh; Bolton, Eleanor M.; Bradley, J. Andrew; Pettigrew, Gavin J.] Univ Cambridge, Sch Clin Med, Cambridge CB2 0QQ, England.
[Willis, Richard] Emory Yerkes, NIH Tetramer Facil, 954 Gatewood Rd, Atlanta, GA 30329 USA.
RP Pettigrew, GJ (reprint author), Univ Cambridge, Sch Clin Med, Cambridge CB2 0QQ, England.
EM gjp25@cam.ac.uk
OI motallebzadeh, reza/0000-0002-5399-9546; Saeb-Parsy,
Kourosh/0000-0002-0633-3696
FU British Heart Foundation; National Institute of Health Research
Cambridge Biomedical Research Centre; National Institute of Health
Research Blood and Transplant Research Unit; Wellcome Trust; Raymond
Scholarship; Academy of Medical Sciences/Wellcome Trust starter grant;
Beverly Sackler Scholarship
FX This work was supported by a British Heart Foundation project grant, the
National Institute of Health Research Cambridge Biomedical Research
Centre, and the National Institute of Health Research Blood and
Transplant Research Unit. J.M.A. was supported by a Wellcome Trust
Clinical Research Training Fellowship and Raymond and Beverly Sackler
Scholarships. K.S.-P. was supported by an Academy of Medical
Sciences/Wellcome Trust starter grant.
NR 49
TC 2
Z9 2
U1 0
U2 1
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 FEB 9
PY 2016
VL 14
IS 5
BP 1232
EP 1245
DI 10.1016/j.celrep.2015.12.099
PG 14
WC Cell Biology
SC Cell Biology
GA DD0NG
UT WOS:000369616100023
PM 26804905
ER
PT J
AU Dhombres, F
Bodenreider, O
AF Dhombres, Ferdinand
Bodenreider, Olivier
TI Interoperability between phenotypes in research and healthcare
terminologies-Investigating partial mappings between HPO and SNOMED CT
SO JOURNAL OF BIOMEDICAL SEMANTICS
LA English
DT Article
DE Partial mapping; Human phenotype; Ontology; Standard terminologies;
Interoperability
ID BIOMEDICAL TERMINOLOGY; ONTOLOGIES; LANGUAGE; DISEASE
AB Background: Identifying partial mappings between two terminologies is of special importance when one terminology is finer-grained than the other, as is the case for the Human Phenotype Ontology (HPO), mainly used for research purposes, and SNOMED CT, mainly used in healthcare.
Objectives: To investigate and contrast lexical and logical approaches to deriving partial mappings between HPO and SNOMED CT.
Methods: 1) Lexical approach-We identify modifiers in HPO terms and attempt to map demodified terms to SNOMED CT through UMLS; 2) Logical approach-We leverage subsumption relations in HPO to infer partial mappings to SNOMED CT; 3) Comparison-We analyze the specific contribution of each approach and evaluate the quality of the partial mappings through manual review.
Results: There are 7358 HPO concepts with no complete mapping to SNOMED CT. We identified partial mappings lexically for 33 % of them and logically for 82 %. We identified partial mappings both lexically and logically for 27 %. The clinical relevance of the partial mappings (for a cohort selection use case) is 49 % for lexical mappings and 67 % for logical mappings.
Conclusions: Through complete and partial mappings, 92 % of the 10,454 HPO concepts can be mapped to SNOMED CT (30 % complete and 62 % partial). Equivalence mappings between HPO and SNOMED CT allow for interoperability between data described using these two systems. However, due to differences in focus and granularity, equivalence is only possible for 30 % of HPO classes. In the remaining cases, partial mappings provide a next-best approach for traversing between the two systems. Both lexical and logical mapping techniques produce mappings that cannot be generated by the other technique, suggesting that the two techniques are complementary to each other. Finally, this work demonstrates interesting properties (both lexical and logical) of HPO and SNOMED CT and illustrates some limitations of mapping through UMLS.
C1 [Dhombres, Ferdinand; Bodenreider, Olivier] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
RP Bodenreider, O (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM olivier@nlm.nih.gov
FU Intramural Research Program of the NIH, National Library of Medicine;
French Gynecology and Obstetrics Association (College National des
Gynecologues et Obstetriciens Francais); Philippe Foundation
FX This work was supported in part by the Intramural Research Program of
the NIH, National Library of Medicine, the French Gynecology and
Obstetrics Association (College National des Gynecologues et
Obstetriciens Francais), and the Philippe Foundation.
NR 25
TC 2
Z9 2
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2041-1480
J9 J BIOMED SEMANT
JI J. Biomed. Semant.
PD FEB 9
PY 2016
VL 7
AR 3
DI 10.1186/s13326-016-0047-3
PG 13
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA DD5FP
UT WOS:000369948400001
PM 26865946
ER
PT J
AU Lei, R
Zhang, K
Wei, YX
Chen, M
Weinstein, LS
Hong, Y
Zhu, MY
Li, HC
Li, HS
AF Lei, Run
Zhang, Ke
Wei, Yanxia
Chen, Min
Weinstein, Lee S.
Hong, Yang
Zhu, Minyan
Li, Hongchang
Li, Huashun
TI G-Protein alpha-Subunit Gs alpha Is Required for Craniofacial
Morphogenesis
SO PLOS ONE
LA English
DT Article
ID STIMULATORY G-PROTEIN; ELEMENT-BINDING PROTEIN; CRANIAL NEURAL CREST;
PARATHYROID-HORMONE REQUIRES; EPIDERMAL-GROWTH-FACTOR; PIERRE-ROBIN
SEQUENCE; INDIAN-HEDGEHOG; BONE-FORMATION; OSTEOBLASTIC CELLS;
CLEFT-PALATE
AB The heterotrimeric G protein subunit Gs alpha couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gs alpha is ubiquitously expressed in many cell types; however, the role of Gs alpha in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gs alpha knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gs alpha knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gs alpha knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gs alpha in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gs alpha is required for neural crest cells-derived craniofacial development.
C1 [Lei, Run; Zhang, Ke; Wei, Yanxia; Li, Huashun] Sichuan Univ, West China Dev & Stem Cell Inst, West China Second Hosp, Chengdu 610064, Sichuan, Peoples R China.
[Lei, Run; Zhang, Ke; Wei, Yanxia; Li, Huashun] Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu 610064, Sichuan, Peoples R China.
[Lei, Run; Zhang, Ke; Li, Hongchang] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Mol Biol Neural Dev, Lab Dev & Regenerat Biol,Inst Biomed & Biotechnol, Shenzhen, Guangdong, Peoples R China.
[Lei, Run; Zhang, Ke; Zhu, Minyan; Li, Huashun] Chinese Acad Sci, Tongji Univ, SARITEX Ctr Stem Cell Engn Translat Med, Shanghai East Hosp,Sch Med, Shanghai, Peoples R China.
[Chen, Min; Weinstein, Lee S.] Natl Inst Diabet & Digest & Kidney Dis, Metab Dis Branch, NIH, Bethesda, MD USA.
[Hong, Yang] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA.
RP Li, HS (reprint author), Sichuan Univ, West China Dev & Stem Cell Inst, West China Second Hosp, Chengdu 610064, Sichuan, Peoples R China.; Li, HS (reprint author), Sichuan Univ, State Key Lab Biotherapy, West China Hosp, Chengdu 610064, Sichuan, Peoples R China.; Li, HC (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Key Lab Mol Biol Neural Dev, Lab Dev & Regenerat Biol,Inst Biomed & Biotechnol, Shenzhen, Guangdong, Peoples R China.; Li, HS (reprint author), Chinese Acad Sci, Tongji Univ, SARITEX Ctr Stem Cell Engn Translat Med, Shanghai East Hosp,Sch Med, Shanghai, Peoples R China.
EM hc.li@siat.ac.cn; huashunli@tongji.edu.cn
FU Ministry of Science & Technology-China [2014CB964600, 2012CB966800,
2013ZX09509104, 2007CB947202, 2009CB941402, 2010CB945600, 2011CB965100,
2009R0002]; National Science Foundation of China [31301125, 30771102,
31071283, 81370457, 81271498]; Shenzhen Peacock Plan
[KQCX20130628112914292]; Shenzhen Key Laboratory for Molecular Biology
of Neural Development [ZDSY20120617112838879]; faculty development
support (West China Women's & Children Hospital & Shenzhen Institutes of
Advanced Technology-CAS & Tongji University Shanghai East Hospital)
FX This work was partially supported by grants from the Ministry of Science
& Technology-China (2014CB964600, 2012CB966800,2013ZX09509104,
2007CB947202,2009CB941402, 2010CB945600, 2011CB965100, 2013ZX09509104,
and 2009R0002), National Science Foundation of China (31301125,
30771102, 31071283,81370457, 81271498), Shenzhen Peacock Plan (No.
KQCX20130628112914292), and faculty development support (West China
Women's & Children Hospital & Shenzhen Institutes of Advanced
Technology-CAS & Tongji University Shanghai East Hospital) and Shenzhen
Key Laboratory for Molecular Biology of Neural Development
(ZDSY20120617112838879). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 87
TC 1
Z9 1
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 9
PY 2016
VL 11
IS 2
AR e0147535
DI 10.1371/journal.pone.0147535
PG 21
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DD6MN
UT WOS:000370038400010
PM 26859889
ER
PT J
AU Liu, LL
Lu, Y
Martinez, J
Bi, YJ
Lian, GJ
Wang, TT
Milasta, S
Wang, J
Yang, M
Liu, GW
Green, DR
Wang, RN
AF Liu, Lingling
Lu, Yun
Martinez, Jennifer
Bi, Yujing
Lian, Gaojian
Wang, Tingting
Milasta, Sandra
Wang, Jian
Yang, Mao
Liu, Guangwei
Green, Douglas R.
Wang, Ruoning
TI Proinflammatory signal suppresses proliferation and shifts macrophage
metabolism from Myc-dependent to HIF1 alpha-dependent
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE metabolism; macrophage; cell cycle; Myc; HIF1 alpha
ID CANCER-CELL METABOLISM; GLUTAMINE-METABOLISM; GLUCOSE-METABOLISM;
NITRIC-OXIDE; C-MYC; ACTIVATED MACROPHAGES; MOUSE MACROPHAGES;
INFLAMMATION; HIF-1-ALPHA; GLYCOLYSIS
AB As a phenotypically plastic cellular population, macrophages change their physiology in response to environmental signals. Emerging evidence suggests that macrophages are capable of tightly coordinating their metabolic programs to adjust their immunological and bioenergetic functional properties, as needed. Upon mitogenic stimulation, quiescent macrophages enter the cell cycle, increasing their bioenergetic and biosynthetic activity to meet the demands of cell growth. Proinflammatory stimulation, however, suppresses cell proliferation, while maintaining a heightened metabolic activity imposed by the production of bactericidal factors. Here, we report that the mitogenic stimulus, colony-stimulating factor 1 (CSF-1), engages a myelocytomatosis viral oncogen (Myc)-dependent transcriptional program that is responsible for cell cycle entry and the up-regulation of glucose and glutamine catabolism in bone marrow-derived macrophages (BMDMs). However, the proinflammatory stimulus, lipopolysaccharide (LPS), suppresses Myc expression and cell proliferation and engages a hypoxia-inducible factor alpha (HIF1 alpha)-dependent transcriptional program that is responsible for heightened glycolysis. The acute deletion of Myc or HIF1a selectively impaired the CSF-1-or LPS-driven metabolic activities in BMDM, respectively. Finally, inhibition of glycolysis by 2-deoxyglucose (2-DG) or genetic deletion of HIF1 alpha suppressed LPS-induced inflammation in vivo. Our studies indicate that a switch from a Myc-dependent to a HIF1 alpha-dependent transcriptional program may regulate the robust bioenergetic support for an inflammatory response, while sparing Myc-dependent proliferation.
C1 [Liu, Lingling; Lian, Gaojian; Wang, Tingting; Wang, Ruoning] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc & Blood Dis, Columbus, OH 43205 USA.
[Liu, Lingling; Lian, Gaojian; Wang, Tingting; Wang, Ruoning] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Hematol Oncol & Blood & Marrow Transplant, Columbus, OH 43205 USA.
[Lu, Yun; Wang, Jian; Liu, Guangwei] Fudan Univ, Sch Basic Med Sci, Ministry Educ, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.
[Lu, Yun; Wang, Jian; Liu, Guangwei] Fudan Univ, Sch Basic Med Sci, Ministry Hlth, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.
[Lu, Yun; Wang, Jian; Liu, Guangwei] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200433, Peoples R China.
[Lu, Yun; Wang, Jian; Liu, Guangwei] Fudan Univ, Inst Immunobiol, Biotherapy Res Ctr, Shanghai 200433, Peoples R China.
[Martinez, Jennifer] NIEHS, Immun Inflammat & Dis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Bi, Yujing] Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing 100101, Peoples R China.
[Lian, Gaojian] Univ South China, Med Res Ctr, Hengyang 421101, Hunan, Peoples R China.
[Milasta, Sandra; Yang, Mao; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
RP Wang, RN (reprint author), Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc & Blood Dis, Columbus, OH 43205 USA.; Wang, RN (reprint author), Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Hematol Oncol & Blood & Marrow Transplant, Columbus, OH 43205 USA.; Liu, GW (reprint author), Fudan Univ, Sch Basic Med Sci, Ministry Educ, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.; Liu, GW (reprint author), Fudan Univ, Sch Basic Med Sci, Ministry Hlth, Key Lab Med Mol Virol, Shanghai 200433, Peoples R China.; Liu, GW (reprint author), Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai 200433, Peoples R China.; Liu, GW (reprint author), Fudan Univ, Inst Immunobiol, Biotherapy Res Ctr, Shanghai 200433, Peoples R China.; Green, DR (reprint author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM liugw@fudan.edu.cn; douglas.green@stjude.org;
ruoning.wang@nationwidechildrens.org
RI Wang, Ruoning/C-1683-2014
FU NIH [R21AI117547, 1R01AI114581]; V Foundation [V2014-001]; American
Cancer Society [128436-RSG-15-180-01-LIB]; National Natural Science
Foundation for General Programs of China [31171407, 81273201]; American
Lebanese Charity; Syrian Associated Charity; NIH
FX This work was supported by NIH Grants R21AI117547 and 1R01AI114581, V
Foundation Grant V2014-001, American Cancer Society Grant
128436-RSG-15-180-01-LIB (to R.W.), National Natural Science Foundation
for General Programs of China Grants 31171407 and 81273201 (to G. Liu),
the American Lebanese and Syrian Associated Charities, and other grants
from the NIH (to D.R.G.).
NR 51
TC 5
Z9 6
U1 8
U2 16
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 FEB 9
PY 2016
VL 113
IS 6
BP 1564
EP 1569
DI 10.1073/pnas.1518000113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9WG
UT WOS:000369571700042
PM 26811453
ER
PT J
AU Zilberman-Rudenko, J
Shawver, LM
Wessel, AW
Luo, YQ
Pelletier, M
Tsai, WXL
Lee, YL
Vonortas, S
Cheng, L
Ashwell, JD
Orange, JS
Siegel, RM
Hanson, EP
AF Zilberman-Rudenko, Jevgenia
Shawver, Linda Monaco
Wessel, Alex W.
Luo, Yongquan
Pelletier, Martin
Tsai, Wanxia Li
Lee, Younglang
Vonortas, Spiridon
Cheng, Laurence
Ashwell, Jonathan D.
Orange, Jordan S.
Siegel, Richard M.
Hanson, Eric P.
TI Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-kappa
B activation and autoinflammatory disease
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE NF-kappa B; autoinflammatory disease; A20; HED-ID; TLR
ID ESSENTIAL MODULATOR MUTATION; ANHIDROTIC ECTODERMAL DYSPLASIA;
IKK-GAMMA; UBIQUITIN-BINDING; TNF RECEPTOR; INCONTINENTIA PIGMENTI;
IMMUNE-DEFICIENCY; IMMUNODEFICIENCY; CHAINS; GENE
AB Receptor-induced NF-kappa B activation is controlled by NEMO, the NF-kappa B essential modulator. Hypomorphic NEMO mutations result in X-linked ectodermal dysplasia with anhidrosis and immunodeficiency, also referred to as NEMO syndrome. Here we describe a distinct group of patients with NEMO C-terminal deletion (Delta CT-NEMO) mutations. Individuals harboring these mutations develop inflammatory skin and intestinal disease in addition to ectodermal dysplasia with anhidrosis and immunodeficiency. Both primary cells from these patients, as well as reconstituted cell lines with this deletion, exhibited increased I kappa B kinase (IKK) activity and production of proinflammatory cytokines. Unlike previously described loss-of-function mutations, Delta CT-NEMO mutants promoted increased NF-kappa B activation in response to TNF and Toll-like receptor stimulation. Investigation of the underlying mechanisms revealed impaired interactions with A20, a negative regulator of NF-kappa B activation, leading to prolonged accumulation of K63-ubiquitinated RIP within the TNFR1 signaling complex. Recruitment of A20 to the C-terminal domain of NEMO represents a novel mechanism limiting NF-kappa B activation by NEMO, and its absence results in autoinflammatory disease.
C1 [Zilberman-Rudenko, Jevgenia; Wessel, Alex W.; Luo, Yongquan; Lee, Younglang; Vonortas, Spiridon; Hanson, Eric P.] NIAMSD, Immunodeficiency & Inflammat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Shawver, Linda Monaco] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Res Inst, Philadelphia, PA 19104 USA.
[Pelletier, Martin; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Tsai, Wanxia Li] NIAMSD, Translat Immunol Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
[Cheng, Laurence] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
[Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Orange, Jordan S.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
RP Hanson, EP (reprint author), NIAMSD, Immunodeficiency & Inflammat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
EM eric.hanson@nih.gov
NR 57
TC 2
Z9 2
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 FEB 9
PY 2016
VL 113
IS 6
BP 1612
EP 1617
DI 10.1073/pnas.1518163113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9WG
UT WOS:000369571700050
PM 26802121
ER
PT J
AU Ju, W
Zhang, ML
Wilson, KM
Petrus, MN
Bamford, RN
Zhang, XH
Guha, R
Ferrer, M
Thomas, CJ
Waldmann, TA
AF Ju, Wei
Zhang, Meili
Wilson, Kelli M.
Petrus, Michael N.
Bamford, Richard N.
Zhang, Xiaohu
Guha, Rajarshi
Ferrer, Marc
Thomas, Craig J.
Waldmann, Thomas A.
TI Augmented efficacy of brentuximab vedotin combined with ruxolitinib
and/or Navitoclax in a murine model of human Hodgkin's lymphoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Hodgkin's lymphoma; ruxolitinib; Navitoclax; brentuximab vedotin
ID REED-STERNBERG CELLS; PHASE-II; DISEASE; ACTIVATION; THERAPY;
INTERLEUKIN-13; EXPRESSION; INHIBITOR; APOPTOSIS; BLOCKADE
AB Despite relative success of therapy for Hodgkin's lymphoma (HL), novel therapeutic agents are needed for patients with refractory or relapsed disease. Recently, anti-PD1 immunotherapy or treatment with the anti-CD30 toxin conjugate brentuximab vedotin (BV) have been associated with remissions; however, the median responses of complete responses (CRs) with the latter were only 6.7 mo. To obtain curative therapy, other effective agents, based on HL biology, would have to be given in combination with BV. Hodgkin's Reed-Sternberg (HRS) cells secrete cytokines including IL-6 and -13, leading to constitutive activation of JAK/STAT signaling. In the present study the JAK1/2 inhibitor ruxolitinib reduced phosphorylation of STAT3 and STAT6 and expression of c-Myc in the HL cell line HDLM-2. These changes were enhanced when, on the basis of a matrix screen of drug combinations, ruxolitinib was combined with the Bcl-2/Bcl-xL inhibitor Navitoclax. The combination augmented expression of Bik, Puma, and Bax, and attenuated Bcl-xL expression and the phosphorylation of Bad. The use of the two-agent combination of either ruxolitinib or Navitoclax with BV or the three-agent combination strongly activated Bax and increased activities of cytochrome c and caspase-9 and -3 that, in turn, led to cleavage of poly(ADP ribose) polymerase and Mcl-1. Either ruxolitinib combined with Navitoclax or BV alone prolonged survival but did not cure HDLM-2 tumor-bearing mice, whereas BV combined with ruxolitinib and/or with Navitoclax resulted in a sustained, complete elimination of the HDLM-2 HL. These studies provide scientific support for a clinical trial to evaluate BV combined with ruxolitinib in select patients with HL.
C1 [Ju, Wei; Zhang, Meili; Petrus, Michael N.; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Meili] Leidos Biomed Res Inc, Lab Anim Sci Program, Frederick, MD 21702 USA.
[Wilson, Kelli M.; Zhang, Xiaohu; Guha, Rajarshi; Ferrer, Marc; Thomas, Craig J.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Bamford, Richard N.] Transponics, Jacobus, PA 17407 USA.
RP Waldmann, TA (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM tawald@helix.nih.gov
FU Division of Pre clinical Innovation, National Center for Advancing
Translational Sciences; Intramural Research Program of the National
Human Genome Research Institute; Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, National
Institutes of Health
FX This work was supported by the Division of Pre clinical Innovation,
National Center for Advancing Translational Sciences; the Intramural
Research Program of the National Human Genome Research Institute; and
the Intramural Research Program of the National Cancer Institute, Center
for Cancer Research, National Institutes of Health.
NR 32
TC 6
Z9 6
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 9
PY 2016
VL 113
IS 6
BP 1624
EP 1629
DI 10.1073/pnas.1524668113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9WG
UT WOS:000369571700052
PM 26811457
ER
PT J
AU Foster, BL
He, BYJ
Honey, CJ
Jerbi, K
Maier, A
Saalmann, YB
AF Foster, Brett L.
He, Biyu J.
Honey, Christopher J.
Jerbi, Karim
Maier, Alexander
Saalmann, Yuri B.
TI Spontaneous Neural Dynamics and Multi-scale Network Organization
SO FRONTIERS IN SYSTEMS NEUROSCIENCE
LA English
DT Review
DE resting-state fMRI; electrocorticography (ECoG); brain networks;
connectivity; neural dynamics
ID INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN POSTEROMEDIAL CORTEX;
RESTING-STATE NETWORKS; DEFAULT-MODE NETWORK; EPISODIC MEMORY RETRIEVAL;
SLOW EEG FLUCTUATIONS; HUMAN CEREBRAL-CORTEX; PRIMARY VISUAL-CORTEX;
HUMAN BRAIN NETWORKS; GAMMA-OSCILLATIONS
AB Spontaneous neural activity has historically been viewed as task-irrelevant noise that should be controlled for via experimental design, and removed through data analysis. However, electrophysiology and functional MRI studies of spontaneous activity patterns, which have greatly increased in number over the past decade, have revealed a close correspondence between these intrinsic patterns and the structural network architecture of functional brain circuits. In particular, by analyzing the large-scale covariation of spontaneous hemodynamics, researchers are able to reliably identify functional networks in the human brain. Subsequent work has sought to identify the corresponding neural signatures via electrophysiological measurements, as this would elucidate the neural origin of spontaneous hemodynamics and would reveal the temporal dynamics of these processes across slower and faster timescales. Here we survey common approaches to quantifying spontaneous neural activity, reviewing their empirical success, and their correspondence with the findings of neuroimaging. We emphasize invasive electrophysiological measurements, which are amenable to amplitude-and phase based analyses, and which can report variations in connectivity with high spatiotemporal precision. After summarizing key findings from the human brain, we survey work in animal models that display similar multi-scale properties. We highlight that, across many spatiotemporal scales, the covariance structure of spontaneous neural activity reflects structural properties of neural networks and dynamically tracks their functional repertoire.
C1 [Foster, Brett L.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
[He, Biyu J.] NINDS, Lab Funct & Mol Imaging, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Honey, Christopher J.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada.
[Jerbi, Karim] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada.
[Maier, Alexander] Vanderbilt Univ, Dept Psychol, Nashville, TN USA.
[Saalmann, Yuri B.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
RP Foster, BL (reprint author), Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
EM blfoster@stanford.edu
OI Saalmann, Yuri/0000-0001-8880-6698; He, Biyu/0000-0003-1549-1351; Maier,
Alexander/0000-0002-7250-502X
FU US National Institute of Mental Health [K99MH103479]; National
Institutes of Health/National Institute of Neurological Disorders and
Stroke; Natural Sciences and Engineering Research Council of Canada
[RGPIN-2014-04465, RGPIN-2015-04854]; Canada Research Chairs program;
Knights Templar Eye Foundation; Whitehall Foundation; Sloan Research
Fellowship; Brain and Behavior Research Foundation [23017]
FX This work is supported by a career development award from the US
National Institute of Mental Health (K99MH103479) to BF; the intramural
research program of the National Institutes of Health/National Institute
of Neurological Disorders and Stroke for BH; a Discovery Grant
(RGPIN-2014-04465) awarded by the Natural Sciences and Engineering
Research Council of Canada to CH; the Canada Research Chairs program and
a Discovery Grant (RGPIN-2015-04854) awarded by the Natural Sciences and
Engineering Research Council of Canada to KJ; a career development award
by the Knights Templar Eye Foundation, a research grant by the Whitehall
Foundation and a Sloan Research Fellowship to AM; a research grant by
the Brain and Behavior Research Foundation (23017) and Whitehall
Foundation to YS. The views presented in this work do not necessarily
reflect those of the National Institutes of Health.
NR 198
TC 3
Z9 3
U1 11
U2 37
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5137
J9 FRONT SYST NEUROSCI
JI Front. Syst. Neurosci.
PD FEB 9
PY 2016
VL 10
AR 7
DI 10.3389/fnsys.2016.00007
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA DD0IA
UT WOS:000369602400001
PM 26903823
ER
PT J
AU Newell, K
Kiggundu, V
Ouma, J
Baghendage, E
Kiwanuka, N
Gray, R
Serwadda, D
Hobbs, CV
Healy, SA
Quinn, TC
Reynolds, SJ
AF Newell, Kevin
Kiggundu, Valerian
Ouma, Joseph
Baghendage, Enos
Kiwanuka, Noah
Gray, Ronald
Serwadda, David
Hobbs, Charlotte V.
Healy, Sara A.
Quinn, Thomas C.
Reynolds, Steven J.
TI Longitudinal household surveillance for malaria in Rakai, Uganda
SO MALARIA JOURNAL
LA English
DT Article
DE Malaria; Epidemiology; Surveillance; Household; Children; Rakai; Africa
ID PLASMODIUM-VIVAX; CHILDREN
AB Background: HIV and malaria exert co-pathogenic effects. Malaria surveillance data are necessary for public health strategies to reduce the burden of disease in high HIV prevalence settings.
Methods: This was a longitudinal cohort study to assess the burden of malaria in rural Rakai, Uganda. Households were visited monthly for 1 year to identify confirmed clinical malaria (CCM), or parasitaemia with temperature > 37.5 degrees C, and asymptomatic parasitaemia (AP). Interviews of the adult or child's caregiver and clinical and laboratory assessments were conducted. Rapid diagnostic testing for malaria and anaemia was performed if participants were febrile and anti-malarial treatment given per Uganda Ministry of Health 2010 guidelines. Blood was drawn at every household visit to assess for parasitaemia, and blood smears were assessed at the Rakai Health Science Programme laboratory.
Results: A total of 1640 participants were enrolled, including 975 children aged 6 months up to 10 years, 393 adult caregivers, and 272 adolescent/adult household members from 393 randomly selected households in two representative communities. 1459 (89 %) participants completed all study visits. CCM was identified in 304 (19 %) participants, with the highest incidence rate for CCM of 0.38 per person-year (ppy) identified in children < 5 years, and rates decreased with age; the rates were 0.27, 0.16, and 0.09 ppy for ages 5-<10 years, 10-<18 years, and adults 18+ years, respectively. AP was identified in 943 (57 %) participants; the incidence rate was 1.99 ppy for < 5 years, 2.72 ppy for 5-<10 years, 2.55 ppy for 10-<18 years, and 0.86 ppy among adults, with 92 % of cases being attributed to Plasmodium falciparum by smear. 994 (61 %) individuals had at least one positive smear; 342 (21 %) had one positive result, 203 (12 %) had two, 115 (7 %) had three, and 334 (21 %) had > 3 positive smears during follow-up. Seasonal rates generally followed the rains and peaked during July, then decreased through November before increasing again.
Conclusions: Plasmodium falciparum infection remains high in rural Uganda. Increased malaria control interventions should be prioritized.
C1 [Newell, Kevin] Res Data & Commun Technol Inc, Garrett Pk, MD USA.
[Kiggundu, Valerian] Off HIV AIDS Global Hlth Bur, USAID Global Hlth Fellows Program, 1300 Penn Ave NW, Washington, DC 20523 USA.
[Ouma, Joseph; Serwadda, David; Reynolds, Steven J.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Baghendage, Enos] Makerere Univ, Walter Reed Project, Kampala, Uganda.
[Kiwanuka, Noah] IAVI, Uganda Program, Entebbe, Uganda.
[Gray, Ronald] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Serwadda, David] Makerere Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
[Hobbs, Charlotte V.] Univ Mississippi, Med Ctr, Dept Pediat, Batson Childrens Hosp,Div Infect Dis, Jackson, MS 39216 USA.
[Healy, Sara A.; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Reynolds, Steven J.] US Embassy Kampala, NIAID NIH ICER Program, POB 7007, Kampala, Uganda.
RP Reynolds, SJ (reprint author), NIAID, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Reynolds, SJ (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD USA.; Reynolds, SJ (reprint author), US Embassy Kampala, NIAID NIH ICER Program, POB 7007, Kampala, Uganda.
EM sjr@jhmi.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases
FX This project has been funded in part from the National Cancer Institute,
National Institutes of Health, under Contract No. HHSN261200800001E and
in part by the Division of Intramural Research of the National Institute
of Allergy and Infectious Diseases. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government. The
content of this manuscript is the sole responsibility of the authors.
The information provided here is not official U.S. Government
information and does not necessarily represent the views or positions of
United States Agency for International Development, the United States
Department of State, nor the United States Government. We are most
grateful to the study participants and the Rakai Community Advisory
Board whose commitment and cooperation made this study possible.
NR 18
TC 0
Z9 0
U1 0
U2 2
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 FEB 9
PY 2016
VL 15
AR 77
DI 10.1186/s12936-016-1128-6
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DC9VG
UT WOS:000369569100004
PM 26861943
ER
PT J
AU Chen, HL
Marder, K
AF Chen, Honglei
Marder, Karen
TI Milk consumption and the risk of nigral degeneration
SO NEUROLOGY
LA English
DT Editorial Material
ID PARKINSONS-DISEASE; DAIRY-PRODUCTS
AB In the era of genetic research for neurodegenerative diseases, less attention has been paid to epidemiologists' search for potential environmental risk factors for Parkinson disease (PD). Epidemiologic evidence suggests that cigarette smoking is associated with about 50% lower risk of PD1 and exposure to certain pesticides such as rotenone and paraquat is associated with doubled risk.(2) Recent studies also suggest that higher concentration of serum urate, an endogenous antioxidant, is associated with a lower risk of PD.(3) Compared with these observations, another epidemiologic finding has been largely neglected. Several prospective studies,(4-7) including the Honolulu-Asia Aging Study (HAAS),(6) have reported that higher consumption of dairy products, or milk alone, was associated with higher risk for PD.
C1 [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Marder, Karen] Columbia Univ, Coll Phys & Surg, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
RP Chen, HL (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
EM chenh2@niehs.nih.gov
OI Chen, Honglei/0000-0003-3446-7779
FU Intramural NIH HHS; NCRR NIH HHS [NIH 1UL1 RR024156-01]; NINDS NIH HHS
[U01NS052592]
NR 10
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 9
PY 2016
VL 86
IS 6
BP 496
EP 497
DI 10.1212/WNL.0000000000002268
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DC9KT
UT WOS:000369541200002
PM 26658908
ER
PT J
AU Abbott, RD
Ross, GW
Petrovitch, H
Masaki, KH
Launer, LJ
Nelson, JS
White, LR
Tanner, CM
AF Abbott, Robert D.
Ross, G. Webster
Petrovitch, Helen
Masaki, Kamal H.
Launer, Lenore J.
Nelson, James S.
White, Lon R.
Tanner, Caroline M.
TI Midlife milk consumption and substantia nigra neuron density at death
SO NEUROLOGY
LA English
DT Article
ID IDIOPATHIC PARKINSONS-DISEASE; CORONARY-HEART-DISEASE; ORGANOCHLORINE
PESTICIDES; DAIRY-PRODUCTS; FUTURE RISK; LIFE-STYLE; MEN; CALIFORNIA;
STROKE; HAWAII
AB Objective:To examine the relationship between midlife milk intake and Parkinson disease (PD) incidence through associations with substantia nigra (SN) neuron density and organochlorine pesticide exposure in decedent brains from the Honolulu-Asia Aging Study.Methods:Milk intake data were collected from 1965 to 1968 in 449 men aged 45-68 years with postmortem examinations from 1992 to 2004. Neuron density (count/mm(2)) was measured in quadrants from a transverse section of the SN. Additional measures included brain residues of heptachlor epoxide, an organochlorine pesticide found at excessively high levels in the milk supply in Hawaii in the early 1980s.Results:Neuron density was lowest in nonsmoking decedents who consumed high amounts of milk (>16 oz/d). After removing cases of PD and dementia with Lewy bodies, adjusted neuron density in all but the dorsomedial quadrant was 41.5% lower for milk intake >16 oz/d vs intake that was less (95% confidence interval 22.7%-55.7%, p < 0.001). Among those who drank the most milk, residues of heptachlor epoxide were found in 9 of 10 brains as compared to 63.4% (26/41) for those who consumed no milk (p = 0.017). For those who were ever smokers, an association between milk intake and neuron density was absent.Conclusions:Milk intake is associated with SN neuron loss in decedent brains unaffected by PD. Whether contamination of milk with organochlorine pesticides has a role in SN neurodegeneration warrants further study.
C1 [Abbott, Robert D.] Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan.
[Abbott, Robert D.; Ross, G. Webster; Petrovitch, Helen; Nelson, James S.; White, Lon R.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Ross, G. Webster] Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA.
[Abbott, Robert D.; Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal H.] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn Ctr Excellence Geriatr, Honolulu, HI 96822 USA.
[Ross, G. Webster; Petrovitch, Helen; White, Lon R.] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Masaki, Kamal H.] Kuakini Med Ctr, Honolulu, HI USA.
[Launer, Lenore J.] NIA, Bethesda, MD 20892 USA.
[Tanner, Caroline M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Tanner, Caroline M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
RP Abbott, RD (reprint author), Shiga Univ Med Sci, Ctr Epidemiol Res Asia, Otsu, Shiga 52021, Japan.; Abbott, RD (reprint author), Pacific Hlth Res & Educ Inst, Honolulu, HI USA.; Abbott, RD (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, John A Hartford Fdn Ctr Excellence Geriatr, Honolulu, HI 96822 USA.
EM rda3e@virginia.edu
FU National Institute on Aging [N01-AG-4-2149, 1 UO1 AG19349, 5 R01
AG017155]; National Heart, Lung, and Blood Institute [N01-HC-05102];
National Institute of Neurological Disorders and Stroke [5 R01
NS041265]; United States Department of the Army [DAMD17-98-1-8621];
Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; Kuakini Medical Center; National Institute on Aging
FX Supported by a contract (N01-AG-4-2149) and grants (1 UO1 AG19349 and 5
R01 AG017155) from the National Institute on Aging, by a contract
(N01-HC-05102) from the National Heart, Lung, and Blood Institute, by a
grant (5 R01 NS041265) from the National Institute of Neurological
Disorders and Stroke, by a grant from the United States Department of
the Army (DAMD17-98-1-8621), by the Office of Research and Development,
Medical Research Service, Department of Veterans Affairs, by the Kuakini
Medical Center, and in part by the Intramural Research Program of the
National Institute on Aging. The information contained in this article
does not necessarily reflect the position or the policy of the US
Government, and no official endorsement should be inferred.
NR 39
TC 4
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 9
PY 2016
VL 86
IS 6
BP 512
EP 519
DI 10.1212/WNL.0000000000002254
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DC9KT
UT WOS:000369541200005
PM 26658906
ER
PT J
AU Langhorne, J
Duffy, PE
AF Langhorne, Jean
Duffy, Patrick E.
TI Expanding the antimalarial toolkit: Targeting host-parasite interactions
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Review
ID FALCIPARUM-INFECTED ERYTHROCYTES; MURINE CEREBRAL MALARIA;
TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; BRAIN ENDOTHELIAL-CELLS;
PLASMODIUM-FALCIPARUM; LIVER INFECTION; MONOCLONAL-ANTIBODY;
APICOMPLEXAN PARASITES; INSECTICIDE RESISTANCE
AB Recent successes in malaria control are threatened by drug-resistant Plasmodium parasites and insecticide-resistant Anopheles mosquitoes, and first generation vaccines offer only partial protection. New research approaches have highlighted host as well as parasite molecules or pathways that could be targeted for interventions. In this study, we discuss host-parasite interactions at the different stages of the Plasmodium life cycle within the mammalian host and the potential for therapeutics that prevent parasite migration, invasion, intracellular growth, or egress from host cells, as well as parasite-induced pathology.
C1 [Langhorne, Jean] Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England.
[Duffy, Patrick E.] NIAAA, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
RP Langhorne, J (reprint author), Francis Crick Inst, Mill Hill Lab, London NW7 1AA, England.
EM jean.langhorne@crick.ac.uk
FU Francis Crick Institute; UK Medical Research Council [U117584248];
Cancer Research UK; Wellcome Trust [WT104777MA]; Intramural Research
Program of the National Institute of Allergy and Infectious Diseases of
the National Institutes of Health
FX J. Langhorne is supported by the Francis Crick Institute, which receives
its funding from the UK Medical Research Council (grant U117584248),
Cancer Research UK, and the Wellcome Trust (grant WT104777MA). P.E.
Duffy is supported by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health.
NR 114
TC 2
Z9 2
U1 4
U2 8
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD FEB 8
PY 2016
VL 213
IS 2
BP 143
EP 153
DI 10.1084/jem.20151677
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA DI3FK
UT WOS:000373383700003
PM 26834158
ER
PT J
AU Kumar, JS
Wei, BR
Madigan, JP
Simpson, RM
Hall, MD
Gottesman, MM
AF Kumar, Jeyan S.
Wei, Bih-Rong
Madigan, James P.
Simpson, R. Mark
Hall, Matthew D.
Gottesman, Michael M.
TI Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta
barrier
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CANCER RESISTANCE PROTEIN; PREGNANT NONHUMAN PRIMATE; P-GLYCOPROTEIN;
MULTIDRUG TRANSPORTER; DRUG TRANSPORTERS; FETAL EXPOSURE; EXPRESSION;
BRAIN; CELLS; GLYBURIDE
AB Physiologic barriers such as the blood placenta barrier (BPB) and the blood brain barrier protect the underlying parenchyma from pathogens and toxins. ATP-binding cassette (ABC) transporters are transmembrane proteins found at these barriers, and function to efflux xenobiotics and maintain chemical homeostasis. Despite the plethora of ex vivo and in vitro data showing the function and expression of ABC transporters, no imaging modality exists to study ABC transporter activity in vivo at the BPB. In the present study, we show that in vitro models of the placenta possess ABCG2 activity and can specifically transport D-luciferin, the endogenous substrate of firefly luciferase. To test ABCG2 transport activity at the BPB, we devised a breeding strategy to generate a bioluminescent pregnant mouse model to demonstrate transporter function in vivo. We found that coadministering the ABCG2 inhibitors Ko143 and gefitinib with D-luciferin increased bioluminescent signal from fetuses and placentae, whereas the control P-gp inhibitor DCPQ had no effect. We believe that our bioluminescent pregnant mouse model will facilitate greater understanding of the BPB and ABCG2 activity in health and disease.
C1 [Kumar, Jeyan S.; Madigan, James P.; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
[Wei, Bih-Rong; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU NIH
FX This research was made possible through the National Institutes of
Health (NIH) Medical Research Scholars Program, a public-private
partnership supported jointly by the NIH and generous contributions to
the Foundation for the NIH from Pfizer Inc., The Doris Duke Charitable
Foundation, The Newport Foundation, The American Association for Dental
Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive
Company, as well as other private donors. For a complete list, please
visit the Foundation website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram. We would like to thank Ethan Tyler, of NIH Medical Arts, for his
assistance in the preparation of Figure 4, panels A-C. We would also
like to thank George Leiman for editorial assistance.
NR 39
TC 1
Z9 1
U1 1
U2 11
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 FEB 8
PY 2016
VL 6
AR 20418
DI 10.1038/srep20418
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9UT
UT WOS:000369567800001
PM 26853103
ER
PT J
AU Winn, AK
Salo, PM
Klein, C
Sever, ML
Harris, SF
Johndrow, D
Crockett, PW
Cohn, RD
Zeldin, DC
AF Winn, Amber K.
Salo, Paeivi M.
Klein, Cynthia
Sever, Michelle L.
Harris, Shawn F.
Johndrow, David
Crockett, Patrick W.
Cohn, Richard D.
Zeldin, Darryl C.
TI Efficacy of an in-home test kit in reducing dust mite allergen levels:
results of a randomized controlled pilot study
SO JOURNAL OF ASTHMA
LA English
DT Article
DE indoor allergens; Dust mites; dust mite allergen; intervention trials;
D. farinae; D. pteronyssinus
ID PRECAUTION ADOPTION PROCESS; PROCESS MODEL; ASTHMA; BEHAVIOR
AB Background: Dust mite allergens can induce allergic sensitization and exacerbate asthma symptoms. Although dust mite reduction and control strategies exist, few asthmatics employ them. Objectives: We examined whether an in-home test kit, which quantifies dust mite allergen levels, resulted in behavioral changes in implementation and maintenance of mite reduction strategies and helped reduce allergen levels in homes of dust mite-sensitive children. Methods: We enrolled 60 households of children aged 5-15 with parent-reported dust mite allergy into a randomized controlled trial. Intervention homes (N = 30) received educational material about reducing dust mites and test kits at 1, 2, 5 and 8 months. Control homes (N = 30) received only educational material. At baseline, 6 and 12 months, study staff visited all homes, collected dust samples from three locations and obtained information about parents' mite reduction behaviors by questionnaire. Allergen concentrations (Der f 2/Der p2) in dust were assessed by immunoassays. After adjusting for visit and location, allergen concentrations in intervention and control homes were compared using mixed effects model analysis. Results: In the intervention homes, allergen concentrations in the child's bedroom and living room floors were significantly reduced over time compared to control homes. Although not all location-specific differences in allergen concentrations were statistically significant, combining data across locations, there was a differential reduction in allergen concentrations in the intervention group versus the control group (p = 0.02). Conclusion: The use of in-home test kits along with education may beneficially influence behaviors and attitudes toward dust mite reduction strategies and help reduce residential dust mite allergen levels.
C1 [Winn, Amber K.; Salo, Paeivi M.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Klein, Cynthia] ABT Associates Inc, Atlanta, GA USA.
[Sever, Michelle L.] Rho Inc, Chapel Hill, NC USA.
[Harris, Shawn F.; Johndrow, David; Crockett, Patrick W.; Cohn, Richard D.] Social & Sci Syst Inc, Durham, NC USA.
RP Zeldin, DC (reprint author), NIEHS, NIH, POB 12233,MD A2-05, Res Triangle Pk, NC 27709 USA.
EM Zeldin@niehs.nih.gov
FU US Department of Health and Human Services, National Institutes of
Health [HHSN291200555553C/N01-ES-55553]
FX This material is published by permission of the [Social & Scientific
Systems, Inc.] for the [US Department of Health and Human Services,
National Institutes of Health] under Contract No.
[HHSN291200555553C/N01-ES-55553]. The US Government retains for itself,
and others acting on its behalf, a paid-up, non-exclusive, and
irrevocable worldwide licence in said article to reproduce, prepare
derivative works, distribute copies to the public, and perform publicly
and display publicly, by or on behalf of the Government.
NR 23
TC 1
Z9 1
U1 3
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0277-0903
EI 1532-4303
J9 J ASTHMA
JI J. Asthma
PD FEB 7
PY 2016
VL 53
IS 2
BP 133
EP 138
DI 10.3109/02770903.2015.1072721
PG 6
WC Allergy; Respiratory System
SC Allergy; Respiratory System
GA DG9SZ
UT WOS:000372425400005
PM 26308287
ER
PT J
AU Golub, SA
Thompson, LI
Kowalczyk, WJ
AF Golub, Sarit A.
Thompson, Louisa I.
Kowalczyk, William J.
TI Affective differences in Iowa Gambling Task performance associated with
sexual risk taking and substance use among HIV-positive and HIV-negative
men who have sex with men
SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY
LA English
DT Article
DE Decision making; Iowa Gambling Task; Anxiety; Sexual; risk taking;
Substance use
ID SOMATIC MARKER HYPOTHESIS; MULTICENTER AIDS COHORT; TIMELINE
FOLLOW-BACK; DECISION-MAKING; DEPRESSIVE SYMPTOMS; PSYCHOMETRIC
PROPERTIES; EXECUTIVE FUNCTIONS; ALCOHOL DEPENDENCE; PREFRONTAL CORTEX;
SENSATION SEEKING
AB We investigated the relationship between emotional distress and decision making in sexual risk and substance use behavior among 174 (ages 25 to 50 years, 53% black) men who have sex with men (MSM), a population at increased risk for HIV. The sample was stratified by HIV status. Measures of affective decision making, depression, anxiety, sex acts, and substance use during the past 60 days were collected at our research center. Negative binomial regression models were used to examine the relationship between age, HIV status, anxiety, depression, and IGT performance in the prediction of number of risky sex acts and substance use days. Among those without anxiety or depression, both number of risky sex acts and drug use days decreased with better performance during risky trials (i.e., last two blocks) of the IGT. For those with higher rates of anxiety, but not depression, IGT risk trial performance and risky sex acts increased concomitantly. Anxiety also interacted with IGT performance across all trials to predict substance use, such that anxiety was associated with greater substance use among those with better IGT performance. The opposite was true for those with depression, but only during risk trials. HIV-positive participants reported fewer substance use days than HIV-negative participants, but there was no difference in association between behavior and IGT performance by HIV status. Our findings suggest that anxiety may exacerbate risk-taking behavior when affective decision-making ability is intact. The relationship between affective decision making and risk taking may be sensitive to different profiles of emotional distress, as well as behavioral context. Investigations of affective decision making in sexual risk taking and substance use should examine different distress profiles separately, with implications for HIV prevention efforts.
C1 [Golub, Sarit A.] CUNY Hunter Coll, Dept Psychol, New York, NY 10065 USA.
[Golub, Sarit A.; Thompson, Louisa I.] CUNY, Grad Ctr, Doctoral Program Psychol, New York, NY USA.
[Kowalczyk, William J.] NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Branch, Baltimore, MD USA.
RP Golub, SA (reprint author), CUNY Hunter Coll, Dept Psychol, 695 Pk Ave, New York, NY 10065 USA.
EM sarit.golub@hunter.cuny.edu
OI Kowalczyk, William/0000-0001-8026-285X
FU National Institute on Drug Abuse of the National Institutes of Health
[R21A026792]
FX Research reported in this paper was supported by the National Institute
on Drug Abuse of the National Institutes of Health [award number
R21A026792] (Golub, principal investigator, PI).
NR 89
TC 1
Z9 1
U1 14
U2 24
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1380-3395
EI 1744-411X
J9 J CLIN EXP NEUROPSYC
JI J. Clin. Exp. Neuropsychol.
PD FEB 7
PY 2016
VL 38
IS 2
BP 141
EP 157
DI 10.1080/13803395.2015.1085495
PG 17
WC Psychology, Clinical; Clinical Neurology; Psychology
SC Psychology; Neurosciences & Neurology
GA DA5EO
UT WOS:000367825800001
PM 26745769
ER
PT J
AU Heazell, AEP
Siassakos, D
Blencowe, H
Burden, C
Bhutta, ZA
Cacciatore, J
Dang, N
Das, J
Flenady, V
Gold, KJ
Mensah, OK
Millum, J
Nuzum, D
O'Donoghue, K
Redshaw, M
Rizvi, A
Roberts, T
Saraki, HET
Storey, C
Wojcieszek, AM
Downe, S
AF Heazell, Alexander E. P.
Siassakos, Dimitrios
Blencowe, Hannah
Burden, Christy
Bhutta, Zulfiqar A.
Cacciatore, Joanne
Dang, Nghia
Das, Jai
Flenady, Vicki
Gold, Katherine J.
Mensah, Olivia K.
Millum, Joseph
Nuzum, Daniel
O'Donoghue, Keelin
Redshaw, Maggie
Rizvi, Arjumand
Roberts, Tracy
Saraki, H. E. Toyin
Storey, Claire
Wojcieszek, Aleena M.
Downe, Soo
CA Lancet Ending Preventable Stillbir
Lancet Ending Preventable Stillbir
TI Stillbirths: economic and psychosocial consequences
SO LANCET
LA English
DT Article
ID FOLLOW-UP INTERVENTION; PERINATAL LOSS; PREGNANCY LOSS; MATERNAL
MORTALITY; NEONATAL DEATH; COST-EFFECTIVENESS; DEPRESSIVE SYMPTOMS;
PARENTS EXPERIENCES; MOTHERS EXPERIENCE; BEREAVED PARENTS
AB Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity.
C1 [Heazell, Alexander E. P.] Univ Manchester, Inst Human Dev, Fac Med & Human Sci, Manchester, Lancs, England.
[Heazell, Alexander E. P.] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Heazell, Alexander E. P.; Siassakos, Dimitrios; Flenady, Vicki; Gold, Katherine J.; Storey, Claire; Wojcieszek, Aleena M.] Int Stillbirth Alliance, New York, NY USA.
[Siassakos, Dimitrios; Burden, Christy] Univ Bristol, Acad Ctr Womens Hlth, Bristol, Avon, England.
[Siassakos, Dimitrios; Burden, Christy] Southmead Hosp, Bristol, Avon, England.
[Blencowe, Hannah] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, Ctr Maternal Reprod & Child Hlth, London WC1, England.
[Bhutta, Zulfiqar A.] Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON M5G 1X8, Canada.
[Bhutta, Zulfiqar A.; Das, Jai; Rizvi, Arjumand] Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan.
[Cacciatore, Joanne] Arizona State Univ, Tempe, AZ USA.
[Dang, Nghia] Hanoi Vinmec Int Gen Hosp, Inst Reprod & Family Hlth, Hanoi, Vietnam.
[Flenady, Vicki; Wojcieszek, Aleena M.] Univ Queensland, Mater Res Inst, Brisbane, Qld, Australia.
[Gold, Katherine J.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA.
[Gold, Katherine J.] Univ Michigan, Dept Obstet, Ann Arbor, MI 48109 USA.
[Mensah, Olivia K.] Krachi Midwifery Training Sch, Kete Krach, Ghana.
[Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Nuzum, Daniel; O'Donoghue, Keelin] Cork Univ, Matern Hosp, Univ Coll Cork, Dept Obstet & Gynaecol, Cork, Ireland.
[Redshaw, Maggie] Univ Oxford, Nuffield Dept Populat Hlth, Natl Perinatal Epidemiol Unit, Oxford, England.
[Roberts, Tracy] Univ Birmingham, Sch Hlth & Populat Sci, Hlth Econ Unit, Birmingham, W Midlands, England.
[Saraki, H. E. Toyin] Wellbeing Fdn Africa, Lagos, Nigeria.
[Downe, Soo] Univ Cent Lancashire, ReaCH Grp, Preston PR1 2HE, Lancs, England.
St Marys Hosp, Maternal & Fetal Hlth Res Ctr, Manchester M13 9WL, Lancs, England.
RP Heazell, AEP (reprint author), St Marys Hosp, Maternal & Fetal Hlth Res Ctr, Manchester M13 9WL, Lancs, England.
EM alexander.heazell@manchester.ac.uk
RI Siassakos, Dimitrios/A-6859-2012; Flenady, Vicki/O-9609-2014;
OI O'Donoghue, Keelin/0000-0002-4616-2887; Burden,
Christy/0000-0001-6409-5238; Wojcieszek, Aleena/0000-0001-8099-6087;
Froen Froen, Jahn Frederik/0000-0001-9390-8509; Siassakos,
Dimitrios/0000-0002-1078-9856; Nuzum, Daniel/0000-0002-9907-5680
FU Save the Children/Saving Newborn Lives; Holly Martin Stillbirth Research
Fund; National Institutes of Health Clinical Center; UK Policy Research
Programme in the Department of Health; Tommy's and by a Clinician
Scientist Fellowship from the UK National Institute of Health Research;
National Institute for Health Research (NIHR); National Institutes of
Health; Mater Research Institute, University of Queensland, Australia
FX HB received grants from Save the Children/Saving Newborn Lives. DS is a
member of Department of Health Stillbirth task-and-finish groups, and
the PRactical Obstetric Multi-Professional Training maternity
foundation. AEPH received grants from Tommy's during the conduct of the
paper and was funded by the Holly Martin Stillbirth Research Fund to do
qualitative analysis. JM was also supported, in part, by intramural
funds from the National Institutes of Health Clinical Center. The views
expressed are the author's own and do not represent the position or
policy of the US National Institutes of Health, Public Health Service,
or the Department of Health and Human Services. This Series paper also
reports on independent studies which are part funded by the UK Policy
Research Programme in the Department of Health. AEPH is supported by
Tommy's and by a Clinician Scientist Fellowship from the UK National
Institute of Health Research. This Series paper provides independent
research funded by the National Institute for Health Research (NIHR).
The views expressed are those of the authors and not necessarily those
of the National Health Service, the NIHR, or the Department of Health.
KJG receives salary support through a K23 training grant from the
National Institutes of Health. None of the funding bodies had any
influence on the content and scope of the paper. We thank Mater Research
Institute, University of Queensland, Australia, for funding the
International Stillbirth Alliance questionnaire. We thank Bishal
Mohindru for his assistance in the costs analysis for care in subsequent
pregnancies.
NR 111
TC 15
Z9 16
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 6
PY 2016
VL 387
IS 10018
BP 604
EP 616
DI 10.1016/S0140-6736(15)00836-3
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DD3PV
UT WOS:000369835800038
PM 26794073
ER
PT J
AU Ewen, JB
Pillai, AS
McAuliffe, D
Lakshmanan, BM
Ament, K
Hallett, M
Crone, NE
Mostofsky, SH
AF Ewen, Joshua B.
Pillai, Ajay S.
McAuliffe, Danielle
Lakshmanan, Balaji M.
Ament, Katarina
Hallett, Mark
Crone, Nathan E.
Mostofsky, Stewart H.
TI Practicing Novel, Praxis-Like Movements: Physiological Effects of
Repetition
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE motor learning; attention; praxis; gesture production; EEG;
event-related desynchronization; repetition suppression
ID EVENT-RELATED SYNCHRONIZATION; BAND OSCILLATIONS; HAND MOVEMENTS;
MU-RHYTHM; IMITATION; EEG; ACTIVATION; APRAXIA; CONNECTIVITY;
AUTOMATICITY
AB Our primary goal was to develop and validate a task that could provide evidence about how humans learn praxis gestures, such as those involving the use of tools. To that end, we created a video-based task in which subjects view a model performing novel, meaningless one-handed actions with kinematics similar to praxis gestures. Subjects then imitated the movements with their right hand. Trials were repeated six times to examine practice effects. EEG was recorded during the task. As a control, subjects watched videos of a model performing a well-established (over learned) tool-use gesture. These gestures were also imitated six times. Demonstrating convergent validity, EEG measures of task-related cortical activation were similar in topography and frequency between the novel gesture task and the overlearned, praxis gesture task. As in studies assessing motor skill learning with simpler tasks, cortical activation during novel gesture learning decreased as the same gestures were repeated. In the control condition, repetition of overlearned tool-use gestures were also associated with reductions in activation, though to a lesser degree. Given that even overlearned, praxis gestures show constriction of EEG activity with repetition, it is possible that that attentional effects drive some of the repetition effects seen in EEG measures of activation during novel gesture repetition.
C1 [Ewen, Joshua B.; Pillai, Ajay S.; McAuliffe, Danielle; Lakshmanan, Balaji M.; Mostofsky, Stewart H.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Clin Neurophysiol Lab, Baltimore, MD USA.
[Ewen, Joshua B.; Pillai, Ajay S.; Crone, Nathan E.; Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Ewen, Joshua B.] Johns Hopkins Univ, Krieger Sch Arts & Sci, Dept Psychol & Brain Sci, Baltimore, MD USA.
[Ament, Katarina; Mostofsky, Stewart H.] Kennedy Krieger Inst, Ctr Neurodev & Imaging Res, Baltimore, MD USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Mostofsky, Stewart H.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
RP Ewen, JB (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, Clin Neurophysiol Lab, Baltimore, MD USA.; Ewen, JB (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.; Ewen, JB (reprint author), Johns Hopkins Univ, Krieger Sch Arts & Sci, Dept Psychol & Brain Sci, Baltimore, MD USA.
EM ewen@kennedykrieger.org
FU National Institute of Neurological Disorders and Stroke/National
Institutes of Health [K23NS073626, R21NS091569, R01NS048527]; Autism
Speaks
FX This work was funded by the National Institute of Neurological Disorders
and Stroke/National Institutes of Health (Intramural Program - MH;
K23NS073626 and R21NS091569 to JE; and R01NS048527 to SM) and Autism
Speaks (to SM).
NR 39
TC 0
Z9 0
U1 0
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD FEB 5
PY 2016
VL 10
AR 22
DI 10.3339/fnhum.2016.00022
PG 10
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA DC7QW
UT WOS:000369416300002
PM 26903835
ER
PT J
AU Friis, S
Madsen, DH
Bugge, TH
AF Friis, Stine
Madsen, Daniel H.
Bugge, Thomas H.
TI Distinct Developmental Functions of Prostasin (CAP1/PRSS8) Zymogen and
Activated Prostasin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPIDERMAL BARRIER FUNCTION; PROTEOLYTIC CASCADE; PROTEASE;
DIFFERENTIATION; LOCALIZATION; HOMEOSTASIS; CHANNELS
AB The membrane-anchored serine prostasin (CAP1/PRSS8) is essential for barrier acquisition of the interfollicular epidermis and for normal hair follicle development. Consequently, prostasin null mice die shortly after birth. Prostasin is found in two forms in the epidermis: a one-chain zymogen and a two-chain proteolytically active form, generated by matriptase-dependent activation site cleavage. Here we used gene editing to generate mice expressing only activation site cleavage-resistant (zymogen-locked) endogenous prostasin. Interestingly, these mutant mice displayed normal interfollicular epidermal development and postnatal survival, but had defects in whisker and pelage hair formation. These findings identify two distinct in vivo functions of epidermal prostasin: a function in the interfollicular epidermis, not requiring activation site cleavage, that can be mediated by the zymogen-locked version of prostasin and a proteolysis-dependent function of activated prostasin in hair follicles, dependent on zymogen conversion by matriptase.
C1 [Friis, Stine; Madsen, Daniel H.; Bugge, Thomas H.] NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 3A-308, Bethesda, MD 20892 USA.
[Friis, Stine] Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet Dis Biol, Sect Mol Dis Biol, DK-2100 Copenhagen, Denmark.
[Madsen, Daniel H.] Copenhagen Univ Hosp, Ctr Canc Immune Therapy, DK-2730 Herlev, Denmark.
RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 3A-308, Bethesda, MD 20892 USA.
EM thomas.bugge@nih.gov
OI Madsen, Daniel Hargboel/0000-0002-3183-6201
FU NIDCR Intramural Research Program; Harboe Foundation; Lundbeck
Foundation; Foundation of 17.12.1981
FX This work was supported by the NIDCR Intramural Research Program (to T.
H. B.) and by The Harboe Foundation, The Lundbeck Foundation, and the
Foundation of 17.12.1981. (to S. F.). The authors declare that they have
no conflicts of interest with the contents of this article. The content
is solely the responsibility of the author and does not necessarily
represent the official views of the National Institutes of Health.
NR 16
TC 3
Z9 3
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 FEB 5
PY 2016
VL 291
IS 6
BP 2577
EP 2582
DI 10.1074/jbc.C115.706721
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DD0RK
UT WOS:000369626900004
PM 26719335
ER
PT J
AU Nelson, SM
Shay, AE
James, JL
Carlson, BA
Urban, JF
Prabhu, KS
AF Nelson, Shakira M.
Shay, Ashley E.
James, Jannaal L.
Carlson, Bradley A.
Urban, Joseph F., Jr.
Prabhu, K. Sandeep
TI Selenoprotein Expression in Macrophages Is Critical for Optimal
Clearance of Parasitic Helminth Nippostrongylus brasiliensis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ALTERNATIVELY ACTIVATED MACROPHAGES; NEMATODE-INDUCED ALTERATIONS;
RECEPTOR PPAR-GAMMA; GENE-EXPRESSION; UP-REGULATION; SELENIUM
DEFICIENCY; MURINE MACROPHAGES; IMMUNE-RESPONSE; IN-VIVO; CELLS
AB The plasticity of macrophages is evident in helminthic parasite infections, providing protection from inflammation. Previously we demonstrated that the micronutrient selenium induces a phenotypic switch in macrophage activation from a classically activated (pro-inflammatory; M1/CAM) toward an alternatively activated (anti-inflammatory; M2/AAM) phenotype, where cyclooxygenase (COX)-dependent cyclopentenone prostaglandin J(2) (15d-PGJ(2)) plays a key role. Here, we hypothesize that dietary selenium modulates macrophage polarization toward an AAM phenotype to assist in the increasing clearance of adult Nippostrongylus brasiliensis, a gastrointestinal nematode parasite. Mice on a selenium-adequate (0.08 ppm) diet significantly augmented intestinal AAM presence while decreasing adult worms and fecal egg production when compared with infection of mice on selenium-deficient (<0.01 ppm) diet. Further increase in dietary selenium to supraphysiological levels (0.4 ppm) had very little or no impact on worm expulsion. Normal adult worm clearance and enhanced AAM marker expression were observed in the selenium-supplemented Trsp(fl/fl)Cre(WT) mice that express selenoproteins driven by tRNA(Sec) (Trsp), whereas N. brasiliensis-infected Trsp(fl/fl)Cre(LysM) selenium-supplemented mice showed a decreased clearance, with lowered intestinal expression of several AAM markers. Inhibition of the COX pathway with indomethacin resulted in delayed worm expulsion in selenium-adequate mice. This was rescued with 15d-PGJ(2), which partially recapitulated the effect of selenium supplementation on fecal egg output in addition to increasing markers of AAMs in the small intestine. Antagonism of PPAR gamma blocked the effect of selenium. These results suggest that optimal expression of selenoproteins and selenium-dependent production of COX-derived endogenous prostanoids, such as Delta(12)-PGJ(2) and 15d-PGJ(2), may regulate AAM activation to enhance anti-helminthic parasite responses.
C1 [Nelson, Shakira M.; Shay, Ashley E.; James, Jannaal L.; Prabhu, K. Sandeep] Penn State Univ, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA.
[Nelson, Shakira M.; Shay, Ashley E.; James, Jannaal L.; Prabhu, K. Sandeep] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Nelson, Shakira M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA.
[Urban, Joseph F., Jr.] ARS, USDA, Beltsville Human Nutr Res Ctr, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA.
RP Prabhu, KS (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 115 Henning Bldg, University Pk, PA 16802 USA.
EM ksprabhu@psu.edu
FU National Institutes of Health Public Health Service Grant [DK077152];
United States Department of Agriculture National Institute of Food and
Agriculture Hatch Project [4475]; National Institutes of Health
Predoctoral Training Grant [T32 AI074551]; Agricultural Research Service
of the United States Department of Agriculture [1235-5100-058]
FX This work was supported, in whole or in part, by National Institutes of
Health Public Health Service Grant DK077152 and United States Department
of Agriculture National Institute of Food and Agriculture Hatch Project
4475 (to K. S. P.), National Institutes of Health Predoctoral Training
Grant T32 AI074551 (to A. E. S.), and the Agricultural Research Service
of the United States Department of Agriculture (1235-5100-058) (to J. F.
U.). The authors declare that they have no conflicts of interest with
the contents of this article. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 49
TC 2
Z9 3
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD FEB 5
PY 2016
VL 291
IS 6
BP 2787
EP 2798
DI 10.1074/jbc.M115.684738
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DD0RK
UT WOS:000369626900019
PM 26644468
ER
PT J
AU Arizpe, J
Kravitz, DJ
Walsh, V
Yovel, G
Baker, CI
AF Arizpe, Joseph
Kravitz, Dwight J.
Walsh, Vincent
Yovel, Galit
Baker, Chris I.
TI Differences in Looking at Own- and Other-Race Faces Are Subtle and
Analysis-Dependent: An Account of Discrepant Reports
SO PLOS ONE
LA English
DT Article
ID ERRONEOUS STATISTICAL MAPS; ABOLISH CULTURAL-DIVERSITY; EYE-MOVEMENT
DIFFERENCES; RECOGNITION ALGORITHMS; FUNCTIONAL LOCALIZERS; SCAN FACES;
BIAS; IDENTIFICATION; EXPERIENCE; TRACKING
AB The Other-Race Effect (ORE) is the robust and well-established finding that people are generally poorer at facial recognition of individuals of another race than of their own race. Over the past four decades, much research has focused on the ORE because understanding this phenomenon is expected to elucidate fundamental face processing mechanisms and the influence of experience on such mechanisms. Several recent studies of the ORE in which the eye-movements of participants viewing own-and other-race faces were tracked have, however, reported highly conflicting results regarding the presence or absence of differential patterns of eye-movements to own-versus other-race faces. This discrepancy, of course, leads to conflicting theoretical interpretations of the perceptual basis for the ORE. Here we investigate fixation patterns to own-versus other-race (African and Chinese) faces for Caucasian participants using different analysis methods. While we detect statistically significant, though subtle, differences in fixation pattern using an Area of Interest (AOI) approach, we fail to detect significant differences when applying a spatial density map approach. Though there were no significant differences in the spatial density maps, the qualitative patterns matched the results from the AOI analyses reflecting how, in certain contexts, Area of Interest (AOI) analyses can be more sensitive in detecting the differential fixation patterns than spatial density analyses, due to spatial pooling of data with AOIs. AOI analyses, however, also come with the limitation of requiring a priori specification. These findings provide evidence that the conflicting reports in the prior literature may be at least partially accounted for by the differences in the statistical sensitivity associated with the different analysis methods employed across studies. Overall, our results suggest that detection of differences in eye-movement patterns can be analysis-dependent and rests on the assumptions inherent in the given analysis.
C1 [Arizpe, Joseph; Kravitz, Dwight J.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Arizpe, Joseph; Walsh, Vincent] UCL, Inst Cognit Neurosci, Appl Cognit Neurosci Grp, Mortimer St, London, England.
[Arizpe, Joseph] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
[Arizpe, Joseph] Le Bonheur Childrens Hosp, Memphis, TN USA.
[Kravitz, Dwight J.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Yovel, Galit] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel.
RP Arizpe, J (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.; Arizpe, J (reprint author), UCL, Inst Cognit Neurosci, Appl Cognit Neurosci Grp, Mortimer St, London, England.; Arizpe, J (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.; Arizpe, J (reprint author), Le Bonheur Childrens Hosp, Memphis, TN USA.
EM JosephArizpe@ucl.ac.uk
RI Arizpe, Joseph/N-1399-2014
OI Arizpe, Joseph/0000-0001-8958-7757
FU National Institutes of Mental Health [MH002909-07]; United States-Israel
Binational Science Foundation [2007034]; National Institutes of Mental
Health; United States-Israel Binational Science Foundation
FX The Intramural Program of the National Institutes of Mental Health
(https://intramural.nimh.nih.gov), grant number MH002909-07, funded JA,
DJK, and CIB. The United States-Israel Binational Science Foundation
(http://www.bsf.org.il), for application number 2007034, funded GY. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.; This work was supported by
the Intramural Program of the National Institutes of Mental Health and
by the United States-Israel Binational Science Foundation.
NR 65
TC 1
Z9 1
U1 4
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 FEB 5
PY 2016
VL 11
IS 2
AR e0148253
DI 10.1371/journal.pone.0148253
PG 25
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9PR
UT WOS:000369554000058
PM 26849447
ER
PT J
AU Chu, C
Bottaro, DP
Betenbaugh, MJ
Shiloach, J
AF Chu, Chia
Bottaro, Donald P.
Betenbaugh, Michael J.
Shiloach, Joseph
TI Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation
and Anchorage-Independence in MDCK Cells
SO PLOS ONE
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION;
PROTEIN-FREE CULTURE; SCATTER FACTOR; CANCER PROGRESSION; CHO-CELLS;
C-MET; MATRIX METALLOPROTEINASES; KINASE ACTIVATION; SIGNALING PATHWAY
AB The epithelial-mesenchymal transition (EMT) is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage-dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5). The comparison identified several genes involved in the EMT process that were differentially expressed between the anchorage-dependent and the anchorage-independent MDCK cell lines. The hepatocyte growth factor gene (hgf) was found to be over-expressed in the engineered MDCK-siat7e cells at both transcription and protein expression levels. Phosphorylation analysis of the MET receptor tyrosine kinase confirmed the activation of an autocrine loop of the HGF/MET signaling pathway in the MDCK-siat7e cells. When MET activities were suppressed by using the small-molecular inhibitor drug PF-02341066 (Crizotinib), the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells. These observations indicate that the MET receptor plays a central role in the growth properties of the MDCK cells and its phosphorylation status is likely dependent on sialylation. Further investigation of the downstream signaling targets in the MET network showed that the degree of MDCK cell adhesion correlated with secretion levels of a matrix metalloproteinase, MMP1, suggesting a role of metalloproteinases in the EMT process. These results demonstrate that in addition to its application in biotechnology processes, MDCK-siat7e may serve as a model cell for metastasis studies to decipher the sequence of events leading up to the activation of EMT.
C1 [Chu, Chia; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Chu, Chia; Betenbaugh, Michael J.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD USA.
[Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chu, Chia] Pfizer Inc, Bioproc Res & Dev, Chesterfield, MO USA.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
EM Josephs@niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX Funding was provided by the Intramural program at the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 64
TC 0
Z9 0
U1 2
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 FEB 5
PY 2016
VL 11
IS 2
AR e0148075
DI 10.1371/journal.pone.0148075
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9PR
UT WOS:000369554000038
PM 26848584
ER
PT J
AU Davis, KN
Tao, R
Li, C
Gao, Y
Gondre-Lewis, MC
Lipska, BK
Shin, JH
Xie, B
Ye, TZ
Weinberger, DR
Kleinman, JE
Hyde, TM
AF Davis, Kasey N.
Tao, Ran
Li, Chao
Gao, Yuan
Gondre-Lewis, Marjorie C.
Lipska, Barbara K.
Shin, Joo Heon
Xie, Bin
Ye, Tianzhang
Weinberger, Daniel R.
Kleinman, Joel E.
Hyde, Thomas M.
TI GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in
Schizophrenia and Affective Disorders
SO PLOS ONE
LA English
DT Article
ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; BIPOLAR DISORDER;
MESSENGER-RNA; GENE-EXPRESSION; GABA SYNTHESIS; VISUAL-CORTEX; MICE
LACKING; RAT-BRAIN; IN-VIVO
AB Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.
C1 [Davis, Kasey N.; Lipska, Barbara K.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Davis, Kasey N.; Tao, Ran; Li, Chao; Gao, Yuan; Shin, Joo Heon; Xie, Bin; Ye, Tianzhang; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.] Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.; Hyde, Thomas M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Johns Hopkins Univ Med Campus, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.; Hyde, Thomas M.] Johns Hopkins Univ, Sch Med, Neurol, Johns Hopkins Univ Med Campus, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
[Davis, Kasey N.; Gondre-Lewis, Marjorie C.] Howard Univ, Coll Med, Dept Anat, Lab Neurodev, Washington, DC 20059 USA.
RP Hyde, TM (reprint author), Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
EM thomas.hyde@libd.org
RI Lipska, Barbara/E-4569-2017
NR 49
TC 1
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U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 5
PY 2016
VL 11
IS 2
AR e0148558
DI 10.1371/journal.pone.0148558
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9PR
UT WOS:000369554000124
PM 26848839
ER
PT J
AU Li, SX
Barrett, BS
Guo, KJ
Kassiotis, G
Hasenkrug, KJ
Dittmer, U
Gibbert, K
Santiago, ML
AF Li, Sam X.
Barrett, Bradley S.
Guo, Kejun
Kassiotis, George
Hasenkrug, Kim J.
Dittmer, Ulf
Gibbert, Kathrin
Santiago, Mario L.
TI Tetherin/BST-2 promotes dendritic cell activation and function during
acute retrovirus infection
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; FRIEND-VIRUS; IN-VIVO;
IMMUNODEFICIENCY-VIRUS; HIV-1 RELEASE; C57BL/6 MICE; NK CELLS;
RESPONSES; REPLICATION
AB Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.
C1 [Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Santiago, Mario L.] Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.
[Li, Sam X.; Santiago, Mario L.] Univ Colorado Denver, Dept Immunol & Microbiol, Aurora, CO 80045 USA.
[Kassiotis, George] Francis Crick Inst, Mill Hill Lab, London, England.
[Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Dittmer, Ulf; Gibbert, Kathrin] Univ Duisburg Essen, Univ Hosp Essen, Inst Virol, Essen, Germany.
RP Santiago, ML (reprint author), Univ Colorado Denver, Dept Med, Aurora, CO 80045 USA.; Santiago, ML (reprint author), Univ Colorado Denver, Dept Immunol & Microbiol, Aurora, CO 80045 USA.
EM mario.santiago@ucdenver.edu
FU National Institutes of Health [R21 AI112418, R01 AI116603]; Colorado
Clinical and Translational Sciences Institute [TL1 T4000155]; Molecular
Pathogenesis of Infectious Disease Grant [T32 AI052066]; National
Institutes of Health Division of Intramural Research; German Research
Association [DFG-TRR60]; University of Colorado Denver Early Career
Scholar Program
FX This work was supported by the National Institutes of Health R21
AI112418 and R01 AI116603 (to M.L.S.), Colorado Clinical and
Translational Sciences Institute Grant TL1 T4000155 (to S.X.L.),
Molecular Pathogenesis of Infectious Disease Grant T32 AI052066 (to
S.X.L.), the National Institutes of Health Division of Intramural
Research (to K.J.H.), the German Research Association (DFG-TRR60) (to
K.G. and U.D.) and the University of Colorado Denver Early Career
Scholar Program (to M.L.S.). We thank Paul Bieniasz and Rachel
Liberatore for providing the Tetherin KO mice. We also thank Philippa
Marrack, John Kappler, Claudia Jakubzick, Thomas Morrison, David Barton,
J. David Beckham, Ross Kedl, Cara Wilson and Stephanie Dillon for
valuable scientific advice and discussions.
NR 68
TC 4
Z9 4
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 5
PY 2016
VL 6
AR 20425
DI 10.1038/srep20425
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC7FR
UT WOS:000369385300003
PM 26846717
ER
PT J
AU van der Straten, A
Brown, ER
Marrazzo, JM
Chirenje, MZ
Liu, K
Gomez, K
Marzinke, MA
Piper, JM
Hendrix, CW
AF van der Straten, Ariane
Brown, Elizabeth R.
Marrazzo, Jeanne M.
Chirenje, Michael Z.
Liu, Karen
Gomez, Kailazarid
Marzinke, Mark A.
Piper, Jeanna M.
Hendrix, Craig W.
CA MTN-003 VOICE Protocol Team
TI Divergent adherence estimates with pharmacokinetic and behavioural
measures in the MTN-003 (VOICE) study
SO JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
LA English
DT Article
DE microbicide; pre-exposure prophylaxis; adherence measurement;
pharmacokinetic drug detection; HIV
ID ANTIRETROVIRAL PREEXPOSURE PROPHYLAXIS; PLACEBO-CONTROLLED TRIAL;
HIV-PREVENTION TRIALS; SOUTH-AFRICA; FEM-PREP; TRANSGENDER WOMEN;
MICROBICIDE TRIAL; ORAL PREEXPOSURE; SEXUAL-ACTIVITY; DRUG DETECTION
AB Introduction: In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting.
Methods: We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer-assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations <0.31 ng/mL in plasma (oral group) and <8.5 ng/swab in vaginal group were defined as "PK non-adherent.'' Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model.
Results: In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, 510% of the cohort reported low/none use with any behavioural measure and accuracy was low (543%). None of the regression models had an AUC >0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting.
Conclusions: PK measures indicated similarly low adherence for the oral and vaginal groups. No behavioural measure accurately predicted PK non-adherence. Accurate real-time measures to monitor product adherence are urgently needed.
C1 [van der Straten, Ariane] RTI Int, WGHI, San Francisco, CA 94104 USA.
[van der Straten, Ariane] Univ Calif San Francisco, Dept Med, CAPS, San Francisco, CA USA.
[Brown, Elizabeth R.; Liu, Karen] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Brown, Elizabeth R.; Marrazzo, Jeanne M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Brown, Elizabeth R.; Marrazzo, Jeanne M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Chirenje, Michael Z.] Univ Zimbabwe, UCSF Res Collaborat, Harare, Zimbabwe.
[Gomez, Kailazarid] FHI360, Durham, NC USA.
[Marzinke, Mark A.; Hendrix, Craig W.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Piper, Jeanna M.] NIAID, DAIDS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP van der Straten, A (reprint author), RTI Int, 351 Calif St,Suite 500, San Francisco, CA 94104 USA.
EM ariane@rti.org
RI Hendrix, Craig/G-4182-2014;
OI Hendrix, Craig/0000-0002-5696-8665; Marrazzo, Jeanne/0000-0002-9277-7364
FU U.S. National Institutes of Health (NIH) [MTN-003]; National Institute
of Allergy and Infectious Diseases [UM1AI068633, UM1AI068615,
UM1AI106707]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; National Institute of Mental Health
FX We are grateful to the study participants and to the entire study team.
The full MTN-003 study team can be viewed at
http://www.mtnstopshiv.org/people/emailgroups/86/cards. The U.S.
National Institutes of Health (NIH) funded MTN-003. The Microbicide
Trials Network is funded by the National Institute of Allergy and
Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with
co-funding from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development and the National Institute of Mental
Health, all components of the NIH. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH. The IND sponsors, Gilead sciences [VireadTM,
TruvadaTM] and CONRAD [Tenofovir 1% gel], supplied the products used in
this study.
NR 53
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Z9 1
U1 1
U2 4
PU INT AIDS SOCIETY
PI GENEVA
PA AVENUE DE FRANCE 23, GENEVA, 1202, SWITZERLAND
SN 1758-2652
J9 J INT AIDS SOC
JI J. Int. AIDS Soc.
PD FEB 4
PY 2016
VL 19
AR 20642
DI 10.7448/IAS.19.1.20642
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DM2IR
UT WOS:000376170800001
PM 26850270
ER
PT J
AU Franco, CA
Jones, ML
Bernabeu, MO
Vion, AC
Barbacena, P
Fan, JQ
Mathivet, T
Fonseca, CG
Ragab, A
Yamaguchi, TP
Coveney, PV
Lang, RA
Gerhardt, H
AF Franco, Claudio A.
Jones, Martin L.
Bernabeu, Miguel O.
Vion, Anne-Clemence
Barbacena, Pedro
Fan, Jieqing
Mathivet, Thomas
Fonseca, Catarina G.
Ragab, Anan
Yamaguchi, Terry P.
Coveney, Peter V.
Lang, Richard A.
Gerhardt, Holger
TI Non-canonical Wnt signalling modulates the endothelial shear stress flow
sensor in vascular remodelling
SO ELIFE
LA English
DT Article
ID GROWTH-FACTOR; VE-CADHERIN; BLOOD-FLOW; YOLK-SAC; ANGIOGENESIS; CELLS;
PROTEIN; MOUSE; PLASTICITY; REGRESSION
AB Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.
C1 [Franco, Claudio A.; Jones, Martin L.; Vion, Anne-Clemence; Ragab, Anan; Gerhardt, Holger] Francis Crick Inst, London Res Inst, Lincolns Inn Labs, Vasc Biol Lab, London, England.
[Franco, Claudio A.; Barbacena, Pedro; Fonseca, Catarina G.] Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal.
[Bernabeu, Miguel O.] Univ Edinburgh, Usher Inst, Ctr Med Informat, Edinburgh, Midlothian, Scotland.
[Bernabeu, Miguel O.; Coveney, Peter V.] UCL, Dept Chem, Ctr Computat Sci, London, England.
[Vion, Anne-Clemence; Gerhardt, Holger] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Fan, Jieqing; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Visual Syst Grp, Cincinnati, OH 45229 USA.
[Mathivet, Thomas; Gerhardt, Holger] Vesalius Res Ctr, Vasc Patterning Lab, Leuven, Belgium.
[Mathivet, Thomas; Gerhardt, Holger] Vesalius Res Ctr, Vasc Patterning Lab, Dept Oncol, Leuven, Belgium.
[Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Gerhardt, Holger] German Ctr Cardiovasc Res, Berlin, Germany.
[Gerhardt, Holger] Berlin Inst Hlth, Berlin, Germany.
RP Franco, CA; Gerhardt, H (reprint author), Francis Crick Inst, London Res Inst, Lincolns Inn Labs, Vasc Biol Lab, London, England.; Franco, CA (reprint author), Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal.; Gerhardt, H (reprint author), Max Delbruck Ctr Mol Med, Berlin, Germany.; Gerhardt, H (reprint author), Vesalius Res Ctr, Vasc Patterning Lab, Leuven, Belgium.; Gerhardt, H (reprint author), Vesalius Res Ctr, Vasc Patterning Lab, Dept Oncol, Leuven, Belgium.; Gerhardt, H (reprint author), German Ctr Cardiovasc Res, Berlin, Germany.; Gerhardt, H (reprint author), Berlin Inst Hlth, Berlin, Germany.
EM cfranco@medicina.ulisboa.pt; holger.gerhardt@mdc-berlin.de
RI Mathivet, Thomas/L-2663-2016; Franco, Claudio/D-8117-2015;
OI Franco, Claudio/0000-0002-2861-3883; Jones, Martin/0000-0003-0994-5652;
Gerhardt, Holger/0000-0002-3030-0384
FU Cancer Research UK; Fundacao para a Ciencia e Tecnologia
[EXPL/BEX-BCM/2258/2013]; Fonseca Fundacao para a Ciencia e a Tecnologia
[LISBOA-01-0145-FEDER-007391]; European Commission - Marie Curie Actions
[255150]; Fundacao para a Ciencia e a Tecnologia [IF/00412/2012];
UKCOMES [EP/L00030X/1]; European Commission - FP7 Projects [287703,
261507]; Engineering and Physical Sciences Research Council
[EP/I017909/1, EP/I034602/1]; Lister Institute of Preventive Medicine;
Leducq Transatlantic Network Artemis; EMBO Young Investigator Program;
European Research Council [REshape 311719]; BIRAX - Regenerative
Medicine Initiative
FX Cancer Research UK Claudio A Franco, Anne-Clemence Vion Anan Ragab
Holger Gerhardt; Fundacao para a Ciencia e Tecnologia
EXPL/BEX-BCM/2258/2013 Claudio A Franco Catarina G; Fonseca Fundacao
para a Ciencia e a Tecnologia LISBOA-01-0145-FEDER-007391 Claudio A
Franco; European Commission - Marie Curie Actions 255150 Claudio A
Franco; Fundacao para a Ciencia e a Tecnologia IF/00412/2012 Claudio A
Franco; UKCOMES EP/L00030X/1 Miguel O Bernabeu Peter V Coveney; European
Commission - FP7 Projects 287703 Miguel O Bernabeu Peter V Coveney;
European Commission - FP7 Projects 261507 Miguel O Bernabeu Peter V
Coveney; Engineering and Physical Sciences Research Council EP/I017909/1
Miguel O Bernabeu Peter V Coveney; Engineering and Physical Sciences
Research Council EP/I034602/1 Miguel O Bernabeu Peter V Coveney; Lister
Institute of Preventive Medicine Holger Gerhardt; Leducq Transatlantic
Network Artemis Holger Gerhardt; EMBO Young Investigator Program Holger
Gerhardt; European Research Council REshape 311719 Holger Gerhardt;
BIRAX - Regenerative Medicine Initiative Holger Gerhardt
NR 45
TC 6
Z9 6
U1 3
U2 7
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 4
PY 2016
VL 5
AR e07727
DI 10.7554/eLife.07727
PG 22
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DI9IC
UT WOS:000373815100001
PM 26845523
ER
PT J
AU Webster, MT
Manor, U
Lippincott-Schwartz, J
Fan, CM
AF Webster, Micah T.
Manor, Uri
Lippincott-Schwartz, Jennifer
Fan, Chen-Ming
TI Intravital Imaging Reveals Ghost Fibers as Architectural Units Guiding
Myogenic Progenitors during Regeneration
SO CELL STEM CELL
LA English
DT Article
ID MUSCLE SATELLITE CELL; SKELETAL-MUSCLE; STEM-CELLS; PRECURSOR CELLS;
MIGRATION; MOUSE; MOTILITY; PROLIFERATION
AB How resident stem cells and their immediate progenitors rebuild tissues of pre-injury organization and size for proportional regeneration is not well understood. Using 3D, time-lapse intravital imaging for direct visualization of the muscle regeneration process in live mice, we report that extracellular matrix remnants from injured skeletal muscle fibers, "ghost fibers,'' govern muscle stem/progenitor cell behaviors during proportional regeneration. Stem cells were immobile and quiescent without injury whereas their activated progenitors migrated and divided after injury. Unexpectedly, divisions and migration were primarily bi-directionally oriented along the ghost fiber longitudinal axis, allowing for spreading of progenitors throughout ghost fibers. Re-orienting ghost fibers impacted myogenic progenitors' migratory paths and division planes, causing disorganization of regenerated muscle fibers. We conclude that ghost fibers are autonomous, architectural units necessary for proportional regeneration after tissue injury. This finding reinforces the need to fabricate bioengineered matrices that mimic living tissue matrices for tissue regeneration therapy.
C1 [Webster, Micah T.; Fan, Chen-Ming] Carnegie Inst Sci, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA.
[Manor, Uri; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Branch, NIH, Bldg 35A,9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Fan, CM (reprint author), Carnegie Inst Sci, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA.
EM fan@ciwemb.edu
FU NIAMS of NIH [F32AR065366, RO1AR060042]; intramural funds of NICHD of
NIH
FX We thank Fan and Lepper Lab members as well as Drs. Allan Spradling and
Yixian Zheng for reading the manuscript, Ms. S. Satchell and Ms. E.
Dikovsky for maintaining mice, and Dr. Mahmud Siddiqi for microscopy
assistance. Research reported in this publication was supported by the
NIAMS of the NIH under award numbers F32AR065366 (to M.W.) and
RO1AR060042 (to C.-M.F.), as well as intramural funds of the NICHD of
the NIH (to U.M. and J.L.-S.). The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the NIH.
NR 40
TC 12
Z9 12
U1 5
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD FEB 4
PY 2016
VL 18
IS 2
BP 243
EP 252
DI 10.1016/j.stem.2015.11.005
PG 10
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DG8GT
UT WOS:000372321700014
PM 26686466
ER
PT J
AU Ji, X
Dadon, DB
Powell, BE
Fan, ZP
Borges-Rivera, D
Shachar, S
Weintraub, AS
Hnisz, D
Pegoraro, G
Lee, TI
Misteli, T
Jaenisch, R
Young, RA
AF Ji, Xiong
Dadon, Daniel B.
Powell, Benjamin E.
Fan, Zi Peng
Borges-Rivera, Diego
Shachar, Sigal
Weintraub, Abraham S.
Hnisz, Denes
Pegoraro, Gianluca
Lee, Tong Ihn
Misteli, Tom
Jaenisch, Rudolf
Young, Richard A.
TI 3D Chromosome Regulatory Landscape of Human Pluripotent Cells
SO CELL STEM CELL
LA English
DT Article
ID EMBRYONIC STEM-CELLS; HUMAN GENOME; GENE-EXPRESSION; CHROMATIN
ARCHITECTURE; TRANSCRIPTIONAL REGULATION; DOMAIN ARCHITECTURE;
SUPER-ENHANCERS; IDENTITY GENES; EARLY PROMOTER; BINDING SITES
AB In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
C1 [Ji, Xiong; Dadon, Daniel B.; Powell, Benjamin E.; Fan, Zi Peng; Borges-Rivera, Diego; Weintraub, Abraham S.; Hnisz, Denes; Lee, Tong Ihn; Jaenisch, Rudolf; Young, Richard A.] Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
[Dadon, Daniel B.; Borges-Rivera, Diego; Weintraub, Abraham S.; Jaenisch, Rudolf; Young, Richard A.] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Fan, Zi Peng] MIT, Computat & Syst Biol Program, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Shachar, Sigal; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Pegoraro, Gianluca] NCI, High Throughput Imaging Facil HiTIF, NIH, Bethesda, MD 20892 USA.
RP Jaenisch, R; Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.; Jaenisch, R; Young, RA (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM jaenisch@wi.mit.edu; young@wi.mit.edu
RI Young, Richard/F-6495-2012;
OI Young, Richard/0000-0001-8855-8647; Pegoraro,
Gianluca/0000-0003-2843-9464
FU Intramural Research Program of NIH, NCI, Center for Cancer Research;
Erwin Schrodinger Fellowship from Austrian Science Fund (FWF) [J3490];
Ludwig Graduate Fellowship Funds; NIH [HG002668, HD 045022]; Simons
Foundation SFLIFE [286977]
FX We thank Brian J. Abraham and Jill Dowen for data analysis. We thank Tom
Volkert at the Whitehead Genome Technology Core for sequencing. We thank
Wendy Salmon for assistance with confocal microscopy and Raaji
Alagappan, Dongdong Fu, and Tenzin Lungjangwa for preparation of mouse
embryonic fibroblasts. This research was in part supported by the
Intramural Research Program of the NIH, NCI, Center for Cancer Research.
This work was supported by an Erwin Schrodinger Fellowship (J3490) from
the Austrian Science Fund (FWF) (to D.H.), Ludwig Graduate Fellowship
Funds (A.S.W.), NIH Grants HG002668 (to R.A.Y.) and HD 045022 (to R.J.),
and a grant from the Simons Foundation SFLIFE 286977 (to R.J.). R.J. is
a founder of Fate Therapeutics and R.A.Y. is a founder of Syros
Pharmaceuticals.
NR 74
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD FEB 4
PY 2016
VL 18
IS 2
BP 262
EP 275
DI 10.1016/j.stem.2015.11.007
PG 14
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DG8GT
UT WOS:000372321700016
PM 26686465
ER
PT J
AU Schick, UM
Jain, D
Hodonsky, CJ
Morrison, JV
Davis, JP
Brown, L
Sofer, T
Conomos, MP
Schurmann, C
McHugh, CP
Nelson, SC
Vadlamudi, S
Stilp, A
Plantinga, A
Baier, L
Bien, SA
Gogarten, SM
Laurie, CA
Taylor, KD
Liu, YM
Auer, PL
Franceschini, N
Szpiro, A
Rice, K
Kerr, KF
Rotter, JI
Hanson, RL
Papanicolaou, G
Rich, SS
Loos, RJF
Browning, BL
Browning, SR
Weir, BS
Laurie, CC
Mohlke, KL
North, KE
Thornton, TA
Reiner, AP
AF Schick, Ursula M.
Jain, Deepti
Hodonsky, Chani J.
Morrison, Jean V.
Davis, James P.
Brown, Lisa
Sofer, Tamar
Conomos, Matthew P.
Schurmann, Claudia
McHugh, Caitlin P.
Nelson, Sarah C.
Vadlamudi, Swarooparani
Stilp, Adrienne
Plantinga, Anna
Baier, Leslie
Bien, Stephanie A.
Gogarten, Stephanie M.
Laurie, Cecelia A.
Taylor, Kent D.
Liu, Yongmei
Auer, Paul L.
Franceschini, Nora
Szpiro, Adam
Rice, Ken
Kerr, Kathleen F.
Rotter, Jerome I.
Hanson, Robert L.
Papanicolaou, George
Rich, Stephen S.
Loos, Ruth J. F.
Browning, Brian L.
Browning, Sharon R.
Weir, Bruce S.
Laurie, Cathy C.
Mohlke, Karen L.
North, Kari E.
Thornton, Timothy A.
Reiner, Alex P.
TI Genome-wide Association Study of Platelet Count Identifies
Ancestry-Specific Loci in Hispanic/Latino Americans
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-1; GENETIC-VARIATION; AFRICAN-AMERICAN;
SEQUENCE; THROMBOCYTOPENIA; POPULATION; INFERENCE; VARIANTS; MUTATIONS;
BINDING
AB Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 x 10 (28)) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits.
C1 [Schick, Ursula M.; Bien, Stephanie A.; Reiner, Alex P.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA.
[Schick, Ursula M.; Schurmann, Claudia; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Schick, Ursula M.; Schurmann, Claudia; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Jain, Deepti; Morrison, Jean V.; Brown, Lisa; Sofer, Tamar; Conomos, Matthew P.; McHugh, Caitlin P.; Nelson, Sarah C.; Stilp, Adrienne; Plantinga, Anna; Gogarten, Stephanie M.; Laurie, Cecelia A.; Szpiro, Adam; Rice, Ken; Kerr, Kathleen F.; Browning, Brian L.; Browning, Sharon R.; Weir, Bruce S.; Laurie, Cathy C.; Thornton, Timothy A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hodonsky, Chani J.; Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Davis, James P.; Vadlamudi, Swarooparani; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Baier, Leslie; Hanson, Robert L.] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 445 North 5th St, Phoenix, AZ 85004 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Taylor, Kent D.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Torrance, CA 90502 USA.
[Liu, Yongmei] Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA.
[Auer, Paul L.] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Papanicolaou, George] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Rich, Stephen S.] Univ Virginia, Dept Med, Div Endocrinol, Charlottesville, VA 22908 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
RP Reiner, AP (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA.
EM apreiner@uw.edu
RI Browning, Sharon/B-1530-2008; Browning, Brian/A-1178-2010; Schurmann,
Claudia/L-1204-2016;
OI Browning, Sharon/0000-0001-7251-9715; Browning,
Brian/0000-0001-6454-6633; Schurmann, Claudia/0000-0003-4158-9192;
Nelson, Sarah/0000-0002-2109-6465; Gogarten,
Stephanie/0000-0002-7231-9745; Davis, James/0000-0002-8715-7857; Sofer,
Tamar/0000-0001-8520-8860
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233];
University of Miami [N01-HC65234]; Albert Einstein College of Medicine
[N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State
University [N01-HC65237]; National Institute on Minority Health and
Health Disparities; National Institute on Deafness and Other
Communication Disorders; National Institute of Dental and Craniofacial
Research (NIDCR); National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) [DK063491]; National Institute of Neurological
Disorders and Stroke; NIH Office of Dietary; NHLBI; NIDCR
[HHSN268201300005C AM03, MOD03]; National Center for Advancing
Translational Sciences [UL1TR000124]; Intramural Research Program of the
NIDDK [HHSB268201200054C]; Illumina; Andrea and Charles Bronfman
Philanthropies [R01-GM110068]; [1R01DK101855-01]; [13GRNT16490017];
[R01 DK072193]
FX We thank the participants and staff of the Hispanic Community Health
Study/Study of Latinos (HCHS/SOL). The baseline examination of HCHS/SOL
was supported by contracts from the National Heart, Lung, and Blood
Institute (NHLBI) to the University of North Carolina (N01-HC65233),
University of Miami (N01-HC65234), Albert Einstein College of Medicine
(N01-HC65235), Northwestern University (N01-HC65236), and San Diego
State University (N01-HC65237). The National Institute on Minority
Health and Health Disparities, National Institute on Deafness and Other
Communication Disorders, National Institute of Dental and Craniofacial
Research (NIDCR), National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), National Institute of Neurological Disorders
and Stroke, and NIH Office of Dietary Supplements additionally
contributed funding to HCHS/SOL. The Genetic Analysis Center at the
University of Washington was supported by NHLBI and NIDCR contracts
(HHSN268201300005C AM03 and MOD03). Additional analysis support was
provided by 1R01DK101855-01 and 13GRNT16490017. Genotyping was also
supported by National Center for Advancing Translational Sciences
UL1TR000124 and NIDDK DK063491 to the Southern California Diabetes
Endocrinology Research Center. Additional support for rs117672662
functional studies was provided by R01 DK072193. This research was also
supported in part by the Intramural Research Program of the NIDDK,
contract no. HHSB268201200054C, and Illumina. S.R.B. was supported by
R01-GM110068. We thank Dr. Nick Patterson and the Simons Genome
Diversity Project for kindly providing Australo-Melanesian sequence
data. The Mount Sinai IPM Biobank Program is supported by the Andrea and
Charles Bronfman Philanthropies.
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 4
PY 2016
VL 98
IS 2
BP 229
EP 242
DI 10.1016/j.ajhg.2015.12.003
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA DE3BR
UT WOS:000370502300001
PM 26805783
ER
PT J
AU Santos-Cortez, RLP
Faridi, R
Rehman, AU
Lee, K
Ansar, M
Wang, X
Morell, RJ
Isaacson, R
Belyantseva, IA
Dai, H
Acharya, A
Qaiser, TA
Muhammad, D
Ali, RA
Shams, S
Hassan, MJ
Shahzad, S
Raza, SI
Bashir, ZEH
Smith, JD
Nickerson, DA
Bamshad, MJ
Riazuddin, S
Ahmad, W
Friedman, TB
Leal, SM
AF Santos-Cortez, Regie Lyn P.
Faridi, Rabia
Rehman, Atteeq U.
Lee, Kwanghyuk
Ansar, Muhammad
Wang, Xin
Morell, Robert J.
Isaacson, Rivka
Belyantseva, Inna A.
Dai, Hang
Acharya, Anushree
Qaiser, Tanveer A.
Muhammad, Dost
Ali, Rana Amjad
Shams, Sulaiman
Hassan, Muhammad Jawad
Shahzad, Shaheen
Raza, Syed Irfan
Bashir, Zil-e-Huma
Smith, Joshua D.
Nickerson, Deborah A.
Bamshad, Michael J.
Riazuddin, Sheikh
Ahmad, Wasim
Friedman, Thomas B.
Leal, Suzanne M.
CA Univ Washington Ctr Mendelian Geno
TI Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants
within S1PR2
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR;
ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; HAIR-CELLS; INNER-EAR;
SPHINGOSINE-1-PHOSPHATE; S1P(2); ACTIVATION; MUTATIONS
AB The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among similar to 120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2.
C1 [Santos-Cortez, Regie Lyn P.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Dai, Hang; Acharya, Anushree; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA.
[Faridi, Rabia; Rehman, Atteeq U.; Morell, Robert J.; Belyantseva, Inna A.; Friedman, Thomas B.] NIDCD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Faridi, Rabia; Qaiser, Tanveer A.; Bashir, Zil-e-Huma] Univ Punjab, Ctr Excellence Mol Biol, Lahore 54550, Pakistan.
[Ansar, Muhammad; Raza, Syed Irfan; Ahmad, Wasim] Quaid I Azam Univ, Dept Biochem, Fac Biol Sci, Islamabad 45320, Pakistan.
[Isaacson, Rivka] Kings Coll London, Dept Chem, Fac Nat & Math Sci, London WC2R 2LS, England.
[Muhammad, Dost] Chandka Med Coll, Larkana 77150, Sindh, Pakistan.
[Ali, Rana Amjad; Riazuddin, Sheikh] Univ Lahore, Lahore 54550, Pakistan.
[Shams, Sulaiman] Abdul Wali Khan Univ, Dept Biochem, Mardan 23200, Khyber Pakhtunk, Pakistan.
[Hassan, Muhammad Jawad] Natl Univ Sci & Technol, Dept Healthcare Biotechnol, Atta Ur Rahman Sch Appl Biosci ASAB, Islamabad 44000, Pakistan.
[Shahzad, Shaheen] Int Islamic Univ, Dept Biotechnol & Bioinformat, Islamabad 44000, Pakistan.
[Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Riazuddin, Sheikh] Allama Iqbal Med Res Ctr, Jinnah Hosp Complex, Lahore 54550, Pakistan.
[Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Islamabad 44000, Pakistan.
RP Leal, SM (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Ctr Stat Genet, Houston, TX 77030 USA.
EM sleal@bcm.edu
RI Ansar, Muhammad/H-5967-2011;
OI Ansar, Muhammad/0000-0001-5891-7063; Isaacson, Rivka
Leah/0000-0002-9978-8904
FU NIH intramural funds from the National Institute on Deafness and Other
Communication Disorders (NIDCD) [DC000039-18]; Higher Education
Commission of Pakistan; NIH-NIDCD [R01 DC011651, R01 DC003594]; NIH
[N01-HG-65403]; National Human Genome Research Institute; National
Heart, Lung and Blood Institute [U54HG006493]
FX We are very grateful to the families that participated in this study.
This work was supported by NIH intramural funds from the National
Institute on Deafness and Other Communication Disorders (NIDCD)
DC000039-18 (to T.B.F.), the Higher Education Commission of Pakistan (to
S.R. and W.A.), and NIH-NIDCD grants R01 DC011651 and R01 DC003594 (to
S.M.L.). Genome-wide genotyping was performed at the Center for
Inherited Disease Research, which is funded through the NIH to The Johns
Hopkins University, Contract Number N01-HG-65403 (to S.M.L.). Exome
sequencing for family DEM4154 was provided by the University of
Washington Center for Mendelian Genomics and was funded by the National
Human Genome Research Institute and the National Heart, Lung and Blood
Institute grant U54HG006493 to D.A.N., Jay Shendure, and M.J.B.
Sequencing work for family PKDF1400 utilized the computational resources
of the NIH HPC Biowulf cluster.
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 4
PY 2016
VL 98
IS 2
BP 331
EP 338
DI 10.1016/j.ajhg.2015.12.004
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DE3BR
UT WOS:000370502300009
PM 26805784
ER
PT J
AU Kane, MS
Davids, M
Adams, C
Wolfe, LA
Cheung, HW
Gropman, A
Huang, Y
Ng, BG
Freeze, HH
Adams, DR
Gahl, WA
Boerkoel, CF
AF Kane, Megan S.
Davids, Mariska
Adams, Christopher
Wolfe, Lynne A.
Cheung, Helen W.
Gropman, Andrea
Huang, Yan
Ng, Bobby G.
Freeze, Hudson H.
Adams, David R.
Gahl, William A.
Boerkoel, Cornelius F.
CA NISC Comparative Sequencing Progra
TI Mitotic Intragenic Recombination: A Mechanism of Survival for Several
Congenital Disorders of Glycosylation
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID CDG-IA; MUTATIONS; PMM2; DEFICIENCY; PHENOTYPE; DISEASE; REVERSION
AB Congenital disorders of glycosylation (CDGs) are disorders of abnormal protein glycosylation that affect multiple organ systems. Because most CDGs have been described in only a few individuals, our understanding of the associated phenotypes and the mechanisms of individual survival are limited. In the process of studying two siblings, aged 6 and 11 years, with MOGS-CDG and biallelic MOGS (mannosyl-oligosaccharide glucosidase) mutations (GenBank: NM_006302.2; c.[65C>A; 329G>A] p.[Ala22Glu; Arg110His]; c.[370C>T] p.[Gln124*]), we noted that their survival was much longer than the previous report of MOGS-CDG, in a child who died at 74 days of age. Upon mutation analysis, we detected multiple MOGS genotypes including wild-type alleles in their cultured fibroblast and peripheral blood DNA. Further analysis of DNA from cultured fibroblasts of six individuals with compound heterozygous mutations of PMM2 (PMM2-CDG), MPI (MPI-CDG), ALG3 (ALG3-CDG), ALG12 (ALG12-CDG), DPAGT1 (DPAGT1-CDG), and ALG1 (ALG1-CDG) also identified multiple genotypes including wild-type alleles for each. Droplet digital PCR showed a ratio of nearly 1: 1 wild-type to mutant alleles for most, but not all, mutations. This suggests that mitotic recombination contributes to the survival and the variable expressivity of individuals with compound heterozygous CDGs. This also provides an explanation for prior observations of a reduced frequency of homozygous mutations and might contribute to increased levels of residual enzyme activity in cultured fibroblasts of individuals with MPI- and PMM2-CDGs.
C1 [Kane, Megan S.; Davids, Mariska; Adams, Christopher; Wolfe, Lynne A.; Cheung, Helen W.; Gropman, Andrea; Huang, Yan; Adams, David R.; Gahl, William A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.
[Kane, Megan S.; Davids, Mariska; Adams, Christopher; Cheung, Helen W.; Huang, Yan; Adams, David R.; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Gropman, Andrea] Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA.
[Ng, Bobby G.; Freeze, Hudson H.] Sanford Burnham Prebys Med Discovery Inst, Human Genet Program, La Jolla, CA 92037 USA.
[Boerkoel, Cornelius F.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
RP Kane, MS; Gahl, WA (reprint author), NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bldg 10, Bethesda, MD 20892 USA.; Kane, MS; Gahl, WA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM megan.kane@nih.gov; gahlw@helix.nih.gov
OI Freeze, Hudson/0000-0001-6316-0501
FU Rocket Fund; [DKR0199551]
FX H.H.F. is supported by DKR0199551 and The Rocket Fund.
NR 31
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U1 2
U2 3
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 4
PY 2016
VL 98
IS 2
BP 339
EP 346
DI 10.1016/j.ajhg.2015.12.007
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DE3BR
UT WOS:000370502300010
PM 26805780
ER
PT J
AU Hoshina, H
Slipchenko, M
Prozument, K
Verma, D
Schmidt, MW
Ivanic, J
Vilesov, AF
AF Hoshina, Hiromichi
Slipchenko, Mikhail
Prozument, Kirin
Verma, Deepak
Schmidt, Michael W.
Ivanic, Joseph
Vilesov, Andrey F.
TI Infrared Spectroscopy and Structure of (NO)(n) Clusters
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID NITRIC-OXIDE DIMER; NO DIMER; HELIUM NANODROPLETS; ELECTRONIC STATES;
SUPERFLUID-HELIUM; NITROGEN MATRIX; LIQUID-HELIUM; NU(5) BAND;
MOLECULES; SPECTRUM
AB Nitrogen oxide clusters (NO) have been studied in He droplets via infrared depletion spectroscopy and by quantum chemical calculations. The v(1) and v(5) bands of cis- ON-NO dimer have been observed at 1868.2 and 1786.5 cm(-1), respectively. Furthermore, spectral bands of the trimer and tetramer have been located in the vicinity of the corresponding dimer bands in accord with computed frequencies that place NO-stretch bands of dinner, trimer, and tetramer within a few wavenumbers of each other. In addition, a new line at 1878.1 cm(-1) close to the band origin of single molecules was assigned to vander Waals bound dimers of (NO)(nu), which are stabilized due to the rapid cooling in He droplets. Spectra of larger clusters (n > 5), have broad unresolved features in the vicinity of the dimer bands. Experiments and calculations indicate that trimers consist of a dimer and a loosely bound third molecule, whereas the tetramer consists of two weakly bound dimers.
C1 [Hoshina, Hiromichi; Slipchenko, Mikhail; Prozument, Kirin; Verma, Deepak; Vilesov, Andrey F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
[Schmidt, Michael W.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
[Schmidt, Michael W.] Iowa State Univ, Ames Lab, US DOE, Ames, IA 50011 USA.
[Ivanic, Joseph] Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, DSITP, Frederick, MD 21702 USA.
[Hoshina, Hiromichi] RIKEN, Terahertz Sensing & Imaging Res Team, Aoba Ku, 1399 Aramaki Aoba, Sendai, Miyagi 9800845, Japan.
[Slipchenko, Mikhail] Purdue Univ, Sch Mat Engn, W Lafayette, IN 47907 USA.
[Prozument, Kirin] Argonne Natl Lab, Chem Sci & Engn Div, 9700 South Cass Ave,Bldg 200, Argonne, IL 60439 USA.
RP Vilesov, AF (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.; Ivanic, J (reprint author), Frederick Natl Lab Canc Res, Adv Biomed Comp Ctr, DSITP, Frederick, MD 21702 USA.
EM joseph.ivanic@nih.gov; vilesov@usc.edu
RI Prozument, Kirill/F-7865-2013; Hoshina, Hiromichi/H-7395-2014
OI Prozument, Kirill/0000-0003-3045-8429;
FU National Science Foundation [CHE-1362535]; US Department of Energy,
Office of Basic Energy Sciences, Geosciences and Biosciences
[DE-AC01-07CH11358]; federal funds from the National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX This material is based upon work supported by the National Science
Foundation under Grant CHE-1362535 to A.F.V. M.W.S. was supported by
funds provided by the US Department of Energy, Office of Basic Energy
Sciences, Geosciences and Biosciences, to the Ames Laboratory,
administered by Iowa State University under Contract DE-AC01-07CH11358.
J.I. was supported with federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 56
TC 0
Z9 0
U1 4
U2 16
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 FEB 4
PY 2016
VL 120
IS 4
BP 527
EP 534
DI 10.1021/acs.jpca.5b10228
PG 8
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA DD2ST
UT WOS:000369773200007
PM 26756475
ER
PT J
AU Chakrabarti, M
Jang, H
Nussinov, R
AF Chakrabarti, Mayukh
Jang, Hyunbum
Nussinov, Ruth
TI Comparison of the Conformations of KRAS Isoforms, K-Ras4A and K-Ras4B,
Points to Similarities and Significant Differences
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID SMALL GTPASE K-RAS4B; K-RAS 4A; HYPERVARIABLE REGION;
MOLECULAR-DYNAMICS; CANCER-THERAPY; EXON 4A; N-RAS; PROTEIN; 4B;
LOCALIZATION
AB Human HRAS, KRAS, and NRAS genes encode four isoforms of Ras, a p2,1 GTPase. Mutations in KRAS account for the majority of RAS-driven cancers. The KRAS has two splice variants, K-Ras4A and K-Ras4B. Due to their reversible palmitoylation, K-Ras4A and N-Ras have bimodal signaling states. K-Ras4A and K-Ras4B differ in four catalytic domain residues (G1S1R/D153E/K165Q/H166Y) and in their disordered C-terminal hypervariable region (HVR). In K-Ras4A, the HVR is not as strongly positively charged as in K-Ras4B (+6e vs +9e). Here, we performed all-atom molecular dynamics simulations to elucidate isoform-specific differences between the two splice variants. We observe that the catalytic domain of GDP-bound K-Ras4A has a more exposed nucleotide binding pocket than K-Ras4B, and the dynamic fluctuations in switch I and II regions also differ; may influence guanine nucleotide exchange. We further observe that like K-Kas4B, full-length K-Ras4A exhibits nucleotide dependent HVR fluctuations; however, these fluctuations differ between the GDP-bound forms of K-Ras4A and K-Ras4B. Unlike K-Ras4B where the HVR tends to cover the effector binding region, in K-Ras4A, autoinhibited states are unstable. With lesser charge, the K-Ras4A HVR collapses on itself, making it less available for binding the catalytic domain. Since the HVRs of N- and H-Ras are weakly charged (+1e and +2e, respectively), autoinhibition may be a unique feature of K-Ras4B.
C1 [Chakrabarti, Mayukh; Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Chakrabarti, Mayukh] NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
EM NussinoR@helix.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of NIH,
Frederick National Lab, Center for Cancer Research
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. This research
was supported [in part] by the Intramural Research Program of NIH,
Frederick National Lab, Center for Cancer Research. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government. All simulations have been performed using the
high-performance computational facilities of the Biowulf PC/Linux
cluster at the National Institutes of Health, Bethesda, MD.
NR 73
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Z9 3
U1 1
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD FEB 4
PY 2016
VL 120
IS 4
BP 667
EP 679
DI 10.1021/acs.jpcb.5b11110
PG 13
WC Chemistry, Physical
SC Chemistry
GA DD2SS
UT WOS:000369773100008
PM 26761128
ER
PT J
AU Chung, HS
Louis, JM
Gopich, IV
AF Chung, Hoi Sung
Louis, John M.
Gopich, Irina V.
TI Analysis of Fluorescence Lifetime and Energy Transfer Efficiency in
Single-Molecule Photon Trajectories of Fast-Folding Proteins
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID INTRINSICALLY DISORDERED PROTEINS; ALTERNATING-LASER EXCITATION;
TRANSITION PATH TIMES; HIDDEN MARKOV-MODELS; CONFORMATIONAL DYNAMICS;
CORRELATION SPECTROSCOPY; STRUCTURAL DYNAMICS; FRET EXPERIMENTS; DNA;
HISTOGRAMS
AB In single-molecule Forster resonance energy transfer (FRET) spectroscopy, the dynamics of molecular processes are usually determined by analyzing the fluorescence intensity of donor and acceptor dyes. Since FRET efficiency is related to fluorescence lifetimes, additional information can be extracted by analyzing fluorescence intensity and lifetime together. For fast processes where individual states are not well separated in a trajectory, it is not easy to obtain the lifetime information. Here, we present analysis methods to utilize fluorescence lifetime information from single-molecule FRET experiments, and apply these methods to three fast-folding, two-state proteins. By constructing 2D FRET efficiency-lifetime histograms, the correlation can be visualized between the FRET efficiency and fluorescence lifetimes in the presence of the submicrosecond to millisecond dynamics. We extend the previously developed method for analyzing delay times of donor photons to include acceptor delay times. To determine the kinetics and lifetime parameters accurately, we used a maximum likelihood method. We found that acceptor blinking can lead to inaccurate parameters in the donor delay time analysis. This problem can be solved by incorporating acceptor blinking into a model. While the analysis of acceptor delay times is not affected by acceptor blinking, it is more sensitive to the shape of the delay time distribution resulting from a broad conformational distribution in the unfolded state.
C1 [Chung, Hoi Sung; Louis, John M.; Gopich, Irina V.] NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
RP Chung, HS; Gopich, IV (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; irinag@niddk.nih.gov
RI Chung, Hoi Sung/C-2624-2009
FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX We thank A. Szabo for numerous helpful discussions, W. A. Eaton for
helpful comments on the manuscript, and A. Aniana for technical
assistance in the expression and purification of proteins. We
acknowledge use of the National Institute of Diabetes and Digestive and
Kidney Diseases Advanced Mass Spectrometry Core Facility. This work was
supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, NIH.
NR 81
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U1 7
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD FEB 4
PY 2016
VL 120
IS 4
BP 680
EP 699
DI 10.1021/acs.jpcb.5b11351
PG 20
WC Chemistry, Physical
SC Chemistry
GA DD2SS
UT WOS:000369773100009
PM 26812046
ER
PT J
AU Wilder, HK
Raffel, SJ
Barbour, AG
Porcella, SF
Sturdevant, DE
Vaisvil, B
Kapatral, V
Schmitt, DP
Schwan, TG
Lopez, JE
AF Wilder, Hannah K.
Raffel, Sandra J.
Barbour, Alan G.
Porcella, Stephen F.
Sturdevant, Daniel E.
Vaisvil, Benjamin
Kapatral, Vinayak
Schmitt, Daniel P.
Schwan, Tom G.
Lopez, Job E.
TI Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia
turicatae Suggests a Role in Vector Colonization and Initiating
Mammalian Infection
SO PLOS ONE
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; ACIDIC REPETITIVE PROTEINS; CAUSE RELAPSING
FEVER; TRYPANOSOMA-BRUCEI; SURFACE PROTEIN; ANTIGENIC VARIATION;
SALIVARY-GLANDS; IXODES-DAMMINI; FACTOR-H; BURGDORFERI TRANSMISSION
AB Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up-regulated during in vitro cultivation at tick-like growth temperatures (22 degrees C), relative to bacteria grown at 35 degrees C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle.
C1 [Wilder, Hannah K.; Lopez, Job E.] Baylor Coll Med, Dept Pediat, Sect Trop Med, Houston, TX 77030 USA.
[Wilder, Hannah K.; Lopez, Job E.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Raffel, Sandra J.; Schwan, Tom G.] NIAID, Rocky Mt Labs, Lab Zoonot Pathogens, NIH, Hamilton, MT 59840 USA.
[Barbour, Alan G.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
[Barbour, Alan G.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Barbour, Alan G.] Univ Calif Irvine, Dept Ecol & Evolut Biol, Irvine, CA 92717 USA.
[Porcella, Stephen F.; Sturdevant, Daniel E.] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect,NIH, Hamilton, MT 59840 USA.
[Vaisvil, Benjamin; Kapatral, Vinayak; Schmitt, Daniel P.] Igenbio Inc, Chicago, IL USA.
[Lopez, Job E.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
RP Lopez, JE (reprint author), Baylor Coll Med, Dept Pediat, Sect Trop Med, Houston, TX 77030 USA.; Lopez, JE (reprint author), Texas Childrens Hosp, Houston, TX 77030 USA.; Lopez, JE (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
EM job.lopez@bcm.edu
OI Barbour, Alan/0000-0002-0719-5248
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Igenbio, Inc.;
[AI091652]; [AI103724]; [AI065359]
FX This research was supported by AI091652 (JEL), AI103724 (JEL), AI065359
(AGB), and the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. Igenbio, Inc.
provided support in the form of salaries for authors BV, VK and DPS, but
did not have any additional role in the study design, data collection
and analysis, decision to publish, or preparation of the manuscript. The
specific roles of these authors are articulated in the 'author
contributions' section.
NR 61
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U1 3
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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 FEB 4
PY 2016
VL 11
IS 2
AR e0147707
DI 10.1371/journal.pone.0147707
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9PF
UT WOS:000369552800014
PM 26845332
ER
PT J
AU Yeung, EH
Louis, GB
Lawrence, D
Kannan, K
McLain, AC
Caggana, M
Druschel, C
Bell, E
AF Yeung, Edwina H.
Louis, Germaine Buck
Lawrence, David
Kannan, Kurunthachalam
McLain, Alexander C.
Caggana, Michele
Druschel, Charlotte
Bell, Erin
TI Eliciting parental support for the use of newborn blood spots for
pediatric research
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
DE Blood spot; Consent; Newborn Screening
ID SCREENING SAMPLES; TEMPORAL TRENDS; HEALTH RESEARCH; RETENTION;
SPECIMENS; EXPOSURE; CHILDREN; STATE; RECOMMENDATIONS; ORGANOCHLORINE
AB Background: Biomarkers of exposures such as infection or environmental chemicals can be measured in small volumes of blood extracted from newborn dried blood spots (DBS) underscoring their potential utility for population-based research. However, few studies have evaluated the feasibility and utility of this resource; particularly the factors associated with parental consent, and the ability to retrieve banked samples with sufficient remaining volume for epidemiologic research.
Methods: At 8 months postpartum, 5,034 mothers of infants born (2008-2010) in New York (57 counties excluding New York City) were asked to consent for the use of residual DBS for the quantification of cytokines and environmental chemicals. Mothers were part of the Upstate KIDS study, a longitudinal birth cohort designed to evaluate child development through 3 years of age. Information on parental and infant characteristics was obtained from birth certificates and maternal report at 4 months postpartum. Multivariate logistic regression was used to identify factors associated with parental consent and with successful retrieval of DBS.
Results: Sixty-two percent (n = 3125) of parents consented. Factors significantly associated with consent included non-Hispanic ethnicity (odds ratio 2.04; 95 % CI: 1.43-2.94), parity (1.29; 1.05-1.57), maternal obesity (1.42; 1.11-1.80) and reported alcohol use during pregnancy (1.51; 1.12-2.06). However, these associations corresponded to small absolute differences in proportions (4 to 8 %), suggesting that the two groups remained comparable. Infant characteristics such as preterm delivery did not significantly differ by consent status among singletons and only ventilator use (OR 2.39; 95 % CI: 1.06-5.41) remained borderline significant among twins in adjusted analyses. Among consented infants, 99 % had at least one 3.2 mm punch successfully retrieved for biomarker analyses and 84 % had a full DBS circle available.
Conclusion: Parental characteristics varied slightly by consent, and the availability of samples for research purposes was high, demonstrating the feasibility of this resource for population based research.
C1 [Yeung, Edwina H.; Louis, Germaine Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
[Lawrence, David] Ctr Med Sci, Wadsworth Ctr, Immunol Lab, Albany, NY 12203 USA.
[Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Lab Organ Analyt Chem, Albany, NY 12203 USA.
[McLain, Alexander C.] Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC USA.
[Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Lab Human Genet, Albany, NY 12203 USA.
[Druschel, Charlotte] New York State Dept Hlth, Ctr Environm Hlth, Bur Environm & Occupat Epidemiol, Albany, NY 12203 USA.
[Lawrence, David; Kannan, Kurunthachalam; Bell, Erin] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12144 USA.
[Druschel, Charlotte; Bell, Erin] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY 12144 USA.
RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA.
EM yeungedw@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490; Yeung,
Edwina/0000-0002-3851-2613
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD)
[HHSN275201200005C, HHSN267200700019C]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD;
contracts #HHSN275201200005C, #HHSN267200700019C). The authors thank the
Upstate KIDS families and staff for their important contributions.
Findings were presented in abstract and poster form to the American
College of Epidemiology Annual meeting, Silver Spring, MD, Sept 8, 2014.
NR 40
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U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD FEB 4
PY 2016
VL 16
AR 14
DI 10.1186/s12874-016-0120-8
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DC4YI
UT WOS:000369226000001
PM 26846420
ER
PT J
AU Ferreccio, C
Roa, JC
Bambs, C
Vives, A
Corvalan, AH
Cortes, S
Foerster, C
Acevedo, J
Huidobro, A
Passi, A
Toro, P
Covacevich, Y
de la Cruz, R
Koshiol, J
Olivares, M
Miquel, JF
Cruz, F
Silva, R
Quest, AF
Kogan, MJ
Castro, PF
Lavandero, S
AF Ferreccio, Catterina
Carlos Roa, Juan
Bambs, Claudia
Vives, Alejandra
Corvalan, Alejandro H.
Cortes, Sandra
Foerster, Claudia
Acevedo, Johanna
Huidobro, Andrea
Passi, Alvaro
Toro, Pablo
Covacevich, Yerko
de la Cruz, Rolando
Koshiol, Jill
Olivares, Mauricio
Francisco Miquel, Juan
Cruz, Francisco
Silva, Raul
Quest, Andrew F.
Kogan, Marcelo J.
Castro, Pablo F.
Lavandero, Sergio
TI Study protocol for the Maule Cohort (MAUCO) of chronic diseases, Chile
2014-2024
SO BMC PUBLIC HEALTH
LA English
DT Article
DE Prospective studies; Cohort studies; Population surveillance; Chronic
disease/epidemiology; Agricultural workers diseases; Cardiovascular
diseases; Neoplasms/Epidemiology
ID CANCER; ATHEROSCLEROSIS
AB Background: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina's population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina's poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases.
Methods/Design: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Catolica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand-grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data.
Discussion: MAUCO's results will help design public health interventions tailored to agricultural populations in Latin America.
C1 [Ferreccio, Catterina; Carlos Roa, Juan; Bambs, Claudia; Vives, Alejandra; Corvalan, Alejandro H.; Cortes, Sandra; Foerster, Claudia; Acevedo, Johanna; Huidobro, Andrea; Passi, Alvaro; Toro, Pablo; Covacevich, Yerko; de la Cruz, Rolando; Francisco Miquel, Juan; Cruz, Francisco] Pontificia Univ Catolica Chile, Fac Med, Adv Ctr Chron Dis ACCDiS, Alameda 340, Santiago, Chile.
[Huidobro, Andrea; Silva, Raul] Univ Catolica Maule, Fac Med, Talca, Chile.
[Koshiol, Jill] Natl Canc Inst, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, Bethesda, MD USA.
[Olivares, Mauricio] Hosp Santa Rosa de Molina Curico, Curico, Chile.
[Quest, Andrew F.; Lavandero, Sergio] Univ Chile, Fac Med, Adv Ctr Chron Dis ACCDiS, Santiago 7, Chile.
[Kogan, Marcelo J.; Lavandero, Sergio] Univ Chile, Fac Ciencias Quim & Farmaceut, Adv Ctr Chron Dis ACCDiS, Santiago, Chile.
[Lavandero, Sergio] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA.
RP Ferreccio, C (reprint author), Pontificia Univ Catolica Chile, Fac Med, Adv Ctr Chron Dis ACCDiS, Alameda 340, Santiago, Chile.
EM cferrec@med.puc.cl
FU National Commission for Scientific & Technological Research (CONICYT)
for the program Research Centers in Priority Areas (FONDAP) [15130011]
FX This work is funded by National Commission for Scientific &
Technological Research (CONICYT) for the program Research Centers in
Priority Areas (FONDAP) [grant number 15130011], and received material
support from the Facultad Medicina, Universidad Catolica del Maule and
from the Ilustre Municipalidad de Molina (Molina County).
NR 27
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U1 8
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD FEB 4
PY 2016
VL 16
AR 122
DI 10.1186/s12889-015-2454-2
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC8SE
UT WOS:000369489200001
PM 26847446
ER
PT J
AU Kraushaar, DC
Jin, WF
Maunakea, A
Abraham, B
Ha, M
Zhao, KJ
AF Kraushaar, Daniel C.
Jin, Wenfei
Maunakea, Alika
Abraham, Brian
Ha, Misook
Zhao, Keji
TI Genome-wide incorporation dynamics reveal distinct categories of
turnover for the histone variant H3.3 (vol 14, R121, 2013)
SO GENOME BIOLOGY
LA English
DT Correction
C1 [Kraushaar, Daniel C.; Jin, Wenfei; Maunakea, Alika; Abraham, Brian; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ha, Misook] Samsung Elect Corp, Samsung Adv Inst Technol, Yongin 446712, Gyeonggi Do, South Korea.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
NR 1
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 1465-6906
EI 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD FEB 4
PY 2016
VL 17
AR 21
DI 10.1186/s13059-016-0886-3
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DC6YK
UT WOS:000369365300002
PM 26846280
ER
PT J
AU Alderson, TR
Bax, A
AF Alderson, T. Reid
Bax, Ad
TI PARKINSON'S DISEASE Disorder in the court
SO NATURE
LA English
DT Editorial Material
ID ALPHA-SYNUCLEIN; CELL NMR; MULTIMERS
C1 [Alderson, T. Reid; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Alderson, T. Reid] Univ Oxford, Dept Chem, Oxford OX1 3TA, England.
RP Alderson, TR; Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM reid.alderson@nih.gov; bax@nih.gov
NR 12
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Z9 4
U1 6
U2 27
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD FEB 4
PY 2016
VL 530
IS 7588
BP 38
EP 39
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC6BK
UT WOS:000369304500025
PM 26808901
ER
PT J
AU Xia, NN
Zhang, PB
Fang, F
Wang, ZY
Rothstein, M
Angulo, B
Chiang, R
Taylor, J
Pera, RAR
AF Xia, Ninuo
Zhang, Pengbo
Fang, Fang
Wang, Zhengyuan
Rothstein, Megan
Angulo, Benjamin
Chiang, Rosaria
Taylor, James
Pera, Renee A. Reijo
TI Transcriptional comparison of human induced and primary midbrain
dopaminergic neurons
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PARKINSONS-DISEASE; STEM-CELLS; HUMAN ES; RNA-SEQ; DIFFERENTIATION;
PATHWAY; FATE
AB Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson's disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson's Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs.
C1 [Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Angulo, Benjamin; Chiang, Rosaria; Pera, Renee A. Reijo] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Angulo, Benjamin; Chiang, Rosaria; Pera, Renee A. Reijo] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA.
[Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Angulo, Benjamin; Chiang, Rosaria; Pera, Renee A. Reijo] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Rothstein, Megan; Pera, Renee A. Reijo] Montana State Univ, Dept Cell Biol & Neurosci, 207 Montana Hall, Bozeman, MT 59717 USA.
[Wang, Zhengyuan; Taylor, James] NHLBI, Genom Med Div, Hematol Branch, NIH, Rockville, MD 20850 USA.
RP Pera, RAR (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.; Pera, RAR (reprint author), Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA.; Pera, RAR (reprint author), Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.; Pera, RAR (reprint author), Montana State Univ, Dept Cell Biol & Neurosci, 207 Montana Hall, Bozeman, MT 59717 USA.
EM renee.reijopera@montana.edu
RI Fang, Fang/G-7679-2016;
OI Reijo Pera, Renee/0000-0002-6487-1329
NR 26
TC 3
Z9 3
U1 1
U2 14
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 FEB 4
PY 2016
VL 6
AR 20270
DI 10.1038/srep20270
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC5OT
UT WOS:000369271000001
PM 26842779
ER
PT J
AU Torres, OV
O'Dell, LE
AF Torres, Oscar V.
O'Dell, Laura E.
TI Stress is a principal factor that promotes tobacco use in females
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE dependence; nicotine; sex differences; withdrawal; women
ID CORTICOTROPIN-RELEASING-FACTOR; ESTROGEN-RECEPTOR-ALPHA;
PITUITARY-ADRENAL AXIS; SINGLE-DOSE NICOTINE; SEX-DIFFERENCES;
GENDER-DIFFERENCES; SMOKING-CESSATION; CIGARETTE-SMOKING; HPA AXIS;
POSTTRAUMATIC-STRESS
AB Tobacco use is a major economic and health problem. It is particularly concerning that women consume more tobacco products, have a more difficult time quitting smoking, and are less likely to benefit from smoking cessation therapy than men. As a result, women are at higher risk of developing tobacco-related diseases. Clinical evidence suggests that women are more susceptible to anxiety disorders, and are more likely to smoke in order to cope with stress than men. During smoking abstinence, women experience more intense anxiety than men and report that the anxiety-reducing effects of smoking are the main reason for their continued tobacco use and relapse. Consistent with this, pre-clinical studies using rodent models suggest that females display more intense stress during nicotine withdrawal than males. This review posits that in women, stress is a principal factor that promotes the initiation of tobacco use and relapse behavior during abstinence. Studies are reviewed at both the clinical and pre-clinical levels to provide support for our hypothesis that stress plays a central role in promoting tobacco use vulnerability in females. The clinical implications of this work are also considered with regard to treatment approaches and the need for more research to help reduce health disparities produced by tobacco use in women. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Torres, Oscar V.] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[O'Dell, Laura E.] Univ Texas El Paso, Dept Psychol, El Paso, TX 79902 USA.
RP O'Dell, LE (reprint author), Univ Texas El Paso, Dept Psychol, 500 W Univ Ave, El Paso, TX 79968 USA.
EM lodell@utep.edu
FU National Institute on Drug Abuse [R01-DA021274, R24-DA029989,
R25-DA033613]; National Institute of Minority Health Disparities as part
of the UTEP Border Biomedical Research Center [G12MD007592]; Intramural
Research Program of the NIDA Scientific Director's Fellowship for
Diversity in Research (OVT)
FX The authors would like to thank Dr. Luis M. Carcoba, Joseph A. Pipkin
and Rodolfo J. Flores for their helpful comments in the preparation of
this review paper. The authors also appreciate the support that was
provided from The National Institute on Drug Abuse (R01-DA021274,
R24-DA029989 and R25-DA033613) and the National Institute of Minority
Health Disparities (G12MD007592) as part of the UTEP Border Biomedical
Research Center. This work was also partially supported by funds from
the Intramural Research Program of the NIDA Scientific Director's
Fellowship for Diversity in Research (OVT). The authors declare no
conflicts of interest.
NR 182
TC 3
Z9 3
U1 4
U2 46
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
EI 1878-4216
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD FEB 4
PY 2016
VL 65
DI 10.1016/j.pnpbp.2015.04.005
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY9EC
UT WOS:000366709200031
PM 25912856
ER
PT J
AU Li, YJ
Periwal, V
Cushman, SW
Stenkula, KG
AF Li, Yanjun
Periwal, Vipul
Cushman, Samuel W.
Stenkula, Karin G.
TI Adipose cell hypertrophy precedes the appearance of small adipocytes by
3days in C57BL/6 mouse upon changing to a high fat diet
SO ADIPOCYTE
LA English
DT Article
DE mathematical model; high fat diet; adipose cell distribution; fat mass;
cell growth
ID INSULIN-RESISTANCE; OBESITY; ADIPOGENESIS; TISSUE; TERM
AB Adipose tissue is the energy buffer in mammals. The cellularity of adipose tissue has a major role in determining the response of adipose tissue to insulin action. A reduction in the ability of adipose tissue to store ingested caloric excess can lead to dyslipidemia and lipotoxicity, impacting insulin action systemically. The dynamic response of adipose tissue to changes in diet is therefore a crucial aspect of metabolism, and has attracted attention in the context of the ongoing worldwide increase in overweight and obesity and resulting metabolic syndrome dysfunctions. We investigated in a mouse model if there is a specific delay between an increase in caloric intake and the recruitment of new adipocytes, and if there are other changes in adipose tissue dynamics concomitant with such a diet change. By developing a dynamic mathematical model, we found that there is a delay of 3days between the start of a high fat diet and the recruitment of new adipocytes, and that the rate of fat mass increase modulates lipid turnover and adipose cell hypertrophy.
C1 [Li, Yanjun; Periwal, Vipul] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Cushman, Samuel W.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Stenkula, Karin G.] Lund Univ, Dept Expt Med Sci, BMC C11, S-22184 Lund, Sweden.
RP Stenkula, KG (reprint author), Lund Univ, Dept Expt Med Sci, BMC C11, S-22184 Lund, Sweden.
EM karin.stenkula@med.lu.se
NR 17
TC 1
Z9 1
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2162-3945
EI 2162-397X
J9 ADIPOCYTE
JI Adipocyte
PD FEB 3
PY 2016
VL 5
IS 1
BP 81
EP 87
DI 10.1080/21623945.2015.1128588
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DJ0GE
UT WOS:000373879000009
PM 27144099
ER
PT J
AU Konig, IR
Auerbach, J
Gola, D
Held, E
Holzinger, ER
Legault, MA
Sun, R
Tintle, N
Yang, HC
AF Koenig, Inke R.
Auerbach, Jonathan
Gola, Damian
Held, Elizabeth
Holzinger, Emily R.
Legault, Marc-Andre
Sun, Rui
Tintle, Nathan
Yang, Hsin-Chou
TI Machine learning and data mining in complex genomic data-a review on the
lessons learned in Genetic Analysis Workshop 19
SO BMC GENETICS
LA English
DT Article; Proceedings Paper
CT 19th Genetic Analysis Workshop (GAW)
CY AUG 24-27, 2014
CL Vienna, AUSTRIA
ID RANDOM FORESTS; PROBABILITY ESTIMATION; ASSOCIATION; PREDICTION;
DISEASES; SUCCESS; TREES
AB In the analysis of current genomic data, application of machine learning and data mining techniques has become more attractive given the rising complexity of the projects. As part of the Genetic Analysis Workshop 19, approaches from this domain were explored, mostly motivated from two starting points. First, assuming an underlying structure in the genomic data, data mining might identify this and thus improve downstream association analyses. Second, computational methods for machine learning need to be developed further to efficiently deal with the current wealth of data. In the course of discussing results and experiences from the machine learning and data mining approaches, six common messages were extracted. These depict the current state of these approaches in the application to complex genomic data. Although some challenges remain for future studies, important forward steps were taken in the integration of different data types and the evaluation of the evidence. Mining the data for underlying genetic or phenotypic structure and using this information in subsequent analyses proved to be extremely helpful and is likely to become of even greater use with more complex data sets.
C1 [Koenig, Inke R.; Gola, Damian] Med Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, D-23538 Lubeck, Germany.
[Auerbach, Jonathan] Columbia Univ, Dept Stat, New York, NY 10027 USA.
[Held, Elizabeth] Iowa State Univ, Dept Math, Ames, IA 50011 USA.
[Holzinger, Emily R.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD 21224 USA.
[Legault, Marc-Andre] Univ Montreal, Fac Med, 2900 Chemin Tour, Montreal, PQ H3T 1N8, Canada.
[Sun, Rui] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Div Biostat, Shatin, Hong Kong, Peoples R China.
[Tintle, Nathan] Dordt Coll, Dept Math Stat & Comp Sci, Sioux Ctr, IA 51250 USA.
[Yang, Hsin-Chou] Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan.
RP Konig, IR (reprint author), Med Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, D-23538 Lubeck, Germany.
EM inke.koenig@imbs.uni-luebeck.de
RI Konig, Inke/A-4544-2009
FU NHGRI NIH HHS [R15HG006915, R15 HG006915]; NIGMS NIH HHS [NIH
R01GM031575, R01 GM031575]
NR 40
TC 0
Z9 0
U1 7
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD FEB 3
PY 2016
VL 17
SU 2
AR 1
DI 10.1186/s12863-015-0315-8
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DD3IE
UT WOS:000369814600006
PM 26866367
ER
PT J
AU Amdur, RL
Mukherjee, M
Go, A
Barrows, IR
Ramezani, A
Shoji, J
Reilly, MP
Gnanaraj, J
Deo, R
Roas, S
Keane, M
Master, S
Teal, V
Soliman, EZ
Yang, P
Feldman, H
Kusek, JW
Tracy, CM
Raj, DS
AF Amdur, Richard L.
Mukherjee, Monica
Go, Alan
Barrows, Ian R.
Ramezani, Ali
Shoji, Jun
Reilly, Muredach P.
Gnanaraj, Joseph
Deo, Raj
Roas, Sylvia
Keane, Martin
Master, Steve
Teal, Valerie
Soliman, Elsayed Z.
Yang, Peter
Feldman, Harold
Kusek, John W.
Tracy, Cynthia M.
Raj, Dominic S.
CA CRIC Study Investigators
TI Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney
Disease: Findings from the CRIC Study
SO PLOS ONE
LA English
DT Article
ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; STAGE RENAL-DISEASE;
HEMODIALYSIS-PATIENTS; ELEVATED INTERLEUKIN-6; PLASMA INTERLEUKIN-6;
OXIDATIVE STRESS; INFLAMMATION; MORTALITY; INDIVIDUALS
AB Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor-beta, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD.
C1 [Amdur, Richard L.] George Washington Univ, Med Fac Associates, Biostat Core, Washington, DC USA.
[Mukherjee, Monica] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Go, Alan] Kaiser Permanente, Div Res, Oakland, CA USA.
[Barrows, Ian R.] George Washington Univ, Sch Med, Washington, DC USA.
[Ramezani, Ali; Shoji, Jun; Raj, Dominic S.] George Washington Univ, Sch Med, Div Renal Dis & Hypertens, Washington, DC USA.
[Reilly, Muredach P.; Deo, Raj] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Gnanaraj, Joseph] Bridgeport Hosp, Bridgeport, CT USA.
[Roas, Sylvia] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Keane, Martin] Temple Heart & Vasc Ctr, Philadelphia, PA USA.
[Master, Steve] Univ Penn, Perelman Sch Med, Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Teal, Valerie; Yang, Peter; Feldman, Harold] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA.
[Tracy, Cynthia M.] George Washington Univ, Sch Med, Div Cardiol, Washington, DC USA.
RP Raj, DS (reprint author), George Washington Univ, Sch Med, Div Renal Dis & Hypertens, Washington, DC USA.
EM draj@mfa.gwu.edu
FU National Institutes of Health [R01 DK073665-01A1, 1U01DK099914-01,
1U01DK099924-01]; National Institute of Diabetes and Digestive and
Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021,
U01DK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of
Medicine at the University of Pennsylvania Clinical and Translational
Science Award NIH/NCATS [UL1TR000003]; Johns Hopkins University [UL1
TR-000424]; University of Maryland GCRC [M01 RR-16500]; Clinical and
Translational Science Collaborative of Cleveland; National Center for
Advancing Translational Sciences (NCATS), National Institutes of Health
[UL1TR000439]; NIH roadmap for Medical Research; Michigan Institute for
Clinical and Health Research (MICHR) [UL1TR000433]; University of
Illinois at Chicago CTSA [UL1RR029879]; Tulane University Translational
Research in Hypertension and Renal Biology [P30GM103337]; Kaiser
Permanente NIH/NCRR UCSF-CTSI [UL1 RR-024131]
FX Dr. Dominic S. Raj is supported by R01 DK073665-01A1, 1U01DK099914-01
and 1U01DK099924-01 from the National Institutes of Health. Funding for
the CRIC Study was obtained under a cooperative agreement from National
Institute of Diabetes and Digestive and Kidney Diseases (U01DK060990,
U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980,
U01DK060963, and U01DK060902). In addition, this work was supported in
part by: the Perelman School of Medicine at the University of
Pennsylvania Clinical and Translational Science Award NIH/NCATS
UL1TR000003, Johns Hopkins University UL1 TR-000424, University of
Maryland GCRC M01 RR-16500, Clinical and Translational Science
Collaborative of Cleveland, UL1TR000439 from the National Center for
Advancing Translational Sciences (NCATS) component of the National
Institutes of Health and NIH roadmap for Medical Research, Michigan
Institute for Clinical and Health Research (MICHR) UL1TR000433,
University of Illinois at Chicago CTSA UL1RR029879, Tulane University
Translational Research in Hypertension and Renal Biology P30GM103337,
Kaiser Permanente NIH/NCRR UCSF-CTSI UL1 RR-024131.
NR 52
TC 3
Z9 3
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 FEB 3
PY 2016
VL 11
IS 2
AR e0148189
DI 10.1371/journal.pone.0148189
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC9OF
UT WOS:000369550200095
PM 26840403
ER
PT J
AU Liu, CH
Ren, J
Liu, PK
AF Liu, Christina H.
Ren, Jiaqian
Liu, Philip K.
TI Amphetamine manipulates monoamine oxidase-A level and behavior using
theranostic aptamers of transcription factors AP-1/NF-kB
SO JOURNAL OF BIOMEDICAL SCIENCE
LA English
DT Article
DE Acute stress; Addiction; Bipolar; Oxidative stress; Parkinson dementia;
Protein-targeted delivery; Theranostics
ID MAJOR DEPRESSIVE DISORDER; TRANSGENIC RATS EVIDENCE; GENE PROMOTER;
MAO-A; DECOY OLIGODEOXYNUCLEOTIDES; FUNCTIONAL POLYMORPHISM; PANIC
DISORDER; POINT MUTATION; LIVING BRAINS; ACUTE STRESS
AB Background: Monoamine oxidase (MAO) enzymes play a critical role in controlling the catabolism of monoamine neurotransmitters and biogenic trace amines and behavior in humans. However, the mechanisms that regulate MAO are unclear. Several transcription factor proteins are proposed to modulate the transcription of MAO gene, but evidence supporting these hypotheses is controversial. We aimed to investigate the mechanism of gene transcription regulator proteins on amphetamine-induced behavior. We applied aptamers containing a DNA binding sequence, as well as a random sequence (without target) to study the modulation of amphetamine-induced MAO levels and hyperactivity in living mice.
Methods: We pretreated in adult male C57black6 mice (Taconic Farm, Germantown, NY) (n >= 3 litters at a time), 2 to 3 months of age (23 +/- 2 gm body weight) with double-stranded (ds) DNA aptamers with sequence specific to activator protein-1 (5ECdsAP1), nuclear factor-kappa beta (5ECdsNF-kB), special protein-1 (5ECdsSP-1) or cyclicAMP responsive element binding (5ECdsCreB) protein binding regions, 5ECdsRan [a random sequence without target], single-stranded AP-1 (5ECssAP-1) (8 nmol DNA per kg) or saline (5 mu l, intracerebroventricular [icv] injection) control before amphetamine administration (4 mg/kg, i.p.). We then measured and analyzed locomotor activities and the level of MAO-A and MAO-B activity.
Results: In the pathological condition of amphetamine exposure, we showed here that pretreatment with 5ECdsAP1 and 5ECdsNF-kB reversed the decrease of MAO-A activity (p < 0.05, t test), but not activity of the B isomer (MAO-B), in the ventral tegmental area (VTA) and substantia nigra (SN) of C57black6 mice. The change in MAO-A level coincided with a reversed amphetamine-induced restless behavior of mice. Pretreatments with saline, 5ECdsCreB, 5ECdsSP-1, 5ECdsRan or 5ECssAP-1 had no effect.
Conclusion: Our data lead us to conclude that elevation of AP-1 or NF-kB indirectly decreases MAO-A protein levels which, in turn, diminishes MAO-A ability in the VTA of the mesolimbic dopaminergic pathway that has been implicated in cells under stress especially in the SN and VTA. This study has implications for design for the treatment of drug exposure and perhaps Parkinson's dementia.
C1 [Liu, Christina H.; Ren, Jiaqian; Liu, Philip K.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Liu, Christina H.] NIH, 6707 Democracy Blvd,Suite 200, Bethesda, MD 20892 USA.
RP Liu, PK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM Philip.Liu@mgh.harvard.edu
OI Liu, Philip K./0000-0003-2149-3564
FU [R01DA029889]; [R01EB013768]; [NS045776]
FX We thank Drs. M. Schwartzchild for allowing us to use the locomotion
detection device and Charng-Ming Liu for modified aptamer ds-sODN. We
also thank Ms. N. Eusemann for assistance with editing the manuscript.
This project was supported by research grants R01DA029889 and
R01EB013768 to PKL, NS045776 to the MGH Neuroscience Center.
NR 45
TC 1
Z9 1
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1021-7770
EI 1423-0127
J9 J BIOMED SCI
JI J. Biomed. Sci.
PD FEB 3
PY 2016
VL 23
AR 21
DI 10.1186/s12929-016-0239-2
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DC8WN
UT WOS:000369500700001
PM 26841904
ER
PT J
AU Leet, AI
Boyce, AM
Ibrahim, KA
Wientroub, S
Kushner, H
Collins, MT
AF Leet, Arabella I.
Boyce, Alison M.
Ibrahim, Khalda A.
Wientroub, Shlomo
Kushner, Harvey
Collins, Michael T.
TI Bone-Grafting in Polyostotic Fibrous Dysplasia
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY G-PROTEIN; PROXIMAL FEMUR;
NATURAL-HISTORY; STEM-CELLS; CHILDREN; MUTATION
AB Background: Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time.
Methods: The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty-nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival.
Results: Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years).
Conclusions: Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention.
C1 [Leet, Arabella I.; Boyce, Alison M.; Ibrahim, Khalda A.; Wientroub, Shlomo; Kushner, Harvey; Collins, Michael T.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Boyce, Alison M.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Boyce, Alison M.] Childrens Natl Hlth Syst, Div Endocrinol & Diabet, Washington, DC USA.
[Boyce, Alison M.] Childrens Natl Hlth Syst, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC USA.
[Ibrahim, Khalda A.] Johns Hopkins Univ, Dept Orthoped, Baltimore, MD USA.
[Wientroub, Shlomo] Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Pediat Orthoped,Dana Childrens Hosp, IL-69978 Tel Aviv, Israel.
[Kushner, Harvey] Biomed Comp Res Inst, Philadelphia, PA USA.
RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
EM mcollins@mail.nih.gov
FU Division of Intramural Research, National Institute of Dental and
Craniofacial Research, National Institutes of Health; Bone Health
Program, Division of Orthopaedics and Sports Medicine, Children's
National Health System; Fibrous Dysplasia Foundation
FX This work was supported by internal funding from the Division of
Intramural Research, National Institute of Dental and Craniofacial
Research, National Institutes of Health (A.M.B. and M.T.C.), the Bone
Health Program, Division of Orthopaedics and Sports Medicine, Children's
National Health System (A.M.B.). The work was also supported by a grant
from the Fibrous Dysplasia Foundation awarded to one author (A.I.L.).
Funds were used to provide salary support to one of the authors
(K.A.I.).
NR 31
TC 4
Z9 4
U1 0
U2 2
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
EI 1535-1386
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD FEB 3
PY 2016
VL 98A
IS 3
BP 211
EP 219
DI 10.2106/JBJS.0.00547
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA DC4EK
UT WOS:000369173000009
PM 26842411
ER
PT J
AU Maerkens, A
Olive, M
Schreiner, A
Feldkirchner, S
Schessl, J
Uszkoreit, J
Barkovits, K
Guttsches, AK
Theis, V
Eisenacher, M
Tegenthoff, M
Goldfarb, LG
Schroder, R
Schoser, B
van der Ven, PFM
Furst, DO
Vorgerd, M
Marcus, K
Kley, RA
AF Maerkens, A.
Olive, M.
Schreiner, A.
Feldkirchner, S.
Schessl, J.
Uszkoreit, J.
Barkovits, K.
Guettsches, A. K.
Theis, V.
Eisenacher, M.
Tegenthoff, M.
Goldfarb, L. G.
Schroeder, R.
Schoser, B.
van der Ven, P. F. M.
Fuerst, D. O.
Vorgerd, M.
Marcus, K.
Kley, R. A.
TI New insights into the protein aggregation pathology in myotilinopathy by
combined proteomic and immunolocalization analyses
SO ACTA NEUROPATHOLOGICA COMMUNICATIONS
LA English
DT Article
DE Myotilinopathy; Myofibrillar myopathy; Protein aggregation; Laser
microdissection; Mass spectrometry; Immunolocalization study
ID ALPHA-B-CRYSTALLIN; GIRDLE MUSCULAR-DYSTROPHY; LINKS ACTIN-FILAMENTS;
MYOFIBRILLAR MYOPATHY; SKELETAL-MUSCLE; HEAT-SHOCK; SARCOMERIC PROTEIN;
DESMIN POSITIVITY; FILAMIN; BINDING
AB Introduction: Myofibrillar myopathies are characterized by progressive muscle weakness and impressive abnormal protein aggregation in muscle fibers. In about 10 % of patients, the disease is caused by mutations in the MYOT gene encoding myotilin. The aim of our study was to decipher the composition of protein deposits in myotilinopathy to get new information about aggregate pathology.
Results: Skeletal muscle samples from 15 myotilinopathy patients were included in the study. Aggregate and control samples were collected from muscle sections by laser microdissection and subsequently analyzed by a highly sensitive proteomic approach that enables a relative protein quantification. In total 1002 different proteins were detected. Seventy-six proteins showed a significant over-representation in aggregate samples including 66 newly identified aggregate proteins. Z-disc-associated proteins were the most abundant aggregate components, followed by sarcolemmal and extracellular matrix proteins, proteins involved in protein quality control and degradation, and proteins with a function in actin dynamics or cytoskeletal transport. Forty over-represented proteins were evaluated by immunolocalization studies. These analyses validated our mass spectrometric data and revealed different regions of protein accumulation in abnormal muscle fibers. Comparison of data from our proteomic analysis in myotilinopathy with findings in other myofibrillar myopathy subtypes indicates a characteristic basic pattern of aggregate composition and resulted in identification of a highly sensitive and specific diagnostic marker for myotilinopathy.
Conclusions: Our findings i) indicate that main protein components of aggregates belong to a network of interacting proteins, ii) provide new insights into the complex regulation of protein degradation in myotilinopathy that may be relevant for new treatment strategies, iii) imply a combination of a toxic gain-of-function leading to myotilin-positive protein aggregates and a loss-of-function caused by a shift in subcellular distribution with a deficiency of myotilin at Z-discs that impairs the integrity of myofibrils, and iv) demonstrate that proteomic analysis can be helpful in differential diagnosis of protein aggregate myopathies.
C1 [Maerkens, A.; Schreiner, A.; Guettsches, A. K.; Tegenthoff, M.; Vorgerd, M.; Kley, R. A.] Ruhr Univ Bochum, Univ Hosp Bergmannsheil, Heimer Inst Muscle Res, Dept Neurol, Buerkle de la Camp Pl 1, D-44789 Bochum, Germany.
[Maerkens, A.; Uszkoreit, J.; Barkovits, K.; Theis, V.; Eisenacher, M.; Marcus, K.] Ruhr Univ Bochum, Med Proteom Ctr, D-44801 Bochum, Germany.
[Olive, M.] Hosp Univ Bellvitge, IDIBELL, Dept Pathol, Inst Neuropathol, Barcelona, Spain.
[Olive, M.] Hosp Univ Bellvitge, IDIBELL, Neuromuscular Unit, Inst Neuropathol, Barcelona, Spain.
[Olive, M.] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain.
[Feldkirchner, S.; Schessl, J.; Schoser, B.] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80336 Munich, Germany.
[Theis, V.] Ruhr Univ Bochum, Inst Anat, Dept Cytol, D-44801 Bochum, Germany.
[Goldfarb, L. G.] NIH, Clin Neurogenet, MSC 9404, Bethesda, MD USA.
[Schroeder, R.] Univ Hosp Erlangen, Inst Neuropathol, D-91054 Erlangen, Germany.
[van der Ven, P. F. M.; Fuerst, D. O.] Univ Bonn, Inst Cell Biol, D-53121 Bonn, Germany.
RP Kley, RA (reprint author), Ruhr Univ Bochum, Univ Hosp Bergmannsheil, Heimer Inst Muscle Res, Dept Neurol, Buerkle de la Camp Pl 1, D-44789 Bochum, Germany.
EM rudolf.kley@rub.de
RI Eisenacher, Martin/J-8044-2014; Schroder, Rolf/B-2774-2011;
OI Eisenacher, Martin/0000-0003-2687-7444; Olive,
Montse/0000-0001-5727-0165; Uszkoreit, Julian/0000-0001-7522-4007;
Schoser, Benedikt/0000-0002-2757-8131
NR 65
TC 7
Z9 7
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-5960
J9 ACTA NEUROPATHOL COM
JI Acta Neuropathol. Commun.
PD FEB 3
PY 2016
VL 4
AR 8
DI 10.1186/s40478-016-0280-0
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA DC4YD
UT WOS:000369225400001
PM 26842778
ER
PT J
AU LeBlanc, AK
Breen, M
Choyke, P
Dewhirst, M
Fan, TM
Gustafson, DL
Helman, LJ
Kastan, MB
Knapp, DW
Levin, WJ
London, C
Mason, N
Mazcko, C
Olson, PN
Page, R
Teicher, BA
Thamm, DH
Trent, JM
Vail, DM
Khanna, C
AF LeBlanc, Amy K.
Breen, Matthew
Choyke, Peter
Dewhirst, Mark
Fan, Timothy M.
Gustafson, Daniel L.
Helman, Lee J.
Kastan, Michael B.
Knapp, Deborah W.
Levin, Wendy J.
London, Cheryl
Mason, Nicola
Mazcko, Christina
Olson, Patricia N.
Page, Rodney
Teicher, Beverly A.
Thamm, Douglas H.
Trent, Jeffrey M.
Vail, David M.
Khanna, Chand
TI Perspectives from man's best friend: National Academy of Medicine's
Workshop on Comparative Oncology
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CANCER
C1 [LeBlanc, Amy K.; Choyke, Peter; Helman, Lee J.; Mazcko, Christina; Khanna, Chand] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Breen, Matthew] N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27607 USA.
[Dewhirst, Mark] Duke Univ, Sch Med, Durham, NC 27710 USA.
[Dewhirst, Mark; Kastan, Michael B.] Duke Canc Inst, Durham, NC 27710 USA.
[Fan, Timothy M.] Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA.
[Gustafson, Daniel L.; Page, Rodney; Thamm, Douglas H.] Colorado State Univ, Coll Vet Med & Biomed Sci, Flint Anim Canc Ctr, Ft Collins, CO 80523 USA.
[Knapp, Deborah W.] Purdue Univ, Dept Vet Clin Sci, W Lafayette, IN 47907 USA.
[Levin, Wendy J.] Fate Therapeut Inc, San Diego, CA 92121 USA.
[London, Cheryl; Mason, Nicola] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA.
[Olson, Patricia N.] Olson Consulting Anim Hlth & Welf, Ft Collins, CO 80528 USA.
[Teicher, Beverly A.] NCI, Div Canc Treatment & Diag, Mol Pharmacol Branch, Bethesda, MD 20892 USA.
[Trent, Jeffrey M.] Translat Genom Res Inst TGen, Phoenix, AZ 85004 USA.
[Vail, David M.] Univ Wisconsin, Sch Vet Med, Dept Med Sci, Madison, WI 53706 USA.
[Khanna, Chand] Ethos Discovery, Washington, DC 20009 USA.
[Khanna, Chand] Ethos Vet Hlth, Burlington, MA 01803 USA.
RP LeBlanc, AK (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM amy.leblanc@nih.gov
RI London, Cheryl/E-6561-2012; Thamm, Douglas/I-5976-2013
OI Thamm, Douglas/0000-0002-8914-7767
FU U.S. National Institutes of Health (NIH), NCI, Center for Cancer
Research
FX This research was supported in part by the Intramural Research Program
of the U.S. National Institutes of Health (NIH), NCI, Center for Cancer
Research. The results and interpretations do not reflect the views of
the US government.
NR 10
TC 3
Z9 3
U1 2
U2 7
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD FEB 3
PY 2016
VL 8
IS 324
AR 324ps5
DI 10.1126/scitranslmed.aaf0746
PG 4
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DC4CC
UT WOS:000369166600002
PM 26843188
ER
PT J
AU Minor, W
Dauter, Z
Helliwell, JR
Jaskolski, M
Wlodawer, A
AF Minor, Wladek
Dauter, Zbigniew
Helliwell, John R.
Jaskolski, Mariusz
Wlodawer, Alexander
TI Safeguarding Structural Data Repositories against Bad Apples
SO STRUCTURE
LA English
DT Article
ID PROTEIN STRUCTURES; CAUTIONARY-TALE; ALWAYS-GO; CRYSTALLOGRAPHY;
CARBOPLATIN; VALIDATION; CISPLATIN; CHEMISTRY
AB Structural biology research generates large amounts of data, some deposited in public databases or repositories, but a substantial remainder never becomes available to the scientific community. In addition, some of the deposited data contain less or more serious errors that may bias the results of data mining. Thorough analysis and discussion of these problems is needed to ameliorate this situation. This perspective is an attempt to propose some solutions and encourage both further discussion and action on the part of the relevant organizations, in particular the PDB and various bodies of the International Union of Crystallography.
C1 [Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
[Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA.
[Helliwell, John R.] Univ Manchester, Sch Chem, Manchester M13 9PL, Lancs, England.
[Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, PL-60780 Poznan, Poland.
[Jaskolski, Mariusz] Adam Mickiewicz Univ, Fac Chem, Dept Crystallog, PL-60780 Poznan, Poland.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
EM wladek@iwonka.med.virginia.edu
OI Minor, Wladek/0000-0001-7075-7090
FU NIH
FX W.M. is a co-founder and stockholder of HKL Research Inc., a company
that distributes various structural biology software. W.M. is a
recipient of NIH grants for work mentioned herein. All authors presented
their individual views at various international and national meetings,
workshops, and schools, and some of their travel expenses were paid by
organizers.
NR 21
TC 6
Z9 6
U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD FEB 2
PY 2016
VL 24
IS 2
BP 216
EP 220
DI 10.1016/j.str.2015.12.010
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI5VD
UT WOS:000373567700002
PM 26840827
ER
PT J
AU Jeong, H
Kim, JS
Song, S
Shigematsu, H
Yokoyama, T
Hyun, J
Ha, NC
AF Jeong, Hyeongseop
Kim, Jin-Sik
Song, Saemee
Shigematsu, Hideki
Yokoyama, Takeshi
Hyun, Jaekyung
Ha, Nam-Chul
TI Pseudoatomic Structure of the Tripartite Multidrug Efflux Pump
AcrAB-TolC Reveals the Intermeshing Cogwheel-like Interaction between
AcrA and TolC
SO STRUCTURE
LA English
DT Article
ID EM STRUCTURE DETERMINATION; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI;
ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; MEMBRANE PROTEIN; TIP REGION;
HAIRPIN; GENES; MODEL
AB The resistance-nodulation-division type tripartite pump AcrAB-TolC and its homologs are responsible for multidrug resistance in Gram-negative bacteria by expelling a wide variety of toxic substrates. The three essential components, AcrA, AcrB, and TolC, must function in concert with each respective binding partner within the complex. In this study, we report an 8.2-angstrom resolution cryo-electron microscopy (cryo-EM) 3D reconstruction of the complex that consists of an AcrAB fusion protein and a chimeric TolC protein. The pseudoatomic structure derived from the cryo-EM reconstruction clearly demonstrates a model only compatible with the adaptor bridging mechanism, wherein the funnel-like AcrA hexamer forms an intermeshing cogwheel-like interaction with the alpha-barrel tip region of TolC. These observations provide a structural milestone for understanding multidrug resistance in pathogenic Gram-negative bacteria, and may also lead to the design of new antibacterial drugs.
C1 [Jeong, Hyeongseop; Hyun, Jaekyung] Korea Basic Sci Inst, Nanobio Electron Microscopy Res Team, Daejeon 305806, South Korea.
[Kim, Jin-Sik; Song, Saemee; Ha, Nam-Chul] Seoul Natl Univ, Res Inst Agr & Life Sci, Ctr Food Safety & Toxicol, Dept Agr Biotechnol,Ctr Food & Bioconvergence, Seoul 151921, South Korea.
[Shigematsu, Hideki; Yokoyama, Takeshi] RIKEN, Ctr Life Sci Technol, Div Struct & Synthet Biol, Yokohama, Kanagawa 2300045, Japan.
[Kim, Jin-Sik] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Hyun, J (reprint author), Korea Basic Sci Inst, Nanobio Electron Microscopy Res Team, Daejeon 305806, South Korea.; Ha, NC (reprint author), Seoul Natl Univ, Res Inst Agr & Life Sci, Ctr Food Safety & Toxicol, Dept Agr Biotechnol,Ctr Food & Bioconvergence, Seoul 151921, South Korea.
EM hjk002@kbsi.re.kr; hanc210@snu.ac.kr
RI Shigematsu, Hideki/E-1052-2017
OI Shigematsu, Hideki/0000-0003-3951-8651
FU Ministry of Science, ITC, and Future Planning, Republic of Korea
[NRF-2014R1A2A1A11050283]; Korea Basic Science Institute [T35518]; JSPS
KAKENHI [15H01656]
FX This study was supported by the Ministry of Science, ITC, and Future
Planning, Republic of Korea (NRF-2014R1A2A1A11050283), Korea Basic
Science Institute (Grant T35518), and in part by JSPS KAKENHI (No.
15H01656). Cryo-EM data collection was carried out at the RIKEN Center
for Life Science Technologies.
NR 24
TC 3
Z9 3
U1 2
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD FEB 2
PY 2016
VL 24
IS 2
BP 272
EP 276
DI 10.1016/j.str.2015.12.007
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DI5VD
UT WOS:000373567700008
PM 26777412
ER
PT J
AU Kalaora, S
Barnea, E
Merhavi-Shoham, E
Qutob, N
Teer, JK
Shimony, N
Schachter, J
Rosenberg, SA
Besser, MJ
Admon, A
Samuels, Y
AF Kalaora, Shelly
Barnea, Eilon
Merhavi-Shoham, Efrat
Qutob, Nouar
Teer, Jamie K.
Shimony, Nilly
Schachter, Jacob
Rosenberg, Steven A.
Besser, Michal J.
Admon, Arie
Samuels, Yardena
TI Use of HLA peptidomics and whole exome sequencing to identify human
immunogenic neo-antigens
SO ONCOTARGET
LA English
DT Article
DE HLA; TILs
ID T-CELLS; TUMOR; MELANOMA; CANCER; IMMUNOTHERAPY; LYMPHOCYTES;
NEOANTIGENS; PROTEOMICS; PATIENT; PROTEIN
AB The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.
C1 [Kalaora, Shelly; Qutob, Nouar; Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Barnea, Eilon; Admon, Arie] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Merhavi-Shoham, Efrat; Shimony, Nilly; Schachter, Jacob; Besser, Michal J.] Chaim Sheba Med Ctr, Ella Lemelbaum Inst Melanoma, IL-52621 Tel Hashomer, Israel.
[Teer, Jamie K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Biostat & Bioinformat, Tampa, FL 33682 USA.
[Teer, Jamie K.] Res Inst, Tampa, FL USA.
[Rosenberg, Steven A.] NIH, Natl Canc Inst, Bethesda, MD USA.
[Besser, Michal J.] Tel Aviv Univ, Sackler Sch Med, Dept Clin Microbiol & Immunol, IL-69978 Tel Aviv, Israel.
RP Samuels, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM Yardena.Samuels@weizmann.ac.il
FU Intramural Research Programs of National Cancer Institute; Israel
Science Foundation [1604/13, 877/13]; ERC [StG-335377]; 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; Hamburger Family; Greta Koppel SCLC fund
FX We thank the Genomics and Bioinformatic units at the Israel National
Center for Personalized Medicine (INCPM) for help with sample
preparation, sequencing and analyzing the data, as well as Dr. Isadora
Cohen and Dr. Alona Keren-Paz for critical reading and editing of the
manuscript. This work was supported by the Intramural Research Programs
of the National Cancer Institute. Y.S. is supported by the Israel
Science Foundation grant numbers 1604/13 and 877/13, the ERC
(StG-335377), 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 and
the Hamburger Family. E.M., N.S., J.S. and M.J.B. are supported by Haya
and Nehemia Lemelbaum. A.A. is supported by The Greta Koppel SCLC fund.
NR 21
TC 10
Z9 10
U1 0
U2 9
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 2
PY 2016
VL 7
IS 5
BP 5110
EP 5117
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD5HD
UT WOS:000369952800003
PM 26819371
ER
PT J
AU Iyer, SV
Parrales, A
Begani, P
Narkar, A
Adhikari, AS
Martinez, LA
Iwakuma, T
AF Iyer, Swathi V.
Parrales, Alejandro
Begani, Priya
Narkar, Akshay
Adhikari, Amit S.
Martinez, Luis A.
Iwakuma, Tomoo
TI Allele-specific silencing of mutant p53 attenuates dominant-negative and
gain-of-function activities
SO ONCOTARGET
LA English
DT Article
DE mutant p53; allele-specific siRNA silencing; gain of function; oncogene
addiction; dominant negative
ID LI-FRAUMENI-SYNDROME; BREAST-CANCER CELLS; GENE-EXPRESSION; ONCOGENE
ADDICTION; RNA INTERFERENCE; HER2/NEU GENE; CYCLE ARREST; SIRNA;
THERAPY; RESISTANCE
AB Many p53 hotspot mutants not only lose the transcriptional activity, but also show dominant-negative (DN) and oncogenic gain-of-function (GOF) activities. Increasing evidence indicates that knockdown of mutant p53 (mutp53) in cancer cells reduces their aggressive properties, suggesting that survival and proliferation of cancer cells are, at least partially, dependent on the presence of mutp53. However, these p53 siRNAs can downregulate both wild-type p53 (wtp53) and mutp53, which limits their therapeutic applications. In order to specifically deplete mutp53, we have developed allele-specific siRNAs against p53 hotspot mutants and validated their biological effects in the absence or presence of wtp53. First, the mutp53-specific siRNAs selectively reduced protein levels of matched p53 mutants with minimal reduction in wtp53 levels. Second, downregulation of mutp53 in cancer cells expressing a mutp53 alone (p53(mut)) resulted in significantly decreased cell proliferation and migration. Third, transfection of mutp53-specific siRNAs in cancer cells expressing both wtp53 and mutp53 also reduced cell proliferation and migration with increased transcripts of p53 downstream target genes, which became further profound when cells were treated with an MDM2 inhibitor Nutlin-3a or a chemotherapeutic agent doxorubicin. These results indicate that depletion of mutp53 by its specific siRNA restored endogenous wtp53 activity in cells expressing both wtp53 and mutp53. This is the first study demonstrating biological effects and therapeutic potential of allele-specific silencing of mutp53 by mutp53-specific siRNAs in cancer cells expressing both wtp53 and mutp53, thus providing a novel strategy towards targeted cancer therapies.
C1 [Iyer, Swathi V.; Parrales, Alejandro; Begani, Priya; Narkar, Akshay; Iwakuma, Tomoo] Univ Kansas, Med Ctr, Univ Kansas Canc Ctr, Dept Canc Biol, Kansas City, KS 66103 USA.
[Adhikari, Amit S.] NCI, Ctr Canc Res, Ctr Adv Preclin Res, Frederick, MD 21701 USA.
[Martinez, Luis A.] Stony Brook Sch Med, Dept Pathol, Stony Brook, NY USA.
RP Iwakuma, T (reprint author), Univ Kansas, Med Ctr, Univ Kansas Canc Ctr, Dept Canc Biol, Kansas City, KS 66103 USA.
EM tiwakuma@kumc.edu
FU NIH [1-R01-CA174735-01A1, P30-GM103495, P30-CA168524]
FX This project is supported by NIH 1-R01-CA174735-01A1 (T.I.),
P30-GM103495 (B.T.), and P30-CA168524 (R.A.J.) grants.
NR 56
TC 1
Z9 1
U1 0
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 2
PY 2016
VL 7
IS 5
BP 5401
EP 5415
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD5HD
UT WOS:000369952800023
PM 26700961
ER
PT J
AU Luo, F
Sun, BF
Li, HQ
Xu, Y
Liu, Y
Liu, XL
Lu, L
Li, J
Wang, QL
Wei, SF
Shi, L
Lu, XL
Liu, QZ
Zhang, AH
AF Luo, Fei
Sun, Baofei
Li, Huiqiao
Xu, Yuan
Liu, Yi
Liu, Xinlu
Lu, Lu
Li, Jun
Wang, Qingling
Wei, Shaofeng
Shi, Le
Lu, Xiaolin
Liu, Qizhan
Zhang, Aihua
TI A MALAT1/HIF-2a feedback loop contributes to arsenite carcinogenesis
SO ONCOTARGET
LA English
DT Article
DE IncRNAs; HIFs; arsenite; carcinogenesis
ID LONG NONCODING RNAS; MESSENGER-RNA; EPITHELIAL-CELLS; NEOPLASTIC
TRANSFORMATION; MALIGNANT-TRANSFORMATION; HEPATOCELLULAR-CARCINOMA;
DIFFERENTIAL EXPRESSION; FACTOR-I; HYPOXIA; CANCER
AB Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is also not known if IncRNAs are involved in arsenic-induced liver carcinogenesis. We have found that MALAT1, a non-coding RNA, is over-expressed in the sera of people exposed to arsenite and in hepatocellular carcinomas (HCCs), and MALAT1 has a close relation with the clinicopathological characteristics of HCC. In addition, hypoxia-inducible factor (HIF)-2a is up-regulated in HCCs, and MALAT1 and HIF-2a have a positive correlation in HCC tissues. During the malignant transformation of human hepatic epithelial (L-02) cells induced by a low concentration (2.0 mu M) of arsenite, MALAT1 and HIF-2a are increased. In addition, arsenite-induced MALAT1 causes disassociation of the von Hippel-Lindau (VHL) protein from HIF-2a, therefore, alleviating VHL-mediated HIF-2a ubiquitination, which causes HIF-2a accumulation. In turn, HIF-2a transcriptionally regulates MALAT1, thus forming a positive feedback loop to ensure expression of arsenite-induced MALAT1 and HIF-2a, which are involved in malignant transformation. Moreover, MALAT1 and HIF-2a promote the invasive and metastatic capacities of arsenite-induced transformed L-02 cells and in HCC-LM3 cells. The capacities of MALAT1 and HIF-2a to promote tumor growth are validated in mouse xenograft models. In mice, arsenite induces an inflammatory response, and MALAT1 and HIF-2a are over-expressed. Together, these findings suggest that the MALAT1/HIF-2a feedback loop is involved in regulation of arsenite-induced malignant transformation. Our results not only confirm a novel mechanism involving reciprocal regulation between MALAT1 and HIF-2a, but also expand the understanding of the carcinogenic potential of arsenite.
C1 [Luo, Fei; Xu, Yuan; Liu, Yi; Liu, Xinlu; Lu, Lu; Shi, Le; Lu, Xiaolin; Liu, Qizhan] Nanjing Med Univ, Inst Toxicol, Sch Publ Hlth, Nanjing 211166, Jiangsu, Peoples R China.
[Luo, Fei; Xu, Yuan; Liu, Yi; Liu, Xinlu; Lu, Lu; Shi, Le; Lu, Xiaolin; Liu, Qizhan] Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China.
[Sun, Baofei; Li, Jun; Wang, Qingling; Wei, Shaofeng; Zhang, Aihua] Guiyang Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Environm Pollut Monitoring & Dis Control, Guiyang 550025, Guizhou, Peoples R China.
[Li, Huiqiao] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing 211166, Jiangsu, Peoples R China.
[Xu, Yuan] NCI, Thorac & GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Liu, QZ (reprint author), Nanjing Med Univ, Inst Toxicol, Sch Publ Hlth, Nanjing 211166, Jiangsu, Peoples R China.; Liu, QZ (reprint author), Nanjing Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Modern Toxicol, Nanjing 211166, Jiangsu, Peoples R China.; Zhang, AH (reprint author), Guiyang Med Univ, Sch Publ Hlth, Minist Educ, Key Lab Environm Pollut Monitoring & Dis Control, Guiyang 550025, Guizhou, Peoples R China.
EM drqzliu@hotmail.com; aihuagzykd@163.com
FU Natural Science Foundations of China [81273114, 81430077, 81302467];
Postgraduate Innovation Project of Jiangsu province [CXZZ14_0421,
CXZZ14_0951, KYLX15_0974]; Priority Academic Program Development of
Jiangsu Higher Education Institutions
FX This work was supported by the Natural Science Foundations of China
(81273114, 81430077, 81302467), the Postgraduate Innovation Project of
Jiangsu province (CXZZ14_0421, CXZZ14_0951, and KYLX15_0974), and the
Priority Academic Program Development of Jiangsu Higher Education
Institutions (2010).
NR 58
TC 6
Z9 6
U1 2
U2 4
PU IMPACT JOURNALS LLC
PI ORCHARD PARK
PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD FEB 2
PY 2016
VL 7
IS 5
BP 5769
EP 5787
PG 19
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DD5HD
UT WOS:000369952800049
PM 26735578
ER
PT J
AU Santhanakrishnan, R
Wang, N
Larson, MG
Magnani, JW
McManus, DD
Lubitz, SA
Ellinor, PT
Cheng, S
Vasan, RS
Lee, DS
Wang, TJ
Levy, D
Benjamin, EJ
Ho, JE
AF Santhanakrishnan, Rajalakshmi
Wang, Na
Larson, Martin G.
Magnani, Jared W.
McManus, David D.
Lubitz, Steven A.
Ellinor, Patrick T.
Cheng, Susan
Vasan, Ramachandran S.
Lee, Douglas S.
Wang, Thomas J.
Levy, Daniel
Benjamin, Emelia J.
Ho, Jennifer E.
TI Atrial Fibrillation Begets Heart Failure and Vice Versa Temporal
Associations and Differences in Preserved Versus Reduced Ejection
Fraction
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; epidemiology; heart failure; mortality; ventricular
function; left
ID VENTRICULAR SYSTOLIC DYSFUNCTION; PROGNOSTIC-SIGNIFICANCE; RISK;
MORTALITY; PREVALENCE; DISEASE; STROKE; METAANALYSIS; COMMUNITY;
FIBROSIS
AB Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction.
Methods and Results We studied Framingham Heart Study participants with new-onset AF or HF between 1980 and 2012. Among 1737 individuals with new AF (mean age, 7512 years; 48% women), more than one third (37%) had HF. Conversely, among 1166 individuals with new HF (mean age, 79 +/- 11 years; 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HF with preserved ejection fraction (multivariable-adjusted hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.48-3.70; no AF as referent) versus HF with reduced ejection fraction (HR, 1.32; 95% CI, 0.83-2.10), with a trend toward difference between HF subtypes (P for difference=0.06). Prevalent HF was associated with incident AF (HR, 2.18; 95% CI, 1.26-3.76; no HF as referent). The presence of both AF and HF portended greater mortality risk compared with neither condition, particularly among individuals with new HF with reduced ejection fraction and prevalent AF (HR, 2.72; 95% CI, 2.12-3.48) compared with new HF with preserved ejection fraction and prevalent AF (HR, 1.83; 95% CI, 1.41-2.37; P for difference=0.02).
Conclusions AF occurs in more than half of individuals with HF, and HF occurs in more than one third of individuals with AF. AF precedes and follows HF with both preserved and reduced ejection fraction, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.
C1 [Santhanakrishnan, Rajalakshmi; Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA.
[Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.; Magnani, Jared W.; Cheng, Susan; Vasan, Ramachandran S.; Lee, Douglas S.; Benjamin, Emelia J.; Ho, Jennifer E.] NHLBI, Bethesda, MD USA.
[Larson, Martin G.; Magnani, Jared W.; Cheng, Susan; Vasan, Ramachandran S.; Benjamin, Emelia J.; Ho, Jennifer E.] Boston Univ, Framingham Heart Study, Boston, MA USA.
[McManus, David D.; Benjamin, Emelia J.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Boston, MA 02125 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.; Ho, Jennifer E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.; Ho, Jennifer E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard, Program Med Populat Genet, Cambridge, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] MIT, Cambridge, MA 02139 USA.
[Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol,Dept Med, Boston, MA USA.
[Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON M5S 1A1, Canada.
[Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5S 1A1, Canada.
[Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA.
[Levy, Daniel] NHLBI, Div Intramural Res, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA.
RP Ho, JE (reprint author), Massachusetts Gen Hosp, CPZN 185 Cambridge St,3224, Boston, MA 02114 USA.
EM jho1@mgh.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195, HHSN268201500001I]; National Institutes of Health
[K23-HL116780, 1R01HL128914, 2R01HL092577, 3R01HL092577-06S1]; Boston
University School of Medicine, Department of Medicine Career Investment
Award (Boston, MA); National Institutes of Health/National Heart, Lung
and Blood Institute [K23HL114724]; Doris Duke Charitable Foundation
Clinical Scientist Development Award [2014105]
FX This work was partially supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (contracts N01-HC-25195 and
HHSN268201500001I). This work was supported by the National Institutes
of Health (K23-HL116780 to Dr Ho, 1R01HL128914 to Dr Benjamin,
2R01HL092577 and 3R01HL092577-06S1 to Drs Benjamin and Ellinor). Dr Ho
is supported by a Boston University School of Medicine, Department of
Medicine Career Investment Award (Boston, MA). Dr Lubitz is supported by
National Institutes of Health/National Heart, Lung and Blood Institute
K23HL114724 and Doris Duke Charitable Foundation Clinical Scientist
Development Award 2014105.
NR 44
TC 18
Z9 19
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD FEB 2
PY 2016
VL 133
IS 5
BP 484
EP 492
DI 10.1161/CIRCULATIONAHA.115.018614
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DD1IB
UT WOS:000369673400006
PM 26746177
ER
PT J
AU Goldstein, O
Nayshool, O
Nefussy, B
Traynor, BJ
Renton, AE
Gana-Weisz, M
Drory, VE
Orr-Urtreger, A
AF Goldstein, Orly
Nayshool, Omri
Nefussy, Beatrice
Traynor, Bryan J.
Renton, Alan E.
Gana-Weisz, Mali
Drory, Vivian E.
Orr-Urtreger, Avi
TI OPTN 691_692insAG is a founder mutation causing recessive ALS and
increased risk in heterozygotes
SO NEUROLOGY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; DNA-SEQUENCING DATA; PARKINSON-DISEASE;
FAMILIAL ALS; OPTINEURIN; GENE; JEWISH; POPULATION; FRAMEWORK; ONSET
AB Objective:To detect genetic variants underlying familial and sporadic amyotrophic lateral sclerosis (ALS).Methods:We analyzed 2 founder Jewish populations of Moroccan and Ashkenazi origins and ethnic matched controls. Exome sequencing of 2 sisters with ALS from Morocco was followed by genotyping the identified causative null mutation in 379 unrelated patients with ALS and 1,000 controls. The shared risk haplotype was characterized using whole-genome single nucleotide polymorphism array.Results:We identified 5 unrelated patients with ALS homozygous for the null 691_692insAG mutation in the optineurin gene (OPTN), accounting for 5.8% of ALS of Moroccan origin and 0.3% of Ashkenazi. We also identified a high frequency of heterozygous carriers among patients with ALS, 8.7% and 2.9%, respectively, compared to 0.75% and 1.0% in controls. The risk of carriers for ALS was significantly increased, with odds ratio of 13.46 and 2.97 in Moroccan and Ashkenazi Jews, respectively. We determined that 691_692insAG is a founder mutation in the tested populations with a minimal risk haplotype of 58.5 Kb, encompassing the entire OPTN gene.Conclusions:Our data show that OPTN 691_692insAG mutation is a founder mutation in Moroccan and Ashkenazi Jews. This mutation causes autosomal recessive ALS and significantly increases the risk to develop the disease in heterozygous carriers, suggesting both a recessive mode of inheritance and a dominant with incomplete penetrance. These data emphasize the important role of OPTN in ALS pathogenesis, and demonstrate the complex genetics of ALS, as the same mutation leads to different phenotypes and appears in 2 patterns of inheritance.
C1 [Goldstein, Orly; Nayshool, Omri; Gana-Weisz, Mali; Orr-Urtreger, Avi] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel.
[Nefussy, Beatrice; Drory, Vivian E.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, Neuromuscular Serv, IL-69978 Tel Aviv, Israel.
[Traynor, Bryan J.; Renton, Alan E.] Natl Inst Aging, Neurogenet Lab, Bethesda, MD USA.
[Drory, Vivian E.; Orr-Urtreger, Avi] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
RP Orr-Urtreger, A (reprint author), Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel.; Orr-Urtreger, A (reprint author), Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
EM aviorr@tasmc.health.gov.il
FU Adelis Foundation; ALS Association [47717]; Kahn Foundation; Packard
Center for ALS Research; Muscular Dystrophy Association; US NIH,
National Institute on Aging [Z01-AG000949-02]
FX Supported by Adelis Foundation, ALS Association grant 47717, Kahn
Foundation, Packard Center for ALS Research, Muscular Dystrophy
Association, and in part by the Intramural Research Programs of the US
NIH, National Institute on Aging (Z01-AG000949-02).
NR 39
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD FEB 2
PY 2016
VL 86
IS 5
BP 446
EP 453
DI 10.1212/WNL.0000000000002334
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DD1HZ
UT WOS:000369673200008
PM 26740678
ER
PT J
AU Harouaka, D
Engle, RE
Wollenberg, K
Diaz, G
Tice, AB
Zamboni, F
Govindarajan, S
Alter, H
Kleiner, DE
Farci, P
AF Harouaka, Djamila
Engle, Ronald E.
Wollenberg, Kurt
Diaz, Giacomo
Tice, Ashley B.
Zamboni, Fausto
Govindarajan, Sugantha
Alter, Harvey
Kleiner, David E.
Farci, Patrizia
TI Diminished viral replication and compartmentalization of hepatitis C
virus in hepatocellular carcinoma tissue
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hepatitis C virus; hepatocellular carcinoma; HCV RNA levels; HCV
quasispecies; liver
ID BLOOD MONONUCLEAR-CELLS; LIKELIHOOD APPROACH; NONCANCEROUS LIVER;
MAXIMUM-LIKELIHOOD; RNA; EXPRESSION; HEPATOCYTES; INFECTION; SEQUENCES;
EVOLUTION
AB Analysis of hepatitis C virus (HCV) replication and quasispecies distribution within the tumor of patients with HCV-associated hepatocellular carcinoma (HCC) can provide insight into the role of HCV in hepatocarcinogenesis and, conversely, the effect of HCC on the HCV lifecycle. In a comprehensive study of serum and multiple liver specimens from patients with HCC who underwent liver transplantation, we found a sharp and significant decrease in HCV RNA in the tumor compared with surrounding nontumorous tissues, but found no differences in multiple areas of control non-HCC cirrhotic livers. Diminished HCV replication was not associated with changes in miR-122 expression. HCV genetic diversity was significantly higher in livers containing HCC compared with control non-HCC cirrhotic livers. Tracking of individual variants demonstrated changes in the viral population between tumorous and nontumorous areas, the extent of which correlated with the decline in HCV RNA, suggesting HCV compartmentalization within the tumor. In contrast, compartmentalization was not observed between nontumorous areas and serum, or in controls between different areas of the cirrhotic liver or between liver and serum. Our findings indicate that HCV replication within the tumor is restricted and compartmentalized, suggesting segregation of specific viral variants in malignant hepatocytes.
C1 [Harouaka, Djamila; Engle, Ronald E.; Tice, Ashley B.; Farci, Patrizia] NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Diaz, Giacomo] Univ Cagliari, Dept Biomed Sci, I-09100 Cagliari, Italy.
[Zamboni, Fausto] Brotzu Hosp, Liver Transplantat Ctr, I-09100 Cagliari, Italy.
[Govindarajan, Sugantha] Univ So Calif, Rancho Los Amigos, Dept Pathol, Los Angeles, CA 90242 USA.
[Alter, Harvey] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Farci, P (reprint author), NIAID, Hepat Pathogenesis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.; Alter, H (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM halter@dtm.cc.nih.gov; pfarci@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Clinical Center; National Cancer Institute;
Fondazione Banco di Sardegna [739/2011.1045]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases, Clinical Center, and National Cancer Institute. G.
D. received a grant from Fondazione Banco di Sardegna (739/2011.1045).
NR 58
TC 8
Z9 8
U1 1
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 2
PY 2016
VL 113
IS 5
BP 1375
EP 1380
DI 10.1073/pnas.1516879113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC2YO
UT WOS:000369085100076
PM 26787866
ER
PT J
AU Dekker, JD
Park, D
Shaffer, AL
Kohlhammer, H
Deng, W
Lee, BK
Ippolito, GC
Georgiou, G
Iyer, VR
Staudt, LM
Tucker, HO
AF Dekker, Joseph D.
Park, Daechan
Shaffer, Arthur L., III
Kohlhammer, Holger
Deng, Wei
Lee, Bum-Kyu
Ippolito, Gregory C.
Georgiou, George
Iyer, Vishwanath R.
Staudt, Louis M.
Tucker, Haley O.
TI Subtype-specific addiction of the activated B-cell subset of diffuse
large B-cell lymphoma to FOXP1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE FOXP1; DLBCL; lymphoma
ID ESSENTIAL TRANSCRIPTIONAL REGULATOR; GENE-EXPRESSION; MOLECULAR
SUBTYPES; DOWN-REGULATION; KAPPA-B; DIFFERENTIATION; SURVIVAL; PROTEIN;
PROLIFERATION; MATURATION
AB High expression of the forkhead box P1 (FOXP1) transcription factor distinguishes the aggressive activated B cell (ABC) diffuse large B-cell lymphoma (DLBCL) subtype from the better prognosis germinal center B-cell (GCB)-DLBCL subtype and is highly correlated with poor outcomes. A genetic or functional role for FOXP1 in lymphomagenesis, however, remains unknown. Here, we report that sustained FOXP1 expression is vital for ABC-DLBCL cell-line survival. Genome-wide analyses revealed direct and indirect FOXP1 transcriptional enforcement of ABC-DLBCL hallmarks, including the classical NF-kappa B and MYD88 (myeloid differentiation primary response gene 88) pathways. FOXP1 promoted gene expression underlying transition of the GCB cell to the plasmablast-the transient B-cell stage targeted in ABC-DLBCL transformation-by antagonizing pathways distinctive of GCB-DLBCL, including that of the GCB "master regulator," BCL6 (B-cell lymphoma 6). Cell-line derived FOXP1 target genes that were highly correlated with FOXP1 expression in primary DLBCL accurately segregated the corresponding clinical subtypes of a large cohort of primary DLBCL isolates and identified conserved pathways associated with ABC-DLBCL pathology.
C1 [Dekker, Joseph D.; Park, Daechan; Deng, Wei; Lee, Bum-Kyu; Ippolito, Gregory C.; Georgiou, George; Iyer, Vishwanath R.; Tucker, Haley O.] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
[Park, Daechan; Ippolito, Gregory C.; Georgiou, George] Univ Texas Austin, Cockrell Sch Engn, Dept Chem Engn, Austin, TX 78712 USA.
[Shaffer, Arthur L., III; Kohlhammer, Holger; Staudt, Louis M.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Tucker, HO (reprint author), Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.; Staudt, LM (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM lstaudt@mail.nih.gov; haleytucker@austin.utexas.edu
OI Park, Daechan/0000-0003-4991-5247
FU Intramural Research Program of the National Institutes of Health (NIH)
National Cancer Institute, Center for Cancer Research; Lymphoma Research
Foundation [300463]; NIH [R01CA31534, R01CA130075, R01CA95548]; Cancer
Prevention Research Institute of Texas (CPRIT) [RP120348, RP120459];
Marie Betzner Morrow Centennial Endowment; CPRIT [RP120194, RP100612]
FX We thank Chhaya Das and Maya Ghosh for help with ChIP and cell culture.
Anti-FOXP1 rabbit polyclonal antisera were kindly provided by Dr. Edward
Morrissey. Library preparation and Illumina ChIP-seq were performed at
the NGS core of the MD Anderson Cancer Center. Access to the datasets
from the Genotypes and Phenotypes database (dbGaP) (accession no.
phs000235) was essential for this study. The dbGaP data were generated
by the Cancer Genome Characterization Initiative (CGCI). The Texas
Advanced Computing Center (TACC) at The University of Texas at Austin
was vital for providing computing resources that have contributed to
this manuscript's results (https://www.tacc.utexas.edu/). Support for
this work was provided by the Intramural Research Program of the
National Institutes of Health (NIH) National Cancer Institute, Center
for Cancer Research (L.M.S., A.L.S., and H.K.); Lymphoma Research
Foundation Fellowship 300463 (to J.D.D.); NIH Grant R01CA31534; Cancer
Prevention Research Institute of Texas (CPRIT) Grants RP120348 and
RP120459; and the Marie Betzner Morrow Centennial Endowment (H.O.T.).
This work was also supported in part by NIH Grants R01CA130075 and
R01CA95548 and CPRIT Grants RP120194 (to V.R.I.) and RP100612 (to G.
G.).
NR 54
TC 6
Z9 6
U1 2
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 2
PY 2016
VL 113
IS 5
BP E577
EP E586
DI 10.1073/pnas.1524677113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DC2YO
UT WOS:000369085100014
PM 26787899
ER
PT J
AU Machida, S
Hayashida, R
Takaku, M
Fukuto, A
Sun, JY
Kinomura, A
Tashiro, S
Kurumizaka, H
AF Machida, Shinichi
Hayashida, Ryota
Takaku, Motoki
Fukuto, Atsuhiko
Sun, Jiying
Kinomura, Aiko
Tashiro, Satoshi
Kurumizaka, Hitoshi
TI Relaxed Chromatin Formation and Weak Suppression of Homologous Pairing
by the Testis-Specific Linker Histone H1T
SO BIOCHEMISTRY
LA English
DT Article
ID NUCLEOSOME CORE PARTICLE; STRAND-EXCHANGE; MAMMALIAN SPERMIOGENESIS;
RAD51 PROTEIN; ANGSTROM RESOLUTION; STRUCTURAL BASIS; H1-LIKE PROTEIN;
VARIANT H2A.BBD; TERMINAL DOMAIN; IN-VITRO
AB Linker histones bind to nucleosomes and compact polynucleosomes into a higher-order: chromatin configuration. Somatic and germ cell-specific linker histone subtypes have been identified and may have distinct functions. In this study; we reconstituted polynucleosomes containing human histones H1.2 and H1T, as representative somatic and germ cell-specific linker histones, respectively, and found that HIT forms less compacted chromatin, as compared to H1.2. An in vitro homologous pairing assay revealed that H1T weakly inhibited RAD51/RAD54-mediated homologous pairing in chromatin, although the somatic H1 subtypes, H1.0, H1.1, H1.2, H1.3, H1.4, and H1.53 substantially suppressed it. An in vivo recombination assay revealed that H1T overproduction minimally affected the recombination frequency, but significant suppression was observed When H1.2 was overproduced in human cells. These results suggested that the testis-specific linker histone, H1T, possesses a Specific function to produce the chromatin architecture required for proper chromosome regulation, such as homologous recombination.
C1 [Machida, Shinichi; Hayashida, Ryota; Takaku, Motoki; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
[Fukuto, Atsuhiko; Sun, Jiying; Kinomura, Aiko; Tashiro, Satoshi] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Cellular Biol, Minami Ku, 1-2-3 Kasumi, Hiroshima 7348553, Japan.
[Kurumizaka, Hitoshi] Waseda Univ, Inst Med Oriented Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
[Takaku, Motoki] NIEHS, Epigenet & Stem Cell Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Kurumizaka, H (reprint author), Waseda Univ, Grad Sch Adv Sci & Engn, Struct Biol Lab, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.; Kurumizaka, H (reprint author), Waseda Univ, Inst Med Oriented Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM kurumizaka@waseda.jp
FU MEXT KAKENHI [25116002]; JSPS KAKENHI [25250023, 26890023]; Platform
Project for Supporting Drug Discovery and Life Science Research
(Platform for Drug Discovery, Informatics, and Structural Life Science);
Ministry of Education, Culture, Sports, Science and Technology (MEXT);
Japan Agency for Medical Research and Development (AMED); Waseda
Research Institute for Science and Engineering
FX This work was supported in part by MEXT KAKENHI Grant 25116002 (to
H.K.), JSPS KAKENHI Grant 25250023 (to H.K.), and Grant 26890023 (to
S.M.) and was also partially supported by grants from the Platform
Project for Supporting Drug Discovery and Life Science Research
(Platform for Drug Discovery, Informatics, and Structural Life Science),
from the Ministry of Education, Culture, Sports, Science and Technology
(MEXT), and the Japan Agency for Medical Research and Development (AMED)
(to H.K). H.K. was also supported by the Waseda Research Institute for
Science and Engineering.
NR 64
TC 2
Z9 2
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 2
PY 2016
VL 55
IS 4
BP 637
EP 646
DI 10.1021/acs.biochem.5b01126
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DC8LT
UT WOS:000369471800003
PM 26757249
ER
PT J
AU Merrins, MJ
Poudel, C
McKenna, JP
Ha, J
Sherman, A
Bertram, R
Satin, LS
AF Merrins, Matthew J.
Poudel, Chetan
McKenna, Joseph P.
Ha, Joon
Sherman, Arthur
Bertram, Richard
Satin, Leslie S.
TI Phase Analysis of Metabolic Oscillations and Membrane Potential in
Pancreatic Islet beta-Cells
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PULSATILE INSULIN-SECRETION; PURINE NUCLEOTIDE CYCLE; GLYCOLYTIC
PATHWAY; CA2+; GLUCOSE; CALCIUM; MODEL; DEHYDROGENASE; ACTIVATION;
MECHANISMS
AB Metabolism in islet beta-cells displays oscillations that can trigger pulses of electrical activity and insulin secretion. There has been a decades-long debate among islet biologists about whether metabolic oscillations are intrinsic or occur in response to oscillations in intracellular Ca2+ that result from bursting electrical activity. In this article, the dynamics of oscillatory metabolism were investigated using five different optical reporters. Reporter activity was measured simultaneously with membrane potential bursting to determine the phase relationships between the metabolic oscillations and electrical activity. Our experimental findings suggest that Ca2+ entry into beta-cells stimulates the rate of mitochondrial metabolism, accounting for the depletion of glycolytic intermediates during each oscillatory burst. We also performed Ca2+ clamp tests in which we clamped membrane potential with the K-ATP channel-opener diazoxide and KCl to fix Ca2+ at an elevated level. These tests confirm that metabolic oscillations do not require Ca2+ oscillations, but show that Ca2+ plays a larger role in shaping metabolic oscillations than previously suspected. A dynamical picture of the mechanisms of oscillations emerged that requires the restructuring of contemporary mathematical beta-cell models, including our own dual oscillator model. In the companion article, we modified our model to account for these new data.
C1 [Merrins, Matthew J.; Poudel, Chetan] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Endocrinol Diabet & Metab, Madison, WI USA.
[Merrins, Matthew J.; Poudel, Chetan] Univ Wisconsin, Dept Biomol Chem, Sch Med & Publ Hlth, Madison, WI USA.
[Merrins, Matthew J.; Poudel, Chetan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[McKenna, Joseph P.; Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.
[McKenna, Joseph P.; Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
[McKenna, Joseph P.; Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
[Ha, Joon; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Satin, Leslie S.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Satin, Leslie S.] Univ Michigan, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA.
RP Satin, LS (reprint author), Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.; Satin, LS (reprint author), Univ Michigan, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA.
EM lsatin@umich.edu
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [R01-DK46409, K01-DK101683]; NIH
FX This work was supported by the National Institutes of Health National
Institute of Diabetes and Digestive and Kidney Diseases, including
grants R01-DK46409 to L.S.S. and K01-DK101683 to M.J.M. A.S. and J.H.
were supported by the Intramural Research Program of the NIH.
NR 39
TC 4
Z9 4
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 2
PY 2016
VL 110
IS 3
BP 691
EP 699
DI 10.1016/j.bpj.2015.12.029
PG 9
WC Biophysics
SC Biophysics
GA DC8KH
UT WOS:000369467800018
PM 26840733
ER
PT J
AU McKenna, JP
Ha, J
Merrins, MJ
Satin, LS
Sherman, A
Bertram, R
AF McKenna, Joseph P.
Ha, Joon
Merrins, Matthew J.
Satin, Leslie S.
Sherman, Arthur
Bertram, Richard
TI Ca2+ Effects on ATP Production and Consumption Have Regulatory Roles on
Oscillatory Islet Activity
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PANCREATIC BETA-CELLS; PULSATILE INSULIN-SECRETION; METABOLIC
OSCILLATIONS; GLYCOLYTIC OSCILLATIONS; ELECTRICAL-ACTIVITY;
GLUCOSE-METABOLISM; CALCIUM; PHOSPHOFRUCTOKINASE; MODEL; MEMBRANE
AB Pancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in beta-cell metabolism, intracellular Ca2+ concentration, and bursting electrical activity. The mechanisms that maintain an oscillatory response are not fully understood, yet several models have been proposed. Only some can account for experiments supporting that metabolism is intrinsically oscillatory in beta-cells. The dual oscillator model (DOM) implicates glycolysis as the source of oscillatory metabolism. In the companion article, we use recently developed biosensors to confirm that glycolysis is oscillatory and further elucidate the coordination of metabolic and electrical signals in the insulin secretory pathway. In this report, we modify the DOM by incorporating an established link between metabolism and intracellular Ca2+ to reconcile model predictions with experimental observations from the companion article. With modification, we maintain the distinguishing feature of the DOM, oscillatory glycolysis, but introduce the ability of Ca2+ influx to reshape glycolytic oscillations by promoting glycolytic efflux. We use the modified model to explain measurements from the companion article and from previously published experiments with islets.
C1 [McKenna, Joseph P.; Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.
[Ha, Joon; Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Merrins, Matthew J.] Univ Wisconsin, Dept Med, Div Endocrinol Diabet & Metab, Sch Med & Publ Hlth, Madison, WI USA.
[Merrins, Matthew J.] Univ Wisconsin, Dept Biomol Chem, Sch Med & Publ Hlth, Madison, WI USA.
[Merrins, Matthew J.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Satin, Leslie S.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Satin, Leslie S.] Univ Michigan, Brehm Diabet Ctr, Ann Arbor, MI 48109 USA.
[Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.; Bertram, R (reprint author), Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.; Bertram, R (reprint author), Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
EM bertram@math.fsu.edu
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [R01-DK46409, K01-DK101683]; Intramural
Research Program of the National Institutes of Health (National
Institute of Diabetes and Digestive and Kidney Diseases)
FX This work was partially supported by the National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (grant
No. R01-DK46409 to L.S.S. and grant No. K01-DK101683 to M.J.M.). A.S.
and J.H. were supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Diabetes and
Digestive and Kidney Diseases).
NR 46
TC 1
Z9 1
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD FEB 2
PY 2016
VL 110
IS 3
BP 733
EP 742
DI 10.1016/j.bpj.2015.11.3526
PG 10
WC Biophysics
SC Biophysics
GA DC8KH
UT WOS:000369467800022
PM 26840737
ER
PT J
AU Vogtmann, E
Goedert, JJ
AF Vogtmann, Emily
Goedert, James J.
TI Epidemiologic studies of the human microbiome and cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Review
DE microbiome; cancer; epidemiology; case-control study; cohort study
ID BILIARY-TRACT CANCER; HUMAN GUT MICROBIOME; HELICOBACTER-PYLORI;
COLORECTAL-CANCER; FECAL MICROBIOTA; GASTRIC-CANCER; PANCREATIC-CANCER;
HODGKIN-LYMPHOMA; TOOTH LOSS; RISK
AB The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment.
C1 [Vogtmann, Emily] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM goedertj@mail.nih.gov
FU National Cancer Institute Intramural Research Program [ZIA-CP-010214]
FX We thank our many microbiome and epidemiology collaborators for advice
and inspiration. This work was supported by the National Cancer
Institute Intramural Research Program, ZIA-CP-010214.
NR 51
TC 11
Z9 13
U1 12
U2 51
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 2
PY 2016
VL 114
IS 3
BP 237
EP 242
DI 10.1038/bjc.2015.465
PG 6
WC Oncology
SC Oncology
GA DC4XM
UT WOS:000369223600001
PM 26730578
ER
PT J
AU Sung, HN
Garcia-Closas, M
Chang-Claude, J
Blows, FM
Ali, HR
Figueroa, J
Nevanlinna, H
Fagerholm, R
Heikkila, P
Blomqvist, C
Giles, GG
Milne, RL
Southey, MC
McLean, C
Mannermaa, A
Kosma, VM
Kataja, V
Sironen, R
Couch, FJ
Olson, JE
Hallberg, E
Olswold, C
Cox, A
Cross, SS
Kraft, P
Tamimi, RM
Eliassen, AH
Schmidt, MK
Bolla, MK
Wang, Q
Easton, D
Howat, WJ
Coulson, P
Pharoah, PDP
Sherman, ME
Yang, XHR
AF Sung, Hyuna
Garcia-Closas, Montserrat
Chang-Claude, Jenny
Blows, Fiona M.
Ali, H. Raza
Figueroa, Jonine
Nevanlinna, Heli
Fagerholm, Rainer
Heikkila, Paivi
Blomqvist, Carl
Giles, Graham G.
Milne, Roger L.
Southey, Melissa C.
McLean, Catriona
Mannermaa, Arto
Kosma, Veli-Matti
Kataja, Vesa
Sironen, Reijo
Couch, Fergus J.
Olson, Janet E.
Hallberg, Emily
Olswold, Curtis
Cox, Angela
Cross, Simon S.
Kraft, Peter
Tamimi, Rulla M.
Eliassen, A. Heather
Schmidt, Marjanka K.
Bolla, Manjeet K.
Wang, Qin
Easton, Douglas
Howat, William J.
Coulson, Penny
Pharoah, Paul D. P.
Sherman, Mark E.
Yang, Xiaohong R.
TI Heterogeneity of luminal breast cancer characterised by
immunohistochemical expression of basal markers
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; luminal A tumour; CK5/6; EGFR; tumour characteristics;
risk factors
ID MOLECULAR PORTRAITS; TUMORS; CLASSIFICATION; PHENOTYPE; SUBTYPES; RISK
AB Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours.
Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))- and EGFR) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case-case comparison was performed using unconditional logistic regression.
Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index.
Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations.
C1 [Sung, Hyuna; Figueroa, Jonine; Sherman, Mark E.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Breast Canc Res, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
[Blows, Fiona M.] Univ Cambridge, Dept Oncol, Worts Causeway, Cambridge CB1 8RN, England.
[Ali, H. Raza] Univ Cambridge, Canc Res UK Cambridge Inst, Robinson Way, Cambridge CB2 0RE, England.
[Nevanlinna, Heli; Fagerholm, Rainer] Helsinki Univ Hosp, Dept Obstet & Gynecol, POB 700, Helsinki 00029, Finland.
[Nevanlinna, Heli; Fagerholm, Rainer] Univ Helsinki, POB 700, Helsinki 00029, Finland.
[Heikkila, Paivi] Helsinki Univ Hosp, Dept Pathol, POB 400, Helsinki 00029, Finland.
[Blomqvist, Carl] Helsinki Univ Hosp, Dept Oncol, POB 400, Helsinki 00029, Finland.
[Heikkila, Paivi; Blomqvist, Carl] Univ Helsinki, POB 400, Helsinki 00029, Finland.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, 615 St Kilda Rd, Melbourne, Vic 3004, Australia.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic 3010, Australia.
[McLean, Catriona] Alfred Hosp, Anat Pathol, Commercial Rd, Prahran, Vic 3181, Australia.
[Mannermaa, Arto; Kosma, Veli-Matti; Sironen, Reijo] Univ Eastern Finland, Canc Ctr Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, Yliopistonranta 1,POB 1627, Kuopio 70211, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Sironen, Reijo] Kuopio Univ Hosp, Imaging Ctr, Dept Clin Pathol, POB 100, Kys Kuopio 70029, Finland.
[Kataja, Vesa] Jyvaskyla Cent Hosp, Cent Finland Hlth Care Dist, Adm Bldg 6-2,Keskussairaalantie 19, Jyvaskyla 40620, Finland.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Stabile 2-42,200 First St SW, Rochester, MN 55905 USA.
[Olson, Janet E.; Hallberg, Emily; Olswold, Curtis] Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
[Kraft, Peter] Harvard Univ, TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 677 Huntington Ave, Boston, MA 02115 USA.
[Tamimi, Rulla M.; Eliassen, A. Heather] Harvard Univ, Sch Med, Channing Div Network Med, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA.
[Tamimi, Rulla M.; Eliassen, A. Heather] Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA.
[Tamimi, Rulla M.; Eliassen, A. Heather] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
[Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
[Bolla, Manjeet K.; Wang, Qin; Easton, Douglas; Pharoah, Paul D. P.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Easton, Douglas; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England.
[Howat, William J.] Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England.
[Coulson, Penny] Inst Canc Res, Div Genet & Epidemiol, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England.
RP Sung, HN (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM hyuna.sung@nih.gov
OI Giles, Graham/0000-0003-4946-9099
FU Helsinki University Central Hospital Research Fund; Academy of Finland
[266528]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius
Foundation; Breast Cancer Research Foundation; National Institutes of
Health Specialized Program of Research Excellence (SPORE) in Breast
Cancer [CA116201]; R01 grants [CA128978, CA176785]; Grohne Family;
Cancer Council Victoria; VicHealth; NHMRC [209057, 251533, 396414,
504711]; Victorian Cancer Registry (VCR); Australian Institute of Health
and Welfare (AIHW); National Death Index (NDI); National Institutes of
Health/National Cancer Institute [UM1 CA186107, P01 CA 87969];
Intramural Research Program of US NIH, NCI, Division of Cancer
Epidemiology and Genetics (DCEG); Yorkshire Cancer Research [S295, S299,
S305PA]; Sheffield Experimental Cancer Medicine Centre; Cancer Research
UK [C490/A16561]; Biomedical Research Centre at the University of
Cambridge; special Government Funding of Kuopio University Hospital
grants; Cancer Fund of North Savo; Finnish Cancer Organizations;
University of Eastern Finland
FX The Helsinki Breast Cancer Study (HEBCS) thanks Kristiina Aittomaki,
Kirsimari Aaltonen, Taru A Muranen, Karl von Smitten, and Irja Erkkila
for their kind help with the patient samples and data. The Study of
Epidemiology and Risk factors in Cancer Heredity (SEARCH) thanks Elena
Provenzano and Marie Mack. The HEBCS was supported by The Helsinki
University Central Hospital Research Fund, Academy of Finland (266528),
the Finnish Cancer Society, and The Nordic Cancer Union and the Sigrid
Juselius Foundation. The Mayo Clinic Breast Cancer Study (MCBCS) was
supported by The Breast Cancer Research Foundation, the National
Institutes of Health Specialized Program of Research Excellence (SPORE)
in Breast Cancer (CA116201), R01 grants (CA128978 and CA176785), and the
Grohne Family. The Melbourne Collaborative Cohort Study (MCCS) was
supported by The Cancer Council Victoria, VicHealth, NHMRC (209057,
251533, 396414, and 504711), Victorian Cancer Registry (VCR) and the
Australian Institute of Health and Welfare (AIHW), including the
National Death Index (NDI). The Nurses' Health Study (NHS) was supported
by National Institutes of Health/National Cancer Institute (UM1 CA186107
and P01 CA 87969). The NHS thanks the following state cancer registries
for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY,
LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN,
TX, VA, WA, WY. The Polish Breast Cancer Study (PBCS) was supported by
Intramural Research Program of US NIH, NCI, Division of Cancer
Epidemiology and Genetics (DCEG). The Sheffield Breast Cancer Study
(SBCS) was supported by Yorkshire Cancer Research (S295, S299, and
S305PA) and Sheffield Experimental Cancer Medicine Centre. The SEARCH
was supported by Cancer Research UK (C490/A16561), the Biomedical
Research Centre at the University of Cambridge. The Kuopio Breast Cancer
Project (KBCP) was supported by The special Government Funding of Kuopio
University Hospital grants, Cancer Fund of North Savo, the Finnish
Cancer Organizations, the strategic funding of the University of Eastern
Finland.
NR 23
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD FEB 2
PY 2016
VL 114
IS 3
BP 298
EP 304
DI 10.1038/bjc.2015.437
PG 7
WC Oncology
SC Oncology
GA DC4XM
UT WOS:000369223600009
PM 26679376
ER
PT J
AU Taichman, DB
Backus, J
Baethge, C
Bauchner, H
de Leeuw, PW
Drazen, JM
Fletcher, J
Frizelle, FA
Groves, T
Haileamlak, A
James, A
Laine, C
Peiperl, L
Pinborg, A
Sahni, P
Wu, SN
AF Taichman, Darren B.
Backus, Joyce
Baethge, Christopher
Bauchner, Howard
de Leeuw, Peter W.
Drazen, Jeffrey M.
Fletcher, John
Frizelle, Frank A.
Groves, Trish
Haileamlak, Abraham
James, Astrid
Laine, Christine
Peiperl, Larry
Pinborg, Anja
Sahni, Peush
Wu, Sinan
TI Sharing clinical trial data: a proposal from the International Committee
of Medical Journal Editors
SO CANADIAN MEDICAL ASSOCIATION JOURNAL
LA English
DT Editorial Material
C1 [Backus, Joyce] Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA.
RP Taichman, DB (reprint author), Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA.
EM DTaichman@mail.acponline.org
NR 1
TC 2
Z9 2
U1 0
U2 1
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 FEB 2
PY 2016
VL 188
IS 2
BP 91
EP 92
DI 10.1503/cmaj.151465
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DC6HJ
UT WOS:000369320300001
PM 26792811
ER
PT J
AU Woodford, MR
Truman, AW
Dunn, DM
Jensen, SM
Cotran, R
Bullard, R
Abouelleil, M
Beebe, K
Wolfgeher, D
Wierzbicki, S
Post, DE
Caza, T
Tsutsumi, S
Panaretou, B
Kron, SJ
Trepel, JB
Landas, S
Prodromou, C
Shapiro, O
Stetler-Stevenson, WG
Bourboulia, D
Neckers, L
Bratslavsky, G
Mollapour, M
AF Woodford, Mark R.
Truman, Andrew W.
Dunn, Diana M.
Jensen, Sandra M.
Cotran, Richard
Bullard, Renee
Abouelleil, Mourad
Beebe, Kristin
Wolfgeher, Donald
Wierzbicki, Sara
Post, Dawn E.
Caza, Tiffany
Tsutsumi, Shinji
Panaretou, Barry
Kron, Stephen J.
Trepel, Jane B.
Landas, Steve
Prodromou, Chrisostomos
Shapiro, Oleg
Stetler-Stevenson, William G.
Bourboulia, Dimitra
Neckers, Len
Bratslavsky, Gennady
Mollapour, Mehdi
TI Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma
Sensitivity and Selectivity to Hsp90 Inhibitors
SO CELL REPORTS
LA English
DT Article
ID SPINDLE-ASSEMBLY CHECKPOINT; SHOCK TRANSCRIPTION FACTOR; MITOTIC
CHECKPOINT; SACCHAROMYCES-CEREVISIAE; STEROID-RECEPTOR; PROTEIN
PHOSPHATASE; TUMOR SELECTIVITY; IN-VIVO; CHAPERONE; KINASE
AB The molecular chaperone Hsp90 protects deregulated signaling proteins that are vital for tumor growth and survival. Tumors generally display sensitivity and selectivity toward Hsp90 inhibitors; however, the molecular mechanism underlying this phenotype remains undefined. We report that the mitotic checkpoint kinase Mps1 phosphorylates a conserved threonine residue in the amino-domain of Hsp90. This, in turn, regulates chaperone function by reducing Hsp90 ATPase activity while fostering Hsp90 association with kinase clients, including Mps1. Phosphorylation of Hsp90 is also essential for the mitotic checkpoint because it confers Mps1 stability and activity. We identified Cdc14 as the phosphatase that dephosphorylates Hsp90 and disrupts its interaction with Mps1. This causes Mps1 degradation, thus providing a mechanism for its inactivation. Finally, Hsp90 phosphorylation sensitizes cells to its inhibitors, and elevated Mps1 levels confer renal cell carcinoma selectivity to Hsp90 drugs. Mps1 expression level can potentially serve as a predictive indicator of tumor response to Hsp90 inhibitors.
C1 [Woodford, Mark R.; Dunn, Diana M.; Cotran, Richard; Bullard, Renee; Abouelleil, Mourad; Wierzbicki, Sara; Post, Dawn E.; Shapiro, Oleg; Bourboulia, Dimitra; Bratslavsky, Gennady; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA.
[Woodford, Mark R.; Dunn, Diana M.; Bullard, Renee; Post, Dawn E.; Bourboulia, Dimitra; Mollapour, Mehdi] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, 750 E Adams St, Syracuse, NY 13210 USA.
[Woodford, Mark R.; Dunn, Diana M.; Cotran, Richard; Bullard, Renee; Abouelleil, Mourad; Wierzbicki, Sara; Post, Dawn E.; Shapiro, Oleg; Bourboulia, Dimitra; Bratslavsky, Gennady; Mollapour, Mehdi] SUNY Upstate Med Univ, Canc Res Inst, 750 E Adams St, Syracuse, NY 13210 USA.
[Truman, Andrew W.] Univ N Carolina, Dept Biol Sci, Charlotte, NC 28223 USA.
[Wolfgeher, Donald; Kron, Stephen J.] Univ Chicago, Dept Mol Genet & Cell Biol, 920 E 58Th St, Chicago, IL 60637 USA.
[Caza, Tiffany; Landas, Steve] SUNY Upstate Med Univ, Dept Pathol, 750 E Adams St, Syracuse, NY 13210 USA.
[Panaretou, Barry] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England.
[Prodromou, Chrisostomos] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England.
[Jensen, Sandra M.; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Beebe, Kristin; Tsutsumi, Shinji; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Trepel, Jane B.] NCI, Dev Therapeut Branch, Ctr Canc Res, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Dept Biochem & Mol Biol, 750 E Adams St, Syracuse, NY 13210 USA.; Mollapour, M (reprint author), SUNY Upstate Med Univ, Canc Res Inst, 750 E Adams St, Syracuse, NY 13210 USA.
EM mollapom@upstate.edu
OI Woodford, Mark/0000-0002-6737-2832; Dunn, Diana/0000-0003-3244-0599
FU NCI [R01 CA164492]; Wellcome Trust [095605/Z11/Z]; SUNY Upstate Medical
University; Foundation for Upstate Medical University; One Square Mile
of Hope Foundation; Carol M. Baldwin Breast Cancer Fund
FX The authors thank Dr. W. Feng and Mr. A. McCulley for insightful
scientific discussion and helpful comments. We are grateful to Dr. J.
Johnson (University of Idaho) for STE11 Delta N plasmid, Dr. T. Haystead
(Duke University) for the Hsp90 inhibitor SNX2112, Dr. W. Ying (Synta
Pharmaceuticals) for the Hsp90 inhibitor ganetespib, Dr. D. Masison
(National Institute of Diabetes and Digestive and Kidney Diseases) for
Sti1 antibody, Dr. M. Snyder (Stanford University) for Cdc55-GST and
Cdc14-GST constructs, and Dr. C. Boone (University of Toronto) for the
mps1-1 strain. This work was supported with funds from NCI R01 CA164492
(S.J.K.), Wellcome Trust 095605/Z11/Z (C.P.), SUNY Upstate Medical
University, Foundation for Upstate Medical University, One Square Mile
of Hope Foundation, and Carol M. Baldwin Breast Cancer Fund (M. M.,
D.B., M.R.W, D.D).
NR 35
TC 5
Z9 5
U1 2
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD FEB 2
PY 2016
VL 14
IS 4
BP 872
EP 884
DI 10.1016/j.celrep.2015.12.084
PG 13
WC Cell Biology
SC Cell Biology
GA DC3FH
UT WOS:000369104500017
PM 26804907
ER
PT J
AU Montefiori, L
Wuerffel, R
Roqueiro, D
Lajoie, B
Guo, CY
Gerasimova, T
De, S
Wood, W
Becker, KG
Dekker, J
Liang, J
Sen, R
Kenter, AL
AF Montefiori, Lindsey
Wuerffel, Robert
Roqueiro, Damian
Lajoie, Bryan
Guo, Changying
Gerasimova, Tatiana
De, Supriyo
Wood, William
Becker, Kevin G.
Dekker, Job
Liang, Jie
Sen, Ranjan
Kenter, Amy L.
TI Extremely Long-Range Chromatin Loops Link Topological Domains to
Facilitate a Diverse Antibody Repertoire
SO CELL REPORTS
LA English
DT Article
ID HEAVY-CHAIN GENE; B-CELL FATE; LYMPHOCYTE DEVELOPMENT; GENOMIC
INTERACTIONS; IMMUNOGLOBULIN LOCI; V(D)J RECOMBINATION; INTRONIC
ENHANCER; NUCLEAR LAMINA; IGH LOCUS; ORGANIZATION
AB Early B cell development is characterized by large-scale Igh locus contraction prior to V(D)J recombination to facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates locus contraction remains unclear. We have combined high-resolution chromosome conformation capture (3C) techniques with 3D DNA FISH to identify three conserved topological subdomains. Each of these topological folds encompasses a major V-H gene family that become juxtaposed in pro-B cells via megabase-scale chromatin looping. The transcription factor Pax5 organizes the subdomain that spans the V(H)J558 gene family. In its absence, the J558 V-H genes fail to associate with the proximal V-H genes, thereby providing a plausible explanation for reduced V(H)J558 gene rearrangements in Pax5-deficient pro-B cells. We propose that Igh locus contraction is the cumulative effect of several independently controlled chromatin subdomains that provide the structural infrastructure to coordinate optimal antigen receptor assembly.
C1 [Montefiori, Lindsey; Guo, Changying; Gerasimova, Tatiana; Sen, Ranjan] NIA, Gene Regulat Sect, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Wuerffel, Robert; Kenter, Amy L.] Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA.
[Roqueiro, Damian; Liang, Jie] Univ Illinois, Coll Med, Dept Bioengn, Chicago, IL 60612 USA.
[Lajoie, Bryan; Dekker, Job] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
[Lajoie, Bryan; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Program Syst Biol, Worcester, MA 01605 USA.
[De, Supriyo; Wood, William; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Sen, R (reprint author), NIA, Gene Regulat Sect, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.; Kenter, AL (reprint author), Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA.
EM senranja@grc.nia.nih.gov; star1@uic.edu
OI De, Supriyo/0000-0002-2075-7655
FU National Institutes of Health [RO1AI052400, R21AI117687, HG003143,
HG00459, GM079804]; National Science Foundation [DBI 1062328,
MCB-1415589]; Chicago Biomedical Consortium; Searle Funds at The Chicago
Community Trust; W.M. Keck Foundation; Intramural Research Program of
the National Institute on Aging (Baltimore, MD)
FX This work was supported by the National Institutes of Health
(RO1AI052400, R21AI117687 to A.K., HG003143 and HG00459 to J.D.,
GM079804 to J.L.), National Science Foundation (DBI 1062328 and
MCB-1415589 to J.L.), the Chicago Biomedical Consortium with support
from the Searle Funds at The Chicago Community Trust (to A.K. and J.L.),
the W.M. Keck Foundation (to J.D.), and Intramural Research Program of
the National Institute on Aging (Baltimore, MD) (to R.S.). We thank G.
Gursoy for helpful discussions and Dr. J. Pongubala for the
Pax5-deficient pro-B cell line.
NR 31
TC 3
Z9 3
U1 5
U2 7
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 FEB 2
PY 2016
VL 14
IS 4
BP 896
EP 906
DI 10.1016/j.celrep.2015.12.083
PG 11
WC Cell Biology
SC Cell Biology
GA DC3FH
UT WOS:000369104500019
PM 26804913
ER
PT J
AU Hojyo, S
Sarkander, J
Manne, C
Mursell, M
Hanazawa, A
Zimmel, D
Zhu, JF
Paul, WE
Fillatreau, S
Lohning, M
Radbruch, A
Tokoyoda, K
AF Hojyo, Shintaro
Sarkander, Jana
Maenne, Christian
Mursell, Mathias
Hanazawa, Asami
Zimmel, David
Zhu, Jinfang
Paul, William E.
Fillatreau, Simon
Loehning, Max
Radbruch, Andreas
Tokoyoda, Koji
TI B Cells Negatively Regulate the Establishment of cD49b(+)T-bet(+)
Resting Memory T Helper Cells in the Bone Marrow
SO FRONTIERS IN IMMUNOLOGY
LA English
DT Article
DE resting memory; CD4 T helper cells; B cells; bone marrow; T-bet
ID KRUPPEL-LIKE FACTOR-2; LIVED PLASMA-CELLS; TRANSCRIPTION FACTOR;
VIRAL-INFECTION; CD8-T-CELL MEMORY; HUMORAL IMMUNITY; CD4-T-CELL HELP;
CD4(+); EXPRESSION; LYMPHOCYTES
AB During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs) to the bone marrow (BM) in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen-experienced CD4 T cells in the BM synchronizes the number of CD49b(+)T-bet(+) antigen-experienced CD4 T cells in the spleen. CD49b(+)T-bet(+) antigen-experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b(+)T-bet(+) precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages.
C1 [Hojyo, Shintaro; Sarkander, Jana; Maenne, Christian; Mursell, Mathias; Hanazawa, Asami; Zimmel, David; Fillatreau, Simon; Loehning, Max; Radbruch, Andreas; Tokoyoda, Koji] Leibniz Inst, Deutsch Rheuma Forschungszentrum Berlin, Berlin, Germany.
[Zimmel, David; Loehning, Max] Charite, Dept Rheumatol & Clin Immunol, Expt Immunol & Osteoarthrit Res, D-13353 Berlin, Germany.
[Zhu, Jinfang] NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Paul, William E.] Inst Necker Enfants Malad, INSERM, U1151, CNRS,UMR 8253, Paris, France.
[Fillatreau, Simon] Univ Paris 05, Sorbonne Paris Cite, Fac Med, Paris, France.
[Fillatreau, Simon] Hop Necker Enfants Malad, AP HP, Paris, France.
RP Tokoyoda, K (reprint author), Leibniz Inst, Deutsch Rheuma Forschungszentrum Berlin, Berlin, Germany.
EM tokoyoda@drfz.de
RI Zhu, Jinfang/B-7574-2012
FU Leibniz Association; Alexander von Humboldt-Foundation; NIH, NIAID;
German Research Foundation [SFB650, TP28, LO1542/3-1]; German Federal
Ministry of Education and Research [0316164G]; Volkswagen Foundation;
Willy Robert Pitzer Foundation
FX We thank A. Awada, Y. Keziban, Y. Yamasaki, T. Geske, H. Hecker-Kia, H.
Schliemann, J. Kirsch, T. Kaiser, I. Sakwa, V. Holecska, and S. Ebel for
expert technical assistance. This work is supported by the Leibniz
Association (International Leibniz Research Cluster "ImmunoMemory"). SH
is supported by the Alexander von Humboldt-Foundation. JZ and WP are
supported by the Intramural Research Program of NIH, NIAID. ML is
supported by the German Research Foundation (SFB650, grant TP28, and
grant LO1542/3-1), the German Federal Ministry of Education and Research
(e:Bio/T-Sys grant 0316164G), Volkswagen Foundation (Lichtenberg
Program), and Willy Robert Pitzer Foundation (Osteoarthritis Research
Program).
NR 47
TC 2
Z9 2
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-3224
J9 FRONT IMMUNOL
JI Front. Immunol.
PD FEB 2
PY 2016
VL 7
AR 26
DI 10.3389/fimmu.2016.00026
PG 8
WC Immunology
SC Immunology
GA DC3HY
UT WOS:000369111600001
PM 26870041
ER
PT J
AU Taichman, DB
Backus, J
Baethge, C
Bauchner, H
de Leeuw, PW
Drazen, JM
Fletcher, J
Frizelle, FA
Groves, T
Haileamlak, A
James, A
Laine, C
Peiperl, L
Pinborg, A
Sahni, P
Wu, SN
AF Taichman, Darren B.
Backus, Joyce
Baethge, Christopher
Bauchner, Howard
de Leeuw, Peter W.
Drazen, Jeffrey M.
Fletcher, John
Frizelle, Frank A.
Groves, Trish
Haileamlak, Abraham
James, Astrid
Laine, Christine
Peiperl, Larry
Pinborg, Anja
Sahni, Peush
Wu, Sinan
TI Sharing Clinical Trial Data A Proposal From the International Committee
of Medical Journal Editors
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Backus, Joyce] US Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA.
[Baethge, Christopher] Deutsch Arzteblatt, Cologne, Germany.
EM dtaichman@acponline.org
NR 1
TC 17
Z9 17
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 2
PY 2016
VL 315
IS 5
BP 467
EP 468
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DC2LZ
UT WOS:000369049500015
PM 26792562
ER
PT J
AU Keenan, T
Zhao, W
Rasheed, A
Ho, WK
Malik, R
Felix, JF
Young, R
Shah, N
Samuel, M
Sheikh, N
Mucksavage, ML
Shah, O
Li, J
Morley, M
Laser, A
Mallick, NH
Zaman, KS
Ishaq, M
Rasheed, SZ
Memon, FUR
Ahmed, F
Hanif, B
Lakhani, MS
Fahim, M
Ishaq, M
Shardha, NK
Ahmed, N
Mahmood, K
Iqbal, W
Akhtar, S
Raheel, R
O'Donnell, CJ
Hengstenberg, C
Marz, W
Kathiresan, S
Samani, N
Goel, A
Hopewell, JC
Chambers, J
Cheng, YC
Sharma, P
Yang, Q
Rosand, J
Boncoraglio, GB
Kazmi, SU
Hakonarson, H
Kottgen, A
Kalogeropoulos, A
Frossard, P
Kamal, A
Dichgans, M
Cappola, T
Reilly, MP
Danesh, J
Rader, DJ
Voight, BF
Saleheen, D
AF Keenan, Tanya
Zhao, Wei
Rasheed, Asif
Ho, Weang K.
Malik, Rainer
Felix, Janine F.
Young, Robin
Shah, Nabi
Samuel, Maria
Sheikh, Nasir
Mucksavage, Megan L.
Shah, Omar
Li, Jin
Morley, Michael
Laser, Annika
Mallick, Nadeem Hayat
Zaman, Khan Shah
Ishaq, Mohammad
Rasheed, Syed Zahed
Memon, Fazal-ur-Rehman
Ahmed, Faisal
Hanif, Bashir
Lakhani, Muhammad Shakir
Fahim, Muhammad
Ishaq, Madiha
Shardha, Naresh Kumar
Ahmed, Naveeduddin
Mahmood, Khalid
Iqbal, Waseem
Akhtar, Saba
Raheel, Rabia
O'Donnell, Christopher J.
Hengstenberg, Christian
Maerz, Winifred
Kathiresan, Sekar
Samani, Nilesh
Goel, Anuj
Hopewell, Jemma C.
Chambers, John
Cheng, Yu-Ching
Sharma, Pankaj
Yang, Qiong
Rosand, Jonathan
Boncoraglio, Giorgio B.
Kazmi, Shahana Urooj
Hakonarson, Hakon
Koettgen, Anna
Kalogeropoulos, Andreas
Frossard, Philippe
Kamal, Ayeesha
Dichgans, Martin
Cappola, Thomas
Reilly, Muredach P.
Danesh, John
Rader, Daniel J.
Voight, Benjamin F.
Saleheen, Danish
TI Causal Assessment of Serum Urate Levels in Cardiometabolic Diseases
Through a Mendelian Randomization Study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE genetic; pleiotropy; single nucleotide polymorphism
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; URIC-ACID;
BLOOD-PRESSURE; GENETIC-VARIANTS; COMMON VARIANTS; ISCHEMIC-STROKE;
ARTERY-DISEASE; INCREASED RISK; LOCI
AB BACKGROUND Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain.
OBJECTIVES Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF).
METHODS This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls.
RESULTS Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations.
CONCLUSIONS Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions. (C) 2016 by the American College of Cardiology Foundation.
C1 [Keenan, Tanya; Zhao, Wei; Mucksavage, Megan L.; Shah, Omar; Kathiresan, Sekar; Reilly, Muredach P.; Rader, Daniel J.; Saleheen, Danish] Univ Penn, Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Keenan, Tanya; Kathiresan, Sekar] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Rasheed, Asif; Shah, Nabi; Samuel, Maria; Fahim, Muhammad; Ishaq, Madiha; Shardha, Naresh Kumar; Akhtar, Saba; Raheel, Rabia; Frossard, Philippe; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Ho, Weang K.; Young, Robin; Sheikh, Nasir; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Malik, Rainer; Dichgans, Martin] Univ Munich, Med Ctr, Inst Stroke & Dementia Res ISD, Munich, Germany.
[Felix, Janine F.] Erasmus MC, Dept Epidemiol, Univ Med Ctr Rotterdam, Amsterdam, Netherlands.
[Felix, Janine F.] NGI NCHA, Leiden, Netherlands.
[Li, Jin; Hakonarson, Hakon] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Morley, Michael] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Laser, Annika] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Laser, Annika] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Mallick, Nadeem Hayat] Punjab Inst Cardiol, Lahore, Pakistan.
[Zaman, Khan Shah] Natl Inst Cardiovasc Dis, Karachi, Pakistan.
[Ishaq, Mohammad; Rasheed, Syed Zahed] Karachi Inst Heart Dis, Karachi, Pakistan.
[Memon, Fazal-ur-Rehman] Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan.
[Ahmed, Faisal] Liaquat Natl Hosp, Dept Cardiol, Karachi, Pakistan.
[Hanif, Bashir; Lakhani, Muhammad Shakir] Tabba Heart Inst, Dept Cardiol, Karachi, Pakistan.
[Ahmed, Naveeduddin] Liaquat Natl Hosp, Dept Neurol, Karachi, Pakistan.
[Mahmood, Khalid] Dow Univ Hlth Sci, Civil Hosp, Dept Med, Karachi, Pakistan.
[Iqbal, Waseem] Lahore Gen Hosp, Dept Med, Lahore, Pakistan.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hengstenberg, Christian] Univ Hosp Regensburg, Internal Med Cardiol 2, Regensburg, Germany.
[Maerz, Winifred] Med Univ Graz, Clin Inst Med, Graz, Austria.
[Maerz, Winifred] Med Univ Graz, Chem Lab Diagnost, Graz, Austria.
[Maerz, Winifred] Heidelberg Univ, Mannheim Med Fac, Med Clin 5, Mannheim, Germany.
[Maerz, Winifred] Synlab Lab Serv GmbH, Synlab Acad, Mannheim, Germany.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Samani, Nilesh] Univ Leicester, Glenfield Gen Hosp, Dept Cardiovasc Sci, Clin Sci Wing, Leicester, Leics, England.
[Goel, Anuj] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Hopewell, Jemma C.] Univ Oxford, Div Cardiovasc Sci, Oxford, England.
[Chambers, John] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Cheng, Yu-Ching] Univ Maryland, Sch Med, Dept Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA.
[Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, London, England.
[Sharma, Pankaj] Hammersmith Hosp, London, England.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care, Boston, MA 02114 USA.
[Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol, Dept Cerebrovasc Dis, Milan, Italy.
[Kazmi, Shahana Urooj] Univ Karachi, Dept Microbiol, Karachi, Pakistan.
[Koettgen, Anna] Univ Freiburg, Renal Div, Univ Med Ctr Freiburg, Hugstetter Str 55, D-79106 Freiburg, Germany.
[Koettgen, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Kalogeropoulos, Andreas] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[Kamal, Ayeesha] Aga Khan Univ, Div Neurol, Dept Med, Karachi, Pakistan.
[Cappola, Thomas; Reilly, Muredach P.] Univ Penn, Cardiovasc Div, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Univ Penn, Dept Syst Pharmacol & Translat Therapeut, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Univ Penn, Dept Genet, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
[Saleheen, Danish] Univ Penn, Dept Biostat & Epidemiol, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
RP Voight, BF (reprint author), Univ Penn, Dept Syst Pharmacol & Translat Therapeut, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.; Voight, BF (reprint author), Univ Penn, Dept Genet, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.; Saleheen, D (reprint author), Univ Penn, Dept Biostat & Epidemiol, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bvoight@upenn.edu; saleheen@mail.med.upenn.edu
RI Boncoraglio, Giorgio/B-8647-2011;
OI Zhao, Wei/0000-0002-8301-9297
FU Italian Ministry of Health [RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC
2010/LR8]; [FP6 LSHM-CT-2007-037273]
FX For the CEDIR (Cerebrovascular Diseases Registry) (Milano, Italy), the
authors would like to acknowledge: Eugenio A. Parati and Emilio Ciusani
from Fondazione IRCCS Istituto Neurologico "Carlo Besta" of Milan, who
contributed to collection and genotyping of cases within CEDIR
(Cerebrovascular Diseases Registry), funded by Annual Research Funding
of the Italian Ministry of Health (Grant Numbers: RC 2007/LR6, RC
2008/LR6; RC 2009/LR8; RC 2010/LR8). Simona Barlera and Maria Grazia
Franzosi from Istituto di Ricerche Farmacologiche "Mario Negri" of Milan
contributed to collection and genotyping of the PROCARDIS controls,
funded by FP6 LSHM-CT-2007-037273.
NR 49
TC 8
Z9 8
U1 5
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 2
PY 2016
VL 67
IS 4
BP 407
EP 416
DI 10.1016/j.jacc.2015.10.086
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DB6HO
UT WOS:000368615600009
PM 26821629
ER
PT J
AU Chew, EY
Launer, L
Bernstein, P
AF Chew, Emily Y.
Launer, Lenore
Bernstein, Paul
TI Prevalence and Cost of Office Visits Prior to Colonoscopy for Colon
Cancer Screening
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID SUPPLEMENTATION; TRIAL
C1 [Chew, Emily Y.] NIH, Clin Trials Branch, Bldg 10, Bethesda, MD 20892 USA.
[Launer, Lenore] NIH, Neuroepidemiol Sect, Bldg 10, Bethesda, MD 20892 USA.
[Bernstein, Paul] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA.
RP Chew, EY (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD FEB 2
PY 2016
VL 315
IS 5
BP 514
EP 515
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DC2LZ
UT WOS:000369049500026
ER
PT J
AU Ishii, K
Barrett, AJ
AF Ishii, Kazusa
Barrett, Austin J.
TI Novel immunotherapeutic approaches for the treatment of acute leukemia
(myeloid and lymphoblastic)
SO THERAPEUTIC ADVANCES IN HEMATOLOGY
LA English
DT Review
DE immune-editing; leukemia; immunotherapy
ID STEM-CELL TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; REGULATORY
T-CELLS; GRAFT-VERSUS-LEUKEMIA; HISTONE DEACETYLASE INHIBITOR;
NATURAL-KILLER-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; TRANS-RETINOIC ACID;
PHASE-II TRIAL; BONE-MARROW-TRANSPLANTATION
AB There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures.
C1 [Barrett, Austin J.] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Ishii, Kazusa] NHLBI, Hematol Branch, US Natl Inst Hlth, Bldg 10, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM barrettjj@mail.nih.gov
NR 214
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2040-6207
EI 2040-6215
J9 THER ADV HEMATOL
JI Ther. Adv. Hematol.
PD FEB
PY 2016
VL 7
IS 1
BP 17
EP 39
DI 10.1177/2040620715616544
PG 23
WC Hematology
SC Hematology
GA DW4YP
UT WOS:000383649200002
PM 26834952
ER
PT J
AU William, WN
Papadimitrakopoulou, V
Lee, JJ
Mao, L
Cohen, EEW
Lin, HY
Gillenwater, AM
Martin, JW
Lingen, MW
Boyle, JO
Shin, DM
Vigneswaran, N
Shinn, N
Heymach, JV
Wistuba, II
Tang, XM
Kim, ES
Saintigny, P
Blair, EA
Meiller, T
Gutkind, JS
Myers, J
El-Naggar, A
Lippman, SM
AF William, William N., Jr.
Papadimitrakopoulou, Vassiliki
Lee, J. Jack
Mao, Li
Cohen, Ezra E. W.
Lin, Heather Y.
Gillenwater, Ann M.
Martin, Jack W.
Lingen, Mark W.
Boyle, Jay O.
Shin, Dong M.
Vigneswaran, Nadarajah
Shinn, Nancy
Heymach, John V.
Wistuba, Ignacio I.
Tang, Ximing
Kim, Edward S.
Saintigny, Pierre
Blair, Elizabeth A.
Meiller, Timothy
Gutkind, J. Silvio
Myers, Jeffrey
El-Naggar, Adel
Lippman, Scott M.
TI Erlotinib and the Risk of Oral Cancer The Erlotinib Prevention of Oral
Cancer (EPOC) Randomized Clinical Trial
SO JAMA ONCOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; NECK-CANCER; PHASE-II;
PREMALIGNANT LESIONS; GENOMIC INSTABILITY; PLUS CETUXIMAB;
BETA-CAROTENE; HEAD; ISOTRETINOIN
AB IMPORTANCE Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking.
OBJECTIVE To test if the epidermal growth factor receptor inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs.
DESIGN The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients.
INTERVENTIONS Oral erlotinib treatment (150mg/d) or placebo for 12 months.
MAIN OUTCOMES AND MEASURES Oral cancer-free survival (CFS).
RESULTS A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo-and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio [HR], 1.27; 95% CI, 0.68-2.38; P=.45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P=.01). Increased EGFR gene copy number correlated with LOH-positive status (P<.001) and lower CFS (P=.01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P=.01).
CONCLUSIONS AND RELEVANCE In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting.
C1 [William, William N., Jr.; Papadimitrakopoulou, Vassiliki; Mao, Li; Shin, Dong M.; Heymach, John V.; Wistuba, Ignacio I.; Tang, Ximing; Kim, Edward S.; Saintigny, Pierre; Lippman, Scott M.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd,Unit 432, Houston, TX 77004 USA.
[Lee, J. Jack; Lin, Heather Y.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Mao, Li; Meiller, Timothy] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Mao, Li; Meiller, Timothy] Univ Maryland, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA.
[Cohen, Ezra E. W.; Gutkind, J. Silvio; Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Cohen, Ezra E. W.] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Gillenwater, Ann M.; Martin, Jack W.; Myers, Jeffrey] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Lingen, Mark W.] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Boyle, Jay O.] Mem Sloan Kettering Canc Ctr, Dept Head & Neck Surg, 1275 York Ave, New York, NY 10021 USA.
[Shin, Dong M.] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA.
[Vigneswaran, Nadarajah] Univ Texas Houston, Sch Dent, Dept Diagnost & Biomed Sci, Houston, TX USA.
[Shinn, Nancy] Univ Texas MD Anderson Canc Ctr, Dept Palliat Care Med, Houston, TX 77030 USA.
[Wistuba, Ignacio I.; Tang, Ximing] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
[Kim, Edward S.] Carolinas Healthcare Syst, Levine Canc Inst, Charlotte, NC USA.
[Saintigny, Pierre] Canc Res Ctr Lyon, INSERM U1052, Lyon, France.
[Saintigny, Pierre] Canc Res Ctr Lyon, CNRS UMR 5286, Lyon, France.
[Blair, Elizabeth A.] Univ Chicago, Dept Surg, Sect Otolaryngol Head & Neck Surg, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[El-Naggar, Adel] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
RP William, WN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd,Unit 432, Houston, TX 77004 USA.; Lippman, SM (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr,Ste 0658, La Jolla, CA 92093 USA.
EM wnwillia@mdanderson.org; slippman@ucsd.edu
FU OSI Pharmaceuticals; National Cancer Institute [P01 CA106451, P50
CA097007, P30 CA016672]; Cancer Prevention and Research Institute of
Texas grant [RP140464]; Conquer Cancer Foundation Career Development
Award
FX This work was financially supported by OSI Pharmaceuticals, by National
Cancer Institute grants P01 CA106451 (Dr Lippman), P50 CA097007 (Dr
Lippman), and P30 CA016672, by Cancer Prevention and Research Institute
of Texas grant RP140464 (Dr William), and by Conquer Cancer Foundation
Career Development Award (Dr William). OSI Pharmaceuticals also provided
drug supply.
NR 40
TC 8
Z9 8
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD FEB
PY 2016
VL 2
IS 2
BP 209
EP 216
DI 10.1001/jamaoncol.2015.4364
PG 8
WC Oncology
SC Oncology
GA DW5JL
UT WOS:000383680200014
PM 26540028
ER
PT J
AU Takebe, N
Yang, SX
AF Takebe, Naoko
Yang, Sherry X.
TI Sonic hedgehog signaling pathway and gallbladder cancer: targeting with
precision medicine approach
SO CHINESE CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID WHOLE-EXOME; VISMODEGIB; CARCINOMA
C1 [Takebe, Naoko] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Takebe, N (reprint author), 9609 Med Ctr Dr,MSC9739, Rockville, MD 20852 USA.
EM Takeben@mail.nih.gov; sherry.yang@nih.gov
NR 16
TC 1
Z9 1
U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2304-3865
EI 2304-3873
J9 CHIN CLIN ONCOL
JI Chin. Clin. Oncol.
PD FEB
PY 2016
VL 5
IS 1
AR UNSP 1
DI 10.3978/j.issn.2304-3865.2016.01.02
PG 3
WC Oncology
SC Oncology
GA EB7OL
UT WOS:000387577700001
PM 26932425
ER
PT J
AU Ito, T
Jensen, RT
AF Ito, Tetsuhide
Jensen, Robert T.
TI Imaging in multiple endocrine neoplasia type 1: recent studies show
enhanced sensitivities but increased controversies
SO INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY
LA English
DT Review
DE endoscopic ultrasound; hyperparathyroidism; insulinoma; MEN1; MRI;
pancreatic neuroendocrine tumor; somatostatin-receptor scintigraphy;
thymic carcinoid; Zollinger-Ellison syndrome
ID ZOLLINGER-ELLISON-SYNDROME; PANCREATIC NEUROENDOCRINE TUMORS;
SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ISLET-CELL TUMORS; SELECTIVE
INTRAARTERIAL INJECTION; ENETS CONSENSUS GUIDELINES; LONG-TERM-FOLLOW;
ENDOSCOPIC ULTRASONOGRAPHY; DUODENAL GASTRINOMAS; SURGICAL-MANAGEMENT
AB In multiple endocrine neoplasia type 1 (MEN1) patients, a number of recent studies compare the ability of different, new imaging modalities to existing modalities to localize the important neuroendocrine tumors (NETs) that contribute to their decreased life expectancy (pancreatic NETs [pNETs] and thymic carcinoids). These included the use of Ga-68-DOTATOC-PET/CT, endoscopic ultrasound and MRI. The current paper analyzes these results in light of current guidelines and controversies involved in the treatment/management of MEN1 patients. Particular attention is paid to results in these studies with thymic carcinoids and nonfunctional pNETs/gastrinomas, which recent studies show are particularly important in determining long-term survival. These studies show a number of promising imaging results but also raise a number of controversies, which will need to be addressed both in their use initially and for serial studies in these patients.
C1 [Ito, Tetsuhide] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
[Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20817 USA.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20817 USA.
EM robertj@bdg10.niddk.nih.gov
FU Intramural NIH HHS [Z01 DK053101-20, Z01 DK053200-17, Z99 DK999999]
NR 131
TC 4
Z9 4
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 2045-0869
EI 2045-0877
J9 INT J ENDOCR ONCOL
JI Int. J. Endocr. Oncol.
PD FEB
PY 2016
VL 3
IS 1
BP 53
EP 66
DI 10.2217/ije.15.29
PG 14
WC Oncology
SC Oncology
GA EB6NI
UT WOS:000387500400007
PM 26834963
ER
PT J
AU Lopez, G
Monestime, G
Sidransky, E
AF Lopez, Grisel
Monestime, Gianina
Sidransky, Ellen
TI Clinical studies of GBA1-associated parkinsonism: progress and
challenges
SO NEURODEGENERATIVE DISEASE MANAGEMENT
LA English
DT Editorial Material
DE dementia with Lewy bodies; Gaucher disease; GBA1 mutations;
glucocerebrosidase; lysosome; Parkinson disease; parkinsonism
ID GAUCHER-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; ALPHA-SYNUCLEIN; GBA;
MANIFESTATIONS; MULTICENTER; DEFICIENCY; RISK
C1 [Lopez, Grisel; Monestime, Gianina; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS
NR 20
TC 2
Z9 2
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-2024
EI 1758-2032
J9 NEURODEGENER DIS MAN
JI Neurodegener. Dis. Manag.
PD FEB
PY 2016
VL 6
IS 1
BP 1
EP 4
DI 10.2217/nmt.15.68
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA EB5XN
UT WOS:000387454300001
PM 26782311
ER
PT J
AU Bantle, AE
Chow, LS
Steffen, LM
Wang, Q
Hughes, J
Durant, NH
Ingram, KH
Reis, JP
Schreiner, PJ
AF Bantle, Anne E.
Chow, Lisa S.
Steffen, Lyn M.
Wang, Qi
Hughes, John
Durant, Nefertiti H.
Ingram, Katherine H.
Reis, Jared P.
Schreiner, Pamela J.
TI Association of Mediterranean diet and cardiorespiratory fitness with the
development of pre-diabetes and diabetes: the Coronary Artery Risk
Development in Young Adults (CARDIA) study
SO BMJ OPEN DIABETES RESEARCH & CARE
LA English
DT Article
ID PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; INSULIN-RESISTANCE; OLIVE OIL;
FOLLOW-UP; TYPE-2; PREVENTION; WOMEN; MEN; INTERVENTION
AB Objective: To better understand the association between a modified Mediterranean diet pattern in young adulthood, cardiorespiratory fitness in young adulthood, and the odds of developing pre-diabetes or diabetes by middle age.
Research design and methods: Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have pre-diabetes or diabetes at baseline (year 0 (Y0), ages 18-30) and who had data available at the Y0 and year 25 (Y25) visits were included in this analysis (n=3358). Polytomous logistic regression models were used to assess the association between baseline dietary intake and fitness data and odds of pre-diabetes or diabetes by middle age (Y25, ages 43-55).
Results: At the Y25 visit, 1319 participants (39%) had pre-diabetes and 393 (12%) had diabetes. Higher baseline fitness was associated with lower odds of pre-diabetes and of diabetes at Y25. After adjustment for covariates, each SD increment in treadmill duration (181 s) was associated with lower odds for prediabetes (OR 0.85, 95% CI 0.75 to 0.95, p=0.005) and for diabetes (OR 0.71, 95% CI 0.60 to 0.85, p=0.0002) when compared to normal glycemia. A modified Mediterranean diet pattern was not associated with either pre-diabetes or diabetes. No interaction between cardiorespiratory fitness and dietary intake was observed, but baseline fitness remained independently associated with incident pre-diabetes and diabetes following adjustment for diet.
Conclusions: Higher cardiorespiratory fitness in young adulthood, but not a modified Mediterranean diet pattern, is associated with lower odds of pre-diabetes and of diabetes in middle age.
C1 [Bantle, Anne E.; Chow, Lisa S.] Univ Minnesota, Dept Med, Div Endocrinol & Diabet, Box 736 UMHC, Minneapolis, MN 55455 USA.
[Steffen, Lyn M.; Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Wang, Qi] Univ Minnesota, Clin & Translat Sci Inst, Minneapolis, MN USA.
[Hughes, John] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[Durant, Nefertiti H.] Univ Alabama Birmingham, Dept Pediat, Div Pediat & Adolescent Med, Birmingham, AL USA.
[Ingram, Katherine H.] Kennesaw State Univ, Dept Exercise Sci & Sport Management, Kennesaw, GA USA.
[Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bldg 10, Bethesda, MD 20892 USA.
RP Bantle, AE (reprint author), Univ Minnesota, Dept Med, Div Endocrinol & Diabet, Box 736 UMHC, Minneapolis, MN 55455 USA.
EM bant0015@umn.edu
FU NHLBI NIH HHS [HHSN268201300026C, HHSN268200900041C, HHSN268201300025C,
HHSN268201300027C, HHSN268201300028C, HHSN268201300029C]; NIDDK NIH HHS
[P30 DK079626, T32 DK007203]
NR 35
TC 0
Z9 0
U1 5
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2052-4897
J9 BMJ OPEN DIAB RES CA
JI BMJ Open Diab. Res. Care
PD FEB
PY 2016
VL 4
IS 1
AR e000229
DI 10.1136/bmjdrc-2016-000229
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA EA1DQ
UT WOS:000386333100054
PM 27648287
ER
PT J
AU Ventetuolo, CE
Mitra, N
Wan, F
Manichaikul, A
Barr, RG
Johnson, C
Bluemke, DA
Lima, JAC
Tandri, H
Ouyang, P
Kawut, SM
AF Ventetuolo, Corey E.
Mitra, Nandita
Wan, Fei
Manichaikul, Ani
Barr, R. Graham
Johnson, Craig
Bluemke, David A.
Lima, Joao A. C.
Tandri, Hari
Ouyang, Pamela
Kawut, Steven M.
TI Oestradiol metabolism and androgen receptor genotypes are associated
with right ventricular function
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID PULMONARY ARTERIAL-HYPERTENSION; CATECHOL-O-METHYLTRANSFERASE; PRESERVED
EJECTION FRACTION; BREAST-CANCER; HEART-FAILURE; RISK-FACTORS;
PORTOPULMONARY HYPERTENSION; POSTMENOPAUSAL WOMEN; ESTROGEN METABOLISM;
SEX-DIFFERENCES
AB Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown.
We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively.
In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p<7.2x10(-6)) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF.
Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure.
C1 [Ventetuolo, Corey E.] Brown Univ, Alpert Med Sch, Dept Med & Hlth Serv, Providence, RI 02912 USA.
[Ventetuolo, Corey E.] Brown Univ, Alpert Med Sch, Dept Policy & Practice, Providence, RI 02912 USA.
[Mitra, Nandita; Wan, Fei] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
[Johnson, Craig] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA.
[Lima, Joao A. C.; Tandri, Hari; Ouyang, Pamela] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Kawut, Steven M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.
RP Ventetuolo, CE (reprint author), Rhode Isl Hosp, Div Pulm Crit Care & Sleep, APC 747,593 Eddy St, Providence, RI 02903 USA.
EM corey_ventetuolo@brown.edu
OI Ventetuolo, Corey /0000-0002-4223-4775; Manichaikul,
Ani/0000-0002-5998-795X; Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health [P20GM103652, K24 HL103844]; National
Heart, Lung, and Blood Institute (NHLBI); NHLBI [N02-HL-64278]; American
Heart Association [11FTF7400032]; [R01-HL086719]; [N01-HC-95159];
[N01-HC-95160]; [N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163];
[N01-HC-95164]; [N01-HC-95165]; [N01-HC-95166]; [N01-HC-95167];
[N01-HC-95168]; [N01-HC-95169]; [UL1-TR-001079]; [UL1-TR-000040]
FX This work was completed with support from the American Heart Association
11FTF7400032, National Institutes of Health P20GM103652 and K24
HL103844. MESA 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
R01-HL086719, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167,
N01-HC-95168, N01-HC-95169, UL1-TR-001079, and UL1-TR-000040. Funding
for SHARe genotyping was provided by NHLBI Contract N02-HL-64278.
Funding information for this article has been deposited with FundRef.
NR 48
TC 7
Z9 7
U1 1
U2 3
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 FEB
PY 2016
VL 47
IS 2
BP 553
EP 563
DI 10.1183/13993003.01083-2015
PG 11
WC Respiratory System
SC Respiratory System
GA DY7CJ
UT WOS:000385286600026
PM 26647441
ER
PT J
AU Lin, YC
Winokur, P
Blake, A
Wu, TX
Manischewitz, J
King, LR
Romm, E
Golding, H
Bielekova, B
AF Lin, Yen Chih
Winokur, Paige
Blake, Andrew
Wu, Tianxia
Manischewitz, Jody
King, Lisa R.
Romm, Elena
Golding, Hana
Bielekova, Bibiana
TI Patients with MS under daclizumab therapy mount normal immune responses
to influenza vaccination
SO NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
LA English
DT Article
ID HIGH-YIELD PROCESS; MULTIPLE-SCLEROSIS; DOUBLE-BLIND; ALPHA-CHAIN;
T-CELLS; INTERLEUKIN-2; ANTIBODY; RECEPTOR; TRIAL; LYMPHOCYTES
AB Objective: The purpose of this study was to assess the potential immunosuppressive role of daclizumab, a humanized monoclonal antibody against the a chain of the interleukin 2 receptor, in vivo, by comparing immune responses to the 2013 seasonal influenza vaccination between patients with multiple sclerosis (MS) on long-term daclizumab therapy and controls.
Methods: Previously defined subpopulations of adaptive immune cells known to correlate with the immune response to the influenza vaccination were evaluated by 12-color flow cytometry in 23 daclizumab-treated patients with MS and 14 MS or healthy controls before (D0) and 1 day (D1) and 7 days (D7) after administration of the 2013 Afluria vaccine. Neutralizing antibody titers and CD4(+), CD8(+) T cell, B cell, and natural killer cell proliferation to 3 strains of virus contained in the Afluria vaccine were assessed at D0, D7, and 180 days postvaccination.
Results: Daclizumab-treated patients and controls demonstrated comparable, statistically significant expansions of previously defined subpopulations of activated CD8(+) T cells and B cells that characterize the development of effective immune responses to the influenza vaccine, while proliferation of T cells to influenza and control antigens was diminished in the daclizumab cohort. All participants fulfilled FDA criteria for seroconversion or seroprotection in antibody assays.
Conclusion: Despite the mild immunosuppressive effects of daclizumab in vivo demonstrated by an increased incidence of infectious complications in clinical trials, patients with MS under daclizumab therapy mount normal antibody responses to influenza vaccinations. Neurol Neuroimmunol Neuroinflamm 2016;3:e196; doi: 10.1212/NXI.0000000000000196
C1 [Lin, Yen Chih; Winokur, Paige; Blake, Andrew; Romm, Elena; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Wu, Tianxia] NINDS, Clin Neurosci Program, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, CBER, Rockville, MD 20857 USA.
[Bielekova, Bibiana] NIH, Ctr Human Immunol, Bldg 10, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM bibi.bielekova@nih.gov
NR 26
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2332-7812
J9 NEUROL-NEUROIMMUNOL
JI Neurol.-Neuroimmunol. Neuroinflammation
PD FEB
PY 2016
VL 3
IS 1
AR e196
DI 10.1212/NXI.0000000000000196
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DX7MT
UT WOS:000384572500014
PM 26848487
ER
PT J
AU Banerjee, H
Verma, M
AF Banerjee, Hiren
Verma, Mukesh
TI Intraoperative brain cancer detection with Raman spectroscopy in humans
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
C1 [Banerjee, Hiren] Univ N Carolina, Elizabeth City State Univ, Dept Biol & Pharmaceut Sci, Campus Box 930,1704 Weeksville Rd, Elizabeth City, NC 27909 USA.
[Verma, Mukesh] NCI, Methods & Technol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20850 USA.
RP Banerjee, H (reprint author), Univ N Carolina, Elizabeth City State Univ, Dept Biol & Pharmaceut Sci, Campus Box 930,1704 Weeksville Rd, Elizabeth City, NC 27909 USA.
EM docbanerjee@hotmail.com
NR 1
TC 0
Z9 0
U1 1
U2 1
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD FEB
PY 2016
VL 4
IS 4
AR 68
DI 10.3978/j.issn.2305-5839.2015.11.16
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DY0MX
UT WOS:000384792000005
PM 27004215
ER
PT J
AU Hoxha, J
Chandar, P
He, Z
Cimino, J
Hanauer, D
Weng, CH
AF Hoxha, Julia
Chandar, Praveen
He, Zhe
Cimino, James
Hanauer, David
Weng, Chunhua
TI DREAM: Classification scheme for dialog acts in clinical research query
mediation
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Clinical research query mediation dialog; Dialog act modeling; Dialog
annotation scheme; Human-human conversation analysis
ID SYSTEMS
AB Clinical data access involves complex but opaque communication between medical researchers and query analysts. Understanding such communication is indispensable for designing intelligent human machine dialog systems that automate query formulation. This study investigates email communication and proposes a novel scheme for classifying dialog acts in clinical research query mediation. We analyzed 315 email messages exchanged in the communication for 20 data requests obtained from three institutions. The messages were segmented into 1333 utterance units. Through a rigorous process, we developed a classification scheme and applied it for dialog act annotation of the extracted utterances. Evaluation results with high inter-annotator agreement demonstrate the reliability of this scheme. This dataset is used to contribute preliminary understanding of dialog acts distribution and conversation flow in this dialog space. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Hoxha, Julia; Chandar, Praveen; He, Zhe; Weng, Chunhua] Columbia Univ, Dept Biomed Informat, 622 W 168th St,PH-20, New York, NY 10032 USA.
[Cimino, James] NIH, Lab Informat Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Hanauer, David] Univ Michigan, Dept Pediat, Sch Informat, Ann Arbor, MI 48109 USA.
RP Weng, CH (reprint author), Columbia Univ, Dept Biomed Informat, 622 W 168th St,PH-20, New York, NY 10032 USA.
EM chunhua@columbia.edu
RI He, Zhe/E-1549-2017
OI He, Zhe/0000-0003-3608-0244
FU National Library of Medicine [R01LM009886]
FX This work was supported by The National Library of Medicine Grants
R01LM009886 (PI: Weng). We thank Dr. Julia Hirschberg for the precious
feedback.
NR 43
TC 1
Z9 1
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD FEB
PY 2016
VL 59
BP 89
EP 101
DI 10.1016/j.jbi.2015.11.011
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA DX9HJ
UT WOS:000384703900007
PM 26657707
ER
PT J
AU Dey, S
Li, XX
Teng, RF
Alnaeeli, M
Chen, ZY
Rogers, H
Noguchi, CT
AF Dey, Soumyadeep
Li, Xiaoxia
Teng, Ruifeng
Alnaeeli, Mawadda
Chen, ZhiYong
Rogers, Heather
Noguchi, Constance Tom
TI Erythropoietin regulates POMC expression via STAT3 and potentiates
leptin response
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Article
DE erythropoietin; POMC; hypothalamus and neuroendocrinology; gene
expression
ID DIET-INDUCED OBESITY; ENDOTHELIAL-CELLS; RECEPTOR; MICE; NEURONS;
HOMEOSTASIS; WEIGHT; BRAIN; PROLIFERATION; MELANOCORTIN
AB The arcuate nucleus of the hypothalamus is essential for metabolic homeostasis and responds to leptin by producing several neuropeptides including proopiomelanocortin (POMC). We previously reported that high-dose erythropoietin (Epo) treatment in mice while increasing hematocrit reduced body weight, fat mass, and food intake and increased energy expenditure. Moreover, we showed that mice with Epo receptor (EpoR) restricted to erythroid cells (DEpoRE) became obese and exhibited decreased energy expenditure. Epo/EpoR signaling was found to promote hypothalamus POMC expression independently from leptin. Herein we used WT and DEpoRE mice and hypothalamus-derived neural culture system to study the signaling pathways activated by Epo in POMC neurons. We show that Epo stimulation activated STAT3 signaling and upregulated POMC expression in WT neural cultures. DEpoRE mice hypothalamus showed reduced POMC levels and lower STAT3 phosphorylation, with and without leptin treatment, compared to in vivo and ex vivo WT controls. Collectively, these data show that Epo regulates hypothalamus POMC expression via STAT3 activation, and provide a previously unrecognized link between Epo and leptin response.
C1 [Dey, Soumyadeep; Li, Xiaoxia; Teng, Ruifeng; Alnaeeli, Mawadda; Chen, ZhiYong; Rogers, Heather; Noguchi, Constance Tom] NIDDK, Mol Med Branch, NIH, Bldg 10,Room 9N319,10 Ctr Dr MSC 1822, Bethesda, MD 20892 USA.
[Li, Xiaoxia] Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100191, Peoples R China.
RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Room 9N319,10 Ctr Dr MSC 1822, Bethesda, MD 20892 USA.
EM connien@helix.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, NIH, Bethesda, USA
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, NIH,
Bethesda, USA.
NR 44
TC 0
Z9 0
U1 0
U2 2
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
EI 1479-6813
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD FEB
PY 2016
VL 56
IS 2
BP 55
EP 67
DI 10.1530/JME-15-0171
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DS3XO
UT WOS:000380716200003
PM 26563310
ER
PT J
AU Hewitt, SC
Winuthayanon, W
Korach, KS
AF Hewitt, Sylvia C.
Winuthayanon, Wipawee
Korach, Kenneth S.
TI What's new in estrogen receptor action in the female reproductive tract
SO JOURNAL OF MOLECULAR ENDOCRINOLOGY
LA English
DT Review
DE estrogen receptors; gene expression; gene regulation; hormone action;
uterus/endometrium
ID EPITHELIAL-CELL PROLIFERATION; DEOXYRIBONUCLEIC-ACID-BINDING; MUTATION
PROVIDES EVIDENCE; NUCLEAR RECEPTOR; IN-VIVO; GENE-EXPRESSION;
TRANSCRIPTION FACTORS; TARGETED DISRUPTION; REGULATED GENES; C/EBP-BETA
AB Estrogen receptor alpha (ERa) is a critical player in development and function of the female reproductive system. Perturbations in ERa response can affect wide-ranging aspects of health in humans as well as in livestock and wildlife. Because of its long-known and broad impact, ERa mechanisms of action continue to be the focus on cutting-edge research efforts. Consequently, novel insights have greatly advanced understanding of every aspect of estrogen signaling. In this review, we attempt to briefly outline the current understanding of ERa mediated mechanisms in the context of the female reproductive system.
C1 [Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Receptor Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Winuthayanon, Wipawee] Washington State Univ, Coll Vet Med, Sch Mol Biosci, Pullman, WA 99164 USA.
RP Korach, KS (reprint author), NIEHS, Receptor Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU Division of Intramural Research of the NIEHS/NIH [1ZIAES070065]
FX Research support for studies reported in this review was provided by the
Division of Intramural Research of the NIEHS/NIH 1ZIAES070065 to K S K.
NR 128
TC 7
Z9 7
U1 3
U2 7
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0952-5041
EI 1479-6813
J9 J MOL ENDOCRINOL
JI J. Mol. Endocrinol.
PD FEB
PY 2016
VL 56
IS 2
BP R55
EP R71
DI 10.1530/JME-15-0254
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DS3XO
UT WOS:000380716200002
PM 26826253
ER
PT J
AU Nguyen, KL
Tian, X
Alam, S
Mehari, A
Leung, SW
Seamon, C
Allen, D
Minniti, CP
Sachdev, V
Arai, AE
Kato, GJ
AF Kim-Lien Nguyen
Tian, Xin
Alam, Shoaib
Mehari, Alem
Leung, Steve W.
Seamon, Catherine
Allen, Darlene
Minniti, Caterina P.
Sachdev, Vandana
Arai, Andrew E.
Kato, Gregory J.
TI Elevated transpulmonary gradient and cardiac magnetic resonance-derived
right ventricular remodeling predict poor outcomes in sickle cell
disease
SO HAEMATOLOGICA
LA English
DT Letter
DE pulmonary hypertension; magnetic resonance imaging; right ventricle;
cardiomyopathy; sickle cell disease
ID RIGHT HEART CATHETERIZATION; PULMONARY-HYPERTENSION; MORTALITY; ANEMIA;
ADULTS
C1 [Alam, Shoaib; Sachdev, Vandana] Lung & Blood Inst, Cardiovasc & Pulm Branch, Bethesda, MD USA.
[Mehari, Alem; Seamon, Catherine; Allen, Darlene; Minniti, Caterina P.; Kato, Gregory J.] Lung & Blood Inst, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD USA.
[Tian, Xin] NHLBI, Off Biostat Res, Bethesda, MD USA.
[Kim-Lien Nguyen; Mehari, Alem; Leung, Steve W.; Arai, Andrew E.] Howard Univ, Coll Med, Washington, DC USA.
[Kim-Lien Nguyen] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA USA.
[Kim-Lien Nguyen] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Kato, Gregory J.] Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA.
[Kato, Gregory J.] Univ Pittsburgh, Adult Sickle Cell Ctr Excellence, Pittsburgh, PA USA.
[Minniti, Caterina P.] Montefiore Med Ctr, Sickle Cell Ctr, Div Hematol Oncol, New York, NY USA.
[Leung, Steve W.] Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA.
RP Kato, GJ (reprint author), Lung & Blood Inst, Sickle Cell Vasc Dis Sect, Hematol Branch, Bethesda, MD USA.; Kato, GJ (reprint author), Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA USA.; Kato, GJ (reprint author), Univ Pittsburgh, Adult Sickle Cell Ctr Excellence, Pittsburgh, PA USA.
EM katogj@upmc.edu
RI Kato, Gregory/I-7615-2014; Leung, Steve/E-5624-2011;
OI Kato, Gregory/0000-0003-4465-3217; Leung, Steve/0000-0003-2832-2258;
Nguyen, Kim-Lien/0000-0002-8854-2976
FU NHLBI NIH HHS [ZIA HL006011, ZIA HL004607, ZIA HL006012, ZIA HL006015,
ZIA HL006137, ZID HL006140, ZIE HL006139]; PHS HHS [1ZIAHL004607,
1ZIAHL006011, 1ZIAHL006012, 1ZIAHL006015, 1ZIAHL006137, 1ZIDHL006140,
1ZIEHL006139]
NR 15
TC 2
Z9 2
U1 1
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD FEB
PY 2016
VL 101
IS 2
BP E40
EP E43
DI 10.3324/haematol.2015.125229
PG 4
WC Hematology
SC Hematology
GA DQ4EI
UT WOS:000379156300001
PM 26589907
ER
PT J
AU Xu, L
Ma, X
Bagattin, A
Mueller, E
AF Xu, L.
Ma, X.
Bagattin, A.
Mueller, E.
TI The transcriptional coactivator PGC1 alpha protects against hyperthermic
stress via cooperation with the heat shock factor HSF1
SO CELL DEATH & DISEASE
LA English
DT Article
ID MICE; PROTEINS; DISEASE; PGC-1; BIOGENESIS; MECHANISMS; APOPTOSIS;
COMPLEX; OBESITY
AB Heat shock proteins (HSPs) are required for the clearance of damaged and aggregated proteins and have important roles in protein homeostasis. It has been shown that the heat shock transcription factor, HSF1, orchestrates the transcriptional induction of these stress-regulated chaperones; however, the coregulatory factors responsible for the enhancement of HSF1 function on these target genes have not been fully elucidated. Here, we demonstrate that the cold-inducible coactivator, PGC1 alpha, also known for its role as a regulator of mitochondrial and peroxisomal biogenesis, thermogenesis and cytoprotection from oxidative stress, regulates the expression of HSPs in vitro and in vivo and modulates heat tolerance. Mechanistically, we show that PGC1 alpha physically interacts with HSF1 on HSP promoters and that cells and mice lacking PGC1 alpha have decreased HSPs levels and are more sensitive to thermal challenges. Taken together, our findings suggest that PGC1 alpha protects against hyperthermia by cooperating with HSF1 in the induction of a transcriptional program devoted to the cellular protection from thermal insults.
C1 [Xu, L.; Ma, X.; Bagattin, A.; Mueller, E.] NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8D12, Bethesda, MD 20814 USA.
RP Mueller, E (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8D12, Bethesda, MD 20814 USA.
EM elisabettam@mail.nih.gov
FU funds of the NIDDK Intramural Research Program of the NIH
FX We thank Pasha Sarraf for comments and are grateful to Bruce Spiegelman
(Harvard Medical School) and Carl Wu (National Cancer Institute) for
kindly providing reagents. This research was supported by funds of the
NIDDK Intramural Research Program of the NIH.
NR 34
TC 0
Z9 0
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD FEB
PY 2016
VL 7
AR e2102
DI 10.1038/cddis.2016.22
PG 9
WC Cell Biology
SC Cell Biology
GA DP5JG
UT WOS:000378531500001
PM 26890141
ER
PT J
AU Neychev, V
Sadowski, SM
Zhu, J
Allgaeuer, M
Kilian, K
Meltzer, P
Kebebew, E
AF Neychev, V.
Sadowski, S. M.
Zhu, J.
Allgaeuer, M.
Kilian, K.
Meltzer, P.
Kebebew, E.
TI Neuroendocrine Tumor of the Pancreas as a Manifestation of Cowden
Syndrome: A Case Report
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PTEN MUTATION; HAMARTOMA; DISEASE; PATHWAY; CELLS; GENE
AB Context: Germline mutations in the phosphatase and tensin homolog (PTEN) tumor suppressor gene are found in the majority of patients with Cowden syndrome (CS), who have an increased risk of breast, thyroid, and endometrial cancer. According to our current understanding of genetic changes in the PTEN gene and the resultant phenotypic features of CS, pancreatic neuroendocrine tumors (NETs) are not considered part of the clinical spectrum of CS.
Case description: We report a unique case of an advanced NET of the pancreas in a patient with CS. The germline DNA sequencing confirmed the clinical diagnosis of CS and revealed a PTEN mutation c.697C -> T (p.R233*) causing a premature stop codon in exon 7. The tumor DNA sequencing showed no loss of heterozygosity or any copy number changes and no other deleterious genetic alterations, including those commonly mutated in sporadic pancreatic NETs: MEN1, ATRX, DAXX, TP53, and genes involved in the mammalian target of rapamycin pathway. In addition, the high-throughput transcriptome analyzed by RNA-seq did not reveal any missed genetic alterations, aberrant splicing variants, gene fusions, or gene expression alterations. The immunohistochemical staining of the tumor for PTEN revealed an abnormal, uniformly strong cytoplasmic staining of tumor cells with virtually absent nuclear staining.
Conclusion: The results from genetic testing and histopathological techniques used to confirm CS diagnosis and characterize this unusual tumor tempted us to believe that in this case, the pancreatic NET was not a sporadic malignancy that occurred by coincidence, but rather represented a new entity in the spectrum of malignancies associated with CS.
C1 [Neychev, V.; Sadowski, S. M.; Kebebew, E.] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Zhu, J.; Kilian, K.; Meltzer, P.] NIH, Mol Genet Sect, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
[Allgaeuer, M.] NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU National Cancer Institute [NCT02315625]
FX This work was supported by the National Cancer Institute (NCT02315625).
NR 18
TC 0
Z9 0
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2016
VL 101
IS 2
BP 353
EP 358
DI 10.1210/jc.2015-3684
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DP6XI
UT WOS:000378642700003
PM 26678657
ER
PT J
AU Bornstein, SR
Allolio, B
Arlt, W
Barthel, A
Don-Wauchope, A
Hammer, GD
Husebye, ES
Merke, DP
Murad, MH
Stratakis, CA
Torpy, DJ
AF Bornstein, Stefan R.
Allolio, Bruno
Arlt, Wiebke
Barthel, Andreas
Don-Wauchope, Andrew
Hammer, Gary D.
Husebye, Eystein S.
Merke, Deborah P.
Murad, M. Hassan
Stratakis, Constantine A.
Torpy, David J.
TI Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine
Society Clinical Practice Guideline
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GLUCOCORTICOID REPLACEMENT THERAPY; AUTOIMMUNE ADDISONS-DISEASE; SHORT
SYNACTHEN TEST; INSULIN TOLERANCE-TEST; QUALITY-OF-LIFE; 1 MU-G;
SUBCUTANEOUS HYDROCORTISONE INFUSION; CORTICOTROPIN-RELEASING-HORMONE;
ADRENOCORTICOTROPIN STIMULATION TEST; X-LINKED ADRENOLEUKODYSTROPHY
AB Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency.
Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review.
Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence.
Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.
Conclusions: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 mu g) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (similar to 8 mg/m(2)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.
C1 [Bornstein, Stefan R.; Barthel, Andreas] Univ Klinikum Dresden, Med Klin & Poliklin 3, D-01307 Dresden, Germany.
[Bornstein, Stefan R.] Kings Coll London, Dept Endocrinol & Diabet, London WC2R 2LS, England.
[Allolio, Bruno] Univ Hosp Wurzburg, Endocrine & Diabet Unit, Dept Internal Med 1, D-97080 Wurzburg, Germany.
[Allolio, Bruno] Univ Wurzburg, Comprehens Heart Failure Ctr, D-97080 Wurzburg, Germany.
[Arlt, Wiebke] Univ Birmingham, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands, England.
[Barthel, Andreas] Endokrinol Ruhr, D-44866 Bochum, Germany.
[Don-Wauchope, Andrew] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4L8, Canada.
[Don-Wauchope, Andrew] Hamilton Reg Lab Med Program, Hamilton, ON L8N 4A6, Canada.
[Hammer, Gary D.] Univ Michigan, Dept Internal Med, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA.
[Hammer, Gary D.] Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA.
[Husebye, Eystein S.] Univ Bergen, Dept Clin Sci, N-5021 Bergen, Norway.
[Husebye, Eystein S.] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway.
[Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20814 USA.
[Murad, M. Hassan] Mayo Clin, Div Prevent Med, Rochester, MN 55905 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Torpy, David J.] Univ Adelaide, Endocrine & Metab Unit, Royal Adelaide Hosp, Adelaide, SA 5000, Australia.
RP Bornstein, SR (reprint author), Endocrine Soc, 2055 L St NW,Suite 600, Washington, DC 20036 USA.
EM govt-prof@endocrine.org
FU Medical Research Council [G0900567]
NR 181
TC 41
Z9 44
U1 4
U2 12
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2016
VL 101
IS 2
BP 364
EP 389
DI 10.1210/jc.2015-1710
PG 26
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DP6XI
UT WOS:000378642700005
PM 26760044
ER
PT J
AU Hoffmann, U
Massaro, JM
D'Agostino, RB
Kathiresan, S
Fox, CS
O'Donnell, CJ
AF Hoffmann, Udo
Massaro, Joseph M.
D'Agostino, Ralph B., Sr.
Kathiresan, Sekar
Fox, Caroline S.
O'Donnell, Christopher J.
TI Cardiovascular Event Prediction and Risk Reclassification by Coronary,
Aortic, and Valvular Calcification in the Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE coronary disease; prognosis; risk factors
ID ARTERY CALCIUM; COMPUTED-TOMOGRAPHY; DISEASE; ASSOCIATION; MORTALITY;
ATHEROSCLEROSIS; STROKE; DISCRIMINATION; POPULATION; MORBIDITY
AB Background-We determined whether vascular and valvular calcification predicted incident major coronary heart disease, cardiovascular disease (CVD), and all-cause mortality independent of Framingham risk factors in the community-based Framingham Heart Study.
Methods and Results-Coronary artery calcium (CAC), thoracic and abdominal aortic calcium, and mitral or aortic valve calcium were measured by cardiac computed tomography in participants free of CVD. Participants were followed for a median of 8 years. Multivariate Cox proportional hazards models were used to determine association of CAC, thoracic and abdominal aortic calcium, and mitral and aortic valve calcium with end points. Improvement in discrimination beyond risk factors was tested via the C-statistic and net reclassification index. In this cohort of 3486 participants (mean age 50 +/- 10 years; 51% female), CAC was most strongly associated with major coronary heart disease, followed by major CVD, and all-cause mortality independent of Framingham risk factors. Among noncoronary calcifications, mitral valve calcium was associated with major CVD and all-cause mortality independent of Framingham risk factors and CAC. CAC significantly improved discriminatory value beyond risk factors for coronary heart disease (area under the curve 0.78-0.82; net reclassification index 32%, 95% CI 11-53) but not for CVD. CAC accurately reclassified 85% of the 261 patients who were at intermediate (5-10%) 10-year risk for coronary heart disease based on Framingham risk factors to either low risk (n=172; no events observed) or high risk (n=53; observed event rate 8%).
Conclusions-CAC improves discrimination and risk reclassification for major coronary heart disease and CVD beyond risk factors in asymptomatic community-dwelling persons and accurately reclassifies two-thirds of the intermediate-risk population.
C1 [Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02115 USA.
[Hoffmann, Udo; Kathiresan, Sekar; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA.
[Massaro, Joseph M.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; Fox, Caroline S.; O'Donnell, Christopher J.] Boston Univ, Framingham, MA USA.
[Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA.; Hoffmann, U (reprint author), Harvard Univ, Sch Med, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
FU NIH Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, HL076784, AG028321, HL070100, HL060040, HL080124,
HL071039, HL077447, HL107385]
FX This work was supported by the NIH Heart, Lung, and Blood Institute's
Framingham Heart Study (contract no. N01-HC-25195, HL076784, AG028321,
HL070100, HL060040, HL080124, HL071039, HL077447, and HL107385). The
study sponsors had no role in the design and conduct of the study;
collection, management, analysis, and interpretation o the data; and
preparation, review, or approval of the manuscript.
NR 30
TC 2
Z9 2
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD FEB
PY 2016
VL 5
IS 2
AR e003144
DI 10.1161/JAHA.115.003144
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO9TW
UT WOS:000378131100023
ER
PT J
AU McAreavey, D
Vidal, JS
Aspelund, T
Eiriksdottir, G
Schelbert, EB
Kjartansson, O
Cao, JJ
Thorgeirsson, G
Sigurdsson, S
Garcia, M
Harris, TB
Launer, LJ
Gudnason, V
Arai, AE
AF McAreavey, Dorothea
Vidal, Jean-Sebastien
Aspelund, Thor
Eiriksdottir, Gudny
Schelbert, Erik B.
Kjartansson, Olafur
Cao, Jie J.
Thorgeirsson, Gudmundur
Sigurdsson, Sigurdur
Garcia, Melissa
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Arai, Andrew E.
TI Midlife Cardiovascular Risk Factors and Late-Life Unrecognized and
Recognized Myocardial Infarction Detect by Cardiac Magnetic Resonance:
ICELAND-MI, the AGES-Reykjavik Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE epidemiology; hypertension; magnetic resonance imaging; myocardial
infarction; risk factors
ID CORONARY-HEART-DISEASE; ASSOCIATION DETECTION PROJECT; SYSTOLIC
BLOOD-PRESSURE; REGRESSION DILUTION; RANDOMIZED-TRIAL; OLDER-ADULTS;
PREVALENCE; MEN; PROGNOSIS; MORTALITY
AB Background-Associations of atherosclerosis risk factors with unrecognized myocardial infarction (UMI) are unclear. We investigated associations of midlife risk factors with UMI and recognized MI (RMI) detected 31 years later by cardiac magnetic resonance.
Methods and Results-The Reykjavik Study (1967-1991) collected serial risk factors in subjects, mean (SD) age 48 (7) years. In ICELAND-MI (2004-2007), 936 survivors (76 (5) years) were evaluated by cardiac magnetic resonance. Analysis included logistic regression and random effects modeling. Comparisons are relative to subjects without MI. At baseline midlife evaluation, a modified Framingham risk score was significantly higher in RMI and in UMI versus no MI (7.4 (6.3)%; 7.1 (6.2)% versus 5.4 (5.8)%, P<0.001). RMI and UMI were more frequent in men (65%, 64% versus 43%; P<0.0001). Baseline systolic and diastolic blood pressure were significantly higher in UMI (138 (17) mm Hg versus 133 (17) mm Hg; P<0.006; 87 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Diastolic BP was significantly higher in RMI (88 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Cholesterol and triglycerides were significantly higher in RMI (6.7 (1.1) mmol/L versus 6.2 (1.1) mmol/L; P=0.0005; and 1.4 (0.7) mmol/L versus 1.1 (0.7) mmol/L; P<0.003). Cholesterol trended higher in UMI (P=0.08). Serial midlife systolic BP was significantly higher in UMI versus no MI (beta [SE] = 2.69 [1.28] mm Hg, P=0.04). Serial systolic and diastolic BP were significantly higher in RMI versus no MI (4.12 [1.60] mm Hg, P=0.01 and 2.05 [0.91] mm Hg, P=0.03) as were cholesterol (0.43 [0.11] mmol/L, P=0.0001) and triglycerides (0.3 [0.06] mmol/L, P<0.0001).
Conclusions-Midlife vascular risk factors are associated with UMI and RMI detected by cardiac magnetic resonance 31 years later. Systolic blood pressure was the most significant modifiable risk factor associated with later UMI.
C1 [McAreavey, Dorothea] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Vidal, Jean-Sebastien] Hop Broca, AP HP, Serv Gerontol 1, Paris, France.
[Vidal, Jean-Sebastien] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Aspelund, Thor; Eiriksdottir, Gudny; Kjartansson, Olafur; Thorgeirsson, Gudmundur; Sigurdsson, Sigurdur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor; Thorgeirsson, Gudmundur; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Schelbert, Erik B.; Cao, Jie J.; Arai, Andrew E.] NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP McAreavey, D (reprint author), 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM dmcareavey@cc.nih.gov
OI Vidal, Jean-Sebastien/0000-0001-6770-0720
FU National Institutes of Health in Bethesda, MD [NO1-AG-1-2100]; National
Institute of Aging Intramural Research Program in Bethesda, MD; NHLBI
Intramural Research Program in Bethesda, MD [Contract 1 Z01
HL004607-08CE]; NIH Clinical Center in Bethesda, MD; Hjartavernd (the
Icelandic Heart Association), Kopavogur in Iceland; Althingi (the
Icelandic Parliament), Reykjavik in Iceland
FX This study was supported by a contract from the National Institutes of
Health (NO1-AG-1-2100), the National Institute of Aging Intramural
Research Program, the NHLBI Intramural Research Program (Contract 1 Z01
HL004607-08CE), the NIH Clinical Center, all in Bethesda, MD and the
Hjartavernd (the Icelandic Heart Association), Kopavogur, and the
Althingi (the Icelandic Parliament), Reykjavik, both in Iceland. There
were no relationships with industry.
NR 59
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD FEB
PY 2016
VL 5
IS 2
AR e002420
DI 10.1161/JAHA.115.002420
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO9TW
UT WOS:000378131100033
ER
PT J
AU Therkelsen, KE
Abraham, TM
Pedley, A
Massaro, JM
Sutherland, P
Hoffmann, U
Fox, CS
AF Therkelsen, Kate E.
Abraham, Tobin M.
Pedley, Alison
Massaro, Joseph M.
Sutherland, Patrice
Hoffmann, Udo
Fox, Caroline S.
TI Association Between Prolactin and Incidence of Cardiovascular Risk
Factors in the Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE epidemiology; hormones; obesity; population
ID HORMONE-BINDING GLOBULIN; SIGNAL-TRANSDUCTION; PLASMA PROLACTIN;
BODY-WEIGHT; WOMEN; MEN; BROMOCRIPTINE; HYPERTENSION; FAT; TESTOSTERONE
AB Background-Prolactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors.
Methods and Results-Our sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable-adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5-mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91-1.23, P=0.46). Some exceptions were of note. In women, for each 5-mg/dL increment in prolactin, we observed increased odds of low high-density lipoprotein cholesterol at follow-up (odds ratio 1.50, 95% CI 1.18-1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5-mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18-2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04-2.78, P=0.03).
Conclusions-Prolactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.
C1 [Therkelsen, Kate E.; Pedley, Alison; Sutherland, Patrice; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Abraham, Tobin M.; Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, 75 Francis St, Boston, MA 02115 USA.
[Abraham, Tobin M.; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Fox, Caroline S.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
RP Fox, CS (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
FU NIH; [N01-HC-25195]
FX The Framingham Heart Study of the National Heart, Lung and Blood
Institute is supported by contract N01-HC-25195. Abraham is supported by
an NIH-sponsored T32 training grant.
NR 39
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD FEB
PY 2016
VL 5
IS 2
AR e002640
DI 10.1161/JAHA.115.002640
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DO9TW
UT WOS:000378131100051
ER
PT J
AU Mroczkowski, MM
Goes, FS
Riddle, MA
Grados, MA
Bienvenu, OJ
Greenberg, BD
Fyer, AJ
Mccracken, JT
Rauch, SL
Murphy, DL
Knowles, JA
Piacentini, J
Cullen, B
Rasmussen, SA
Pauls, DL
Nestadt, G
Samuels, J
AF Mroczkowski, M. M.
Goes, F. S.
Riddle, M. A.
Grados, M. A.
Bienvenu, O. J.
Greenberg, B. D.
Fyer, A. J.
Mccracken, J. T.
Rauch, S. L.
Murphy, D. L.
Knowles, J. A.
Piacentini, J.
Cullen, B.
Rasmussen, S. A.
Pauls, D. L.
Nestadt, G.
Samuels, J.
TI Dependent personality, separation anxiety disorder and other anxiety
disorders in OCD
SO PERSONALITY AND MENTAL HEALTH
LA English
DT Article
ID SCHIZOPHRENIA; RELIABILITY; PREDICTORS; RATIONALE; INTERVIEW; SCHEDULE;
12-MONTH; CHILDREN; VERSION; SAMPLE
AB Background - The purpose of this study was to investigate whether dependent personality and/or general personality dimensions might explain the strong relationships between separation anxiety disorder (Sep-AD) and three other anxiety disorders (agoraphobia, panic disorder and social anxiety disorder) in individuals with obsessive compulsive disorder (OCD).
Methods - Using data from 509 adult participants collected during the OCD Collaborative Genetic Study, we used logistic regression models to evaluate the relationships between Sep-AD, dependent personality score, general personality dimensions and three additional anxiety disorders.
Results - The dependent personality score was strongly associated with Sep-AD and the other anxiety disorders in models adjusted for age at interview, age at onset of OC symptoms and worst ever OCD severity score. Several general personality dimensions, especially neuroticism, extraversion and conscientiousness, were also related to Sep-AD and the other anxiety disorders. Sep-AD was not independently related to these anxiety disorders, in multivariate models including general personality and dependent personality disorder scores.
Conclusions - The results suggest that Sep-AD in childhood and these other anxiety disorders in adulthood are consequences of dependent personality disorder (for agoraphobia and panic disorder) or introversion (for social phobia). It is unknown whether these results would be similar in a non-OCD sample. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Mroczkowski, M. M.; Fyer, A. J.] Columbia Univ Coll Phys & Surg, Dept Psychiat, 722 W 168th St, New York, NY 10032 USA.
[Goes, F. S.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Cullen, B.; Nestadt, G.; Samuels, J.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Greenberg, B. D.; Rasmussen, S. A.] Brown Univ, Dept Psychiat & Human Behav, Alpert Med Sch, Providence, RI 02912 USA.
[Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Mccracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
[Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
[Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
RP Samuels, J (reprint author), Dept Psychiat & Behav Sci, 550 N Broadway 902, Baltimore, MD 21205 USA.
EM jsamuel1@jhmi.edu
OI Samuels, Jack/0000-0002-6715-7905
NR 27
TC 1
Z9 1
U1 4
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1932-8621
EI 1932-863X
J9 PERSONAL MENT HEALTH
JI Personal. Ment. Health
PD FEB
PY 2016
VL 10
IS 1
BP 22
EP 28
DI 10.1002/pmh.1321
PG 7
WC Psychiatry; Psychology, Social
SC Psychiatry; Psychology
GA DO9VL
UT WOS:000378136000003
PM 26542617
ER
PT J
AU Moore, RA
Head, MW
Ironside, JW
Ritchie, DL
Zanusso, G
Choi, YP
Priola, SA
AF Moore, Roger A.
Head, Mark W.
Ironside, James W.
Ritchie, Diane L.
Zanusso, Gianluigi
Choi, Young Pyo
Priola, Suzette A.
TI The Distribution of Prion Protein Allotypes Differs Between Sporadic and
Iatrogenic Creutzfeldt-Jakob Disease Patients
SO PLOS PATHOGENS
LA English
DT Article
ID SPONGIFORM ENCEPHALOPATHY; TRANSMISSION PROPERTIES; CODON-129
POLYMORPHISM; SHOTGUN PROTEOMICS; AMYLOID FORMATION; INCUBATION-TIME;
AGENT STRAIN; PRNP GENE; SCRAPIE; PRP
AB Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrPSc). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrPC) into infectious PrPSc. By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrPSc. In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrPC allotype to PrPSc in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrPSc with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrPC containing an M or V at residue 129 having a similar propensity to mis-fold into PrPSc thus causing sCJD. By contrast, PrPSc with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrPSc containing V at residue 129. In both types of CJD, the PrPSc allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrPSc allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD.
C1 [Moore, Roger A.; Priola, Suzette A.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Head, Mark W.; Ironside, James W.; Ritchie, Diane L.] Univ Edinburgh, Sch Clin Sci, Ctr Clin Brain Sci, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland.
[Zanusso, Gianluigi] Univ Verona, Dept Neurol & Movement Sci, I-37100 Verona, Italy.
[Choi, Young Pyo] Korea Brain Res Inst, Dept Neural Dev & Dis, Daegu, South Korea.
RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM spriola@nih.gov
OI Head, Mark/0000-0003-2034-8613; Ironside, James/0000-0001-5869-2108
FU National Institute of Allergy & Infectious Disease, National Institutes
of Health [AI000752-19]; Korea Brain Research Institute Research Program
of the Ministry of Science, ICT, and Future Planning [2231-415];
Department of Health; Scottish Government [PR-ST-0614-00008]
FX This research was supported by intramural research program of the
National Institute of Allergy & Infectious Disease, National Institutes
of Health (Recipient: SAP, Grant number AI000752-19,
http://www.niaid.nih.gov/Pages/default.aspx). Support for Young Pyo Choi
was also provided by the Korea Brain Research Institute Research Program
of the Ministry of Science, ICT, and Future Planning (2231-415,
http://www.incf.org/activities/projects/koreanbrain-research-institute).
The National CJD Research & Surveillance Unit is funded by the Policy
Research Programme (http://prp-ccf.org.uk/) of the Department of Health
and the Scottish Government (http://www.gov.scot/, Recipients: MWH, JWI;
Grant number PR-ST-0614-00008). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript
NR 53
TC 3
Z9 3
U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD FEB
PY 2016
VL 12
IS 2
AR e1005416
DI 10.1371/journal.ppat.1005416
PG 21
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DP0BP
UT WOS:000378152900017
PM 26840342
ER
PT J
AU Fichman, G
Guterman, T
Damron, J
Adler-Abramovich, L
Schmidt, J
Kesselman, E
Shimon, LJW
Ramamoorthy, A
Talmon, Y
Gazit, E
AF Fichman, Galit
Guterman, Tom
Damron, Joshua
Adler-Abramovich, Lihi
Schmidt, Judith
Kesselman, Ellina
Shimon, Linda J. W.
Ramamoorthy, Ayyalusamy
Talmon, Yeshayahu
Gazit, Ehud
TI Spontaneous structural transition and crystal formation in minimal
supramolecular polymer model
SO SCIENCE ADVANCES
LA English
DT Article
ID AROMATIC PEPTIDE AMPHIPHILES; AMINO-ACID DERIVATIVES; TECHNOLOGICAL
APPLICATIONS; DIPEPTIDE HYDROGELATOR; PHYSICAL-PROPERTIES;
BUILDING-BLOCKS; BETA-SHEETS; NANOSTRUCTURES; STATE; BIOMATERIALS
AB The association of building blocks into supramolecular polymers allows the fabrication of diverse functional architectures at the nanoscale. The use of minimal assembly units to explore polymer dynamics and phase transitions significantly contributes to the application of polymer physicochemical paradigms in the field of supramolecular polymers. We present a minimal model that displays spontaneous coordinated structural transitions between micro-and nanostructures, hydrogels with nanoscale order, and single crystals. The simple amphiphilic 9-fluorenylmethoxycarbonyl-3,4-dihydroxyphenylalanine (Fmoc-DOPA) modified amino acid undergoes a noninduced transition from spherical assemblies into nanofibrils followed by sol-gel transition, nanotube formation via intermediate assembly, and crystallization within the gel. Notably, the transition kinetics is slow enough to allow both multistage and multiscale characterization of the supramolecular arrangement using electron microscopy, vibrational and circular dichroism spectroscopies, nuclear magnetic resonance, and x-ray crystallography. This minimalistic system is the first comprehensive model for a complete spontaneous structural transition between diverse states governed by distinct molecular interactions.
C1 [Fichman, Galit; Guterman, Tom; Adler-Abramovich, Lihi; Gazit, Ehud] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-6997801 Tel Aviv, Israel.
[Damron, Joshua; Ramamoorthy, Ayyalusamy] Univ Michigan, Biophys, Ann Arbor, MI 48109 USA.
[Damron, Joshua; Ramamoorthy, Ayyalusamy] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Adler-Abramovich, Lihi] Tel Aviv Univ, Goldschleger Sch Dent Med, Dept Oral Biol, IL-6997801 Tel Aviv, Israel.
[Schmidt, Judith; Kesselman, Ellina; Talmon, Yeshayahu] Technion Israel Inst Technol, Dept Chem Engn, IL-32000 Haifa, Israel.
[Shimon, Linda J. W.] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel.
[Gazit, Ehud] Tel Aviv Univ, Iby & Aladar Fleischman Fac Engn, Dept Mat Sci & Engn, IL-6997801 Tel Aviv, Israel.
[Fichman, Galit] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
RP Gazit, E (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-6997801 Tel Aviv, Israel.; Gazit, E (reprint author), Tel Aviv Univ, Iby & Aladar Fleischman Fac Engn, Dept Mat Sci & Engn, IL-6997801 Tel Aviv, Israel.
EM ehudg@post.tau.ac.il
RI Gazit, Ehud/C-3715-2011;
OI Gazit, Ehud/0000-0001-5764-1720; Fichman, Galit/0000-0001-5060-0723
NR 60
TC 3
Z9 3
U1 8
U2 12
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 2375-2548
J9 SCI ADV
JI Sci. Adv.
PD FEB
PY 2016
VL 2
IS 2
AR e1500827
DI 10.1126/sciadv.1500827
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DP7YU
UT WOS:000378715900007
PM 26933679
ER
PT J
AU Isaacson, B
Bullova, P
Frone, M
Click, A
Hamplova, B
Rabaglia, J
Woodruff, S
Nwariaku, F
Kathuria, A
Pacak, K
Ghayee, HK
AF Isaacson, Brandon
Bullova, Petra
Frone, Megan
Click, Arielle
Hamplova, Barbora
Rabaglia, Jennifer
Woodruff, Stacey
Nwariaku, Fiemu
Kathuria, Amita
Pacak, Karel
Ghayee, Hans K.
TI AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED
HIF-2 alpha SIGNALING
SO ENDOCRINE PRACTICE
LA English
DT Article
ID ENDOCRINE NEOPLASIA TYPE-2; NECK PARAGANGLIOMAS; MUTATIONS;
PHEOCHROMOCYTOMA; MANAGEMENT; HEAD; POLYCYTHEMIA; DIAGNOSIS
AB Objective: To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catechol-amine-producing temporal bone paraganglioma (PGL).
Methods: Evaluation of a SDHC mutation-positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1 alpha (HIF-1 alpha) and 2 alpha (HIF-2 alpha).
Results: A 66-year-old man was noted to have a lytic skull base mass during work-up for his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine catecholamines and metanephrines revealed marked elevation of norepinephrine and normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial excision of skull base tumor was performed, which upon further examination revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy expression of TH and HIF-2 alpha but reduced expression of HIF-1 alpha. The remaining skull base PGL was treated with adjuvant radiation therapy. The patient's normetanephrine levels significantly decreased after surgery and radiation.
Conclusion: Here, we report an unusual case of a patient presenting with a germline SDHC mutation-related functional PGL along with concomitant primary hyperparathyroidism. The present case illustrates that overexpression of HIF-2 alpha but not of HIF-1 alpha is linked to the pathogenesis of SDHC mutation-related PGL, and it may be responsible for the aggressive clinical behavior of a usually indolent course of SDHC-related PGLs.
C1 [Isaacson, Brandon] Univ Texas Southwestern Med Ctr UTSW, Dept Otolaryngol Head & Neck Surg, Dallas, TX USA.
[Bullova, Petra; Hamplova, Barbora; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Bullova, Petra] Slovak Acad Sci, Inst Virol, Dept Mol Med, Bratislava, Slovakia.
[Frone, Megan] Univ Texas SW Med Ctr Dallas, Canc Genet, Dallas, TX 75390 USA.
[Click, Arielle] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
[Hamplova, Barbora] Charles Univ Prague, Dept Med, Gen Fac Hosp, Prague, Czech Republic.
[Hamplova, Barbora] Charles Univ Prague, Fac Med 1, Prague, Czech Republic.
[Rabaglia, Jennifer; Woodruff, Stacey; Nwariaku, Fiemu] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA.
[Kathuria, Amita; Ghayee, Hans K.] Univ Florida, Coll Med, Dept Internal Med, Div Endocrinol, 1601 SW Archer Rd, Gainesville, FL 32608 USA.
RP Ghayee, HK (reprint author), Univ Florida, Coll Med, Dept Internal Med, Div Endocrinol, 1601 SW Archer Rd, Gainesville, FL 32608 USA.; Ghayee, HK (reprint author), Malcom Randall VA Med Ctr, 1601 SW Archer Rd, Gainesville, FL 32608 USA.
EM hans.ghayee@medicine.ufl.edu
FU North American Neuroendocrine Tumor Society (NANETS)
FX We would like to acknowledge support for this research from the North
American Neuroendocrine Tumor Society (NANETS) to H.K.G.
NR 18
TC 1
Z9 1
U1 1
U2 1
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD FEB
PY 2016
VL 22
IS 2
BP 190
EP 195
DI 10.4158/EP15889.OR
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DO7NB
UT WOS:000377968200008
PM 26492543
ER
PT J
AU Duffy, AG
Makarova-Rusher, OV
Pratt, D
Kleiner, DE
Fioravanti, S
Walker, M
Carey, S
Figg, WD
Steinberg, SM
Anderson, V
Levy, E
Krishnasamy, V
Wood, BJ
Jones, J
Citrin, DE
Greten, TF
AF Duffy, Austin G.
Makarova-Rusher, Oxana V.
Pratt, Drew
Kleiner, David E.
Fioravanti, Suzanne
Walker, Melissa
Carey, Stephanie
Figg, William Douglas
Steinberg, Seth M.
Anderson, Victoria
Levy, Elliot
Krishnasamy, Venkatesh
Wood, Bradford J.
Jones, Jennifer
Citrin, Deborah E.
Greten, Tim F.
TI A pilot study of AMP-224, a PD-L2 Fc fusion protein, in combination with
stereotactic body radiation therapy (SBRT) in patients with metastatic
colorectal cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 21-23, 2016
CL San Francisco, CA
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Gastrointestinal Malignancies Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NIH, Radiol & Imaging Sci, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
NIH, Dept Radiat Oncol, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2016
VL 34
IS 4
SU S
MA 560
PG 1
WC Oncology
SC Oncology
GA DO9MB
UT WOS:000378109600540
ER
PT J
AU Duffy, AG
Makarova-Rusher, OV
Pratt, D
Kleiner, DE
Alewine, C
Fioravanti, S
Walker, M
Carey, S
Figg, WD
Steinberg, SM
Anderson, V
Levy, E
Krishnasamy, V
Wood, BJ
Jones, J
Citrin, DE
Greten, TF
AF Duffy, Austin G.
Makarova-Rusher, Oxana V.
Pratt, Drew
Kleiner, David E.
Alewine, Christine
Fioravanti, Suzanne
Walker, Melissa
Carey, Stephanie
Figg, William Douglas
Steinberg, Seth M.
Anderson, Victoria
Levy, Elliot
Krishnasamy, Venkatesh
Wood, Bradford J.
Jones, Jennifer
Citrin, Deborah E.
Greten, Tim F.
TI A pilot study of immune checkpoint inhibition (tremelimumab and/or
MEDI4736) in combination with radiation therapy in patients with
unresectable pancreatic cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 21-23, 2016
CL San Francisco, CA
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
NCI, Thorac & Gastrointestinal Malignancies Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Gastrointestinal Malignancies Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NIH, Radiol & Imaging Sci, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
NIH, Dept Radiat Oncol, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2016
VL 34
IS 4
SU S
MA TPS470
PG 1
WC Oncology
SC Oncology
GA DO9MB
UT WOS:000378109600452
ER
PT J
AU Le, DT
Uram, JN
Wang, H
Kemberling, H
Eyring, A
Bartlett, B
Goldberg, RM
Crocenzi, TS
Fisher, GA
Lee, JJ
Greten, TF
Laheru, D
Azad, NS
Donehower, RC
Luber, B
Koshiji, M
Eshleman, JR
Anders, RA
Vogelstein, B
Diaz, LA
AF Le, Dung T.
Uram, Jennifer N.
Wang, Hao
Kemberling, Holly
Eyring, Aleksandra
Bartlett, Bjarne
Goldberg, Richard M.
Crocenzi, Todd S.
Fisher, George A.
Lee, James J.
Greten, Tim F.
Laheru, Dan
Azad, Nilofer Saba
Donehower, Ross C.
Luber, Brandon
Koshiji, Minori
Eshleman, James R.
Anders, Robert A.
Vogelstein, Bert
Diaz, Luis A.
TI PD-1 blockade in mismatch repair deficient non-colorectal
gastrointestinal cancers.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 21-23, 2016
CL San Francisco, CA
C1 Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Richard J Solove Res Inst, Columbus, OH 43210 USA.
Providence Canc Ctr, Portland, OR USA.
Stanford Univ, Sch Med, Stanford, CA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
NCI, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Canc Ctr, Baltimore, MD USA.
Merck & Co Inc, Kenilworth, NJ USA.
Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
NR 0
TC 2
Z9 2
U1 3
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 FEB 1
PY 2016
VL 34
IS 4
SU S
MA 195
PG 1
WC Oncology
SC Oncology
GA DO9MB
UT WOS:000378109600189
ER
PT J
AU Makarova-Rusher, OV
Ulahannan, SV
Greten, TF
Duffy, AG
AF Makarova-Rusher, Oxana V.
Ulahannan, Susanna Varkey
Greten, Tim F.
Duffy, Austin G.
TI Pancreatic squamous cell carcinoma: Epidemiology, clinicopathologic
characteristics, and outcomes.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 21-23, 2016
CL San Francisco, CA
C1 NIH, NCI, Bldg 10, Bethesda, MD 20892 USA.
Canc & Blood Care, Ponca City, OK USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2016
VL 34
IS 4
SU S
MA 220
PG 1
WC Oncology
SC Oncology
GA DO9MB
UT WOS:000378109600214
ER
PT J
AU Park, JW
Park, JM
Green, JE
Kim, HK
AF Park, Jun Won
Park, Jung Min
Green, Jeffrey E.
Kim, Hark K.
TI Long-term effect of Wnt/beta-catenin small molecule inhibitor CWP232291
on intestinal carcinogenesis in novel GEM model deficient in Smad4 and
p53.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Gastrointestinal Cancers Symposium
CY JAN 21-23, 2016
CL San Francisco, CA
C1 Natl Canc Ctr, Biomol Funct Res Branch, Goyang, South Korea.
NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
Natl Canc Ctr, Goyang, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2016
VL 34
IS 4
SU S
MA 594
PG 1
WC Oncology
SC Oncology
GA DO9MB
UT WOS:000378109600572
ER
PT J
AU Arias, SA
Miller, I
Camargo, CA
Sullivan, AF
Goldstein, AB
Allen, MH
Manton, AP
Boudreaux, ED
AF Arias, Sarah A.
Miller, Ivan
Camargo, Carlos A., Jr.
Sullivan, Ashley F.
Goldstein, Amy B.
Allen, Michael H.
Manton, Anne P.
Boudreaux, Edwin D.
TI Factors Associated With Suicide Outcomes 12 Months After Screening
Positive for Suicide Risk in the Emergency Department
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID PHYSICAL ILLNESS
AB Objective: The main objective was to identify which patient characteristics have the strongest association with suicide outcomes in the 12 months after an index emergency department (ED) visit.
Methods: Data were analyzed fromthe first two phases of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE). The ED-SAFE study, a quasi-experimental, interrupted time-series design, involved participation from eight general medical EDs across the United States. Participants included adults presenting to the ED with active suicidal ideation or an attempt in the past week. Data collection included baseline interview; six-and 12-month chart reviews; and six-, 12-, 24-, 36-, and 52-week telephone follow-up assessments. Regression analyses were conducted.
Results: Among 874 participants, the median age was 37 years (interquartile range 27-47), with 56% of the sample being female (N=488), 74% white (N=649), and 13% Hispanic (N=113). At baseline, 577 (66%) participants had suicidal ideation only, whereas 297 (34%) had a suicide attempt in the past week. Data sufficient to determine outcomes were available for 782 (90%). In the 12 months after the index ED visit, 195 (25%) had documentation of at least one suicide attempt or suicide. High school education or less, an ED visit in the preceding six months, prior nonsuicidal self-injury, current alcohol misuse, and suicidal intent or plan were predictive of future suicidal behavior.
Conclusions: Continuing to build an understanding of the factors associated with future suicidal behaviors for this population will help guide design and implementation of improved suicide screening and interventions in the ED and better allocation of scarce resources.
C1 [Arias, Sarah A.; Miller, Ivan] Brown Univ, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Camargo, Carlos A., Jr.; Sullivan, Ashley F.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Allen, Michael H.] Univ Colorado, Depress Ctr & Rocky Mt Crisis Partners, Aurora, CO USA.
[Manton, Anne P.] Cape Cod Hosp, Ctr Behav Hlth Serv, Hyannis, MA USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01605 USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01605 USA.
RP Arias, SA (reprint author), Brown Univ, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
EM sarias@butler.org
RI Allen, Michael/A-8776-2011;
OI Arias, Sarah/0000-0003-1832-8824
FU National Institute of Mental Health [U01MH088278]; Novartis
FX The project described was supported by award U01MH088278 from the
National Institute of Mental Health. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Mental Health or the
National Institutes of Health.; Dr. Allen reports receiving research
support from Novartis. He reports that he has also been a contractor for
Sunovion and Ferrer, an employee of ProPhase, and an advisor for Teva.
The other authors report no financial relationships with commercial
interests.
NR 20
TC 0
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U1 0
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD FEB
PY 2016
VL 67
IS 2
BP 206
EP 213
DI 10.1176/appi.ps.201400513
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DO4SZ
UT WOS:000377775400016
PM 26620285
ER
PT J
AU Louapre, C
Govindarajan, ST
Gianni, C
Cohen-Adad, J
Gregory, MD
Nielsen, AS
Madigan, N
Sloane, JA
Kinkel, RP
Mainero, C
AF Louapre, Celine
Govindarajan, Sindhuja T.
Gianni, Costanza
Cohen-Adad, Julien
Gregory, Michael D.
Nielsen, A. Scott
Madigan, Nancy
Sloane, Jacob A.
Kinkel, Revere P.
Mainero, Caterina
TI Is the Relationship between Cortical and White Matter Pathologic Changes
in Multiple Sclerosis Spatially Specific? A Multimodal 7-T and 3-T MR
Imaging Study with Surface and Tract-based Analysis
SO RADIOLOGY
LA English
DT Article
ID NORMAL APPEARING WHITE; IN-VIVO; 7 T; COGNITIVE IMPAIRMENT;
CEREBRAL-CORTEX; HUMAN BRAIN; CONTRAST; DISCONNECTION; DEMYELINATION;
TRACTOGRAPHY
AB Purpose: To investigate in vivo the spatial specificity of the interdependence between intracortical and white matter (WM) pathologic changes as function of cortical depth and distance from the cortex in multiple sclerosis (MS), and their independent contribution to physical and cognitive disability.
Materials and Methods: This study was institutional review board-approved and participants gave written informed consent. In 34 MS patients and 17 age-matched control participants, 7-T quantitative T2* maps, 3-T T1-weighted anatomic images for cortical surface reconstruction, and 3-T diffusion tensor images (DTI) were obtained. Cortical quantitative T2* maps were sampled at 25%, 50%, 75% depth from pial surface. Tracts of interest were reconstructed by using probabilistic tractography. The relationship between DTI metrics voxelwise of the tracts and cortical integrity in the projection cortex was tested by using multilinear regression models.
Results: In MS, DTI abnormal findings along tracts correlated with quantitative T2* changes (suggestive of iron and myelin loss) at each depth of the cortical projection area (P < .01, corrected). This association, however, was not spatially specific because abnormal findings in WM tracts also related to cortical pathologic changes outside of the projection cortex of the tract (P < .001). Expanded Disability Status Scale pyramidal score was predicted by axial diffusivity along the corticospinal tract (beta = 4.6 x 10(3); P < .001), Symbol Digit Modalities Test score by radial diffusivity along the cingulum (beta = -4.3 x 10(4); P < .01), and T2* in the cingulum cortical projection at 25% depth (beta = -1.7; P < .05).
Conclusion: Intracortical and WM injury are concomitant pathologic processes in MS, which are not uniquely distributed according to a tract-cortex-specific pattern; their association may reflect a common stage-dependent mechanism. (C) RSNA, 2015
C1 [Louapre, Celine; Govindarajan, Sindhuja T.; Gianni, Costanza; Mainero, Caterina] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA.
[Louapre, Celine; Gianni, Costanza; Mainero, Caterina] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Cohen-Adad, Julien] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3C 3A7, Canada.
[Gregory, Michael D.] NIMH, Sect Integrat Neuroimaging, NIH, Bethesda, MD 20892 USA.
[Nielsen, A. Scott] Virginia Mason Med Ctr, Dept Neurol & Neurosurg, Seattle, WA 98101 USA.
[Madigan, Nancy; Sloane, Jacob A.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Kinkel, Revere P.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
RP Mainero, C (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA.; Mainero, C (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
EM caterina@nmr.mgh.harvard.edu
OI Gianni, Costanza/0000-0002-4018-169X
FU National Institutes of Health [R01NS078322-01-A1, NCRR P41-RR14075,
5T32NS51151-5]
FX This research was supported by the National Institutes of Health (grants
R01NS078322-01-A1, NCRR P41-RR14075, and 5T32NS51151-5).
NR 39
TC 1
Z9 1
U1 1
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD FEB
PY 2016
VL 278
IS 2
BP 524
EP 535
DI 10.1148/radiol.2015150486
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DO3SQ
UT WOS:000377702200027
PM 26334679
ER
PT J
AU Zhang, Y
Maurizi, MR
AF Zhang, Yang
Maurizi, Michael R.
TI Mitochondrial ClpP activity is required for cisplatin resistance in
human cells.
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Article
DE HClpP; HClpXP; Mitochondria; ATP7A; Copper transport; Apoptosis
ID HEREDITARY SPASTIC PARAPLEGIA; ENERGY-DEPENDENT PROTEASES;
CROSS-RESISTANCE; PROTEIN-DEGRADATION; MATRIX PROTEASES;
MAMMALIAN-CELLS; BACTERIAL CLPX; LON PROTEASE; FACTOR AIF; CANCER
AB In human cells ClpP and ClpX are imported into the mitochondrial matrix, where they interact to form the ATP dependent protease ClpXP and play a role in the mitochondrial unfolded protein response. We find that reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin, a widely used anti -cancer drug. Conversely, overexpression of HClpP desensitizes cells to cisplatin. Overexpression of inactive HClpP-S97A had no effect Cisplatin resistance correlated with decreased cellular accumulation of cisplatin and decreased levels of diguanosine-cisplatin adducts in both mitochondrial and genomic DNA. In contrast, higher levels of cisplatin-DNA adducts were found in cells in which HClpP had been depleted. Changes in the levels of ClpP had no effect on the levels of CTR1, a copper transporter that contributes to cisplatin uptake. However, the levels of ATP7A and ATP7B, copper efflux pumps that help eliminate cisplatin from cells, were increased when HClpP was overexpressed. HClpP levels were elevated in cervical carcinoma cells (KB-CP20) and hepatoma cells (BEL-7404-CP20) independently selected for cisplatin resistance. The data indicate that robust HClpXP activity positively affects the ability of cells to efflux cisplatin and suggest that targeting HCIpP or HClpX would offer a novel mechanism for sensitizing cancer cells to cisplatin. Published by Elsevier B.V.
C1 [Zhang, Yang; Maurizi, Michael R.] NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Bldg 37 Room 2128,37 Convent Dr, Bethesda, MD 20892 USA.
EM mmaurizi@helix.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health, Bethesda, MD
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health, Bethesda, MD. The authors would like to thank Dr. Duck Yeon Lee,
National Heart, Lung, and Blood Institute, Bethesda, MD and Dr. Kent
Warnken of Thermo Fisher Scientific, Lanham, MD for, respectively,
atomic absorption and ICP mass spectrometric measurements of platinum.
NR 61
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 0006-3002
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD FEB
PY 2016
VL 1862
IS 2
BP 252
EP 264
DI 10.1016/j.bbadis.2015.12.005
PG 13
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA DN9SH
UT WOS:000377420500012
PM 26675528
ER
PT J
AU Thomason, LC
Court, DL
AF Thomason, Lynn C.
Court, Donald L.
TI Evidence that bacteriophage lambda lysogens may induce in response to
the proton motive force uncoupler CCCP
SO FEMS MICROBIOLOGY LETTERS
LA English
DT Article
DE bacteriophage.; prophage induction; DNA damage; Mitomycin C; carbonyl
cyanide m-chlorophenyl hydrazone (CCCP); uncoupler
ID ESCHERICHIA-COLI; REPRESSOR; GENE; PHOSPHORYLATION; TRANSCRIPTION;
SWITCHES; CLEAVAGE; SYSTEM
AB We describe a genetic beta-galactoside reporter system using a disk diffusion assay on MacConkey Lactose agar petri plates to monitor maintenance of the bacteriophage lambda prophage state and viral induction in Escherichia coli K-12. Evidence is presented that the phage. major lytic promoters, pL and pR, are activated when cells containing the reporters are exposed to the energy poison carbonyl cyanide m-chlorophenyl hydrazine, CCCP. This uncoupler of oxidative phosphorylation inhibits ATP synthesis by collapsing the proton motive force. Expression of the lambda lytic promoters in response to CCCP requires host RecA function and an autocleavable CI repressor, as does SOS induction of the lambda prophage that occurs by a DNA damage-dependent pathway. lambda Cro function is required for CCCP-mediated activation of the lambda lytic promoters. CCCP does not induce an sfi-lacZ SOS reporter.
C1 [Thomason, Lynn C.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, GRCBL Mol Control & Genet Sect, Basic Sci Program, Frederick, MD 21702 USA.
[Thomason, Lynn C.; Court, Donald L.] NCI, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Thomason, LC (reprint author), NCI Frederick, Gene Regulat & Chromosome Biol Lab, Bldg 539 Rm 243,1050 Boyle St, Frederick, MD 21702 USA.
EM thomasol@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Trans National
Institutes of Health/Food and Drug Administration Intramural Biodefense
Program Grant of the National Institutes of Allergy and Infectious
Disease; National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported, in part, by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research, and in part by a Trans National Institutes of
Health/Food and Drug Administration Intramural Biodefense Program Grant
of the National Institutes of Allergy and Infectious Disease (to
D.L.C.). This project has also been partly funded with federal funds
from the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E.
NR 31
TC 0
Z9 0
U1 4
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0378-1097
EI 1574-6968
J9 FEMS MICROBIOL LETT
JI FEMS Microbiol. Lett.
PD FEB
PY 2016
VL 363
IS 3
AR fnv244
DI 10.1093/femsle/fnv244
PG 6
WC Microbiology
SC Microbiology
GA DN8BV
UT WOS:000377305000009
ER
PT J
AU Nathan, N
Tyburczy, ME
Hamieh, L
Wang, JA
Brown, GT
Lee, CCR
Kwiatkowski, DJ
Moss, J
Darling, TN
AF Nathan, Neera
Tyburczy, Magdalena E.
Hamieh, Lana
Wang, Ji-an
Brown, G. Thomas
Lee, Chyi-Chia Richard
Kwiatkowski, David J.
Moss, Joel
Darling, Thomas N.
TI Nipple Angiofibromas with Loss of TSC2 Are Associated with Tuberous
Sclerosis Complex
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
C1 [Nathan, Neera; Wang, Ji-an; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Nathan, Neera; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Tyburczy, Magdalena E.; Hamieh, Lana; Kwiatkowski, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Brown, G. Thomas; Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
EM thomas.darling@usuhs.edu
OI Darling, Thomas/0000-0002-5161-1974
FU Intramural NIH HHS [Z01 HL002541-12]; NCI NIH HHS [P01 CA120964,
1P01CA120964]; NIAMS NIH HHS [NIH R01AR062080, R01 AR062080]
NR 10
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 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD FEB
PY 2016
VL 136
IS 2
BP 535
EP 538
PG 4
WC Dermatology
SC Dermatology
GA DN6XE
UT WOS:000377219000030
PM 26824744
ER
PT J
AU Hurt, DE
Suzuki, S
Mayama, T
Charmandari, E
Kino, T
AF Hurt, Darrell E.
Suzuki, Shigeru
Mayama, Takafumi
Charmandari, Evangelia
Kino, Tomoshige
TI Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor
Ligand-Binding Domains
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID NUCLEAR RECEPTOR; POINT MUTATION; TRANSCRIPTIONAL ACTIVITY; RESISTANCE;
COACTIVATORS; GENE; GR; STRESS; SYSTEM; MOTIF
AB Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects. Several calculated parameters including interaction energy for dexamethasone or the LXXLL peptide indicate that destruction of ligand-binding pocket (LBP) is a primary character. Their LBP defects are driven primarily by loss/reduction of the electrostatic interaction formed by R611 and T739 of the receptor to dexamethasone and a subsequent conformational mismatch, which deacylcortivazol resolves with its large phenylpyrazole moiety and efficiently stimulates transcriptional activity of the mutant receptors with LBP defect. Reduced affinity of the LXXLL peptide to AF-2 is caused mainly by disruption of the electrostatic bonds to the noncore leucine residues of this peptide that determine the peptide's specificity to GR, as well as by reduced noncovalent interaction against core leucines and subsequent exposure of the AF-2 surface to solvent. The results reveal molecular defects of pathologic mutant receptors and provide important insights to the actions of wild-type GR.
C1 [Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Rockville, MD 20852 USA.
[Suzuki, Shigeru; Mayama, Takafumi; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Suzuki, Shigeru] Asahikawa Med Univ, Dept Pediat, Asahikawa, Hokkaido 0788510, Japan.
[Charmandari, Evangelia] Univ Athens, Sch Med, Dept Pediat 1, Div Endocrinol Metab & Diabet,Aghia Sophia Childr, GR-11527 Athens, Greece.
[Kino, Tomoshige] Sidra Med & Res Ctr, Dept Expt Therapeut, Div Expt Biol, Doha, Qatar.
RP Kino, T (reprint author), Sidra Med & Res Ctr, Dept Expt Therapeut, Div Expt Biol, Out Patient Clin, 5th Floor,Room C5-340,POB 26999,Al Luqta St, Doha, Qatar.
EM tkino@sidra.org
RI Charmandari, Evangelia/B-6701-2011
FU Intramural Research Program of Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
[Z01 HD008732-05 HNT]; Sirda Medical and Research Center; Asahikawa
Medical University
FX This work was supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(Z01 HD008732-05 HNT), National Institutes of Health, and Sirda Medical
and Research Center. S.S. was supported by the Asahikawa Medical
University.
NR 34
TC 3
Z9 3
U1 1
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD FEB
PY 2016
VL 30
IS 2
BP 173
EP 188
DI 10.1210/me.2015-1177
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DN6SN
UT WOS:000377206500003
PM 26745667
ER
PT J
AU Broderick, JP
Palesch, YY
Janis, LS
AF Broderick, Joseph P.
Palesch, Yuko Y.
Janis, L. Scott
CA Natl Inst Hlth StrokeNet
TI The National Institutes of Health StrokeNet A User's Guide
SO STROKE
LA English
DT Editorial Material
C1 [Broderick, Joseph P.] Univ Cincinnati, Dept Neurol & Rehabil Med, Neurosci Inst, Acad Hlth Ctr, Cincinnati, OH 45267 USA.
[Broderick, Joseph P.] Univ Cincinnati, Dept Radiol, Neurosci Inst, Acad Hlth Ctr, Cincinnati, OH 45267 USA.
[Palesch, Yuko Y.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA.
[Janis, L. Scott] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Broderick, JP (reprint author), Univ Cincinnati, Dept Neurol & Rehabil Med, Neurosci Inst, 260 Stetson St,Suite 2300,POB 670525, Cincinnati, OH 45267 USA.
EM joseph.broderick@uc.edu
FU NINDS NIH HHS [NS087748, U01 NS086872, U01 NS087748, U01NS086872]
NR 0
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD FEB
PY 2016
VL 47
IS 2
BP 301
EP 303
DI 10.1161/STROKEAHA.115.011743
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DN4MD
UT WOS:000377040200012
PM 26715457
ER
PT J
AU Bartlett, ST
Markmann, JF
Johnson, P
Korsgren, O
Hering, BJ
Scharp, D
Kay, TWH
Bromberg, J
Odorico, JS
Weir, GC
Bridges, N
Kandaswamy, R
Stock, P
Friend, P
Gotoh, M
Cooper, DKC
Park, CG
O'Connell, P
Stabler, C
Matsumoto, S
Ludwig, B
Choudhary, P
Kovatchev, B
Rickels, MR
Sykes, M
Wood, K
Kraemer, K
Hwa, A
Stanley, E
Ricordi, C
Zimmerman, M
Greenstein, J
Montanya, E
Otonkoski, T
AF Bartlett, Stephen T.
Markmann, James F.
Johnson, Paul
Korsgren, Olle
Hering, Bernhard J.
Scharp, David
Kay, Thomas W. H.
Bromberg, Jonathan
Odorico, Jon S.
Weir, Gordon C.
Bridges, Nancy
Kandaswamy, Raja
Stock, Peter
Friend, Peter
Gotoh, Mitsukazu
Cooper, David K. C.
Park, Chung-Gyu
O'Connell, Phillip
Stabler, Cherie
Matsumoto, Shinichi
Ludwig, Barbara
Choudhary, Pratik
Kovatchev, Boris
Rickels, Michael R.
Sykes, Megan
Wood, Kathryn
Kraemer, Kristy
Hwa, Albert
Stanley, Edward
Ricordi, Camillo
Zimmerman, Mark
Greenstein, Julia
Montanya, Eduard
Otonkoski, Timo
TI Report from IPITA-TTS Opinion Leaders Meeting on the Future of beta-Cell
Replacement
SO TRANSPLANTATION
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; PANCREAS-KIDNEY TRANSPLANTATION; ISLET ALLOGRAFT
SURVIVAL; SUBCUTANEOUS INSULIN INFUSION; CLOSED-LOOP CONTROL;
ASSOCIATION CONSENSUS STATEMENT; PORCINE ENDOGENOUS RETROVIRUS;
UNDERTAKING CLINICAL-TRIALS; TYPE-2 DIABETES-MELLITUS; ANTITHYMOCYTE
GLOBULIN INDUCTION
C1 [Bartlett, Stephen T.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA.
[Markmann, James F.; Bromberg, Jonathan] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA.
[Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England.
[Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Hering, Bernhard J.; Kandaswamy, Raja] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Box 242 UMHC, Minneapolis, MN 55455 USA.
[Scharp, David] Prodo Labs LLC, Irvine, CA USA.
[Scharp, David] Scharp Lacy Res Inst, Irvine, CA USA.
[Kay, Thomas W. H.] St Vincents Hosp, St Vincents Inst Med Res, Dept Med, Fitzroy, Vic 3065, Australia.
[Kay, Thomas W. H.] Univ Melbourne, Melbourne, Vic 3010, Australia.
[Odorico, Jon S.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Div Transplantat, Madison, WI USA.
[Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Weir, Gordon C.] Harvard Univ, Sch Med, Boston, MA USA.
[Bridges, Nancy; Kraemer, Kristy] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Stock, Peter] Univ San Francisco, Med Ctr, Div Transplantat, San Francisco, CA 94117 USA.
[Gotoh, Mitsukazu] Fukushima Med Univ, Dept Surg, Fukushima, Japan.
[Cooper, David K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA.
[Park, Chung-Gyu] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Xenotransplantat Res Ctr,Dept Microbiol & Immunol, Seoul, South Korea.
[O'Connell, Phillip] Univ Sydney, Westmead Hosp, Westmead Millennium Inst, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia.
[Stabler, Cherie; Ricordi, Camillo] Univ Miami, Sch Med, Diabet Res Inst, Coral Gables, FL 33124 USA.
[Matsumoto, Shinichi] Natl Ctr Global Hlth & Med, Tokyo, Japan.
[Matsumoto, Shinichi] Otsuka Pharmaceut Factory Inc, Naruto, Japan.
[Ludwig, Barbara] Tech Univ Dresden, Dept Med 3, D-01062 Dresden, Germany.
[Ludwig, Barbara] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Ctr, Paul Langerhans Inst Dresden, Dresden, Germany.
[Ludwig, Barbara] DZD German Ctr Diabet Res, Dresden, Germany.
[Choudhary, Pratik] Kings Coll London, Weston Educ Ctr, Diabet Res Grp, London WC2R 2LS, England.
[Kovatchev, Boris] Univ Virginia, Ctr Diabet Technol, Charlottesville, VA USA.
[Rickels, Michael R.] Univ Penn, Dept Med, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Sykes, Megan] Coulmbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA.
[Hwa, Albert] Juvenile Diabet Res Fdn, New York, NY USA.
[Stanley, Edward] Murdoch Childrens Res Inst, Parkville, Vic, Australia.
[Stanley, Edward] Monash Univ, Melbourne, Vic 3004, Australia.
[Zimmerman, Mark] BetaLogics, Raritan, NJ USA.
[Greenstein, Julia] Juvenile Diabet Res Fdn, Discovery Res, New York, NY USA.
[Montanya, Eduard] Univ Barcelona, Hosp Univ Bellvitge, CIBERDEM, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain.
[Otonkoski, Timo] Univ Helsinki, Childrens Hosp, Helsinki, Finland.
[Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, Helsinki, Finland.
RP Markmann, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 517, Boston, MA 02114 USA.
EM jmarkmann@partners.org
RI Stabler, Cherie/E-8227-2011;
OI Ricordi, Camillo/0000-0001-8092-7153
FU Diabetes Research and Wellness Foundation; Dompe Pharmaceuticals;
beta-O2 Technologies LTD; Novartis Pharmaceuticals; Sanofi; JDRF
FX This work was supported by generous educational grants by the Diabetes
Research and Wellness Foundation and Dompe Pharmaceuticals. Additional
funding was provided by beta-O2 Technologies LTD, Novartis
Pharmaceuticals, Sanofi and the JDRF.
NR 381
TC 10
Z9 10
U1 5
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD FEB
PY 2016
VL 100
SU 2
BP S1
EP S44
DI 10.1097/TP.0000000000001055
PG 44
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA DN5QN
UT WOS:000377125300001
PM 26840096
ER
PT J
AU Dalziel, BD
Bjornstad, ON
van Panhuis, WG
Burke, DS
Metcalf, CJE
Grenfell, BT
AF Dalziel, Benjamin D.
Bjornstad, Ottar N.
van Panhuis, Willem G.
Burke, Donald S.
Metcalf, C. Jessica E.
Grenfell, Bryan T.
TI Persistent Chaos of Measles Epidemics in the Prevaccination United
States Caused by a Small Change in Seasonal Transmission Patterns
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID CHILDHOOD DISEASES; DYNAMICS; MODELS; VACCINATION; METAPOPULATIONS;
STOCHASTICITY; FLUCTUATIONS; HIERARCHIES; INFECTIONS; COPENHAGEN
AB Epidemics of infectious diseases often occur in predictable limit cycles. Theory suggests these cycles can be disrupted by high amplitude seasonal fluctuations in transmission rates, resulting in deterministic chaos. However, persistent deterministic chaos has never been observed, in part because sufficiently large oscillations in transmission rates are uncommon. Where they do occur, the resulting deep epidemic troughs break the chain of transmission, leading to epidemic extinction, even in large cities. Here we demonstrate a new path to locally persistent chaotic epidemics via subtle shifts in seasonal patterns of transmission, rather than through high-amplitude fluctuations in transmission rates. We base our analysis on a comparison of measles incidence in 80 major cities in the prevaccination era United States and United Kingdom. Unlike the regular limit cycles seen in the UK, measles cycles in US cities consistently exhibit spontaneous shifts in epidemic periodicity resulting in chaotic patterns. We show that these patterns were driven by small systematic differences between countries in the duration of the summer period of low transmission. This example demonstrates empirically that small perturbations in disease transmission patterns can fundamentally alter the regularity and spatiotemporal coherence of epidemics.
C1 [Dalziel, Benjamin D.; Metcalf, C. Jessica E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Dalziel, Benjamin D.; Metcalf, C. Jessica E.; Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[van Panhuis, Willem G.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Dalziel, Benjamin D.] Oregon State Univ, Dept Integrat Biol, Corvallis, OR 97331 USA.
RP Grenfell, BT (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.; Grenfell, BT (reprint author), Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.; Grenfell, BT (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM Grenfell@princeton.edu
OI /0000-0002-5704-8094; Dalziel, Benjamin/0000-0002-9674-2783
FU Bill and Melinda Gates Foundation; RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health; Bill and Melinda
Gates Foundation [49276]; US National Institute of General Medical
Sciences [5U54GM088491]
FX This work was funded by the Bill and Melinda Gates Foundation
(www.gatesfoundation.org/)(CJEM, BTG, ONB), and the RAPIDD program of
the Science & Technology Directorate, Department of Homeland Security
and the Fogarty International Center, National Institutes of Health
(http://www.fic.nih.gov/about/staff/pages/epidemiology-population.aspx)
(CJEM, BTG, ONB). WGVP and DSB would like to thank the Bill and Melinda
Gates Foundation (Grant 49276, Evaluation of Candidate Vaccine
Technologies Using Computational Models) and the US National Institute
of General Medical Sciences
(http://www.nigms.nih.gov/Pages/default.aspx)(Grant 5U54GM088491,
Computational Models of Infectious Disease Threats) for their support.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 49
TC 3
Z9 3
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2016
VL 12
IS 2
AR e1004655
DI 10.1371/journal.pcbi.1004655
PG 12
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DM8AL
UT WOS:000376582900033
PM 26845437
ER
PT J
AU Greischar, MA
Mideo, N
Read, AF
Bjornstad, ON
AF Greischar, Megan A.
Mideo, Nicole
Read, Andrew F.
Bjornstad, Ottar N.
TI Quantifying Transmission Investment in Malaria Parasites
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM GAMETOCYTES; REVERSE-TRANSCRIPTION PCR;
WITHIN-HOST COMPETITION; REPRODUCTIVE RESTRAINT; SEX-RATIOS; FITNESS
COSTS; CHABAUDI; INFECTIVITY; EVOLUTION; QUANTIFICATION
AB Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.
C1 [Greischar, Megan A.; Read, Andrew F.; Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
[Greischar, Megan A.; Read, Andrew F.; Bjornstad, Ottar N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Greischar, Megan A.; Mideo, Nicole] Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON, Canada.
[Read, Andrew F.; Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Read, Andrew F.; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Greischar, MA (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.; Greischar, MA (reprint author), Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.; Greischar, MA (reprint author), Univ Toronto, Dept Ecol & Evolutionary Biol, Toronto, ON, Canada.
EM megan.greischar@utoronto.ca
FU National Institute of General Medical Sciences, NIH [R01GM089932];
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; Bill and Melinda Gates Foundation; National Science Foundation
[DEB-1354819]; Human Frontiers Science Program [RGP0046/2013]; Natural
Sciences and Engineering Research Council of Canada
FX This work was funded by the National Institute of General Medical
Sciences, NIH grant R01GM089932 (AFR), the RAPIDD program of the Science
& Technology Directorate, Department of Homeland Security and the
Fogarty International Center, National Institutes of Health (ONB, AFR),
the Bill and Melinda Gates Foundation (ONB) and National Science
Foundation (ONB, DEB-1354819), the Human Frontiers Science Program (NM,
grant number RGP0046/2013), the Natural Sciences and Engineering
Research Council of Canada (NM). The funders had no role in the
analysis, decision to publish or the manuscript preparation.
NR 41
TC 2
Z9 2
U1 3
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2016
VL 12
IS 2
AR e1004718
DI 10.1371/journal.pcbi.1004718
PG 16
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DM8AL
UT WOS:000376582900040
PM 26890485
ER
PT J
AU Gattinoni, L
AF Gattinoni, Luca
TI Adoptive T cell transfer: Imagining the next generation of cancer
immunotherapies
SO SEMINARS IN IMMUNOLOGY
LA English
DT Editorial Material
DE Cancer immunotherapy; Adoptive T cell transfer; TCR engineered T cells;
CAR engineered T cells; Neoantigens; T cell differentiation; Stem
cell-like T cells; T cell reprogramming; MicroRNA therapeutics; Tumor
microenvironment
ID THERAPY
C1 [Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
RP Gattinoni, L (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM gattinol@mail.nih.gov
RI Gattinoni, Luca/A-2281-2008
OI Gattinoni, Luca/0000-0003-2239-3282
NR 20
TC 0
Z9 0
U1 2
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD FEB
PY 2016
VL 28
IS 1
BP 1
EP 2
DI 10.1016/j.smim.2016.03.019
PG 2
WC Immunology
SC Immunology
GA DM3AM
UT WOS:000376219200001
PM 27161516
ER
PT J
AU Geldres, C
Savoldo, B
Dotti, G
AF Geldres, Claudia
Savoldo, Barbara
Dotti, Gianpietro
TI Chimeric antigen receptor-redirected T cells return to the bench
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE Chimeric antigen receptor; Adoptive immunotherapy
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MEMORY STEM-CELLS; ANTITUMOR-ACTIVITY;
IN-VIVO; SAFETY SWITCH; SPACER DOMAIN; SUICIDE GENE; SOLID TUMORS;
LYMPHOCYTES; LYMPHOMA
AB While the clinical progress of chimeric antigen receptor T cell (CAR-T) immunotherapy has garnered attention to the field, our understanding of the biology of these chimeric molecules is still emerging. Our aim within this review is to bring to light the mechanistic understanding of these multi-modular receptors and how these individual components confer particular properties to CAR-Ts. In addition, we will discuss extrinsic factors that can be manipulated to influence CAR-T performance such as choice of cellular population, culturing conditions and additional modifications that enhance their activity particularly in solid tumors. Finally, we will also consider the emerging toxicity associated with CAR-Ts. By breaking apart the CAR and examining the role of each piece, we can build a better functioning cellular vehicle for optimized treatment of cancer patients. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Geldres, Claudia] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Savoldo, Barbara] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Savoldo, Barbara; Dotti, Gianpietro] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Dotti, Gianpietro] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
RP Dotti, G (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.; Dotti, G (reprint author), Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA.
EM Claudia.Geldres@mail.nih.gov; barbar@email.unc.edu; gdotti@med.unc.edu
FU NCI NIH HHS [R01 CA142636, P50 CA126752]
NR 74
TC 5
Z9 5
U1 2
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD FEB
PY 2016
VL 28
IS 1
BP 3
EP 9
DI 10.1016/j.smim.2015.12.001
PG 7
WC Immunology
SC Immunology
GA DM3AM
UT WOS:000376219200002
PM 26797495
ER
PT J
AU Lu, YC
Robbins, PF
AF Lu, Yong-Chen
Robbins, Paul F.
TI Cancer immunotherapy targeting neoantigens
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE Cancer immunotherapy; Tumor immunology; Neoantigen; Mutation
ID CYTOLYTIC T-LYMPHOCYTES; RENAL-CELL CARCINOMA; COMPLETE
TUMOR-REGRESSION; POINT MUTATION; HUMAN-MELANOMA; METASTATIC MELANOMA;
LUNG-CARCINOMA; ANTI-PD-L1 ANTIBODY; CTLA-4 BLOCKADE; HIGH-FREQUENCY
AB Neoantigens are antigens encoded by tumor-specific mutated genes. Studies in the past few years have suggested a key role for neoantigens in cancer immunotherapy. Here we review the discoveries of neoantigens in the past two decades and the current advances in neoantigen identification. We also discuss the potential benefits and obstacles to the development of effective cancer immunotherapies targeting neoantigens. Published by Elsevier Ltd
C1 [Lu, Yong-Chen; Robbins, Paul F.] NCI, Surg Branch, NIH, Bldg 10-CRC,Rm 3W-3864,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
RP Lu, YC; Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10-CRC,Rm 3W-3864,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM Yong-Chen.Lu@nih.gov; Paul_Robbins@nih.gov
FU Intramural Research Program of National Cancer Institute
FX The authors thank Todd Prickett and Lucas McDuffie for suggestions and
discussions. This work was supported by the Intramural Research Program
of National Cancer Institute.
NR 74
TC 11
Z9 11
U1 5
U2 10
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD FEB
PY 2016
VL 28
IS 1
BP 22
EP 27
DI 10.1016/j.smim.2015.11.002
PG 6
WC Immunology
SC Immunology
GA DM3AM
UT WOS:000376219200004
PM 26653770
ER
PT J
AU Ji, Y
Hocker, JD
Gattinoni, L
AF Ji, Yun
Hocker, James D.
Gattinoni, Luca
TI Enhancing adoptive T cell immunotherapy with microRNA therapeutics
SO SEMINARS IN IMMUNOLOGY
LA English
DT Review
DE Microrna (miRNA); Tumor immunotherapy; Adoptive cell transfer; T cell
differentiation; CD8(+) T cells
ID ADAPTIVE IMMUNE-RESPONSES; ANTITUMOR-ACTIVITY; EFFECTOR FUNCTION;
IN-VIVO; TGF-BETA; RETROVIRAL TRANSDUCTION; TRANSCRIPTIONAL CONTROL;
METASTATIC MELANOMA; REGULATES EFFECTOR; CANCER REGRESSION
AB Adoptive T cell-based immunotherapies can mediate complete and durable regressions in patients with advanced cancer, but current response rates remain inadequate. Maneuvers to improve the fitness and antitumor efficacy of transferred T cells have been under extensive exploration in the field. Small non-coding microRNAs have emerged as critical modulators of immune system homeostasis and T cell immunity. Here, we summarize recent advances in our understanding of the role of microRNAs in regulating T cell activation, differentiation, and function. We also discuss how microRNA therapeutics could be employed to fine-tune T cell receptor signaling and enhance T cell persistence and effector functions, paving the way for the next generation of adoptive immunotherapies. Published by Elsevier Ltd
C1 [Ji, Yun; Hocker, James D.; Gattinoni, Luca] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
RP Ji, Y; Gattinoni, L (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jiyun@mail.nih.gov; gattinol@mail.nih.gov
RI Ji, Yun/B-7245-2009; Gattinoni, Luca/A-2281-2008
OI Ji, Yun/0000-0001-6340-7009; Gattinoni, Luca/0000-0003-2239-3282
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research, National Institutes of Health [ZIA-BC011480]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, National
Institutes of Health (ZIA-BC011480).
NR 130
TC 3
Z9 3
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-5323
J9 SEMIN IMMUNOL
JI Semin. Immunol.
PD FEB
PY 2016
VL 28
IS 1
BP 45
EP 53
DI 10.1016/j.smim.2015.11.006
PG 9
WC Immunology
SC Immunology
GA DM3AM
UT WOS:000376219200007
PM 26710685
ER
PT J
AU Kim, CW
Asai, D
Kang, JH
Kishimura, A
Mori, T
Katayama, Y
AF Kim, Chan Woo
Asai, Daisuke
Kang, Jeong-Hun
Kishimura, Akihiro
Mori, Takeshi
Katayama, Yoshiki
TI Reversal of efflux of an anticancer drug in human drug-resistant breast
cancer cells by inhibition of protein kinase C alpha (PKC alpha)
activity
SO TUMOR BIOLOGY
LA English
DT Article
DE Drug resistance; P-glycoprotein; Protein kinase C alpha; Protein kinase
inhibitor; Anticancer drug
ID OVERCOMING MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; STEM-CELLS; ABC
TRANSPORTERS; CARCINOMA-CELLS; MCF-7 CELLS; MODULATION; EXPRESSION;
PHOSPHORYLATION; MECHANISMS
AB P-glycoprotein (Pgp) is a 170-kDa transmembrane protein that mediates the efflux of anticancer drugs from cells. Pgp overexpression has a distinct role in cells exhibiting multidrug resistance (MDR). We examined reversal of drug resistance in human MDR breast cancer cells by inhibition of protein kinase C alpha (PKC alpha) activity, which is associated with Pgp-mediated efflux of anticancer drugs. PKC alpha activity was confirmed by measurement of phosphorylation levels of a PKC alpha-specific peptide substrate (FKKQGSFAKKK-NH2), showing relatively higher basal activity in drug-resistant MCF-7/ADR cells (84 %) than that in drug-sensitive MCF-7 cells (63 %). PKC alpha activity was effectively suppressed by the PKC inhibitor, Ro-31-7549, and reversal of intracellular accumulation of doxorubicin was observed by inhibition of PKC alpha activity in MCF-7/ADR cells compared with their intrinsic drug resistance. Importantly, increased accumulation of doxorubicin could enhance the therapeutic efficacy of doxorubicin in MDR cells significantly. These results suggest a potential for overcoming MDR via inhibition of PKC alpha activity with conventional anticancer drugs.
C1 [Kim, Chan Woo; Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki] Kyushu Univ, Fac Engn, Dept Appl Chem, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.
[Asai, Daisuke] St Marianna Univ, Sch Med, Dept Microbiol, Miyamae Ku, 2-16-1 Sugao, Kawasaki, Kanagawa 2168511, Japan.
[Kang, Jeong-Hun] Natl Cerebral & Cardiovasc Ctr, Res Inst, Div Biopharmaceut & Pharmacokinet, 5-7-1 Fujishiro Dai, Suita, Osaka 5658565, Japan.
[Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki] Kyushu Univ, Grad Sch Syst Life Sci, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.
[Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki] Kyushu Univ, Ctr Future Chem, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.
[Katayama, Yoshiki] Kyushu Univ, Int Res Ctr Mol Syst, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.
[Katayama, Yoshiki] Kyushu Univ, Ctr Adv Med Innovat, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
[Katayama, Yoshiki] Kyushu Univ, Innovat Ctr Med Redox Nav, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
[Kim, Chan Woo] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Mori, T; Katayama, Y (reprint author), Kyushu Univ, Fac Engn, Dept Appl Chem, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.; Mori, T; Katayama, Y (reprint author), Kyushu Univ, Grad Sch Syst Life Sci, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.; Mori, T; Katayama, Y (reprint author), Kyushu Univ, Ctr Future Chem, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.; Katayama, Y (reprint author), Kyushu Univ, Int Res Ctr Mol Syst, Nishi Ku, 744 Motooka, Fukuoka 8190395, Japan.; Katayama, Y (reprint author), Kyushu Univ, Ctr Adv Med Innovat, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.; Katayama, Y (reprint author), Kyushu Univ, Innovat Ctr Med Redox Nav, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM mori.takeshi.880@m.kyushu-u.ac.jp; ykatatcm@mail.cstm.kyushu-u.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology of Japan;
KRIBB Research Initiative Program (Korean Biomedical Scientist
Fellowship Program), Korea Research Institute of Bioscience and
Biotechnology, Republic of Korea
FX We thank Professor Masahiro Goto (Kyushu University) for assistance in
CLSM studies and Dr. Ick Chan Kwon for the kind gift of the MCF-7/ADR
cell line. We also thank Ms. Sigemi Terakubo and Ms. Ninyo Okamura (St.
Marianna University School of Medicine) for technical assistance. This
work was supported by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science and Technology of Japan,
and a grant from the KRIBB Research Initiative Program (Korean
Biomedical Scientist Fellowship Program), Korea Research Institute of
Bioscience and Biotechnology, Republic of Korea (C.W.K.).
NR 36
TC 3
Z9 3
U1 2
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1010-4283
EI 1423-0380
J9 TUMOR BIOL
JI Tumor Biol.
PD FEB
PY 2016
VL 37
IS 2
BP 1901
EP 1908
DI 10.1007/s13277-015-3963-4
PG 8
WC Oncology
SC Oncology
GA DK0HK
UT WOS:000374593300057
PM 26323260
ER
PT J
AU Tsetsarkin, KA
Chen, RB
Weaver, SC
AF Tsetsarkin, Konstantin A.
Chen, Rubing
Weaver, Scott C.
TI Interspecies transmission and chikungunya virus emergence
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID AEDES-ALBOPICTUS MOSQUITOS; INDIAN-OCEAN; SOUTHEASTERN SENEGAL;
EVOLUTIONARY RATES; DENGUE-FEVER; EAST-AFRICA; OUTBREAK; EPIDEMIC;
VECTOR; SPREAD
AB Chikungunya virus (CHIKV) causes severe, debilitating, often chronic arthralgia with high attack rates, resulting in severe morbidity and economic costs to affected communities. Since its first well-documented emergence in Asia in the 1950s, CHIKV has infected millions and, since 2007, has spread widely, probably via viremic travelers, to initiate urban transmission in Europe, the South Pacific, and the Americas. Some spread has been facilitated by adaptive envelope glycoprotein substitutions that enhance transmission by the new vector, Aedes albopictus. Although epistatic constraints may prevent the impact of these mutations in Asian strains now circulating in the Americas, as well as in African CHIKV strains imported into Brazil last year, these constraints could eventually be overcome over time to increase the transmission by A. albopictus in rural and temperate regions. Another major determinant of CHIKV endemic stability in the Americas will be its ability to spill back into an enzootic cycle involving sylvatic vectors and nonhuman primates, an opportunity exploited by yellow fever virus but apparently not by dengue viruses.
C1 [Tsetsarkin, Konstantin A.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Rubing; Weaver, Scott C.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Chen, Rubing; Weaver, Scott C.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Weaver, Scott C.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
RP Weaver, SC (reprint author), Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.; Weaver, SC (reprint author), Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.; Weaver, SC (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
EM sweaver@utmb.edu
RI Weaver, Scott/D-6490-2011
FU NIH [AI069145]; Department of Homeland Security [HSHQDC-13-C-B0009]
FX This research was supported by NIH grant AI069145 and by grant
HSHQDC-13-C-B0009, from the Department of Homeland Security entitled
'Whole Genome Approach to Microbial Forensics Technical Focus Area -3.'
NR 64
TC 8
Z9 8
U1 1
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD FEB
PY 2016
VL 16
BP 143
EP 150
DI 10.1016/j.coviro.2016.02.007
PG 8
WC Virology
SC Virology
GA DK2AK
UT WOS:000374716800021
PM 26986235
ER
PT J
AU Ruckwardt, TJ
Morabito, KM
Graham, BS
AF Ruckwardt, Tracy J.
Morabito, Kaitlyn M.
Graham, Barney S.
TI Determinants of early life immune responses to RSV infection
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; NEUTRALIZING ANTIBODY; LUNG DEVELOPMENT;
DENDRITIC CELLS; INFLUENZA-VIRUS; MOUSE MODEL; INFANTS; VACCINE;
DISEASE; FETAL
AB Respiratory syncytial virus causes significant morbidity and mortality in both developed and developing countries, and a vaccine that adequately protects from severe disease remains an important unmet need. RSV disease has an inordinate impact on the very young, and the physical and immunological immaturity of early life complicates vaccine design. Defining and targeting the functional capacities of early life immune responses and controlling responses during primary antigen exposure with selected vaccine delivery approaches will be important for protecting infants by active immunization. Alternatively, vaccination of older children and pregnant mothers may ameliorate disease burden indirectly until infants reach about six months of age, when they can generate more effective anti-RSV immune responses.
C1 [Ruckwardt, Tracy J.; Morabito, Kaitlyn M.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Ruckwardt, TJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM truckwardt@mail.nih.gov
FU NIAID
FX The authors are financially supported by intramural NIAID.
NR 56
TC 2
Z9 2
U1 3
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD FEB
PY 2016
VL 16
BP 151
EP 157
DI 10.1016/j.coviro.2016.01.003
PG 7
WC Virology
SC Virology
GA DK2AK
UT WOS:000374716800022
PM 26986236
ER
PT J
AU Bao, W
Michels, KB
Tobias, DK
Li, S
Chavarro, JE
Gaskins, AJ
Vaag, AA
Hu, FB
Zhang, CL
AF Bao, Wei
Michels, Karin B.
Tobias, Deirdre K.
Li, Shanshan
Chavarro, Jorge E.
Gaskins, Audrey J.
Vaag, Allan A.
Hu, Frank B.
Zhang, Cuilin
TI Parental smoking during pregnancy and the risk of gestational diabetes
in the daughter
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Gestational diabetes mellitus; maternal smoking during pregnancy
ID MATERNAL SMOKING; IN-UTERO; CHILDHOOD OBESITY; EXPOSURE; QUESTIONNAIRE;
REPRODUCIBILITY; METAANALYSIS; MELLITUS; VALIDITY; DISEASE
AB Background: Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter.
Methods: We included 15 665 singleton pregnancies from 10 152 women in the Nurses' Health Study II cohort whose mothers participated in the Nurses' Mothers' Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs).
Results: We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and a parts per thousand yen25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend = 0.01). Further adjustment for the women's perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter.
Conclusions: Maternal heavy smoking (a parts per thousand yen25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms.
C1 [Bao, Wei; Li, Shanshan; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Bao, Wei] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
[Michels, Karin B.; Chavarro, Jorge E.; Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Michels, Karin B.; Chavarro, Jorge E.; Hu, Frank B.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Michels, Karin B.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA.
[Tobias, Deirdre K.; Vaag, Allan A.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Tobias, Deirdre K.] Harvard Univ, Sch Med, Boston, MA USA.
[Tobias, Deirdre K.; Chavarro, Jorge E.; Gaskins, Audrey J.; Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Vaag, Allan A.] Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov
OI Bao, Wei/0000-0002-7301-5786
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN275201000020C]; National Institutes of Health [DK58845,
CA50385, P30 DK46200, UM1 CA176726]; Intramural Research Program of the
National Cancer Institute, Research Contract from the National Cancer
Institute [N02-RC-17027]; National Cancer Institute [P.O. 263 MQ
411027]; American Diabetes Association [7-12-MN-34]; National Institute
of Diabetes and Digestive and Kidney Diseases [DK58845, T32-DK007703-16]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (contract No.
HHSN275201000020C). The Nurses' Health Study II was funded by research
grants DK58845, CA50385, P30 DK46200 and UM1 CA176726 from the National
Institutes of Health. The Nurses' Mothers' Cohort Study was funded by
the Intramural Research Program of the National Cancer Institute,
Research Contract N02-RC-17027 from the National Cancer Institute, and
by P.O. 263 MQ 411027 from the National Cancer Institute. D.T. was
supported by a mentored fellowship from the American Diabetes
Association (No. 7-12-MN-34) and a K01 grant from National Institute of
Diabetes and Digestive and Kidney Diseases (DK58845). A.G. was supported
by a training grant from National Institute of Diabetes and Digestive
and Kidney Diseases (T32-DK007703-16).
NR 36
TC 2
Z9 2
U1 7
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2016
VL 45
IS 1
BP 160
EP 169
DI 10.1093/ije/dyv334
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DJ5ER
UT WOS:000374230100023
PM 26748845
ER
PT J
AU Hyland, PL
Zhang, H
Yang, Q
Yang, HH
Hu, N
Lin, SW
Su, H
Wang, LM
Wang, CY
Ding, T
Fan, JH
Qiao, YL
Sung, H
Wheeler, W
Giffen, C
Burdett, L
Wang, ZM
Lee, MP
Chanock, SJ
Dawsey, SM
Freedman, ND
Abnet, CC
Goldstein, AM
Yu, K
Taylor, PR
AF Hyland, Paula L.
Zhang, Han
Yang, Qi
Yang, Howard H.
Hu, Nan
Lin, Shih-Wen
Su, Hua
Wang, Lemin
Wang, Chaoyu
Ding, Ti
Fan, Jin-Hu
Qiao, You-Lin
Sung, Hyuna
Wheeler, William
Giffen, Carol
Burdett, Laurie
Wang, Zhaoming
Lee, Maxwell P.
Chanock, Stephen J.
Dawsey, Sanford M.
Freedman, Neal D.
Abnet, Christian C.
Goldstein, Alisa M.
Yu, Kai
Taylor, Philip R.
TI Pathway, in silico and tissue-specific expression quantitative analyses
of oesophageal squamous cell carcinoma genome-wide association studies
data
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Post-GWAS; pathways; genes; SNP; eQTLs; oesophageal cancer
ID BITTER TASTE RECEPTORS; SUSCEPTIBILITY LOCI; RISK-FACTORS; GASTRIC
ADENOCARCINOMA; SEGREGATION ANALYSIS; CHINESE POPULATIONS;
ALCOHOL-CONSUMPTION; GENETIC-VARIANTS; SHANXI PROVINCE; IDENTIFIES 3
AB Background: Oesophageal cancer is the fourth leading cause of cancer death in China where essentially all cases are histologically oesophageal squamous cell carcinoma (ESCC). Agnostic pathway-based analyses of genome-wide association study (GWAS) data combined with tissue-specific expression quantitative trait loci (eQTL) analysis and publicly available functional data can identify biological pathways and/or genes enriched with functionally-relevant disease-associated variants.
Method: We used the adaptive multilocus joint test to analyse 1827 pathways containing 6060 genes using GWAS data from 1942 ESCC cases and 2111 controls with Chinese ancestry. We examined the function of risk alleles using in silico and eQTL analyses in oesophageal tissues.
Results: Associations with ESCC risk were observed for 36 pathways predominantly involved in apoptosis, cell cycle regulation and DNA repair and containing known GWAS-associated genes. After excluding genes with previous GWAS signals, candidate pathways (and genes) for ESCC risk included taste transduction (KEGG_hsa04742; TAS2R13, TAS2R42, TAS2R14, TAS2R46,TAS2R50), long-patch base excision repair (Reactome_pid; POLD2) and the metabolics pathway (KEGG_hsa01100; MTAP, GAPDH, DCTD, POLD2, AMDHD1). We identified and validated CASP8 rs13016963 and IDH2 rs11630814 as eQTLs, and CASP8 rs3769823 and IDH2 rs4561444 as the potential functional variants in high-linkage disequilibrium with these single nucleotide polymorphisms (SNPs), respectively. Further, IDH2 mRNA levels were down-regulated in ESCC (tumour:normal-fold change = 0.69, P = 6.75E-14).
Conclusion: Agnostic pathway-based analyses and integration of multiple types of functional data provide new evidence for the contribution of genes in taste transduction and metabolism to ESCC susceptibility, and for the functionality of both established and new ESCC risk-related SNPs.
C1 [Hyland, Paula L.; Zhang, Han; Yang, Qi; Hu, Nan; Lin, Shih-Wen; Su, Hua; Wang, Lemin; Sung, Hyuna; Wang, Zhaoming; Chanock, Stephen J.; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Yu, Kai; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yang, Howard H.; Lee, Maxwell P.] NCI, Lab Basic Res, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ding, Ti] Shanxi Canc Hosp, Taiyuan, Peoples R China.
[Fan, Jin-Hu; Qiao, You-Lin] Canc Inst Hosp, Dept Epidemiol, Beijing, Peoples R China.
[Wheeler, William; Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
[Burdett, Laurie; Wang, Zhaoming] Leidos Biomed Res Inc, Canc Genom Res Lab, Frederick, MD USA.
RP Hyland, PL (reprint author), NIH, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA.
EM hylandpl@mail.nih.gov
RI Zhang, Han/K-2118-2016; Abnet, Christian/C-4111-2015;
OI Zhang, Han/0000-0001-7977-9616; Abnet, Christian/0000-0002-3008-7843;
Qiao, You-Lin/0000-0001-6380-0871
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This research was funded by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics.
NR 66
TC 1
Z9 1
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2016
VL 45
IS 1
BP 206
EP 220
DI 10.1093/ije/dyv294
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DJ5ER
UT WOS:000374230100027
PM 26635288
ER
PT J
AU Langston, RG
Rudenko, IN
Cookson, MR
AF Langston, Rebekah G.
Rudenko, Iakov N.
Cookson, Mark R.
TI The function of orthologues of the human Parkinson's disease gene LRRK2
across species: implications for disease modelling in preclinical
research
SO BIOCHEMICAL JOURNAL
LA English
DT Review
DE animal models; dopaminergic neurons; GTPase; kinase; LRRK2 homologue;
neurodegeneration; preclinical research
ID REPEAT KINASE 2; AUTOSOMAL-DOMINANT PARKINSONISM; LRRK2(R1441G)
TRANSGENIC MOUSE; SYNAPTIC VESICLE ENDOCYTOSIS; DOPAMINERGIC-NEURONS;
CAENORHABDITIS-ELEGANS; ALPHA-SYNUCLEIN; GTP-BINDING;
LEUCINE-RICH-REPEAT-KINASE-2 LRRK2; PROTEIN INTERACTIONS
AB In the period since LRRK2 (leucine-rich repeat kinase 2) was identified as a causal gene for late-onset autosomal dominant parkinsonism, a great deal of work has been aimed at understanding whether the LRRK2 protein might be a druggable target for Parkinson's disease (PD). As part of this effort, animal models have been developed to explore both the normal and the pathophysiological roles of LRRK2. However, LRRK2 is part of a wider family of proteins whose functions in different organisms remain poorly understood. In this review, we compare the information available on biochemical properties of LRRK2 homologues and orthologues from different species from invertebrates (e.g. Caenorhabditis elegans and Drosophila melanogaster) to mammals. We particularly discuss the mammalian LRRK2 homologue, LRRK1, and those species where there is only a single LRRK homologue, discussing examples where each of the LRRK family of proteins has distinct properties as well as those cases where there appear to be functional redundancy. We conclude that uncovering the function of LRRK2 orthologues will help to elucidate the key properties of human LRRK2 as well as to improve understanding of the suitability of different animal models for investigation of LRRK2-related PD.
C1 [Langston, Rebekah G.; Rudenko, Iakov N.; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Rudenko, Iakov N.] SUNY Stony Brook, Hlth Sci Ctr T16, Dept Internal Med, Room 020, Stony Brook, NY 11790 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 142
TC 3
Z9 3
U1 6
U2 9
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD FEB 1
PY 2016
VL 473
BP 221
EP 232
DI 10.1042/BJ20150985
PN 3
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DK2ZP
UT WOS:000374784700002
PM 26811536
ER
PT J
AU Bratton, D
Fernandez-Boyanapalli, R
Falcone, EL
Zerbe, C
Marciano, B
Holland, SM
AF Bratton, Donna
Fernandez-Boyanapalli, Ruby
Falcone, Emilia Liana
Zerbe, Christa
Marciano, Beatrix
Holland, Steven M.
TI Impaired Efferocytosis and Production of Mitochondrial Reactive Oxygen
Species (mitoROS) By Monocytes in Human Chronic Granulomatous Disease
(CGD) Is Reversed By Treatment with the Ppargamma Agonist Pioglitazone
(Pio)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Bratton, Donna; Fernandez-Boyanapalli, Ruby] Natl Jewish Hlth, Denver, CO USA.
[Falcone, Emilia Liana; Zerbe, Christa; Marciano, Beatrix] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 579
BP AB176
EP AB176
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403025
ER
PT J
AU Brown, KR
Zabel, RA
Calatroni, A
Visness, C
Sivaprasad, U
Matsui, E
West, JB
Makhija, MM
Gill, MA
Kim, H
Kattan, M
Pillai, DK
Gern, JE
Busse, WW
Togias, A
Liu, AH
Hershey, GKK
AF Brown, Kari R.
Zabel, Rebecca A.
Calatroni, Agustin
Visness, Cynthia
Sivaprasad, Umasundari
Matsui, Elizabeth
West, Joseph B.
Makhija, Melanie M.
Gill, Michelle A.
Kim, Haejin
Kattan, Meyer
Pillai, Dinesh K.
Gern, James E.
Busse, William W.
Togias, Alkis
Liu, Andrew H.
Hershey, Gurjit K. Khurana
TI Endotypes of Difficult-to-Control Asthma in Inner City Children Differ
By Race
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Brown, Kari R.; Hershey, Gurjit K. Khurana] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Zabel, Rebecca A.; Calatroni, Agustin; Visness, Cynthia] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Sivaprasad, Umasundari] Cincinnati Childrens Hosp Med Ctr, Div Asthma Res, Cincinnati, OH 45229 USA.
[Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[West, Joseph B.] Boston Univ, Med Ctr, Boston, MA USA.
[Makhija, Melanie M.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Gill, Michelle A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kim, Haejin] Henry Ford Hlth Syst, Div Allergy & Clin Immunol, Detroit, MI USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Pillai, Dinesh K.] Childrens Natl Hlth Syst, Washington, DC USA.
[Gern, James E.] Univ Wisconsin, Madison, WI USA.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Togias, Alkis] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Liu, Andrew H.] Childrens Hosp Colorado, Aurora, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 582
BP AB177
EP AB177
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403028
ER
PT J
AU Croston, TL
Nayak, AP
Lemons, AR
Goldsmith, WT
Kashon, ML
Germolec, DM
Beezhold, DH
Green, BJ
AF Croston, Tara L.
Nayak, Ajay P.
Lemons, Angela R.
Goldsmith, W. Travis
Kashon, Michael L.
Germolec, Dori M.
Beezhold, Donald H.
Green, Brett J.
TI Pulmonary MicroRNA Expression Profiles Associated with Subchronic
Aspergillus fumigatus Exposure
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Croston, Tara L.; Nayak, Ajay P.; Lemons, Angela R.; Green, Brett J.] NIOSH, Allergy & Clin Immunol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Goldsmith, W. Travis] NIOSH, Engn & Control Technol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Kashon, Michael L.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Germolec, Dori M.] Natl Inst Environm Hlth Sci, Toxicol Branch, Div Natl Toxicol Program, Res Triangle Pk, NC USA.
[Beezhold, Donald H.] NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 889
BP AB272
EP AB272
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005404085
ER
PT J
AU Esquivel, AT
Busse, WW
Calatroni, A
Gergen, PJ
Grindle, K
Gruchalla, RS
Kattan, M
Kercsmar, C
Hershey, GKK
Kim, H
Lebeau, P
Liu, AH
Szefler, SJ
Teach, SJ
Pongracic, JA
West, JB
Wildfire, J
Gern, JE
AF Esquivel, Ann T.
Busse, William W.
Calatroni, Agustin
Gergen, Peter J.
Grindle, Kristine
Gruchalla, Rebecca S.
Kattan, Meyer
Kercsmar, Carolyn
Hershey, Gurjit K. Khurana
Kim, Haejin
Lebeau, Petra
Liu, Andrew H.
Szefler, Stanley J.
Teach, Stephen J.
Pongracic, Jacqueline A.
West, Joseph B.
Wildfire, Jeremy
Gern, James E.
TI Omalizumab Decreases Rates of Cold Symptoms in Inner-City Children with
Allergic Asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Esquivel, Ann T.; Busse, William W.; Grindle, Kristine; Gern, James E.] Univ Wisconsin, Madison, WI USA.
[Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bldg 10, Bethesda, MD 20892 USA.
[Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kattan, Meyer] NewYork Presbyterian Columbia, New York, NY USA.
[Kercsmar, Carolyn; Hershey, Gurjit K. Khurana] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Kim, Haejin] Henry Ford Hlth Syst, Div Allergy & Clin Immunol, Detroit, MI USA.
[Lebeau, Petra] Rho, Denver, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Szefler, Stanley J.] Childrens Hosp Colorado, Breathing Inst, Aurora, CO USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA.
[Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[West, Joseph B.] Boston Univ, Med Ctr, Boston, MA USA.
[Wildfire, Jeremy] Rho Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 286
BP AB87
EP AB87
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005401223
ER
PT J
AU Kim, D
Beaven, MA
Kulinski, J
Desai, A
Cruse, G
Prussin, C
Komarow, HD
Carter, MC
Metcalfe, DD
Olivera, A
AF Kim, Dokyun
Beaven, Michael A.
Kulinski, Joseph
Desai, Avanti
Cruse, Glenn
Prussin, Calman
Komarow, Hirsh D.
Carter, Melody C.
Metcalfe, Dean D.
Olivera, Ana
TI Constitutive KIT Activity and IL-6 Production in Mast Cells Alters
Levels of Reactive Oxygen Species (ROS) and the Scavenger Protein DJ-1
in Mastocytosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kim, Dokyun; Kulinski, Joseph; Desai, Avanti; Cruse, Glenn; Prussin, Calman; Komarow, Hirsh D.; Carter, Melody C.; Metcalfe, Dean D.; Olivera, Ana] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 919
BP AB281
EP AB281
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005404114
ER
PT J
AU Kirshenbaum, AS
Leerkes, M
Desai, A
Metcalfe, DD
AF Kirshenbaum, Arnold S.
Leerkes, Maarten
Desai, Avanti
Metcalfe, Dean D.
TI Anti-Apoptosis and Cell Survival Gene Expression Profile in LAD2 Cells
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kirshenbaum, Arnold S.; Desai, Avanti; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Leerkes, Maarten] NIAID, Bioinformat & Computat Biosci Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 248
BP AB76
EP AB76
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005401186
ER
PT J
AU Kovacs, NC
Nelsen, L
Kirby, SY
Benjamin, K
Moshkovich, O
Holland-Thomas, N
Klion, AD
Khoury, P
Steinfeld, J
AF Kovacs, Nicholas C.
Nelsen, Linda
Kirby, Suyong Yun
Benjamin, Katy
Moshkovich, Olga
Holland-Thomas, Nicole
Klion, Amy D.
Khoury, Paneez
Steinfeld, Jonathan
TI Patient-Reported Symptoms from a Diverse Group of Subjects with
Hypereosinophilic Syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kovacs, Nicholas C.; Klion, Amy D.; Khoury, Paneez] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Nelsen, Linda; Kirby, Suyong Yun; Steinfeld, Jonathan] GlaxoSmithKline, King Of Prussia, PA USA.
[Benjamin, Katy; Moshkovich, Olga] ICON, Gaithersburg, MD USA.
[Holland-Thomas, Nicole] Leidos Biomedical Res Inc, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 548
BP AB167
EP AB167
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402238
ER
PT J
AU Kuang, FL
Khoury, P
Ware, JM
Klion, AD
AF Kuang, Fei Li
Khoury, Paneez
Ware, JeanAnne M.
Klion, Amy D.
TI Long Term Outcomes of Mepolizumab Treatment Compared to Conventional
Therapy for Subjects with HES
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kuang, Fei Li; Khoury, Paneez; Ware, JeanAnne M.; Klion, Amy D.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 552
BP AB168
EP AB168
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402242
ER
PT J
AU Legrand, F
Landolina, NA
Levi-Schaffer, F
Klion, AD
AF Legrand, Fanny
Landolina, Nadine A.
Levi-Schaffer, Francesca
Klion, Amy D.
TI Siglec-7 on Peripheral Blood Eosinophils: Surface Expression and
Functional Analysis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Legrand, Fanny; Klion, Amy D.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Landolina, Nadine A.; Levi-Schaffer, Francesca] Hebrew Univ Jerusalem, Jerusalem, Israel.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 549
BP AB167
EP AB167
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402239
ER
PT J
AU Lin, AA
Nutman, TB
AF Lin, Adora A.
Nutman, Thomas B.
TI IL-10 Differentially Regulates IgE and IgG4 Production through Indirect
Effects on Naive B Cells
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Lin, Adora A.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Nutman, Thomas B.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 622
BP AB191
EP AB191
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403068
ER
PT J
AU Liu, AH
Babineau, DC
Zabel, RA
Zoratti, EM
Pongracic, JA
O'Connor, GT
Wood, RA
Hershey, GKK
Kercsmar, C
Gruchalla, RS
Kattan, M
Teach, SJ
Arbes, SJ
Gergen, PJ
Togias, A
Visness, C
Busse, WW
AF Liu, Andrew H.
Babineau, Denise C.
Zabel, Rebecca A.
Zoratti, Edward M.
Pongracic, Jacqueline A.
O'Connor, George T.
Wood, Robert A.
Hershey, Gurjit K. Khurana
Kercsmar, Carolyn
Gruchalla, Rebecca S.
Kattan, Meyer
Teach, Stephen J.
Arbes, Samuel J., Jr.
Gergen, Peter J.
Togias, Alkis
Visness, Cynthia
Busse, William W.
TI Identification of Pathways to Asthma Severity in Inner-City Children
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Liu, Andrew H.] Univ Colorado, Childrens Hosp Colorado, Sch Med, Aurora, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Babineau, Denise C.; Arbes, Samuel J., Jr.; Visness, Cynthia] Rho Inc, Chapel Hill, NC USA.
[Babineau, Denise C.; Zabel, Rebecca A.; Visness, Cynthia] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Zoratti, Edward M.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Zoratti, Edward M.] Henry Ford Hlth Syst, Detroit, MI USA.
[Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Hershey, Gurjit K. Khurana] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Hershey, Gurjit K. Khurana] Univ Cincinnati, Cincinnati, OH USA.
[Kercsmar, Carolyn] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Gruchalla, Rebecca S.] UT Southwestern Med Ctr, Dallas, TX USA.
[Kattan, Meyer] New York Presbyterian Columbia, New York, NY USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bldg 10, Bethesda, MD 20892 USA.
[Gergen, Peter J.; Togias, Alkis] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 31
BP AB10
EP AB10
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005400032
ER
PT J
AU Milligan, KL
Purev, E
Childs, R
Milner, JD
AF Milligan, Ki Lee
Purev, Enkhtsetseg
Childs, Richard
Milner, Joshua D.
TI Systemic Hypersensitivity to G-CSF in a Healthy Donor Followed By
Successful Drug Challenge Allowing Stem Cell Donation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Milligan, Ki Lee; Purev, Enkhtsetseg; Childs, Richard] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 733
BP AB225
EP AB225
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403179
ER
PT J
AU Mueller, G
Randall, TA
Glesner, J
Pedersen, L
Perera, L
Edwards, LL
DeRose, E
Chapman, MD
London, R
Pomes, A
AF Mueller, Geoffrey
Randall, Thomas A.
Glesner, Jill
Pedersen, Lars
Perera, Lalith
Edwards, Lori L.
DeRose, Eugene
Chapman, Martin D.
London, Robert
Pomes, Anna
TI Structural, Serological, and Genomic Analyses of the Major Mite Allergen
Der p 23
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Mueller, Geoffrey; Randall, Thomas A.; Pedersen, Lars; Perera, Lalith; Edwards, Lori L.; DeRose, Eugene; London, Robert] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Glesner, Jill; Chapman, Martin D.; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 876
BP AB267
EP AB267
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005404072
ER
PT J
AU Nayak, AP
Croston, TL
Lemons, AR
Goldsmith, WT
Kashon, ML
Germolec, DM
Beezhold, DH
Green, BJ
AF Nayak, Ajay P.
Croston, Tara L.
Lemons, Angela R.
Goldsmith, W. Travis
Kashon, Michael L.
Germolec, Dori M.
Beezhold, Donald H.
Green, Brett J.
TI The Murine Pulmonary Proteomic Profile Associated with Allergic
Aspergillus Fumigatus Exposure
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Nayak, Ajay P.; Green, Brett J.] NIOSH, Allergy & Clin Immunol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Croston, Tara L.; Lemons, Angela R.] NIOSH, CDC, ACIB, Morgantown, WV USA.
[Goldsmith, W. Travis] NIOSH, Engn & Control Technol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Kashon, Michael L.] NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
[Germolec, Dori M.] NIEHS, Toxicol Program, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
[Beezhold, Donald H.] NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 594
BP AB181
EP AB181
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005403040
ER
PT J
AU Pongracic, JA
Zabel, RA
Babineau, DC
Zoratti, EM
O'Connor, GT
Wood, RA
Hershey, GKK
Kercsmar, C
Gruchalla, RS
Kattan, M
Teach, SJ
Arbes, SJ
Busse, WW
Gergen, PJ
Togias, A
Visness, C
Liu, AH
AF Pongracic, Jacqueline A.
Zabel, Rebecca A.
Babineau, Denise C.
Zoratti, Edward M.
O'Connor, George T.
Wood, Robert A.
Hershey, Gurjit K. Khurana
Kercsmar, Carolyn
Gruchalla, Rebecca S.
Kattan, Meyer
Teach, Stephen J.
Arbes, Samuel J., Jr.
Busse, William W.
Gergen, Peter J.
Togias, Alkis
Visness, Cynthia
Liu, Andrew H.
TI Characteristics That Distinguish Difficult-to-Control Asthma in
Inner-City Children
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Zabel, Rebecca A.; Babineau, Denise C.; Arbes, Samuel J., Jr.; Visness, Cynthia] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Zoratti, Edward M.] Henry Ford Hlth Syst, Detroit, MI USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Hershey, Gurjit K. Khurana] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Kercsmar, Carolyn] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bldg 10, Bethesda, MD 20892 USA.
[Togias, Alkis] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Liu, Andrew H.] Childrens Hosp Colorado, Aurora, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 25
BP AB8
EP AB8
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005400026
ER
PT J
AU Randall, TA
Ogburn, RN
Xu, YR
Roberts, JH
Morgan, MS
Rider, SD
London, R
Arlian, LG
Fitzgerald, MC
Mueller, G
Vyszenski-Moher, DL
AF Randall, Thomas A.
Ogburn, Ryenne N.
Xu, Yingron
Roberts, Julia H.
Morgan, Marjorie S.
Rider, S. Dean
London, Robert
Arlian, Larry G.
Fitzgerald, Michael C.
Mueller, Geoffrey
Vyszenski-Moher, DiAnn L.
TI Are Dust Mite Allergens More Abundant or More Stable Than Other
Dermatophagoides Pteronyssinus Proteins?
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Randall, Thomas A.; London, Robert; Mueller, Geoffrey] NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
[Ogburn, Ryenne N.; Xu, Yingron; Roberts, Julia H.; Fitzgerald, Michael C.] Duke Univ, Dayton, OH USA.
[Morgan, Marjorie S.; Rider, S. Dean; Arlian, Larry G.; Vyszenski-Moher, DiAnn L.] Wright State Univ, Dayton, OH 45435 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 878
BP AB268
EP AB268
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005404074
ER
PT J
AU Zoratti, EM
Zabel, RA
Babineau, DC
Pongracic, JA
O'Connor, GT
Wood, RA
Hershey, GKK
Kercsmar, C
Gruchalla, RS
Kattan, M
Teach, SJ
Arbes, SJ
Visness, C
Busse, WW
Gergen, PJ
Togias, A
Liu, AH
AF Zoratti, Edward M.
Zabel, Rebecca A.
Babineau, Denise C.
Pongracic, Jacqueline A.
O'Connor, George T.
Wood, Robert A.
Hershey, Gurjit K. Khurana
Kercsmar, Carolyn
Gruchalla, Rebecca S.
Kattan, Meyer
Teach, Stephen J.
Arbes, Samuel J., Jr.
Visness, Cynthia
Busse, William W.
Gergen, Peter J.
Togias, Alkis
Liu, Andrew H.
TI Levels of Allergy Cluster with Asthma Severity in Inner-City Children.
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY MAR 04-07, 2016
CL Los Angeles, CA
SP Amer Acad Allergy, Asthma & Immunol
C1 [Zoratti, Edward M.] Henry Ford Hlth Syst, Detroit, MI USA.
[Zabel, Rebecca A.; Babineau, Denise C.; Arbes, Samuel J., Jr.; Visness, Cynthia] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[O'Connor, George T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Hershey, Gurjit K. Khurana; Kercsmar, Carolyn] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kattan, Meyer] New York Presbyterian Columbia, New York, NY USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Gergen, Peter J.; Togias, Alkis] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Liu, Andrew H.] Childrens Hosp Colorado, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 7
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD FEB
PY 2016
VL 137
IS 2
SU S
MA 334
BP AB103
EP AB103
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DK6BI
UT WOS:000375005402025
ER
PT J
AU Shapiro, CL
Jacobsen, PB
Henderson, T
Hurria, A
Nekhlyudov, L
Ng, A
Surbone, A
Mayer, DK
Rowland, JH
AF Shapiro, Charles L.
Jacobsen, Paul B.
Henderson, Tara
Hurria, Arti
Nekhlyudov, Larissa
Ng, Andrea
Surbone, Antonella
Mayer, Deborah K.
Rowland, Julia H.
TI ASCO Core Curriculum for Cancer Survivorship Education
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; AMERICAN SOCIETY;
CHILDHOOD-CANCER; BREAST-CANCER; FERTILITY PRESERVATION; DEPRESSIVE
SYMPTOMS; ADULT SURVIVORS; FOLLOW-UP; CARE
AB The number of individuals who will be diagnosed with cancer and experience personal cures (ie, dying from some other cause and not cancer) or live for extended periods after cancer treatment is increasing exponentially. By 2025, there will be nearly 20 million survivors, approximately two thirds over the age of 60. The ASCO Survivorship Committee, in partnership with ASCO Professional Committee, has developed this core curriculum and competencies for health care providers, training programs, and policymaking organizations. Adapted from Institute of Medicine recommendations for survivorship care, the curriculum and competencies include surveillance for recurrence and second malignancies; long-term and late effects; health promotion and prevention; psychosocial well-being; and special populations including adolescent and young adult survivors, older adult cancer survivors, and the caregivers of cancer survivors. Finally, an area the importance of which cannot be emphasized enough is communication and care coordination. It is our belief that doctors and other allied health professionals require special expertise tomanagethe exponentially expanding evidence-based and best practice recommendations to provide care for cancer survivors.
C1 [Shapiro, Charles L.] Icahn Sch Med Mt Sinai, One Gustave Levy Pl,Box 1079, New York, NY 10029 USA.
NYU, Sch Med, New York, NY USA.
Univ Tampa, Tampa, FL 33606 USA.
Univ Chicago, Chicago, IL 60637 USA.
City Hope Natl Med Ctr, Duarte, CA USA.
Harvard Vanguard Med Associates, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ N Carolina, Chapel Hill, NC USA.
NCI, Bethesda, MD 20892 USA.
RP Shapiro, CL (reprint author), Icahn Sch Med Mt Sinai, One Gustave Levy Pl,Box 1079, New York, NY 10029 USA.
EM charles.shapiro@mssm.edu
NR 71
TC 3
Z9 3
U1 2
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD FEB
PY 2016
VL 12
IS 2
BP 145
EP +
DI 10.1200/JOP.2015.009449
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DJ6LS
UT WOS:000374325300017
PM 26813926
ER
PT J
AU Onukwugha, E
Petrelli, NJ
Castro, KM
Gardner, JF
Jayasekera, J
Goloubeva, O
Tan, MT
McNamara, EJ
Zaren, HA
Asfeldt, T
Bearden, JD
Salner, AL
Krasna, MJ
Das, IP
Clauser, SB
AF Onukwugha, Eberechukwu
Petrelli, Nicholas J.
Castro, Kathleen M.
Gardner, James F.
Jayasekera, Jinani
Goloubeva, Olga
Tan, Ming T.
McNamara, Erica J.
Zaren, Howard A.
Asfeldt, Thomas
Bearden, James D., III
Salner, Andrew L.
Krasna, Mark J.
Das, Irene Prabhu
Clauser, Steve B.
TI Impact of Multidisciplinary Care on Processes of Cancer Care: A
Multi-Institutional Study
SO JOURNAL OF ONCOLOGY PRACTICE
LA English
DT Article
ID THORACIC MALIGNANCY CONFERENCE; BREAST-CANCER; LUNG-CANCER;
DECISION-MAKING; ASSESSMENT-TOOL; TUMOR BOARDS; TEAM; MANAGEMENT;
SURVIVAL; QUALITY
AB Purpose
The role of multidisciplinary care (MDC) on cancer care processes is not fully understood. We investigated the impact of MDC on the processes of care at cancer centers within the National Cancer Institute Community Cancer Centers Program (NCCCP).
Methods
The study used data from patients diagnosed with stage IIB to III rectal cancer, stage III colon cancer, and stage III non-small-cell lung cancer at 14 NCCCP cancer centers from 2007 to 2012. We used an MDC development assessment tool-with levels ranging from evolving MDC (low) to achieving excellence (high)- to measure the level of MDC implementation in seven MDC areas, such as case planning and physician engagement. Descriptive statistics and cluster-adjusted regression models quantified the association between MDC implementation and processes of care, including time from diagnosis to treatment receipt.
Results
A total of 1,079 patients were examined. Compared with patients with colon cancer treated at cancer centers reporting low MDC scores, time to treatment receipt was shorter for patients with colon cancer treated at cancer centers reporting high or moderate MDC scores for physician engagement (hazard ratio [HR] for high physician engagement, 2.66; 95% CI, 1.70 to 4.17; HR for moderate physician engagement, 1.50; 95% CI, 1.19 to 1.89) and longer for patients with colon cancer treated at cancer centers reporting high 2MDC scores for case planning (HR, 0.65; 95% CI, 0.49 to 0.85). Results for patients with rectal cancer were qualitatively similar, and there was no statistically significant difference among patients with lung cancer.
Conclusion
MDC implementation level was associated with processes of care, and direction of association varied across MDC assessment areas.
C1 Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
NCI, Rockville, MD USA.
St Joseph Med Ctr, Inst Canc, Towson, MD USA.
Christiana Care, Helen F Graham Canc Ctr, Wilmington, DE USA.
Amer Coll Surg, Chicago, IL USA.
St Josephs Candler Hosp Syst, Nancy N & JC Lewis Canc & Res Pavil, Savannah, GA USA.
Sanford Canc Ctr, Sioux Falls, SD USA.
Gibbs Canc Ctr & Res Inst, Spartanburg, SC USA.
Hartford Hosp, Helen & Harry Gray Canc Ctr, Hartford, CT 06115 USA.
RP Onukwugha, E (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Hlth Serv Res, 220 Arch St, Baltimore, MD 21201 USA.
EM eonukwug@rx.umaryland.edu
FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E]; PHS
HHS [HHSN261200800001E]
NR 37
TC 3
Z9 3
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 1554-7477
EI 1935-469X
J9 J ONCOL PRACT
JI J. Oncol. Pract.
PD FEB
PY 2016
VL 12
IS 2
BP 155
EP +
DI 10.1200/JOP.2015.004200
PG 14
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DJ6LS
UT WOS:000374325300022
PM 26464497
ER
PT J
AU Ahmadi, B
Alimohammadian, M
Yaseri, M
Majidi, A
Boreiri, M
Islami, F
Poustchi, H
Derakhshan, MH
Feizesani, A
Pourshams, A
Abnet, CC
Brennan, P
Dawsey, SM
Kamangar, F
Boffetta, P
Sadjadi, A
Malekzadeh, R
AF Ahmadi, Batoul
Alimohammadian, Masoomeh
Yaseri, Mehdi
Majidi, Azam
Boreiri, Majid
Islami, Farhad
Poustchi, Hossein
Derakhshan, Mohammad H.
Feizesani, Akabar
Pourshams, Akram
Abnet, Christian C.
Brennan, Paul
Dawsey, Sanford M.
Kamangar, Farin
Boffetta, Paolo
Sadjadi, Alireza
Malekzadeh, Reza
TI Multimorbidity: Epidemiology and Risk Factors in the Golestan Cohort
Study, Iran: A Cross-Sectional Analysis
SO MEDICINE
LA English
DT Article
ID GASTROESOPHAGEAL-REFLUX DISEASE; ESOPHAGEAL CANCER; POPULATION;
PREVALENCE; MORTALITY; OBESITY; WOMEN; OPIUM
AB Advances in medicine and health policy have resulted in growing of older population, with a concurrent rise in multimorbidity, particularly in Iran, as a country transitioning to a western lifestyle, and in which the percent of the population over the age of 60 years is increasing. This study aims to assess multimorbidity and the associated risk factors in Iran.We used data from 50,045 participants (age 40-75 y) in the Golestan Cohort Study, including data on demographics, lifestyle habits, socioeconomic status, and anthropometric indices. Multimorbidity was defined as the presence of 2 or more out of 8 self-reported chronic conditions, including cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, gastroesophageal reflux disease, tuberculosis, and cancer. Multivariate logistic regression models were used to examine the associations between multiple different factors and the risk factors.Multimorbidity prevalence was 19.4%, with the most common chronic diseases being gastroesophageal reflux disease (76.7%), cardiovascular diseases (72.7%), diabetes (25.3%), and chronic obstructive pulmonary disease (21.9%). The odds of multimorbidity was 2.56-fold higher at the age of >60 years compared with that at <50 years (P<0.001), and 2.11-fold higher in women than in men (P<0.001). Other factors associated with higher risk of multimorbidity included non-Turkmen ethnicity, low education, unemployment, low socioeconomic status, physical inactivity, overweight, obesity, former smoking, opium and alcohol use, and poor oral health.Apart from advanced age and female sex, the most important potentially modifiable lifestyle factors, including excess body weight and opium use, and opium user, are associated with multimorbidity. Policies aiming at controlling multimorbidity will require a multidimensional approach to reduce modifiable risk factors in the younger population in developing countries alongside adopting efficient strategies to improve life quality in the older population.
C1 [Ahmadi, Batoul] Univ Tehran Med Sci, Sch Publ Hlth, Dept Hlth Management & Econ, Tehran, Iran.
[Alimohammadian, Masoomeh; Majidi, Azam; Boreiri, Majid; Islami, Farhad; Poustchi, Hossein; Feizesani, Akabar; Pourshams, Akram; Kamangar, Farin; Sadjadi, Alireza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Digest Dis Res Inst, Tehran, Iran.
[Alimohammadian, Masoomeh; Boreiri, Majid; Poustchi, Hossein; Derakhshan, Mohammad H.; Feizesani, Akabar; Pourshams, Akram; Sadjadi, Alireza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Oncol Res Ctr, Digest Dis Res Inst, Tehran, Iran.
[Alimohammadian, Masoomeh] Univ Tehran Med Sci, Sch Publ Hlth, Dept Human Ecol, Tehran, Iran.
[Yaseri, Mehdi] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran.
[Islami, Farhad] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30329 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Derakhshan, Mohammad H.] Univ Glasgow, Div Cardiovasc & Med Sci, Gastroenterol Sect, Glasgow, Lanark, Scotland.
[Pourshams, Akram] Univ Tehran Med Sci, Liver & Pancreatic biliary Res Ctr, Digest Dis Res Inst, Tehran, Iran.
[Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Boffetta, Paolo] Int Agcy Res Canc, Genet Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
RP Sadjadi, A (reprint author), Univ Tehran Med Sci, Digest Dis Res Inst, Tehran, Iran.
EM sadjadia@gmail.com
RI Derakhshan, Mohammad/K-8694-2016; Abnet, Christian/C-4111-2015;
OI Abnet, Christian/0000-0002-3008-7843; Yaseri, Mehdi/0000-0002-4066-873X
FU Digestive Disease Research Center of Tehran University of Medical
Sciences [0-82-603]; International Agency for Research on Cancer
FX This study was supported by the Digestive Disease Research Center of
Tehran University of Medical Sciences (grant No 0-82-603) and in part by
the International Agency for Research on Cancer. We wish to thank the
study participants for their cooperation over many years and the Behvarz
working in the study areas for their help.
NR 55
TC 2
Z9 2
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD FEB
PY 2016
VL 95
IS 7
AR e2756
DI 10.1097/MD.0000000000002756
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DK2ZA
UT WOS:000374782900025
PM 26886618
ER
PT J
AU Coghill, AE
Shiels, MS
Suneja, G
Engels, EA
AF Coghill, Anna E.
Shiels, Meredith S.
Suneja, Gita
Engels, Eric A.
TI All-Cause and Cancer-Specific Mortality Among Patients With Cancer
Infected or Not Infected With HIV Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Coghill, Anna E.; Shiels, Meredith S.; Engels, Eric A.] NCI, Rockville, MD USA.
[Suneja, Gita] Univ Utah, Sch Med, Salt Lake City, UT USA.
RP Coghill, AE (reprint author), NCI, Rockville, MD USA.
FU Intramural NIH HHS
NR 5
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2016
VL 34
IS 4
BP 390
EP U174
DI 10.1200/JCO.2015.64.6026
PG 2
WC Oncology
SC Oncology
GA DJ6NZ
UT WOS:000374331500022
PM 26598741
ER
PT J
AU Feingold, PL
Kwong, MLM
Sabesan, A
Sorber, R
Rudloff, U
AF Feingold, Paul L.
Kwong, Mei Li M.
Sabesan, Arvind
Sorber, Rebecca
Rudloff, Udo
TI Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for
gastric cancer and other less common disease histologies: is it time?
SO JOURNAL OF GASTROINTESTINAL ONCOLOGY
LA English
DT Review
DE Metastatic gastric cancer; peritoneal carcinomatosis; cytoreductive
surgery (CRS); heated intraperitoneal chemotherapy (HIPEC); systematic
review
ID CHEMOHYPERTHERMIC PERITONEAL PERFUSION; ADRENAL-CORTICAL CARCINOMA;
CARBON-ADSORBED MITOMYCIN; SOFT-TISSUE SARCOMA; LONG-TERM SURVIVAL;
SYSTEMIC CHEMOTHERAPY; PANCREATIC-CANCER; COLORECTAL-CANCER; ADJUVANT
CHEMOTHERAPY; PROGNOSTIC-FACTORS
AB Gastric cancer is the fourth most commonly diagnosed cancer worldwide, and once spread to the peritoneum, has a 5-year survival of less than 5%. Recent years have demonstrated advances in the use of cytoreductive surgery (CRS) in combination with heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis due to various malignancies. The frequent desmoplastic stroma and poor vascularization impeding drug delivery particularly in the diffuse form of gastric cancer is thought to provide a sound rationale for a regionalized treatment approach in this disease. Here, we seek to review the available data to define the role of CRS and HIPEC in gastric cancer metastatic to the peritoneal surface, and furthermore, analyze the use of CRS and HIPEC in malignancies less commonly treated with the regionalized perfusion approach.
C1 [Feingold, Paul L.; Kwong, Mei Li M.; Sabesan, Arvind; Sorber, Rebecca; Rudloff, Udo] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Rudloff, U (reprint author), NCI, Thorac & Gastrointestinal Oncol Branch, Gastrointestinal Oncol Sect, Ctr Canc Res, Bldg 10 Hatfield CRC,Room 4-5950, Bethesda, MD 20892 USA.
EM rudloffu@mail.nih.gov
OI Feingold, Paul/0000-0002-3194-4309
NR 67
TC 2
Z9 4
U1 1
U2 6
PU PIONEER BIOSCIENCE PUBL CO
PI HONG KONG
PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG,
00000, PEOPLES R CHINA
SN 2078-6891
EI 2219-679X
J9 J GASTROINTEST ONCOL
JI J. Gastrointest. Oncol.
PD FEB
PY 2016
VL 7
IS 1
BP 87
EP 98
DI 10.3978/j.issn.2078-6891.2015.098
PG 12
WC Oncology
SC Oncology
GA DK6UE
UT WOS:000375060100010
PM 26941987
ER
PT J
AU Goodman, RA
Ling, SM
Briss, PA
Parrish, RG
Salive, ME
Finke, BS
AF Goodman, Richard A.
Ling, Shari M.
Briss, Peter A.
Parrish, R. Gibson
Salive, Marcel E.
Finke, Bruce S.
TI Multimorbidity Patterns in the United States: Implications for Research
and Clinical Practice
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE; HEALTH; PREVALENCE; ADULTS; COMORBIDITIES;
DEPRESSION; STRATEGIES; GUIDELINES; ARTHRITIS
C1 [Goodman, Richard A.] US Dept HHS, Off Assistant Secretary Hlth, Washington, DC 20201 USA.
[Goodman, Richard A.; Briss, Peter A.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Mailstop K40,4770 Buford Highway NE, Atlanta, GA 30341 USA.
[Ling, Shari M.] Ctr Medicare, Baltimore, MD USA.
[Ling, Shari M.] Ctr Medicaid Serv, Baltimore, MD USA.
[Goodman, Richard A.; Parrish, R. Gibson] Publ Hlth Informat Inst, Decatur, GA USA.
[Salive, Marcel E.] NIA, NIH, Bethesda, MD 20892 USA.
[Ling, Shari M.; Finke, Bruce S.] Indian Hlth Serv, Nashville Area, Nashville, TN USA.
RP Briss, PA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Mailstop K40,4770 Buford Highway NE, Atlanta, GA 30341 USA.
EM pxb5@cdc.gov
NR 40
TC 4
Z9 4
U1 3
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD FEB
PY 2016
VL 71
IS 2
BP 215
EP 220
DI 10.1093/gerona/glv199
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4XY
UT WOS:000374212600009
PM 26714567
ER
PT J
AU Brown, PJ
Roose, SP
Zhang, J
Wall, M
Rutherford, BR
Ayonayon, HN
Butters, MA
Harris, T
Newman, AB
Satterfield, S
Simonsick, EM
Yaffe, K
AF Brown, Patrick J.
Roose, Steven P.
Zhang, Jun
Wall, Melanie
Rutherford, Bret R.
Ayonayon, Hilsa N.
Butters, Meryl A.
Harris, Tamara
Newman, Anne B.
Satterfield, Suzanne
Simonsick, Eleanor M.
Yaffe, Kristine
TI Inflammation, Depression, and Slow Gait: A High Mortality Phenotype in
Later Life
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Frailty; Depression; Inflammation; Slow Gait; Mortality
ID OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL PERFORMANCE; INTERFERON-ALPHA;
BASAL GANGLIA; HEALTH; SPEED; FRAILTY; AGE; TRAJECTORIES
AB Background. Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality.
Methods. Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression >= 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality.
Results. For each outcome, low-probability (n(inflammation) = 1,656, n(slow gait) = 1,471, n(depression) = 1,458), increasing-probability (n(inflammation) = 847, n slow gait = 880, n(depression) = 1,062), and consistently high-probability (n(inflammation) = 572, n(slow gait) = 724, n(depression) = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r=.40, p<.001) and depression (r=.49, p<.001). Although worsening trajectories of inflammation were independently associated with mortality (p<.001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p<.01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations.
Conclusions. Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed.
C1 [Brown, Patrick J.; Roose, Steven P.; Zhang, Jun; Wall, Melanie; Rutherford, Bret R.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Div Geriatr Psychiat, New York, NY USA.
[Zhang, Jun; Wall, Melanie] Columbia Univ, Mailman Sch Publ Health, Div Biostat, New York, NY 10027 USA.
[Ayonayon, Hilsa N.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Butters, Meryl A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Harris, Tamara] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Med & Clin & Translat Sci, Pittsburgh, PA 15260 USA.
[Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Simonsick, Eleanor M.] NIA, Harbor Hosp, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
RP Brown, PJ (reprint author), Columbia Univ Coll Phys & Surg, Columbia Univ, Mailman Sch Publ Hlth, Div Geriatr Psychiat,New York State Psychiat Inst, 1051 Riverside Dr,Unit 126, New York, NY 10032 USA.
EM pb2410@cumc.columbia.edu
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute on Aging (NINR)
[R01-NR012459]; National Institute for Mental Health [K23-MH099097];
Intramural Research Program of the NIH, National Institute on Aging
FX This research was supported by National Institute on Aging
(N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050;
and NINR grant R01-NR012459) and the National Institute for Mental
Health (K23-MH099097). This research was also supported by the
Intramural Research Program of the NIH, National Institute on Aging.
NR 43
TC 5
Z9 5
U1 6
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD FEB
PY 2016
VL 71
IS 2
BP 221
EP 227
DI 10.1093/gerona/glv156
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4XY
UT WOS:000374212600010
PM 26392405
ER
PT J
AU Murphy, RA
Hagaman, AK
Reinders, I
Steeves, JA
Newman, AB
Rubin, SM
Satterfield, S
Kritchevsky, SB
Yaffe, K
Ayonayon, HN
Nagin, DS
Simonsick, EM
Penninx, BWJH
Harris, TB
AF Murphy, Rachel A.
Hagaman, Ashley K.
Reinders, Ilse
Steeves, Jeremy A.
Newman, Anne B.
Rubin, Susan M.
Satterfield, Suzanne
Kritchevsky, Stephen B.
Yaffe, Kristine
Ayonayon, Hilsa N.
Nagin, Daniel S.
Simonsick, Eleanor M.
Penninx, Brenda W. J. H.
Harris, Tamara B.
CA Hlth ABC Study
TI Depressive Trajectories and Risk of Disability and Mortality in Older
Adults: Longitudinal Findings From the Health, Aging, and Body
Composition Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Depression; Mood; Aging; Geriatric; Function
ID NATIONAL COMORBIDITY SURVEY; CHRONIC KIDNEY-DISEASE; PRIMARY-CARE
PATIENTS; UNITED-STATES; INFLAMMATORY MARKERS; SOCIOECONOMIC-STATUS;
MAJOR DEPRESSION; EXCESS MORTALITY; SEX-DIFFERENCES; SHORT-FORM
AB Background. Depression and disability are closely linked. Less is known regarding clinical and subclinical depressive symptoms over time and risk of disability and mortality.
Methods. Responses to the Center for Epidemiologic Studies Short Depression scale (CES-D10) were assessed over a 4-year period in men (n = 1032) and women (n = 1070) aged 70-79 years initially free from disability. Depressive symptom trajectories were defined with group-based models. Disability (2 consecutive reports of severe difficulty walking one-quarter mile or climbing 10 steps) and mortality were determined for 9 subsequent years. Hazard ratios (HRs) were estimated using Cox proportional hazards adjusted for covariates.
Results. Three trajectories were identified: persistently nondepressed (54% of men, 54% of women, mean baseline CES-D10: 1.16 and 1.46), mildly depressed and increasing (40% of men, 38% of women, mean baseline CES-D10: 3.60 and 4.35), and depressed and increasing (6% of men, 8% of women, mean baseline CES-D10: 7.44 and 9.61). Disability and mortality rates per 1,000 person years were 41.4 and 60.3 in men and 45.8 and 41.9 in women. Relative to nondepressed, men in the mildly depressed (HR = 1.45, 95% confidence interval [CI] 1.11-1.89) and depressed trajectories (HR = 2.12, 95% CI 1.33-3.38) had increased disability; women in the depressed trajectory had increased disability (HR = 2.02, 95% CI 1.37-2.96). Men in the mildly depressed (HR = 1.24, 95% CI 1.01-1.52) and depressed trajectories (HR = 1.63, 95% CI 1.10-2.41) had elevated mortality risk; women exhibited no mortality risk.
Conclusions. Trajectories of depressive symptoms without recovery may predict disability and mortality in apparently healthy older populations, thus underscoring the importance of monitoring depressive symptoms in geriatric care.
C1 [Murphy, Rachel A.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
[Murphy, Rachel A.; Reinders, Ilse; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Hagaman, Ashley K.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ USA.
[Reinders, Ilse] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands.
[Reinders, Ilse] Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Steeves, Jeremy A.] NCI, Canc Prevent Fellowship Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15260 USA.
[Rubin, Susan M.; Yaffe, Kristine; Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA.
[Nagin, Daniel S.] Carnegie Mellon Univ, Heinz Coll, Pittsburgh, PA 15213 USA.
[Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
RP Murphy, RA (reprint author), Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
EM rachel.murphy@ubc.ca
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging (NIA); NIA [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
[R01-NR-012459]; Wake Forest University Claude D. Pepper Older Americans
for Independence Center [1P30AG21332]; Pittsburgh Claude D. Pepper
Center [P30 AG024827]; Banting Postdoctoral Fellowship
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging (NIA);
the NIA Contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106; NIA
Grant R01-AG028050, National Institute of Nursing Research Grant
R01-NR-012459, the Wake Forest University Claude D. Pepper Older
Americans for Independence Center (1P30AG21332); and the Pittsburgh
Claude D. Pepper Center (P30 AG024827). R. A. M. was supported by a
Banting Postdoctoral Fellowship.
NR 46
TC 3
Z9 3
U1 4
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD FEB
PY 2016
VL 71
IS 2
BP 228
EP 235
DI 10.1093/gerona/glv139
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4XY
UT WOS:000374212600011
PM 26273025
ER
PT J
AU Bianchi, L
Ferrucci, L
Cherubini, A
Maggio, M
Bandinelli, S
Savino, E
Brombo, G
Zuliani, G
Guralnik, JM
Landi, F
Volpato, S
AF Bianchi, Lara
Ferrucci, Luigi
Cherubini, Antonio
Maggio, Marcello
Bandinelli, Stefania
Savino, Elisabetta
Brombo, Gloria
Zuliani, Giovanni
Guralnik, Jack M.
Landi, Francesco
Volpato, Stefano
TI The Predictive Value of the EWGSOP Definition of Sarcopenia: Results
From the InCHIANTI Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Sarcopenia; Aging; Disability; Mortality; Hospitalization
ID EUROPEAN WORKING GROUP; SKELETAL-MUSCLE MASS; OLDER-PEOPLE EWGSOP; LOW
LEAN MASS; PHYSICAL PERFORMANCE; RISK-FACTOR; MORTALITY; STRENGTH;
DISABILITY; MOBILITY
AB Background. Sarcopenia is associated with increased risk of adverse outcomes in older people. Aim of the study was to explore the predictive value of the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic algorithm in terms of disability, hospitalization, and mortality and analyze the specific role of grip strength and walking speed as diagnostic criteria for sarcopenia.
Methods. Longitudinal analysis of 538 participants enrolled in the InCHIANTI study. Sarcopenia was defined as having low muscle mass plus low grip strength or low gait speed (EWGSOP criteria). Muscle mass was assessed using bioimpedance analysis. Cox proportional and logistic regression models were used to assess risk of death, hospitalization, and disability for sarcopenic people and to investigate the individual contributions of grip strength and walking speed to the predictive value of the EWGSOP's algorithm.
Results. Prevalence of EWGSOP-defined sarcopenia at baseline was 10.2%. After adjusting for potential confounders, sarcopenia was associated with disability (odds ratio 3.15; 95% confidence interval [CI] 1.41-7.05), hospitalization (hazard ratio [HR] 1.57; 95% CI 1.03-2.41), and mortality (HR 1.88; 95% CI 0.91-3.91). The association between an alternative sarcopenic phenotype, defined only by the presence of low muscle mass and low grip strength, and both disability and mortality were similar to the association with the phenotypes defined by low muscle mass and low walking speed or by the EWGSOP algorithm.
Conclusions. The EWGSOP's phenotype is a good predictor of incident disability, hospitalization and death. Assessment of only muscle weakness, in addition to low muscle mass, provided similar predictive value as compared to the original algorithm.
C1 [Bianchi, Lara; Savino, Elisabetta; Brombo, Gloria; Zuliani, Giovanni; Volpato, Stefano] Univ Ferrara, Dept Med Sci, Via Savonarola 9, I-44100 Ferrara, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Cherubini, Antonio] IRCCS INRCA, Geriatr, Ancona, Italy.
[Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Clin & Expt Med, I-43100 Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Landi, Francesco] Univ Cattolica Sacro Cuore, Dept Gerontol & Geriatr Sci, Rome, Italy.
[Volpato, Stefano] Univ Ferrara, Sch Med, Ctr Clin Epidemiol, I-44100 Ferrara, Italy.
RP Volpato, S (reprint author), Univ Ferrara, Dept Med Sci, Via Savonarola 9, I-44100 Ferrara, Italy.
EM vlt@unife.it
RI VOLPATO, STEFANO/H-2977-2014;
OI VOLPATO, STEFANO/0000-0003-4335-6034; Cherubini,
Antonio/0000-0003-0261-9897
FU U.S. National Institute on Aging [N01-AG-5-0002]; National Institute on
Aging, National Institutes of Health, Baltimore, Maryland
FX The InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by
the U.S. National Institute on Aging (Contract: N01-AG-5-0002);
supported in part by the Intramural research program of the National
Institute on Aging, National Institutes of Health, Baltimore, Maryland.
NR 36
TC 10
Z9 10
U1 5
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD FEB
PY 2016
VL 71
IS 2
BP 259
EP 264
DI 10.1093/gerona/glv129
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DJ4XY
UT WOS:000374212600015
PM 26333772
ER
PT J
AU Basu, SK
Lee, S
Sakchaisri, K
Walia, V
Westlake, CJ
Morrison, DK
Johnson, PF
AF Basu, Sandip K.
Lee, Sook
Sakchaisri, Krisada
Walia, Vijay
Westlake, Christopher J.
Morrison, Deborah K.
Johnson, Peter F.
TI Oncogenic Ras signaling involves formation of perinuclear CK2 alpha nd
p-ERK1/2 signaling complexes that require the KSR-1 scaffold protein and
endosomal trafficking
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 4th AACR International Conference on Frontiers in Basic Cancer Research
CY OCT 23-26, 2015
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Basu, Sandip K.; Lee, Sook; Sakchaisri, Krisada; Johnson, Peter F.] NCI Frederick, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD USA.
[Walia, Vijay; Westlake, Christopher J.; Morrison, Deborah K.] NCI Frederick, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 1
PY 2016
VL 76
SU 3
MA A35
PG 2
WC Oncology
SC Oncology
GA DJ4FB
UT WOS:000374159700029
ER
PT J
AU Kuppusamy, B
Mendoza-Villaneuva, D
Summers, G
Sharan, S
Sterneck, E
AF Kuppusamy, Balamurugan
Mendoza-Villaneuva, Daniel
Summers, Glenn
Sharan, Shikha
Sterneck, Esta
TI The CEBPD transcription factor: A signaling hub for promotion of cancer
cell stemness
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 4th AACR International Conference on Frontiers in Basic Cancer Research
CY OCT 23-26, 2015
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Kuppusamy, Balamurugan; Mendoza-Villaneuva, Daniel; Summers, Glenn; Sharan, Shikha; Sterneck, Esta] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 1
PY 2016
VL 76
SU 3
MA A17
PG 2
WC Oncology
SC Oncology
GA DJ4FB
UT WOS:000374159700014
ER
PT J
AU Lucas, PJ
Gress, RE
AF Lucas, Philip J.
Gress, Ronald E.
TI Differential effect of microenvironment on tumor phenotype using an
immature T cell lymphoma mouse model
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 4th AACR International Conference on Frontiers in Basic Cancer Research
CY OCT 23-26, 2015
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Lucas, Philip J.; Gress, Ronald E.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 1
PY 2016
VL 76
SU 3
MA B09
PG 2
WC Oncology
SC Oncology
GA DJ4FB
UT WOS:000374159700043
ER
PT J
AU Mayekar, MK
Huggins, CJ
Martin, N
Saylor, KL
Gonit, M
Jailwala, P
Kasoji, M
Haines, DC
Quinones, OA
Johnson, PF
AF Mayekar, Manasi K.
Huggins, Christopher J.
Martin, Nancy
Saylor, Karen L.
Gonit, Mesfin
Jailwala, Parthav
Kasoji, Manjula
Haines, Diana C.
Quinones, Octavio A.
Johnson, Peter F.
TI C/EBPG: A critical stress response regulator with a pro-oncogenic role
SO CANCER RESEARCH
LA English
DT Meeting Abstract
CT 4th AACR International Conference on Frontiers in Basic Cancer Research
CY OCT 23-26, 2015
CL Philadelphia, PA
SP Amer Assoc Canc Res
C1 [Mayekar, Manasi K.; Huggins, Christopher J.; Martin, Nancy; Gonit, Mesfin; Johnson, Peter F.] NCI, Frederick, MD 21701 USA.
[Saylor, Karen L.; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C.; Quinones, Octavio A.] Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD FEB 1
PY 2016
VL 76
SU 3
MA PR02
PG 2
WC Oncology
SC Oncology
GA DJ4FB
UT WOS:000374159700098
ER
PT J
AU Dent, AE
Malhotra, I
Wang, XL
Babineau, D
Yeo, KT
Anderson, T
Kimmel, RJ
Angov, E
Lanar, DE
Narum, D
Dutta, S
Richards, J
Beeson, JG
Crabb, BS
Cowman, AF
Horii, T
Muchiri, E
Mungai, PL
King, CL
Kazura, JW
AF Dent, Arlene E.
Malhotra, Indu
Wang, Xuelie
Babineau, Denise
Yeo, Kee Thai
Anderson, Timothy
Kimmel, Rhonda J.
Angov, Evelina
Lanar, David E.
Narum, David
Dutta, Sheetij
Richards, Jack
Beeson, James G.
Crabb, Brendan S.
Cowman, Alan F.
Horii, Toshihiro
Muchiri, Eric
Mungai, Peter L.
King, Christopher L.
Kazura, James W.
TI Contrasting Patterns of Serologic and Functional Antibody Dynamics to
Plasmodium falciparum Antigens in a Kenyan Birth Cohort
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID MEROZOITE SURFACE PROTEIN-1; APICAL MEMBRANE ANTIGEN-1;
INVASION-INHIBITORY ANTIBODIES; IN-VITRO GROWTH; ERYTHROCYTE-BINDING
ANTIGENS; NATURALLY ACQUIRED-IMMUNITY; INFECTED ERYTHROCYTES; MALARIA
VACCINE; ESCHERICHIA-COLI; AOTUS-NANCYMAI
AB IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.
C1 [Dent, Arlene E.; Malhotra, Indu; Kimmel, Rhonda J.; Mungai, Peter L.; King, Christopher L.; Kazura, James W.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Dent, Arlene E.; Yeo, Kee Thai] Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Wang, Xuelie; Babineau, Denise] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Anderson, Timothy] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Angov, Evelina; Lanar, David E.; Dutta, Sheetij] Walter Reed Army Inst Res, Malaria Vaccine Branch, Silver Spring, MD USA.
[Narum, David] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
[Richards, Jack; Beeson, James G.; Crabb, Brendan S.] Burnet Inst, Melbourne, Vic, Australia.
[Beeson, James G.] Monash Univ, Dept Microbiol, Melbourne, Vic 3004, Australia.
[Cowman, Alan F.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia.
[Horii, Toshihiro] Osaka Univ, Microbial Dis Res Inst, Dept Mol Protozool, Suita, Osaka 565, Japan.
[Muchiri, Eric; Mungai, Peter L.] Minist Publ Hlth & Sanitat, Div Vector Borne & Neglected Trop Dis, Nairobi, Kenya.
[Babineau, Denise] Rho Fed Syst Div, Chapel Hill, NC USA.
[Anderson, Timothy] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA.
RP Dent, AE (reprint author), Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.; Dent, AE (reprint author), Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
EM arlene.dent@case.edu
FU HHS \ NIH \ National Institute of Allergy and Infectious Diseases
(NIAID) [AI098511, AI064667, AI09519]
FX HHS vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Arlene E. Dent under
grant number AI098511. HHS vertical bar NIH vertical bar National
Institute of Allergy and Infectious Diseases (NIAID) provided funding to
Christopher L. King under grant number AI064667. HHS vertical bar NIH
vertical bar National Institute of Allergy and Infectious Diseases
(NIAID) provided funding to James W. Kazura under grant number AI09519.
NR 92
TC 2
Z9 2
U1 3
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD FEB
PY 2016
VL 23
IS 2
BP 104
EP 116
DI 10.1128/CVI.00452-15
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DI4SI
UT WOS:000373489200004
PM 26656119
ER
PT J
AU Stephen, EH
Chandra, A
King, RB
AF Stephen, Elizabeth Hervey
Chandra, Anjani
King, Rosalind Berkowitz
TI Supply of and demand for assisted reproductive technologies in the
United States: clinic- and population-based data, 1995-2010
SO FERTILITY AND STERILITY
LA English
DT Article
DE ART utilization; ever use of medical help to get pregnant; ART cycles;
live birth deliveries; births
ID TREATMENT TRIAL; INFERTILITY; SERVICES; SURVEILLANCE; DISPARITIES; WOMEN
AB Objective: To study national-level trends in assisted reproduction technology (ART) treatments and outcomes as well as the characteristics of women who have sought this form of infertility treatment.
Design: Population-based study.
Setting: Not applicable.
Patient(s): For CDC: All reporting clinics from 1996-2010. For NSFG: for the logistic analysis, sample comprising 2,325 women aged 22-44 years who have ever used medical help to get pregnant, excluding women who used only miscarriage prevention services.
Intervention(s): None.
Main Outcome Measure(s): CDC data (number of cycles, live birth deliveries, live births, patient diagnoses); and NSFG data (individual use of ART procedures).
Result(s): Between 1995 and 2010, use of ART increased. Parity and age are strong predictors of using ART procedures. The other correlates are higher education, having had tubal surgery, and having a current fertility problem.
Conclusion(s): The two complementary data sets highlight the trends of ART use. An increase in the use of ART services over this time period is seen in both data sources. Nulliparous women aged 35-39 years are the most likely to have ever used ART services. (C) 2016 by American Society for Reproductive Medicine.
C1 [Stephen, Elizabeth Hervey] Georgetown Univ, Sch Foreign Serv, ICC 301, Washington, DC 20057 USA.
[Chandra, Anjani] CDC Natl Ctr Hlth Stat, Reprod Stat Branch, Div Vital Stat, Hyattsville, MD USA.
[King, Rosalind Berkowitz] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Demog & Behav Sci Branch, Bethesda, MD USA.
RP Stephen, EH (reprint author), Georgetown Univ, Sch Foreign Serv, ICC 301, Washington, DC 20057 USA.
EM stepheel@georgetown.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [AHD12020001-1-0-1]
FX The National Center for Health Statistics (NCHS) conducts the National
Survey of Family Growth, one of the primary data sources for this
analysis. The Eunice Kennedy Shriver National Institute of Child Health
and Human Development provides financial support through Project Number
AHD12020001-1-0-1. NCHS Research Ethics Review Board approval was
obtained for the NSFG protocols for 2002 (# 2002-02) and 2006-2010 (#
2006-01). The findings and conclusions in this paper are those of the
authors and do not necessarily represent the official position of the
organizations at which they are employed. The authors have no financial
considerations or involvements for this paper.
NR 40
TC 2
Z9 2
U1 1
U2 4
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 FEB
PY 2016
VL 105
IS 2
BP 451
EP 458
DI 10.1016/j.fertnstert.2015.10.007
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DI3NR
UT WOS:000373405900035
PM 26597629
ER
PT J
AU Royster, GD
Nelson, AN
Harris, JC
Connell, MT
Heitmann, RJ
Wolff, EF
AF Royster, G. Donald
Nelson, Amanda N.
Harris, Justine C.
Connell, Matthew T.
Heitmann, Ryan J.
Wolff, Erin F.
TI RAPAMYCIN EXPANDS T-REGULATORY CELLS AND IMPROVES IMPLANTATION AND LIVE
BIRTH RATES IN A MURINE MODEL
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 64th Annual Meeting of the Pacific-Coast-Reproductive-Society
CY MAR 09-13, 2016
CL Rancho Mirage, CA
SP Pacific Coast Reprod Soc
C1 [Royster, G. Donald; Nelson, Amanda N.] Walter Reed Natl Mil Med Ctr, Reprod Endocrinol & Infertil, Bethesda, MD USA.
[Royster, G. Donald; Harris, Justine C.; Connell, Matthew T.; Wolff, Erin F.] NIH, Program Reprod & Adult Endocrinol, Bldg 10, Bethesda, MD 20892 USA.
[Heitmann, Ryan J.] Madigan Army Med Ctr, Reprod Endocrinol & Infertil, Tacoma, WA 98431 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 FEB
PY 2016
VL 105
IS 2
SU S
MA O-10
BP E8
EP E8
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DI3NK
UT WOS:000373405200011
ER
PT J
AU Miller, JL
Eldadah, BA
Padgett, L
AF Miller, Jeri L.
Eldadah, Basil A.
Padgett, Lynne
TI Palliative Care Research Funding Across the NIH and ACS: Who, What,
When, Where, Why, and How?
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Meeting Abstract
CT Annual Assembly of the
American-Academy-of-Hospice-and-Palliative-Medicine and the
Hospice-and-Palliative-Nurses-Association
CY MAR 09-12, 2016
CL Chicago, IL
SP Amer Acad Hosp & Palliat Med, Hosp & Palliat Nurses Assoc
C1 [Miller, Jeri L.] NINR, Bethesda, MD 20892 USA.
[Eldadah, Basil A.] NIA, Bethesda, MD 20892 USA.
[Padgett, Lynne] Amer Canc Soc, Atlanta, GA 30329 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 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD FEB
PY 2016
VL 51
IS 2
MA FR405
BP 347
EP 347
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA DI4MB
UT WOS:000373472900112
ER
PT J
AU Kim, H
Lee, SJ
Davies-Venn, C
Kim, JS
Yang, BY
Yao, ZS
Kim, I
Paik, CH
Bluemke, DA
AF Kim, Heejung
Lee, Sung-Jin
Davies-Venn, Cynthia
Kim, Jin Su
Yang, Bo Yeun
Yao, Zhengsheng
Kim, Insook
Paik, Chang H.
Bluemke, David A.
TI Cu-64-DOTA as a surrogate positron analog of Gd-DOTA for cardiac
fibrosis detection with PET: pharmacokinetic study in a rat model of
chronic MI
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE Cu-64-DOTA; PET imaging; myocardial infarction; pharmacokinetics;
extracellular volume
ID CARDIOVASCULAR MAGNETIC-RESONANCE; EXTRACELLULAR VOLUME FRACTION
AB Objectives
The aim of this study was to investigate the pharmacokinetics of Cu-64-DOTA (1,4,7,10-azacyclododecane-N,N ',N '',N '''-tetraacetic acid), a positron surrogate analog of the late gadolinium (Gd)-enhancement cardiac magnetic resonance agent, Gd-DOTA, in a rat model of chronic myocardial infarction (MI) and its microdistribution in the cardiac fibrosis by autoradiography.
Methods
DOTA was labeled with Cu-64-acetate. CD rats (n=5) with MI by left anterior descending coronary artery ligation and normal rats (n=6) were injected intravenously with Cu-64-DOTA (18.5 MBq, 0.02 mmol DOTA/kg). Dynamic PET imaging was performed for 60 min after injection. F-18-Fluorodeoxyglucose ([F-18]-FDG) PET imaging was performed to identify the viable myocardium. For the region of interest analysis, the Cu-64-DOTA PET image was coregistered to the [F-18]-FDG PET image. To validate the PET images, slices of heart samples from the base to the apex were analyzed using autoradiography and by histological staining with Masson's trichrome.
Results
Cu-64-DOTA was rapidly taken up in the infarct area. The time-activity curves demonstrated that Cu-64-DOTA concentrations in the blood, fibrotic tissue, and perfusion-rich organs peaked within a minute post injection; thereafter, it was rapidly washed out in parallel with blood clearance and excreted through the renal system. The blood clearance curve was biphasic, with a distribution half-life of less than 3 min and an elimination half-life of similar to 21.8 min. The elimination half-life of Cu-64-DOTA from the focal fibrotic tissue (similar to 22.4 min) and the remote myocardium (similar to 20.1 min) was similar to the blood elimination half-life. Consequently, the uptake ratios of focal fibrosis-to-blood and remote myocardium-to-blood remained stable for the time period between 10 and 60 min. The corresponding ratios obtained from images acquired from 30 to 60 min were 1.09 and 0.59, respectively, indicating that the concentration of Cu-64-DOTA in the focal fibrosis was 1.85 (1.09/0.59) times greater than that in the remote myocardium. Thus, this finding indicates that the extracellular volume fraction was 1.85 times greater in the focal fibrosis than in the remote myocardium. The accumulation of Cu-64-DOTA in fibrotic tissue was further supported by autoradiography and histology images. The autoradiography images of Cu-64-DOTA in the fibrotic tissues were qualitatively superimposed over the histology images of the fibrotic tissues. The histology images of the infarct areas were characterized by a heterogeneous distribution of thin bands of fibrotic collagen, myocytes, and expanded extracellular space.
Conclusion
Cu-64-DOTA is a useful surrogate positron analog of Gd-DOTA, enabling quantitative measurement of the uptake values in fibrotic tissues by dynamic PET imaging and calculation of the extracellular volume fractions of the fibrotic tissues. At a microscopic level, the distribution of Cu-64-DOTA is nonuniform, corresponding to the heterogeneous distribution of expanded extracellular space in the setting of MI.
C1 [Kim, Heejung; Lee, Sung-Jin; Davies-Venn, Cynthia; Kim, Jin Su; Yang, Bo Yeun; Yao, Zhengsheng; Paik, Chang H.; Bluemke, David A.] NIH, Radiopharmaceut Lab, Div Nucl Med, Radiol & Imaging Sci,Clin Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kim, Jin Su] Korea Inst Radiol & Med Sci, Mol Imaging Res Ctr, Seoul, South Korea.
[Kim, Insook] Leidos Biomed Res Inc, Appl & Dev Res Directorate, Frederick, MD USA.
RP Paik, CH (reprint author), NIH, Radiopharmaceut Lab, Div Nucl Med, Radiol & Imaging Sci,Clin Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cpaik@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E (Dr Insook Kim). The authors thank Dr
Roberto Maass-Morano for his critical review and comments, Dr Lawrence
P. Szajek for providing 64Cu chloride, and Dr Kenneth Cheng
for providing [18F]-FDG. They also thank Eden Dejene for her
technical assistance with the in-vitro studies.
NR 18
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD FEB
PY 2016
VL 37
IS 2
BP 188
EP 196
DI 10.1097/MNM.0000000000000417
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DI4ZS
UT WOS:000373508500012
PM 26488428
ER
PT J
AU Jarow, JP
Ahmed, HU
Choyke, PL
Taneja, SS
Scardino, PT
AF Jarow, Jonathan P.
Ahmed, Hashim U.
Choyke, Peter L.
Taneja, Samir S.
Scardino, Peter T.
TI Partial Gland Ablation for Prostate Cancer: Report of a Food and Drug
Administration, American Urological Association, and Society of Urologic
Oncology Public Workshop
SO UROLOGY
LA English
DT Article
ID FOCAL THERAPY; CONSENSUS PANEL; ULTRASOUND; PATHWAY; BIOPSY
AB OBJECTIVE To summarize the discussion that took place at a public workshop, co-sponsored by the U.S. Food and Drug Administration, the American Urological Association, and Society of Urologic Oncology reviewing the current state of the art for partial gland ablation (PGA) for the management of patients with prostate cancer. The purpose of this workshop was to discuss potential indications, current available evidence, and designs for future trials to provide the evidence needed by patients and providers to decide how and when to use PGA.
METHODS A workshop evaluating PGA for prostate cancer was held in New Orleans, Louisiana, in May 2015. Invited experts representing all stakeholders and attendees discussed the regulatory development of medical products, technology available, potential indications, and designs of trials to evaluate this modality of therapy.
RESULTS The panel presented the current information on the technologies available to perform PGA, the potential indications, and results of prior consensus conferences. Use of magnetic resonance imaging for patient selection, guide therapy, and follow-up was discussed. Designs of trials to assess PGA outcomes were discussed.
CONCLUSION The general consensus was that currently available technologies are capable of selective ablation with reasonable accuracy, but that criteria for patient selection remain debatable, and long-term cancer control remains to be established in properly designed and well-performed prospective clinical trials. Concerns include the potential for excessive, unnecessary use in patients with low-risk cancer and, conversely, that current diagnostic techniques may underestimate the extent and aggressiveness of some cancers, leading to inadequate treatment. Published by Elsevier Inc.
C1 US FDA, CDER Off Med Policy, Silver Spring, MD USA.
UCL, Div Surg & Intervent Sci, London, England.
NCI, Ctr Canc Res, Reston, VA USA.
NYU, Langone Med Ctr, Div Urol Oncol, New York, NY USA.
Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.
RP Jarow, JP (reprint author), Off Med Policy, WO51 RM6338,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM jonathan.jarow@fda.hhs.gov
FU Sonacare Inc.; Trod Medical; Sophiris Biocorp; Biobot; Hitachi-Aloka
FX Hashim U. Ahmed received clinical trial funding from Sonacare Inc., and
also funding for conference travel and honoraria for lectures at courses
organized by the said company. He is currently a paid proctor for HIFU.
He also received current clinical trial funding from Trod Medical and
Sophiris Biocorp. He is previous Consultant for protocol writing at
Steba Biotech and is current Consultant for protocol writing for Exact
Imaging. He previously received resources from Angiodynamics Inc.
through free device and probe use within investigator-led clinical
trial. At present, he received resources from Hitachi through free probe
use within investigator led clinical trial. Samir S. Taneja is a paid
consultant to Hitachi-Aloka and a study investigator for Steba-Biotech
and Trod Medical. He received funding from Biobot and Hitachi-Aloka. The
remaining authors declare that they have no relevant financial
interests.
NR 27
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2016
VL 88
BP 8
EP 13
DI 10.1016/j.urology.2015.11.018
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DI4IW
UT WOS:000373464600006
PM 26621480
ER
PT J
AU Fascelli, M
Rais-Bahrami, S
Sankineni, S
Brown, AM
George, AK
Ho, R
Frye, T
Kilchevsky, A
Chelluri, R
Abboud, S
Siddiqui, MM
Merino, MJ
Wood, BJ
Choyke, PL
Pinto, PA
Turkbey, B
AF Fascelli, Michele
Rais-Bahrami, Soroush
Sankineni, Sandeep
Brown, Anna M.
George, Arvin K.
Ho, Richard
Frye, Thomas
Kilchevsky, Amichai
Chelluri, Raju
Abboud, Steven
Siddiqui, M. Minhaj
Merino, Maria J.
Wood, Bradford J.
Choyke, Peter L.
Pinto, Peter A.
Turkbey, Baris
TI Combined Biparametric Prostate Magnetic Resonance Imaging and
Prostate-specific Antigen in the Detection of Prostate Cancer: A
Validation Study in a Biopsy-naive Patient Population
SO UROLOGY
LA English
DT Article
ID GUIDED BIOPSY; MRI; MEN
AB OBJECTIVE To validate the use of biparametric (T2- and diffusion-weighted) magnetic resonance imaging (B-MRI) and prostate-specific antigen (PSA) or PSA density (PSAD) in a biopsy-naive cohort at risk for prostate cancer (PCa).
METHODS All patients (n = 59) underwent PSA screening and digital rectal exam prior to a B-MRI followed by MRI or transrectal ultrasound fusion-guided targeted biopsy. Previously reported composite formulas incorporating screen positive lesions (SPL) on B-MRI and PSA or PSAD were developed to maximize PCa detection. For PSA, a patient was considered screen positive if PSA level + 6 x (the number of SPL) > 14. For PSAD, screening was positive if PSAD x 14 + (the number of SPL) > 4.25. These schemes were employed in this new test set to validate the initial formulas. Performance assessment of these formulas was determined for all cancer detection and for tumors with Gleason >= 3 + 4.
RESULTS Screen positive lesions on B-MRI had the highest sensitivity (95.5%) and negative predictive value of 71.4% compared with PSA and PSAD. B-MRI significantly improved sensitivity (43.2-72.7%, P = .0002) when combined with PSAD. The negative predictive value of PSA increased with B-MRI, achieving 91.7% for B-MRI and PSA for Gleason >= 3 + 4. Overall accuracies of the composite equations were 81.4% (B-MRI and PSA) and 78.0% (B-MRI and PSAD).
CONCLUSION Validation with a biopsy-naive cohort demonstrates the parameter SPL performed better than PSA or PSAD alone in accurately detecting PCa. The combined use of B-MRI, PSA, and PSAD resulted in improved accuracy for detecting clinically significant PCa. 2016 Published by Elsevier Inc.
C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris] NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Room B3B85, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, Dept Radiol & Imaging Serv, NIH Clin Ctr, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Alabama Birmingham, Dept Urol, Birmingham, AL USA.
Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA.
Univ Maryland, Div Urol, Dept Surg, Baltimore, MD 21201 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,Room B3B85, Bethesda, MD 20892 USA.
EM ismail.turkbey@nih.gov
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; NIH Center for Interventional Oncology; NIH;
Pfizer Inc.; Doris Duke Charitable Foundation; Newport Foundation;
American Association for Dental Research; Howard Hughes Medical
Institute; Colgate-Palmolive Company
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, and the NIH
Center for Interventional Oncology. This research was also made possible
by the National Institutes of Health (NIH) Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH from Pfizer Inc.,
The Doris Duke Charitable Foundation, The Newport Foundation, The
American Association for Dental Research, The Howard Hughes Medical
Institute, and the Colgate-Palmolive Company, as well as other private
donors. For a complete list, please visit the Foundation website at:
http://fnih.org/.
NR 23
TC 14
Z9 14
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2016
VL 88
BP 125
EP 132
DI 10.1016/j.urology.2015.09.035
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA DI4IW
UT WOS:000373464600032
PM 26680244
ER
PT J
AU George, AK
Rais-Bahrami, S
Fascelli, M
Turkbeyc, B
AF George, Arvin K.
Rais-Bahrami, Soroush
Fascelli, Michele
Turkbeyc, Baris
TI Combined Biparametric Prostate Magnetic Resonance Imaging and
Prostate-specific Antigen in the Detection of Prostate Cancer: A
Validation Study in a Biopsy-naive Patient Population REPLY
SO UROLOGY
LA English
DT Editorial Material
C1 [George, Arvin K.; Rais-Bahrami, Soroush; Fascelli, Michele] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Rais-Bahrami, Soroush] Univ Alabama Birmingham, Dept Urol & Radiol, Birmingham, AL USA.
[Turkbeyc, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP George, AK (reprint author), NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD FEB
PY 2016
VL 88
BP 133
EP 134
DI 10.1016/j.urology.2015.09.044
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA DI4IW
UT WOS:000373464600034
PM 26964791
ER
PT J
AU Aflaki, E
Moaven, N
Borger, DK
Lopez, G
Westbroek, W
Chae, JJ
Marugan, J
Patnaik, S
Maniwang, E
Gonzalez, AN
Sidransky, E
AF Aflaki, Elma
Moaven, Nima
Borger, Daniel K.
Lopez, Grisel
Westbroek, Wendy
Chae, Jae Jin
Marugan, Juan
Patnaik, Samarjit
Maniwang, Emerson
Gonzalez, Ashley N.
Sidransky, Ellen
TI Lysosomal storage and impaired autophagy lead to inflammasome activation
in Gaucher macrophages
SO AGING CELL
LA English
DT Article
DE autophagy; Gaucher disease; glucocerebrosidase; inflammasome;
interleukin-1 beta; lysosome; macrophage
ID NF-KAPPA-B; TRANSCRIPTION FACTOR; IL-1-BETA PRODUCTION; GENE-EXPRESSION;
DISEASE; GLUCOCEREBROSIDASE; IMMUNITY; DEGRADATION; PATHWAY; CELLS
AB Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide macrophages, the accumulation of glucosylceramide in lysosomes and the secretion of inflammatory cytokines. However, the connection between this lysosomal storage and inflammation is not clear. Studying macrophages derived from peripheral monocytes from patients with type 1 Gaucher disease with genotype N370S/N370S, we confirmed an increased secretion of interleukins IL-1 beta and IL-6. In addition, we found that activation of the inflammasome, a multiprotein complex that activates caspase-1, led to the maturation of IL-1 beta in Gaucher macrophages. We show that inflammasome activation in these cells is the result of impaired autophagy. Treatment with the small-molecule glucocerebrosidase chaperone NCGC758 reversed these defects, inducing autophagy and reducing IL-1 beta secretion, confirming the role of the deficiency of lysosomal glucocerebrosidase in these processes. We found that in Gaucher macrophages elevated levels of the autophagic adaptor p62 prevented the delivery of inflammasomes to autophagosomes. This increase in p62 led to activation of p65-NF-kB in the nucleus, promoting the expression of inflammatory cytokines and the secretion of IL-1 beta. This newly elucidated mechanism ties lysosomal dysfunction to inflammasome activation, and may contribute to the massive organomegaly, bone involvement and increased susceptibility to certain malignancies seen in Gaucher disease. Moreover, this link between lysosomal storage, impaired autophagy, and inflammation may have implications relevant to both Parkinson disease and the aging process. Defects in these basic cellular processes may also provide new therapeutic targets.
C1 [Aflaki, Elma; Moaven, Nima; Borger, Daniel K.; Lopez, Grisel; Westbroek, Wendy; Maniwang, Emerson; Gonzalez, Ashley N.; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Bethesda, MD 20892 USA.
[Chae, Jae Jin] NHGRI, Inflammatory Dis Sect, Bethesda, MD 20892 USA.
[Chae, Jae Jin; Marugan, Juan] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1E623 35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Division of Intramural Research, National Human Genome Research
Institute
FX Division of Intramural Research, National Human Genome Research
Institute.
NR 47
TC 9
Z9 9
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2016
VL 15
IS 1
BP 77
EP 88
DI 10.1111/acel.12409
PG 12
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DH6CQ
UT WOS:000372879000009
PM 26486234
ER
PT J
AU Torisu, K
Singh, KK
Torisu, T
Lovren, F
Liu, J
Pan, Y
Quan, A
Ramadan, A
Al-Omran, M
Pankova, N
Boyd, SR
Verma, S
Finkel, T
AF Torisu, Kumiko
Singh, Krishna K.
Torisu, Takehiro
Lovren, Fina
Liu, Jie
Pan, Yi
Quan, Adrian
Ramadan, Azza
Al-Omran, Mohammed
Pankova, Natalie
Boyd, Shelley R.
Verma, Subodh
Finkel, Toren
TI Intact endothelial autophagy is required to maintain vascular lipid
homeostasis
SO AGING CELL
LA English
DT Editorial Material
DE autophagy; lipids; atherosclerosis; mouse
ID LOW-DENSITY-LIPOPROTEIN; LYSOSOMAL ACID LIPASE; BARRIER FUNCTION;
DEFICIENT MICE; ATHEROSCLEROSIS; CHOLESTEROL; METABOLISM; DISEASE;
CELLS; RESTRICTION
AB The physiological role of autophagic flux within the vascular endothelial layer remains poorly understood. Here, we show that in primary endothelial cells, oxidized and native LDL stimulates autophagosome formation. Moreover, by both confocal and electron microscopy, excess native or modified LDL appears to be engulfed within autophagic structures. Transient knockdown of the essential autophagy gene ATG7 resulted in higher levels of intracellular I-125-LDL and oxidized LDL (OxLDL) accumulation, suggesting that in endothelial cells, autophagy may represent an important mechanism to regulate excess, exogenous lipids. The physiological importance of these observations was assessed using mice containing a conditional deletion of ATG7 within the endothelium. Following acute intravenous infusion of fluorescently labeled OxLDL, mice lacking endothelial expression of ATG7 demonstrated prolonged retention of OxLDL within the retinal pigment epithelium(RPE) and choroidal endothelium of the eye. In a chronic model of lipid excess, we analyzed atherosclerotic burden in ApoE(-/-) mice with or without endothelial autophagic flux. The absence of endothelial autophagy markedly increased atherosclerotic burden. Thus, in both an acute and chronic in vivo model, endothelial autophagy appears critically important in limiting lipid accumulation within the vessel wall. As such, strategies that stimulate autophagy, or prevent the age-dependent decline in autophagic flux, might be particularly beneficial in treating atherosclerotic vascular disease.
C1 [Torisu, Kumiko; Torisu, Takehiro; Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Singh, Krishna K.; Lovren, Fina; Pan, Yi; Quan, Adrian; Ramadan, Azza; Verma, Subodh] Univ Toronto, Div Cardiac Surg, 30 Bond St, Toronto, ON M5B 1W8, Canada.
[Singh, Krishna K.; Al-Omran, Mohammed] Univ Toronto, Div Vasc Surg, 30 Bond St, Toronto, ON M5B 1W8, Canada.
[Pankova, Natalie; Boyd, Shelley R.] Univ Toronto, Dept Ophthalmol & Vis Sci, Keenan Res Ctr Biomed Sci, St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada.
RP Finkel, T (reprint author), NIH, Bldg 10-CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA.; Verma, S (reprint author), St Michaels Hosp, 8th Floor,30 Bond St, Toronto, ON M5B 1W8, Canada.
EM vermasu@smh.ca; finkelt@nih.gov
FU Canadian Institutes of Health Research; Intramural NIH HHS
NR 35
TC 4
Z9 4
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD FEB
PY 2016
VL 15
IS 1
BP 187
EP 191
DI 10.1111/acel.12423
PG 5
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DH6CQ
UT WOS:000372879000021
PM 26780888
ER
PT J
AU Scahill, L
Sukhodolsky, DG
Anderberg, E
Dimitropoulos, A
Dziura, J
Aman, MG
McCracken, J
Tierney, E
Hallett, V
Katz, K
Vitiello, B
McDougle, C
AF Scahill, Lawrence
Sukhodolsky, Denis G.
Anderberg, Emily
Dimitropoulos, Anastasia
Dziura, James
Aman, Michael G.
McCracken, James
Tierney, Elaine
Hallett, Victoria
Katz, Karol
Vitiello, Benedetto
McDougle, Christopher
TI Sensitivity of the modified Children's Yale-Brown Obsessive Compulsive
Scale to detect change: Results from two multi-site trials
SO AUTISM
LA English
DT Article
DE autism spectrum disorder; clinical trials; outcome measurement;
repetitive behavior; risperidone
ID AUTISM-SPECTRUM DISORDERS; PERVASIVE DEVELOPMENTAL DISORDERS; ABERRANT
BEHAVIOR CHECKLIST; REPETITIVE BEHAVIORS; PEDIATRIC PSYCHOPHARMACOLOGY;
CLINICAL-TRIAL; RESEARCH UNITS; DOUBLE-BLIND; PLACEBO; ADOLESCENTS
AB Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder to detect change with treatment. Study 1 included 52 subjects assigned to placebo and 49 subjects to risperidone under double-blind conditions. In Study 2, 49 subjects received risperidone only and 75 subjects received risperidone plus parent training. The combined sample consisted of 187 boys and 38 girls (aged 4-17 years). At the medication-free baseline, the internal consistency on the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder total score was excellent (Cronbach's alpha = 0.84) and the mean scores were similar across the four groups. Compared to placebo in Study 1, all three active treatment groups showed significant improvement (effect sizes: 0.74-0.88). There were no differences between active treatment groups. These results indicate that the Children's Yale-Brown Obsessive Compulsive Scale modified for autism spectrum disorder has acceptable test-retest as evidenced by the medium to high correlations in the placebo group and demonstrated sensitivity to change with treatment.
C1 [Scahill, Lawrence] Emory Univ, Atlanta, GA 30322 USA.
[Sukhodolsky, Denis G.; Dziura, James; Katz, Karol] Yale Univ, New Haven, CT 06520 USA.
[Anderberg, Emily] Univ Washington, Brigham Young Univ, Seattle, WA 98195 USA.
[Dimitropoulos, Anastasia] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Aman, Michael G.] Ohio State Univ, Columbus, OH 43210 USA.
[McCracken, James] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Tierney, Elaine] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Hallett, Victoria] Kings Coll London, London WC2R 2LS, England.
[Vitiello, Benedetto] NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD USA.
[McDougle, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Scahill, L (reprint author), Emory Univ, Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
EM lawrence.scahill@emory.edu
OI Sukhodolsky, Denis/0000-0002-5401-792X
FU US National Institute of Mental Health [N01MH70009, U10MH66764,
R01MH099021]
FX This research received grant funding from the US National Institute of
Mental Health contract N01MH70009, grants U10MH66764, R01MH099021 (L.
Scahill, Principal Investigator)
NR 40
TC 0
Z9 0
U1 2
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1362-3613
EI 1461-7005
J9 AUTISM
JI Autism
PD FEB
PY 2016
VL 20
IS 2
BP 145
EP 152
DI 10.1177/1362361315574889
PG 8
WC Psychology, Developmental
SC Psychology
GA DH6DB
UT WOS:000372880100003
PM 25882391
ER
PT J
AU Nussinov, R
Udgaonkar, JB
AF Nussinov, Ruth
Udgaonkar, Jayant B.
TI Editorial overview: Folding and binding: Dynamic conformational
heterogeneity is pivotal to cell life
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Editorial Material
C1 [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Udgaonkar, Jayant B.] Tata Inst Fundamental Res, Natl Ctr Biol Sci, GKVK Campus, Bengaluru 560065, India.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.; Nussinov, R (reprint author), Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.; Udgaonkar, JB (reprint author), Tata Inst Fundamental Res, Natl Ctr Biol Sci, GKVK Campus, Bengaluru 560065, India.
EM NussinoR@helix.nih.gov; jayant@ncbs.res.in
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD FEB
PY 2016
VL 36
BP IV
EP VI
DI 10.1016/j.sbi.2016.01.012
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DH3IR
UT WOS:000372681200001
PM 26873135
ER
PT J
AU Banerjee, A
Jang, H
Nussinov, R
Gaponenko, V
AF Banerjee, Avik
Jang, Hyunbum
Nussinov, Ruth
Gaponenko, Vadim
TI The disordered hypervariable region and the folded catalytic domain of
oncogenic K-Ras4B partner in phospholipid binding
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID RAS FORMS DIMERS; K-RAS; H-RAS; N-RAS; PLASMA-MEMBRANE;
PHOSPHATIDIC-ACID; TARGETING RAS; PROTEIN; ACTIVATION; ASSOCIATION
AB The C-terminal hypervariable region (HVR) of the splice variant KRAS4B is disordered. Classically, the role of the posttranslationally-modified HVR is to navigate Ras in the cell and to anchor it in localized plasma membrane regions. Here, we propose additional regulatory roles, including auto-inhibition by shielding the effector binding site in the GDP-bound state and release upon GTP binding and in the presence of certain oncogenic mutations. The released HVR can interact with calmodulin. We show that oncogenic mutations (G12V/G12D) modulate the HVR-phospholipid binding specificity, resulting in preferential interactions with phosphatidic acid. The shifts in the conformational preferences and binding specificity in the disordered state exemplify the critical role of the unstructured tail of K-Ras4B in cancer.
C1 [Banerjee, Avik] Univ Illinois, Dept Chem, Chicago, IL 60607 USA.
[Jang, Hyunbum; Nussinov, Ruth] NCI, Canc & Inflammat Program, Basic Sci Program, Leidos Biomed Res Inc,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
RP Gaponenko, V (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
EM vadimg@uic.edu
FU American Cancer Society Grant [RGS-09-057-01-GMC]; National Cancer
Institute [R01 CA135341, R01 CA188427]; National Heart, Lung, and Blood
Institute [R21 HL118588]; National Cancer Institute, National Institutes
of Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX We gratefully acknowledge the generous support from the American Cancer
Society Grant RGS-09-057-01-GMC, the National Cancer Institute Grants
R01 CA135341 and R01 CA188427, and the National Heart, Lung, and Blood
Institute Grant R21 HL118588 to V.G. This project has been funded in
whole or in part with Federal funds from the National Cancer Institute,
National Institutes of Health, under contract number HHSN261200800001E.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government. This research was supported (in
part) by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 56
TC 8
Z9 8
U1 4
U2 7
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD FEB
PY 2016
VL 36
BP 10
EP 17
DI 10.1016/j.sbi.2015.11.010
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DH3IR
UT WOS:000372681200004
PM 26709496
ER
PT J
AU Hall, TMT
AF Hall, Traci M. Tanaka
TI De-coding and re-coding RNA recognition by PUF and PPR repeat proteins
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID PUMILIO-HOMOLOGY DOMAIN; SINGLE-STRANDED RNA; BINDING-SPECIFICITY;
STRUCTURAL BASIS; MODULAR RECOGNITION; MITOCHONDRIAL RNA; SEQUENCE;
SCAFFOLD; CODE; ARABIDOPSIS
AB PUF and PPR proteins are two families of alpha-helical repeat proteins that recognize single-stranded RNA sequences. Both protein families hold promise as scaffolds for designed RNA binding domains. A modular protein RNA recognition code was apparent from the first crystal structures of a PUF protein in complex with RNA, and recent studies continue to advance our understanding of natural PUF protein recognition (de-coding) and our ability to engineer specificity (re-coding). Degenerate recognition motifs make de-coding specificity of individual PPR proteins challenging. Nevertheless, re-coding PPR protein specificity using a consensus recognition code has been successful.
C1 [Hall, Traci M. Tanaka] Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Hall, TMT (reprint author), Natl Inst Environm Hlth Sci, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM hall4@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences
FX I am grateful for the input of my colleagues at NIEHS, G Mueller and T
Teramoto. This work was supported by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 49
TC 2
Z9 2
U1 1
U2 5
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD FEB
PY 2016
VL 36
BP 116
EP 121
DI 10.1016/j.sbi.2016.01.010
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DH3IR
UT WOS:000372681200016
PM 26874972
ER
PT J
AU Bjornsson, ES
Hoofnagle, JH
AF Bjornsson, Einar S.
Hoofnagle, Jay H.
TI Categorization of Drugs Implicated in Causing Liver Injury: Critical
Assessment Based on Published Case Reports
SO HEPATOLOGY
LA English
DT Article
ID CAUSALITY ASSESSMENT METHODS; ADVERSE REACTIONS; HIV-INFECTION;
RECHALLENGE; POPULATION; INDINAVIR; HEPATITIS; OUTCOMES; DISEASE
AB An important element in assessing causality in drug-induced liver injury is whether the implicated agent is known to cause hepatotoxicity. We classified drugs into categories based on the number of published reports of convincingly documented, clinically apparent, idiosyncratic liver injury. Drugs described in the website LiverTox (http://livertox.nih.gov) were classified into five categories based on the number of published cases (category A, >= 50; category B, 12-49; category C, 4-11; category D, 1-3; category E, none). Case reports in categories C and D were individually reanalyzed using the Roussel Uclaf Causality Assessment Method. Drugs with fatal cases or with rechallenge were noted. Among 671 individual drugs or closely related agents, 353 (53%) were considered convincingly linked to liver injury in published case reports; 48 (13%) were assigned to category A, 76 (22%) were assigned to category B, 96 (27%) were assigned to category C, and 126 (36%) were assigned to category D. Another 7 (2%) were direct hepatotoxins but only in high doses and placed in a separate category (T). The remaining 318 (47%) drugs had no convincing case report of hepatoxicity in the literature (category E). All except one in category A have been available since 1999, 98% had at least one fatal case and 89% a positive rechallenge. In category B, 54% had a fatal case and 41% a rechallenge. Drugs in categories C and D less frequently had instances of fatal (23% and 7%) or rechallenge cases (26% and 11%). Conclusion: Documentation of hepatoxicity in the medical literature is variable, and many published instances do not stand up to critical review. A standardized system for categorizing drugs for hepatotoxicity potential will help develop objective and reliable, computer-based instruments for assessing causality in drug-induced liver injury.
C1 [Bjornsson, Einar S.] Natl Univ Hosp Iceland, IS-101 Reykjavik, Iceland.
[Bjornsson, Einar S.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
RP Bjornsson, ES (reprint author), Natl Univ Hosp Iceland, Gastroenterol & Hepatol, IS-101 Reykjavik, Iceland.; Hoofnagle, JH (reprint author), NIH, Liver Dis Res Branch, Room 655,6707 Democracy Blvd, Bethesda, MD 20892 USA.
EM einarsb@landspitali.is; hoofnaglej@extra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX Supported in part by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health.
NR 24
TC 11
Z9 11
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2016
VL 63
IS 2
BP 590
EP 603
DI 10.1002/hep.28323
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DI1ZZ
UT WOS:000373296800016
PM 26517184
ER
PT J
AU Xu, MJ
Feng, DC
Gao, B
AF Xu, Mingjiang
Feng, Dechun
Gao, Bin
TI Lipocalin-2 (NGAL/LCN2), a "Help-Me" Signal in Organ Inflammation Reply
SO HEPATOLOGY
LA English
DT Letter
C1 [Xu, Mingjiang; Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Xu, MJ (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2016
VL 63
IS 2
BP 671
EP 672
DI 10.1002/hep.27928
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DI1ZZ
UT WOS:000373296800025
PM 26053944
ER
PT J
AU Feng, DC
Xu, MJ
Gao, B
AF Feng, Dechun
Xu, Mingjiang
Gao, Bin
TI Evidence for IL-6/STAT3-Independent Induction of Lipocalin-2 in the
Liver of Mice Infected With Escherichia coli Reply
SO HEPATOLOGY
LA English
DT Letter
ID INTERLEUKIN-6-DEFICIENT MICE
C1 [Feng, Dechun; Xu, Mingjiang; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
RP Feng, DC (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
FU Intramural NIH HHS [Z99 AA999999]
NR 4
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD FEB
PY 2016
VL 63
IS 2
BP 674
EP 675
DI 10.1002/hep.27846
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DI1ZZ
UT WOS:000373296800029
PM 25865955
ER
PT J
AU Wells, JA
Glassman, AR
Jampol, LM
Aiello, LP
Antoszyk, AN
Baker, CW
Bressler, NM
Browning, DJ
Connor, CG
Elman, MJ
Ferris, FL
Friedman, SM
Melia, M
Pieramici, DJ
Sun, JK
Beck, RW
AF Wells, John A.
Glassman, Adam R.
Jampol, Lee M.
Aiello, Lloyd Paul
Antoszyk, Andrew N.
Baker, Carl W.
Bressler, Neil M.
Browning, David J.
Connor, Crystal G.
Elman, Michael J.
Ferris, Frederick L.
Friedman, Scott M.
Melia, Michele
Pieramici, Dante J.
Sun, Jennifer K.
Beck, Roy W.
CA Diabetic Retinopathy Clinical Res
TI Association of Baseline Visual Acuity and Retinal Thickness With 1-Year
Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic
Macular Edema
SO JAMA OPHTHALMOLOGY
LA English
DT Article
AB IMPORTANCE Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment.
OBJECTIVE To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography.
DESIGN, SETTING, AND PARTICIPANTS Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015.
INTERVENTIONS Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol.
MAIN OUTCOMES AND MEASURES One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (>400 mu m) or thinner (250 to 399 mu m) CST.
RESULTS In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39%(17% to 60%) for aflibercept vs bevacizumab, 25%(5% to 46%) for ranibizumab vs bevacizumab, and 13%(-8% to 35%) for aflibercept vs ranibizumab.
CONCLUSIONS AND RELEVANCE These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients.
C1 [Wells, John A.] Palmetto Retina Ctr, W Columbia, SC 33647 USA.
[Glassman, Adam R.; Connor, Crystal G.; Melia, Michele; Beck, Roy W.] Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA.
[Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Aiello, Lloyd Paul; Sun, Jennifer K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA.
[Antoszyk, Andrew N.; Browning, David J.] Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA.
[Baker, Carl W.] Paducah Retinal Ctr, Paducah, KY USA.
[Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA.
[Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA.
[Friedman, Scott M.] Florida Retina Consultants, Winter Haven, FL USA.
[Pieramici, Dante J.] Calif Retina Consultants, Santa Barbara, CA USA.
RP Glassman, AR (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Ste 350, Tampa, FL 33647 USA.
EM drcrstat2@jaeb.org
OI VanderBeek, Brian L./0000-0003-4953-118X
FU National Eye Institute and the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, US
Department of Health and Human Services [EY14231, EY23207]; Genentech;
National Eye Institute and the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, US
Department of Health and Human Services (National Institutes of Health)
[EY18817 from the]
FX This study was supported through a cooperative agreement from the
National Eye Institute and the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health, US
Department of Health and Human Services (grants EY14231, EY23207, and
EY18817 from the National Institutes of Health). Regeneron
Pharmaceutical provided the aflibercept and Genentech provided the
ranibizumab for the study. Genentech also provided funding for blood
pressure cuffs and the collection of serum and urine that are not part
of the main study results reported herein.
NR 3
TC 8
Z9 8
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD FEB
PY 2016
VL 134
IS 2
BP 127
EP 134
DI 10.1001/jamaophthalmol.2015.4599
PG 8
WC Ophthalmology
SC Ophthalmology
GA DH1JK
UT WOS:000372540000007
PM 26605836
ER
PT J
AU Chew, EY
AF Chew, Emily Y.
TI Drilling Deeper for Treatment Choices in Diabetic Macular Edema
SO JAMA OPHTHALMOLOGY
LA English
DT Editorial Material
C1 [Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, Clin Trials Branch, NIH, Bldg 10 Clin Res Ctr,Room 3-2531,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, Clin Trials Branch, NIH, Bldg 10 Clin Res Ctr,Room 3-2531,10 Ctr Dr, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD FEB
PY 2016
VL 134
IS 2
BP 135
EP 136
DI 10.1001/jamaophthalmol.2015.4652
PG 2
WC Ophthalmology
SC Ophthalmology
GA DH1JK
UT WOS:000372540000008
PM 26606738
ER
PT J
AU Mollica, MA
Underwood, W
Homish, GG
Homish, DL
Orom, H
AF Mollica, Michelle A.
Underwood, Willie, III
Homish, Gregory G.
Homish, D. Lynn
Orom, Heather
TI Spirituality is associated with better prostate cancer treatment
decision making experiences
SO JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Prostate cancer; Decision making; Spirituality; Conflict; Localized
ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; PSYCHOLOGICAL ADJUSTMENT;
THE-LITERATURE; HEALTH; MEN; RELIGION; SUPPORT; SCALE; INTERVENTION
AB This study examined whether spiritual beliefs are associated with greater decision-making satisfaction, lower decisional conflict and decision-making difficulty with the decision-making process in newly diagnosed men with prostate cancer. Participants were 1114 men diagnosed with localized prostate cancer who had recently made their treatment decision, but had not yet been treated. We used multivariable linear regression to analyze relationships between spirituality and decision-making satisfaction, decisional conflict, and decision-making difficulty, controlling for optimism and resilience, and clinical and sociodemographic factors. Results indicated that greater spirituality was associated with greater decision-making satisfaction (B = 0.02; p < 0.001), less decisional conflict (B = -0.42; p < 0.001), and less decision-making difficulty (B = -0.08; p < 0.001). These results confirm that spiritual beliefs may be a coping resource during the treatment decision-making process. Providing opportunities for patients to integrate their spiritual beliefs and their perceptions of their cancer diagnosis and trajectory could help reduce patient uncertainty and stress during this important phase of cancer care continuum.
C1 [Mollica, Michelle A.; Homish, Gregory G.; Homish, D. Lynn; Orom, Heather] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, 320 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA.
[Mollica, Michelle A.] Natl Canc Inst, Canc Prevent Div, Rockville, MD USA.
[Underwood, Willie, III] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
RP Mollica, MA (reprint author), SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, 320 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA.; Mollica, MA (reprint author), Natl Canc Inst, Canc Prevent Div, Rockville, MD USA.
EM mm89@buffalo.edu; Willie.underwood@roswellpark.org; ghomish@buffalo.edu;
dlhomish@buffalo.edu; horom@buffalo.edu
FU NCI [R01 CA152425]
FX NCI R01 CA152425.
NR 44
TC 0
Z9 0
U1 3
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0160-7715
EI 1573-3521
J9 J BEHAV MED
JI J. Behav. Med.
PD FEB
PY 2016
VL 39
IS 1
BP 161
EP 169
DI 10.1007/s10865-015-9662-1
PG 9
WC Psychology, Clinical
SC Psychology
GA DH8AC
UT WOS:000373014500015
PM 26243642
ER
PT J
AU McHale, SM
Davis, KD
Green, K
Casper, L
Kan, ML
Kelly, EL
King, RB
Okechukwu, C
AF McHale, Susan M.
Davis, Kelly D.
Green, Kaylin
Casper, Lynne
Kan, Marni L.
Kelly, Erin L.
King, Rosalind Berkowitz
Okechukwu, Cassandra
TI Effects of a Workplace Intervention on Parent-Child Relationships
SO JOURNAL OF CHILD AND FAMILY STUDIES
LA English
DT Article
DE Parent-adolescent relationships; Parental employment; Work and family;
Workplace intervention; Randomized trial
ID WORK-FAMILY CONFLICT; SUPPORTIVE SUPERVISOR BEHAVIORS; MIDDLE CHILDHOOD;
TIME SQUEEZE; LIFE; ADOLESCENCE; ADJUSTMENT; VALIDATION; QUALITY; MOTHER
AB This study tested whether effects of a workplace intervention, aimed at promoting employees' schedule control and supervisor support for personal and family life, had implications for parent-adolescent relationships; we also tested whether parent-child relationships differed as a function of how many intervention program sessions participants attended. Data came from a group randomized trial of a workplace intervention, delivered in the information technology division of a Fortune 500 company. Analyses focused on 125 parent-adolescent dyads that completed baseline and 12-month follow- up home interviews. Results revealed no main effects of the intervention, but children of employees who attended 75 % or more program sessions reported more time with their parent and more parent education involvement compared to adolescents whose parents attended- 75 % of sessions, and they tended to report more time with parent and more parental solicitation of information about their experiences compared to adolescents whose parents were randomly assigned to the usual practice condition.
C1 [McHale, Susan M.; Davis, Kelly D.] Penn State Univ, 114 Henderson, University Pk, PA 16802 USA.
[Green, Kaylin] Montana State Univ, Bozeman, MT 59717 USA.
[Casper, Lynne] Univ So Calif, Los Angeles, CA USA.
[Kan, Marni L.] RTI, Res Triangle Pk, NC USA.
[Kelly, Erin L.] Univ Minnesota, Minneapolis, MN USA.
[King, Rosalind Berkowitz] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Okechukwu, Cassandra] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
RP McHale, SM (reprint author), Penn State Univ, 114 Henderson, University Pk, PA 16802 USA.
EM mchale@psu.edu
FU National Institutes of Health; Centers for Disease Control and
Prevention: Eunice Kennedy Shriver National Institute of Child Health
and Human Development [U01HD051217, U01HD051218, U01HD051256,
U01HD051276]; National Institute on Aging [U01AG027669]; Office of
Behavioral and Science Sciences Research; National Institute for
Occupational Safety and Health [U01OH008788, U01HD059773]; William T.
Grant Foundation; Alfred P Sloan Foundation; Administration for Children
and Families
FX This research was conducted as part of the Work, Family and Health
Network (www.WorkFamilyHealthNetwork.org), which is funded by a
cooperative agreement through the National Institutes of Health and the
Centers for Disease Control and Prevention: Eunice Kennedy Shriver
National Institute of Child Health and Human Development (Grant Nos.
U01HD051217, U01HD051218, U01HD051256, U01HD051276), National Institute
on Aging (Grant No. U01AG027669), Office of Behavioral and Science
Sciences Research, and National Institute for Occupational Safety and
Health (Grant Nos. U01OH008788, U01HD059773). Grants from the William T.
Grant Foundation, Alfred P Sloan Foundation, and the Administration for
Children and Families have provided additional funding. The contents of
this publication are solely the responsibility of the authors and do not
necessarily represent the official views of these institutes and
offices. Special acknowledgement goes to Extramural Staff Science
Collaborator, Rosalind Berkowitz King, Ph. D. and Lynne Casper, Ph. D.
for design of the original Workplace, Family, Health and Well-Being
Network Initiative. We also wish to express our gratitude to the
worksites, employers, and employees who participated in this research
and to Emily Fidler and Rosalie Ammerman for their assistance in
preparing this paper.
NR 36
TC 1
Z9 1
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1062-1024
EI 1573-2843
J9 J CHILD FAM STUD
JI J. Child Fam. Stud.
PD FEB
PY 2016
VL 25
IS 2
BP 553
EP 561
DI 10.1007/s10826-015-0254-z
PG 9
WC Family Studies; Psychology, Developmental; Psychiatry
SC Family Studies; Psychology; Psychiatry
GA DI5YN
UT WOS:000373576500017
PM 26957897
ER
PT J
AU Choi, H
Qian, M
Kim, MG
Zheng, HR
Choi, HK
Zhang, B
Shung, KK
AF Choi, Hojong
Qian, Ming
Kim, Min Gon
Zheng, Hairong
Choi, Ho Kyung
Zhang, Bo
Shung, K. Kirk
TI Analog Wideband Receiver Architecture for High Frequency Ultrasound
Instrumentation
SO JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS
LA English
DT Article
DE Receiver; Limiter; Preamplifier; Ultrasound Instrumentation
ID DESIGN; BIOMICROSCOPY; ARRAY; FPGA
AB This paper describes analog wideband receiver architecture consisting of a limiter and preamplifier, which reduces loss and increases bandwidth of high frequency ultrasound instrumentation. Typical analog front-end receivers do not perform well at high frequency operation because of limited bandwidth and high loss due to their inherent architecture. Parasitic impedances caused by the electronic interconnections also affect the loss and bandwidth performance of analog front-end receivers. In order to overcome these issues, we designed new analog wideband receiver architecture. The proposed receiver produced lower loss and wider bandwidth compared to a one of the commercial receiver such as Panametrics 5900PR. This is because the loss of the transistor-diode-based limiter (-0.1 dB) is lower than that of the commercial limiter (-5.9 dB) at 70 MHz and the bandwidth of the designed preamplifier (>120 MHz) is wider than that of the Panametrics 5900PR (118 MHz). Our receiver design provides an alternative solution for high frequency ultrasound instrumentation.
C1 [Choi, Hojong] Kumoh Natl Inst Technol, Dept Med IT Convergence Engn, Gumi 730701, Gyeongbuk, South Korea.
[Qian, Ming; Zheng, Hairong] Chinese Acad Sci, Shenzhen Inst Adv Technol, Paul C Lauterbur Res Ctr Biomed Imaging, Shenzhen 518055, Peoples R China.
[Kim, Min Gon; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Kim, Min Gon; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Choi, Ho Kyung] Bowtech, Dept Syst Integrat, Seoul 133822, South Korea.
[Zhang, Bo] Tongji Univ, Sch Med, East Hosp, Dept Ultrasound Med, Shanghai 200120, Peoples R China.
RP Choi, H (reprint author), Kumoh Natl Inst Technol, Dept Med IT Convergence Engn, Gumi 730701, Gyeongbuk, South Korea.; Qian, M (reprint author), Chinese Acad Sci, Shenzhen Inst Adv Technol, Paul C Lauterbur Res Ctr Biomed Imaging, Shenzhen 518055, Peoples R China.; Choi, HK (reprint author), Bowtech, Dept Syst Integrat, Seoul 133822, South Korea.; Zhang, B (reprint author), Tongji Univ, Sch Med, East Hosp, Dept Ultrasound Med, Shanghai 200120, Peoples R China.
FU National Institutes of Health Grant [P41-EB002182]; National Basic
Research Program of China [2015CB755500]; National Science Foundation
Grants of China [11272329]; National Sci-Tech Supporting Plan
[2012BAI13B01]; Shenzhen International Collaboration and Quality of
Working life (QWL) Program - Ministry of Trade, Industry and Energy of
South Korea [GJHZ20120617111428312]
FX This research was supported by National Institutes of Health Grant
#P41-EB002182, National Basic Research Program of China #2015CB755500,
National Science Foundation Grants of China #11272329, National Sci-Tech
Supporting Plan #2012BAI13B01, Shenzhen International Collaboration
#GJHZ20120617111428312 and Quality of Working life (QWL) Program funded
by the Ministry of Trade, Industry and Energy of South Korea.
NR 21
TC 0
Z9 0
U1 1
U2 1
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 2156-7018
EI 2156-7026
J9 J MED IMAG HEALTH IN
JI J. Med. Imaging Health Inform.
PD FEB
PY 2016
VL 6
IS 1
BP 47
EP 52
DI 10.1166/jmihi.2016.1578
PG 6
WC Mathematical & Computational Biology; Radiology, Nuclear Medicine &
Medical Imaging
SC Mathematical & Computational Biology; Radiology, Nuclear Medicine &
Medical Imaging
GA DH3EI
UT WOS:000372669900005
ER
PT J
AU Choi, SH
Ruggiero, D
Sorice, R
Song, C
Nutile, T
Smith, AV
Concas, MP
Traglia, M
Barbieri, C
Ndiaye, NC
Stathopoulou, MG
Lagou, V
Maestrale, GB
Sala, C
Debette, S
Kovacs, P
Lind, L
Lamont, J
Fitzgerald, P
Tonjes, A
Gudnason, V
Toniolo, D
Pirastu, M
Bellenguez, C
Vasan, RS
Ingelsson, E
Leutenegger, AL
Johnson, AD
DeStefano, AL
Visvikis-Siest, S
Seshadri, S
Ciullo, M
AF Choi, Seung Hoan
Ruggiero, Daniela
Sorice, Rossella
Song, Ci
Nutile, Teresa
Smith, Albert Vernon
Concas, Maria Pina
Traglia, Michela
Barbieri, Caterina
Ndiaye, Ndeye Coumba
Stathopoulou, Maria G.
Lagou, Vasiliki
Maestrale, Giovanni Battista
Sala, Cinzia
Debette, Stephanie
Kovacs, Peter
Lind, Lars
Lamont, John
Fitzgerald, Peter
Toenjes, Anke
Gudnason, Vilmundur
Toniolo, Daniela
Pirastu, Mario
Bellenguez, Celine
Vasan, Ramachandran S.
Ingelsson, Erik
Leutenegger, Anne-Louise
Johnson, Andrew D.
DeStefano, Anita L.
Visvikis-Siest, Sophie
Seshadri, Sudha
Ciullo, Marina
TI Six Novel Loci Associated with Circulating VEGF Levels Identified by a
Meta-analysis of Genome-Wide Association Studies
SO PLOS GENETICS
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; MOTOR-NEURON DEGENERATION; SOLUBLE GUANYLYL
CYCLASE; BREAST-CANCER RISK; CLINICAL-SIGNIFICANCE; SIGNALING PATHWAY;
FACTOR EXPRESSION; PROSTATE-CANCER; FACTOR GENE; TRANSFORMING
GROWTH-FACTOR-BETA-1
AB Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79x10(-13)), rs74506613 (JMJD1C, P = 1.17x10(-19)), rs4782371 (ZFPM1, P = 1.59x10(-9)) and rs2639990 (ZADH2, P = 1.72x10(-8)), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52x10(-18); rs7043199, VLDLR-AS1, P = 5.12x10(-14)) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39x10(-1467); rs1740073, C6orf223, P = 2.34x10(-17); rs6993770, ZFPM2, P = 2.44x10(-60); rs2375981, KCNV2, P = 1.48x10(-100)). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases.
C1 [Choi, Seung Hoan; Debette, Stephanie; DeStefano, Anita L.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Choi, Seung Hoan; DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Choi, Seung Hoan; Vasan, Ramachandran S.; DeStefano, Anita L.; Seshadri, Sudha] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Ruggiero, Daniela; Sorice, Rossella; Nutile, Teresa; Ciullo, Marina] CNR, Inst Genet & Biophys, Naples, Italy.
[Song, Ci; Johnson, Andrew D.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Populat Sci Branch, Framingham, MA USA.
[Song, Ci; Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
[Song, Ci] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Concas, Maria Pina; Maestrale, Giovanni Battista; Pirastu, Mario] CNR, Inst Populat Genet, Sassari, Italy.
[Traglia, Michela; Barbieri, Caterina; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Ndiaye, Ndeye Coumba; Stathopoulou, Maria G.; Visvikis-Siest, Sophie] Univ Lorraine, Fac Pharm, UMR INSERM U1122, IGE PCV Interact Gene Environm Physiopathol Cardi, Nancy, France.
[Lagou, Vasiliki] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Lagou, Vasiliki] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Debette, Stephanie] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.
[Debette, Stephanie] INSERM, U897, Bordeaux, France.
[Kovacs, Peter] Univ Leipzig, IFB Adipos Dis, D-04109 Leipzig, Germany.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Lamont, John; Fitzgerald, Peter] Randox Labs, Crumlin, Ireland.
[Toenjes, Anke] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany.
[Bellenguez, Celine] Inst Pasteur, F-59019 Lille, France.
[Bellenguez, Celine] INSEM, U744, Lille, France.
[Bellenguez, Celine] Univ Lille Nord France, Lille, France.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Leutenegger, Anne-Louise] INSERM, U946, Paris, France.
[Leutenegger, Anne-Louise] Univ Paris Diderot, Sorbonne Paris Cite, IUH, UMR S 946, Paris, France.
RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.; Seshadri, S (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.; Ciullo, M (reprint author), CNR, Inst Genet & Biophys, Naples, Italy.
EM suseshad@bu.edu; ciullo@igb.cnr.it
RI Visvikis-Siest, Sophie/H-2324-2014; ruggiero, daniela/K-5638-2016;
Stathopoulou, Maria/H-7324-2016; Johnson, Andrew/G-6520-2013;
Leutenegger, Anne-Louise/B-5597-2009; Smith, Albert Vernon/K-5150-2015;
OI Visvikis-Siest, Sophie/0000-0001-8104-8425; ruggiero,
daniela/0000-0003-3898-7827; Stathopoulou, Maria/0000-0003-4376-2083;
Leutenegger, Anne-Louise/0000-0002-1302-4357; Smith, Albert
Vernon/0000-0003-1942-5845; NUTILE, TERESA/0000-0001-7062-8352;
Ramachandran, Vasan/0000-0001-7357-5970
FU NIH [N01-AG012100]; NIA; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); Italian Ministry of Universities
[PON03PE_00060_7]; FP6 [Vasoplus-037254]; Assessorato Ricerca Regione
Campania; Fondazione con il SUD [2011-PDR-13]; Istituto Banco di
Napoli-Fondazione; National Heart, Lung, and Blood Institute
[N01-HC-25195, HL-077477, HL093029, HL-K24-04334]; Affymetrix, Inc
[N02-HL-6 to 4278]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine; Boston Medical Center;
National Institute of Neurological Disorders and Stroke [NS17950];
National Institute of Aging [AG031287, AG08122, U0149505, AG033193,
AG033040, P30AG013846]; Italian Ministry of Education, University and
Research [MERIT RBNE08NKH7_007]; Uppsala University, Uppsala University
Hospital; Swedish Research Council for Infrastructures; Swedish Research
Council; Swedish Heart-Lung Foundation; Compagnia di San Paolo, Torino,
Italy; Fondazione Cariplo, Italy; Telethon Italy; Ministry of Health;
German Research Council [SFB- 1052]; German Diabetes Association; DHFD
(Diabetes Hilfs- und Forschungsfonds Deutschland); Federal Ministry of
Education and Research (BMBF), Germany [FKZ: 01EO1001]; European
Community [HEALTH-F4-2007-201413]; INSERM; Collaborative BioIntelligence
Program; "Caisse Nationale d'Assurance Maladies des Travailleurs
Salaries" (CNAM); "Institut National de la Sante et de la Recherche
Medicale" (INSERM); Region Lorraine; Communaute Urbaine du Grand Nancy;
"Henri Poincare" University of Nancy I
FX The AGES study has been funded by NIH contract N01-AG012100, the NIA
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament). The Cilento
study, including Gioi population, was supported by the Italian Ministry
of Universities (PON03PE_00060_7), FP6 (Vasoplus-037254), the
Assessorato Ricerca Regione Campania, the Fondazione con il SUD
(2011-PDR-13), and the Istituto Banco di Napoli-Fondazione to MC. The
Family Heart Study (FHS) work was supported by the National Heart, Lung,
and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195)
and its contract with Affymetrix, Inc, for genotyping services (contract
No. N02-HL-6 to 4278). A portion of this research utilized the Linux
Cluster for Genetic Analysis funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. This study was also supported by grants from
the National Heart, Lung, and Blood Institute (HL-077477, HL093029,
HL-K24-04334), the National Institute of Neurological Disorders and
Stroke (NS17950), and the National Institute of Aging (AG031287,
AG08122, U0149505, AG033193, AG033040, and P30AG013846). The Ogliastra
Genetic Park (OGP) study was supported by the Italian Ministry of
Education, University and Research (MERIT RBNE08NKH7_007). For the PIVUS
study, the genotyping was performed by the SNP&SEQ Technology Platform
in Uppsala (www.genotyping.se). The SNP Technology Platform is supported
by Uppsala University, Uppsala University Hospital and the Swedish
Research Council for Infrastructures. CS and EI were supported by grants
from the Swedish Research Council and the Swedish Heart-Lung Foundation
when working with this article. The Val Borbera (VB) study was supported
by funds from Compagnia di San Paolo, Torino, Italy; Fondazione Cariplo,
Italy; Telethon Italy; Ministry of Health, Ricerca Finalizzata 2008 and
2011-2012 and Public Health Genomics Project 2010. The Sorbs work was
supported by grants from the German Research Council (SFB- 1052 "Obesity
mechanisms" to Michael Stumvoll, AT and PK), from the German Diabetes
Association (to AT and PK) and from the DHFD (Diabetes Hilfs- und
Forschungsfonds Deutschland to Michael Stumvoll and PK). IFB Adiposity
Diseases is supported by the Federal Ministry of Education and Research
(BMBF), Germany, FKZ: 01EO1001. Dr. Inga Prokopenko and VL were
partially funded through the European Community's Seventh Framework
Programme (FP7/2007-2013), ENGAGE project, grant agreement
HEALTH-F4-2007-201413. The Hypertensive Adults (HT) adults samples and
data used in the present study are part of the Biological Resources
Center (BRC) "Interactions Gene-Environnement en Physiopathologie Cardio
Vasculaire" IGEPCV) in Nancy, France. This work was funded through
INSERM and the Collaborative BioIntelligence Program. The STANISLAS
Family study samples and data used in the present study are part of the
Biological Resources Center (BRC) "Interactions Gene-Environnement en
Physiopathologie Cardio Vasculaire" IGE-PCV) in Nancy, France. The
STANISLAS Family Study, as part of the BRC, was supported by the "Caisse
Nationale d'Assurance Maladies des Travailleurs Salaries" (CNAM), the
"Institut National de la Sante et de la Recherche Medicale" (INSERM),
the "Region Lorraine", the "Communaute Urbaine du Grand Nancy", and the
"Henri Poincare" University of Nancy I. This work was also funded
through the Collaborative BioIntelligence Program.; The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 100
TC 1
Z9 1
U1 3
U2 5
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 FEB
PY 2016
VL 12
IS 2
AR e1005874
DI 10.1371/journal.pgen.1005874
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA DH1OI
UT WOS:000372554100047
PM 26910538
ER
PT J
AU Shin, MH
He, YL
Marrogi, E
Piperdi, S
Ren, L
Khanna, C
Gorlick, R
Liu, CY
Huang, J
AF Shin, Min Hwa
He, Yunlong
Marrogi, Eryney
Piperdi, Sajida
Ren, Ling
Khanna, Chand
Gorlick, Richard
Liu, Chengyu
Huang, Jing
TI A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective
Cancer Cells
SO PLOS GENETICS
LA English
DT Article
ID HUMAN OSTEOSARCOMA; CBF-BETA; IN-VIVO; PATHWAY; RUNX2; MICE;
DIFFERENTIATION; AMPLIFICATION; OSTEOBLASTS; MECHANISMS
AB The inactivation of p53 creates a major challenge for inducing apoptosis in cancer cells. An attractive strategy is to identify and subsequently target the survival signals in p53 defective cancer cells. Here we uncover a RUNX2-mediated survival signal in p53 defective cancer cells. The inhibition of this signal induces apoptosis in cancer cells but not non-transformed cells. Using the CRISPR technology, we demonstrate that p53 loss enhances the apoptosis caused by RUNX2 knockdown. Mechanistically, RUNX2 provides the survival signal partially through inducing MYC transcription. Cancer cells have high levels of activating histone marks on the MYC locus and concomitant high MYC expression. RUNX2 knockdown decreases the levels of these histone modifications and the recruitment of the Menin/MLL1 (mixed lineage leukemia 1) complex to the MYC locus. Two inhibitors of the Menin/MLL1 complex induce apoptosis in p53 defective cancer cells. Together, we identify a RUNX2-mediated epigenetic mechanism of the survival of p53 defective cancer cells and provide a proof-of-principle that the inhibition of this epigenetic axis is a promising strategy to kill p53 defective cancer cells.
C1 [Shin, Min Hwa; He, Yunlong; Marrogi, Eryney; Huang, Jing] NCI, Canc & Stem Cell Epigenet Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Piperdi, Sajida; Gorlick, Richard] Childrens Hosp Montefiore, Div Pediat Hematol Oncol, Bronx, NY USA.
[Ren, Ling; Khanna, Chand] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core Facil, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
RP Huang, J (reprint author), NCI, Canc & Stem Cell Epigenet Sect, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
EM huangj3@mail.nih.gov
RI Huang, Jing/A-2566-2009; He, Yunlong/D-1278-2017
OI Huang, Jing/0000-0002-7163-5156;
FU National Cancer Institute (US) [1ZIABC011504-02]
FX This work was supported by the National Cancer Institute (US) intramural
grant, 1ZIABC011504-02, http://www.cancer.gov/. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 3
Z9 4
U1 3
U2 5
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 FEB
PY 2016
VL 12
IS 2
AR e1005884
DI 10.1371/journal.pgen.1005884
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA DH1OI
UT WOS:000372554100054
PM 26925584
ER
PT J
AU Takahashi, S
Liao, QH
Van Boeckel, TP
Xing, WJ
Sun, JL
Hsiao, VY
Metcalf, CJE
Chang, ZR
Liu, FF
Zhang, J
Wu, JT
Cowling, BJ
Leung, GM
Farrar, JJ
van Doorn, HR
Grenfell, BT
Yu, HJ
AF Takahashi, Saki
Liao, Qiaohong
Van Boeckel, Thomas P.
Xing, Weijia
Sun, Junling
Hsiao, Victor Y.
Metcalf, C. Jessica E.
Chang, Zhaorui
Liu, Fengfeng
Zhang, Jing
Wu, Joseph T.
Cowling, Benjamin J.
Leung, Gabriel M.
Farrar, Jeremy J.
van Doorn, H. Rogier
Grenfell, Bryan T.
Yu, Hongjie
TI Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of
Enterovirus Serotypes and Implications for Vaccination
SO PLOS MEDICINE
LA English
DT Article
ID COXSACKIEVIRUS A16; NEUTRALIZING ANTIBODY; GENETIC EVOLUTION; MEASLES
EPIDEMICS; CROSS-REACTIVITY; UNITED-STATES; INFECTIONS; CHILDREN;
MALAYSIA; SURVEILLANCE
AB Background
Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus.
Methods and Findings
Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptibleinfected- recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R-0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16.
Conclusions The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden.
C1 [Takahashi, Saki; Van Boeckel, Thomas P.; Hsiao, Victor Y.; Metcalf, C. Jessica E.; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Liao, Qiaohong; Xing, Weijia; Sun, Junling; Chang, Zhaorui; Liu, Fengfeng; Zhang, Jing; Yu, Hongjie] Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China.
[Metcalf, C. Jessica E.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA.
[Wu, Joseph T.; Cowling, Benjamin J.; Leung, Gabriel M.] Univ Hong Kong, Li Ka Shing Fac Med, WHO Collaborating Ctr Infect Dis Epidemiol & Cont, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Farrar, Jeremy J.; van Doorn, H. Rogier] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[van Doorn, H. Rogier] Univ Oxford, Nuffield Dept Med, Ctr Trop Med, Oxford, England.
[Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Grenfell, BT (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.; Yu, HJ (reprint author), Chinese Ctr Dis Control & Prevent, Div Infect Dis, Key Lab Surveillance & Early Warning Infect Dis, Beijing, Peoples R China.; Grenfell, BT (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM grenfell@princeton.edu; yuhj@chinacdc.cn
FU National Science Fund for Distinguished Young Scholars [81525023];
National Natural Science Foundation of China [81473031]; Li Ka Shing
Oxford Global Health Programme [B9RST00-B900.57]; Science and Technology
Directorate, Department of Homeland Security [HSHQDC-12-C-00058];
Fulbright Program (TPVB); Bill & Melinda Gates Foundation [OPP1094793];
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security; Fogarty International Center; National Institutes of
Health (CJEM); National Institutes of Health (BTG); Harvard Center for
Communicable Disease Dynamics from National Institute of General Medical
Sciences [U54 GM088558]; Health and Medical Research Fund from the
Government of the Hong Kong Special Administrative Region; Wellcome
Trust; Li Ka Shing Oxford Global Health Programme (JJF); Wellcome Trust
Programme Grant [089276/Z/09/Z]
FX This work is supported by the National Science Fund for Distinguished
Young Scholars (No. 81525023) (HY), the National Natural Science
Foundation of China (No. 81473031) (HY), the Li Ka Shing Oxford Global
Health Programme (No. B9RST00-B900.57) (HY), the Science and Technology
Directorate, Department of Homeland Security contract HSHQDC-12-C-00058
(TPVB, CJEM, BTG), the Fulbright Program (TPVB), the Bill & Melinda
Gates Foundation (OPP1094793) (CJEM,BTG), the RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security and
the Fogarty International Center, National Institutes of Health (CJEM,
BTG), the Harvard Center for Communicable Disease Dynamics from the
National Institute of General Medical Sciences (grant no. U54 GM088558)
(JTW, BJC, GML), a commissioned grant from the Health and Medical
Research Fund from the Government of the Hong Kong Special
Administrative Region (JTW, BJC, GML), the Wellcome Trust (JJF), the Li
Ka Shing Oxford Global Health Programme (JJF), and the Wellcome Trust
Programme Grant 089276/Z/09/Z (HRvD). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 72
TC 2
Z9 4
U1 10
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD FEB
PY 2016
VL 13
IS 2
AR e1001958
DI 10.1371/journal.pmed.1001958
PG 29
WC Medicine, General & Internal
SC General & Internal Medicine
GA DH8JF
UT WOS:000373038600007
PM 26882540
ER
PT J
AU Bland, DM
Hinnebusch, BJ
AF Bland, David M.
Hinnebusch, B. Joseph
TI Feeding Behavior Modulates Biofilm-Mediated Transmission of Yersinia
pestis by the Cat Flea, Ctenocephalides felis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID EARLY-PHASE TRANSMISSION; PLAGUE-ENDEMIC REGION; OROPSYLLA-MONTANA
SIPHONAPTERA; RICKETTSIA-FELIS; BARTONELLA-HENSELAE; XENOPSYLLA-CHEOPIS;
BORNE TRANSMISSION; PLASMINOGEN-ACTIVATOR; UNBLOCKED FLEAS; POTENTIAL
ROLE
AB Background
The cat flea, Ctenocephalides felis, is prevalent worldwide, will parasitize animal reservoirs of plague, and is associated with human habitations in known plague foci. Despite its pervasiveness, limited information is available about the cat flea's competence as a vector for Yersinia pestis. It is generally considered to be a poor vector, based on studies examining early-phase transmission during the first week after infection, but transmission potential by the biofilm-dependent proventricular-blocking mechanism has never been systematically evaluated. In this study, we assessed the vector competence of cat fleas by both mechanisms. Because the feeding behavior of cat fleas differs markedly from important rat flea vectors, we also examined the influence of feeding behavior on transmission dynamics.
Methodology/Principal
Findings Groups of cat fleas were infected with Y. pestis and subsequently provided access to sterile blood meals twice-weekly, 5 times per week, or daily for 4 weeks and monitored for infection, the development of proventricular biofilm and blockage, mortality, and the ability to transmit. In cat fleas allowed prolonged, daily access to blood meals, mimicking their natural feeding behavior, Y. pestis did not efficiently colonize the digestive tract and could only be transmitted during the first week after infection. In contrast, cat fleas that were fed intermittently, mimicking the feeding behavior of the efficient vector Xenopsylla cheopis, could become blocked and regularly transmitted Y. pestis for 3-4 weeks by the biofilm-mediated mechanism, but early-phase transmission was not detected.
Conclusions
The normal feeding behavior of C. felis, more than an intrinsic resistance to infection or blockage by Y. pestis, limits its vector competence. Rapid turnover of midgut contents results in bacterial clearance and disruption of biofilm accumulation in the proventriculus. Anatomical features of the cat flea foregut may also restrict transmission by both early-phase and proventricular biofilm-dependent mechanisms.
C1 [Bland, David M.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Bland, DM (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM david.bland@nih.gov
OI Bland, David/0000-0002-5052-5599
FU Intramural Research Program of National Institute of Allergy and
Infectious Diseases, National Institues of Health
FX This study was funded by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institues of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 63
TC 1
Z9 1
U1 4
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2016
VL 10
IS 2
AR e0004413
DI 10.1371/journal.pntd.0004413
PG 25
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1TH
UT WOS:000372567300030
PM 26829486
ER
PT J
AU Faleiro, RJ
Kumar, R
Bunn, PT
Singh, N
Chauhan, SB
Sheel, M
Amante, FH
de Oca, MM
Edwards, CL
Ng, SS
Best, SE
Haque, A
Beattie, L
Hafner, LM
Sacks, D
Nylen, S
Sundar, S
Engwerda, CR
AF Faleiro, Rebecca J.
Kumar, Rajiv
Bunn, Patrick T.
Singh, Neetu
Chauhan, Shashi Bhushan
Sheel, Meru
Amante, Fiona H.
de Oca, Marcela Montes
Edwards, Chelsea L.
Ng, Susanna S.
Best, Shannon E.
Haque, Ashraful
Beattie, Lynette
Hafner, Louise M.
Sacks, David
Nylen, Susanne
Sundar, Shyam
Engwerda, Christian R.
TI Combined Immune Therapy for the Treatment of Visceral Leishmaniasis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CELL-MEDIATED-IMMUNITY; CHEMICALLY-MODIFIED FLAGELLIN; REGULATORY
T-CELLS; DONOVANI INFECTION; CANCER-THERAPY; RESPONSES; IL-10; BLOCKADE;
IMMUNOTHERAPY; DISTINCT
AB Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor-related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFN gamma production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti-parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti-parasitic drug. Critically, these results also highlight potential negative effects of combining different immune modulation strategies.
C1 [Faleiro, Rebecca J.; Kumar, Rajiv; Bunn, Patrick T.; Sheel, Meru; Amante, Fiona H.; de Oca, Marcela Montes; Edwards, Chelsea L.; Ng, Susanna S.; Best, Shannon E.; Haque, Ashraful; Beattie, Lynette; Engwerda, Christian R.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Faleiro, Rebecca J.; Hafner, Louise M.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Kumar, Rajiv] Netaji Subhas Inst Technol, New Delhi, India.
[Kumar, Rajiv; Singh, Neetu; Chauhan, Shashi Bhushan; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.
[Bunn, Patrick T.] Griffith Univ, Inst Glyc, Gold Coast, Australia.
[de Oca, Marcela Montes; Edwards, Chelsea L.] Univ Queensland, Sch Med, Brisbane, Qld, Australia.
[Ng, Susanna S.] Griffith Univ, Sch Nat Sci, Nathan, Qld 4111, Australia.
[Sacks, David] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Nylen, Susanne] Karolinska Inst, Stockholm, Sweden.
RP Kumar, R; Engwerda, CR (reprint author), QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.; Kumar, R (reprint author), Netaji Subhas Inst Technol, New Delhi, India.; Kumar, R (reprint author), Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India.
EM Rajiv.Kumar@qimrberghofer.edu.au; chrisE@qimr.edu.au
OI Engwerda, Christian/0000-0003-2813-4804; Ng, Susanna/0000-0002-8494-7722
FU Australia-India Strategic Research fund; National Health and Medical
Research Council of Australia; National Institute of Allergy and
Infectious Diseases, National Institutes of Health Tropical Medicine
Research Centre grant [2P50AI074321]; Indian Department of Science and
Technology INSPIRE scheme; Indian Government Department of Biotechnology
FX This work was supported by grants and Fellowships from the
Australia-India Strategic Research fund made available by the Australian
government Department of Innovation, Industry, Science and Research and
Indian Government Department of Biotechnology, the National Health and
Medical Research Council of Australia, a National Institute of Allergy
and Infectious Diseases, National Institutes of Health Tropical Medicine
Research Centre grant (2P50AI074321) and the Indian Department of
Science and Technology INSPIRE scheme. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
TC 1
Z9 1
U1 2
U2 7
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 FEB
PY 2016
VL 10
IS 2
AR e0004415
DI 10.1371/journal.pntd.0004415
PG 21
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1TH
UT WOS:000372567300032
PM 26872334
ER
PT J
AU Forshey, BM
Reiner, RC
Olkowski, S
Morrison, AC
Espinoza, A
Long, KC
Vilcarromero, S
Casanova, W
Wearing, HJ
Halsey, ES
Kochel, TJ
Scott, TW
Stoddard, ST
AF Forshey, Brett M.
Reiner, Robert C.
Olkowski, Sandra
Morrison, Amy C.
Espinoza, Angelica
Long, Kanya C.
Vilcarromero, Stalin
Casanova, Wilma
Wearing, Helen J.
Halsey, Eric S.
Kochel, Tadeusz J.
Scott, Thomas W.
Stoddard, Steven T.
TI Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID NEUTRALIZING ANTIBODY-LEVELS; HEMORRHAGIC-FEVER; TIME-INTERVAL;
INFECTION; THAILAND; VACCINES; MONKEYS; DISEASE; ILLNESS; DENV-2
AB Background
Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or antiviral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide lifelong protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region.
Methodology/Principal Findings
We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7).
Conclusions/Significance
Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.
C1 [Forshey, Brett M.; Morrison, Amy C.; Espinoza, Angelica; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.] US Naval Med Res Unit 6, Lima, Peru.
[Forshey, Brett M.; Morrison, Amy C.; Espinoza, Angelica; Vilcarromero, Stalin; Halsey, Eric S.; Kochel, Tadeusz J.] US Naval Med Res Unit 6, Iquitos, Peru.
[Reiner, Robert C.] Indiana Univ, Sch Publ Hlth, Bloomington, IN USA.
[Reiner, Robert C.; Scott, Thomas W.; Stoddard, Steven T.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Olkowski, Sandra; Morrison, Amy C.; Long, Kanya C.; Scott, Thomas W.; Stoddard, Steven T.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Long, Kanya C.] Andrews Univ, Dept Biol, Berrien Springs, MI 49104 USA.
[Casanova, Wilma] Univ Nacl Amazonia Peruana, Iquitos, Peru.
[Casanova, Wilma] Direcc Reg Salud Loreto, Iquitos, Peru.
[Wearing, Helen J.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Forshey, Brett M.] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD USA.
RP Forshey, BM (reprint author), US Naval Med Res Unit 6, Lima, Peru.; Forshey, BM (reprint author), US Naval Med Res Unit 6, Iquitos, Peru.; Forshey, BM (reprint author), Armed Forces Hlth Surveillance Ctr, Silver Spring, MD USA.
EM brett.m.forshey.ctr@mail.mil
OI Vilcarromero, Stalin/0000-0002-9097-0638
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
Science and Technology Directory, Department of Homeland Security;
National Institutes of Health [RO1 AI-42332, RO1 AI069341, U01GM097661,
P01 AI098670]; Fogarty International Center, National Institutes of
Health; Innovative Vector Control Consortium; United States Department
of Defense Global Emerging Infections Systems Research Program
[847705.82000.25GB.B0016]; Military Infectious Disease Research Program
[6000 RAD1.S.B0302, S0002 04 LI, DOD S0017 03LI, DOD 32519, S0088 06
NM]; Deployed Warfighter Protection Program [DOD S0002 04]; Wellcome
Trust [08571]
FX This work was supported by the Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directory, Department of Homeland Security, and Fogarty International
Center, National Institutes of Health; National Institutes of Health
(grants RO1 AI-42332, RO1 AI069341, U01GM097661and P01 AI098670);
Innovative Vector Control Consortium; United States Department of
Defense Global Emerging Infections Systems Research Program (Work Unit
Number: 847705.82000.25GB.B0016); Military Infectious Disease Research
Program (Work Unit Number: 6000 RAD1.S.B0302, S0002 04 LI, DOD S0017
03LI, DOD 32519, and S0088 06 NM); Deployed Warfighter Protection
Program (DOD S0002 04); and Wellcome Trust (08571). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 39
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Z9 6
U1 2
U2 3
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 FEB
PY 2016
VL 10
IS 2
AR e0004398
DI 10.1371/journal.pntd.0004398
PG 17
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DH1TH
UT WOS:000372567300022
PM 26848841
ER
PT J
AU Nowicka, U
Hoffman, M
Randles, L
Shi, XS
Khavrutskii, L
Stefanisko, K
Tarasova, NI
Darwin, KH
Walters, KJ
AF Nowicka, Urszula
Hoffman, Morgan
Randles, Leah
Shi, Xiaoshan
Khavrutskii, Lyuba
Stefanisko, Karen
Tarasova, Nadya I.
Darwin, K. Heran
Walters, Kylie J.
TI Mycobacterium tuberculosis copper-regulated protein SocB is an
intrinsically disordered protein that folds upon interaction with a
synthetic phospholipid bilayer
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE SocB; Mycobacterium tuberculosis (Mtb); intrinsically disordered
proteins; synthetic phospholipid bilayer; membrane protein
ID SECONDARY STRUCTURE ANALYSES; UBIQUITIN-LIKE PROTEIN; PREDICTION;
SERVER; PUP
AB Multiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB (small orf induced by copper A and B), which is induced by copper and repressed by RicR (regulated in copper repressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure. We find that SocB lacks evidence for secondary structure, with no thermal cooperative unfolding event, according to circular dichroism measurements. 2D NMR spectra similarly exhibit hallmarks of a disordered structural state, which is also supported by analyzing SocB diffusion. Altogether, these findings suggest that by itself SocB is intrinsically disordered. Interestingly, SocB interacts with a synthetic phospholipid bilayer and becomes helical, which suggests that it may be membrane-associated. (C) 2015 Wiley Periodicals, Inc.
C1 [Nowicka, Urszula; Hoffman, Morgan; Randles, Leah; Walters, Kylie J.] NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Hoffman, Morgan] Middletown High Sch, Middletown, MD 21769 USA.
[Shi, Xiaoshan; Darwin, K. Heran] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
[Khavrutskii, Lyuba; Stefanisko, Karen; Tarasova, Nadya I.] NCI, Synthet Biol Facil, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Walters, KJ (reprint author), NCI, Prot Proc Sect, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM kylie.walters@nih.gov
FU Werner H. Kirsten student internship program
FX Morgan Hoffman was funded in part by the Werner H. Kirsten student
internship program. We are grateful to Dr. Sergey Tarasov and Dr.
Marzena Dyba for technical assistance. K.H.D. thanks Dr. Vincenz Unger
for helpful discussions.
NR 29
TC 1
Z9 1
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
EI 1097-0134
J9 PROTEINS
JI Proteins
PD FEB
PY 2016
VL 84
IS 2
BP 193
EP 200
DI 10.1002/prot.24970
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DI2TC
UT WOS:000373350800001
PM 26650755
ER
PT J
AU Elmore, SA
Dixon, D
Hailey, JR
Harada, T
Herbert, RA
Maronpot, RR
Nolte, T
Rehg, JE
Rittinghausen, S
Rosol, TJ
Satoh, H
Vidal, JD
Willard-Mack, CL
Creasy, DM
AF Elmore, Susan A.
Dixon, Darlene
Hailey, James R.
Harada, Takanori
Herbert, Ronald A.
Maronpot, Robert R.
Nolte, Thomas
Rehg, Jerold E.
Rittinghausen, Susanne
Rosol, Thomas J.
Satoh, Hiroshi
Vidal, Justin D.
Willard-Mack, Cynthia L.
Creasy, Dianne M.
TI Recommendations from the INHAND Apoptosis/Necrosis Working Group
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE apoptosis; necrosis; single cell necrosis; cell death; INHAND; guidance
ID PROGRAMMED CELL-DEATH; OLIGONUCLEOSOMAL DNA FRAGMENTATION; DETECT
APOPTOSIS; IMMUNE-SYSTEM; IN-SITU; NECROSIS; NECROPTOSIS; ACTIVATION;
ACID; EXCITOTOXICITY
AB Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms single cell necrosis and apoptosis interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:
Use necrosis and apoptosis as separate diagnostic terms.
Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).
Use the combined term apoptosis/single cell necrosis when
There is no requirement or need to split the processes, or
When the nature of cell death cannot be determined with certainty, or
When both processes are present together.
The diagnosis should be based primarily on the morphological features in H&E-stained sections. When needed, additional, special techniques to identify and characterize apoptosis can also be used.
C1 [Elmore, Susan A.; Herbert, Ronald A.] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
[Dixon, Darlene] NIEHS, Div NTP, Natl Toxicol Program Lab, Mol Pathogenesis Grp, POB 12233, Res Triangle Pk, NC 27709 USA.
[Hailey, James R.] Covance Inc, Chantilly, VA USA.
[Harada, Takanori] Inst Environm Toxicol, Joso, Ibaraki, Japan.
[Maronpot, Robert R.] Maronpot Consulting LLC, Raleigh, NC USA.
[Nolte, Thomas] Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
[Rehg, Jerold E.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Rittinghausen, Susanne] Fraunhofer Inst Toxicol & Expt Med ITEM, Hannover, Germany.
[Rosol, Thomas J.] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA.
[Satoh, Hiroshi] Iwate Univ, Morioka, Iwate 020, Japan.
[Vidal, Justin D.] Vet Path Serv Inc VPS, Mason, OH USA.
[Willard-Mack, Cynthia L.; Creasy, Dianne M.] Envigo, E Millstone, NJ USA.
RP Elmore, SA (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM elmore@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Environmental Health Sciences (NIEHS)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported [in part] by the Intramural Research Program of
the National Institutes of Health (NIH) and National Institute of
Environmental Health Sciences (NIEHS).
NR 64
TC 3
Z9 3
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2016
VL 44
IS 2
BP 173
EP 188
DI 10.1177/0192623315625859
PG 16
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DH0KL
UT WOS:000372473000004
PM 26879688
ER
PT J
AU Churchill, SR
Morgan, DL
Kissling, GE
Travlos, GS
King-Herbert, AP
AF Churchill, Sheba R.
Morgan, Daniel L.
Kissling, Grace E.
Travlos, Gregory S.
King-Herbert, Angela P.
TI Impact of Environmental Enrichment Devices on NTP In Vivo Studies
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE environmental enrichment; animal welfare; laboratory animals; rats; mice
ID NEST-BUILDING BEHAVIOR; ZERO DOSE CONTROL; LABORATORY RATS; STRESS
RESPONSES; MALE-MICE; CORTICOSTERONE; PREFERENCES; TEMPERATURE;
AGGRESSION; PARAMETERS
AB The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices.
C1 [Churchill, Sheba R.; Morgan, Daniel L.; Kissling, Grace E.; Travlos, Gregory S.; King-Herbert, Angela P.] NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA.
RP Churchill, SR (reprint author), NIEHS, POB 12233,MD B3-06, Res Triangle Pk, NC 27709 USA.
EM sheba.churchill@nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Environmental Health Sciences (NIEHS)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported [in part] by the Intramural Research Program of
the National Institutes of Health (NIH) and National Institute of
Environmental Health Sciences (NIEHS).
NR 49
TC 1
Z9 1
U1 2
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD FEB
PY 2016
VL 44
IS 2
BP 233
EP 245
DI 10.1177/0192623315625330
PG 13
WC Pathology; Toxicology
SC Pathology; Toxicology
GA DH0KL
UT WOS:000372473000008
PM 26873679
ER
PT J
AU He, Y
Li, QDQT
Guo, SC
AF He, Yu
Li, Qingdi Quentin
Guo, Song Chao
TI Taurine Attenuates Dimethylbenz[a]anthracene-induced Breast
Tumorigenesis in Rats: A Plasma Metabolomic Study
SO ANTICANCER RESEARCH
LA English
DT Article
DE Taurine; metabolomics; breast cancer; rat animal model; Warburg effect;
metabolic alteration
ID AMINO-ACID PROFILES; CANCER-PATIENTS; GLUCOSE-METABOLISM; LUNG-CANCER;
CELLS; APOPTOSIS; NUTRITION; BIOMARKER; TUMORS
AB Breast cancer is the most common malignancy and the leading cause of cancer-related mortality in women worldwide. Taurine, the most abundant free amino acid, plays a role in several biological processes in humans and has been shown to have activity against breast cancer and other tumors. To investigate the role and mechanism of taurine action in breast cancer, we used dimethylbenz[a]anthracene (DMBA)induced breast carcinogenesis in rats as a model of breast cancer. The administration of taurine significantly reduced the DMBA-induced breast cancer rate from 80% to 40% in rats (p<0.05). Metabolomic studies using time-of-flight gas chromatography-mass spectrometry identified 23 differential metabolites in the plasma of taurine-administered rats. Bioinformatic analysis further revealed that these metabolites are involved in multiple metabolic pathways, including energy, glucose, amino acid, and nucleic acid metabolism, suggesting that the antitumor activity of taurine in rats is mediated through altered metabolism of breast cancer cells. We propose that these differential metabolites may be potential biomarkers for monitoring cancer therapy and prognosis in the clinic. This study provides a scientific basis for further investigations of the antitumor mechanism of taurine and the development of novel therapeutic strategies to treat breast cancer.
C1 [He, Yu] Guangxi Med Univ, Affiliated Hosp 1, Dept Nutr, Nanning 530021, Peoples R China.
[Guo, Song Chao] Guangxi Med Univ, Sch Publ Hlth, Nanning 530021, Peoples R China.
[Li, Qingdi Quentin] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Guo, SC (reprint author), Guangxi Med Univ, Sch Publ Hlth, Nanning 530021, Peoples R China.
EM 2433164518@qq.com
FU Department of Science and Technology of Guangxi Province [03201215002]
FX This work was supported by a grant from the Department of Science and
Technology of Guangxi Province (the Plan for Guangxi Science and
Technology Basic Condition Platform Construction Projects; No.
03201215002).
NR 40
TC 1
Z9 1
U1 0
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD FEB
PY 2016
VL 36
IS 2
BP 533
EP 543
PG 11
WC Oncology
SC Oncology
GA DG7GS
UT WOS:000372253400007
PM 26851007
ER
PT J
AU Kamada, M
Shiroma, EJ
Harris, TB
Lee, IM
AF Kamada, Masamitsu
Shiroma, Eric J.
Harris, Tamara B.
Lee, I-Min
TI Comparison of physical activity assessed using hip- and wrist-worn
accelerometers
SO GAIT & POSTURE
LA English
DT Article
DE Exercise; Epidemiology; Step counts; Measurement; Objective monitoring
ID RANDOMIZED CONTROLLED-TRIAL; SEDENTARY BEHAVIOR; PRIMARY PREVENTION;
WOMENS HEALTH; VALIDATION; ALGORITHMS; MONITORS; DISEASE; CANCER; SAMPLE
AB Objectives: It is unclear how physical activity estimates differ when assessed using hip- vs wrist-worn accelerometers. The objective of this study was to compare physical activity assessed by hip- and wrist-worn accelerometers in free-living older women.
Design: A cross-sectional study collecting data in free-living environment.
Methods: Participants were from the Women's Health Study, in which an ancillary study is objectively measuring physical activity using accelerometers (ActiGraph GT3X+). We analyzed data from 94 women (mean (SD) age = 71.9 (6.0) years) who wore a hip-worn and wrist-worn accelerometers simultaneously for 7 days.
Results: Using triaxial data (vector magnitude, VM), total activity volume (counts per day) between the two locations was moderately correlated (Spearman's r = 0.73). Hip and wrist monitors wear locations identically classified 71% individuals who were at the highest 40% or lowest 40% of their respective distributions. Similar patterns and slightly stronger agreements were observed when examining steps instead of VM counts.
Conclusions: Accelerometer-assessed physical activity using hip- vs wrist-worn devices was moderately correlated in older, free-living women. However, further research needs to be conducted to examine comparisons of specific activities or physical activity intensity levels. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Kamada, Masamitsu; Shiroma, Eric J.; Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, 900 Commonwealth Ave East, Boston, MA 02215 USA.
[Kamada, Masamitsu] Natl Inst Hlth & Nutr, Dept Hlth Promot & Exercise, Shinjuku Ku, 1-23-1 Toyama, Tokyo 1628636, Japan.
[Shiroma, Eric J.; Harris, Tamara B.] NIA, NIH, 31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA.
[Lee, I-Min] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA.
RP Kamada, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, 900 Commonwealth Ave East,3rd Floor, Boston, MA 02215 USA.
EM kamada@gakushikai.jp
RI Kamada, Masamitsu/H-4411-2011
OI Kamada, Masamitsu/0000-0003-1703-076X
FU Paffenbarger-Blair Fund for Epidemiological Research on Physical
Activity of the ACSM; National Institutes of Health [CA154647,
CA047988]; JSPS Postdoctoral Fellowship for Research Abroad; Intramural
Research Program of the National Institutes of Health, National
Institute on Aging
FX We are grateful to the staff of the Women's Health Study (Brigham and
Women's Hospital), particularly Ara Sarkissian, MM, Bonnie Church, BA,
Colby Smith, BS, and Jane Jones, MEd. None of the persons named were
compensated. This research was supported by the Paffenbarger-Blair Fund
for Epidemiological Research on Physical Activity of the ACSM and
research grants CA154647 and CA047988 from the National Institutes of
Health. MK is supported by a JSPS Postdoctoral Fellowship for Research
Abroad. EJS and TBH are supported by the Intramural Research Program of
the National Institutes of Health, National Institute on Aging. The
funding bodies did not have a role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 27
TC 1
Z9 1
U1 6
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0966-6362
EI 1879-2219
J9 GAIT POSTURE
JI Gait Posture
PD FEB
PY 2016
VL 44
BP 23
EP 28
DI 10.1016/j.gaitpost.2015.11.005
PG 6
WC Neurosciences; Orthopedics; Sport Sciences
SC Neurosciences & Neurology; Orthopedics; Sport Sciences
GA DH0PV
UT WOS:000372487000005
PM 27004628
ER
PT J
AU Bando, H
Takebe, N
AF Bando, Hideaki
Takebe, Naoko
TI Perspectives on research activity in the USA on Cancer Precision
Medicine
SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
DE precision medicine; National Cancer Institute (NCI); NCI-MATCH; National
Clinical Trials Network (NCTN)
AB The National Cancer Institute-Molecular Analysis for Therapy Choice trial is a clinical trial that will analyze various genetic statuses of patients' tumors to determine whether they contain abnormalities which can be a target for an available drug. National Cancer Institute-Molecular Analysis for Therapy Choice seeks to determine whether improved outcomes can be achieved when cancer treatments are personalized based on molecular abnormalities found in individual patients. As a master protocol, or basket trial, National Cancer Institute-Molecular Analysis for Therapy Choice can add or remove treatments as indicated over the duration of the study. Each treatment will be used in a unique arm, or sub-study, of the trial. The trial initially has 10 arms, each of which will enroll patients to a specific molecularly targeted treatment. It is ultimately anticipated that 20-25 drugs or combination treatments will be tested. To be eligible for the study, participants must have an advanced solid tumor or lymphoma that is no longer responding or never responded to the standard therapy. National Cancer Institute-Molecular Analysis for Therapy Choice investigators plan to obtain tumor biopsy specimens from as many as 3000 patients initially. To identify multiple genetic abnormalities that may respond to the targeted drugs selected for the trial, next-generation deoxyribonucleic acid and ribonucleic acid sequencing will be done in the genetic testing laboratories, analyzing for >4000 different variants across 143 genes. The drugs included in the trial have all either been approved by the US Food and Drug Administration for another cancer indication or are still being tested in other clinical trials, but have shown some clinical levels of evidence against tumors with a particular genetic alteration.
C1 [Bando, Hideaki] Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.
[Takebe, Naoko] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr MSC9739, Bethesda, MD 20852 USA.
RP Bando, H (reprint author), Natl Canc Ctr Hosp East, Dept Gastroenterol & Gastrointestinal Oncol, 6-5-1 Kashiwanoha, Kashiwa, Chiba, Japan.; Takebe, N (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 9609 Med Ctr Dr MSC9739, Bethesda, MD 20852 USA.
EM hbando@east.ncc.go.jp; Takeben@mail.nih.gov
NR 8
TC 0
Z9 0
U1 2
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0368-2811
EI 1465-3621
J9 JPN J CLIN ONCOL
JI Jpn. J. Clin. Oncol.
PD FEB
PY 2016
VL 46
IS 2
BP 106
EP 110
DI 10.1093/jjco/hyv162
PG 5
WC Oncology
SC Oncology
GA DH2KN
UT WOS:000372614500002
PM 26531706
ER
PT J
AU Tynell, J
Westenius, V
Ronkko, E
Munster, VJ
Melen, K
Osterlund, P
Julkunen, I
AF Tynell, Janne
Westenius, Veera
Ronkko, Esa
Munster, Vincent J.
Melen, Krister
Osterlund, Pamela
Julkunen, Ilkka
TI Middle East respiratory syndrome coronavirus shows poor replication but
significant induction of antiviral responses in human monocyte-derived
macrophages and dendritic cells
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID DIPEPTIDYL PEPTIDASE 4; MERS-COV; DROMEDARY CAMELS; SARS-CORONAVIRUS;
GENE-EXPRESSION; SPIKE PROTEIN; INTERFERON ANTAGONISTS; FUNCTIONAL
RECEPTOR; ACCESSORY PROTEINS; VIRUS
AB In this study we assessed the ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to replicate and induce innate immunity in human monocyte-derived macrophages and dendritic cells (MDDCs), and compared it with severe acute respiratory syndrome coronavirus (SARS-CoV). Assessments of viral protein and RNA levels in infected cells showed that both viruses were impaired in their ability to replicate in these cells. Some induction of IFN-lambda 1, CXCL10 and MxA mRNAs in both macrophages and MDDCs was seen in response to MERS-CoV infection, but almost no such induction was observed in response to SARS-CoV infection. ELISA and Western blot assays showed clear production of CXCL10 and MxA in MERS-CoV-infected macrophages and MDDCs. Our data suggest that SARS-CoV and MERS-CoV replicate poorly in human macrophages and MDDCs, but MERS-CoV is nonetheless capable of inducing a readily detectable host innate immune response. Our results highlight a clear difference between the viruses in activating host innate immune responses in macrophages and MDDCs, which may contribute to the pathogenesis of infection.
C1 [Tynell, Janne; Westenius, Veera; Ronkko, Esa; Melen, Krister; Osterlund, Pamela; Julkunen, Ilkka] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Julkunen, Ilkka] Univ Turku, Dept Virol, Turku, Finland.
RP Tynell, J (reprint author), Natl Inst Hlth & Welf THL, Helsinki, Finland.
EM janne.tynell@thl.fi
RI Osterlund, Pamela/L-2528-2015;
OI Osterlund, Pamela/0000-0002-2229-6661; Munster,
Vincent/0000-0002-2288-3196; Tynell, Janne/0000-0001-6930-5230
FU Medical Research Council of the Academy of Finland [252252, 255780];
Sigrid Juselius Foundation; Finnish Cultural Foundation; Jenny and Antti
Wihuri Foundation; Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported by the Medical Research Council of the Academy
of Finland (project numbers 252252 and 255780), the Sigrid Juselius
Foundation, Finnish Cultural Foundation, and Jenny and Antti Wihuri
Foundation. The authors wish to thank Hanna Valtonen for expert
technical assistance, Sinikka Latvala for help in preparing macrophages
and MDDCs, and Susanna Sissonen for training and guidance in Biosafety
Level 3 practices. We are indebted to Dr Ron A. M. Fouchier (Erasmus
Medical Center, Rotterdam, the Netherlands) for providing us with the
MERS-CoV and SARS-CoV viruses. V. J. M. is supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 56
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U1 2
U2 3
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD FEB
PY 2016
VL 97
BP 344
EP 355
DI 10.1099/jgv.0.000351
PN 2
PG 12
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA DG4ST
UT WOS:000372063600011
PM 26602089
ER
PT J
AU Evans, TI
Li, HY
Schafer, JL
Klatt, NR
Hao, XP
Traslavina, RP
Estes, JD
Brenchley, JM
Reeves, RK
AF Evans, Tristan I.
Li, Haiying
Schafer, Jamie L.
Klatt, Nichole R.
Hao, Xing-Pei
Traslavina, Ryan P.
Estes, Jacob D.
Brenchley, Jason M.
Reeves, R. Keith
TI SIV-induced Translocation of Bacterial Products in the Liver Mobilizes
Myeloid Dendritic and Natural Killer Cells Associated With Liver Damage
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; liver disease; microbial translocation; myeloid dendritic cells;
natural killer cells; SIV
ID SIMIAN IMMUNODEFICIENCY VIRUS; IMMUNE ACTIVATION; RHESUS MACAQUES;
MICROBIAL TRANSLOCATION; HIV-INFECTION; HEPATITIS-C; NK CELLS; PIGTAIL
MACAQUES; EXPRESSION; DISEASE
AB Disruption of the mucosal epithelium during lentivirus infections permits translocation of microbial products into circulation, causing immune activation and driving disease. Although the liver directly filters blood from the intestine and is the first line of defense against gut-derived antigens, the effects of microbial products on the liver are unclear. In livers of normal macaques, minute levels of bacterial products were detectable, but increased 20-fold in simian immunodeficiency virus (SIV)-infected animals. Increased microbial products in the liver induced production of the chemoattractant CXCL16 by myeloid dendritic cells (mDCs), causing subsequent recruitment of hypercytotoxic natural killer (NK) cells expressing the CXCL16 receptor, CXCR6. Microbial accumulation, mDC activation, and cytotoxic NK cell frequencies were significantly correlated with markers of liver damage, and SIV-infected animals consistently had evidence of hepatitis and fibrosis. Collectively, these data indicate that SIV-associated accumulation of microbial products in the liver initiates a cascade of innate immune activation, resulting in liver damage.
C1 [Evans, Tristan I.; Reeves, R. Keith] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA.
[Li, Haiying; Schafer, Jamie L.; Reeves, R. Keith] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.
[Klatt, Nichole R.] Univ Washington, Dept Pharmaceut, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA.
[Hao, Xing-Pei; Traslavina, Ryan P.; Estes, Jacob D.] Frederick Natl Lab, Leidos Biomed Res Inc, AIDS & Canc Virus Program, Bethesda, MD USA.
[Brenchley, Jason M.] NIAID, Program Barrier Immun & Repair, Immunopathogenesis Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Reeves, RK (reprint author), Ctr Virol & Vaccine Res, 3 Blackfan Circle,CLS1024, Boston, MA 02215 USA.
EM rreeves@bidmc.harvard.edu
FU Center for HIV/AIDS Vaccine Immunology (CHAVI)/HIV Vaccine Trials
Network (HVTN) Early Career Investigator (National Institutes of Health
[NIH]) [U19 AI067854]; American Foundation for AIDS Research (amFAR)
[108547-53-RGRL]; Center for Aids Research (CFAR) Developmental [P30
AI060354]; NIH [R21 AI118468]; Division of Intramural Research/National
Institute of Allergy and Infectious Diseases/NIH; National Cancer
Institute, NIH [HHSN261200800001E]
FX This work was supported by Center for HIV/AIDS Vaccine Immunology
(CHAVI)/HIV Vaccine Trials Network (HVTN) Early Career Investigator
(National Institutes of Health [NIH] grant U19 AI067854), American
Foundation for AIDS Research (amFAR) (108547-53-RGRL), Center for Aids
Research (CFAR) Developmental (P30 AI060354), and NIH (R21 AI118468)
grants to R. K. R. Funding for this study was provided in part by the
Division of Intramural Research/National Institute of Allergy and
Infectious Diseases/NIH and with federal funds from the National Cancer
Institute, NIH, under Contract No. HHSN261200800001E.
NR 48
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U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2016
VL 213
IS 3
BP 361
EP 369
DI 10.1093/infdis/jiv404
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XB
UT WOS:000372436000006
PM 26238685
ER
PT J
AU Goedert, JJ
Martin, MP
Vitale, F
Lauria, C
Whitby, D
Qi, Y
Gao, XJ
Carrington, M
AF Goedert, James J.
Martin, Maureen P.
Vitale, Francesco
Lauria, Carmela
Whitby, Denise
Qi, Ying
Gao, Xiaojiang
Carrington, Mary
TI Risk of Classic Kaposi Sarcoma With Combinations of Killer
Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A
Population-Based Case-control Study
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Kaposi sarcoma; Italy; case-control study; human genetics; major
histocompatibility complex; human leukocyte antigens; natural
killer-cell immunoglobulin-like receptors
ID NASOPHARYNGEAL CARCINOMA; HLA-C; ASSOCIATIONS; KIR; HERPESVIRUS;
DISEASE; GENES; CELLS; POLYMORPHISMS; RECOGNITION
AB Background. Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS.
Methods.In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals.
Results.In both the discovery and validation cohorts, KS was associated with HLA-A*11:01 (adjusted OR for the combined cohorts, 0.4; P = .002) and HLA-C*07:01 (adjusted OR, 1.6; P = .002). Consistent associations across cohorts were also observed with activating KIR3DS1 plus HLA-B Bw4-80I and homozygosity for HLA-C group 1. With KIR3DS1 plus HLA-B Bw4-80I, the KSHV seroprevalence was 40% lower (adjusted OR for the combined cohorts, 0.6; P = .01), but the KS risk was 2-fold higher (adjusted OR, 2.1; P = .002). Similarly, the KSHV seroprevalence was 40% lower (adjusted OR, 0.6; P = .01) but the KS risk 80% higher with HLA-C group 1 homozygosity (adjusted OR, 1.8; P = .005).
Conclusions.KIR-mediated NK cell activation may decrease then risk of KSHV infection but enhance KSHV dissemination and progression to KS if infection occurs.
C1 [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Martin, Maureen P.; Qi, Ying; Gao, Xiaojiang; Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Whitby, Denise] Frederick Natl Lab Canc Res, Leidos Biomed Res, Viral Oncol Sect, AIDS & Canc Virus Program, Frederick, MD USA.
[Martin, Maureen P.; Qi, Ying; Gao, Xiaojiang; Carrington, Mary] MIT, Ragon Inst MGH, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Martin, Maureen P.; Qi, Ying; Gao, Xiaojiang; Carrington, Mary] Harvard Univ, Cambridge, MA 02138 USA.
[Vitale, Francesco] Univ Palermo, Dipartimento Igiene & Microbiol Giuseppe DAlessan, I-90133 Palermo, Italy.
[Lauria, Carmela] Lega Italiana Lotta Contro & Tumori Sez Ragusa, Ragusa, Italy.
RP Goedert, JJ (reprint author), 9609 Med Ctr Dr,Rm 6E106,MSC 9767, Bethesda, MD 20892 USA.
EM goedertj@mail.nih.gov
FU National Cancer Intramural Research Program [ZIA CP 010214]; Frederick
National Laboratory for Cancer Research [HHSN261200800001E]
FX This work was supported by the National Cancer Intramural Research
Program (ZIA CP 010214) and the Frederick National Laboratory for Cancer
Research (contract HHSN261200800001E).
NR 39
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U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2016
VL 213
IS 3
BP 432
EP 438
DI 10.1093/infdis/jiv413
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XB
UT WOS:000372436000015
PM 26268853
ER
PT J
AU Borisevich, V
Lee, B
Hickey, A
DeBuysscher, B
Broder, CC
Feldmann, H
Rockx, B
AF Borisevich, Viktoriya
Lee, Benhur
Hickey, Andrew
DeBuysscher, Blair
Broder, Christopher C.
Feldmann, Heinz
Rockx, Barry
TI Escape From Monoclonal Antibody Neutralization Affects Henipavirus
Fitness In Vitro and In Vivo
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE henipavirus; neutralizing antibody; monoclonal antibody; neutralization
escape
ID NIPAH VIRUS; ATTACHMENT GLYCOPROTEIN; HAMSTER MODEL; VIRAL ENTRY;
HENDRA; FUSION; PATHOGENESIS; RECOGNITION; PROTECTION; ACTIVATION
AB Henipaviruses are zoonotic viruses that can cause severe and acute respiratory diseases and encephalitis in humans. To date, no vaccine or treatments are approved for human use. The presence of neutralizing antibodies is a strong correlate of protection against lethal disease in animals. However, since RNA viruses are prone to high mutation rates, the possibility that these viruses will escape neutralization remains a potential concern. In the present study, we generated neutralization-escape mutants, using 6 different monoclonal antibodies, and studied the effect of these neutralization-escape mutations on in vitro and in vivo fitness. These data provide a mechanism for overcoming neutralization escape by use of cocktails of cross-neutralizing monoclonal antibodies that recognize residues within the glycoprotein that are important for virus replication and virulence.
C1 [Borisevich, Viktoriya; Rockx, Barry] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Rockx, Barry] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Borisevich, Viktoriya; Rockx, Barry] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA.
[Rockx, Barry] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA.
[DeBuysscher, Blair; Feldmann, Heinz; Rockx, Barry] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Lee, Benhur] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Hickey, Andrew; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD USA.
[Rockx, Barry] Natl Inst Publ Hlth & Environm, Dept Rare & Emerging Viral Infect & Response, Ctr Infect Dis Control, POB 1, NL-3720 BA Bilthoven, Netherlands.
RP Rockx, B (reprint author), Natl Inst Publ Hlth & Environm, Dept Rare & Emerging Viral Infect & Response, Ctr Infect Dis Control, POB 1, NL-3720 BA Bilthoven, Netherlands.
EM barry.rockx@rivm.nl
FU Department of Pathology and Institute for Human Infections and Immunity,
University of Texas Medical Branch; Intramural Research Program,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH); NIH, Department of Health and Human Services
[AI054715]
FX This work was supported by the Department of Pathology and Institute for
Human Infections and Immunity, University of Texas Medical Branch (to B.
R.); the Intramural Research Program, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (NIH); and the NIH,
Department of Health and Human Services (grant AI054715 to C. C. B.).
NR 26
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U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2016
VL 213
IS 3
BP 448
EP 455
DI 10.1093/infdis/jiv449
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XB
UT WOS:000372436000017
PM 26357909
ER
PT J
AU Harrington, WE
Fried, M
Duffy, PE
AF Harrington, Whitney E.
Fried, Michal
Duffy, Patrick E.
TI Defending the Use of Sulfadoxine-Pyrimethamine for Intermittent
Preventive Treatment for Malaria in Pregnancy: A Short-Sighted Strategy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID WOMEN; FACILITATION; PARASITES
C1 [Harrington, Whitney E.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98122 USA.
[Fried, Michal; Duffy, Patrick E.] NIAID, NIH, Rockville, MD USA.
RP Harrington, WE (reprint author), Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Pediat, Seattle, WA 98122 USA.
EM wharring@uw.edu
FU NICHD NIH HHS [T32 HD007233, 5T32HD007233-34]; NIGMS NIH HHS [T32
GM007266]
NR 7
TC 1
Z9 1
U1 2
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2016
VL 213
IS 3
BP 496
EP 497
DI 10.1093/infdis/jiv420
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DG9XB
UT WOS:000372436000022
PM 26290607
ER
PT J
AU Costello, RB
Desvigne-Nickens, P
Regan, K
Ershow, A
AF Costello, R. B.
Desvigne-Nickens, P.
Regan, K.
Ershow, A.
TI THE EVIDENCE BASE IS SCANT FOR NUTRITION'S ROLE IN HEART FAILURE: MORE
RESEARCH IS NEEDED
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research (AFMR)
CY FEB 18-20, 2016
CL New Orleans, LA
SP Amer Federat Med Res
C1 [Costello, R. B.; Regan, K.; Ershow, A.] Natl Inst Hlth, Bethesda, MD USA.
[Desvigne-Nickens, P.] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2016
VL 64
IS 2
MA 80
BP 520
EP 521
DI 10.1136/jim-2015-000035.80
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6FX
UT WOS:000372179700088
ER
PT J
AU Smith, SL
Shaner, C
Coligan, JE
Kim, S
Brand, D
Rosloniec, E
Stuart, J
Kang, A
Myers, L
AF Smith, S. L.
Shaner, C.
Coligan, J. E.
Kim, S.
Brand, D.
Rosloniec, E.
Stuart, J.
Kang, A.
Myers, L.
TI T-CELL CYTOKINE SUPPRESSION INDUCED BY STIMULATION OF LEUKOCYTE
ASSOCIATED IMMUNOGLOBULIN-LIKE RECEPTOR-1 (LAIR-1)
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research (AFMR)
CY FEB 18-20, 2016
CL New Orleans, LA
SP Amer Federat Med Res
C1 [Smith, S. L.; Shaner, C.; Kim, S.; Brand, D.; Rosloniec, E.; Stuart, J.; Kang, A.; Myers, L.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Coligan, J. E.] NIAID, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2016
VL 64
IS 2
MA 379
BP 644
EP 644
DI 10.1136/jim-2015-000035.381
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6FX
UT WOS:000372179700389
ER
PT J
AU Marchegiani, SM
Kim, S
Scanlon, V
Corsi, A
Golden, A
AF Marchegiani, S. M.
Kim, S.
Scanlon, V.
Corsi, A.
Golden, A.
TI PHENOLOGS: REDEFINING THE STUDY OF HUMAN DISEASE IN MODEL ORGANISMS
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research (AFMR)
CY FEB 18-20, 2016
CL New Orleans, LA
SP Amer Federat Med Res
C1 [Marchegiani, S. M.] Walter Reed Natl Mil Med Ctr, Silver Spring, MD USA.
[Marchegiani, S. M.; Kim, S.; Golden, A.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Scanlon, V.; Corsi, A.] Catholic Univ Amer, Washington, DC 20064 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1081-5589
EI 1708-8267
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2016
VL 64
IS 2
MA 561
BP 718
EP 718
DI 10.1136/jim-2015-000035.563
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DG6FX
UT WOS:000372179700569
ER
PT J
AU Dutzan, N
Abusleme, L
Konkel, JE
Moutsopoulos, NM
AF Dutzan, Nicolas
Abusleme, Loreto
Konkel, Joanne E.
Moutsopoulos, Niki M.
TI Isolation, Characterization and Functional Examination of the Gingival
Immune Cell Network
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Immunology; Issue 108; oral; gingival; periodontitis; oral immune cell
network; tissue immunity; oral mucosal immunity
ID PERIODONTITIS
AB Immune cell networks in tissues play a vital role in mediating local immunity and maintaining tissue homeostasis, yet little is known of the resident immune cell populations in the oral mucosa and gingiva. We have established a technique for the isolation and study of immune cells from murine gingival tissues, an area of constant microbial exposure and a vulnerable site to a common inflammatory disease, periodontitis. Our protocol allows for a detailed phenotypic characterization of the immune cell populations resident in the gingiva, even at steady state. Our procedure also yields sufficient cells with high viability for use in functional studies, such as the assessment of cytokine secretion ex vivo. This combination of phenotypic and functional characterization of the gingival immune cell network should aid towards investigating the mechanisms involved in oral immunity and periodontal homeostasis, but will also advance our understanding of the mechanisms involved in local immunopathology.
C1 [Dutzan, Nicolas; Abusleme, Loreto; Moutsopoulos, Niki M.] NIDCR, Oral Immun & Inflammat Unit, NIH, Bethesda, MD USA.
[Konkel, Joanne E.] Univ Manchester, Fac Life Sci, Manchester Immunol Grp, Manchester M13 9PL, Lancs, England.
[Konkel, Joanne E.] Univ Manchester, Manchester Collaborat Ctr Inflammat Res, Manchester M13 9PL, Lancs, England.
RP Moutsopoulos, NM (reprint author), NIDCR, Oral Immun & Inflammat Unit, NIH, Bethesda, MD USA.; Konkel, JE (reprint author), Univ Manchester, Fac Life Sci, Manchester Immunol Grp, Manchester M13 9PL, Lancs, England.; Konkel, JE (reprint author), Univ Manchester, Manchester Collaborat Ctr Inflammat Res, Manchester M13 9PL, Lancs, England.
EM joanne.konkel@manchester.ac.uk; nmoutsopoulos@dir.nidr.nih.gov
FU NIDCR; Wellcome Trust Stepping Stones Fellowship [097820/Z/11/B];
Manchester Collaborative Centre for Inflammation Research grant
FX Authors were funded in part by the intramural program of NIDCR (N.M.M)
and supported by a Wellcome Trust Stepping Stones Fellowship
(097820/Z/11/B to J.E.K) and by a Manchester Collaborative Centre for
Inflammation Research grant (to J.E.K). The authors thank Teresa Wild
for critically reviewing the manuscript.
NR 11
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Z9 0
U1 4
U2 4
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2016
IS 108
AR e53736
DI 10.3791/53736
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH0WF
UT WOS:000372504100067
ER
PT J
AU Ellis, MA
Grandinetti, G
Fichter, KM
AF Ellis, Matthew A.
Grandinetti, Giovanna
Fichter, Katye M.
TI Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical
Applications
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Chemistry; Issue 108; Quantum dots; Synthesis; Indium Phosphide;
Cellular Imaging; Nanoparticles; Fluorescence
ID IMAGE-ANALYSIS; LIVE CELLS; NANOCRYSTALS; TOXICITY; KINETICS
AB Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, quantum dots should be highly fluorescent and small/monodisperse in size. While commonly used cadmium-based quantum dots possess these qualities, they are potentially toxic due to the possible release of Cd2+ ions through nanoparticle degradation. Indium-based quantum dots, specifically InP/ZnS, have recently been explored as a viable alternative to cadmium-based quantum dots due to their relatively similar fluorescence characteristics and size. The synthesis presented here uses standard hot-injection techniques for effective nanoparticle growth; however, nanoparticle properties such as size, emission wavelength, and emission intensity can drastically change due to small changes in the reaction conditions. Therefore, reaction conditions such temperature, reaction duration, and precursor concentration should be maintained precisely to yield reproducible products. Because quantum dots are not inherently soluble in aqueous solutions, they must also undergo surface modification to impart solubility in water. In this protocol, an amphiphilic polymer is used to interact with both hydrophobic ligands on the quantum dot surface and bulk solvent water molecules. Here, a detailed protocol is provided for the synthesis of highly fluorescent InP/ZnS quantum dots that are suitable for use in biomedical applications.
C1 [Ellis, Matthew A.; Fichter, Katye M.] Missouri State Univ, Dept Chem, Columbia, MO USA.
[Grandinetti, Giovanna] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Ctr Mol Microscopy, Frederick, MD USA.
RP Fichter, KM (reprint author), Missouri State Univ, Dept Chem, Columbia, MO USA.
EM KFichter@missouristate.edu
FU Department of Chemistry at Missouri State University; Graduate College
at Missouri State University
FX The authors gratefully acknowledge the Department of Chemistry and the
Graduate College at Missouri State University for their support of this
project. We also acknowledge the Electron Microscopy Laboratory at the
Frederick National Laboratory for Cancer Research for use of their
transmission electron microscope and carbon-coated grids.
NR 24
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U1 8
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PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2016
IS 108
AR e53684
DI 10.3791/53684
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH0WF
UT WOS:000372504100061
PM 26891282
ER
PT J
AU Zhang, J
Petralia, RS
Wang, YX
Diamond, JS
AF Zhang, Jun
Petralia, Ronald S.
Wang, Ya-Xian
Diamond, Jeffrey S.
TI High-Resolution Quantitative Immunogold Analysis of Membrane Receptors
at Retinal Ribbon Synapses
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 108; retinal neurobiology; synaptic and perisynaptic
distribution; immunogold electron microscopy; retinal ganglion cell;
NMDA; AMPA; PSD-95
ID GANGLION-CELL LAYER; NMDA RECEPTORS; RAT RETINA; SYNAPTIC LOCALIZATION;
GLUTAMATE RECEPTORS; MAMMALIAN RETINA; HAIR-CELLS; AMPA; ORGANIZATION;
PROTEINS
AB Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from bipolar cells. Synaptic excitation of RGCs is mediated postsynaptically by NMDA receptors (NMDARs) and AMPA receptors (AMPARs). Physiological data have indicated that glutamate receptors at RGCs are expressed not only in postsynaptic but also in perisynaptic or extrasynaptic membrane compartments. However, precise anatomical locations for glutamate receptors at RGC synapses have not been determined. Although a high-resolution quantitative analysis of glutamate receptors at central synapses is widely employed, this approach has had only limited success in the retina. We developed a postembedding immunogold method for analysis of membrane receptors, making it possible to estimate the number, density and variability of these receptors at retinal ribbon synapses. Here we describe the tools, reagents, and the practical steps that are needed for: 1) successful preparation of retinal fixation, 2) freeze-substitution, 3) postembedding immunogold electron microscope (EM) immunocytochemistry and, 4) quantitative visualization of glutamate receptors at ribbon synapses.
C1 [Zhang, Jun; Diamond, Jeffrey S.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
[Petralia, Ronald S.; Wang, Ya-Xian] Natl Inst Deafness & Other Commun Disorders, Adv Imaging Core, NIH, Bethesda, MD USA.
RP Zhang, J (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
EM junzhang@ninds.nih.gov
RI Diamond, Jeffrey/C-1835-2015
OI Diamond, Jeffrey/0000-0002-1770-2629
FU Intramural Programs of the National Institute of Neurological Disorders
and Stroke (NINDS); National Institute on Deafness and Other
Communication Disorders (NIDCD) of the National Institutes of Health
(NIH)
FX This work was supported by the Intramural Programs of the National
Institute of Neurological Disorders and Stroke (NINDS) and National
Institute on Deafness and Other Communication Disorders (NIDCD), of the
National Institutes of Health (NIH). We thank the NINDS EM facility and
the NIDCD advanced imaging core (code # ZIC DC 000081-03) for
assistance.
NR 36
TC 0
Z9 0
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2016
IS 108
AR e53547
DI 10.3791/53547
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH0WF
UT WOS:000372504100032
ER
PT J
AU Haraldsdottir, A
Torfadottir, JE
Valdimarsdottir, UA
Aspelund, T
Harris, TB
Launer, LJ
Gudnason, V
Steingrimsdottir, L
AF Haraldsdottir, Alfheidur
Torfadottir, Johanna E.
Valdimarsdottir, Unnur A.
Aspelund, Thor
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Steingrimsdottir, Laufey
TI Fish and fish-liver oil consumption in adolescence and midlife and risk
of CHD in older women
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Fish; Fish oil; CHD; Early-life diet; Women
ID CORONARY-HEART-DISEASE; N-3 FATTY-ACIDS; YOUNG-ADULTS;
CARDIOVASCULAR-DISEASE; MORTALITY; HEALTH; COHORT; METAANALYSIS;
CHILDHOOD; BENEFITS
AB Objective To study the association of fish and fish-liver oil consumption across the lifespan with CHD later in life among Icelandic women, with special emphasis on the effects of consumption in adolescence.
Design Prevalence association study. Logistic regression was used to estimate odds ratios and 95 % confidence intervals of CHD according to fish or fish-liver oil exposure. Models were adjusted for age, education, concurrent diet and other known risk factors.
Setting The study was nested within the AGES-Reykjavik Study, conducted in Reykjavik, Iceland.
Subjects Participants were 3326 women aged 66-96 years, with available information on CHD status at entry to the study and information on fish and fish-liver oil consumption during midlife and adolescence. Dietary habits were assessed retrospectively using a validated FFQ.
Results CHD was identified in 234 (79 %) women. Compared with women with no intake of fish-liver oil in adolescence or midlife, women who consumed fish-liver oil at least three times weekly in adolescence or in midlife had a decreased risk of CHD (OR=062; 95 % CI 045, 085 and OR=068; 95 % CI 050, 094, respectively). No associations were observed between fish intake (>2 portions/week v. 2 portions/week) in adolescence or midlife and CHD in this population with high fish intake.
Conclusions Fish-liver oil consumption, from early life, may reduce the risk of CHD in older women. Lifelong nutrition may be of importance in the prevention of CHD in older women.
C1 [Haraldsdottir, Alfheidur; Torfadottir, Johanna E.; Steingrimsdottir, Laufey] Univ Iceland, Fac Food Sci & Nutr, Unit Nutr Res, IS-101 Reykjavik, Iceland.
[Haraldsdottir, Alfheidur; Torfadottir, Johanna E.; Valdimarsdottir, Unnur A.; Aspelund, Thor] Univ Iceland, Ctr Publ Hlth Sci, IS-101 Reykjavik, Iceland.
[Valdimarsdottir, Unnur A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
RP Haraldsdottir, A (reprint author), Univ Iceland, Fac Food Sci & Nutr, Unit Nutr Res, IS-101 Reykjavik, Iceland.; Haraldsdottir, A (reprint author), Univ Iceland, Ctr Publ Hlth Sci, IS-101 Reykjavik, Iceland.
EM alh1@hi.is
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU National Institutes of Health [N01-AG-12100]; Intramural Research
Program of the National Institute on Aging; Icelandic Heart Association;
Icelandic Parliament; National Institute on Aging; Icelandic Parlament
FX Financial support: This present analysis received no specific grant from
any funding agency in the public, commercial or not-for-profit sectors.
The AGES-Reykjavik Study was funded by the National Institutes of Health
(contract number N01-AG-12100); the Intramural Research Program of the
National Institute on Aging; the Icelandic Heart Association; and the
Icelandic Parliament. The funding agencies (National Institute on Aging,
Icelandic Heart Association and Icelandic Parlament) for the
AGES-Reykjavik Study had no role in the design, analysis or writing of
this article.
NR 31
TC 0
Z9 0
U1 0
U2 1
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
EI 1475-2727
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD FEB
PY 2016
VL 19
IS 2
BP 318
EP 325
DI 10.1017/S1368980015001020
PG 8
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA DH2TR
UT WOS:000372639900013
PM 25882499
ER
PT J
AU Davarpanah, N
AF Davarpanah, Nicole
TI A call to oncologists to right the wrongs of the Affordable Care Act
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
ID HEALTH-INSURANCE
C1 [Davarpanah, Nicole] NCI, Med Oncol Serv, Bethesda, MD 20892 USA.
RP Davarpanah, N (reprint author), NCI, Med Oncol Serv, Bethesda, MD 20892 USA.
EM nicole.davarpanah@gmail.com
NR 28
TC 0
Z9 0
U1 0
U2 0
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 4
EP 8
DI 10.1053/j.seminoncol.2016.01.003
PG 5
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900003
PM 26970118
ER
PT J
AU Simon, R
Geyer, S
Subramanian, J
Roychowdhury, S
AF Simon, Richard
Geyer, Susan
Subramanian, Jyothi
Roychowdhury, Sameek
TI The Bayesian basket design for genomic variant-driven phase II trials
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Basket clinical trials; Genomic clinical trials; Actionable mutations
ID CLINICAL-TRIALS; CANCER
AB Basket clinical trials are a new category of early clinical trials in which a treatment is evaluated in a population of patients with tumors of various histologic types and primary sites selected for containing specific genomic abnormalities. The objective of such studies is generally to discover histologic types in which the treatment is active. Basket trials are early discovery trials whose results should be confirmed in expanded histology specific cohorts. In this report, we develop a design for planning, monitoring, and analyzing basket trials. A website for using the new design is available at https://brbnci.shinyapps.io/BasketTrials/ and the software is available at GitHub in the "Basket Trials" repository of account brbnci. (C) 2016 The Authors Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
C1 [Simon, Richard] NCI, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
[Geyer, Susan] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Subramanian, Jyothi] Emmes Corp, Rockville, MD USA.
[Subramanian, Jyothi] Ohio State Univ, Dept Internal Med, James Canc Ctr, Columbus, OH 43210 USA.
RP Simon, R (reprint author), NCI, Div Canc Treatment & Diag, 9609 Med Ctr Dr, Rockville, MD 20892 USA.
EM rsimon@nih.gov
NR 9
TC 6
Z9 6
U1 7
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 13
EP 18
DI 10.1053/j.seminonco1.2016.01.002
PG 6
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900005
PM 26970120
ER
PT J
AU Dunn, BK
Umar, A
Richmond, E
AF Dunn, Barbara K.
Umar, Asad
Richmond, Ellen
TI Introduction: Cancer chemoprevention and its context
SO SEMINARS IN ONCOLOGY
LA English
DT Editorial Material
ID SURGICAL ADJUVANT BREAST; STAR P-2 TRIAL; PROSTATE-CANCER; MOLECULAR
TARGETS; BOWEL PROJECT; PREVENTION; TAMOXIFEN; CARCINOGENESIS;
HETEROGENEITY; RALOXIFENE
C1 [Dunn, Barbara K.] NCI, Div Canc Prevent Chemoprevent Agent, Dev Res Grp, Bethesda, MD 20892 USA.
[Umar, Asad; Richmond, Ellen] NCI, Canc Prevent Div, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA.
RP Dunn, BK (reprint author), NCI, Div Canc Prevent Chemoprevent Agent, Dev Res Grp, Bethesda, MD 20892 USA.
EM dunnb@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 28
TC 0
Z9 0
U1 2
U2 4
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 19
EP 21
DI 10.1053/j.seminoncol.2015.11.002
PG 3
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900006
PM 26970121
ER
PT J
AU Ryan, BM
Faupel-Badger, JM
AF Ryan, Brid M.
Faupel-Badger, Jessica M.
TI The hallmarks of premalignant conditions: a molecular basis for cancer
prevention
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Preneoplastic lesions; Chemoprevention; Screening; Tumor subtypes; Risk
ID TRANSGENERATIONAL EPIGENETIC INHERITANCE; RANDOMIZED CONTROLLED-TRIALS;
CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; CARCINOMA IN-SITU;
BREAST-CANCER; STEM-CELLS; LUNG-CANCER; HELICOBACTER-PYLORI;
GENE-EXPRESSION
AB The hallmarks Of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures. Published by Elsevier Inc.
C1 [Ryan, Brid M.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.
[Faupel-Badger, Jessica M.] Natl Inst Gen Med Sci, Bethesda, MD 20892 USA.
RP Ryan, BM (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA.; Faupel-Badger, JM (reprint author), Natl Inst Gen Med Sci, Bethesda, MD 20892 USA.
EM ryanb@mail.nih.gov; badgerje@mail.nih.gov
OI Ryan, Brid/0000-0003-0038-131X
FU Intramural NIH HHS [Z99 CA999999]
NR 188
TC 1
Z9 1
U1 3
U2 9
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 22
EP 35
DI 10.1053/j.seminonco1.2015.09.007
PG 14
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900007
PM 26970122
ER
PT J
AU Meerzaman, D
Dunn, BK
Lee, M
Chen, QR
Yan, CH
Ross, S
AF Meerzaman, Daoud
Dunn, Barbara K.
Lee, Maxwell
Chen, Qingrong
Yan, Chunhua
Ross, Sharon
TI The promise of omics-based approaches to cancer prevention
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Genomics; Bioinformatics; Next generation sequencing/NGS; NGS software
tools; Computational analysis
ID GENERATION SEQUENCING DATA; NUMBER VARIATION DETECTION; DNA METHYLATION
ANALYSIS; SOMATIC POINT MUTATIONS; BREAST-CANCER; RNA-SEQ; EXPRESSION
ANALYSIS; GENE-EXPRESSION; LUNG-CANCER; BIOCONDUCTOR PACKAGE
AB Cancer is a complex category of diseases caused in large part by genetic or genomic, transcriptomic, and epigenetic or epigenomic,alterations in affected cells and the surrounding microenvironment. Carcinogenesis reflects the clonal expansion of cells that progressively acquire these genetic and epigenetic alterations changes that, in turn, lead to modifications at the RNA level. Gradually advancing technology and most recently, the advent of next-generation sequencing (NGS), combined with bioinformatics analytic tools, have revolutionized our ability to interrogate cancer cells. The ultimate goal is to apply these high-throughput technologies to the various aspects of clinical cancer care: cancer-risk assessment, diagnosis, as well as target identification for treatment and prevention. In this article, we emphasize how the knowledge gained through large-scale omics-oriented approaches, with a focus on variations at the level of nucleic acids, can inform the field of chemoprevention. Published by Elsevier Inc.
C1 [Meerzaman, Daoud; Chen, Qingrong; Yan, Chunhua] NCI, Ctr Biomed Informat & Informat Technol, Computat Genom & Bioinformat Grp, NIH, Rockville, MD 20852 USA.
[Dunn, Barbara K.; Ross, Sharon] NCI, Chemoprevent Agent Dev Res Grp, NIH, Bethesda, MD 20892 USA.
[Lee, Maxwell] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Meerzaman, D (reprint author), NCI, Ctr Biomed Informat & Informat Technol, Computat Genom & Bioinformat Support Grp, NIH, 9609 Med Ctr Dr,1W466, Rockville, MD 20850 USA.
EM meerzamd@mail.nih.gov
NR 112
TC 2
Z9 2
U1 2
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 36
EP 48
DI 10.1053/j.seminoncol.2015.09.004
PG 13
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900008
PM 26970123
ER
PT J
AU Umar, A
Steele, VE
Menter, DG
Hawk, ET
AF Umar, Asad
Steele, Vernon E.
Menter, David G.
Hawk, Ernest T.
TI Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Non-steroidal anti-inflammatory drugs; (NSAID); Inflammation; Aspirin;
Cancer prevention
ID LOW-DOSE ASPIRIN; PROSTAGLANDIN-E SYNTHASE; FAMILIAL ADENOMATOUS
POLYPOSIS; RANDOMIZED CONTROLLED-TRIAL; REGULATORY T-CELLS; SPORADIC
COLORECTAL ADENOMAS; INDIVIDUAL PARTICIPANT DATA; SUPPRESSOR-CELLS;
COLON-CANCER; IN-VITRO
AB Various clinical and epidemiologic studies show that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase inhibitors (COXIBs) help prevent cancer. Since eicosanoid metabolism is the main inhibitory targets of these drugs the resulting molecular and biological impact is generally accepted. As our knowledge base and technology progress we are learning that additional targets may be involved. This review attempts to summarize these new developments in the field. Published by Elsevier Inc.
C1 [Umar, Asad; Steele, Vernon E.] NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E454,MSC 9787, Bethesda, MD 20892 USA.
[Menter, David G.; Hawk, Ernest T.] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
RP Umar, A (reprint author), NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E454,MSC 9787, Bethesda, MD 20892 USA.
EM umara@mail.nih.gov
NR 228
TC 8
Z9 9
U1 11
U2 17
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 65
EP 77
DI 10.1053/j.seminonco1.2015.09.010
PG 13
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900010
PM 26970125
ER
PT J
AU Richmond, E
Umar, A
AF Richmond, Ellen
Umar, Asad
TI Mechanisms of esophageal adenocarcinoma formation and approaches to
chemopreventive intervention
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Esophageal adenocarcinoma; Chemoprevention; Barrett's esophagus; Cell of
origin; Somatic evolution
ID HELICOBACTER-PYLORI INFECTION; SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B;
BARRETTS-ESOPHAGUS; GASTRIC CARDIA; COLON CARCINOGENESIS; GENOMIC
INSTABILITY; CANCER-RISK; DNA-DAMAGE; TUMOR MICROENVIRONMENT
AB The incidence of esophageal adenocarcinoma (EAC), a debilitating and highly lethal malignancy, has risen dramatically over the past 40 years in the United,States and other Western countries. To reverse this trend, EAC prevention and early detection efforts by clinicians, academic researchers and endoscope manufacturers have targeted Barrett's esophagus (BE), the widely accepted EAC precursor lesion. Data from surgical, endoscopic and pre-clinical investigations strongly support the malignant potential of BE. For patients with BE, the risk of developing EAC has been estimated at 11- to 125-fold greater than that of the individual at average risk. Nevertheless, screening for BE in symptomatic patients (ie, with symptoms of reflux) and surveillance in patients diagnosed with BE have not had a substantial impact on the incidence, morbidity or mortality of EAC; the overwhelming majority of EAC patients are diagnosed without a pre-operative diagnosis of BE. This article will discuss the current state of the science of esophageal adenocarcinoma prevention, including ideas about carcinogenesis and its underlying genomic and molecular level mechanisms, and suggest strategies for a systems approach to targeted preventive management. Published by Elsevier Inc.
C1 [Richmond, Ellen; Umar, Asad] NCI, Canc Prevent Div, 9609 Med Ctr Dr, Rockville, MD 20852 USA.
RP Richmond, E (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Rockville, MD 20852 USA.
EM richmone@mail.nih.gov
NR 93
TC 1
Z9 1
U1 4
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 78
EP 85
DI 10.1053/j.seminoncol.2015.12.001
PG 8
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900011
PM 26970126
ER
PT J
AU Heckman-Stoddard, BM
Gandini, S
Puntoni, M
Dunn, BK
DeCensi, A
Szabo, E
AF Heckman-Stoddard, Brandy M.
Gandini, Sara
Puntoni, Matteo
Dunn, Barbara K.
DeCensi, Andrea
Szabo, Eva
TI Repurposing old drugs to chemoprevention: the case of metformin
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Metformin; Chemoprevention; Repurposing
ID ACTIVATED PROTEIN-KINASE; PREVENTS LIVER TUMORIGENESIS; ABERRANT CRYPT
FOCI; EARLY BREAST-CANCER; FEMALE SHR MICE; LIFE-SPAN; OPPORTUNITY
NEOADJUVANT; MAMMARY CARCINOGENESIS; ENDOMETRIAL CANCER; PRESURGICAL
TRIAL
AB Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models or more recent epidemiological studies. The purpose of this paper is to examine metformin's chemopreventive potential by reviewing relevant mechanisms of action, preclinical evidence of efficacy, updated epidemiologic evidence after correction for potential biases and confounders, and recently completed and ongoing clinical trials. Although repurposing drugs with well described mechanisms of action and safety profiles is an appealing strategy for cancer prevention, there is no substitute for well executed late phase clinical trials to define efficacy and populations that are most likely to benefit from an intervention. Published by Elsevier Inc.
C1 [Heckman-Stoddard, Brandy M.; Dunn, Barbara K.; Szabo, Eva] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Gandini, Sara] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy.
[Puntoni, Matteo] EO Osped Galliera, Off Sci Director, Genoa, Italy.
[DeCensi, Andrea] EO Osped Galliera, Div Med Oncol, Genoa, Italy.
[DeCensi, Andrea] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy.
RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E-102, Bethesda, MD 20892 USA.
EM szaboe@mail.nih.gov
RI Puntoni, Matteo/J-5440-2016;
OI Puntoni, Matteo/0000-0002-7908-0626; Gandini, Sara/0000-0002-1348-4548
FU Italian Association for Cancer Research AIRC [IG 12072]; Italian
Ministry of Health [RF-2009-1532226]; Italian League Against Cancer
[14/08]
FX The study was supported by grants from the Italian Association for
Cancer Research AIRC (IG 12072), the Italian Ministry of Health
(RF-2009-1532226), and the Italian League Against Cancer (14/08) to
Andrea DeCensi. Andrea DeCensi's work was partially performed during a
sabbatical at the Division of Cancer Prevention, National Cancer
Institute, National Institutes of Health.
NR 67
TC 6
Z9 6
U1 5
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 123
EP 133
DI 10.1053/j.seminoncol.2015.09.009
PG 11
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900016
PM 26970131
ER
PT J
AU Walcott, FL
Patel, J
Lubet, R
Rodriguez, L
Calzone, KA
AF Walcott, Farzana L.
Patel, Jigar
Lubet, Ronald
Rodriguez, Luz
Calzone, Kathleen A.
TI Hereditary cancer syndromes as model systems for chemopreventive agent
development
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Chemoprevention; Hereditary cancer; Lynch syndrome; Li-Fraumeni
syndrome; HBOC
ID FAMILIAL ADENOMATOUS POLYPOSIS; NONPOLYPOSIS COLORECTAL-CANCER;
LI-FRAUMENI-SYNDROME; ALTERNATIVELY SPLICED REGION; MAMMARY
EPITHELIAL-CELLS; BRCA2 MUTATION CARRIERS; NEGATIVE BREAST-CANCER; DNA
MISMATCH REPAIR; LYNCH-SYNDROME; APC MUTATIONS
AB Research in chemoprevention has undergone a shift in emphasis for pragmatic reasons from large, phase III randomized studies to earlier phase studies focused on safety, mechanisms, and utilization of surrogate endpoints such as biomarkers instead of cancer incidence. This transition permits trials to be conducted in smaller populations and at substantially reduced costs while still yielding valuable information. This article will summarize some of the current chemoprevention challenges and the justification for the use of animal models to facilitate identification and testing of chemopreventive agents as illustrated though four inherited cancer syndromes. Preclinical models of inherited cancer syndromes serve as prototypical systems in which chemopreventive agents can be developed for ultimate application to both the sporadic and inherited cancer settings. Published by Elsevier Inc.
C1 [Walcott, Farzana L.; Patel, Jigar] NCI, NIH, Canc Prevent Div, Bethesda, MD 20892 USA.
[Lubet, Ronald] NCI, NIH, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
[Rodriguez, Luz] NCI, NIH, Canc Prevent Div, Gastrointestinal & Other Canc Res, Bethesda, MD 20892 USA.
[Calzone, Kathleen A.] NCI, NIH, Ctr Canc Res, Genet Branch, 37 Convent Dr,Bldg 37,Room 3039,MSC 4256, Bethesda, MD 20892 USA.
RP Calzone, KA (reprint author), NCI, NIH, Ctr Canc Res, Genet Branch, 37 Convent Dr,Bldg 37,Room 3039,MSC 4256, Bethesda, MD 20892 USA.; Walcott, FL (reprint author), NCI, NIH, Canc Prevent Div, Canc Prevent Fellowship Program, 9609 Med Ctr Dr,5E522, Rockville, MD 20850 USA.
EM Farzana.walcott@nih.gov; calzonek@mail.nih.gov
NR 139
TC 1
Z9 1
U1 0
U2 3
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 134
EP 145
DI 10.1053/j.seminoncol.2015.09.015
PG 12
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900017
PM 26970132
ER
PT J
AU Wojtowicz, ME
Dunn, BK
Umar, A
AF Wojtowicz, Malgorzata E.
Dunn, Barbara K.
Umar, Asad
TI Immunologic approaches to cancer prevention-current status, challenges,
and future perspectives
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Tumor immunity; Cancer immunoprevention; Tumor antigens; Cancer vaccines
ID REGULATORY T-CELLS; IMMUNE CHECKPOINT BLOCKADE; HER2/NEU PEPTIDE E75;
EARLY BREAST-CANCER; CARCINOMA IN-SITU; GM-CSF VACCINE; INTRAEPITHELIAL
NEOPLASIA; HUMAN-PAPILLOMAVIRUS; HUMAN TELOMERASE; CLINICAL-TRIAL
AB The potential of the immune system to recognize and reject tumors has been investigated for more than a century. However, only recently impressive breakthroughs in cancer immunotherapy have been seen with the use of checkpoint inhibitors. The experience with various immune-based strategies in the treatment of late cancer highlighted the importance of negative impact advanced disease has on immunity. Consequently, use of immune modulation for cancer prevention rather than therapy has gained considerable attention, with many promising results seen already in preclinical and early clinical studies. Although not without challenges, these results provide much excitement and optimism that successful cancer immunoprevention could be within our reach. In this review we will discuss the current state of predominantly primary and secondary cancer immunoprevention, relevant research, potential barriers, and future directions. Published by Elsevier Inc.
C1 [Wojtowicz, Malgorzata E.; Dunn, Barbara K.; Umar, Asad] NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E454,MSC 9787, Bethesda, MD 20892 USA.
RP Wojtowicz, ME (reprint author), NCI, Canc Prevent Div, NIH, 9609 Med Ctr Dr,Room 5E454,MSC 9787, Bethesda, MD 20892 USA.
EM wojtowim@mail.nih.gov
NR 126
TC 4
Z9 4
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 161
EP 172
DI 10.1053/j.seminoncol.2015.11.001
PG 12
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900020
PM 26970135
ER
PT J
AU Goncalves, PH
Montezuma-Rusca, JM
Yarchoan, R
Uldrick, TS
AF Goncalves, Priscila H.
Montezuma-Rusca, Jairo M.
Yarchoan, Robert
Uldrick, Thomas S.
TI Cancer prevention in HIV-infected populations
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE HIV; Neoplasms; Kaposi sarcoma; AIDS-related lymphoma; HPV vaccines
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS;
HEPATITIS-C VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; ACTIVE ANTIRETROVIRAL
THERAPY; SQUAMOUS INTRAEPITHELIAL LESIONS; NON-HODGKIN-LYMPHOMA; T-CELL
RESPONSES; CARDIOVASCULAR-DISEASE EVENTS; AIDS-DEFINING MALIGNANCIES
AB People living with human immunodeficiency virus (HIV) are living longer since the advent of effective combined antiretroviral therapy (cART). While cART substantially decreases the risk of developing some cancers, HIV-infected individuals remain at high risk for Kaposi sarcoma, lymphoma, and several solid tumors. Currently HIV-infected patients represent an aging group, and malignancies have become a leading cause of morbidity and mortality. Tailored cancer-prevention strategies are needed for this population. In this review we describe the etiologic agents and pathogenesis of common malignancies in the setting of HIV, as well as current evidence for cancer prevention strategies and screening programs. Published by Elsevier Inc.
C1 [Goncalves, Priscila H.; Yarchoan, Robert; Uldrick, Thomas S.] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Montezuma-Rusca, Jairo M.] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Uldrick, TS (reprint author), 10 Ctr Dr,Room 6N-106,MSC 1868, Bethesda, MD 20892 USA.
EM uldrickts@mail.nih.gov
FU Intramural Research Program, National Cancer Institute (NCI), NIH
FX This research was supported by the Intramural Research Program, National
Cancer Institute (NCI), NIH.
NR 234
TC 2
Z9 2
U1 2
U2 3
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
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 173
EP 188
DI 10.1053/j.seminoncol.2015.09.011
PG 16
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900021
PM 26970136
ER
PT J
AU Shoernaker, RH
Suen, CS
Holmes, CA
Fay, JR
Steele, VE
AF Shoernaker, Robert H.
Suen, Chen S.
Holmes, Cathy A.
Fay, Judith R.
Steele, Vernon E.
TI The National Cancer Institute's PREVENT Cancer Preclinical Drug
Development Program: overview, current projects, animal models, agent
development strategies, and molecular targets
SO SEMINARS IN ONCOLOGY
LA English
DT Review
DE Cancer; Preclinical support; Immunoprevention; Chemoprevention
ID CELL LUNG-CANCER; SPORADIC COLORECTAL ADENOMAS; PHASE-II TRIAL;
PANCREATIC-CANCER; FALLOPIAN-TUBE; INHALED CORTICOSTEROIDS; SEROUS
CARCINOMA; OVARIAN-CANCER; FOLLOW-UP; CARCINOGENESIS
AB The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline. Published by Elsevier Inc.
C1 [Shoernaker, Robert H.; Suen, Chen S.; Steele, Vernon E.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Holmes, Cathy A.; Fay, Judith R.] CCS Associates Inc, Mountain View, CA USA.
RP Shoernaker, RH (reprint author), 9609 Med Ctr Dr,Room 5E452,MSC 9787, Bethesda, MD 20892 USA.
EM Shoemakr@mail.nih.gov
FU PREVENT Cancer Program [HHSN261201200013I, HHSN261201200015I,
HSN261201200020I, HHSN261201200021I]
FX The authors thank the members of the External Steering Panel for advice
and guidance in developing and operating the PREVENT Cancer Program, the
many members of the Scientific Review Panel for their efforts in
providing peer review for applications submitted to the Program, and
members of the Management and Administration Committee for ongoing
efforts to ensure efficient operation of the Program. We also thank the
investigators for performing the studies referenced in this publication
which were funded by the PREVENT Cancer Program under contracts:
HHSN261201200013I; HHSN261201200015I; HSN261201200020I;
HHSN261201200021I. We also thank the staff at CCS Associates for
research support and editorial review of the manuscript.
NR 62
TC 1
Z9 2
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
EI 1532-8708
J9 SEMIN ONCOL
JI Semin. Oncol.
PD FEB
PY 2016
VL 43
IS 1
BP 189
EP 197
DI 10.1053/j.seminonco1.2015.09.008
PG 9
WC Oncology
SC Oncology
GA DH3KM
UT WOS:000372685900022
PM 26970137
ER
PT J
AU McCullough, LE
Chen, J
Cho, YH
Khankari, NK
Bradshaw, PT
White, AJ
Garbowski, G
Teitelbaum, SL
Terry, MB
Neugut, AI
Hibshoosh, H
Santella, RM
Gammon, MD
AF McCullough, Lauren E.
Chen, Jia
Cho, Yoon Hee
Khankari, Nikhil K.
Bradshaw, Patrick T.
White, Alexandra J.
Garbowski, Gail
Teitelbaum, Susan L.
Terry, Mary Beth
Neugut, Alfred I.
Hibshoosh, Hanina
Santella, Regina M.
Gammon, Marilie D.
TI DNA methylation modifies the association between obesity and survival
after breast cancer diagnosis
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Body mass index; Epigenetics; Methylation; Breast cancer; Survival
ID CPG ISLAND HYPERMETHYLATION; PROMOTER HYPERMETHYLATION; LINE-1
METHYLATION; COLORECTAL-CANCER; POOR-PROGNOSIS; LONG-ISLAND; GENE;
TUMOR; HYPOMETHYLATION; CELL
AB Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the luminometric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI a parts per thousand yen 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43-4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43-12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR = 1.81; 95 % CI = 1.19-2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45-4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation.
C1 [McCullough, Lauren E.; Gammon, Marilie D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Chen, Jia; Teitelbaum, Susan L.] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA.
[Chen, Jia] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
[Chen, Jia] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA.
[Cho, Yoon Hee; Garbowski, Gail; Santella, Regina M.] Columbia Univ, Dept Environm Hlth Sci, New York, NY 10032 USA.
[Khankari, Nikhil K.] Vanderbilt Univ, Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Bradshaw, Patrick T.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA.
[White, Alexandra J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Terry, Mary Beth; Neugut, Alfred I.] Columbia Univ, Dept Epidemiol, New York, NY 10032 USA.
[Neugut, Alfred I.] Columbia Univ, Dept Med, New York, NY 10032 USA.
[Hibshoosh, Hanina] Columbia Univ, Dept Pathol, New York, NY 10032 USA.
RP McCullough, LE (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
EM lauren.mccullough@emory.edu
FU National Cancer Institute [R25CA057726, UO1CA/ES66572, R01CA66572,
R01CA109753, 3R01CA109753-04S1]; National Institutes of Environmental
Health and Sciences [P30ES009089, P30ES10126]; Department of Defense
[BC972772]
FX This work was supported in part by Grants from the National Cancer
Institute (R25CA057726, UO1CA/ES66572, R01CA66572, R01CA109753,
3R01CA109753-04S1); the National Institutes of Environmental Health and
Sciences (P30ES009089, P30ES10126); and the Department of Defense
(BC972772).
NR 56
TC 1
Z9 1
U1 4
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD FEB
PY 2016
VL 156
IS 1
BP 183
EP 194
DI 10.1007/s10549-016-3724-0
PG 12
WC Oncology
SC Oncology
GA DG7IU
UT WOS:000372258800019
PM 26945992
ER
PT J
AU Diamond, EL
Durham, BH
Haroche, J
Yao, Z
Ma, J
Parikh, SA
Wang, ZM
Choi, J
Kim, E
Cohen-Aubart, F
Lee, SCW
Gao, YJ
Micol, JB
Campbell, P
Walsh, MP
Sylvester, B
Dolgalev, I
Aminova, O
Heguy, A
Zappile, P
Nakitandwe, J
Ganzel, C
Dalton, JD
Ellison, DW
Estrada-Veras, J
Lacouture, M
Gahl, WA
Stephens, PJ
Miller, VA
Ross, JS
Ali, SM
Briggs, SR
Fasan, O
Block, J
Heritier, S
Donadieu, J
Solit, DB
Hyman, DM
Baselga, J
Janku, F
Taylor, BS
Park, CY
Amoura, Z
Dogan, A
Emile, JF
Rosen, N
Gruber, TA
Abdel-Wahab, O
AF Diamond, Eli L.
Durham, Benjamin H.
Haroche, Julien
Yao, Zhan
Ma, Jing
Parikh, Sameer A.
Wang, Zhaoming
Choi, John
Kim, Eunhee
Cohen-Aubart, Fleur
Lee, Stanley Chun-Wei
Gao, Yijun
Micol, Jean-Baptiste
Campbell, Patrick
Walsh, Michael P.
Sylvester, Brooke
Dolgalev, Igor
Aminova, Olga
Heguy, Adriana
Zappile, Paul
Nakitandwe, Joy
Ganzel, Chezi
Dalton, James D.
Ellison, David W.
Estrada-Veras, Juvianee
Lacouture, Mario
Gahl, William A.
Stephens, Philip J.
Miller, Vincent A.
Ross, Jeffrey S.
Ali, Siraj M.
Briggs, Samuel R.
Fasan, Omotayo
Block, Jared
Heritier, Sebastien
Donadieu, Jean
Solit, David B.
Hyman, David M.
Baselga, Jose
Janku, Filip
Taylor, Barry S.
Park, Christopher Y.
Amoura, Zahir
Dogan, Ahmet
Emile, Jean-Francois
Rosen, Neal
Gruber, Tanja A.
Abdel-Wahab, Omar
TI Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
SO CANCER DISCOVERY
LA English
DT Article
ID LANGERHANS CELL HISTIOCYTOSIS; ERDHEIM-CHESTER DISEASE; POSITIVE
LUNG-CANCER; ORAL MEK INHIBITOR; CLONAL HEMATOPOIESIS; PHASE-II;
EXPRESSION PROFILES; SOMATIC MUTATIONS; GENE-EXPRESSION; HIGH PREVALENCE
AB Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans cell histiocytosis (LCH) and non-Langerhans cell histiocytosis (non-LCH), respectively. The discovery of BRAF(V600E) mutations in approximately 50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of patients with BRAF(V600E)-wild-type non-LCH are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole-exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in patients with BRAF(V600E)-wild-type non-LCH. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of patients with MAP2K1- and ARAF-mutated non-LCH using MEK and RAF inhibitors, respectively, resulted in clinical efficacy, demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders.
SIGNIFICANCE: We provide the first description of kinase fusions in systemic histiocytic neoplasms and activating ARAF and MAP2K1 mutations in non-Langerhans histiocytic neoplasms. Refractory patients with MAP2K1- and ARAF-mutant histiocytoses had clinical responses to MEK inhibition and sorafenib, respectively, highlighting the importance of comprehensive genomic analysis of these disorders. (C) 2015 AACR.
C1 [Diamond, Eli L.; Briggs, Samuel R.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA.
[Durham, Benjamin H.; Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
[Haroche, Julien; Cohen-Aubart, Fleur; Amoura, Zahir] Hop La Pitie Salpetriere, Internal Med Serv, Paris, France.
[Yao, Zhan; Gao, Yijun; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA.
[Ma, Jing; Choi, John; Walsh, Michael P.; Nakitandwe, Joy; Dalton, James D.; Ellison, David W.; Gruber, Tanja A.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Parikh, Sameer A.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA.
[Wang, Zhaoming] St Jude Childrens Res Hosp, Dept Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Kim, Eunhee; Lee, Stanley Chun-Wei; Micol, Jean-Baptiste; Sylvester, Brooke; Solit, David B.; Taylor, Barry S.; Park, Christopher Y.; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Campbell, Patrick; Gruber, Tanja A.] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Dolgalev, Igor; Aminova, Olga; Heguy, Adriana; Zappile, Paul] NYU, Langone Med Ctr, Genome Technol Ctr, New York, NY USA.
[Ganzel, Chezi] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel.
[Estrada-Veras, Juvianee; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Lacouture, Mario] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10065 USA.
[Stephens, Philip J.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.] Fdn Med, Cambridge, MA USA.
[Fasan, Omotayo] Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA.
[Block, Jared; Emile, Jean-Francois] Carolinas Pathol Grp, Hematopathol, Charlotte, NC USA.
[Heritier, Sebastien; Donadieu, Jean] Trousseau Hosp, French Reference Ctr Langerhans Cell Histiocytosi, Paris, France.
[Heritier, Sebastien; Donadieu, Jean] Univ Versailles, EA4340, Boulogne, France.
[Hyman, David M.; Baselga, Jose] Mem Sloan Kettering Canc Ctr, Dept Med, Dev Therapeut, New York, NY 10065 USA.
[Janku, Filip] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA.
[Emile, Jean-Francois] Hop Univ Ambroise Pare, AP HP, Pathol Serv, Boulogne, France.
[Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10065 USA.
RP Abdel-Wahab, O (reprint author), Mem Sloan Kettering Canc Ctr, Zuckerman 802, 802 Zuckerman Res Bldg,415 East 68th St, New York, NY 10065 USA.
EM abdelwao@mskcc.org
RI Kim, Eunhee/Q-9162-2016; Heritier, Sebastien/D-8139-2017;
OI Kim, Eunhee/0000-0001-7143-7769; Heritier,
Sebastien/0000-0003-0384-6370; Dolgalev, Igor/0000-0003-4451-126X;
Durham, Benjamin/0000-0001-8090-5448; Diamond, Eli/0000-0001-5456-5961
FU American Society of Hematology; Erdheim-Chester Disease Global Alliance;
Society of Memorial Sloan Kettering Cancer Center (MSKCC); Geoffrey
Beene Research Center of MSKCC; Translational and Integrative Medicine
Research Fund of MSKCC; Worldwide Cancer Research Fund; NIH
[1K08CA160647-01]; Josie Robertson Investigator Program; Damon Runyon
Clinical Investigator Award; Evans Foundation
FX B.H. Durham is supported by the American Society of Hematology Senior
Research Training Awards for Fellows. E.L. Diamond, D.M. Hyman, and O.
Abdel-Wahab are supported by grants from Erdheim-Chester Disease Global
Alliance, the Society of Memorial Sloan Kettering Cancer Center (MSKCC),
the Geoffrey Beene Research Center of MSKCC, and Translational and
Integrative Medicine Research Fund of MSKCC. E. Kim is supported by the
Worldwide Cancer Research Fund. O. Abdel-Wahab is supported by an NIH
K08 Clinical Investigator Award (1K08CA160647-01), the Josie Robertson
Investigator Program, and a Damon Runyon Clinical Investigator Award
with support from the Evans Foundation.
NR 47
TC 17
Z9 17
U1 2
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD FEB
PY 2016
VL 6
IS 2
BP 154
EP 165
DI 10.1158/2159-8290.CD-15-0913
PG 12
WC Oncology
SC Oncology
GA DG8HF
UT WOS:000372323000024
PM 26566875
ER
PT J
AU Schiffman, M
Burk, RD
AF Schiffman, Mark
Burk, Robert D.
TI Sholom Wacholder: In Memoriam (1955-2015)
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Biographical-Item
C1 [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
RP Schiffman, M (reprint author), Room 6E544,9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM schiffmm@exchange.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2016
VL 25
IS 2
BP 229
EP 230
DI 10.1158/1055-9965.EPI-15-1201
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6DS
UT WOS:000372173000001
PM 26795949
ER
PT J
AU Chubak, J
Garcia, MP
Burnett-Hartman, AN
Zheng, YY
Corley, DA
Halm, EA
Singal, AG
Klabunde, CN
Doubeni, CA
Kamineni, A
Levin, TR
Schottinger, JE
Green, BB
Quinn, VP
Rutter, CM
AF Chubak, Jessica
Garcia, Michael P.
Burnett-Hartman, Andrea N.
Zheng, Yingye
Corley, Douglas A.
Halm, Ethan A.
Singal, Amit G.
Klabunde, Carrie N.
Doubeni, Chyke A.
Kamineni, Aruna
Levin, Theodore R.
Schottinger, Joanne E.
Green, Beverly B.
Quinn, Virginia P.
Rutter, Carolyn M.
CA PROSPR Consortium
TI Time to Colonoscopy after Positive Fecal Blood Test in Four US Health
Care Systems
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CANCER SCREENING-PROGRAM; OCCULT BLOOD; FOLLOW-UP; COLORECTAL-CANCER;
DIAGNOSTIC EVALUATION; RANDOMIZED-TRIAL; COLON EVALUATION; TASK-FORCE;
PATIENT; IMPROVEMENT
AB Background: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy.
Methods: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan-Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models.
Results: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P < 0.001). Median days to colonoscopy ranged from 41 (95% CI, 40-41) to 174 95% CI, 123-343); percent followed-up by 12 months ranged from 58.1% 95% CI, 51.6%-63.7%) to 83.8% 95% CI, 83.4%-84.3%) and differences across health care systems were also observed at 1, 2, 3, and 6 months. Increasing age and comorbidity score were associated with lower follow-up rates.
Conclusion: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests.
Impact: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. (C) 2016 AACR.
C1 [Chubak, Jessica; Kamineni, Aruna; Green, Beverly B.] Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA.
[Garcia, Michael P.; Burnett-Hartman, Andrea N.; Zheng, Yingye] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Burnett-Hartman, Andrea N.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Corley, Douglas A.] Kaiser Permanente No Calif, Oakland, CA USA.
[Halm, Ethan A.; Singal, Amit G.] Univ Texas SW Med Ctr Dallas, Dept Internal Med & Clin Sci, Dallas, TX 75390 USA.
[Klabunde, Carrie N.] NIH, Off Director, Rockville, MD USA.
[Doubeni, Chyke A.] Univ Penn, Perelman Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA.
[Levin, Theodore R.] Kaiser Permanente Med Ctr, Walnut Creek, CA USA.
[Schottinger, Joanne E.; Quinn, Virginia P.] Kaiser Permanente So Calif, Pasadena, CA 91101 USA.
[Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA.
RP Chubak, J (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA.
EM chubak.j@ghc.org
FU National Center for Advancing Translational Sciences [KL2 TR000421]; NCI
at the NIH [U01CA163304, U54CA163261, U54CA163262, U54CA163308]
FX A. Burnett-Hartman was funded by National Center for Advancing
Translational Sciences KL2 TR000421 and NCI at the NIH U01CA163304. J.
Chubak, A. Kamineni, B.B. Green, and C.M. Rutter were funded by NCI at
the NIH U54CA163261. D.A. Corley, T.R. Levin, C.A. Doubeni, V.P. Quinn,
and J.E. Schottinger were funded by NCI at the NIH U54CA163262. A.G.
Singal and E.A. Halm were funded by NCI at the NIH U54CA163308. M.P.
Garcia and Y. Zheng were funded by NCI at the NIH U01CA163304. C.N.
Klabunde is an employee of NCI at the NIH.
NR 35
TC 10
Z9 10
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2016
VL 25
IS 2
BP 344
EP 350
DI 10.1158/1055-9965.EPI-15-0470
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6DS
UT WOS:000372173000015
PM 26843520
ER
PT J
AU Sinha, R
Chen, J
Amir, A
Vogtmann, E
Shi, JX
Inman, KS
Flores, R
Sampson, J
Knight, R
Chia, N
AF Sinha, Rashmi
Chen, Jun
Amir, Amnon
Vogtmann, Emily
Shi, Jianxin
Inman, Kristin S.
Flores, Roberto
Sampson, Joshua
Knight, Rob
Chia, Nicholas
TI Collecting Fecal Samples for Microbiome Analyses in Epidemiology Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID 16S RIBOSOMAL-RNA; COLORECTAL-CANCER; DNA EXTRACTION; PARTICIPATION;
SEQUENCES; TAXONOMY; COHORT; READS; RISK
AB Background: The need to develop valid methods for sampling and analyzing fecal specimens for microbiome studies is increasingly important, especially for large population studies.
Methods: Some of the most important attributes of any sampling method are reproducibility, stability, and accuracy. We compared seven fecal sampling methods [no additive, RNAlater, 70% ethanol, EDTA, dry swab, and pre/post development fecal occult blood test (FOBT)] using 16S rRNA microbiome profiling in two laboratories. We evaluated nine commonly used microbiome metrics: abundance of three phyla, two alpha-diversities, and four beta-diversities. We determined the technical reproducibility, stability at ambient temperature, and accuracy.
Results: Although microbiome profiles showed systematic biases according to sample method and time at ambient temperature, the highest source of variation was between individuals. All collection methods showed high reproducibility. FOBT and RNAlater resulted in the highest stability without freezing for 4 days. In comparison with no-additive samples, swab, FOBT, and 70% ethanol exhibited the greatest accuracy when immediately frozen.
Conclusions: Overall, optimal stability and reproducibility were achieved using FOBT, making this a reasonable sample collection method for 16S analysis.
Impact: Having standardized method of collecting and storing stable fecal samples will allow future investigations into the role of gut microbiota in chronic disease etiology in large population studies. (C) 2015 AACR.
C1 [Sinha, Rashmi; Vogtmann, Emily] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Jun; Chia, Nicholas] Mayo Clin, Microbiome Program, Ctr Individualized Med, Rochester, MN USA.
[Chen, Jun; Chia, Nicholas] Mayo Clin, Hlth Sci Res, Rochester, MN USA.
[Amir, Amnon; Knight, Rob] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Vogtmann, Emily] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Shi, Jianxin; Sampson, Joshua] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Inman, Kristin S.] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA.
[Flores, Roberto] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Knight, Rob] Univ Calif San Diego, Dept Comp Sci & Engn, San Diego, CA 92103 USA.
[Chia, Nicholas] Mayo Clin, Dept Surg, Rochester, MN USA.
[Chia, Nicholas] Mayo Coll, Biomed Engn & Physiol, Rochester, MN USA.
RP Sinha, R (reprint author), NCI, 9609 Med Ctr Dr,RM 6E336 MSC 9768, Bethesda, MD 20892 USA.
EM sinhar@exchange.nih.gov; chia.nicholas@mayo.edu
FU Intramural Research Program of the NCI; NIH [1R01CA179243]; Howard
Hughes Medical Institute; Sloan Foundation
FX This work was supported by the Intramural Research Program of the NCI.
N. Chia was supported by a grant from the NIH (1R01CA179243), and R.
Knight was supported by the Howard Hughes Medical Institute and the
Sloan Foundation awards.
NR 33
TC 11
Z9 11
U1 11
U2 18
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2016
VL 25
IS 2
BP 407
EP 416
DI 10.1158/1055-9965.EPI-15-0951
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DG6DS
UT WOS:000372173000023
PM 26604270
ER
PT J
AU Lopez, AM
Pruthi, S
Boughey, JC
Perloff, M
Hsu, CH
Lang, JE
Ley, M
Frank, D
Taverna, JA
Chow, HHS
AF Lopez, Ana Maria
Pruthi, Sandhya
Boughey, Judy C.
Perloff, Marjorie
Hsu, Chiu-Hsieh
Lang, Julie E.
Ley, Michele
Frank, Denise
Taverna, Josephine A.
Chow, H-H. Sherry
TI Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens
in Postmenopausal Women with Increased Breast Cancer Risk
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; ADJUVANT HORMONAL-THERAPY;
TANDEM MASS-SPECTROMETRY; PLASMA ESTROGEN-LEVELS; AROMATASE INHIBITORS;
PHASE-I; ANASTROZOLE; TAMOXIFEN; PREVENTION
AB Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability. (C) 2015 AACR.
C1 [Lopez, Ana Maria] Univ Utah, Dept Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Pruthi, Sandhya] Mayo Clin, Dept Internal Med, Rochester, MN USA.
[Boughey, Judy C.] Mayo Clin, Dept Surg, Rochester, MN USA.
[Perloff, Marjorie] NCI, Canc Prevent Div, Rockville, MD USA.
[Hsu, Chiu-Hsieh; Ley, Michele; Frank, Denise; Taverna, Josephine A.; Chow, H-H. Sherry] Univ Arizona, Ctr Canc, 1515 N Campbell Ave, Tucson, AZ 85724 USA.
[Lang, Julie E.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Surg, Los Angeles, CA 90033 USA.
RP Chow, HHS (reprint author), Univ Arizona, Ctr Canc, 1515 N Campbell Ave, Tucson, AZ 85724 USA.
EM schow@email.arizona.edu
OI Lopez, Ana Maria/0000-0002-2759-5353
FU NCI [N01CN35158]; Arizona Cancer Center Support Grant [CA023074]
FX This work was supported by a contract (N01CN35158 to H-H.S. Chow) from
the NCI and the Arizona Cancer Center Support Grant (CA023074). Clinical
Trial Registration: clinicaltrials.gov identifier: NCT01077453.
NR 29
TC 0
Z9 0
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD FEB
PY 2016
VL 9
IS 2
BP 142
EP 148
DI 10.1158/1940-6207.CAPR-15-0322
PG 7
WC Oncology
SC Oncology
GA DG3YC
UT WOS:000372006100005
PM 26667449
ER
PT J
AU Gierach, GL
Patel, DA
Pfeiffer, RM
Figueroa, JD
Linville, L
Papathomas, D
Johnson, JM
Chicoine, RE
Herschorn, SD
Shepherd, JA
Wang, J
Malkov, S
Vacek, PM
Weaver, DL
Fan, B
Mahmoudzadeh, AP
Palakal, M
Xiang, J
Oh, H
Horne, HN
Sprague, BL
Hewitt, SM
Brinton, LA
Sherman, ME
AF Gierach, Gretchen L.
Patel, Deesha A.
Pfeiffer, Ruth M.
Figueroa, Jonine D.
Linville, Laura
Papathomas, Daphne
Johnson, Jason M.
Chicoine, Rachael E.
Herschorn, Sally D.
Shepherd, John A.
Wang, Jeff
Malkov, Serghei
Vacek, Pamela M.
Weaver, Donald L.
Fan, Bo
Mahmoudzadeh, Amir Pasha
Palakal, Maya
Xiang, Jackie
Oh, Hannah
Horne, Hisani N.
Sprague, Brian L.
Hewitt, Stephen M.
Brinton, Louise A.
Sherman, Mark E.
TI Relationship of Terminal Duct Lobular Unit Involution of the Breast with
Area and Volume Mammographic Densities
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID CANCER RISK; TISSUE COMPOSITION; FIBROGLANDULAR TISSUE; ASSOCIATION;
AGE; PATTERNS; BIOPSY; WOMEN
AB Elevated mammographic density (MD) is an established breast cancer risk factor. Reduced involution of terminal duct lobular units (TDLU), the histologic source of most breast cancers, has been associated with higher MD and breast cancer risk. We investigated relationships of TDLU involution with area and volumetric MD, measured throughout the breast and surrounding biopsy targets (perilesional). Three measures inversely related to TDLU involution (TDLU count/mm(2), median TDLU span, median acini count/TDLU) assessed in benign diagnostic biopsies from 348 women, ages 40-65, were related to MD area (quantified with thresholding software) and volume (assessed with a density phantom) by analysis of covariance, stratified by menopausal status and adjusted for confounders. Among premenopausal women, TDLU count was directly associated with percent perilesional MD (P trend = 0.03), but not with absolute dense area/volume. Greater TDLU span was associated with elevated percent dense area/volume (P trend<0.05) and absolute perilesionalMD (P = 0.003). Acini count was directly associated with absolute perilesional MD (P = 0.02). Greater TDLU involution (all metrics) was associated with increased nondense area/volume (P trend <= 0.04). Among postmenopausal women, TDLU measures were not significantly associated with MD. Among premenopausal women, reduced TDLU involution was associated with higher area and volumetric MD, particularly in perilesional parenchyma. Data indicating that TDLU involution and MD are correlated markers of breast cancer risk suggest that associations of MD with breast cancer may partly reflect amounts of at-risk epithelium. If confirmed, these results could suggest a prevention paradigm based on enhancing TDLU involution and monitoring efficacy by assessing MD reduction. (C)2015 AACR.
C1 [Gierach, Gretchen L.; Patel, Deesha A.; Figueroa, Jonine D.; Linville, Laura; Papathomas, Daphne; Palakal, Maya; Xiang, Jackie; Oh, Hannah; Horne, Hisani N.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chicoine, Rachael E.; Herschorn, Sally D.; Vacek, Pamela M.; Weaver, Donald L.; Sprague, Brian L.] Univ Vermont, Burlington, VT USA.
[Johnson, Jason M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Shepherd, John A.; Wang, Jeff; Malkov, Serghei; Fan, Bo; Mahmoudzadeh, Amir Pasha] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Patel, Deesha A.] Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Evanston, IL USA.
[Figueroa, Jonine D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Linville, Laura] George Washington Sch Med & Hlth Studies, Washington, DC USA.
[Wang, Jeff] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan.
[Horne, Hisani N.] US FDA, Silver Spring, MD USA.
RP Gierach, GL (reprint author), NCI, 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov
RI Gierach, Gretchen/E-1817-2016;
OI Gierach, Gretchen/0000-0002-0165-5522; Hewitt,
Stephen/0000-0001-8283-1788
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics of the NCI; NCI [U01CA70013, U54CA163303, 1R21CA157254]; Breast
Cancer Research Stamp Funds from the NCI [U01CA70013, U54CA163303,
1R21CA157254]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the NCI. Breast Cancer
Research Stamp Funds and cooperative agreement U01CA70013 and
U54CA163303 (to B.M. Geller, P.M. Vacek, D.L. Weaver, R.E. Chicoine,
S.D. Herschorn, and B. Sprague) and 1R21CA157254 (to J.A. Shepherd, S.
Malkov, B. Fan, and A.P. Mahmoudzadeh) from the NCI funded some of the
data collection and image analysis for this study.
NR 39
TC 7
Z9 7
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD FEB
PY 2016
VL 9
IS 2
BP 149
EP 158
DI 10.1158/1940-6207.CAPR-15-0282
PG 10
WC Oncology
SC Oncology
GA DG3YC
UT WOS:000372006100006
PM 26645278
ER
PT J
AU Wang, MJ
Devarajan, K
Singal, AG
Marrero, JA
Dai, JL
Feng, ZD
Rinaudo, JAS
Srivastava, S
Evans, A
Hann, HW
Lai, YZ
Yang, HS
Block, TM
Mehta, A
AF Wang, Mengjun
Devarajan, Karthik
Singal, Amit G.
Marrero, Jorge A.
Dai, Jianliang
Feng, Ziding
Rinaudo, Jo Ann S.
Srivastava, Sudhir
Evans, Alison
Hann, Hie-Won
Lai, Yinzhi
Yang, Hushan
Block, Timothy M.
Mehta, Anand
TI The Doylestown Algorithm: A Test to Improve the Performance of AFP in
the Detection of Hepatocellular Carcinoma
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ALPHA-FETOPROTEIN LEVELS; CHRONIC HEPATITIS-B; HALT-C TRIAL; FUCOSYLATED
GLYCOPROTEINS; PROTEOMIC ANALYSIS; RISK-FACTORS; SERUM; BIOMARKERS;
CIRRHOSIS; DISEASE
AB Biomarkers for the early diagnosis of hepatocellular carcinoma (HCC) are needed to decrease mortality from this cancer. However, as new biomarkers have been slow to be brought to clinical practice, we have developed a diagnostic algorithm that utilizes commonly used clinical measurements in those at risk of developing HCC. Briefly, as alpha-fetoprotein (AFP) is routinely used, an algorithm that incorporated AFP values along with four other clinical factors was developed. Discovery analysis was performed on electronic data from patients who had liver disease (cirrhosis) alone or HCC in the background of cirrhosis. The discovery set consisted of 360 patients from two independent locations. A logistic regression algorithm was developed that incorporated log-transformed AFP values with age, gender, alkaline phosphatase, and alanine aminotransferase levels. We define this as the Doylestown algorithm. In the discovery set, the Doylestown algorithm improved the overall performance of AFP by 10%. In subsequent external validation in over 2,700 patients from three independent sites, the Doylestown algorithm improved detection of HCC as compared with AFP alone by 4% to 20%. In addition, at a fixed specificity of 95%, the Doylestown algorithm improved the detection of HCC as compared with AFP alone by 2% to 20%. In conclusion, the Doylestown algorithm consolidates clinical laboratory values, with age and gender, which are each individually associated with HCC risk, into a single value that can be used for HCC risk assessment. As such, it should be applicable and useful to the medical community that manages those at risk for developing HCC. (C) 2015 AACR.
C1 [Wang, Mengjun; Mehta, Anand] Drexel Univ, Coll Med, Room 18307 New Coll Bldg,245 North 15th St, Philadelphia, PA 19102 USA.
[Devarajan, Karthik] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Singal, Amit G.; Marrero, Jorge A.] Univ Texas Southwestern, Div Digest & Liver Dis, Dallas, TX USA.
[Dai, Jianliang; Feng, Ziding] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Div Quantitat Sci, Houston, TX 77030 USA.
[Rinaudo, Jo Ann S.; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Evans, Alison] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19102 USA.
[Hann, Hie-Won; Lai, Yinzhi; Yang, Hushan] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Block, Timothy M.] Baruch Blumberg Inst, Doylestown, PA USA.
RP Mehta, A (reprint author), Drexel Univ, Coll Med, Room 18307 New Coll Bldg,245 North 15th St, Philadelphia, PA 19102 USA.
EM anand.mehta@drexelmed.edu
FU NCI [R01 CA120206, U01 CA168856, P30 CA 06927]; Hepatitis B Foundation;
Commonwealth of Pennsylvania
FX This work was supported by grants R01 CA120206 (A. Mehta), U01 CA168856
(A. Mehta), and P30 CA 06927 (K. Devarajan) from the NCI, the Hepatitis
B Foundation, and an appropriation from The Commonwealth of Pennsylvania
(T.M. Block).
NR 31
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD FEB
PY 2016
VL 9
IS 2
BP 172
EP 179
DI 10.1158/1940-6207.CAPR-15-0186
PG 8
WC Oncology
SC Oncology
GA DG3YC
UT WOS:000372006100008
PM 26712941
ER
PT J
AU Sessa, R
Yuen, D
Wan, S
Rosner, M
Padmanaban, P
Ge, SK
Smith, A
Fletcher, R
Baudhuin-Kessel, A
Yamaguchi, TP
Lang, RA
Chen, L
AF Sessa, Roberto
Yuen, Don
Wan, Stephanie
Rosner, Michael
Padmanaban, Preethi
Ge, Shaokui
Smith, April
Fletcher, Russell
Baudhuin-Kessel, Ariane
Yamaguchi, Terry P.
Lang, Richard A.
Chen, Lu
TI Monocyte-derived Wnt5a regulates inflammatory lymphangiogenesis
SO CELL RESEARCH
LA English
DT Letter
ID DISEASE; LYMPHATICS
C1 [Sessa, Roberto; Yuen, Don; Wan, Stephanie; Rosner, Michael; Padmanaban, Preethi; Chen, Lu] Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA.
[Sessa, Roberto; Yuen, Don; Wan, Stephanie; Rosner, Michael; Padmanaban, Preethi; Ge, Shaokui; Chen, Lu] Univ Calif Berkeley, Ctr Eye Dis & Dev, Program Vis Sci, Berkeley, CA 94720 USA.
[Sessa, Roberto; Yuen, Don; Wan, Stephanie; Rosner, Michael; Padmanaban, Preethi; Ge, Shaokui; Chen, Lu] Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
[Smith, April; Lang, Richard A.] Cincinnati Childrens Hosp Med Ctr, Visual Syst Grp, Cincinnati, OH 45229 USA.
[Fletcher, Russell; Baudhuin-Kessel, Ariane] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
[Yamaguchi, Terry P.] NIH, Ctr Canc Res, Frederick, MD USA.
RP Chen, L (reprint author), Univ Calif Berkeley, Vis Sci Grad Grp, Berkeley, CA 94720 USA.; Chen, L (reprint author), Univ Calif Berkeley, Ctr Eye Dis & Dev, Program Vis Sci, Berkeley, CA 94720 USA.; Chen, L (reprint author), Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA.
EM chenlu@berkeley.edu
FU NEI NIH HHS [R01 EY017392, R01 EY021636]
NR 12
TC 2
Z9 2
U1 1
U2 1
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD FEB
PY 2016
VL 26
IS 2
BP 262
EP 265
DI 10.1038/cr.2015.105
PG 4
WC Cell Biology
SC Cell Biology
GA DG4SH
UT WOS:000372062300014
PM 26337801
ER
PT J
AU Lee, MR
Rohn, MCH
Tanda, G
Leggio, L
AF Lee, Mary R.
Rohn, Matthew C. H.
Tanda, Gianluigi
Leggio, Lorenzo
TI Targeting the Oxytocin System to Treat Addictive Disorders: Rationale
and Progress to Date
SO CNS DRUGS
LA English
DT Article
ID CONDITIONED PLACE PREFERENCE; CHRONIC MORPHINE TREATMENT;
COCAINE-SEEKING BEHAVIOR; MEDIAL PREFRONTAL CORTEX; PAIR BOND FORMATION;
PROLYL-D-LEUCINE; INTRANASAL OXYTOCIN; NUCLEUS-ACCUMBENS;
NEUROHYPOPHYSEAL HORMONES; SUBTHALAMIC NUCLEUS
AB The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning, and memory processes. As such, there is increasing interest in oxytocin as a potential treatment for addictions. The endogenous oxytocin system is itself altered by short- or long-term exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin administration on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis, and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction.
C1 [Lee, Mary R.; Rohn, Matthew C. H.; Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA.
[Lee, Mary R.; Rohn, Matthew C. H.; Leggio, Lorenzo] NIDA, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA.
[Tanda, Gianluigi] NIDA, Medicat Dev Program, Mol Targets & Medicat Discovery Branch, Baltimore, MD 20892 USA.
[Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA.
RP Lee, MR (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA.; Lee, MR (reprint author), NIDA, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA.
EM leemary@mail.nih.gov
RI Tanda, Gianluigi/B-3318-2009; Leggio, Lorenzo/M-2972-2016
OI Tanda, Gianluigi/0000-0001-9526-9878;
FU Bench-to-Bedside (B2B) Grant - National Institutes of Health (NIH)
Office of Behavioral and Social Sciences Research (OBSSR); Division of
Intramural Clinical and Biological Research of the National Institute on
Alcohol Abuse and Alcoholism (NIAAA) [ZIA-AA000218]; Intramural Research
Program (IRP) of the National Institute on Drug Abuse (NIDA)
[ZIA-AA000218]; Medication Development Program of the NIDA IRP
FX The work was supported by (1) a Bench-to-Bedside (B2B) Grant [primary
investigator [PI]: Lee) funded by the National Institutes of Health
(NIH) Office of Behavioral and Social Sciences Research (OBSSR); (2) NIH
intramural funding ZIA-AA000218 (Section on Clinical
Psychoneuroendocrinology and Neuropsychopharmacology; PI: Leggio),
jointly supported by the Division of Intramural Clinical and Biological
Research of the National Institute on Alcohol Abuse and Alcoholism
(NIAAA) and the Intramural Research Program (IRP) of the National
Institute on Drug Abuse (NIDA); and (3) the Medication Development
Program of the NIDA IRP. The content of this review is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 105
TC 3
Z9 3
U1 5
U2 16
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1172-7047
EI 1179-1934
J9 CNS DRUGS
JI CNS Drugs
PD FEB
PY 2016
VL 30
IS 2
BP 109
EP 123
DI 10.1007/s40263-016-0313-z
PG 15
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DG2VR
UT WOS:000371928200003
PM 26932552
ER
PT J
AU Pulanic, D
Desnica, L
Vrhovac, R
Nemet, D
Wolff, D
Greinix, H
Pavletic, SZ
AF Pulanic, Drazen
Desnica, Lana
Vrhovac, Radovan
Nemet, Damir
Wolff, Daniel
Greinix, Hildegard
Pavletic, Steven Z.
TI Chronic graft-vs-host disease in 2016: a major challenge and an
opportunity
SO CROATIAN MEDICAL JOURNAL
LA English
DT Editorial Material
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; MEASURING
THERAPEUTIC RESPONSE; CLINICAL-TRIALS; ANCILLARY THERAPY; SUPPORTIVE
CARE; CRITERIA; DIAGNOSIS; DESIGN; BLOOD
C1 [Pulanic, Drazen; Desnica, Lana; Vrhovac, Radovan; Nemet, Damir] Univ Hosp Ctr Zagreb, Div Hematol, Dept Internal Med, Zagreb, Croatia.
[Pulanic, Drazen; Vrhovac, Radovan; Nemet, Damir] Univ Zagreb, Sch Med, Zagreb 41001, Croatia.
[Pulanic, Drazen; Nemet, Damir] Josip Juraj Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia.
[Wolff, Daniel] Univ Regensburg, Med Ctr, Dept Internal Med 3, D-93053 Regensburg, Germany.
[Greinix, Hildegard] Med Univ Graz, Div Hematol, Graz, Austria.
[Pavletic, Steven Z.] NCI, Graft Versus Host & Autoimmun Sect, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Pulanic, D (reprint author), Univ Hosp Ctr Zagreb, Div Hematol, Dept Internal Med, Zagreb, Croatia.; Pulanic, D (reprint author), Univ Zagreb, Sch Med, Zagreb 41001, Croatia.; Pulanic, D (reprint author), Josip Juraj Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia.
EM dpulanic@yahoo.com
NR 17
TC 0
Z9 0
U1 0
U2 0
PU MEDICINSKA NAKLADA
PI ZAGREB
PA VLASKA 69, HR-10000 ZAGREB, CROATIA
SN 0353-9504
EI 1332-8166
J9 CROAT MED J
JI Croat. Med. J.
PD FEB
PY 2016
VL 57
IS 1
BP 1
EP 3
DI 10.3325/cmj.2016.57.1
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DG2RS
UT WOS:000371916000001
PM 26935608
ER
PT J
AU Peric, Z
Desnica, L
Durakovic, N
Ostojic, A
Pulanic, D
Serventi-Seiwerth, R
Prenc, E
Basak, G
Vrhovac, R
Pavletic, SZ
Nemet, D
AF Peric, Zinaida
Desnica, Lana
Durakovic, Nadira
Ostojic, Alen
Pulanic, Drazen
Serventi-Seiwerth, Ranka
Prenc, Ema
Basak, Grzegorz
Vrhovac, Radovan
Pavletic, Steven Z.
Nemet, Damir
TI Which questionnaires should we use to evaluate quality of life in
patients with chronic graft-vs-host disease?
SO CROATIAN MEDICAL JOURNAL
LA English
DT Article
ID HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT;
BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; LONG-TERM SURVIVORS;
CONTROLLED CLINICAL-TRIAL; FUNCTIONAL STATUS; HEALTH SURVEY;
EUROPEAN-ORGANIZATION; EXERCISE PROGRAM
AB Aim To investigate the ability of two standard quality of life (QOL) questionnaires - The Short Form (36-item) Health Survey (SF-36) and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30) to evaluate QOL in patients with chronic graft-vs-host disease (cGVHD) graded according to National Institutes of Health (NIH) consensus criteria.
Methods In this cross-sectional study, QOL was assessed in patients who underwent allogeneic stem cell transplantation (allo-SCT) at the University Hospital Centre Zagreb and were alive and in complete remission for more than one year after allo-SCT.
Results The study included 58 patients, 38 patients with cGVHD and 20 controls, patients without cGVHD. Patients with cGVHD scored according to the NIH criteria had significantly lower scores of global health status and lower QOL on all SF-36 subscales and most of QLQ C30 functional subscales (P < 0.050 for all comparisons). Furthermore, patients with active cGVHD had significantly lower QOL scores than patients with inactive cGVHD, and this difference was most evident in physical functioning subscale of SF-36 (P = 0.0007) and social functioning subscale of QLQ C30 (P = 0.009).
Conclusion cGVHD scored according to the NIH criteria is correlated with patient-reported QOL, particularly in the physical domains as detected by SF-36. QLQ C30 questionnaire adds more information on social functioning and should be used as a valuable tool in the evaluation of social domains in cGVHD patients.
C1 [Peric, Zinaida; Durakovic, Nadira; Pulanic, Drazen; Vrhovac, Radovan; Nemet, Damir] Univ Zagreb, Sch Med, Dept Internal Med, Zagreb 41001, Croatia.
[Desnica, Lana; Durakovic, Nadira; Ostojic, Alen; Pulanic, Drazen; Serventi-Seiwerth, Ranka; Vrhovac, Radovan; Nemet, Damir] Univ Hosp Ctr Zagreb, Div Hematol, Dept Internal Med, Zagreb, Croatia.
[Pulanic, Drazen] JJ Strossmayer Univ Osijek, Fac Med Osijek, Osijek, Croatia.
[Prenc, Ema] Croatian Cooperat Grp Hematol Dis, Zagreb, Croatia.
[Basak, Grzegorz] Med Univ Warsaw, Dept Hematol Oncol & Internal Dis, Warsaw, Poland.
[Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA.
RP Peric, Z (reprint author), Univ Zagreb, Sch Med, Dept Internal Med, Zagreb 41001, Croatia.
EM zina_peric@yahoo.com
FU Unity Through Knowledge Fund project entitled "Clinical And Biological
Factors Determining Severity and Activity of Chronic Graft-Versus-Host
Disease After Allogeneic Hematopoietic Stem Cell Transplantation";
Center for Cancer Research; National Cancer Institute, National
Institutes of Health, USA
FX This work was funded by the Unity Through Knowledge Fund project
entitled "Clinical And Biological Factors Determining Severity and
Activity of Chronic Graft-Versus-Host Disease After Allogeneic
Hematopoietic Stem Cell Transplantation". It was also partly supported
by the Center for Cancer Research, the intramural program of the
National Cancer Institute, National Institutes of Health, USA.
NR 50
TC 1
Z9 1
U1 1
U2 2
PU MEDICINSKA NAKLADA
PI ZAGREB
PA VLASKA 69, HR-10000 ZAGREB, CROATIA
SN 0353-9504
EI 1332-8166
J9 CROAT MED J
JI Croat. Med. J.
PD FEB
PY 2016
VL 57
IS 1
BP 6
EP 15
DI 10.3325/cmj.2016.57.6
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DG2RS
UT WOS:000371916000003
PM 26935610
ER
PT J
AU Wang, ZM
Seow, WJ
Shiraishi, K
Hsiung, CA
Matsuo, K
Liu, J
Chen, KX
Yamji, T
Yang, Y
Chang, IS
Wu, C
Hong, YC
Burdett, L
Wyatt, K
Chung, CC
Li, SCA
Yeager, M
Hutchinson, A
Hu, W
Caporaso, N
Landi, MT
Chatterjee, N
Song, MS
Fraumeni, JF
Kohno, T
Yokota, J
Kunitoh, H
Ashikawa, K
Momozawa, Y
Daigo, Y
Mitsudomi, T
Yatabe, Y
Hida, T
Hu, ZB
Dai, JC
Ma, HX
Jin, GF
Song, B
Wang, ZH
Cheng, SS
Yin, ZH
Li, XL
Ren, YW
Guan, P
Chang, J
Tan, W
Chen, CJ
Chang, GC
Tsai, YH
Su, WC
Chen, KY
Huang, MS
Chen, YM
Zheng, H
Li, HX
Cui, P
Guo, H
Xu, P
Liu, L
Iwasaki, M
Shimazu, T
Tsugane, S
Zhu, JJ
Jiang, GN
Fei, K
Park, JY
Kim, YH
Sung, JS
Park, KH
Kim, YT
Jung, YJ
Kang, CH
Park, IK
Kim, HN
Jeon, HS
Choi, JE
Choi, YY
Kim, JH
Oh, IJ
Kim, YC
Sung, SW
Kim, JS
Yoon, HI
Kweon, SS
Shin, MH
Seow, A
Chen, Y
Lim, WY
Liu, JJ
Wong, MP
Lee, VHF
Bassig, BA
Tucker, M
Berndt, SI
Chow, WH
Ji, BT
Wang, JW
Xu, J
Sihoe, ADL
Ho, JCM
Chan, JKC
Wang, JC
Lu, DR
Zhao, XY
Zhao, ZH
Wu, JJ
Chen, HY
Jin, L
Wei, FS
Wu, GP
An, SJ
Zhang, XC
Su, J
Wu, YL
Gao, YT
Xiang, YB
He, XZ
Li, JH
Zheng, W
Shu, XO
Cai, QY
Klein, R
Pao, W
Lawrence, C
Hosgood, HD
Hsiao, CF
Chien, LH
Chen, YH
Chen, CH
Wang, WC
Chen, CY
Wang, CL
Yu, CJ
Chen, HL
Su, YC
Tsai, FY
Chen, YS
Li, YJ
Yang, TY
Lin, CC
Yang, PC
Wu, TC
Lin, DX
Zhou, BS
Yu, JM
Shen, HB
Kubo, M
Chanock, SJ
Rothman, N
Lan, Q
AF Wang, Zhaoming
Seow, Wei Jie
Shiraishi, Kouya
Hsiung, Chao A.
Matsuo, Keitaro
Liu, Jie
Chen, Kexin
Yamji, Taiki
Yang, Yang
Chang, I-Shou
Wu, Chen
Hong, Yun-Chul
Burdett, Laurie
Wyatt, Kathleen
Chung, Charles C.
Li, Shengchao A.
Yeager, Meredith
Hutchinson, Amy
Hu, Wei
Caporaso, Neil
Landi, Maria T.
Chatterjee, Nilanjan
Song, Minsun
Fraumeni, Joseph F., Jr.
Kohno, Takashi
Yokota, Jun
Kunitoh, Hideo
Ashikawa, Kyota
Momozawa, Yukihide
Daigo, Yataro
Mitsudomi, Tetsuya
Yatabe, Yasushi
Hida, Toyoaki
Hu, Zhibin
Dai, Juncheng
Ma, Hongxia
Jin, Guangfu
Song, Bao
Wang, Zhehai
Cheng, Sensen
Yin, Zhihua
Li, Xuelian
Ren, Yangwu
Guan, Peng
Chang, Jiang
Tan, Wen
Chen, Chien-Jen
Chang, Gee-Chen
Tsai, Ying-Huang
Su, Wu-Chou
Chen, Kuan-Yu
Huang, Ming-Shyan
Chen, Yuh-Min
Zheng, Hong
Li, Haixin
Cui, Ping
Guo, Huan
Xu, Ping
Liu, Li
Iwasaki, Motoki
Shimazu, Taichi
Tsugane, Shoichiro
Zhu, Junjie
Jiang, Gening
Fei, Ke
Park, Jae Yong
Kim, Yeul Hong
Sung, Jae Sook
Park, Kyong Hwa
Kim, Young Tae
Jung, Yoo Jin
Kang, Chang Hyun
Park, In Kyu
Kim, Hee Nam
Jeon, Hyo-Sung
Choi, Jin Eun
Choi, Yi Young
Kim, Jin Hee
Oh, In-Jae
Kim, Young-Chul
Sung, Sook Whan
Kim, Jun Suk
Yoon, Ho-Il
Kweon, Sun-Seog
Shin, Min-Ho
Seow, Adeline
Chen, Ying
Lim, Wei-Yen
Liu, Jianjun
Wong, Maria Pik
Lee, Victor Ho Fun
Bassig, Bryan A.
Tucker, Margaret
Berndt, Sonja I.
Chow, Wong-Ho
Ji, Bu-Tian
Wang, Junwen
Xu, Jun
Sihoe, Alan Dart Loon
Ho, James C. M.
Chan, John K. C.
Wang, Jiu-Cun
Lu, Daru
Zhao, Xueying
Zhao, Zhenhong
Wu, Junjie
Chen, Hongyan
Jin, Li
Wei, Fusheng
Wu, Guoping
An, She-Juan
Zhang, Xu-Chao
Su, Jian
Wu, Yi-Long
Gao, Yu-Tang
Xiang, Yong-Bing
He, Xingzhou
Li, Jihua
Zheng, Wei
Shu, Xiao-Ou
Cai, Qiuyin
Klein, Robert
Pao, William
Lawrence, Charles
Hosgood, H. Dean, III
Hsiao, Chin-Fu
Chien, Li-Hsin
Chen, Ying-Hsiang
Chen, Chung-Hsing
Wang, Wen-Chang
Chen, Chih-Yi
Wang, Chih-Liang
Yu, Chong-Jen
Chen, Hui-Ling
Su, Yu-Chun
Tsai, Fang-Yu
Chen, Yi-Song
Li, Yao-Jen
Yang, Tsung-Ying
Lin, Chien-Chung
Yang, Pan-Chyr
Wu, Tangchun
Lin, Dongxin
Zhou, Baosen
Yu, Jinming
Shen, Hongbing
Kubo, Michiaki
Chanock, Stephen J.
Rothman, Nathaniel
Lan, Qing
TI Meta-analysis of genome-wide association studies identifies multiple
lung cancer susceptibility loci in never-smoking Asian women
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RECOMBINATION HOTSPOTS; JAPANESE POPULATION; NONCODING RNAS; CELL
CARCINOMA; HAN CHINESE; RISK; VARIANTS; MELANOMA; GLIOMA; ADENOCARCINOMA
AB Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 x 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 x 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 x 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.
C1 [Wang, Zhaoming; Burdett, Laurie; Wyatt, Kathleen; Chung, Charles C.; Li, Shengchao A.; Yeager, Meredith; Hutchinson, Amy] Leidos Biomed Res Inc, Canc Genom Res Lab, Gaithersburg, MD USA.
[Wang, Zhaoming; Seow, Wei Jie; Burdett, Laurie; Wyatt, Kathleen; Chung, Charles C.; Li, Shengchao A.; Yeager, Meredith; Hutchinson, Amy; Hu, Wei; Caporaso, Neil; Landi, Maria T.; Chatterjee, Nilanjan; Song, Minsun; Fraumeni, Joseph F., Jr.; Bassig, Bryan A.; Tucker, Margaret; Berndt, Sonja I.; Chow, Wong-Ho; Ji, Bu-Tian; Chanock, Stephen J.; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Shiraishi, Kouya; Kohno, Takashi] Natl Canc Ctr, Div Genome Biol, 1-1 Tsukiji 5 chome, Tokyo, Japan.
[Hsiung, Chao A.; Hsiao, Chin-Fu; Chien, Li-Hsin; Chen, Ying-Hsiang; Chen, Hui-Ling; Su, Yu-Chun; Chen, Yi-Song] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Chang, I-Shou; Chen, Chung-Hsing; Tsai, Fang-Yu] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi 464, Japan.
[Liu, Jie; Song, Bao; Wang, Zhehai; Cheng, Sensen; Yu, Jinming] Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Oncol, Jinan, Peoples R China.
[Chen, Kexin; Zheng, Hong; Li, Haixin; Cui, Ping] Tianjin Med Univ Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Epidemiol & Biostat, Tianjin, Peoples R China.
[Yamji, Taiki; Iwasaki, Motoki; Shimazu, Taichi; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Grp, Tokyo 104, Japan.
[Yang, Yang; Zhu, Junjie; Jiang, Gening; Fei, Ke] Shanghai Pulm Hosp, Shanghai, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Wu, Chen; Chang, Jiang; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Prevent Med, Seoul, South Korea.
[Kim, Young Tae; Jung, Yoo Jin; Kang, Chang Hyun; Park, In Kyu] Seoul Natl Univ, Coll Med, Dept Thorac & Cardiovasc Surg, Canc Res Inst, Seoul, South Korea.
[Yokota, Jun] Inst Predict & Personalized Med Canc, Canc Genome Biol Grp, Barcelona, Spain.
[Kunitoh, Hideo] Japanese Red Cross Med Ctr, Dept Med Oncol, Tokyo, Japan.
[Ashikawa, Kyota; Momozawa, Yukihide; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Lab Genotyping Dev, Yokohama, Kanagawa, Japan.
[Daigo, Yataro] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan.
[Mitsudomi, Tetsuya] Kinki Univ, Sch Med, Div Thorac Surg, Sayama, Osaka 589, Japan.
[Yatabe, Yasushi] Aichi Canc Ctr, Cent Hosp, Dept Pathol & Mol Diagnost, Nagoya, Aichi 464, Japan.
[Hida, Toyoaki] Aichi Canc Ctr, Cent Hosp, Dept Thorac Oncol, Nagoya, Aichi 464, Japan.
[Hu, Zhibin; Dai, Juncheng; Ma, Hongxia; Jin, Guangfu; Shen, Hongbing] Nanjing Med Univ, Dept Epidemiol & Biostat,Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Collaborat Innovat Ctr Canc Personalized Med, Nanjing, Jiangsu, Peoples R China.
[Yin, Zhihua; Li, Xuelian; Ren, Yangwu; Guan, Peng; Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang North New Area, 77 Puhe Rd, Shenyang 110001, Peoples R China.
[Yin, Zhihua; Li, Xuelian; Ren, Yangwu; Guan, Peng; Zhou, Baosen] Univ Liaoning Prov, Key Lab Canc Etiol & Intervent, Shenyang, Peoples R China.
[Chen, Chien-Jen; Li, Yao-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
[Chang, Gee-Chen] Natl Yang Ming Univ, Sch Med, Fac Med, Taipei 112, Taiwan.
[Chang, Gee-Chen; Yang, Tsung-Ying] Taichung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Taichung, Taiwan.
[Tsai, Ying-Huang] Chiayi Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan.
[Su, Wu-Chou; Lin, Chien-Chung] Natl Cheng Kung Univ, Coll Med, Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70101, Taiwan.
[Chen, Kuan-Yu] Natl Cheng Kung Univ, Natl Taiwan Univ Hosp, Dept Internal Med, Div Pulm Med, Tainan 701, Taiwan.
[Chen, Kuan-Yu] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan.
[Yu, Chong-Jen; Yang, Pan-Chyr] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Huang, Ming-Shyan] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Sch Med, Dept Internal Med, Kaohsiung, Taiwan.
[Chen, Yuh-Min] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan.
[Chen, Yuh-Min] Taipei Med Univ, Coll Med Sci & Technol, Taipei, Taiwan.
[Wang, Wen-Chang] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Translat Med, Taipei, Taiwan.
[Guo, Huan; Wu, Tangchun] Tongji Med Coll, Dept Occupat & Environm Hlth, Wuhan, Peoples R China.
[Guo, Huan; Wu, Tangchun] Tongji Med Coll, Minist Educ, Sch Publ Hlth, Key Lab Environm & Hlth, Wuhan, Peoples R China.
[Liu, Li] Huazhong Univ Sci & Technol, Union Hosp, Dept Oncol, Ctr Canc, Wuhan 430074, Peoples R China.
[Xu, Ping] Wuhan Iron & Steel Grp Corp, Staff Worker Hosp, Dept Oncol, Wuhan, Peoples R China.
[Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu, South Korea.
[Jeon, Hyo-Sung; Choi, Jin Eun; Choi, Yi Young] Kyungpook Natl Univ, Med Ctr, Canc Res Ctr, Daegu, South Korea.
[Kim, Yeul Hong; Sung, Jae Sook; Park, Kyong Hwa] Korea Univ, Coll Med, Anam Hosp, Dept Internal Med,Div Oncol Hematol, Seoul 136705, South Korea.
[Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju, South Korea.
[Kim, Jin Hee] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Environm Hlth, Seoul, South Korea.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Hwasun Hosp, Lung & Esophageal Canc Clin, Hwasun Eup, South Korea.
[Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun Eup, South Korea.
[Oh, In-Jae; Kim, Young-Chul] Chonnam Natl Univ, Sch Med, Dept Internal Med, Gwangju, South Korea.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju, South Korea.
[Sung, Sook Whan] Seoul Natl Univ, Bundang Hosp, Dept Thorac & Cardiovasc Surg, Songnam, South Korea.
[Yoon, Ho-Il] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea.
[Kim, Jun Suk] Korea Univ, Coll Med, Guro Hosp, Div Med Oncol,Dept Internal Med, Seoul 136705, South Korea.
[Seow, Adeline; Chen, Ying; Lim, Wei-Yen; Liu, Jianjun] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Liu, Jianjun] Genome Inst Singapore, Dept Human Genet, Singapore, Singapore.
[Liu, Jianjun] Anhui Med Univ, Sch Life Sci, Hefei, Peoples R China.
[Wong, Maria Pik] Univ Hong Kong, Li Ka Shing LKS Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Lee, Victor Ho Fun] Univ Hong Kong, LKS Fac Med, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China.
[Wang, Junwen] Univ Hong Kong, LKS Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Wang, Junwen] Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China.
[Xu, Jun] Univ Hong Kong, Li Ka Shing LKS Fac Med, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Sihoe, Alan Dart Loon] Univ Hong Kong, Li Ka Shing LKS Fac Med, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Ho, James C. M.] Univ Hong Kong, Li Ka Shing LKS Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li] Fudan Univ, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
[Wang, Jiu-Cun; Lu, Daru; Zhao, Xueying; Zhao, Zhenhong; Wu, Junjie; Chen, Hongyan; Jin, Li] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[An, She-Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi-Long] Guangdong Acad Med Sci, Med Res Ctr, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
[An, She-Juan; Zhang, Xu-Chao; Su, Jian; Wu, Yi-Long] Guangdong Acad Med Sci, Guangdong Gen Hosp, Ctr Canc, Guangzhou, Guangdong, Peoples R China.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Li, Jihua] Qujing Ctr Dis Control & Prevent, Sanjiangdadao, Qujing, Peoples R China.
[Zheng, Wei; Shu, Xiao-Ou; Cai, Qiuyin] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Klein, Robert] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, 1275 York Ave, New York, NY 10021 USA.
[Pao, William] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Lawrence, Charles] WESTAT Corp, Rockville, MD 20850 USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Chen, Chih-Yi] Chung Shan Med Univ, Inst Med, Taichung, Taiwan.
[Chen, Chih-Yi] Chung Shan Med Univ Hosp, Dept Surg, Div Thorac Surg, Taichung 40201, Taiwan.
[Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taoyuan, Taiwan.
RP Wang, ZM (reprint author), NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, 8717 Grovemont Circle,ATC 152B, Gaithersburg, MD 20877 USA.
EM wangzha@mail.nih.gov
RI Jin, Li/C-1468-2009; Wang, Junwen/D-3700-2011; Zheng, Wei/O-3351-2013;
OI Jin, Li/0000-0002-4546-2415; Wang, Junwen/0000-0002-4432-4707; Zheng,
Wei/0000-0003-1226-070X; Mitsudomi, Tetsuya/0000-0001-9860-8505; Yu,
Chong-Jen/0000-0001-5664-9392; Matsuo, Keitaro/0000-0003-1761-6314
FU Japan Agency for Medical Research and Development (AMED); Government to
the National Cancer Center [26-A-1)]; Ministry of Education, Culture,
Sports, Sciences and Technology of the Japanese government; National
Cancer Center Research and Development Fund [23-A-31[toku], 26-A-2];
Ministry of Health, Labour and Welfare of Japan; National Research
Program on Genomic Medicine in Taiwan [DOH99-TD-G-111-028]; National
Research Program for Biopharmaceuticals in Taiwan [MOHW
103-TDU-PB-211-144003, MOST 103-2325-B-400-023]; Bioinformatics Core
Facility for Translational Medicine and Biotechnology Development [MOST
104-2319-B-400-002]; Jinan Science Research Project Foundation
[201102051]; Program for Changjiang Scholars and Innovative Research
Team in University (PCSIRT) in China [IRT_14R40]; National Key
Scientific and Technological Project [2011ZX09307-001-04]; National
Natural Science Foundation of China [81272293]; State Key Program of
National Natural Science of China [81230067]; National Research
Foundation of Korea (NRF) grant - Korea government (MSIP)
[NRF-2014R1A2A2A05003665]; Agency for Science, Technology and Research
(A*STAR), Singapore; US National Institute of Health Grant
[1U19CA148127-01]; intramural program of the US National Institutes of
Health/National Cancer Institute
FX The Japan Lung Cancer Study (JLCS) was supported by a Grant-in-Aid from
the Japan Agency for Medical Research and Development (AMED) for the
Health and Labor Sciences Research Expenses for Commission (the
Practical Research for Innovative Cancer Control:
H26-practical-general-094) and the Management Expenses Grants from the
Government to the National Cancer Center (26-A-1) for Biobank. BioBank
Japan was supported by the Ministry of Education, Culture, Sports,
Sciences and Technology of the Japanese government. The Japan Public
Health Center-based prospective Study (the JPHC Study) was supported by
National Cancer Center Research and Development Fund (23-A-31[toku] and
26-A-2) (since 2011) and a Grant-in-Aid for Cancer Research from the
Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010). The
Taiwan GELAC Study (Genetic Epidemiological Study for Lung
AdenoCarcinoma) was supported by grants from the National Research
Program on Genomic Medicine in Taiwan (DOH99-TD-G-111-028), the National
Research Program for Biopharmaceuticals in Taiwan (MOHW
103-TDU-PB-211-144003, MOST 103-2325-B-400-023) and Bioinformatics Core
Facility for Translational Medicine and Biotechnology Development (MOST
104-2319-B-400-002). This work was also supported by the Jinan Science
Research Project Foundation (201102051), Program for Changjiang Scholars
and Innovative Research Team in University (PCSIRT) in China
(IRT_14R40), the National Key Scientific and Technological Project
(2011ZX09307-001-04), the National Natural Science Foundation of China
(No. 81272293), the State Key Program of National Natural Science of
China (81230067), the National Research Foundation of Korea (NRF) grant
funded by the Korea government (MSIP) (No. NRF-2014R1A2A2A05003665),
Agency for Science, Technology and Research (A*STAR), Singapore and the
US National Institute of Health Grant (1U19CA148127-01). The overall
GWAS project was supported by the intramural program of the US National
Institutes of Health/National Cancer Institute.
NR 43
TC 4
Z9 4
U1 7
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD FEB 1
PY 2016
VL 25
IS 3
BP 620
EP 629
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DG5WH
UT WOS:000372149500017
PM 26732429
ER
PT J
AU Grayson, PC
Kaplan, MJ
AF Grayson, Peter C.
Kaplan, Mariana J.
TI At the Bench: Neutrophil extracellular traps (NETs) highlight novel
aspects of innate immune system involvement in autoimmune diseases
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Review
DE systemic lupus erythematosus; ANCA-associated vasculitis;
atherosclerosis; thrombosis
ID PLASMACYTOID DENDRITIC CELLS; PEPTIDYLARGININE DEIMINASE INHIBITION;
CHRONIC GRANULOMATOUS-DISEASE; FUNCTIONAL TISSUE FACTOR; LOW-DENSITY
GRANULOCYTES; LUPUS-ERYTHEMATOSUS; DNA TRAPS; MICROSCOPIC POLYANGIITIS;
NETTING NEUTROPHILS; VENOUS THROMBOSIS
AB The putative role of neutrophils in host defense against pathogens is a well-recognized aspect of neutrophil function. The discovery of neutrophil extracellular traps has expanded the known range of neutrophil defense mechanisms and catalyzed a discipline of research focused upon ways in which neutrophils can shape the immunologic landscape of certain autoimmune diseases, including systemic lupus erythematosus. Enhanced neutrophil extracellular trap formation and impaired neutrophil extracellular trap clearance may contribute to immunogenicity in systemic lupus erythematosus and other autoimmune diseases by promoting the externalization of modified autoantigens, inducing synthesis of type I IFNs, stimulating the inflammasome, and activating both the classic and alternative pathways of the complement system. Vasculopathy is a central feature of many autoimmune diseases, and neutrophil extracellular traps may contribute directly to endothelial cell dysfunction, atherosclerotic plaque burden, and thrombosis. The elucidation of the subcellular events of neutrophil extracellular trap formation may generate novel, therapeutic strategies that target the innate immune system in autoimmune and vascular diseases.
C1 [Grayson, Peter C.; Kaplan, Mariana J.] NIAMSD, Syst Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Kaplan, MJ (reprint author), NIAMS, Syst Autoimmun Branch, NIH, 10 Ctr Dr,6D 47C, Bethesda, MD 20892 USA.
EM mariana.kaplan@nih.gov
FU Intramural Research Program at the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, U.S. National Institutes of Health
FX This research was supported by the Intramural Research Program at the
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
U.S. National Institutes of Health.
NR 117
TC 26
Z9 26
U1 7
U2 15
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD FEB
PY 2016
VL 99
IS 2
BP 253
EP 264
DI 10.1189/jlb.5BT0615-247R
PG 12
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IK
UT WOS:000371890400005
PM 26432901
ER
PT J
AU Torres, A
Luke, JD
Kullas, AL
Kapilashrami, K
Botbol, Y
Koller, A
Tonge, PJ
Chen, EI
Macian, F
van der Velden, AWM
AF Torres, AnnMarie
Luke, Joanna D.
Kullas, Amy L.
Kapilashrami, Kanishk
Botbol, Yair
Koller, Antonius
Tonge, Peter J.
Chen, Emily I.
Macian, Fernando
van der Velden, Adrianus W. M.
TI Asparagine deprivation mediated by Salmonella asparaginase causes
suppression of activation-induced T cell metabolic reprogramming
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE host; pathogen; bacteria; inhibition; T-lymphocyte
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HELICOBACTER-PYLORI; CATALYTIC MECHANISM;
IMMUNE-RESPONSES; AUTOPHAGY; LYMPHOCYTES; STRATEGIES; PROLIFERATION;
PATHOGENESIS; TYPHIMURIUM
AB Salmonellae are pathogenic bacteria that induce immunosuppression by mechanisms that remain largely unknown. Previously, we showed that a putative type II L-asparaginase produced by Salmonella Typhimurium inhibits T cell responses and mediates virulence in a murine model of infection. Here, we report that this putative L-asparaginase exhibits L-asparagine hydrolase activity required for Salmonella Typhimurium to inhibit T cells. We show that L-asparagine is a nutrient important for T cell activation and that L-asparagine deprivation, such as that mediated by the Salmonella Typhimurium L-asparaginase, causes suppression of activation-induced mammalian target of rapamycin signaling, autophagy, Myc expression, and L-lactate secretion. We also show that L-asparagine deprivation mediated by the Salmonella Typhimurium L-asparaginase causes suppression of cellular processes and pathways involved in protein synthesis, metabolism, and immune response. Our results advance knowledge of a mechanism used by Salmonella Typhimurium to inhibit T cell responses and mediate virulence, and provide new insights into the prerequisites of T cell activation. We propose a model in which L-asparagine deprivation inhibits T cell exit from quiescence by causing suppression of activation-induced metabolic reprogramming.
C1 [Torres, AnnMarie; Luke, Joanna D.; Kullas, Amy L.; van der Velden, Adrianus W. M.] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
[Torres, AnnMarie; Luke, Joanna D.; Kullas, Amy L.; van der Velden, Adrianus W. M.] SUNY Stony Brook, Ctr Infect Dis, Stony Brook, NY 11794 USA.
[Torres, AnnMarie; van der Velden, Adrianus W. M.] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
[Kapilashrami, Kanishk; Tonge, Peter J.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA.
[Kapilashrami, Kanishk; Tonge, Peter J.] SUNY Stony Brook, Inst Chem Biol & Drug Discovery, Stony Brook, NY 11794 USA.
[Koller, Antonius] SUNY Stony Brook, Prote Ctr, Stony Brook, NY 11794 USA.
[Chen, Emily I.] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA.
[Botbol, Yair] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[Torres, AnnMarie] Univ Penn, Philadelphia, PA 19104 USA.
[Kullas, Amy L.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Kapilashrami, Kanishk] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Koller, Antonius; Chen, Emily I.] Herbert Irving Comprehens Canc Ctr, York, NY USA.
RP van der Velden, AWM (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, Ctr Infect Dis, 240 Ctr Mol Med, Stony Brook, NY 11794 USA.
EM a.vandervelden@stonybrook.edu
FU U.S. National Institutes of Health (NIH) [R01AI101221, R21AI092165,
P01AI055621, R01GM102864, P01AG031782]; W. Burghardt Turner Fellowship;
NIH [T32GM007964, U54AI057158, S10RR023680]
FX This research was supported by U.S. National Institutes of Health (NIH)
Grants R01AI101221, R21AI092165, and P01AI055621 (awarded to
A.W.M.v.d.V.), R01GM102864 (awarded to P.J.T.), and P01AG031782 (awarded
to F.M.). A.T. was supported by a W. Burghardt Turner Fellowship and the
NIH under Award Number T32GM007964. L-Asnase II protein was purified
with support from the Northeast Biodefense Center Protein Expression
Core (Dr. Chave), which was funded by NIH Grant U54AI057158. The mass
spectrometer used in this study was purchased with NIH Grant
S10RR023680. The authors thank members of the A.W.M.v.d.V., Carpino,
Karzai, and Zong laboratories for helpful discussions and critical
reagents and Drs. Benach, Bliska, and Thanassi for constructive feedback
on the manuscript.
NR 64
TC 3
Z9 3
U1 1
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD FEB
PY 2016
VL 99
IS 2
BP 387
EP 398
DI 10.1189/jlb.4A0615-252R
PG 12
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA DG2IK
UT WOS:000371890400016
PM 26497246
ER
PT J
AU Nath, A
AF Nath, Avindra
TI Obituary: Richard T. Johnson, MD
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Biographical-Item
C1 [Nath, Avindra] NINDS, Sect Infect Nervous Syst, Bldg 10,Room 7C103,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, Bldg 10,Room 7C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM avindra.nath@nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD FEB
PY 2016
VL 22
IS 1
BP 1
EP 5
DI 10.1007/s13365-015-0412-5
PG 5
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA DG2WH
UT WOS:000371930500001
PM 26727908
ER
PT J
AU Thakur, KT
Lyons, JL
Smith, BR
Shinohara, RT
Mateen, FJ
AF Thakur, Kiran T.
Lyons, Jennifer L.
Smith, Bryan R.
Shinohara, Russell T.
Mateen, Farrah J.
TI Stroke in HIV-infected African Americans: a retrospective cohort study
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE Stroke; African American; Human immunodeficiency virus; Disparity;
United States
AB The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and newonset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84 %) of HIV-infected new-onset stroke inpatients (median age 50 years; 69 % men; median CD4 140/mL; ischemic 77 %; 39 % taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67 %), cigarette smoking (66 %), dyslipidemia (42 %), hepatitis C (48 %), intravenous drug abuse (32 %), and prior myocardial infarction (29 %). Prior aspirin and statin use were uncommon (18 %, 9 %). Unfavorable outcome (mRS score 46, n=22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95 % CI (-0.3, 0), p=0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95 % CI (0.2, 1.8) compared to ischemic stroke, p=0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk.
C1 [Thakur, Kiran T.] Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA.
[Lyons, Jennifer L.; Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA.
[Lyons, Jennifer L.] Brigham & Womens Hosp, Div Neuroinfect Dis, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
[Smith, Bryan R.] NINDS, Sect Infect Nervous Syst, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,627, Boston, MA 02114 USA.
RP Mateen, FJ (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Mateen, FJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 165 Cambridge St,627, Boston, MA 02114 USA.
EM ktt2115@cumc.columbia.edu; fmateen@partners.org
FU Canadian Institutes of Health Research
NR 13
TC 3
Z9 3
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD FEB
PY 2016
VL 22
IS 1
BP 50
EP 55
DI 10.1007/s13365-015-0363-x
PG 6
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA DG2WH
UT WOS:000371930500008
PM 26155903
ER
PT J
AU Yan, XF
Niu, G
Wang, Z
Yang, XY
Kiesewetter, DO
Jacobson, O
Shen, BZ
Chen, XY
AF Yan, Xuefeng
Niu, Gang
Wang, Zhe
Yang, Xiangyu
Kiesewetter, Dale O.
Jacobson, Orit
Shen, Baozhong
Chen, Xiaoyuan
TI Al[F-18]NOTA-T140 Peptide for Noninvasive Visualization of CXCR4
Expression
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE T140; CXCR4; Fluoride-aluminum chelate; F-18; PET
ID CHEMOKINE RECEPTOR CXCR4; POSITRON-EMISSION-TOMOGRAPHY; HUMAN CANCER
XENOGRAFTS; IMAGING AGENTS; BREAST-CANCER; PET; METASTASIS; ANTAGONIST;
TRACER; TUMORS
AB Purpose: Chemokine receptor CXCR4 plays an important role in tumor aggressiveness, invasiveness, and metastasis formation. Quantification of CXCR4 expression by tumors may have an impact on prediction and evaluation of tumor response to therapies. In this study, we developed a robust and straightforward F-18 labeling route of T140, a CXCR4 peptide-based antagonist.
Procedures: T140 derivative was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA) and labeled with Al[F-18]. Al[F-18]NOTA-T140 was evaluated in vitro in cell-based assay and stability in mouse serum and in vivo using CXCR4 positive and negative tumor xenograft models.
Results: Labeling of Al[F-18]NOTA-T140 was completed within 30 min with a radiochemical yield of 58 +/- 5.3 % at the end of synthesis, based on fluoride-18 activity. Al[F-18]NOTA-T140 accumulated in CHO-CXCR4 positive but not negative tumors. Al[F-18]NOTA-T140 uptake in the tumors correlated with CXCR4 protein expression. Moreover, Al[F-18]NOTA-T140 had high accumulation in CXCR4-positive metastatic tumors.
Conclusions: The simplicity of Al[F-18] NOTA-T140 labeling along with its properties to specifically image CXCR4 expression by tumors warrant further clinical application for the diagnosis of CXCR4 clinically.
C1 [Yan, Xuefeng; Shen, Baozhong] Harbin Med Univ, Hosp 4, Dept Radiol, Harbin, Heilongjiang, Peoples R China.
[Yan, Xuefeng; Niu, Gang; Wang, Zhe; Yang, Xiangyu; Kiesewetter, Dale O.; Jacobson, Orit; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.
[Yan, Xuefeng; Shen, Baozhong] Harbin Med Univ, Mol Imaging Ctr, Harbin, Heilongjiang, Peoples R China.
RP Shen, BZ (reprint author), Harbin Med Univ, Hosp 4, Dept Radiol, Harbin, Heilongjiang, Peoples R China.; Jacobson, O; Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA.; Shen, BZ (reprint author), Harbin Med Univ, Mol Imaging Ctr, Harbin, Heilongjiang, Peoples R China.
EM orit.jacobsonweiss@nih.gov; shenbzh@vip.sina.com; shawn.chen@nih.gov
FU National Basic Research Program of China [2015CB931800, 2015CB931803];
National Natural Science Foundation of China [81130028, 31210103913];
Key Grant Project of Heilongjiang Province [GA12C302]; Ph.D. Programs
Foundation of Ministry of Education of China [201123071100203]; Key
Laboratory of Molecular Imaging Foundation (College of Heilongjiang
Province); Intramural Research Program (IRP) of National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health
FX This work was supported, in part, by the National Basic Research Program
of China (2015CB931800 and 2015CB931803), National Natural Science
Foundation of China (81130028 and 31210103913), the Key Grant Project of
Heilongjiang Province (GA12C302), the Ph.D. Programs Foundation of
Ministry of Education of China (201123071100203), the Key Laboratory of
Molecular Imaging Foundation (College of Heilongjiang Province), and the
Intramural Research Program (IRP) of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), National Institutes of
Health.
NR 42
TC 3
Z9 3
U1 4
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD FEB
PY 2016
VL 18
IS 1
BP 135
EP 142
DI 10.1007/s11307-015-0872-2
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DG7JX
UT WOS:000372261700015
PM 26126597
ER
PT J
AU Miszczyk, J
Panek, A
Rawojc, K
Swakon, J
Prasanna, PGS
Rydygier, M
Galas, A
AF Miszczyk, J.
Panek, A.
Rawojc, K.
Swakon, J.
Prasanna, P. G. S.
Rydygier, M.
Galas, A.
TI Effects of 60 MeV Protons and 250 kV X-Rays on Cell Viability
SO ACTA PHYSICA POLONICA A
LA English
DT Article; Proceedings Paper
CT 50th Zakopane School of Physics Symposium
CY MAY 18-23, 2015
CL Zakopane, POLAND
ID GAMMA-RAYS; APOPTOSIS; RADIATION; CANCER; IRRADIATION; CARCINOMA; DEATH
AB Particle radiotherapy such as the one using proton beams, provides a successful treatment approach in many cancer types. However, the cellular and molecular mechanisms by which proton irradiation induces cell death, particularly in a human peripheral blood lymphocyte model has not been examined in detail. Comparative studies of the biological effects, such as cell death, of particle therapy versus conventional X-rays treatment are of utmost importance. Here, we compared the viability of human peripheral blood lymphocyte following in vitro irradiation with protons (therapeutic 60 MeV proton beam) and photon beam (250 kV, X-rays), by applying separate doses within the range of 0.3-4.0 Gy. Cell viability was assessed 1 and 4 h after irradiation with protons and X-rays by the FITC-Annexin V labelling procedure (Apoptotic & Necrotic & Healthy Cells Quantification Kit, Biotium). Results showed that irradiation with both radiation types reduced the number of viable cells in a dose-dependent manner, as assessed as a function of the duration of post-irradiation time. Protons proved more fatal to the cells treated than X-ray photons. This demonstrates a difference in cell viability after irradiation with protons and photons in a human peripheral blood lymphocyte model.
C1 [Miszczyk, J.; Panek, A.] Polish Acad Sci, Inst Nucl Phys, Dept Expt Phys Complex Syst, Krakow, Poland.
[Rawojc, K.] Jagiellonian Univ, Marian Smoluchowski Inst Phys, Krakow, Poland.
[Swakon, J.; Rydygier, M.] Polish Acad Sci, Inst Nucl Phys, Proton Radiotherapy Grp, Cyclotron Ctr Bronowice, Krakow, Poland.
[Prasanna, P. G. S.] NCI, NIH, Bethesda, MD 20892 USA.
[Galas, A.] Jagiellonian Univ, Coll Med, Chair Epidemiol & Prevent Med, Dept Epidemiol, Krakow, Poland.
RP Miszczyk, J (reprint author), Polish Acad Sci, Inst Nucl Phys, Dept Expt Phys Complex Syst, Krakow, Poland.
EM Justyna.Miszczyk@ifj.edu.pl
RI Galas, Aleksander/G-9887-2013
OI Galas, Aleksander/0000-0002-9233-4301
NR 19
TC 0
Z9 0
U1 2
U2 3
PU POLISH ACAD SCIENCES INST PHYSICS
PI WARSAW
PA AL LOTNIKOW 32-46, PL-02-668 WARSAW, POLAND
SN 0587-4246
EI 1898-794X
J9 ACTA PHYS POL A
JI Acta Phys. Pol. A
PD FEB
PY 2016
VL 129
IS 2
BP 222
EP 225
PG 4
WC Physics, Multidisciplinary
SC Physics
GA DF8QV
UT WOS:000371624100018
ER
PT J
AU Chufan, EE
Kapoor, K
Ambudkar, SV
AF Chufan, Eduardo E.
Kapoor, Khyati
Ambudkar, Suresh V.
TI Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis
of the multidrug transporter P-glycoprotein
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE ABC transporter; Drug-binding site; Multidrug resistance; Modulators;
Structural motifs
ID CATALYTIC CYCLE; MAMMALIAN-CELLS; AMINO-ACID; BINDING; ABCB1;
TARIQUIDAR; TURNOVER; RESIDUES; STATE
AB P-glycoprotein (P-gp) is a member of the ATP-binding cassette transporter superfamily. This multidrug transporter utilizes energy from ATP hydrolysis for the efflux of a variety of hydrophobic and amphipathic compounds including anticancer drugs. Most of the substrates and modulators of P-gp stimulate its basal ATPase activity, although some inhibit it. The molecular mechanisms that are in play in either case are unknown. In this report, mutagenesis and molecular modeling studies of P-gp led to the identification of a pair of phenylalanine-tyrosine structural motifs in the transmembrane region that mediate the inhibition of ATP hydrolysis by certain drugs (zosuquidar, elacridar and tariquidar), with high affinity (IC50's ranging from 10 to 30 nM). Upon mutation of any of these residues, drugs that inhibit the ATPase activity of P-gp switch to stimulation of the activity. Molecular modeling revealed that the phenylalanine residues F978 and F728 interact with tyrosine residues Y953 and Y310, respectively, in an edge-to-face conformation, which orients the tyrosines in such a way that they establish hydrogen-bond contacts with the inhibitor. Biochemical investigations along with transport studies in intact cells showed that the inhibitors bind at a high affinity site to produce inhibition of ATP hydrolysis and transport function. Upon mutation, they bind at lower affinity sites, stimulating ATP hydrolysis and only poorly inhibiting transport. These results also reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for-P-gp. Published by Elsevier Inc.
C1 [Chufan, Eduardo E.; Kapoor, Khyati; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 2120, Bethesda, MD 20892 USA.
RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 2120, Bethesda, MD 20892 USA.
EM ambudkar@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX We thank Joshua Sitler and Paola Uscanga for technical assistance with
ATP hydrolysis measurements, Dr. Stewart Durell for assistance with the
molecular modeling studies, and George Leiman for editorial assistance.
We acknowledge Drs. Tanaji Talele (St. John's University, Queens, NY)
and John Colin (The Catholic University of America, Washington DC) for
critical review of the manuscript. This research was supported by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. This study
utilized the high-performance computational capabilities of the Helix
and Biowulf Systems at the National Institutes of Health, Bethesda, MD.
NR 35
TC 7
Z9 7
U1 3
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD FEB 1
PY 2016
VL 101
BP 40
EP 53
DI 10.1016/j.bcp.2015.12.007
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DF7SE
UT WOS:000371557100004
PM 26686578
ER
PT J
AU Bodelon, C
Vinokurova, S
Sampson, JN
den Boon, JA
Walker, JL
Horswill, MA
Korthauer, K
Schiffman, M
Sherman, ME
Zuna, RE
Mitchell, J
Zhang, XJ
Boland, JF
Chaturvedi, AK
Dunn, ST
Newton, MA
Ahlquist, P
Wang, SS
Wentzensen, N
AF Bodelon, Clara
Vinokurova, Svetlana
Sampson, Joshua N.
den Boon, Johan A.
Walker, Joan L.
Horswill, Mark A.
Korthauer, Keegan
Schiffman, Mark
Sherman, Mark E.
Zuna, Rosemary E.
Mitchell, Jason
Zhang, Xijun
Boland, Joseph F.
Chaturvedi, Anil K.
Dunn, S. Terence
Newton, Michael A.
Ahlquist, Paul
Wang, Sophia S.
Wentzensen, Nicolas
TI Chromosomal copy number alterations and HPV integration in cervical
precancer and invasive cancer
SO CARCINOGENESIS
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS GENOMES; CELLULAR FUSION TRANSCRIPTS; LOWER
GENITAL-TRACT; EARLY END-POINTS; INTRAEPITHELIAL NEOPLASIA;
MESSENGER-RNAS; DNA; CARCINOMA; ONCOGENES; LESIONS
AB Chromosomal copy number alterations (CNAs) and human papillomavirus (HPV) DNA integration into the host genome are more frequent in invasive cervical cancers compared to precancers. However, the relationship between CNAs and viral integration is not well understood. We analyzed chromosomal CNAs and HPV DNA integration in 17 biopsies from women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) and 21 biopsies from women diagnosed with invasive cervical carcinoma. All samples were HPV16-positive. HPV DNA integration was evaluated by sequencing of chimeric transcripts or hybrid capture reads. Chromosomal copy number was measured with the aCGH 1 x 1M (Agilent Technologies, Santa Clara, CA). A genomic instability index (GII) was defined as the fraction of the genome with CNAs. The Wilcoxon rank-sum test was used to compare CIN3 and cancer samples. Unsupervised clustering based on CNAs identified two groups corresponding to CIN3 and cancer. Most differential CNAs were found in chromosomes 3 and 8. HPV DNA was present in episomal form in 15 samples and integrated in 23 samples. The mean GII was 0.12 and 0.21 for CIN3 and cancer, respectively (P = 0.039). The GII was significantly higher in integrated samples (mean GII in episomal samples: 0.12; and integrated samples: 0.20; P = 0.02), but not within CIN3 or cancer. Integration sites were more frequently observed in amplified regions than expected by chance (P = 0.008). Our findings demonstrate that GII increases with HPV integration and at the transition from CIN3 to cancer. However, chromosomal instability can occur in the absence of integration, suggesting that it may facilitate integration.
C1 [Bodelon, Clara; Sampson, Joshua N.; Schiffman, Mark; Mitchell, Jason; Zhang, Xijun; Boland, Joseph F.; Chaturvedi, Anil K.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Vinokurova, Svetlana] NN Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[den Boon, Johan A.; Horswill, Mark A.; Ahlquist, Paul] Univ Wisconsin, Morgridge Inst Res, Madison, WI USA.
[den Boon, Johan A.; Ahlquist, Paul] Univ Wisconsin, McArdle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA.
[den Boon, Johan A.; Horswill, Mark A.; Ahlquist, Paul] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA.
[Walker, Joan L.; Zuna, Rosemary E.; Dunn, S. Terence] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Korthauer, Keegan; Newton, Michael A.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA.
[Korthauer, Keegan; Newton, Michael A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, Breast & Gynecol Canc Res Grp, NIH, Bethesda, MD 20892 USA.
[Ahlquist, Paul] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA.
RP Bodelon, C (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM clara.bodelon@nih.gov
RI Chaturvedi, Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU Intramural Research Program of the National Cancer Institute, NIH [P01
CA022443]; Morgridge Institute for Research
FX Intramural Research Program of the National Cancer Institute, NIH grant
P01 CA022443, and by funds from the Morgridge Institute for Research. P.
A. is an investigator of the Howard Hughes Medical Institute.
NR 44
TC 2
Z9 2
U1 3
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD FEB
PY 2016
VL 37
IS 2
BP 188
EP 196
DI 10.1093/carcin/bgv171
PG 9
WC Oncology
SC Oncology
GA DF9QO
UT WOS:000371696300011
PM 26660085
ER
PT J
AU Huang, Y
Yoon, K
Ko, H
Jiao, S
Ito, W
Wu, JY
Yung, WH
Lu, B
Morozov, A
AF Huang, Ying
Yoon, Kristopher
Ko, Ho
Jiao, Song
Ito, Wataru
Wu, Jian-Young
Yung, Wing-Ho
Lu, Bai
Morozov, Alexei
TI 5-HT3a Receptors Modulate Hippocampal Gamma Oscillations by Regulating
Synchrony of Parvalbumin-Positive Interneurons
SO CEREBRAL CORTEX
LA English
DT Article
DE 5-HT3a receptors; CCK interneurons; gamma oscillations; hippocampus; PV
interneurons
ID CENTRAL-NERVOUS-SYSTEM; IN-VITRO; NETWORK OSCILLATIONS; PERISOMATIC
INHIBITION; SYNAPTIC-TRANSMISSION; GABAERGIC NEURONS; PYRAMIDAL NEURONS;
GABA RELEASE; THETA-RHYTHM; CELL-TYPE
AB Gamma-frequency oscillatory activity plays an important role in information integration across brain areas. Disruption in gamma oscillations is implicated in cognitive impairments in psychiatric disorders, and 5-HT3 receptors (5-HT3Rs) are suggested as therapeutic targets for cognitive dysfunction in psychiatric disorders. Using a 5-HT3aR-EGFP transgenic mouse line and inducing gamma oscillations by carbachol in hippocampal slices, we show that activation of 5-HT3aRs, which are exclusively expressed in cholecystokinin (CCK)-containing interneurons, selectively suppressed and desynchronized firings in these interneurons by enhancing spike-frequency accommodation in a small conductance potassium (SK)-channel-dependent manner. Parvalbumin-positive interneurons therefore received diminished inhibitory input leading to increased but desynchronized firings of PV cells. As a consequence, the firing of pyramidal neurons was desynchronized and gamma oscillations were impaired. These effects were independent of 5-HT3aR-mediated CCK release. Our results therefore revealed an important role of 5-HT3aRs in gamma oscillations and identified a novel crosstalk among different types of interneurons for regulation of network oscillations. The functional link between 5-HT3aR and gamma oscillations may have implications for understanding the cognitive impairments in psychiatric disorders.
C1 [Huang, Ying; Yoon, Kristopher; Ito, Wataru; Morozov, Alexei] NIMH, Mol Pathophysiol Lab, Unit Behav Genet, NIH, Bethesda, MD 20892 USA.
[Huang, Ying] Fudan Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Shanghai 200032, Peoples R China.
[Ito, Wataru; Morozov, Alexei] Virginia Tech, Caril Res Inst, Roanoke, VA 24016 USA.
[Jiao, Song] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Ko, Ho; Yung, Wing-Ho] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
[Wu, Jian-Young] Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA.
[Lu, Bai] Tsinghua Univ, Sch Med, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China.
RP Huang, Y (reprint author), 130 Dongan Rd, Shanghai 200032, Peoples R China.
EM yinghuang@shmu.edu.cn
RI Ko, Ho/I-7513-2016; Jiao, Song/L-2803-2015
OI Ko, Ho/0000-0002-0254-3274; Jiao, Song/0000-0003-0496-6454
FU NIMH Intramural Research Program [NIH MH097826]; National Natural
Science Foundation of China [31070931]
FX This work was supported by the NIMH Intramural Research Program, NIH
MH097826, and the National Natural Science Foundation of China
(31070931).
NR 73
TC 3
Z9 3
U1 4
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD FEB
PY 2016
VL 26
IS 2
BP 576
EP 585
DI 10.1093/cercor/bhu209
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA DF7FE
UT WOS:000371522500011
PM 25246509
ER
PT J
AU Lu, HB
Wang, LM
Rea, WW
Brynildsen, JK
Jaime, S
Zuo, YT
Stein, EA
Yang, YH
AF Lu, Hanbing
Wang, Leiming
Rea, William W.
Brynildsen, Julia K.
Jaime, Saul
Zuo, Yantao
Stein, Elliot A.
Yang, Yihong
TI Low- but Not High-Frequency LFP Correlates with Spontaneous BOLD
Fluctuations in Rat Whisker Barrel Cortex
SO CEREBRAL CORTEX
LA English
DT Article
DE barrel cortex; gamma oscillation; delta oscillation; spontaneous
fluctuation; functional connectivity
ID STATE FUNCTIONAL CONNECTIVITY; DEFAULT-MODE NETWORK; MONKEY
VISUAL-CORTEX; BRAIN-FUNCTION; NEURONAL OSCILLATIONS; HEMODYNAMIC
SIGNALS; GAMMA-OSCILLATIONS; WAVELET COHERENCE; MAJOR DEPRESSION;
CINGULATE CORTEX
AB Resting-state magnetic resonance imaging (rsMRI) is thought to reflect ongoing spontaneous brain activity. However, the precise neurophysiological basis of rsMRI signal remains elusive. Converging evidence supports the notion that local field potential (LFP) signal in the high-frequency range correlates with fMRI response evoked by a task (e.g., visual stimulation). It remains uncertain whether this relationship extends to rsMRI. In this study, we systematically modulated LFP signal in the whisker barrel cortex (WBC) by unilateral deflection of rat whiskers. Results show that functional connectivity between bilateral WBC was significantly modulated at the 2 Hz, but not at the 4 or 6 Hz, stimulus condition. Electrophysiologically, only in the low-frequency range (< 5 Hz) was the LFP power synchrony in bilateral WBC significantly modulated at 2 Hz, but not at 4- or 6-Hz whisker stimulation, thus distinguishing these 2 experimental conditions, and paralleling the findings in rsMRI. LFP power synchrony in other frequency ranges was modulated in a way that was neither unique to the specific stimulus conditions nor parallel to the fMRI results. Our results support the hypothesis that emphasizes the role of low-frequency LFP signal underlying rsMRI.
C1 [Lu, Hanbing; Wang, Leiming; Rea, William W.; Brynildsen, Julia K.; Jaime, Saul; Zuo, Yantao; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Rea, William W.] NIDA, Integrat Neurobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Jaime, Saul] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Physiol, San Antonio, TX 78229 USA.
[Zuo, Yantao] Duke Univ, Sch Med, Psychiat & Behav Sci, Durham, NC 27705 USA.
RP Lu, HB (reprint author), 251 Bayview Blvd,Suite 200,Rm 07A727, Baltimore, MD 21224 USA.
EM luha@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, National
Institute of Health
FX This work was supported by the Intramural Research Program, National
Institute on Drug Abuse, National Institute of Health. H.L. benefited
from discussions with Dr Asaf Keller of University of Maryland about EEG
recording in the whisker barrel cortex.
NR 85
TC 4
Z9 4
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD FEB
PY 2016
VL 26
IS 2
BP 683
EP 694
DI 10.1093/cercor/bhu248
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA DF7FE
UT WOS:000371522500021
PM 25331598
ER
PT J
AU Moysi, E
Estes, JD
Petrovas, C
AF Moysi, Eirini
Estes, Jacob D.
Petrovas, Constantinos
TI Novel Imaging Methods for Analysis of Tissue Resident Cells in HIV/SIV
SO CURRENT HIV/AIDS REPORTS
LA English
DT Article
DE HIV; SIV; Imaging; Tissues; HIV pathogenesis; Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; LYMPHOID-TISSUE; VIRAL
LOAD; PATHOGENIC INFECTION; HIV-1 INFECTION; RHESUS MACAQUES; RESPONSES;
REPLICATION; TRANSMISSION
AB The use of advanced tissue-imaging methodologies has greatly facilitated the study of molecular mechanisms and cellular interactions in humans and animal models of disease. Particularly, in HIV research, there is an ever-increasing demand for a comprehensive analysis of immune cell dynamics at tissue level stemming from the need to advance our understanding of those interactions that regulate the generation of adaptive antigen-specific immune responses. The latter is critical for the development of vaccines to elicit broadly neutralizing antibodies as well as for the discovery of novel targets for immuno-therapies to strengthen the cytolytic arm of the immune system at local level. In this review, we focus on current and emerging imaging technologies, discuss their strengths and limitations, and examine how such technologies can inform the development of new treatments and vaccination strategies. We also present some perspective on the future of the technology development.
C1 [Moysi, Eirini] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA.
[Estes, Jacob D.] Leidos Biomedical Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Petrovas, Constantinos] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 40,40 Convent Dr, Bethesda, MD 20892 USA.
RP Petrovas, C (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 40,40 Convent Dr, Bethesda, MD 20892 USA.
EM petrovasc@mail.nih.gov
FU Intramural Research Program of Vaccine Research Center, National
Institutes of Allergy and Infectious Diseases, National Institutes of
Health; Miami Center for AIDS Research (CFAR) Laboratory Core at
University of Miami [P30AI073961]
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health.; The authors would like to
acknowledge the Miami Center for AIDS Research (CFAR) Laboratory Core at
the University of Miami for partially supporting under award number
P30AI073961.
NR 55
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD FEB
PY 2016
VL 13
IS 1
BP 38
EP 43
DI 10.1007/s11904-016-0300-5
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA DG1CM
UT WOS:000371802900005
PM 26830285
ER
PT J
AU Hutsell, BA
Baumann, MH
Partilla, JS
Banks, ML
Vekariya, R
Glennon, RA
Negus, SS
AF Hutsell, Blake A.
Baumann, Michael H.
Partilla, John S.
Banks, Matthew L.
Vekariya, Rakesh
Glennon, Richard A.
Negus, S. Stevens
TI Abuse-related neurochemical and behavioral effects of cathinone and
4-methylcathinone stereoisomers in rats
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Cathinone; 4-Methylcathinone; Stereoselectivity; Intracranial
self-stimulation; Rat; Drug abuse
ID INTRACRANIAL SELF-STIMULATION; MEPHEDRONE 4-METHYLMETHCATHINONE;
METHCATHINONE ANALOGS; AMPHETAMINE ANALOGS; METHYLONE; COCAINE;
NOREPINEPHRINE; TRANSPORTERS; MDPV
AB Cathinone and many of its analogs produce behavioral effects by promoting transporter mediated release of the monoamine neurotransmitters dopamine, norepinephrine and/or serotonin. Stereoselectivity is one determinant of neurochemical and behavioral effects of cathinone analogs. This study compared effectiveness of the S(-) and R(+) enantiomers of cathinone and 4-methylcathinone to produce in vitro monoamine release and in vivo abuse related behavioral effects in rats. For neurochemical studies, drug effects were evaluated on monoamine release through dopamine, norepinephrine, and serotonin transporters (DAT, NET and SERT, respectively) in rat brain synaptosomes. For behavioral studies, drug effects were evaluated on responding for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. The cathinone enantiomers differed in potency [S(-)>R(+)], but both enantiomers were > 50-fold selective at promoting monoamine release through DAT vs. SERT, and both enantiomers produced ICSS facilitation. The 4-methylcathinone enantiomers also differed in potency [S(-)>R(+)]; however, in neurochemical studies, the decrease in potency from S(-) to R(+)4-methylcathinone was less for DAT than for SERT, and as a result, DAT vs. SERT selectivity was greater for R(+) than for S(-)4-methylcathinone (4.1- vs. 1.2-fold). Moreover, in behavioral studies, S(-)4-methylcathinone produced only ICSS depression, whereas R(+)4-methylcathinone produced ICSS facilitation. This study provides further evidence for stereoselectivity in neurochemical and behavioral actions of cathinone analogs. More importantly, stereoselective 4-methylcathinone effects on ICSS illustrate the potential for diametrically opposite effects of enantiomers in a preclinical behavioral assay of abuse potential. (C) 2015 Elsevier B.V. and ECNP. All rights reserved.
C1 [Hutsell, Blake A.; Banks, Matthew L.; Negus, S. Stevens] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA.
[Baumann, Michael H.; Partilla, John S.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD USA.
[Banks, Matthew L.; Negus, S. Stevens] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Vekariya, Rakesh; Glennon, Richard A.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St,POB 980613, Richmond, VA 23298 USA.
EM ssnegus@vcu.edu
RI Banks, Matthew/K-4429-2014; Vekariya, Rakesh/A-2577-2017
OI Banks, Matthew/0000-0003-4949-5246; Vekariya, Rakesh/0000-0001-8292-9793
FU National Institute on Drug Abuse (NIDA) of the National Institutes of
Health [R01 DA033930, T32 DA007027]; NIDA Intramural Research Program
FX Research reported in this publication was supported by the National
Institute on Drug Abuse (NIDA) of the National Institutes of Health
under Award Numbers R01 DA033930 and T32 DA007027, and the NIDA
Intramural Research Program. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 29
TC 3
Z9 3
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD FEB
PY 2016
VL 26
IS 2
BP 288
EP 297
DI 10.1016/j.euroneuro.2015.12.010
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA DG1RC
UT WOS:000371844200011
PM 26738428
ER
PT J
AU Betancourt, TS
Chambers, DA
AF Betancourt, Theresa S.
Chambers, David A.
TI Optimizing an Era of Global Mental Health Implementation Science
SO JAMA PSYCHIATRY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; DISSEMINATION; INTERVENTION
C1 [Betancourt, Theresa S.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA.
[Chambers, David A.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Betancourt, TS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,Bldg 1,Room 1213, Boston, MA 02115 USA.
EM theresa_betancourt@harvard.edu
NR 7
TC 1
Z9 1
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD FEB
PY 2016
VL 73
IS 2
BP 99
EP 100
DI 10.1001/jamapsychiatry.2015.2705
PG 2
WC Psychiatry
SC Psychiatry
GA DF8MS
UT WOS:000371612500001
PM 26720304
ER
PT J
AU Zhang, QJ
You, J
Volkow, ND
Choi, J
Yin, W
Wang, W
Pan, YT
Du, CW
AF Zhang, Qiujia
You, Jiang
Volkow, Nora D.
Choi, Jeonghun
Yin, Wei
Wang, Wei
Pan, Yingtian
Du, Congwu
TI Chronic cocaine disrupts neurovascular networks and cerebral function:
optical imaging studies in rodents
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE brain imaging; optical coherence Doppler tomography; multiwavelength
laser speckle imaging; cocaine; ischemia; angiogenesis
ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-FLOW; SUBARACHNOID HEMORRHAGE; ISCHEMIC
MYOCARDIUM; AFRICAN-AMERICANS; IN-VIVO; ANGIOGENESIS; EXPRESSION; BRAIN;
DYSFUNCTION
AB Cocaine abuse can lead to cerebral strokes and hemorrhages secondary to cocaine's cerebrovascular effects, which are poorly understood. We assessed cocaine's effects on cerebrovascular anatomy and function in the somatosensory cortex of the rat's brain. Optical coherence tomography was used for in vivo imaging of three-dimensional cerebral blood flow (CBF) networks and to quantify CBF velocities (CBFv), and multiwavelength laser-speckle-imaging was used to simultaneously measure changes in CBFv, oxygenated (Delta[HbO(2)]) and deoxygenated hemoglobin (Delta[HbR]) concentrations prior to and after an acute cocaine challenge in chronically cocaine exposed rats. Immunofluorescence techniques on brain slices were used to quantify microvasculature density and levels of vascular endothelial growth factor (VEGF). After chronic cocaine (2 and 4 weeks), CBFv in small vessels decreased, whereas vasculature density and VEGF levels increased. Acute cocaine further reduced CBFv and decreased Delta[HbO(2)] and this decline was larger and longer lasting in 4 weeks than 2 weeks cocaine-exposed rats, which indicates that risk for ischemia is heightened during intoxication and that it increases with chronic exposures. These results provide evidence of cocaine-induced angiogenesis in cortex. The CBF reduction after chronic cocaine exposure, despite the increases in vessel density, indicate that angiogenesis was insufficient to compensate for cocaine-induced disruption of cerebrovascular function. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Zhang, Qiujia; You, Jiang; Choi, Jeonghun; Yin, Wei; Pan, Yingtian; Du, Congwu] SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
[Zhang, Qiujia; Yin, Wei] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Neurol, Wuhan 430030, Peoples R China.
[Volkow, Nora D.] NIAAA, NIH, Bethesda, MD 20857 USA.
RP Du, CW (reprint author), SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA.
EM congwu.du@stonybrook.edu
FU National Institutes of Health (NIH) [R21DA032228, 1R01DA029718,
R01NS084817]; China Scholarship Council; NIH's Intramural Program
FX We especially thank K. Park for assisting with animal surgery and T.
Ontiveros, Kevin Clare for assisting with VEGF image and for ex vitro
imaging analysis. This work was supported in part by National Institutes
of Health (NIH) [Grant Nos. R21DA032228 (YP/CD), 1R01DA029718 (CD/YP),
R01NS084817 (XH/CD)], the China Scholarship Council (QJZ), and NIH's
Intramural Program (NDV). C.D., Y.P., and N.D.V. designed the research;
Q.J.Z., J.Y., and J.H.C. carried out the experiments and data analysis;
W.Y.R. guided VEGF measurement and C.D., Y.P., and W.W. supervised
Q.J.Z. Q.J.Z., C.D., Y.P., and N.D.V. wrote the manuscript and
contributed significantly to discuss the results.
NR 46
TC 0
Z9 0
U1 2
U2 7
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD FEB
PY 2016
VL 21
IS 2
AR 026006
DI 10.1117/1.JBO.21.2.026006
PG 12
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DG0EA
UT WOS:000371735000017
PM 26868475
ER
PT J
AU Sood, R
Hansen, NF
Donovan, FX
Carrington, B
Bucci, D
Maskeri, B
Young, A
Trivedi, NS
Kohlschmidt, J
Stone, RM
Caligiuri, MA
Chandrasekharappa, SC
Marcucci, G
Mullikin, JC
Bloomfield, CD
Liu, P
AF Sood, R.
Hansen, N. F.
Donovan, F. X.
Carrington, B.
Bucci, D.
Maskeri, B.
Young, A.
Trivedi, N. S.
Kohlschmidt, J.
Stone, R. M.
Caligiuri, M. A.
Chandrasekharappa, S. C.
Marcucci, G.
Mullikin, J. C.
Bloomfield, C. D.
Liu, P.
TI Somatic mutational landscape of AML with inv(16) or t(8;21) identifies
patterns of clonal evolution in relapse leukemia
SO LEUKEMIA
LA English
DT Letter
ID ACUTE MYELOID-LEUKEMIA; GROUP-B; ADULT; CANCER; MDS
C1 [Sood, R.; Liu, P.] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Sood, R.; Carrington, B.] NHGRI, Zebrafish Core, NIH, Bethesda, MD 20892 USA.
[Hansen, N. F.; Mullikin, J. C.] NHGRI, Comparat Genom Anal Unit, NIH, Bethesda, MD 20892 USA.
[Donovan, F. X.; Chandrasekharappa, S. C.] NHGRI, Genom Core, NIH, Bethesda, MD 20892 USA.
[Bucci, D.; Kohlschmidt, J.; Caligiuri, M. A.; Marcucci, G.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Maskeri, B.; Young, A.; Mullikin, J. C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Trivedi, N. S.] NHGRI, Bioinformat & Sci Programming Core, NIH, Bethesda, MD 20892 USA.
[Kohlschmidt, J.] Mayo Clin, Alliance Clin Trials Oncol Stat & Data Ctr, Rochester, MN USA.
[Stone, R. M.] Harvard Univ, Med Oncol Hematol Malignancies, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Chandrasekharappa, S. C.] NHGRI, Canc Genom Unit, NIH, Bethesda, MD 20892 USA.
[Marcucci, G.] Hematol Malignancies & Stem Cell Transplantat Ins, Dept Hematol & Hematopoiet Cell Transplantat, Duarte, CA USA.
RP Liu, P (reprint author), NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
EM pliu@mail.nih.gov
FU Intramural NIH HHS [Z01 HG000030-14, Z01 HG000030-13]; NCI NIH HHS [U10
CA180861, U10 CA180850, P30 CA016058, P50 CA140158, U10 CA101140]
NR 17
TC 5
Z9 5
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD FEB
PY 2016
VL 30
IS 2
BP 501
EP 504
DI 10.1038/leu.2015.141
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA DF7TB
UT WOS:000371559400030
PM 26139325
ER
PT J
AU Absinta, M
Sati, P
Ohayon, J
Wu, TX
Filippi, M
Cortese, I
Reich, DS
AF Absinta, Martina
Sati, Pascal
Ohayon, Joan
Wu, Tianxia
Filippi, Massimo
Cortese, Irene
Reich, Daniel S.
TI Failure of Early Repair in Multiple Sclerosis Lesions with Persistent
Paramagnetic rim at 7T MRI
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Absinta, Martina; Sati, Pascal; Ohayon, Joan; Wu, Tianxia; Cortese, Irene] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Absinta, Martina; Filippi, Massimo] San Raffaele Inst, Milan, Italy.
[Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA S1.3
BP 3
EP 3
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100004
ER
PT J
AU Komori, M
Blake, A
Lin, YC
Kosa, P
Ghazali, D
Winokur, P
Natrajan, M
Wuest, SC
Romm, E
Wu, TX
Bielekova, B
AF Komori, Mika
Blake, Andrew
Lin, YenChih
Kosa, Peter
Ghazali, Danish
Winokur, Paige
Natrajan, Muktha
Wuest, Simone C.
Romm, Elena
Wu, Tianxia
Bielekova, Bibiana
TI Combination of biologically related biomarkers quantifies infiltration
of CNS tissue by immune cells in progressive multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Komori, Mika; Blake, Andrew; Lin, YenChih; Kosa, Peter; Ghazali, Danish; Winokur, Paige; Natrajan, Muktha; Wuest, Simone C.; Romm, Elena; Wu, Tianxia; Bielekova, Bibiana] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA S1.6
BP 4
EP 4
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100007
ER
PT J
AU Reich, DS
AF Reich, Daniel S.
TI MRI as an outcome measure in progressive MS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 1
U2 2
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 FEB
PY 2016
VL 22
SU 1
MA S4.2
BP 6
EP 7
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100013
ER
PT J
AU Komori, M
Blake, A
Lin, YC
Kosa, P
Ghazali, D
Winokur, P
Natrajan, M
Wuest, SC
Romm, E
Wu, TX
Bielekova, B
AF Komori, Mika
Blake, Andrew
Lin, YenChih
Kosa, Peter
Ghazali, Danish
Winokur, Paige
Natrajan, Muktha
Wuest, Simone C.
Romm, Elena
Wu, Tianxia
Bielekova, Bibiana
TI Combination of biologically related biomarkers quantifies infiltration
of CNS tissue by immune cells in progressive multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Komori, Mika; Blake, Andrew; Lin, YenChih; Kosa, Peter; Ghazali, Danish; Winokur, Paige; Natrajan, Muktha; Wuest, Simone C.; Romm, Elena; Wu, Tianxia; Bielekova, Bibiana] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA P001
BP 8
EP 9
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100019
ER
PT J
AU Kosa, P
Ghazali, D
Tanigawa, M
Cortese, I
Kelley, W
Snyder, B
Ohayon, J
Fenton, K
Lehky, T
Wu, TX
Bhagavatheeshwaran, G
Barbour, C
Greenwood, M
Bielekova, B
AF Kosa, Peter
Ghazali, Danish
Tanigawa, Makoto
Cortese, Irene
Kelley, William
Snyder, Blake
Ohayon, Joan
Fenton, Kaylan
Lehky, Tanya
Wu, Tianxia
Bhagavatheeshwaran, Govind
Barbour, Christopher
Greenwood, Mark
Bielekova, Bibiana
TI Development of a sensitive outcome for economical drug screening for
progressive multiple sclerosis
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Kosa, Peter; Ghazali, Danish; Tanigawa, Makoto; Cortese, Irene; Kelley, William; Snyder, Blake; Ohayon, Joan; Fenton, Kaylan; Lehky, Tanya; Wu, Tianxia; Bhagavatheeshwaran, Govind; Bielekova, Bibiana] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Barbour, Christopher; Greenwood, Mark] Montana State Univ, Bozeman, MT 59717 USA.
NR 0
TC 0
Z9 0
U1 1
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 FEB
PY 2016
VL 22
SU 1
MA P020
BP 15
EP 16
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100036
ER
PT J
AU Steele, SU
Xia, ZQ
Bakshi, AC
Ohayon, J
von Korff, A
Owen, EK
Clarkson, S
Chibnik, LB
Cortese, I
De Jager, PL
Reich, DS
AF Steele, Sonya U.
Xia, Zongqi
Bakshi, Anshika C.
Ohayon, Joan
von Korff, Alina
Owen, Emily K.
Clarkson, Sarah
Chibnik, Lori B.
Cortese, Irene
De Jager, Philip L.
Reich, Daniel S.
TI Magnetic Resonance Imaging and Clinical Findings in Genetically
Characterized, Asymptomatic First-Degree Relatives of Multiple Sclerosis
Patients
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Steele, Sonya U.; Bakshi, Anshika C.] NINDS, Translat Neuroradiol Unit, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Steele, Sonya U.; Xia, Zongqi; von Korff, Alina; Owen, Emily K.; Clarkson, Sarah; Chibnik, Lori B.; De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, 75 Francis St, Boston, MA 02115 USA.
[Xia, Zongqi; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA USA.
[Ohayon, Joan; Cortese, Irene] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA P034
BP 21
EP 22
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100049
ER
PT J
AU Schindler, MK
Uzel, G
Pittaluga, S
Reich, DS
Cortese, I
AF Schindler, Matthew K.
Uzel, Gulbu
Pittaluga, Stefania
Reich, Daniel S.
Cortese, Irene
TI Cytotoxic T-lymphocyte antigen-4 haploinsufficiency-associated
neuroinflammation: clinical and adiographic features
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Schindler, Matthew K.; Uzel, Gulbu; Pittaluga, Stefania; Cortese, Irene] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA P036
BP 22
EP 23
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100051
ER
PT J
AU Absinta, M
Sati, P
Ohayon, J
Wu, TX
Filippi, M
Cortese, I
Reich, DS
AF Absinta, Martina
Sati, Pascal
Ohayon, Joan
Wu, Tianxia
Filippi, Massimo
Cortese, Irene
Reich, Daniel S.
TI Failure of early repair in Multiple Sclerosis with persistent
paramagnetic RIM at 7T MRI
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Absinta, Martina; Sati, Pascal; Ohayon, Joan; Wu, Tianxia; Cortese, Irene] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Absinta, Martina; Filippi, Massimo] Ist Sci San Raffaele, I-20132 Milan, Italy.
[Reich, Daniel S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA P074
BP 37
EP 38
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100085
ER
PT J
AU Komori, M
Lin, YC
Cortese, I
Blake, A
Ohayon, J
Cherup, J
Maric, D
Kosa, P
Wu, TX
Bielekova, B
AF Komori, Mika
Lin, YenChih
Cortese, Irene
Blake, Andrew
Ohayon, Joan
Cherup, Jamie
Maric, Dragan
Kosa, Peter
Wu, Tianxia
Bielekova, Bibiana
TI Intrathecal Rituximab in progressive MS stopped for insufficient
inhibition of CNS inflammation: a randomized, double-blind,
placebo-controlled study
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT ACTRIMS Forum
CY FEB 18-20, 2016
CL New Orleans, LA
SP ACTRIMS
C1 [Komori, Mika; Lin, YenChih; Cortese, Irene; Blake, Andrew; Ohayon, Joan; Cherup, Jamie; Maric, Dragan; Kosa, Peter; Wu, Tianxia; Bielekova, Bibiana] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2016
VL 22
SU 1
MA LB142
BP 65
EP 65
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DF9CE
UT WOS:000371657100148
ER
PT J
AU Attiyeh, EF
Maris, JM
Lock, R
Reynolds, CP
Kang, MH
Carol, H
Gorlick, R
Kolb, EA
Keir, ST
Wu, JR
Landesman, Y
Shacham, S
Lyalin, D
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Attiyeh, Edward F.
Maris, John M.
Lock, Richard
Reynolds, C. Patrick
Kang, Min H.
Carol, Hernan
Gorlick, Richard
Kolb, E. Anders
Keir, Stephen T.
Wu, Jianrong
Landesman, Yosef
Shacham, Sharon
Lyalin, Dmitry
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Pharmacodynamic and Genomic Markers Associated With Response to the
XPO1/CRM1 Inhibitor Selinexor (KPT-330): A Report From the Pediatric
Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; XPO1 inhibitor
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NUCLEAR EXPORT INHIBITION; ACUTE
MYELOID-LEUKEMIA; MANTLE CELL LYMPHOMA; PHASE-I TRIAL; STAGE 1;
SELECTIVE INHIBITORS; LEPTOMYCIN B; ANTICANCER ACTIVITY;
TUMOR-SUPPRESSOR
AB Background. Selinexor (KPT-330) is an inhibitor of the major nuclear export receptor, exportin 1 (XPO1, also termed chromosome region maintenance 1, CRM1) that has demonstrated activity in preclinical models and clinical activity against several solid and hematological cancers. Procedures. Selinexor was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations from 1.0nM to 10 mu M and against the PPTP in vivo xenograft panels administered orally at a dose of 10 mg/kg thrice weekly for 4 weeks. Results. Selinexor demonstrated cytotoxic activity in vitro, with a median relative IC50 value of 123nM (range 13.0nM to > 10 mu M). Selinexor induced significant differences in event-free survival (EFS) distribution in 29 of 38 (76%) of the evaluable solid tumor xenografts and in five of eight (63%) of the evaluable ALL xenografts. Objective responses (partial or complete responses, PR/CR) were observed for 4 of 38 solid tumor xenografts including Wilms tumor, medulloblastoma (n = 2), and ependymoma models. For the ALL panel, two of eight (25%) xenografts achieved either CR or maintained CR. Two responding xenografts had FBXW7 mutations at R465 and two had SMARCA4 mutations. Selinexor induced p53, p21, and cleaved PARP in several solid tumor models. Conclusions. Selinexor induced regression against several solid tumor and ALL xenografts and slowed tumor growth in a larger number of models. Pharmacodynamic effects for XPO1 inhibition were noted. Defining the relationship between selinexor systemic exposures in mice and humans will be important in assessing the clinical relevance of these results. (c) 2015 Wiley Periodicals, Inc.
C1 [Attiyeh, Edward F.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Attiyeh, Edward F.; Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DC USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Wu, Jianrong] St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Landesman, Yosef; Shacham, Sharon] Karyopharm Therapeut, Newton, MA USA.
[Lyalin, Dmitry; Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, 9609 Med Ctr Dr,RM 5-W414,MSC 9737, Bethesda, MD 20892 USA.
RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, 9609 Med Ctr Dr,RM 5-W414,MSC 9737, Bethesda, MD 20892 USA.
EM Malcolm.Smith@nih.gov
RI Lock, Richard/G-4253-2013;
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216;
CA21765; CA108786
NR 55
TC 4
Z9 4
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2016
VL 63
IS 2
BP 276
EP 286
DI 10.1002/pbc.25727
PG 11
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DD9MD
UT WOS:000370248900015
PM 26398108
ER
PT J
AU Widemann, BC
AF Widemann, Brigitte C.
TI Reply to: Glucarpidase for the Treatment of Methotrexate-Induced Renal
Dysfunction and Delayed Methotrexate Excretion
SO PEDIATRIC BLOOD & CANCER
LA English
DT Letter
C1 [Widemann, Brigitte C.] NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5750, Bethesda, MD 20892 USA.
RP Widemann, BC (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Ctr Canc Res, Bldg 10,Room 1-5750, Bethesda, MD 20892 USA.
EM widemanb@mail.nih.gov
NR 4
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
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD FEB
PY 2016
VL 63
IS 2
BP 366
EP 366
DI 10.1002/pbc.25798
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DD9MD
UT WOS:000370248900033
PM 26488622
ER
PT J
AU Caffino, L
Di Chio, M
Giannotti, G
Venniro, M
Mutti, A
Padovani, L
Cheung, D
Fumagalli, GF
Yew, DT
Fumagalli, F
Chiamulera, C
AF Caffino, Lucia
Di Chio, Marzia
Giannotti, Giuseppe
Venniro, Marco
Mutti, Anna
Padovani, Laura
Cheung, David
Fumagalli, Guido F.
Yew, David T.
Fumagalli, Fabio
Chiamulera, Cristiano
TI The modulation of BDNF expression and signalling dissects the
antidepressant from the reinforcing properties of ketamine: Effects of
single infusion vs. chronic self-administration in rats
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE Ketamine; Reinforcement; Antidepressant; BDNF; Zif-268; Rat
ID FORCED SWIMMING TEST; MEDIAL PREFRONTAL CORTEX; NEUROTROPHIC FACTOR;
MESSENGER-RNA; NUCLEUS-ACCUMBENS; HIPPOCAMPAL BDNF; C-FOS; BRAIN;
COCAINE; ZIF268
AB Ketamine is a drug of abuse with a unique profile, which besides its inherent mechanism of action as a noncompetitive antagonist of the NMDA glutamate receptor, displays both antidepressant and reinforcing properties.
The major aim of our study was to find a molecular signature of ketamine that may help in discriminating between its reinforcing and antidepressant effects. To this end, we focused our attention on BDNF, a neurotrophin that has been shown to play a role in both antidepressant and reinforcing properties of several drugs.
Rats were exposed to self-administer intravenous (IV) ketamine (S/A) for 43 days or to receive a single IV ketamine 0.5 mg/kg, or vehicle infusion. Although the dose we employed is lower than that reported by the literature, it however yields C-max values that correspond to those achieved in humans after antidepressant treatment.
Our results show that while the single infusion of ketamine increased the neurotrophin expression in the hippocampus while reducing it in the ventral striatum, a feature shared with other antidepressants, the repeated self-administration reduced mBDNF expression and its downstream signalling in both ventral striatum and hippocampus. Further, we here show that phosphorylation of Akt is oppositely regulated by ketamine, pointing to this pathway as central to the different actions of the drug.
Taken together, we here point to BDNF and its downstream signalling pathway as a finely tuned mechanism whose modulation might subserve the different features of ketamine. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Di Chio, Marzia; Venniro, Marco; Mutti, Anna; Padovani, Laura; Fumagalli, Guido F.; Chiamulera, Cristiano] Univ Verona, Dept Diagnost & Publ Hlth, Pharmacol Sect, Neuropsychopharmacol Lab, Ple Scuro 10, I-37100 Verona, Italy.
[Caffino, Lucia; Giannotti, Giuseppe; Fumagalli, Fabio] Univ Milan, Dipartimento Sci Farmacol & Biomol, Via Balzaretti 9, I-20133 Milan, Italy.
[Cheung, David; Yew, David T.] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Brain Res Ctr, Shatin, Hong Kong, Peoples R China.
[Venniro, Marco] NIDA, 251 Bayview Blvd, Baltimore, MD 21224 USA.
RP Chiamulera, C (reprint author), Policlin GB Rossi, Sez Farmacol, Ple Scuro 10, I-37134 Verona, Italy.
EM cristiano.chiamulera@univr.it
OI Padovani, Laura/0000-0002-4677-0372; Fumagalli,
Fabio/0000-0002-8814-7706; Giannotti, Giuseppe/0000-0003-0629-4882
FU University of Verona; Zardi-Gori Foundation
FX This study was partly supported by University of Verona "COOPERINT 2012"
bursary to DC. We would also like to thank the Zardi-Gori Foundation for
providing funding to FF.
NR 53
TC 2
Z9 2
U1 2
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD FEB
PY 2016
VL 104
BP 22
EP 30
DI 10.1016/j.phrs.2015.12.014
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DG1QE
UT WOS:000371841800003
PM 26706783
ER
PT J
AU Banerjee, A
Berezhkovskii, A
Nossal, R
AF Banerjee, Anand
Berezhkovskii, Alexander
Nossal, Ralph
TI Kinetics of cellular uptake of viruses and nanoparticles via
clathrin-mediated endocytosis
SO PHYSICAL BIOLOGY
LA English
DT Article
DE nanoparticle; virus; clathrin-mediated endocytosis; random walk; vesicle
formation
ID SIZE-DEPENDENT ENDOCYTOSIS; MAMMALIAN-CELLS; TRANSFERRIN; INITIATION;
MACHINERY; CURVATURE; PARTICLES; COATS; CARGO; ENTRY
AB Several viruses exploit clathrin-mediated endocytosis to gain entry into host cells. This process is also used extensively in biomedical applications to deliver nanoparticles (NPs) to diseased cells. The internalization of these nano-objects is controlled by the assembly of a clathrin-containing protein coat on the cytoplasmic side of the plasma membrane, which drives the invagination of the membrane and the formation of a cargo-containing endocytic vesicle. Current theoretical models of receptor-mediated endocytosis of viruses and NPs do not explicitly take coat assembly into consideration. In this paper we study cellular uptake of viruses and NPs with a focus on coat assembly. We characterize the internalization process by the mean time between the binding of a particle to the membrane and its entry into the cell. Using a coarse-grained model which maps the stochastic dynamics of coat formation onto a one-dimensional random walk, we derive an analytical formula for this quantity. A study of the dependence of the mean internalization time on NP size shows that there is an upper bound above which this time becomes extremely large, and an optimal size at which it attains a minimum. Our estimates of these sizes compare well with experimental data. We also study the sensitivity of the obtained results on coat parameters to identify factors which significantly affect the internalization kinetics.
C1 [Banerjee, Anand; Nossal, Ralph] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
RP Banerjee, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
EM banerjeea3@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
(NIH)-Eunice Kennedy Shriver National Institute of Child Health and
Human Development; Center for Information Technology
FX This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH)-Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and the Center for
Information Technology.
NR 49
TC 1
Z9 1
U1 9
U2 22
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD FEB
PY 2016
VL 13
IS 1
AR 016005
DI 10.1088/1478-3975/13/1/016005
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DF8CT
UT WOS:000371585200005
PM 26871680
ER
PT J
AU Arimbasseri, AG
Maraia, RJ
AF Arimbasseri, Aneeshkumar G.
Maraia, Richard J.
TI A high density of cis-information terminates RNA Polymerase III on a
2-rail track
SO RNA BIOLOGY
LA English
DT Editorial Material
DE Nontemplate strand; RNA Polymerase; RNA Polymerase III; RPC11; RPC37;
RPC53; transcription termination
ID TRANSCRIPTION TERMINATION; ELONGATION COMPLEX; STRUCTURAL BASIS;
CRYSTAL-STRUCTURE; NONTEMPLATE DNA; ACTIVE-CENTER; ARCHITECTURE;
RECOGNITION; INITIATION; REVEALS
AB Transcription termination delineates the 3 ends of transcripts, prevents otherwise runaway RNA polymerase (RNAP) from intruding into downstream genes and regulatory elements, and enables release of the RNAP for recycling. While other eukaryotic RNAPs require complex cis-signals and/or accessory factors to achieve these activities, RNAP III does so autonomously with high efficiency and precision at a simple oligo(dT) stretch of 5-6bp. A basis for this high density cis-information is that both template and nontemplate strands of the RNAP III terminator carry distinct signals for different stages of termination. High-density cis-information is a feature of the RNAP III system that is also reflected by dual functionalities of the tRNA promoters as both DNA and RNA elements. We review emerging developments in RNAP III termination and single strand nontemplate DNA use by other RNAPs. Use of nontemplate signals by RNAPs and associated transcription factors may be prevalent in gene regulation.
C1 [Arimbasseri, Aneeshkumar G.; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, Bethesda, MD USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC USA.
RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, Bethesda, MD USA.; Maraia, RJ (reprint author), US PHS, Commissioned Corps, Washington, DC USA.
EM maraiar@mail.nih.gov
OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688
NR 46
TC 3
Z9 3
U1 3
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD FEB 1
PY 2016
VL 13
IS 2
BP 166
EP 171
DI 10.1080/15476286.2015.1116677
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DG0HE
UT WOS:000371745100008
PM 26636900
ER
PT J
AU Laposky, AD
Van Cauter, E
Diez-Roux, AV
AF Laposky, Aaron D.
Van Cauter, Eve
Diez-Roux, Ana V.
TI Reducing health disparities: the role of sleep deficiency and sleep
disorders
SO SLEEP MEDICINE
LA English
DT Article
DE Sleep deficiency; Obstructive sleep apnea; Health disparities;
Socioeconomic position; Cardiovascular disease; Diabetes
ID RACIAL-DIFFERENCES; BLOOD-PRESSURE; PSYCHIATRIC-DISORDERS;
DIABETES-MELLITUS; INTERVIEW SURVEY; CIRCADIAN CLOCK; DURATION;
ASSOCIATION; DISEASE; APNEA
AB Decrements in sleep health, including insufficient sleep duration, irregular timing of sleep, poor sleep quality, and sleep/circadian disorders, are widespread in modern society and are associated with an array of disease risks and outcomes, including those contributing to health disparities (eg, cardiovascular disease, obesity and diabetes, psychiatric illness, and cancer). Recent findings have uncovered racial/ethnic and socioeconomic position differences in sleep health; however, the contribution of sleep deficiency to health disparities remains largely unexplored, and understanding the underlying causes of disparities in sleep health is only beginning to emerge. In 2011, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop, bringing together sleep and health disparities investigators, to identify research gaps and opportunities to advance sleep and health disparities science. This article provides a brief background and rationale for the workshop, and it disseminates the research recommendations and priorities resulting from the working group discussions. Published by Elsevier B.V.
C1 [Laposky, Aaron D.] NHLBI, NIH, 6701 Rockledge Dr,Suite 10042, Bethesda, MD 20892 USA.
[Van Cauter, Eve] Univ Chicago, Dept Med, 5841 S Maryland Ave,MC 6092, Chicago, IL 60637 USA.
[Diez-Roux, Ana V.] Drexel Univ, Sch Publ Hlth, 3215 Market St, Philadelphia, PA 19104 USA.
RP Laposky, AD (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Suite 10042, Bethesda, MD 20892 USA.
EM laposkya@nhlbi.nih.gov
FU NHLBI Division of Lung Diseases; Division for the Application of
Research Discoveries
FX We would like to acknowledge the contribution of each participant in the
2010 "Reducing Health Disparities: The Role of Sleep Deficiency and
Sleep Disorders" workshop. Gary Bennett, PhD, Duke University; Carla
Boutin-Foster, MD, Cornell University; Joseph Buckhalt, PhD, Auburn
University; Orfeu Buxton, PhD, Harvard Medical School; Mercedes
Carnethon, PhD, FAHA, Northwestern University; Lisa Cooper, MD, MPH,
Johns Hopkins University; Tiffany Gary-Webb, PhD, Columbia University;
Maria Glymour, PhD, Harvard University; Michael Grandner, PhD,
University of Pennsylvania; Lauren Hale, PhD, SUNY, Stony Brook,
Girardin Jean-Louis, PhD, SUNY Downstate Medical Center; Kristen
Knutson, PhD, University of Chicago; Nancy Kressin, PhD, Boston
University; Kenneth Lichstein, PhD, University of Alabama; Karen
Matthews, PhD, University of Pittsburgh School of Medicine; Carlos F.
Mendes de Leon, PhD, University of Michigan; Sanjay Patel, MD, Harvard
Medical School; David Takeuchi, PhD, University of Washington. The
workshop was supported by the NHLBI Division of Lung Diseases and the
Division for the Application of Research Discoveries.
NR 44
TC 5
Z9 5
U1 2
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD FEB
PY 2016
VL 18
BP 3
EP 6
DI 10.1016/j.sleep.2015.01.007
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA DG1ON
UT WOS:000371837500002
PM 26431756
ER
PT J
AU Brady, OJ
Godfray, HCJ
Tatem, AJ
Gething, PW
Cohen, JM
McKenzie, FE
Perkins, TA
Reiner, RC
Tusting, LS
Sinka, ME
Moyes, CL
Eckhoff, PA
Scott, TW
Lindsay, SW
Hay, SI
Smith, DL
AF Brady, Oliver J.
Godfray, H. Charles J.
Tatem, Andrew J.
Gething, Peter W.
Cohen, Justin M.
McKenzie, F. Ellis
Perkins, T. Alex
Reiner, Robert C., Jr.
Tusting, Lucy S.
Sinka, Marianne E.
Moyes, Catherine L.
Eckhoff, Philip A.
Scott, Thomas W.
Lindsay, Steven W.
Hay, Simon I.
Smith, David L.
TI Vectorial capacity and vector control: reconsidering sensitivity to
parameters for malaria elimination
SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
DE Elimination; Malaria; Modelling; Operational research; Policy; Vector
control
ID DOMINANT ANOPHELES VECTORS; DISTRIBUTION MAPS; BIONOMIC PRECIS;
TRANSMISSION INTENSITY; SEEKING BEHAVIOR; AEDES-AEGYPTI; BED NETS;
MOSQUITOS; INFECTION; DYNAMICS
AB Background: Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria.
Methods and Results: Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention.
Conclusions: Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions.
C1 [Brady, Oliver J.; Sinka, Marianne E.; Moyes, Catherine L.; Hay, Simon I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Godfray, H. Charles J.; Sinka, Marianne E.; Smith, David L.] Univ Oxford, Dept Zool, S Parks Rd, Oxford, England.
[Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.; McKenzie, F. Ellis; Perkins, T. Alex; Reiner, Robert C., Jr.; Scott, Thomas W.; Hay, Simon I.; Smith, David L.] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
[Tatem, Andrew J.] Flowminder Fdn, Stockholm, Sweden.
[Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, S Parks Rd, Oxford, England.
[Cohen, Justin M.] Clinton Hlth Access Initiat, Boston, MA USA.
[Perkins, T. Alex] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
[Perkins, T. Alex] Univ Notre Dame, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Reiner, Robert C., Jr.] Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA.
[Tusting, Lucy S.] London Sch Hyg & Trop Med, Dept Dis Control, London WC1, England.
[Eckhoff, Philip A.] Inst Dis Modeling, Bellevue, WA USA.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Lindsay, Steven W.] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
[Hay, Simon I.; Smith, David L.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
RP Brady, OJ (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM oliver.brady@well.ox.ac.uk
OI Cohen, Justin/0000-0003-4481-6784; Hay, Simon/0000-0002-0611-7272;
Tusting, Lucy/0000-0002-6897-8625; Gething, Peter/0000-0001-6759-5449;
Brady, Oliver/0000-0002-3235-2129; Moyes, Catherine/0000-0002-8028-4079
FU Bill & Melinda Gates Foundation [OPP1110495, OPP1119467, OPP1053338,
OPP1081737, OPP1106023, OPP1093011, OPP1106427, 1032350]; National
Institutes of Health/National Institute of Allergy and Infectious
Diseases [U19AI089674, P01AI098670]; Leverhulme Centre for Integrative
Research in Agriculture and Health; 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; Foundation for the National
Institutes of Health through Vector-Based Control of Transmission:
Discovery Research program of the Grand Challenges in Global Health
initiative; Wellcome Trust [095066]
FX This work was supported by the Bill & Melinda Gates Foundation
[#OPP1110495 to DLS, TAP and RCR, #OPP1119467 to OJB and SIH,
#OPP1053338 to SWL, #OPP1081737 to RCR and TWS, #OPP1106023 to PWG,
#OPP1093011 to CLM, #OPP1106427 to AJT and #1032350 to AJT], National
Institutes of Health/National Institute of Allergy and Infectious
Diseases [#U19AI089674 to DLS and SWL and #P01AI098670 to TAP and TWS],
the Leverhulme Centre for Integrative Research in Agriculture and Health
(to LST), 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 (to DLS, TAP, RCR, SWL, TWS, AJT, HCJG and SIH) and
the Foundation for the National Institutes of Health through the
Vector-Based Control of Transmission: Discovery Research program of the
Grand Challenges in Global Health initiative (to HCJG). The Wellcome
Trust (#095066) to SIH. The Vector-Borne Disease Network (VecNet) to MES
and CLM.
NR 74
TC 4
Z9 4
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0035-9203
EI 1878-3503
J9 T ROY SOC TROP MED H
JI Trans. Roy. Soc. Trop. Med. Hyg.
PD FEB
PY 2016
VL 110
IS 2
BP 107
EP 117
DI 10.1093/trstmh/trv113
PG 11
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA DF5VT
UT WOS:000371421400005
PM 26822603
ER
PT J
AU Stone, HB
Bernhard, EJ
Coleman, CN
Deye, J
Capala, J
Mitchell, JB
Brown, JM
AF Stone, Helen B.
Bernhard, Eric J.
Coleman, C. Norman
Deye, James
Capala, Jacek
Mitchell, James B.
Brown, J. Martin
TI Preclinical Data on Efficacy of 10 Drug-Radiation Combinations:
Evaluations, Concerns, and Recommendations
SO TRANSLATIONAL ONCOLOGY
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; SQUAMOUS-CELL CARCINOMA; ADVANCED SOLID
TUMORS; PHASE-I; ADVANCED CANCER; IONIZING-RADIATION; MULTIPLE-MYELOMA;
PREDICTIVE-VALUE; HEALTHY-SUBJECTS; LOCAL-CONTROL
AB BACKGROUND: Clinical testing of new therapeutic interventions requires comprehensive, high-quality preclinical data. Concerns regarding quality of preclinical data have been raised in recent reports. This report examines the data on the interaction of 10 drugs with radiation and provides recommendations for improving the quality, reproducibility, and utility of future studies. The drugs were AZD6244, bortezomib, 17-DMAG, erlotinib, gefitinib, lapatinib, oxaliplatin/Lipoxal, sunitinib (Pfizer, Corporate headquarters, New York, NY), thalidomide, and vorinostat. METHODS: In vitro and in vivo data were tabulated from 125 published papers, including methods, radiation and drug doses, schedules of administration, assays, measures of interaction, presentation and interpretation of data, dosimetry, and conclusions. RESULTS: In many instances, the studies contained inadequate or unclear information that would hamper efforts to replicate or intercompare the studies, and that weakened the evidence for designing and conducting clinical trials. The published reports on these drugs showed mixed results on enhancement of radiation response, except for sunitinib, which was ineffective. CONCLUSIONS: There is a need for improved experimental design, execution, and reporting of preclinical testing of agents that are candidates for clinical use in combination with radiation. A checklist is provided for authors and reviewers to ensure that preclinical studies of drug-radiation combinations meet standards of design, execution, and interpretation, and report necessary information to ensure high quality and reproducibility of studies. Improved design, execution, common measures of enhancement, and consistent interpretation of preclinical studies of drug-radiation interactions will provide rational guidance for prioritizing drugs for clinical radiotherapy trials and for the design of such trials.
C1 [Stone, Helen B.; Bernhard, Eric J.; Coleman, C. Norman; Deye, James; Capala, Jacek] NCI, Radiat Res Program, 9609 Med Ctr Dr,MSC 9727, Rockville, MD 20850 USA.
[Mitchell, James B.] NCI, Radiat Biol Branch, MSC 1002,10 Ctr Dr, Bethesda, MD 20892 USA.
[Brown, J. Martin] Stanford Univ, Radiat & Canc Biol, CCSR S Rm 1255,269 Campus Dr, Stanford, CA 94305 USA.
RP Bernhard, EJ (reprint author), NCI, Radiotherapy Dev Branch, RRP, DCTD,NIH, 9609 Med Ctr Dr,MSC 9727, Rockville, MD 20850 USA.
EM bernhardej@mail.nih.gov
FU National Cancer Institute (NCI) [R01CA149318]
FX This study was funded by the National Cancer Institute (NCI) which
employs co-authors E. J. B., C. N. C., J. D., J. C., and J. B. M. J. M.
B is funded in part by R01CA149318. The work represents the opinion of
all the authors and does not reflect official NCI positions or policies.
NR 76
TC 4
Z9 4
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-5233
J9 TRANSL ONCOL
JI Transl. Oncol.
PD FEB
PY 2016
VL 9
IS 1
BP 46
EP 56
DI 10.1016/j.tranon.2016.01.002
PG 11
WC Oncology
SC Oncology
GA DG2OP
UT WOS:000371907200007
PM 26947881
ER
PT J
AU Liu, Y
Sousa, R
Wang, YX
AF Liu, Yu
Sousa, Rui
Wang, Yun-Xing
TI Specific labeling: An effective tool to explore the RNA world
SO BIOESSAYS
LA English
DT Article
DE label; modified; PLOR; RNA
ID SITE-SPECIFIC MODIFICATION; SINGLE-MOLECULE FLUORESCENCE; ENGINEERED
TWIN RIBOZYME; MESSENGER-RNA; NUCLEIC-ACID; CHEMICAL LIGATION; LIVING
CELLS; TRANSCRIPTION INITIATION; SELENIUM DERIVATIZATION;
MASS-SPECTROMETRY
AB Our knowledge about the functional diversity and importance of RNA in biology has grown enormously over the past three decades and has driven efforts to develop better tools to characterize RNAs. Amongst these tools are methods for preparing specifically labeled or chemically modified RNAs, which are essential for basic research, biomedical, and clinical applications. Understanding the potential and limits of these different RNA synthesis and labeling strategies is important in deciding how to approach the preparation of a particular RNA molecule. Here, we review these various labeling methods and future directions of the field.
C1 [Liu, Yu; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
[Sousa, Rui] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
RP Liu, Y (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
EM liuy13@mail.nih.gov
FU National Cancer Institute
FX We thank the members of Wang lab for discussion. This work was supported
by the Intramural Research Programs of the National Cancer Institute.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US government. Authors have filed patents for PLOR
technology.
NR 115
TC 1
Z9 1
U1 9
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD FEB
PY 2016
VL 38
IS 2
BP 192
EP 200
DI 10.1002/bies.201500119
PG 9
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA DF3SA
UT WOS:000371266200010
PM 26660847
ER
PT J
AU Jensen, RA
Sim, XL
Smith, AV
Li, XH
Jakobsdottir, J
Cheng, CY
Brody, JA
Cotch, MF
Mcknight, B
Klein, R
Wang, JJ
Kifley, A
Harris, TB
Launer, LJ
Taylor, KD
Klein, BEK
Raffel, LJ
Li, X
Ikram, MA
Klaver, CC
van der Lee, SJ
Mutlu, U
Hofman, A
Uitterlinden, AG
Liu, CY
Kraja, AT
Mitchell, P
Gudnason, V
Rotter, JI
Boerwinkle, E
van Duijn, CM
Psaty, BM
Wong, TY
AF Jensen, Richard A.
Sim, Xueling
Smith, Albert Vernon
Li, Xiaohui
Jakobsdottir, Johanna
Cheng, Ching-Yu
Brody, Jennifer A.
Cotch, Mary Frances
Mcknight, Barbara
Klein, Ronald
Wang, Jie Jin
Kifley, Annette
Harris, Tamara B.
Launer, Lenore J.
Taylor, Kent D.
Klein, Barbara E. K.
Raffel, Leslie J.
Li, Xiang
Ikram, M. Arfan
Klaver, Caroline C.
van der Lee, Sven J.
Mutlu, Unal
Hofman, Albert
Uitterlinden, Andre G.
Liu, Chunyu
Kraja, Aldi T.
Mitchell, Paul
Gudnason, Vilmundur
Rotter, Jerome I.
Boerwinkle, Eric
van Duijn, Cornelia M.
Psaty, Bruce M.
Wong, Tien Y.
CA CHARGE Exome Chip Blood Pressure C
TI Novel Genetic Loci Associated With Retinal Microvascular Diameter
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE meta-analysis; genetics; microcirculation; exome; retina
ID GENOME-WIDE ASSOCIATION; BEAVER DAM EYE; VESSEL DIAMETERS;
BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; VASCULAR CALIBER;
ATHEROSCLEROSIS RISK; OLDER PERSONS; HYPERTENSION; DESIGN
AB Background-
There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size.
Methods and Results-
This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1x10(-)(11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4x10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0x10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4x10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5x10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3x10(-04)).
Conclusions-
Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease.
C1 [Jensen, Richard A.; Brody, Jennifer A.; Mcknight, Barbara; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
[Jensen, Richard A.; Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Mcknight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
[Sim, Xueling] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sim, Xueling] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Smith, Albert Vernon; Jakobsdottir, Johanna; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Dept Med, Reykjavik, Iceland.
[Li, Xiaohui; Taylor, Kent D.; Rotter, Jerome I.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90024 USA.
[Cheng, Ching-Yu; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
[Cheng, Ching-Yu; Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore.
[Cheng, Ching-Yu] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Liu, Chunyu] NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA.
[Cotch, Mary Frances; Harris, Tamara B.; Launer, Lenore J.] NIH, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA.
[Wang, Jie Jin; Kifley, Annette; Mitchell, Paul] Univ Sydney, Westmead Millennium Inst, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Raffel, Leslie J.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Ikram, M. Arfan; Klaver, Caroline C.; van der Lee, Sven J.; Mutlu, Unal; Hofman, Albert; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Klaver, Caroline C.; Mutlu, Unal] Erasmus Univ, Med Ctr, Dept Ophthalmol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Liu, Chunyu] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Liu, Chunyu] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Kraja, Aldi T.] Univ Washington, Sch Med, Dept Genet, Div Stat Genom, Seattle, WA 98101 USA.
[Kraja, Aldi T.] Univ Washington, Sch Med, Ctr Genome Sci & Syst Biol, Seattle, WA 98101 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
RP Jensen, RA (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
EM richaj@uw.edu
RI Wang, Jie Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Smith, Albert
Vernon/K-5150-2015
OI Wang, Jie Jin/0000-0001-9491-4898; Smith, Albert
Vernon/0000-0003-1942-5845
FU National Institutes of Health (NIH) through the Intramural Research
Program of the National Institute of Aging [ZIAAG007380]; National Eye
Institute (NEI) [ZIAEY00401]; NIH [N01-AG-1-2100, HHSN268200625226C];
Hjartavernd (the Icelandic Heart Association); Althingi (Icelandic
Parliament); University of Iceland Research Fund; National Heart, Lung,
and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human
Genome Research Institute [U01HG004402]; US Cohorts for Heart and Aging
Research in Genomic Epidemiology (CHARGE) Consortium through the
National Institutes of Health American Recovery and Reinvestment Act
[5RC2HL102419]; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC75150, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083,
N01HC85086, U01HL080295, HL080295, HL087652, HL103612, HL120393,
HL105756, HL068986, N02-HL-6-4278]; National Institute on Aging
[AG023629]; National Center for Advancing Translational Sciences, CTSI
[UL1TR000124]; National Institute of Diabetes and Digestive and Kidney
Disease Diabetes Research Center (DRC) grant [DK063491]; MESA
[N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168,
N01-HC-95169]; National Center for Research Resources [HL071205,
UL1-DR-001079]; National Center for Advancing Translational Sciences,
CTSI grant [UL1TR000124]; National Institute of Diabetes and Digestive
and Kidney Disease Diabetes Research Center (DRC) [DK063491]; National
Medical Research Council (NMRC), Singapore [0796/2003, IRG07nov013,
IRG09nov014, NMRC 1176/2008, STaR/0003/2008, CG/SERI/2010]; Biomedical
Research Council, Singapore [08/1/35/19/550, 09/1/35/19/616]; NMRC
[CSA/033/2012]; Australian National Health and Medical Research Council,
Canberra Australia [974159, 211069, 457349, 512423, 475604, 529912];
NEI/NIH as part of the International AMD Genomics Consortium (IAMDGC),
an international collaborative effort to investigate genetics of
age-related macular degeneration; National Institutes of Health Research
Biomedical Research Centre for Ophthalmology; Moorfields Eye Hospital;
UCL Institute of Ophthalmology, London, United Kingdom; Netherlands
Genomics Initiative/Netherlands Organisation for Scientific Research
(NWO) [050-060-810]; Netherlands Organization for Scientific Research
(NWO) [184021007]; Rainbow Project of the Biobanking and Biomolecular
Research Infrastructure Netherlands [RP10]; [R01HL087641];
[R01HL59367]; [R01HL086694]
FX The Age, Gene, Environment, Susceptibility Study-Reykjavik (AGES): this
research was supported by the National Institutes of Health (NIH)
through the Intramural Research Program of the National Institute of
Aging (ZIAAG007380) and the National Eye Institute (NEI; ZIAEY00401),
NIH contract number N01-AG-1-2100, Hjartavernd (the Icelandic Heart
Association), the Althingi (Icelandic Parliament), and the University of
Iceland Research Fund. We are indebted to Icelandic Heart Association
clinic staff and to the AGES participants whose decision to volunteer
made this study possible. The funders had no role in data collection,
management, analysis and interpretation of the data, preparation,
writing and approval of the article, or decision to submit the article
for publication. The Atherosclerosis Risk in Communities (ARIC): the
study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National
Human Genome Research Institute contract U01HG004402; and NIH contract
HHSN268200625226C. Support for the exome chip genotyping and joint
calling was provided by Building on genome-wide association studies for
NHLBI diseases: the US Cohorts for Heart and Aging Research in Genomic
Epidemiology (CHARGE) Consortium through the National Institutes of
Health American Recovery and Reinvestment Act of 2009 (5RC2HL102419;
principla investigator: E. Boerwinkle). We thank the staff and
participants of the ARIC study for their important contributions. The
Cardiovascular Health Study (CHS): this research was supported by NHLBI
contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC75150,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086;
and NHLBI grants U01HL080295, HL080295, HL087652, HL103612, HL120393,
HL105756, and HL068986 with additional contribution from the National
Institute of Neurological Disorders and Stroke. Additional support was
provided through AG023629 from the National Institute on Aging. A full
list of CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. The provision of genotyping data was
supported in part by the National Center for Advancing Translational
Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes
and Digestive and Kidney Disease Diabetes Research Center (DRC) grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the NIH. Multi-Ethnic
Study of Atherosclerosis (MESA)-MESA family, MESA SHARe, CTSI, DRC: this
research was supported by the MESA contracts N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169, by grant
HL071205 and by UL1-DR-001079 from National Center for Research
Resources. Funding for MESA SHARe genotyping was provided by NHLBI
contract N02-HL-6-4278. The provision of genotyping data was supported
in part by the National Center for Advancing Translational Sciences,
CTSI grant UL1TR000124, and the National Institute of Diabetes and
Digestive and Kidney Disease Diabetes Research Center (DRC) grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center.; The authors thank the participants of the MESA study, the
Coordinating Center, MESA investigators, and study staff for their
valuable contributions. A full list of participating MESA investigators
and institutions can be found at http://www.mesa-nhlbi.org. Singapore
Chinese Eye Study (SCES), Singapore Malay Eye Study (SINDI), and
Singapore Indian Eye Study (SiMES): the SCES, SiMES, and SINDI were
supported by the National Medical Research Council (NMRC), Singapore
(grants 0796/2003, IRG07nov013, IRG09nov014, NMRC 1176/2008,
STaR/0003/2008, and CG/SERI/2010), and Biomedical Research Council,
Singapore (08/1/35/19/550 and 09/1/35/19/616). C.-Y. Cheng was supported
by an award from NMRC (CSA/033/2012). The Singapore Tissue Network and
the Genome Institute of Singapore, Agency for Science, Technology and
Research, Singapore provided services for tissue archival and
genotyping, respectively. The Blue Mountains Eye Study (BMES): the study
has been supported by the Australian National Health and Medical
Research Council, Canberra Australia (grant numbers: 974159, 211069,
457349, 512423, 475604, and 529912, and the funding for Centre for
Clinical Research Excellence in Translational Clinical Research in Eye
Diseases, CCRE in TCR-Eye). The cost of genotyping was funded by the
NEI/NIH as part of the International AMD Genomics Consortium (IAMDGC),
an international collaborative effort to investigate genetics of
age-related macular degeneration. Genotyping was performed at the Center
for Inherited Diseases Research at the Johns Hopkins University, United
States. We also acknowledge the funding body National Institutes of
Health Research Biomedical Research Centre for Ophthalmology, Moorfields
Eye Hospital, and UCL Institute of Ophthalmology, London, United
Kingdom. The generation and management of the Illumina exome chip
version 1.0 array data for the Rotterdam Study (RS-I) were executed by
the Human Genotyping Facility of the Genetic Laboratory of the
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
The exome chip array data set was funded by the Genetic Laboratory of
the Department of Internal Medicine, Erasmus MC, from the Netherlands
Genomics Initiative/Netherlands Organisation for Scientific Research
(NWO)-sponsored Netherlands Consortium for Healthy Aging (project no.
050-060-810); the Netherlands Organization for Scientific Research (NWO;
project number 184021007) and by the Rainbow Project (RP10; Netherlands
Exome Chip Project) of the Biobanking and Biomolecular Research
Infrastructure Netherlands (http://www.bbmri.nl). We thank Mila Jhamai,
Sarah Higgins, and Marijn Verkerk for their help in creating the exome
chip database and Carolina Medina-Gomez, MSc, Lennard Karsten, MSc, and
Linda Broer, PhD for quality control and variant calling. Variants were
called using the best practice protocol developed by Grove et al as part
of the CHARGE Consortium exome chip central calling effort.
NR 51
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2016
VL 9
IS 1
BP 45
EP 54
DI 10.1161/CIRCGENETICS.115.001142
PG 10
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA DF0FI
UT WOS:000371014100007
PM 26567291
ER
PT J
AU Yu, B
Pulit, SL
Hwang, SJ
Brody, JA
Amin, N
Auer, PL
Bis, JC
Boerwinkle, E
Burke, GL
Chakravarti, A
Correa, A
Dreisbach, AW
Franco, OH
Ehret, GB
Franceschini, N
Hofman, A
Lin, DY
Metcalf, GA
Musani, SK
Muzny, D
Palmas, W
Raffel, L
Reiner, A
Rice, K
Rotter, JI
Veeraraghavan, N
Fox, E
Guo, XQ
North, KE
Gibbs, RA
van Duijn, CM
Psaty, BM
Levy, D
Newton-Cheh, C
Morrison, AC
AF Yu, Bing
Pulit, Sara L.
Hwang, Shih-Jen
Brody, Jennifer A.
Amin, Najaf
Auer, Paul L.
Bis, Joshua C.
Boerwinkle, Eric
Burke, Gregory L.
Chakravarti, Aravinda
Correa, Adolfo
Dreisbach, Albert W.
Franco, Oscar H.
Ehret, Georg B.
Franceschini, Nora
Hofman, Albert
Lin, Dan-Yu
Metcalf, Ginger A.
Musani, Solomon K.
Muzny, Donna
Palmas, Walter
Raffel, Leslie
Reiner, Alex
Rice, Ken
Rotter, Jerome I.
Veeraraghavan, Narayanan
Fox, Ervin
Guo, Xiuqing
North, Kari E.
Gibbs, Richard A.
van Duijn, Cornelia M.
Psaty, Bruce M.
Levy, Daniel
Newton-Cheh, Christopher
Morrison, Alanna C.
CA CHARGE Consortium
Natl Heart Lung Blood Inst GO ESP
TI Rare Exome Sequence Variants in CLCN6 Reduce Blood Pressure Levels and
Hypertension Risk
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE genetic variation; hypertension; genome-wide association study; exome;
blood pressure
ID GENOME-WIDE ASSOCIATION; PULSE PRESSURE; MEAN ARTERIAL; DESIGN;
MUTATIONS; TRAITS; GENES; OBJECTIVES; LOCI; ATHEROSCLEROSIS
AB Background-
Rare genetic variants influence blood pressure (BP).
Methods and Results-
Whole-exome sequencing was performed on DNA samples from 17 956 individuals of European ancestry and African ancestry (14 497, first-stage discovery and 3459, second-stage discovery) to examine the effect of rare variants on hypertension and 4 BP traits: systolic BP, diastolic BP, pulse pressure, and mean arterial pressure. Tests of approximate to 170 000 common variants (minor allele frequency, >= 1%; statistical significance, P <= 2.9x10(-7)) and gene-based tests of rare variants (minor allele frequency, < 1%; approximate to 17 000 genes; statistical significance, P <= 1.5x10(-6)) were evaluated for each trait and ancestry, followed by multiethnic meta-analyses. In the first-stage discovery, rare coding variants (splicing, stop-gain, stop-loss, nonsynonymous variants, or indels) in CLCN6 were associated with lower diastolic BP (cumulative minor allele frequency, 1.3%; beta=-3.20; P=4.1x10(-6)) and were independent of a nearby common variant (rs17367504) previously associated with BP. CLCN6 rare variants were also associated with lower systolic BP (beta=-4.11; P=2.8x10(-4)), mean arterial pressure (beta=-3.50; P=8.9x10(-6)), and reduced hypertension risk (odds ratio, 0.72; P=0.017). Meta-analysis of the 2-stage discovery samples showed that CLCN6 was associated with lower diastolic BP at exome-wide significance (cumulative minor allele frequency, 1.1%; beta=-3.30; P=5.0x10(-7)).
Conclusions-
These findings implicate the effect of rare coding variants in CLCN6 in BP variation and offer new insights into BP regulation.
C1 [Yu, Bing; Boerwinkle, Eric; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Pressler St,Suite 453E, Houston, TX 77030 USA.
[Pulit, Sara L.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Pulit, Sara L.; Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Hwang, Shih-Jen; Levy, Daniel] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Hwang, Shih-Jen; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Brody, Jennifer A.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA.
[Amin, Najaf; Franco, Oscar H.; Hofman, Albert; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Auer, Paul L.] Univ Wisconsin Milwaukee, Sch Publ Hlth, Biostat, Milwaukee, WI USA.
[Boerwinkle, Eric; Metcalf, Ginger A.; Muzny, Donna; Veeraraghavan, Narayanan; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Burke, Gregory L.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Ehret, Georg B.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.
[Dreisbach, Albert W.; Musani, Solomon K.; Fox, Ervin] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS USA.
[Ehret, Georg B.] Univ Hosp Geneva, Dept Specialties Internal Med, Div Cardiol, Geneva, Switzerland.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Lin, Dan-Yu] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Palmas, Walter] Columbia Univ, Med Ctr, Dept Med, New York, NY USA.
[Raffel, Leslie] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Raffel, Leslie] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Clin & Translat Sci Inst, Los Angeles, CA 90048 USA.
[Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Rotter, Jerome I.; Guo, Xiuqing] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Levy, Daniel] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Morrison, AC (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Pressler St,Suite 453E, Houston, TX 77030 USA.
EM alanna.c.morrison@uth.tmc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [RC2 HL-103010, RC2
HL-102923, RC2 HL-102924]; NHLBI [RC2 HL-102925, RC2 HL-102926,
HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268-201100009C, HHSN2682011000010C,
HHSN2682011000011C, HHSN2682011000012C, R01HL087641, R01HL59367,
R01HL086694, N01-HC-25195, HHSN268201200036C, HHSN268200800007C,
N01HC55222N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082,
N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756,
R01HL103612, R01HL120393]; National Institutes of Health through the
American Recovery and Reinvestment Act [5RC2HL102419]; Affymetrix, Inc
[N02-HL-6-4278]; National Institute on Aging [R01AG023629R01AG023629];
National Heart, Lung, and Blood Institute [HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268-201300050C]; National Institute on Minority Health and Health
Disparities; MESA [N01-HC-95159, N01-HC-95160, N01-HC-95161,
N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166,
N01-HC-95167, N01-HC-95168, N01-HC-95169]; National Center for Research
Resources [UL1-TR-000040, UL1-RR-025005]; National Center for Advancing
Translational Sciences, CTSI grant [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center
[DK063491]; National Heart, Lung, and Blood Institute, National
Institutes of Health, US Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268-201100004C, HHSN271201100004C]; European
Commission FP6 STRP grant [018947 (LSHG-CT-2006-01947)]; European
Community's Seventh Framework Programme by the European Commission
[HEALTH-F4-2007-201413, QLG2-CT-2002-01254]; Netherlands Organization
for Scientific Research; Russian Foundation for Basic Research [NWO-RFBR
047.017.043]; ZonMw [91111025]; Hersenstichting Nederland [F2013[1]-28];
Netherlands Organisation of Scientific Research Netherlands Organisation
for Scientific Research (NWO) Investments [175.010.2005.011,
911-03-012]; Research Institute for Diseases in the Elderly
[014-93-015]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810];
Netherlands Consortium for Healthy Ageing (NCHA); NGI/NWO [050-060-810];
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC;
complementation project of the Biobanking and Biomolecular Research
Infrastructure Netherlands [CP2010-41]; Erasmus Medical Center and
Erasmus University, Rotterdam; Netherlands Organization for the Health
Research and Development (ZonMw); Research Institute for Diseases in the
Elderly; Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission (DG XII); Municipality
of Rotterdam
FX Funding for GO Exome Sequencing Project was provided by National Heart,
Lung, and Blood Institute (NHLBI) grants RC2 HL-103010 (HeartGO), RC2
HL-102923 (LungGO), and RC2 HL-102924 (WHISP). The exome sequencing was
performed through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926
(SeattleGO). Funding support for Building on GWAS for NHLBI-diseases:
the U.S. CHARGE consortium was provided by the National Institutes of
Health through the American Recovery and Reinvestment Act of 2009
(5RC2HL102419). Sequencing was carried out at the Baylor Genome Center
(U54 HG003273). The Atherosclerosis Risk in Communities (ARIC) study is
carried out as a collaborative study supported by NHLBI contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268-201100009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C), R01HL087641, R01HL59367,
and R01HL086694. The Framingham Heart Study (FHS) was conducted and
supported by the NHLBI in collaboration with Boston University (contract
no. N01-HC-25195), and its contract with Affymetrix, Inc, for
genome-wide genotyping services (contract no. N02-HL-6-4278), for
quality control by FHS investigators using genotypes in the SNP Health
Association Resource project. A portion of this research was conducted
using the Linux Cluster for Genetic Analysis computing resources at
Boston University Medical Campus. The Cardiovascular Health Study (CHS)
research was supported by NHLBI contracts HHSN268201200036C,
HHSN268200800007C, N01HC55222N01HC55222, N01HC85079, N01HC85080,
N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants
U01HL080295, R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with
additional contribution from the National Institute of Neurological
Disorders and Stroke. Additional support was provided through
R01AG023629R01AG023629 from the National Institute on Aging. The Jackson
Heart Study (JHS) was supported by contracts HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C,
HHSN268-201300050C from the National Heart, Lung, and Blood Institute
and the National Institute on Minority Health and Health Disparities.
The Multi-Ethnic Study of Atherosclerosis (MESA) was supported by the
MESA contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167,
N01-HC-95168, and N01-HC-95169 and by grants UL1-TR-000040 and
UL1-RR-025005 from National Center for Research Resources. The provision
of genotyping data was supported in part by the National Center for
Advancing Translational Sciences, CTSI grant UL1TR000124, and the
National Institute of Diabetes and Digestive and Kidney Disease Diabetes
Research Center grant DK063491 to the Southern California Diabetes
Endocrinology Research Center. The Women's Health Initiative (WHI)
program was funded by the National Heart, Lung, and Blood Institute,
National Institutes of Health, US Department of Health and Human
Services through contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268-201100004C, and
HHSN271201100004C." The Erasmus Rucphen Family (ERF) study as a part of
European Special Populations Research Network was supported by European
Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also
received funding from the European Community's Seventh Framework
Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the
European Commission under the programme Quality of Life and Management
of the Living Resources of 5th Framework Programme (no.;
QLG2-CT-2002-01254). High-throughput analysis of the ERF data was
supported by joint grant from Netherlands Organization for Scientific
Research and the Russian Foundation for Basic Research (NWO-RFBR
047.017.043). Exome sequencing analysis in ERF was supported by the
ZonMw grant (project 91111025). N. Amin was supported by the
Hersenstichting Nederland (project no. F2013[1]-28). The generation and
management of GWAS genotype data for the Rotterdam Study (RS) were
supported by the Netherlands Organisation of Scientific Research
Netherlands Organisation for Scientific Research (NWO) Investments (no.
175.010.2005.011 and 911-03-012). This study was funded by the Research
Institute for Diseases in the Elderly (014-93-015; RIDE2), the
Netherlands Genomics Initiative (NGI)/NWO (project nr. 050-060-810) and
Netherlands Consortium for Healthy Ageing (NCHA). The generation and
management of the exome sequencing data for the RS were executed by the
Human Genotyping Facility of the Genetic Laboratory of the Department of
Internal Medicine, Erasmus MC, the Netherlands. The exome sequencing
data set was funded by the NGI/NWO-sponsored NCHA (project no.
050-060-810), by the Genetic Laboratory of the Department of Internal
Medicine, Erasmus MC, and by a complementation project of the Biobanking
and Biomolecular Research Infrastructure Netherlands
(http://www.bbmri.nl; project no. CP2010-41). The RS was funded by
Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands
Organization for the Health Research and Development (ZonMw), the
Research Institute for Diseases in the Elderly, the Ministry of
Education, Culture and Science, the Ministry for Health, Welfare and
Sports, the European Commission (DG XII), and the Municipality of
Rotterdam.
NR 43
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2016
VL 9
IS 1
BP 64
EP 70
DI 10.1161/CIRCGENETICS.115.001215
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA DF0FI
UT WOS:000371014100009
PM 26658788
ER
PT J
AU Belalcazar, LM
Papandonatos, GD
Erar, B
Peter, I
Alkofide, H
Balasubramanyam, A
Brautbar, A
Kahn, SE
Knowler, WC
Ballantyne, CM
McCaffery, JM
Huggins, GS
AF Belalcazar, L. Maria
Papandonatos, George D.
Erar, Bahar
Peter, Inga
Alkofide, Hadeel
Balasubramanyam, Ashok
Brautbar, Ariel
Kahn, Steven E.
Knowler, William C.
Ballantyne, Christie M.
McCaffery, Jeanne M.
Huggins, Gordon S.
CA Look AHEAD Study
TI Lifestyle Intervention for Weight Loss and Cardiometabolic Changes in
the Setting of Glucokinase Regulatory Protein Inhibition Glucokinase
Regulatory Protein-Leu446Pro Variant in Look AHEAD
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE lifestyle; GCKR; behavioral intervention; triglycerides; C-reactive
protein; obesity; diabetes mellitus
ID C-REACTIVE PROTEIN; FASTING PLASMA-GLUCOSE; TYPE-2 DIABETES RISK;
CARDIOVASCULAR-DISEASE; TRIGLYCERIDE LEVELS; REDUCING LIPIDS;
INDIVIDUALS; HOMEOSTASIS; ASSOCIATION; PREVALENCE
AB Background-
Glucokinase regulatory protein (GCKR) inhibitors offer a novel treatment approach for glucose control in diabetes mellitus; however, their cardiometabolic effects, particularly in relation to increased triglycerides and C-reactive protein (CRP) levels, are of concern. GCKR Leu446Pro is a common variant associated with reduced GCKR function, increased triglycerides, and CRP.
Methods and Results-
We investigated whether a 1-year intensive lifestyle intervention (ILI) for weight loss would avert the unfavorable cardiometabolic effects associated with GCKR Leu446Pro when compared with a diabetes mellitus support and education arm in overweight/obese individuals with type 2 diabetes mellitus with triglyceride (n=3214) and CRP (n=1411) data participating in a randomized lifestyle intervention study for weight loss, Action for Health in Diabetes Mellitus (Look AHEAD). Once demographics, medication use and baseline adiposity, and fitness were accounted for, ILI did not modify the baseline association of GCKR-Leu446Pro with elevated triglycerides (beta +/- SE=0.067 +/- 0.013, P=1.5x10(-7) and beta +/- SE=0.052 +/- 0.015, P=5x10(-4)) or with elevated CRP (beta +/- SE=0.136 +/- 0.034, P=5.1x10(-5)and beta +/- SE=0.903 +/- 0.038, P=0.015) in the overall sample and Non-Hispanic Whites, respectively. The lack of a protective effect from ILI at 1 year when compared with diabetes mellitus support and education (ILI versus diabetes mellitus support and education interaction for triglyceride and CRP change, respectively: P=0.64 and 0.37 in the overall sample; P=0.27 and 0.05 in Non-Hispanic Whites) persisted after additional adjustment for changes in adiposity and fitness.
Conclusions-
Moderate improvements in adiposity and fitness with ILI did not mitigate the adverse cardiometabolic effects of GCKR inhibition in overweight/obese individuals with diabetes mellitus.
C1 [Belalcazar, L. Maria; Ballantyne, Christie M.] Univ Texas Med Branch, Dept Internal Med, Div Endocrinol & Metab, Galveston, TX 77555 USA.
[Papandonatos, George D.; Erar, Bahar] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA.
[Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
[Alkofide, Hadeel] Tufts Univ, Sackler Sch Biomed Res, Clin Translat Sci Program, Boston, MA 02111 USA.
[Balasubramanyam, Ashok] Baylor Coll Med, Div Endocrinol Diabet & Metab, Diabet Res Ctr, Translat Metab Unit, Houston, TX 77030 USA.
[Brautbar, Ariel] Baylor Coll Med, Dept Med, Houston, TX 77030 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.
[Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ USA.
[Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[McCaffery, Jeanne M.] Miriam Hosp, Dept Psychiat & Human Behav, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA.
[McCaffery, Jeanne M.] Brown Med Sch, Providence, RI USA.
[Huggins, Gordon S.] Tufts Med Ctr, Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02111 USA.
[Huggins, Gordon S.] Tufts Univ, Boston, MA 02111 USA.
RP Huggins, GS (reprint author), Tufts Med Ctr, MCRI Ctr Translat Genom, Boston, MA 02111 USA.; Huggins, GS (reprint author), Tufts Univ, Sch Med, Boston, MA 02111 USA.
EM ghuggins@tuftsmedicalcenter.org
OI Papandonatos, George/0000-0001-6770-932X; Kahn,
Steven/0000-0001-7307-9002
FU Department of Health and Human Services from the National Institutes of
Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182,
DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135,
DK56992]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Heart, Lung, and Blood Institute; National Institute
of Nursing Research; National Center on Minority Health and Health
Disparities; National Institutes of Health (NIH) Office of Research on
Women's Health; Centers for Disease Control and Prevention; Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases; Johns Hopkins Medical Institutions Bayview General
Clinical Research Center [M01RR02719]; Massachusetts General Hospital
Mallinckrodt General Clinical Research Center [M01RR01066]; University
of Colorado Health Sciences Center General Clinical Research Center
[M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University
of Tennessee at Memphis General Clinical Research Center [M01RR0021140];
University of Pittsburgh General Clinical Research Center [M01RR000056
44]; NIH [DK 046204]; VA Puget Sound Health Care System Medical Research
Service, Department of Veterans Affairs; Frederic C. Bartter General
Clinical Research Center [M01RR01346]; [DK090043-02]; [X01 HG006659];
[HL09051401]
FX This study was funded by DK090043-02 and X01 HG006659 (Drs Papandonatos,
McCaffery, Huggins) and HL09051401 (Drs Belalcazar and Ballantyne). Look
AHEAD was supported by the Department of Health and Human Services
through the following cooperative agreements from the National
Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171,
DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219,
DK57008, DK57135, and DK56992. The following federal agencies have
contributed support: National Institute of Diabetes and Digestive and
Kidney Diseases; National Heart, Lung, and Blood Institute; National
Institute of Nursing Research; National Center on Minority Health and
Health Disparities; National Institutes of Health (NIH) Office of
Research on Women's Health; and the Centers for Disease Control and
Prevention. This research was supported in part by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases. The Indian Health Service (IHS) provided personnel,
medical oversight, and use of facilities. The opinions expressed in this
article are those of the authors and do not necessarily reflect the
views of the IHS or other funding sources. Additional support was
received from The Johns Hopkins Medical Institutions Bayview General
Clinical Research Center (M01RR02719); the Massachusetts General
Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the
University of Colorado Health Sciences Center General Clinical Research
Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520);
the University of Tennessee at Memphis General Clinical Research Center
(M01RR0021140); the University of Pittsburgh General Clinical Research
Center (M01RR000056 44) and NIH grant (DK 046204); the VA Puget Sound
Health Care System Medical Research Service, Department of Veterans
Affairs; and the Frederic C. Bartter General Clinical Research Center
(M01RR01346). The following organizations have committed to make major
contributions to Look AHEAD: Federal Express; Health Management
Resources; Johnson & Johnson, LifeScan Inc; Optifast-Novartis Nutrition;
Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories;
Slim-Fast Foods Company; and Unilever.
NR 32
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2016
VL 9
IS 1
BP 71
EP 78
DI 10.1161/CIRCGENETICS.115.001192
PG 8
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA DF0FI
UT WOS:000371014100010
PM 26578543
ER
PT J
AU Brzeska, H
Koech, H
Pridham, KJ
Korn, ED
Titus, MA
AF Brzeska, Hanna
Koech, Hilary
Pridham, Kevin J.
Korn, Edward D.
Titus, Margaret A.
TI Selective localization of myosin-I proteins in macropinosomes and actin
waves
SO CYTOSKELETON
LA English
DT Article
DE unconventional myosins; BH site; membrane binding; macropinocytosis;
actin waves
ID DICTYOSTELIUM-DISCOIDEUM; UNCONVENTIONAL MYOSINS; DISTINCT FUNCTIONS;
CORTICAL TENSION; PLASMA-MEMBRANE; CRUCIAL ROLE; BINDING; PHAGOCYTOSIS;
CELLS; ENDOCYTOSIS
AB Class I myosins are widely expressed with roles in endocytosis and cell migration in a variety of cell types. Dictyostelium express multiple myosin Is, including three short-tailed (Myo1A, Myo1E, Myo1F) and three long-tailed (Myo1B, Myo1C, Myo1D). Here we report the molecular basis of the specific localizations of short-tailed Myo1A, Myo1E, and Myo1F compared to our previously determined localization of long-tailed Myo1B. Myo1A and Myo1B have common and unique localizations consistent with the various features of their tail region; specifically the BH sites in their tails are required for their association with the plasma membrane and heads are sufficient for relocalization to the front of polarized cells. Myo1A does not localize to actin waves and macropinocytic protrusions, in agreement with the absence of a tail region which is required for these localizations of Myo1B. However, in spite of the overall similarity of their domain structures, the cellular distributions of Myo1E and Myo1F are quite different from Myo1A. Myo1E and Myo1F, but not Myo1A, are associated with macropinocytic cups and actin waves. The localizations of Myo1E and Myo1F in macropinocytic structures and actin waves differ from the localization of Myo1B. Myo1B colocalizes with F-actin in the actin waves and at the tips of mature macropinocytic cups whereas Myo1E and Myo1F are in the interior of actin waves and along the entire surface of macropinocytic cups. Our results point to different mechanisms of targeting of short- and long-tailed myosin Is, and are consistent with these myosins having both shared and divergent cellular functions. (c) 2016 Wiley Periodicals, Inc.
C1 [Brzeska, Hanna; Koech, Hilary; Pridham, Kevin J.; Korn, Edward D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Titus, Margaret A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
RP Brzeska, H (reprint author), NIH, Bldg 50,Rm 2515,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM brzeskah@mail.nih.gov
FU NSF [MCB-1244235]; National Heart, Lung and Blood Institute
FX M. A. Titus was supported by the NSF (MCB-1244235). All other authors
were supported by the intramural program of the National Heart, Lung and
Blood Institute.
NR 81
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U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1949-3584
EI 1949-3592
J9 CYTOSKELETON
JI Cytoskeleton
PD FEB
PY 2016
VL 73
IS 2
BP 68
EP 82
DI 10.1002/cm.21275
PG 15
WC Cell Biology
SC Cell Biology
GA DF5TG
UT WOS:000371414800002
PM 26801966
ER
PT J
AU Bulusu, KC
Guha, R
Mason, DJ
Lewis, RPI
Muratov, E
Motamedi, YK
Cokol, M
Bender, A
AF Bulusu, Krishna C.
Guha, Rajarshi
Mason, Daniel J.
Lewis, Richard P. I.
Muratov, Eugene
Motamedi, Yasaman Kalantar
Cokol, Murat
Bender, Andreas
TI Modelling of compound combination effects and applications to efficacy
and toxicity: state-of-the-art, challenges and perspectives
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID DRUG-DRUG INTERACTIONS; NEGATIVE BREAST-CANCER; NETWORK ANALYSIS;
CARBAMAZEPINE TOXICITY; GRAPEFRUIT JUICE; HERBAL MEDICINES;
GENE-EXPRESSION; SMALL MOLECULES; DISCOVERY; THERAPY
AB The development of treatments involving combinations of drugs is a promising approach towards combating complex or multifactorial disorders. However, the large number of compound combinations that can be generated, even from small compound collections, means that exhaustive experimental testing is infeasible. The ability to predict the behaviour of compound combinations in biological systems, whittling down the number of combinations to be tested, is therefore crucial. Here, we review the current state-of-the-art in the field of compound combination modelling, with the aim to support the development of approaches that, as we hope, will finally lead to an integration of chemical with systems-level biological information for predicting the effect of chemical mixtures.
C1 [Bulusu, Krishna C.; Mason, Daniel J.; Lewis, Richard P. I.; Motamedi, Yasaman Kalantar; Bender, Andreas] Univ Cambridge, Dept Chem, Ctr Mol Informat, Lensfield Rd, Cambridge CB2 1EW, England.
[Guha, Rajarshi] NIH, Div Preclin Innovat, Chem Genom Ctr, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20580 USA.
[Muratov, Eugene] Univ N Carolina, Eshelman Sch Pharm, Lab Mol Modeling, Chapel Hill, NC 27599 USA.
[Cokol, Murat] Sabanci Univ, Fac Engn & Nat Sci, TR-34956 Istanbul, Turkey.
RP Bulusu, KC; Bender, A (reprint author), Univ Cambridge, Dept Chem, Ctr Mol Informat, Lensfield Rd, Cambridge CB2 1EW, England.
EM kcb27@cam.ac.uk; ab454@cam.ac.uk
RI Muratov, Eugene/C-4454-2014; Bender, Andreas/C-6942-2009;
OI Muratov, Eugene/0000-0003-4616-7036; Bender,
Andreas/0000-0002-6683-7546; Lewis, Rich/0000-0001-6642-5771
FU European Research Council (ERC Starting Grant); EPSRC; NIH [GM 096967];
EPA [RD 83499901]; UNC (Junior Faculty Development Award); Turkish
Academy of Sciences GEBIP Programme; Unilever
FX K.B., Y.K.M. and A.B. thank the European Research Council (ERC Starting
Grant 2013 to AB) for funding. D.J.M. thanks Unilever and R.L. thanks
the EPSRC for funding. E.M. thanks the financial support from NIH (GM
096967), EPA (RD 83499901) and UNC (2014 Junior Faculty Development
Award). M.C. was supported by the Turkish Academy of Sciences GEBIP
Programme.
NR 134
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Z9 7
U1 8
U2 21
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
EI 1878-5832
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD FEB
PY 2016
VL 21
IS 2
BP 225
EP 238
DI 10.1016/j.drudis.2015.09.003
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DF5BS
UT WOS:000371367400006
PM 26360051
ER
PT J
AU Fan, RZ
Wang, YF
Chiu, CY
Chen, W
Ren, HB
Li, Y
Boehnke, M
Amos, CI
Moore, JH
Xiong, MM
AF Fan, Ruzong
Wang, Yifan
Chiu, Chi-yang
Chen, Wei
Ren, Haobo
Li, Yun
Boehnke, Michael
Amos, Christopher I.
Moore, Jason H.
Xiong, Momiao
TI Meta-analysis of Complex Diseases at Gene Level with Generalized
Functional Linear Models
SO GENETICS
LA English
DT Article
DE meta-analysis; rare variants; common variants; association mapping;
complex traits; functional data analysis
ID GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAITS; RARE VARIANTS;
SUSCEPTIBILITY LOCI; COMMON
AB We developed generalized functional linear models (GFLMs) to perform a meta-analysis of multiple case-control studies to evaluate the relationship of genetic data to dichotomous traits adjusting for covariates. Unlike the previously developed meta-analysis for sequence kernel association tests (MetaSKATs), which are based on mixed-effect models to make the contributions of major gene loci random, GFLMs are fixed models; i.e., genetic effects of multiple genetic variants are fixed. Based on GFLMs, we developed chi-squared-distributed Rao's efficient score test and likelihood-ratio test (LRT) statistics to test for an association between a complex dichotomous trait and multiple genetic variants. We then performed extensive simulations to evaluate the empirical type I error rates and power performance of the proposed tests. The Rao's efficient score test statistics of GFLMs are very conservative and have higher power than MetaSKATs when some causal variants are rare and some are common. When the causal variants are all rare [i.e., minor allele frequencies (MAF) < 0.03], the Rao's efficient score test statistics have similar or slightly lower power than MetaSKATs. The LRT statistics generate accurate type I error rates for homogeneous genetic-effect models and may inflate type I error rates for heterogeneous genetic-effect models owing to the large numbers of degrees of freedom and have similar or slightly higher power than the Rao's efficient score test statistics. GFLMs were applied to analyze genetic data of 22 gene regions of type 2 diabetes data from a meta-analysis of eight European studies and detected significant association for 18 genes (P < 3.10 x 10(-6)), tentative association for 2 genes (HHEX and HMGA2; P approximate to 10(-5)), and no association for 2 genes, while MetaSKATs detected none. In addition, the traditional additive-effect model detects association at gene HHEX. GFLMs and related tests can analyze rare or common variants or a combination of the two and can be useful in whole-genome and whole-exome association studies.
C1 [Fan, Ruzong; Wang, Yifan; Chiu, Chi-yang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Wei] Univ Pittsburgh, Med Ctr, Div Pulm Med Allergy & Immunol, Pittsburgh, PA 15224 USA.
[Ren, Haobo] Regeneron Pharmaceut Inc, Basking Ridge, NJ 07920 USA.
[Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Li, Yun] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Boehnke, Michael; Xiong, Momiao] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Amos, Christopher I.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA.
[Moore, Jason H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
Univ Texas Houston, Ctr Human Genet, Houston, TX 77225 USA.
RP Fan, RZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA.
EM fanr@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; NIH [R01-EY024226, R01-HG007358, R01-HG006292, R01-HG006703,
LM-009012, LM-010098]; University of Pittsburgh [R01-EY024226]
FX Two anonymous reviewers and the editors, Dr. Chiara Sabatti and Dr. Gary
Churchill, provided very good and insightful comments for us to improve
the manuscript. We greatly thank the European cohorts groups for letting
us analyze the data and use them as examples. Dr. Heather M. Stringham
and Dr. Tanya M. Teslovich kindly sent us the data of the European
cohorts and patiently answered many questions about the cohorts, and we
greatly appreciated them. This study used the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health (http://biowulf.nih.gov). No GWAS data were
generated in this paper. This study was supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health (R.F.,
Y.W., and C.-y.C.), by NIH grants R01-EY024226 and R01-HG007358 (to
W.C.), by the University of Pittsburgh (R.F. is an unpaid collaborator
on grant R01-EY024226), by NIH grants R01-HG006292 and R01-HG006703 (to
Y.L.), and by NIH grants LM-009012 and LM-010098 (to J.H.M).
NR 40
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U1 2
U2 5
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD FEB
PY 2016
VL 202
IS 2
BP 457
EP +
DI 10.1534/genetics.115.180869
PG 27
WC Genetics & Heredity
SC Genetics & Heredity
GA DF4FY
UT WOS:000371304600011
PM 26715663
ER
PT J
AU Bhairavabhotla, R
Kim, YC
Glass, DD
Escobar, TM
Patel, MC
Zahr, R
Nguyen, CK
Kilaru, GK
Muljo, SA
Shevach, EM
AF Bhairavabhotla, Ravikiran
Kim, Yong C.
Glass, Deborah D.
Escobar, Thelma M.
Patel, Mira C.
Zahr, Rami
Nguyen, Cuong K.
Kilaru, Gokhul K.
Muljo, Stefan A.
Shevach, Ethan M.
TI Transcriptome profiling of human FoxP3(+) regulatory T cells
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE Suppressive cells; RNA sequencing; Gene signature; MiRNA; Differentially
expressed; nCounter analysis; RTKN2; LAYN; FoxP3; MiR-146a; MiR-146b;
MiR-21; PNA
ID HYALURONAN RECEPTOR; RHEUMATOID-ARTHRITIS; EXPRESSION; LAYILIN;
EXPANSION; EFFECTOR; PROTEIN; GENES; IDENTIFICATION; DYSREGULATION
AB The major goal of this study was to perform an in depth characterization of the "gene signature" of human FoxP3(+) T regulatory cells (Tregs). Highly purified Tregs and T conventional cells (Tconvs) from multiple healthy donors (HD), either freshly explanted or activated in vitro, were analyzed via RNA sequencing (RNA-seq) and gene expression changes validated using the nCounter system. Additionally, we analyzed microRNA (miRNA) expression using TaqMan low-density arrays. Our results confirm previous studies demonstrating selective gene expression of FoxP3, IKZF2, and CTLA4 in Tregs. Notably, a number of yet uncharacterized genes (RTKN2, LAYN, UTS2, CSF2RB, TRIB1, F5, CECAM4, CD70, ENC1 and NKG7) were identified and validated as being differentially expressed in human Tregs. We further characterize the functional roles of RTKN2 and LAYN by analyzing their roles in vitro human Treg suppression assays by knocking them down in Tregs and overexpressing them in Tconvs. In order to facilitate a better understanding of the human Treg gene expression signature, we have generated from our results a hypothetical interactome of genes and miRNAs in Tregs and Tconvs. Published by Elsevier on behalf of American Society for Histocompatibility and Immunogenetics. Inc.
C1 [Bhairavabhotla, Ravikiran; Kim, Yong C.; Glass, Deborah D.; Escobar, Thelma M.; Zahr, Rami; Nguyen, Cuong K.; Kilaru, Gokhul K.; Muljo, Stefan A.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Patel, Mira C.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Bhairavabhotla, Ravikiran] United Nations Childrens Fund, HIV & AIDS Sect, Programme Div, New York, NY USA.
[Kim, Yong C.] Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060, Bethesda, MD 20814 USA.
[Escobar, Thelma M.] NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY USA.
[Patel, Mira C.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Nguyen, Cuong K.] Inst Populat Hlth & Dev, Cau Giay, Ha Noi, Vietnam.
[Kilaru, Gokhul K.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM EShevach@niaid.nih.gov
RI Nguyen, Cuong/D-7567-2013
OI Nguyen, Cuong/0000-0002-1741-669X
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX These studies were supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 47
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
EI 1879-1166
J9 HUM IMMUNOL
JI Hum. Immunol.
PD FEB
PY 2016
VL 77
IS 2
BP 201
EP 213
DI 10.1016/j.humimm.2015.12.004
PG 13
WC Immunology
SC Immunology
GA DF2RP
UT WOS:000371191800009
PM 26686412
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Meta-analyses: Only as reliable as the primary studies on which they are
based
SO INTERNATIONAL JOURNAL OF NURSING PRACTICE
LA English
DT Letter
C1 [Berger, Vance W.] Univ Maryland, Baltimore, MD 21201 USA.
[Berger, Vance W.] NCI, Biometry Res Grp, Rockville, MD USA.
RP Berger, VW (reprint author), Univ Maryland, Baltimore, MD 21201 USA.; Berger, VW (reprint author), NCI, Biometry Res Grp, Rockville, MD USA.
NR 4
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1322-7114
EI 1440-172X
J9 INT J NURS PRACT
JI Int. J. Nurs. Pract.
PD FEB
PY 2016
VL 22
IS 1
BP 110
EP 110
DI 10.1111/ijn.12364
PG 1
WC Nursing
SC Nursing
GA DF3QT
UT WOS:000371261000014
PM 25355413
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Risk of bias: Worse than it appears
SO INTERNATIONAL JOURNAL OF NURSING PRACTICE
LA English
DT Letter
ID ALLOCATION CONCEALMENT
C1 [Berger, Vance W.] Univ Maryland, NCI, Baltimore, MD 21201 USA.
[Berger, Vance W.] NCI, UMBC, Biometry Res Grp, Rockville, MD USA.
RP Berger, VW (reprint author), Univ Maryland, NCI, Baltimore, MD 21201 USA.; Berger, VW (reprint author), NCI, UMBC, Biometry Res Grp, Rockville, MD USA.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1322-7114
EI 1440-172X
J9 INT J NURS PRACT
JI Int. J. Nurs. Pract.
PD FEB
PY 2016
VL 22
IS 1
BP 111
EP 111
DI 10.1111/ijn.12372
PG 1
WC Nursing
SC Nursing
GA DF3QT
UT WOS:000371261000015
PM 26916061
ER
PT J
AU Seed, TM
Xiao, SY
Manley, N
Nikolich-Zugich, J
Pugh, J
Van den Brink, M
Hirabayashi, Y
Yasutomo, K
Iwama, A
Koyasu, S
Shterev, I
Sempowski, G
Macchiarini, F
Nakachi, K
Kunugi, KC
Hammer, CG
Dewerd, LA
AF Seed, Thomas M.
Xiao, Shiyun
Manley, Nancy
Nikolich-Zugich, Janko
Pugh, Jason
Van den Brink, Marcel
Hirabayashi, Yoko
Yasutomo, Koji
Iwama, Atsushi
Koyasu, Shigeo
Shterev, Ivo
Sempowski, Gregory
Macchiarini, Francesca
Nakachi, Kei
Kunugi, Keith C.
Hammer, Clifford G.
Dewerd, Lawrence A.
TI An interlaboratory comparison of dosimetry for a multi-institutional
radiobiological research project: Observations, problems, solutions and
lessons learned
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
DE animal models; Dosimetry; haematology; radiation; ionizing;
dose-response curve; OSL/TLD dosimeters
AB Purpose: An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. Methods: Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. Results: The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of <= 5%. Comparable rates of 'dosimetric compliance' were noted between OSL- and TLD-based tests. Data analysis showed a highly linear relationship between 'measured' and 'target' doses, with errors falling largely between 0 and 20%. Outliers were most notable for OSL-based tests, while multiple tests by 'non-compliant' laboratories using orthovoltage X-rays contributed heavily to the wide variation in dosing errors. Conclusions: For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized.
C1 [Seed, Thomas M.] Tech Micro Serv Co, 4417 Maple Ave, Bethesda, MD 20814 USA.
[Xiao, Shiyun; Manley, Nancy] Univ Georgia, Dept Genet, Athens, GA 30602 USA.
[Nikolich-Zugich, Janko; Pugh, Jason] Univ Arizona, Arizona Ctr Aging, Dept Immunol, Tucson, AZ USA.
[Van den Brink, Marcel] Mem Sloan Kettering Canc Ctr, Div Hematol Oncol, 1275 York Ave, New York, NY 10021 USA.
[Hirabayashi, Yoko] Natl Inst Hlth Sci, Div Cellular & Mol Toxicol, Tokyo, Japan.
[Yasutomo, Koji] Univ Tokushima, Dept Immunol, Tokushima 770, Japan.
[Iwama, Atsushi] Chiba Univ, Dept Cellular & Mol Med, Chiba, Japan.
[Koyasu, Shigeo] Keio Univ, Dept Microbiol & Immunol, Tokyo, Japan.
[Shterev, Ivo; Sempowski, Gregory] Duke Univ, Dept Pathol, Human Vaccine Inst, Durham, NC 27706 USA.
[Shterev, Ivo; Sempowski, Gregory] Duke Univ, Dept Med, Durham, NC 27706 USA.
[Macchiarini, Francesca] NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Nakachi, Kei] Radiat Effects Res Fdn, Dept Radiobiol & Mol Epidemiol, Hiroshima, Japan.
[Kunugi, Keith C.; Hammer, Clifford G.; Dewerd, Lawrence A.] Univ Wisconsin, Med Radiat Res Ctr, Madison, WI USA.
[Koyasu, Shigeo] RIKEN Ctr, Yokohama, Kanagawa 2300045, Japan.
RP Seed, TM (reprint author), Tech Micro Serv Co, 4417 Maple Ave, Bethesda, MD 20814 USA.
EM tmseed@verizon.net
RI Koyasu, Shigeo/J-5583-2015
OI Koyasu, Shigeo/0000-0001-9585-3038
FU National Institute of Allergy and Infectious Disease/National Institutes
of Health [HHSN272200900059C]
FX This work was supported by a National Institute of Allergy and
Infectious Disease/National Institutes of Health contract (No.
HHSN272200900059C) to the Radiation Effects Research Foundation,
Hiroshima, Japan.
NR 22
TC 1
Z9 1
U1 0
U2 1
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0955-3002
EI 1362-3095
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD FEB 1
PY 2016
VL 92
IS 2
BP 59
EP 70
DI 10.3109/09553002.2015.1106024
PG 12
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DE4SF
UT WOS:000370619700001
PM 26857121
ER
PT J
AU Poole, SA
Pecoraro, A
Subramaniam, G
Woody, G
Vetter, VL
AF Poole, Sabrina A.
Pecoraro, Anna
Subramaniam, Geetha
Woody, George
Vetter, Victoria L.
TI Presence or Absence of QTc Prolongation in Buprenorphine-Naloxone Among
Youth With Opioid Dependence
SO JOURNAL OF ADDICTION MEDICINE
LA English
DT Article
DE buprenorphine-naloxone; QTc interval; Suboxone; young adults
ID TORSADE-DE-POINTES; INTERVAL PROLONGATION; RANDOMIZED-TRIAL; METHADONE;
DRUG; LEVOMETHADYL; ADOLESCENTS; CHILDREN
AB Objectives:
The aim of the study was to evaluate buprenorphine-naloxone effects on the QTc in youth with opioid dependence. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, but is less studied in the youth. It may also reduce the risk of torsades de pointes (TdP)-an uncommon variant of polymorphic ventricular tachycardia-that can result in syncope, ventricular fibrillation, and sudden death.
Methods:
Secondary analysis of the electrocardiogram data from 95 individuals who participated in a multisite trial for youth with opioid dependence. The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc.
Results:
Mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (P = 0.045), and women had longer mean QTc intervals than men (P < 0.0005). Variations in the QTc intervals were observed in some; however, none were above 500 milliseconds-the level at which risk for TdP becomes more significant.
Conclusions:
In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than in DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP.
C1 [Poole, Sabrina A.; Pecoraro, Anna; Woody, George] Univ Penn, Perelman Sch Med, Philadelphia, PA 19106 USA.
[Vetter, Victoria L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Subramaniam, Geetha] NIDA, Ctr Clin Trials Network, Bethesda, MD USA.
RP Poole, SA (reprint author), Univ Penn, Ctr Studies Addict & Treatment, Res Inst, 150 South Independence Mall W, Philadelphia, PA 19106 USA.
EM spoole@mail.med.upenn.edu
FU Center for Clinical Trials Network at the National Institute on Drug
Abuse [5U10 DA1304308, 2K05 DA01700906]
FX Supported by grants 5U10 DA1304308 and 2K05 DA01700906 from the Center
for Clinical Trials Network at the National Institute on Drug Abuse (G.
W., PI).
NR 30
TC 1
Z9 1
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1932-0620
EI 1935-3227
J9 J ADDICT MED
JI J. Addict. Med.
PD FEB
PY 2016
VL 10
IS 1
BP 26
EP 33
DI 10.1097/ADM.0000000000000176
PG 8
WC Substance Abuse
SC Substance Abuse
GA DE0CS
UT WOS:000370293000005
PM 26690291
ER
PT J
AU Tonietto, M
Rizzo, G
Veronese, M
Fujita, M
Zoghbi, SS
Zanotti-Fregonara, P
Bertoldo, A
AF Tonietto, Matteo
Rizzo, Gaia
Veronese, Mattia
Fujita, Masahiro
Zoghbi, Sami S.
Zanotti-Fregonara, Paolo
Bertoldo, Alessandra
TI Plasma radiometabolite correction in dynamic PET studies: Insights on
the available modeling approaches
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Review
DE PET; plasma parent fraction; radiometabolite correction; PPf modeling
ID POSITRON-EMISSION-TOMOGRAPHY; TEST-RETEST REPRODUCIBILITY; ARTERIAL
INPUT FUNCTION; BLOOD-SAMPLING SITE; HUMAN BRAIN; IN-VIVO; METABOLITE
CORRECTION; DOPAMINE TRANSPORTER; KINETIC-ANALYSIS;
BENZODIAZEPINE-RECEPTOR
AB Full kinetic modeling of dynamic PET images requires the measurement of radioligand concentrations in the arterial plasma. The unchanged parent radioligand must, however, be separated from its radiometabolites by chromatographic methods. Thus, only few samples can usually be analyzed and the resulting measurements are often noisy. Therefore, the measurements must be fitted with a mathematical model. This work presents a comprehensive analysis of the different models proposed in the literature to describe the plasma parent fraction (PPf) and of the alternative approaches for radiometabolite correction. Finally, we used a dataset of [C-11]PBR28 brain PET data as a case study to guide the reader through the PPf model selection process.
C1 [Tonietto, Matteo; Rizzo, Gaia; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, Via G Gradenigo 6-B, I-35131 Padua, Italy.
[Veronese, Mattia] Kings Coll London, Dept Neuroimaging, IoPPN, London WC2R 2LS, England.
[Fujita, Masahiro; Zoghbi, Sami S.; Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Zanotti-Fregonara, Paolo] Univ Bordeaux, INCIA UMR CNRS 5287, Bordeaux, France.
RP Bertoldo, A (reprint author), Univ Padua, Dept Informat Engn, Via G Gradenigo 6-B, I-35131 Padua, Italy.
EM bertoldo@dei.unipd.it
RI Veronese, Mattia/A-6012-2013; Rizzo, Gaia/A-8697-2013;
OI Veronese, Mattia/0000-0003-3562-0683; Rizzo, Gaia/0000-0001-7272-8576;
Tonietto, Matteo/0000-0001-9591-5710
FU Intramural Research Program, National Institute of Mental Health
[ZIAMH002795]; UK Medical Research Council programme [G1100809/1]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported in part by the Intramural Research Program, National
Institute of Mental Health (ZIAMH002795) and by UK Medical Research
Council programme (grant no. G1100809/1).
NR 76
TC 0
Z9 0
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD FEB
PY 2016
VL 36
IS 2
BP 326
EP 339
DI 10.1177/0271678X15610585
PG 14
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA DF4EG
UT WOS:000371299800007
PM 26661202
ER
PT J
AU Bernstock, JD
Lee, YJ
Peruzzotti-Jametti, L
Southall, N
Johnson, KR
Maric, D
Volpe, G
Kouznetsova, J
Zheng, W
Pluchino, S
Hallenbeck, JM
AF Bernstock, Joshua D.
Lee, Yang-ja
Peruzzotti-Jametti, Luca
Southall, Noel
Johnson, Kory R.
Maric, Dragan
Volpe, Giulio
Kouznetsova, Jennifer
Zheng, Wei
Pluchino, Stefano
Hallenbeck, John M.
TI A novel quantitative high-throughput screen identifies drugs that both
activate SUMO conjugation via the inhibition of microRNAs 182 and 183
and facilitate neuroprotection in a model of oxygen and glucose
deprivation
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE High-throughput assay development; miRNA; neuroprotection; SUMO
conjugation; translational research
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HISTONE DEACETYLASES; PROTEIN
SUMOYLATION; CEREBRAL-ISCHEMIA; CORTICAL-NEURONS; NMDA RECEPTOR;
LUCIFERASE; BRAIN; ACID; HIBERNATION
AB The conjugation/de-conjugation of Small Ubiquitin-like Modifier (SUMO) has been shown to be associated with a diverse set of physiologic/pathologic conditions. The clinical significance and ostensible therapeutic utility offered via the selective control of the global SUMOylation process has become readily apparent in ischemic pathophysiology. Herein, we describe the development of a novel quantitative high-throughput screening (qHTS) system designed to identify small molecules capable of increasing SUMOylation via the regulation/inhibition of members of the microRNA (miRNA)-182 family. This assay employs a SHSY5Y human neuroblastoma cell line stably transfected with a dual firefly-Renilla luciferase reporter system for identification of specific inhibitors of either miR-182 or miR-183. In this study, we have identified small molecules capable of inducing increased global conjugation of SUMO in both SHSY5Y cells and rat E18-derived primary cortical neurons. The protective effects of a number of the identified compounds were confirmed via an in vitro ischemic model (oxygen/glucose deprivation). Of note, this assay can be easily repurposed to allow high-throughput analyses of the potential drugability of other relevant miRNA(s) in ischemic pathobiology.
C1 [Bernstock, Joshua D.; Lee, Yang-ja; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Bernstock, Joshua D.; Peruzzotti-Jametti, Luca; Volpe, Giulio; Pluchino, Stefano] Univ Cambridge, Div Stem Cell Neurobiol, MRC, Dept Clin Neurosci,Wellcome Trust,Stem Cell Inst, Cambridge, England.
[Southall, Noel; Kouznetsova, Jennifer; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
[Johnson, Kory R.] NINDS, Bioinformat Sect, Informat Technol & Bioinformat Program, Div Intramural Res DIR,NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Hallenbeck, JM (reprint author), NINDS, NIH, Bldg 10 Room 5602,10 Ctr Dr MSC 1401, Bethesda, MD 20892 USA.
EM HallenbJ@ninds.nih.gov
RI Zheng, Wei/J-8889-2014;
OI Zheng, Wei/0000-0003-1034-0757; Peruzzotti-Jametti,
Luca/0000-0002-9396-5607
FU Intramural Research Program of the NINDS/NIH, an IRTA-OxCam Fellowship;
Wellcome Trust [RRZA/057, RG79423]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the Intramural Research Program of the NINDS/NIH, an
IRTA-OxCam Fellowship and by the Wellcome Trust [RRZA/057 and RG79423].
NR 50
TC 2
Z9 2
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD FEB
PY 2016
VL 36
IS 2
BP 426
EP 441
DI 10.1177/0271678X15609939
PG 16
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA DF4EG
UT WOS:000371299800018
PM 26661196
ER
PT J
AU Similuk, MN
Wang, A
Lenardo, MJ
Erby, LH
AF Similuk, Morgan N.
Wang, Angela
Lenardo, Michael J.
Erby, Lori H.
TI Life with a Primary Immune Deficiency: a Systematic Synthesis of the
Literature and Proposed Research Agenda
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Review
DE Quality of life; psychosocial; primary immune deficiency;
patient-centered
ID QUALITY-OF-LIFE; PRIMARY IMMUNODEFICIENCY DISEASES; COMMON VARIABLE
IMMUNODEFICIENCY; PRIMARY ANTIBODY DEFICIENCY; STEM-CELL TRANSPLANT;
HEREDITARY ANGIOEDEMA; INTRAVENOUS IMMUNOGLOBULIN; CHILDREN; HEALTH;
IMPACT
AB The clinical immunology literature is punctuated with research on psychosocial dimensions of illness. Studies investigating the lived experiences and stated needs of patients with primary immune deficiencies and their families are essential to improving clinical management and determining the research questions that matter to patients and other stakeholders. Yet, to move the field forward, a systematic review of literature and proposed agenda is needed.
A systematic review was conducted via PubMed and Scopus to include original research on psychological, social, or behavioral aspects of primary immune deficiencies published between 1999 and 2015. A Title/Abstract keyword search was conducted, 317 candidate article abstracts were manually reviewed, and forward/backward reference searches were completed.
Twenty-nine studies met inclusion criteria. These illuminate the complex psychological, social, and emotional experiences of primary immune deficiency. Themes included the potential for negative psychosocial impact from disease; adaptation over time; the multi-dimensional assessments of quality of life; familial impact; the important roles of hope, developing a sense of control, social support; and addressing anxiety/depression in our patients and their families. Methodological considerations and areas for improvement are discussed.
We propose the research agenda focus on study creativity and rigor, with improved engagement with existing literature and critical study design (e.g., methodology with adequate statistical power, careful variable selection, etc.). This review highlights opportunities to advance psychosocial research and bring a brighter future to clinicians, researchers, and families affected by primary immune deficiency.
C1 [Similuk, Morgan N.; Lenardo, Michael J.] NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
[Wang, Angela] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD 21702 USA.
[Erby, Lori H.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Similuk, MN (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
EM morgan.similuk@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, NIH
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported in part by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, NIH.
NR 48
TC 0
Z9 0
U1 2
U2 3
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 FEB
PY 2016
VL 36
IS 2
BP 123
EP 133
DI 10.1007/s10875-016-0241-1
PG 11
WC Immunology
SC Immunology
GA DF4BQ
UT WOS:000371292700006
PM 26873708
ER
PT J
AU Ockene, JK
Hayes, RB
Churchill, LC
Crawford, SL
Jolicoeur, DG
Murray, DM
Shoben, AB
David, SP
Ferguson, KJ
Huggett, KN
Adams, M
Okuliar, CA
Gross, RL
Bass, PF
Greenberg, RB
Leone, FT
Okuyemi, KS
Rudy, DW
Waugh, JB
Geller, AC
AF Ockene, Judith K.
Hayes, Rashelle B.
Churchill, Linda C.
Crawford, Sybil L.
Jolicoeur, Denise G.
Murray, David M.
Shoben, Abigail B.
David, Sean P.
Ferguson, Kristi J.
Huggett, Kathryn N.
Adams, Michael
Okuliar, Catherine A.
Gross, Robin L.
Bass, Pat F., III
Greenberg, Ruth B.
Leone, Frank T.
Okuyemi, Kola S.
Rudy, David W.
Waugh, Jonathan B.
Geller, Alan C.
TI Teaching Medical Students to Help Patients Quit Smoking: Outcomes of a
10-School Randomized Controlled Trial
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE tobacco dependence treatment; counseling; medical school curriculum;
medical student behaviors; randomized controlled trial; objective
structured clinical examination
ID TOBACCO-CESSATION; EDUCATION; SCHOOLS; CURRICULA; PROGRAM; SKILLS
AB BACKGROUND: Early in medical education, physicians must develop competencies needed for tobacco dependence treatment.
OBJECTIVE: To assess the effect of amulti-modal tobacco dependence treatment curriculum on medical students' counseling skills.
DESIGN: A group-randomized controlled trial (20102014) included ten U.S. medical schools that were randomized to receive either multi-modal tobacco treatment education (MME) or traditional tobacco treatment education (TE).
SETTING/PARTICIPANTS: Students from the classes of 2012 and 2014 at ten medical schools participated. Students from the class of 2012 (N=1345) completed objective structured clinical examinations (OSCEs), and 50 % (N=660) were randomly selected for pre-intervention evaluation. A total of 72.9 % of eligible students (N=1096) from the class of 2014 completed an OSCE and 69.7 % (N=1047) completed pre and post surveys.
INTERVENTIONS: The MME included a Web-based course, a role-play classroom demonstration, and a clerkship booster session. Clerkship preceptors in MME schools participated in an academic detailing module and were encouraged to be role models for third-year students.
MEASUREMENTS: The primary outcome was student tobacco treatment skills using the 5As measured by an objective structured clinical examination (OSCE) scored on a 33-item behavior checklist. Secondary outcomes were student self-reported skills for performing 5As and pharmacotherapy counseling.
RESULTS: Although the difference was not statistically significant, MME students completed more tobacco counseling behaviors on the OSCE checklist (mean 8.7 [SE 0.6] vs. mean 8.0 [SE 0.6], p=0.52) than TE students. Several of the individual Assist and Arrange items were significantly more likely to have been completed by MME students, including suggesting behavioral strategies (11.8 % vs. 4.5 %, p<0.001) and providing information regarding quitline (21.0 % vs. 3.8 %, p<0.001). MME students reported higher self-efficacy for Assist, Arrange, and Pharmacotherapy counseling items (ps=0.05).
LIMITATIONS: Inclusion of only ten schools limits generalizability.
CONCLUSIONS: Subsequent interventions should incorporate lessons learned from this first randomized controlled trial of a multi-modal longitudinal tobacco treatment curriculum in multiple U.S. medical schools.
C1 [Ockene, Judith K.; Hayes, Rashelle B.; Churchill, Linda C.; Crawford, Sybil L.; Jolicoeur, Denise G.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, 55 Lake Ave North, Worcester, MA 01655 USA.
[Murray, David M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Shoben, Abigail B.] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[David, Sean P.] Stanford Univ, Sch Med, Dept Med, Ctr Educ & Res Family & Community Med,Div Gen Med, Palo Alto, CA 94304 USA.
[Ferguson, Kristi J.] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Huggett, Kathryn N.] Creighton Univ, Sch Med, Dept Med, Omaha, NE USA.
[Adams, Michael; Okuliar, Catherine A.; Gross, Robin L.] Georgetown Univ Hosp, Dept Med, Washington, DC 20007 USA.
[Bass, Pat F., III] Louisiana State Univ Hlth Shreveport, Shreveport, LA USA.
[Greenberg, Ruth B.] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Leone, Frank T.] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA.
[Okuyemi, Kola S.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA.
[Rudy, David W.] Univ Kentucky, Coll Med, Lexington, KY USA.
[Waugh, Jonathan B.] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Sch Hlth Profess, Clin & Diagnost Sci Dept, Birmingham, AL USA.
[Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, 665 Huntington Ave, Boston, MA 02115 USA.
RP Ockene, JK (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, 55 Lake Ave North, Worcester, MA 01655 USA.
EM Judith.Ockene@umassmed.edu
OI Murray, David/0000-0003-0797-9269
FU National Cancer Institute (NCI) [5 R01 CA136888]
FX The study was supported by an investigator-initiated grant from the
National Cancer Institute (NCI) 5 R01 CA136888.
NR 39
TC 2
Z9 2
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2016
VL 31
IS 2
BP 172
EP 181
DI 10.1007/s11606-015-3508-y
PG 10
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DF2GQ
UT WOS:000371161000012
PM 26391030
ER
PT J
AU Teague, H
Harris, M
Whelan, J
Comstock, SS
Fenton, JI
Shaikh, SR
AF Teague, Heather
Harris, Mitchel
Whelan, Jarrett
Comstock, Sarah S.
Fenton, Jenifer I.
Shaikh, Saame Raza
TI Short-term consumption of n-3 PUFAs increases murine IL-5 levels, but
IL-5 is not the mechanistic link between n-3 fatty acids and changes in
B-cell populations
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE EPA; DHA; n-3 PUFAs; B cells; IL-5
ID FISH-OIL; LIPID MEDIATORS; IMMUNOLOGICAL SYNAPSE; IMMUNE-RESPONSE;
T-CELLS; ENHANCE; OMEGA-3-FATTY-ACIDS; OBESITY; MICE; ORGANIZATION
AB N-3 polyunsaturated fatty acids (PUFAs) exert immunomodulatory effects on B cells. We previously demonstrated that n-3 PUFAs enhanced the relative percentage and/or frequency of select B2 cell subsets. The objectives here were to determine if n-3 PUFAs (a) could boost cytokines that target B-cell frequency, (b) enhance the frequency of the B1 population and (c) to identify the mechanism by which n-3 PUFAs modify the proportion of B cells. Administration of n-3 PUFAs as fish oil to C57BL/6 mice enhanced secretion of the Th2 cytokine IL-5 but not IL-9 or IL-13. N-3 PUFAs had no influence on the percentage or frequency of peritoneal B1 or B2 cells. Subsequent experiments with IL-5(-/-) knockout mice showed n-3 PUFAs decreased the percentage of bone marrow B220(lo)IgM(hi) cells and increased the proportion and number of splenic IgM(+)IgD(lo)CD21(lo) cells compared to the control. These results, when compared with our previous findings with wild-type mice, suggested IL-5 had no role in mediating the effect of n-3 PUFAs on B-cell populations. To confirm this conclusion, we assayed IL-5 secretion in a diet-induced obesity model in which n-3 PUFAs enhanced the frequency of select B-cell subsets. N-3 PUFA supplementation as ethyl esters to obesogenic diets did not alter circulating IL-5 levels. Altogether, the data establish that n-3 PUFAs as fish oil can increase circulating IL-5 in lean mice, which has implications for several disease end points, but this increase in IL-5 is not the mechanistic link between n-3 PUFAs and changes in B-cell populations. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Teague, Heather; Harris, Mitchel; Whelan, Jarrett; Shaikh, Saame Raza] E Carolina Univ, Dept Biochem & Mol Biol, Greenville, NC 27858 USA.
[Teague, Heather; Harris, Mitchel; Whelan, Jarrett; Shaikh, Saame Raza] E Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC 27858 USA.
[Comstock, Sarah S.; Fenton, Jenifer I.] Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA.
[Fenton, Jenifer I.; Shaikh, Saame Raza] Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA.
[Shaikh, Saame Raza] E Carolina Univ, Dept Microbiol & Immunol, Greenville, NC 27858 USA.
[Teague, Heather] NIH, Bldg 10 CRC,Room 5-5232, Bethesda, MD 20892 USA.
RP Shaikh, SR (reprint author), 115 Heart Dr,Mail Stop 743, Greenville, NC 27834 USA.
EM shaikhsa@ecu.edu
FU National Center for Complementary and Integrative Health at NIH
[R01AT008375]
FX We thank Rasagna Kosaraju for her assistance with the IL-5 knockout
studies. This work was supported in part by a grant from the National
Center for Complementary and Integrative Health at the NIH (R01AT008375)
to S.R.S.
NR 40
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD FEB
PY 2016
VL 28
BP 30
EP 36
DI 10.1016/j.jnutbio.2015.09.012
PG 7
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA DF4YS
UT WOS:000371359100004
PM 26878780
ER
PT J
AU McCutchan, PK
Liu, X
LeardMann, CA
Smith, TC
Boyko, EJ
Gore, KL
Freed, MC
Engel, CC
AF McCutchan, Phoebe K.
Liu, Xian
LeardMann, Cynthia A.
Smith, Tyler C.
Boyko, Edward J.
Gore, Kristie L.
Freed, Michael C.
Engel, Charles C.
TI Deployment, combat, and risk of multiple physical symptoms in the US
military: a prospective cohort study
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Signs and symptoms; Military medicine; Military personnel; Veterans
health; Cohort studies
ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CLINICAL-TRIAL;
PERSIAN-GULF-WAR; SOMATIC SYMPTOMS; MILLENNIUM COHORT; PRIMARY-CARE;
CHRONIC PAIN; IRAQ WAR; SERVICE MEMBERS; HEALTH OUTCOMES
AB Purpose: Multiple physical symptoms (MPS) have historically been observed after deployment to a combat zone and are often disabling in nature. This study examined longitudinal trends in MPS status and its relationship to deployment in U.S. military service members.
Methods: Using longitudinal data from panel 1 participants in the Millennium Cohort Study (n = 76,924), MPS status was assessed at three time points (2001-2008) using the 15 -item Patient Health Questionnaire. Probability of reporting MPS was analyzed using mixed-effects multinomial logit regression, with time and deployment experience as main explanatory variables.
Results: After adjustment for demographic, military, and health characteristics, service members who deployed with combat were significantly more likely to report MPS at each time point compared with those not deployed (odds ratio [OR] and 95% confidence interval [CI] for wave 1 =1.49 [1.47-1.52], wave 2 = 1.73 [1.69-1.78], wave 3 = 2.08 [2.03-2.12]), and those who deployed without combat (OR and CI for wave 1 = 2.66 [2.59-2.74], wave 2 = 1.81 [1.75-1.87]; wave 3 = 1.68 [1.63-1.74]).
Conclusions: Longitudinal trends indicate that the probability of reporting MPS has increased consistently over time only for those deployed, regardless of combat experience. (C) 2016 Elsevier Inc. All rights reserved.
C1 [McCutchan, Phoebe K.; Liu, Xian; Freed, Michael C.] Def Ctr Excellence Psychol Hlth, Deployment Hlth Clin Ctr, Silver Spring, MD USA.
[McCutchan, Phoebe K.; Liu, Xian; Freed, Michael C.] Def Ctr Traumat Brain Injury, Deployment Hlth Clin Ctr, Silver Spring, MD USA.
[McCutchan, Phoebe K.; Liu, Xian; LeardMann, Cynthia A.] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA.
[Liu, Xian; Freed, Michael C.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[LeardMann, Cynthia A.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA USA.
[Smith, Tyler C.] Natl Univ, Sch Hlth & Human Serv, Dept Community Hlth, San Diego, CA USA.
[Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Gore, Kristie L.; Engel, Charles C.] RAND Corp, Behav & Policy Sci, Arlington, VA USA.
[McCutchan, Phoebe K.] Amer Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
[Freed, Michael C.] NIMH, Div Serv & Intervent Res, Serv Res & Clin Epidemiol Branch, 6001 Execut Blvd, Bethesda, MD 20892 USA.
[Engel, Charles C.] RAND Corp, Behav & Policy Sci, 20 Pk Plaza,Suite 920, Boston, MA 02116 USA.
RP McCutchan, PK (reprint author), Amer Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
EM phoebe.mccutchan@gmail.com
FU Management Information Division, U.S. Defense Manpower Data Center
(Seaside, CA); Military Operational Medicine Research Program; U.S. Army
Medical Research and Materiel Command (Fort Detrick, MD); Military
Operational Medicine Research Program of the U.S. Army Medical Research
and Materiel Command, Fort Detrick, Maryland - Department of Defense
[60002]; Deployment Health Clinical Center; VA Puget Sound Health Care
System
FX In addition to the authors, the Millennium Cohort Study team includes
Richard Armenta, PhD, Lauren Bauer, MPH, Madeline Cross, James Davies,
CPT Carrie Donoho, PhD, CDR Dennis Faix, MD, Lt Col Susan Farrish, MD,
Toni Geronimo, Kathleen Gunn, William Lee, Hector Lemus, PhD, Gordon
Lynch, Denise Lovec-Jenkins, David Luxton PhD, Danielle Mitchell,
Kristin Motylinski, Anna Nagel, MPH, Chiping Nieh, PhD, Chris O'Malley,
MPH, Serguey Parkhomovsky, Anet Petrosyan, Christopher Phillips, MD,
MPH, Teresa Powell, MPH, Ben Porter, PhD, Rudy Rull, PhD, Kari Sausedo,
MA, Beverly Sheppard, Steven Speigle, Evelyn Sun, MPH, Valerie Stander,
PhD, Laura Tobin, MPH, Daniel Trone, PhD, Jennifer Walstrom, from the
Deployment Health Research Department, Naval Health Research Center, San
Diego, CA. We thank Hector Lemus, PhD (Naval Health Research Center, San
Diego, CA) for his contribution in providing statistical support and
consultation for this study. In addition, we thank Michelle LeWark from
the Naval Health Research Center (San Diego, CA) for her technical
review and editing of this article. We appreciate the support from the
Management Information Division, U.S. Defense Manpower Data Center
(Seaside, CA); Military Operational Medicine Research Program and U.S.
Army Medical Research and Materiel Command (Fort Detrick, MD).; The
Millennium Cohort Study is funded through the Military Operational
Medicine Research Program of the U.S. Army Medical Research and Materiel
Command, Fort Detrick, Maryland (supported by the Department of Defense,
under work unit no. 60002). The Deployment Health Clinical Center
provided funding for P.K.M., X.L., K.L.G, and M.C.F.'s efforts in this
project. VA Puget Sound Health Care System provided support for E.J.B's
participation in this research. The funding organizations had no role in
the design and conduct of the study; collection, analysis, or
preparation of data; or preparation, review, or approval of the article.
NR 58
TC 1
Z9 1
U1 5
U2 6
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 FEB
PY 2016
VL 26
IS 2
BP 122
EP 128
DI 10.1016/j.annepidem.2015.12.001
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DE8MG
UT WOS:000370889500006
PM 26781443
ER
PT J
AU Petrick, JL
Nguyen, T
Cook, MB
AF Petrick, Jessica L.
Tuyet Nguyen
Cook, Michael B.
TI Temporal trends of esophageal disorders by age in the Cerner Health
Facts database
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Barrett's esophagus; Esophageal cancer; Gastroesophageal reflux disease;
Temporal trends
ID GASTROESOPHAGEAL-REFLUX DISEASE; UNITED-STATES; BARRETT-ESOPHAGUS;
ADENOCARCINOMA; POPULATION; PREVALENCE; SEX
AB Purpose: Esophageal adenocarcinoma incidence has increased approximately 600% over the last 4 decades in the United States. Little research has been conducted on the temporal trends of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE), yet it is important to establish whether these conditions have also increased with time or differ by age.
Methods: The Cerner Health Facts database contains information on 35 million patients between 2001 and 2010. GERD, BE, and esophageal cancer (EC) cases were defined using International Classification of Diseases, ninth edition codes. We calculated age-adjusted rates and 95% confidence intervals for GERD, BE, and EC.
Results: In this population, the overall, all-age rate per 100,000 encounters for GERD was 711.9, BE was 21.6, and EC was 6.1. During 2001-2010, GERD rates increased by approximately 50% and EC rates more than doubled, but BE rates declined by approximately 40%. Trends were similar by age, and all rates were higher in Caucasians and males.
Conclusions: These data indirectly support the idea that increased incidence of EC may be partially due to GERD and raise the provocative hypothesis that BE rates may be decreasing possibly as a forerunner of continued stabilization of esophageal adenocarcinoma rates and a possible subsequent decline. Published by Elsevier Inc.
C1 [Petrick, Jessica L.; Cook, Michael B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-230, Bethesda, MD 20892 USA.
[Tuyet Nguyen] Virginia Commonwealth Univ, Div Gastroenterol, Dept Med Hepatol & Nutr, Med Coll Virginia Campus, Richmond, VA USA.
RP Petrick, JL (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-230, Bethesda, MD 20892 USA.
EM jessica.petrick@nih.gov
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU National Institutes of Health (NIH) Intramural Research Program,
National Cancer Institute; NIH [T32DK007150, UL1TR00005]
FX This research was supported in part by the National Institutes of Health
(NIH) Intramural Research Program, National Cancer Institute; and grants
from NIH (T32DK007150 and UL1TR00005).
NR 13
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD FEB
PY 2016
VL 26
IS 2
BP 151
EP 154
DI 10.1016/j.annepidem.2015.11.004
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DE8MG
UT WOS:000370889500011
PM 26762962
ER
PT J
AU Xia, ZQ
White, CC
Owen, EK
Von Korff, A
Clarkson, SR
McCabe, CA
Cimpean, M
Winn, PA
Hoesing, A
Steele, SU
Cortese, ICM
Chitnis, T
Weiner, HL
Reich, DS
Chibnik, LB
De Jager, PL
AF Xia, Zongqi
White, Charles C.
Owen, Emily K.
Von Korff, Alina
Clarkson, Sarah R.
McCabe, Cristin A.
Cimpean, Maria
Winn, Phoebe A.
Hoesing, Ashley
Steele, Sonya U.
Cortese, Irene C. M.
Chitnis, Tanuja
Weiner, Howard L.
Reich, Daniel S.
Chibnik, Lori B.
De Jager, Philip L.
TI Genes and Environment in Multiple Sclerosis project: A platform to
investigate multiple sclerosis risk
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID RADIOLOGICALLY ISOLATED SYNDROME; GENOME-WIDE ASSOCIATION; BODY-MASS
INDEX; INFECTIOUS-MONONUCLEOSIS; SUSCEPTIBILITY LOCI; SMOKING; OBESITY;
COHORT; AGE; METAANALYSIS
AB The Genes and Environment in Multiple Sclerosis project establishes a platform to investigate the events leading to multiple sclerosis (MS) in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects. Ann Neurol 2016;79:178-189
C1 [Xia, Zongqi; White, Charles C.; Owen, Emily K.; Von Korff, Alina; Clarkson, Sarah R.; Cimpean, Maria; Winn, Phoebe A.; Hoesing, Ashley; Chitnis, Tanuja; Weiner, Howard L.; Chibnik, Lori B.; De Jager, Philip L.] Brigham & Womens Hosp, Program Translat Neuropsychiatr Genom, 75 Francis St, Boston, MA 02115 USA.
[Xia, Zongqi; White, Charles C.; Owen, Emily K.; Von Korff, Alina; Clarkson, Sarah R.; Cimpean, Maria; Winn, Phoebe A.; Hoesing, Ashley; Chitnis, Tanuja; Weiner, Howard L.; Chibnik, Lori B.; De Jager, Philip L.] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Partners Multiple Sclerosis Ctr, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
[Xia, Zongqi; Chitnis, Tanuja; Weiner, Howard L.; Chibnik, Lori B.; De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Xia, Zongqi; White, Charles C.; McCabe, Cristin A.; Chibnik, Lori B.; De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Steele, Sonya U.; Cortese, Irene C. M.; Reich, Daniel S.] Natl Inst Neurol Dis & Stroke, Div Neuroimmunol & Neurovirol, Bethesda, MD USA.
RP De Jager, PL (reprint author), Brigham & Womens Hosp, Dept Neurol, 77 Ave Louis Pasteur,NRB 168, Boston, MA 02115 USA.
EM pdejager@rics.bwh.harvard.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU National Multiple Sclerosis Society [RG-5003-A-2]; NIH National
Institute of Neurological Disorders and Stroke [K08-NS079493];
Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; Clinician Scientist Development Award from the
National Multiple Sclerosis Society; American Academy of Neurology [FAN
1755-A-1]
FX The GEMS study is supported by the National Multiple Sclerosis Society
(RG-5003-A-2; P.L.D.J.), the NIH National Institute of Neurological
Disorders and Stroke (K08-NS079493; Z.X.), and the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke
(S.U.S., I.C.M.C., D.S.R.). Z.X. was a recipient of the Clinician
Scientist Development Award from the National Multiple Sclerosis Society
and the American Academy of Neurology (FAN 1755-A-1). P.L.D.J. was a
Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis
Society (JF2138A1).
NR 49
TC 3
Z9 3
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD FEB
PY 2016
VL 79
IS 2
BP 178
EP 189
DI 10.1002/ana.24560
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DE5AQ
UT WOS:000370643100004
PM 26583565
ER
PT J
AU Contreras, PS
Gonzalez-Zuniga, M
Gonzalez-Hodar, L
Yanez, MJ
Dulcey, A
Marugan, J
Seto, E
Alvarez, AR
Zanlungo, S
AF Contreras, Pablo S.
Gonzalez-Zuniga, Marcelo
Gonzalez-Hodar, Lila
Jose Yanez, Maria
Dulcey, Andres
Marugan, Juan
Seto, Edward
Alvarez, Alejandra R.
Zanlungo, Silvana
TI Neuronal gene repression in Niemann-Pick type C models is mediated by
the c-Abl/HDAC2 signaling pathway
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE Niemann-Pick type C disease; Neuronal genes; Histone deacetylase 2;
Tyrosine kinase c-Abl; Imatinib; GNF2
ID HISTONE DEACETYLASE INHIBITORS; IMPROVES NEUROLOGICAL SYMPTOMS; DISEASE
MOUSE MODEL; ALZHEIMERS-DISEASE; STORAGE DISORDER; APOLIPOPROTEIN-E;
TYROSINE KINASE; CHOLESTEROL; MEMORY; MICE
AB Background: Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of free cholesterol in lysosomes. There are currently no effective FDA-approved treatments for NPC, although in the last years the inhibition of histone deacetylases (HDACs) has emerged as a potential treatment for this disease. However, the molecular mechanisms that deregulate HDAC activity in NPC disease are unknown. Previously our group had shown that the proapoptotic tyrosine kinase c-Abl signaling is activated in NPC neurons. Here, we demonstrate that c-Abl activity increases HDAC2 levels inducing neuronal gene repression of key synaptic genes in NPC models.
Results: Our data show that: i) HDAC2 levels and activity are increased in NPC neuronal models and in Npc1(-/-) mice; ii) inhibition of c-Abl or c-Abl deficiency prevents the increase of HDAC2 protein levels and activity in NPC neuronal models; iii) c-Abl inhibition decreases the levels of HDAC2 tyrosine phosphorylation; iv) treatment with methyl-beta-cyclodextrin and vitamin E decreases the activation of the c-Abl/HDAC2 pathway in NPC neurons; v) in vivo treatment with two c-Abl inhibitors prevents the increase of HDAC2 protein levels in the brain of Npc1(-/-) mice; and vi) c-Abl inhibition prevents HDAC2 recruitment to the promoter of neuronal genes, triggering an increase in their expression.
Conclusion: Our data show the involvement of the c-Abl/HDAC2 signaling pathway in the regulation of neuronal gene expression in NPC neuronal models. Thus, inhibition of c-Abl could be a pharmacological target for preventing the deleterious effects of increased HDAC2 levels in NPC disease. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Contreras, Pablo S.; Gonzalez-Zuniga, Marcelo; Jose Yanez, Maria; Alvarez, Alejandra R.] Pontificia Univ Catolica Chile, Dept Cell & Mol Biol, Santiago 8331010, Chile.
[Contreras, Pablo S.; Jose Yanez, Maria; Alvarez, Alejandra R.] CARE UC Pontificia Univ Catolica Chile, Santiago, Chile.
[Contreras, Pablo S.; Gonzalez-Hodar, Lila; Jose Yanez, Maria] Pontificia Univ Catolica Chile, Fac Med, Dept Gastroenterol, Santiago 8331010, Chile.
[Dulcey, Andres; Marugan, Juan] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Seto, Edward] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA.
[Zanlungo, Silvana] FONDAP Ctr Genome Regulat CGR, Santiago, Chile.
RP Alvarez, AR (reprint author), Pontificia Univ Catolica Chile, Fac Ciencias Biol, Alameda 340, Santiago 8331010, Chile.; Zanlungo, S (reprint author), Pontificia Univ Catolica Chile, Fac Med, Marcoleta 367, Santiago 8330024, Chile.
EM aalvarez@bio.puc.cl; silvana@med.puc.cl
FU Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT)
[1120512, 1110310, 1150186]; Fondo de Fomento al Desarrollo Cientifico y
Tecnologico FONDEF [D10I1077]; Fondo Nacional de Desarrollo de Areas
Prioritarias, FONDAP [15090007]; Center for Genome Regulation (CGR);
Projecto Basal [PFB12/2007]; CONICYT; VRI; MECESUP
FX This study was supported by grants from the Fondo Nacional de Desarrollo
Cientifico y Tecnologico (FONDECYT) (grant numbers 1120512 to A.R.A. and
1110310 and 1150186 to S.Z.); Fondo de Fomento al Desarrollo Cientifico
y Tecnologico FONDEF D10I1077 (to A.R.A. and S.Z.); Fondo Nacional de
Desarrollo de Areas Prioritarias, FONDAP, Project no. 15090007, Center
for Genome Regulation (CGR) to S.Z. and Projecto Basal PFB12/2007,
2013-2017 to A.R.A. M.G-Z. acknowledges support from CONICYT, VRI and
MECESUP. L.G-H. acknowledges support from VRI and P.S.C. and M.J.Y.
acknowledges support from CONICYT.
NR 55
TC 0
Z9 0
U1 3
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD FEB
PY 2016
VL 1859
IS 2
BP 269
EP 279
DI 10.1016/j.bbagrm.2015.11.006
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DE8PK
UT WOS:000370898500005
PM 26603102
ER
PT J
AU Gaudet, MM
Barrdahl, M
Lindstrom, S
Travis, RC
Auer, PL
Buring, JE
Chanock, SJ
Eliassen, AH
Gapstur, SM
Giles, GG
Gunter, M
Haiman, C
Hunter, DJ
Joshi, AD
Kaaks, R
Khaw, KT
Lee, IM
Le Marchand, L
Milne, RL
Peeters, PHM
Sund, M
Tamimi, R
Trichopoulou, A
Weiderpass, E
Yang, XHR
Prentice, RL
Feigelson, HS
Canzian, F
Kraft, P
AF Gaudet, Mia M.
Barrdahl, Myrto
Lindstroem, Sara
Travis, Ruth C.
Auer, Paul L.
Buring, Julie E.
Chanock, Stephen J.
Eliassen, A. Heather
Gapstur, Susan M.
Giles, Graham G.
Gunter, Marc
Haiman, Christopher
Hunter, David J.
Joshi, Amit D.
Kaaks, Rudolf
Khaw, Kay-Tee
Lee, I-Min
Le Marchand, Loic
Milne, Roger L.
Peeters, Petra H. M.
Sund, Malin
Tamimi, Rulla
Trichopoulou, Antonia
Weiderpass, Elisabete
Yang, Xiaohong R.
Prentice, Ross L.
Feigelson, Heather Spencer
Canzian, Federico
Kraft, Peter
TI Interactions between breast cancer susceptibility loci and menopausal
hormone therapy in relationship to breast cancer in the Breast and
Prostate Cancer Cohort Consortium
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Menopausal hormone therapy; Genetic variation
ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INTERACTIONS; RANDOMIZED
CONTROLLED-TRIAL; INITIATIVE CLINICAL-TRIAL; BASE-LINE CHARACTERISTICS;
ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY;
MAMMOGRAPHIC DENSITY; RISK-FACTORS
AB Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values < 1.5 x 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P (interaction) = 1.2 x 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.
C1 [Gaudet, Mia M.; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Barrdahl, Myrto; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Lindstroem, Sara; Hunter, David J.; Joshi, Amit D.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Genet Epidemiol & Stat Genet, 677 Huntington Ave, Boston, MA 02115 USA.
[Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX1 2JD, England.
[Auer, Paul L.; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Auer, Paul L.] Univ Wisconsin, Sch Publ Hlth, Madison, WI USA.
[Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA.
[Chanock, Stephen J.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chanock, Stephen J.] Core Genotyping Facil Frederick Natl Lab Canc Res, Gaithersburg, MD USA.
[Eliassen, A. Heather; Tamimi, Rulla] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Eliassen, A. Heather; Tamimi, Rulla] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr Melbourne, Melbourne, Vic 3004, Australia.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Giles, Graham G.] Monash Univ, Fac Med, Melbourne, Vic 3800, Australia.
[Gunter, Marc] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, South Kensington Campus, London SW7 2AZ, England.
[Haiman, Christopher] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge CB2 0SP, England.
[Lee, I-Min; Tamimi, Rulla] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
[Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3508 Stratenum, Netherlands.
[Peeters, Petra H. M.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, South Kensington Campus, London SW7 2AZ, England.
[Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci Surg, S-90185 Umea, Sweden.
[Trichopoulou, Antonia] Hellen Hlth Fdn, 13 Kaisareias & Alexandroupoleos St, Athens 11527, Greece.
[Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, N-9037 Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Res, Fridtjof Nansens Vei 19, N-0304 Oslo, Norway.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Topeliusgatan 20, Helsinki 00250, Finland.
[Prentice, Ross L.] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA.
[Feigelson, Heather Spencer] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
RP Gaudet, MM (reprint author), Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
EM mia.gaudet@cancer.org
RI Weiderpass, Elisabete/M-4029-2016;
OI Weiderpass, Elisabete/0000-0003-2237-0128; Giles,
Graham/0000-0003-4946-9099
FU US National Institutes of Health; National Cancer Institute
[U01-CA98233-07, U01-CA98710-06, U01-CA98216-06, U01-CA98758-07];
Intramural Research Program of National Institutes of Health; National
Cancer Institute, Division of Cancer Epidemiology and Genetics; American
Cancer Society; Nurses' Health Study [UM1 186107, R01 CA49449]; Nurses'
Health Study II [UM1 176726, R01 CA67262]; Women's Health Study
[CA047988, HL043851, HL080467]; National Heart, Lung, and Blood
Institute, National Institutes of Health; U.S. Department of Health and
Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN2682011000 04C, HHSN271201100004C]; Cancer
Research UK [C570/A11691, C8221/A19170]; [U01 CA164973]
FX This work was supported, in part, by the US National Institutes of
Health, National Cancer Institute (cooperative agreements U01-CA98233-07
to D.J.H., U01-CA98710-06 to M.J.T., U01-CA98216-06 to E.R. and R.K.,
and U01-CA98758-07 to B.E.H.) and Intramural Research Program of
National Institutes of Health and National Cancer Institute, Division of
Cancer Epidemiology and Genetics. The American Cancer Society provided
funds to Drs. Gaudet and Gapstur as well as for the creation,
maintenance, and updating of the Cancer Prevention Study II (CPS-II)
cohort. The Nurses' Health Study (UM1 186107, R01 CA49449), the Nurses'
Health Study II (UM1 176726, R01 CA67262), and the Women's Health Study
(CA047988, HL043851 and HL080467) are supported by grants from the
National Institutes of Health. The WHI program was funded by the
National Heart, Lung, and Blood Institute, National Institutes of
Health, U.S. Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN2682011000 04C, and HHSN271201100004C.'' The
authors thank the WHI investigators and staff for their dedication, and
the study participants for making the program possible. A full listing
of WHI investigators can be found at
http://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20In
vestigator%20Short%20List.pdf. Ruth C Travis was supported by Cancer
Research UK grants (C570/A11691 and C8221/A19170). The Multiethnic
Cohort was supported by grant U01 CA164973.
NR 45
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD FEB
PY 2016
VL 155
IS 3
BP 531
EP 540
DI 10.1007/s10549-016-3681-7
PG 10
WC Oncology
SC Oncology
GA DF0UR
UT WOS:000371055100014
PM 26802016
ER
PT J
AU Duggan, C
Stanczyk, F
Campbell, K
Neuhouser, ML
Baumgartner, RN
Baumgartner, KB
Bernstein, L
Ballard, R
McTiernan, A
AF Duggan, Catherine
Stanczyk, Frank
Campbell, Kristin
Neuhouser, Marian L.
Baumgartner, Richard N.
Baumgartner, Kathy B.
Bernstein, Leslie
Ballard, Rachel
McTiernan, Anne
TI Associations of sex steroid hormones with mortality in women with breast
cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Mortality; Sex steroid hormones
ID BINDING GLOBULIN SHBG; POSTMENOPAUSAL WOMEN; CELLS; ESTRADIOL; RECEPTOR;
TESTOSTERONE; MAMMOGRAPHY; RECURRENCE; EXPRESSION; ESTROGENS
AB Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log-transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer-specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts.
C1 [Duggan, Catherine; Neuhouser, Marian L.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Stanczyk, Frank] Univ So Calif, Keck Sch Med, Dept Obstet Gynecol & Prevent Med, Los Angeles, CA 90033 USA.
[Campbell, Kristin] Univ British Columbia, Fac Med, Vancouver, BC V5Z 1M9, Canada.
[Baumgartner, Richard N.; Baumgartner, Kathy B.] Univ Louisville, James Graham Brown Canc Ctr, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA.
[Ballard, Rachel] NIH, Off Dis Prevent, Bldg 10, Bethesda, MD 20892 USA.
[McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA 98195 USA.
RP Duggan, C (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
EM cduggan@fhcrc.org
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010,
U54-CA116847, U54CA116848, R25-CA94880]; National Institutes of Health
[M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National
Institute of Child Health and Human Development [N01-HD-3-3175];
California Department of Health Services [050Q-8709-S1528]
FX National Cancer Institute (N01-CN-75036-20, N01-CN-05228, N01-PC-67010,
U54-CA116847, U54CA116848, R25-CA94880); National Institutes of Health
(M01-RR-00037); University of New Mexico (NCRR M01-RR-0997); National
Institute of Child Health and Human Development (N01-HD-3-3175);
California Department of Health Services (050Q-8709-S1528).
NR 23
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD FEB
PY 2016
VL 155
IS 3
BP 559
EP 567
DI 10.1007/s10549-016-3704-4
PG 9
WC Oncology
SC Oncology
GA DF0UR
UT WOS:000371055100017
PM 26865065
ER
PT J
AU Schenk, JM
Till, C
Hsing, AW
Stanczyk, FZ
Gong, ZH
Neuhouser, ML
Reichardt, JK
Hoque, AM
Figg, WD
Goodman, PJ
Tangen, CM
Thompson, IM
AF Schenk, Jeannette M.
Till, Cathee
Hsing, Ann W.
Stanczyk, Frank Z.
Gong, Zhihong
Neuhouser, Marian L.
Reichardt, Juergen K.
Hoque, Ashraful M.
Figg, William D.
Goodman, Phyllis J.
Tangen, Catherine M.
Thompson, Ian M.
TI Serum androgens and prostate cancer risk: results from the placebo arm
of the Prostate Cancer Prevention Trial
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Prostate cancer; Androgens; Prostate Cancer Prevention Trial
ID ENDOGENOUS SEX-HORMONES; STEROID-HORMONES; MOLECULAR EPIDEMIOLOGY;
UNITED-STATES; MEN; 5-ALPHA-REDUCTASE; TESTOSTERONE; FINASTERIDE; CYP17
AB Background Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.
Methods In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3 alpha-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.
Results We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA.
Conclusion Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.
C1 [Schenk, Jeannette M.; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
[Till, Cathee; Goodman, Phyllis J.; Tangen, Catherine M.] Fred Hutchinson Canc Res Ctr, SWOG, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
[Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
[Stanczyk, Frank Z.] Univ So Calif, Dept Obstet Gynecol, Los Angeles, CA USA.
[Gong, Zhihong] Roswell Pk Canc Inst, Canc Prevent & Control, Buffalo, NY 14263 USA.
[Reichardt, Juergen K.] James Cook Univ, Div Trop Hlth & Med, Townsville, Qld 4811, Australia.
[Hoque, Ashraful M.] Univ Texas MD Anderson Canc Ctr, Clin Canc Prevent, Houston, TX 77030 USA.
[Figg, William D.] NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Reichardt, Juergen K.] YachayTech Univ, San Miguel De Urcuqui, Ecuador.
RP Schenk, JM (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
EM jschenk@fredhutch.org; ctill@fredhutch.org; Ann.Hsing@CPIC.org;
stanczyk@usc.edu; Zhihong.Gong@RoswellPark.org; mneuhous@fredhutch.org;
jreichardt@yachaytech.edu.ec; ahoque@mdanderson.org;
figgw@helix.nih.gov; pgoodman@fredhutch.org; ctangen@fredhutch.org;
ThompsonI@uthscsa.edu
RI Figg Sr, William/M-2411-2016;
OI Reichardt, Juergen/0000-0001-6458-2773
FU National Cancer Institute [P01-CA108964, UM1-CA182883, U10-CA37429];
Intramural Research Program of the U.S. National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
[P30-CA054174]; Cancer Center Support Grant for the Cancer Therapy and
Research Center at the University of Texas Health Science Center at San
Antonio [P30 CA015704-36]; Cancer Center Support Grant for the Seattle
Cancer Consortium, Seattle, WA of the Early Detection Research Network
[U01 CA086042]
FX This work was funded by the following P01CA108964, UM1-CA182883, and
U10-CA37429 from the National Cancer Institute; Intramural Research
Program of the U.S. National Institutes of Health, National Cancer
Institute, Division of Cancer Epidemiology and Genetics; P30-CA054174,
the Cancer Center Support Grant for the Cancer Therapy and Research
Center at the University of Texas Health Science Center at San Antonio;
P30 CA015704-36, the Cancer Center Support Grant for the Seattle Cancer
Consortium, Seattle, WA; U01 CA086042 of the Early Detection Research
Network. The authors would like to acknowledge that Dr. Ronald K. Ross,
University of Southern California (deceased), participated in the design
of this study.
NR 28
TC 2
Z9 2
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD FEB
PY 2016
VL 27
IS 2
BP 175
EP 182
DI 10.1007/s10552-015-0695-0
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DE9JR
UT WOS:000370953300004
PM 26589415
ER
PT J
AU Nagrani, R
Mhatre, S
Boffetta, P
Rajaraman, P
Badwe, R
Gupta, S
Romieu, I
Parmar, V
Dikshit, R
AF Nagrani, Rajini
Mhatre, Sharayu
Boffetta, Paolo
Rajaraman, Preetha
Badwe, Rajendra
Gupta, Sudeep
Romieu, Isabelle
Parmar, Vani
Dikshit, Rajesh
TI Understanding rural-urban differences in risk factors for breast cancer
in an Indian population
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Rural-urban; Reproductive factors; Anthropometry; Central
obesity
ID BODY-SIZE; REPRODUCTIVE FACTORS; INDUCED-ABORTION; FAT DISTRIBUTION;
SOUTH ASIANS; WOMEN; ASSOCIATION; METAANALYSIS; OBESITY; AGE
AB Purpose Although cancer registry data indicate that there are large differences in breast cancer (BC) rates between rural and urban regions of India, the reasons for these differences are not well understood.
Methods We conducted a hospital based case-control study (1,637 breast cancer cases; 1,515 visitor controls) in Mumbai, India, during the years 2009-2013. Extensive questionnaire data, anthropometry measurement and blood samples were collected on all participants. Using logistic regression models, we estimated risk based on odds ratio (OR) and 95 % confidence intervals (CI) for various reproductive and anthropometric measures, stratified by rural-urban status depending upon residence in first 20 years of life.
Results Waist-to-hip ratio of >= 0.95 compared to ratio <= 0.84 was strongly associated with risk of BC in both rural and urban populations (ORurban = 4.10, 95 % CI 3.03-5.56; ORrural = 3.01, 95 % CI 1.85-4.90). First fullterm pregnancy after the age of 25 compared to first fullterm pregnancy below 20 years of age was associated with risk of BC in both urban and rural women (ORurban = 1.78, 95 % CI 1.32-2.41; ORrural = 2.24, 95 % CI 1.13-4.43). The prevalence of age at first full-term pregnancy was significantly lower in rural (mean age at first full-term pregnancy = 19.39 years) versus urban women (mean age at first full-term pregnancy = 22.62 years), whereas mean waist circumference was much higher in urban women (82.13 cm) compared to rural women (79.26 cm). We did not observe any association between breast feeding and risk of BC.
Conclusions Differences in the prevalence of central adiposity and age at first full-term pregnancy between rural and urban women from India may explain some differences in breast cancer rates between these two populations.
C1 [Nagrani, Rajini; Mhatre, Sharayu; Dikshit, Rajesh] Tata Mem Hosp, Ctr Canc Epidemiol, E Borges Rd, Parel Mumbai 400012, Maharashtra, India.
[Boffetta, Paolo] Mt Sinai Hosp, Icahn Sch Med, Inst Translat Epidemiol, New York, NY 10029 USA.
[Rajaraman, Preetha] US Natl Canc Inst, Ctr Global Hlth, Rockville, MD USA.
[Rajaraman, Preetha] US Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Badwe, Rajendra; Parmar, Vani] Tata Mem Hosp, Dept Surg Oncol, Bombay 400012, Maharashtra, India.
[Gupta, Sudeep] Tata Mem Hosp, Dept Med Oncol, Bombay 400012, Maharashtra, India.
[Romieu, Isabelle] Int Agcy Res Canc, Nutr Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
RP Dikshit, R (reprint author), Tata Mem Hosp, Ctr Canc Epidemiol, E Borges Rd, Parel Mumbai 400012, Maharashtra, India.
EM dixr24@hotmail.com
OI nagrani, rajini/0000-0002-1708-2319
FU International Agency for Research on Cancer and Department of
Biotechnology
FX The work was supported by International Agency for Research on Cancer
and Department of Biotechnology.
NR 38
TC 1
Z9 1
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD FEB
PY 2016
VL 27
IS 2
BP 199
EP 208
DI 10.1007/s10552-015-0697-y
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DE9JR
UT WOS:000370953300006
PM 26589416
ER
PT J
AU Paltiel, O
Tajuddin, SM
Polanker, Y
Yazdgerdi, S
Manor, O
Friedlander, Y
Harlap, S
Calderon-Margalit, R
AF Paltiel, Ora
Tajuddin, Salman M.
Polanker, Yelena
Yazdgerdi, Shoshanah
Manor, Orly
Friedlander, Yechiel
Harlap, Susan
Calderon-Margalit, Ronit
TI Grand multiparity and reproductive cancer in the Jerusalem Perinatal
Study Cohort
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Endometrial cancer; Multiparity; Cohort study; Survival
ID CAUSE-SPECIFIC MORTALITY; NEGATIVE BREAST-CANCER; RISK-FACTORS;
ENDOMETRIAL CANCER; CERVICAL-CANCER; PAROUS WOMEN; 1ST BIRTH; PARITY;
SURVIVAL; POPULATION
AB Objectives Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women.
Study design We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13-55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables.
Results Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54-0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03).
Conclusion Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.
C1 [Paltiel, Ora; Polanker, Yelena; Yazdgerdi, Shoshanah; Manor, Orly; Friedlander, Yechiel; Calderon-Margalit, Ronit] Hadassah Hebrew Univ, Braun Sch Publ Hlth, Jerusalem, Israel.
[Paltiel, Ora] Hadassah Hebrew Univ, Med Ctr, Dept Hematol, POB 12000, IL-91120 Jerusalem, Israel.
[Tajuddin, Salman M.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Harlap, Susan] NYU, Sch Med, New York, NY USA.
RP Paltiel, O (reprint author), Hadassah Hebrew Univ, Braun Sch Publ Hlth, Jerusalem, Israel.; Paltiel, O (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Hematol, POB 12000, IL-91120 Jerusalem, Israel.
EM orap@hadassah.org.il
OI Tajuddin, Salman M./0000-0002-7919-8528
FU Maria Ascoli Foundation, Jerusalem, Israel
FX Supported by the Maria Ascoli Foundation, Jerusalem, Israel, who had no
involvement in the conduct or reporting of the study.
NR 66
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD FEB
PY 2016
VL 27
IS 2
BP 237
EP 247
DI 10.1007/s10552-015-0701-6
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DE9JR
UT WOS:000370953300010
PM 26669321
ER
PT J
AU Hoofnagle, JH
Wright, EC
AF Hoofnagle, Jay H.
Wright, Elizabeth C.
TI Weight Loss from Green Tea Extracts
SO CLINICAL NUTRITION
LA English
DT Letter
C1 [Hoofnagle, Jay H.] NIH, Liver Dis Res Branch, Div Digest Dis & Nutr, Bldg 10, Bethesda, MD 20892 USA.
[Wright, Elizabeth C.] Natl Inst Diabet & Digest Dis, NIH, Bethesda, MD USA.
RP Hoofnagle, JH (reprint author), NIH, Liver Dis Res Branch, Div Digest Dis & Nutr, Bldg 10, Bethesda, MD 20892 USA.
EM Hoofnaglej@extra.niddk.nih.gov
NR 0
TC 0
Z9 0
U1 9
U2 18
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0261-5614
EI 1532-1983
J9 CLIN NUTR
JI Clin. Nutr.
PD FEB
PY 2016
VL 35
IS 1
BP 238
EP 238
DI 10.1016/j.clnu.2015.09.013
PG 1
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DE8RY
UT WOS:000370905600036
PM 26527097
ER
PT J
AU Li, ZD
Pearlman, AH
Hsieh, P
AF Li, Zhongdao
Pearlman, Alexander H.
Hsieh, Peggy
TI DNA mismatch repair and the DNA damage response
SO DNA REPAIR
LA English
DT Article
DE Mismatch repair; Lynch syndrome; DNA damage response; Mutagenesis;
Colorectal cancer
ID INTERSTRAND CROSS-LINKS; BASE EXCISION-REPAIR; REPLICATION PROTEIN-A;
S-PHASE CHECKPOINT; CELL-CYCLE ARREST; IN-VITRO; ATR ACTIVATION;
EXONUCLEASE 1; TRANSLESION SYNTHESIS; METHYLATING AGENTS
AB This review discusses the role of DNA mismatch repair (MMR) in the DNA damage response (DDR) that triggers cell cycle arrest and, in some cases, apoptosis. Although the focus is on findings from mammalian cells, much has been learned from studies in other organisms including bacteria and yeast [1,2]. MMR promotes a DDR mediated by a key signaling kinase, ATM and Rad3-related (ATR), in response to various types of DNA damage including some encountered in widely used chemotherapy regimes. An introduction to the DDR mediated by ATR reveals its immense complexity and highlights the many biological and mechanistic questions that remain. Recent findings and future directions are highlighted. Published by Elsevier B.V.
C1 [Li, Zhongdao; Pearlman, Alexander H.; Hsieh, Peggy] NIDDK, Genet & Biochem Branch, NIH, Bldg 5 Rm 324,5 Mem Dr MSC 0538, Bethesda, MD 20892 USA.
RP Hsieh, P (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5 Rm 324,5 Mem Dr MSC 0538, Bethesda, MD 20892 USA.
EM peggyh@niddk.nih.gov
FU Division of Intramural Research of the National Institute of Diabetes
and Digestive and Kidney Diseases, NIH
FX The authors are supported by the Division of Intramural Research of the
National Institute of Diabetes and Digestive and Kidney Diseases, NIH.
NR 161
TC 5
Z9 5
U1 7
U2 30
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD FEB
PY 2016
VL 38
SI SI
BP 94
EP 101
DI 10.1016/j.dnarep.2015.11.019
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA DE8ON
UT WOS:000370895900012
PM 26704428
ER
PT J
AU Zanotti, KJ
Gearhart, PJ
AF Zanotti, Kimberly J.
Gearhart, Patricia J.
TI Antibody diversification caused by disrupted mismatch repair and
promiscuous DNA polymerases
SO DNA REPAIR
LA English
DT Review
DE Activation-induced deaminase; Class switch recombination; DNA polymerase
eta; Mismatch repair; Somatic hypermutation
ID CLASS-SWITCH RECOMBINATION; INDUCED CYTIDINE DEAMINASE;
ACTIVATION-INDUCED DEAMINASE; DOUBLE-STRAND BREAKS; IG GENE
HYPERMUTATION; CENTER B-CELLS; IMMUNOGLOBULIN VARIABLE GENES; AFFECT
SOMATIC HYPERMUTATION; UNG-DEFICIENT MICE; RNA EDITING ENZYME
AB The enzyme activation-induced deaminase (AID) targets the immunoglobulin loci in activated B cells and creates DNA mutations in the antigen-binding variable region and DNA breaks in the switch region through processes known, respectively, as somatic hypermutation and class switch recombination. AID deaminates cytosine to uracil in DNA to create a U:G mismatch. During somatic hypermutation, the MutS alpha complex binds to the mismatch, and the error-prone DNA polymerase eta generates mutations at A and T bases. During class switch recombination, both MutS alpha and MutL alpha complexes bind to the mismatch, resulting in double-strand break formation and end-joining. This review is centered on the mechanisms of how the MMR pathway is commandeered by B cells to generate antibody diversity. Published by Elsevier B.V.
C1 [Zanotti, Kimberly J.; Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX We thank Robert Maul for helpful discussions and feedback. This research
was supported entirely by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 118
TC 5
Z9 5
U1 5
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD FEB
PY 2016
VL 38
SI SI
BP 110
EP 116
DI 10.1016/j.dnarep.2015.11.011
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA DE8ON
UT WOS:000370895900014
PM 26719140
ER
PT J
AU Fowler, DH
Gattinoni, L
AF Fowler, Daniel H.
Gattinoni, Luca
TI T memory stem cell formation: Caveat mTOR
SO EBIOMEDICINE
LA English
DT Editorial Material
ID DIFFERENTIATION
C1 [Fowler, Daniel H.; Gattinoni, Luca] NIH, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
RP Gattinoni, L (reprint author), NIH, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD FEB
PY 2016
VL 4
BP 3
EP 4
DI 10.1016/j.ebiom.2016.02.019
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DE7HL
UT WOS:000370806400002
PM 26981558
ER
PT J
AU Musselwhite, LW
Andrade, BB
Ellenberg, SS
Tierney, A
Belaunzaran-Zamudio, PF
Rupert, A
Lederman, MM
Sanne, I
Madero, JGS
Sereti, I
AF Musselwhite, Laura W.
Andrade, Bruno B.
Ellenberg, Susan S.
Tierney, Ann
Belaunzaran-Zamudio, Pablo F.
Rupert, Adam
Lederman, Michael M.
Sanne, Ian
Sierra Madero, Juan G.
Sereti, Irini
TI Vitamin D, D-dimer, Interferon gamma, and sCD14 Levels are Independently
Associated with Immune Reconstitution Inflammatory Syndrome: A
Prospective, International Study
SO EBIOMEDICINE
LA English
DT Article
DE IRIS; HIV; Biomarker; Vitamin D; D-Dimer; Inflammatory cytokine
ID STARTING ANTIRETROVIRAL THERAPY; PLASMODIUM-VIVAX MALARIA; PULMONARY
TUBERCULOSIS; D SUPPLEMENTATION; CYTOKINE PROFILE; CONTROLLED-TRIAL;
DOUBLE-BLIND; D DEFICIENCY; HIV; BIOMARKERS
AB To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher D-dimer, interferon gamma (IFN gamma), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFN., and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study. Published by Elsevier B.V. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Musselwhite, Laura W.; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
[Musselwhite, Laura W.] Duke Univ, Duke Hubert Yeargan Ctr Global Hlth, 310 Trent Dr,Duke Box 90518, Durham, NC 27708 USA.
[Andrade, Bruno B.] NIAID, Parasit Dis Lab, NIH, 50 South Dr, Bethesda, MD 20892 USA.
[Andrade, Bruno B.] Fundacao Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz CPqGM, Lab Integrado Microbiol & Imunorregulacao LIMI, Unidade Med Invest, BR-40296710 Salvador, BA, Brazil.
[Andrade, Bruno B.] Jose Silveira Fdn, Brazilian Inst TB Res, Multinat Org Network Sponsoring Translat & Epidem, Salvador, BA, Brazil.
[Ellenberg, Susan S.; Tierney, Ann] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 611 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
[Belaunzaran-Zamudio, Pablo F.; Sierra Madero, Juan G.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Infectol, Mexico City, DF, Mexico.
[Belaunzaran-Zamudio, Pablo F.] Univ Nacl Autonoma Mexico, Fac Med, Div Invest, Mexico City 04510, DF, Mexico.
[Rupert, Adam] Leidos Biomed Inc, 11951 Freedom Dr, Reston, VA 20190 USA.
[Lederman, Michael M.] Case Western Reserve Univ, Sch Med, 2061 Cornell Rd, Cleveland, OH 44106 USA.
[Sanne, Ian] Univ Witwatersrand, Johannesburg, South Africa.
RP Sereti, I (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-07A, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS; NCI NIH HHS
[HHSN261200800001E]; NIAID NIH HHS [1R21AI110335-01, P30 AI045008, UM1
AI069501]; PHS HHS [HHSN261200800001E]
NR 35
TC 3
Z9 3
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD FEB
PY 2016
VL 4
BP 115
EP 123
DI 10.1016/ebiom.2016.01.016
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DE7HL
UT WOS:000370806400022
PM 26981576
ER
PT J
AU Solomon, SD
Claggett, B
Lewis, EF
Desai, A
Anand, I
Sweitzer, NK
O'Meara, E
Shah, SJ
McKinlay, S
Fleg, JL
Sopko, G
Pitt, B
Pfeffer, MA
AF Solomon, Scott D.
Claggett, Brian
Lewis, Eldrin F.
Desai, Akshay
Anand, Inder
Sweitzer, Nancy K.
O'Meara, Eileen
Shah, Sanjiv J.
McKinlay, Sonja
Fleg, Jerome L.
Sopko, George
Pitt, Bertram
Pfeffer, Marc A.
CA TOPCAT Investigators
TI Influence of ejection fraction on outcomes and efficacy of
spironolactone in patients with heart failure with preserved ejection
fraction
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Heart failure with preserved ejection fraction; Spironolactone
ID ALDOSTERONE ANTAGONIST TRIAL
AB Aims While mineralocorticoid receptor antagonists (MRAs) have been shown to benefit patients with reduced left ventricular ejection fraction (LVEF), spironolactone did not reduce the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT trial, which enrolled patients with LVEF of 45% or greater. We utilized data from TOPCAT to assess the relationship between LVEF as well as outcomes and efficacy of spironolactone.
Methods and results We assessed differences in baseline characteristics and outcomes across LVEF categories in 3444 patients with HFpEF, and determined whether LVEF modified the treatment effect of spironolactone. Ejection fraction ranged from 44 to 85%. Patients with higher ejection fraction were older, more likely to be female, less likely to have a history of myocardial infarction, and more likely to have a history of hypertension and diabetes. The incidence of the primary endpoint and cardiovascular death was highest in patients at the lower end of the ejection fraction spectrum. Ejection fraction modified the spironolactone treatment effect, particularly in the patients enrolled in the Americas, for the primary outcome (P = 0.046) and for heart failure hospitalization (P = 0.039), with stronger estimated benefits of spironolactone at the lower end of the ejection fraction spectrum with respect to the primary endpoint (LVEF <50%: HR 0.72, 95% CI 0.50, 1.05; LVEF >= 60%: HR 0.97, 95% CI 0.76, 1.23) and heart failure hospitalization (LVEF <50%: HR 0.76, 95% CI 0.46, 1.27; LVEF >= 60%: HR 0.98, 95% CI 0.74, 1.30).
Conclusion In patients with HFpEF enrolled in TOPCAT, patient characteristics and outcomes varied substantially by LVEF. The potential efficacy of spironolactone was greatest at the lower end of the LVEF spectrum.
C1 [Solomon, Scott D.; Claggett, Brian; Lewis, Eldrin F.; Desai, Akshay; Pfeffer, Marc A.] Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
[Anand, Inder] Minneapolis VA Hosp, Minneapolis, MN USA.
[Sweitzer, Nancy K.] Univ Arizona, Tucson, AZ USA.
[O'Meara, Eileen] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[McKinlay, Sonja] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
[Fleg, Jerome L.; Sopko, George] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[Pitt, Bertram] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Solomon, SD (reprint author), Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
EM ssolomon@rics.bwh.harvard.edu
FU National Heart, Lung, and Blood Institute; National Institutes of Health
[HHSN268200425207C]
FX This work was funded by the National Heart, Lung, and Blood Institute
and National Institutes of Health (contract HHSN268200425207C). The
content of this article does not necessarily represent the views of the
National Heart, Lung, and Blood Institute or of the Department of Health
and Human Services.
NR 15
TC 11
Z9 11
U1 4
U2 4
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 FEB 1
PY 2016
VL 37
IS 5
BP 455
EP 462
DI 10.1093/eurheartj/ehv464
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DE9RQ
UT WOS:000370976200013
PM 26374849
ER
PT J
AU Krupovic, M
Shmakov, S
Makarova, KS
Forterre, P
Koonin, EV
AF Krupovic, Mart
Shmakov, Sergey
Makarova, Kira S.
Forterre, Patrick
Koonin, Eugene V.
TI Recent Mobility of Casposons, Self-Synthesizing Transposons at the
Origin of the CRISPR-Cas Immunity
SO GENOME BIOLOGY AND EVOLUTION
LA English
DT Article
DE casposons; self-synthesizing transposons; CRISPR-Cas; mobile genetic
elements; transposition
ID ARCHAEO-EUKARYOTIC PRIMASE; SINGLE-STRANDED-DNA; ADAPTIVE IMMUNITY;
SPACER ACQUISITION; GENOME EXPANSION; ELEMENTS; EVOLUTION; SYSTEMS;
CLASSIFICATION; SUPERFAMILY
AB Casposons are a superfamily of putative self-synthesizing transposable elements that are predicted to employ a homolog of Cas1 protein as a recombinase and could have contributed to the origin of the CRISPR-Cas adaptive immunity systems in archaea and bacteria. Casposons remain uncharacterized experimentally, except for the recent demonstration of the integrase activity of the Cas1 homolog, and given their relative rarity in archaea and bacteria, original comparative genomic analysis has not provided direct indications of their mobility. Here, we report evidence of casposon mobility obtained by comparison of the genomes of 62 strains of the archaeon Methanosarcina mazei. In these genomes, casposons are variably inserted in three distinct sites indicative of multiple, recent gains, and losses. Some casposons are inserted into other mobile genetic elements that might provide vehicles for horizontal transfer of the casposons. Additionally, many M. mazei genomes contain previously undetected solo terminal inverted repeats that apparently are derived from casposons and could resemble intermediates in CRISPR evolution. We further demonstrate the sequence specificity of casposon insertion and note clear parallels with the adaptation mechanism of CRISPR-Cas. Finally, besides identifying additional representatives in each of the three originally defined families, we describe a new, fourth, family of casposons.
C1 [Krupovic, Mart; Forterre, Patrick] Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, Paris, France.
[Shmakov, Sergey; Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
[Shmakov, Sergey] Skolkovo Inst Sci & Technol, Skolkovo, Russia.
RP Krupovic, M (reprint author), Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, Paris, France.
EM krupovic@pasteur.fr
RI Krupovic, Mart/I-4209-2012
OI Krupovic, Mart/0000-0001-5486-0098
FU European Union [340440]; US Department of Health and Human Services
FX P.F. was supported by the European Union's Seventh Framework Program
(FP/2007-2013)/Project EVOMOBIL - ERC Grant Agreement no. 340440. E.V.K.
and K.S.M. are supported by intramural funds of the US Department of
Health and Human Services (to the National Library of Medicine).
NR 63
TC 4
Z9 4
U1 4
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1759-6653
J9 GENOME BIOL EVOL
JI Genome Biol. Evol.
PD FEB
PY 2016
VL 8
IS 2
BP 375
EP 386
DI 10.1093/gbe/evw006
PG 12
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA DE9QA
UT WOS:000370971700006
PM 26764427
ER
PT J
AU Vidal, NM
Grazziotin, AL
Iyer, LM
Aravind, L
Venancio, TM
AF Vidal, Newton M.
Grazziotin, Ana Laura
Iyer, Lakshminarayan M.
Aravind, L.
Venancio, Thiago M.
TI Transcription factors, chromatin proteins and the diversification of
Hemiptera
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Insect development; Lineage-specific expansion; Genome evolution;
Transcription factor; Transposable element; Rhodnius prolixus
ID DNA-BINDING DOMAIN; DROSOPHILA-MELANOGASTER; TRANSPOSABLE ELEMENTS;
COMPARATIVE GENOMICS; PIPSQUEAK PROTEIN; NATURAL-HISTORY;
GENE-EXPRESSION; HOMEOBOX GENES; THAP DOMAIN; POZ DOMAIN
AB Availability of complete genomes provides a means to explore the evolution of enormous developmental, morphological, and behavioral diversity among insects. Hemipterans in particular show great diversity of both morphology and life history within a single order. To better understand the role of transcription regulators in the diversification of hemipterans, using sequence profile searches and hidden Markov models we computationally analyzed transcription factors (TFs) and chromatin proteins (CPs) in the recently available Rhodnius prolixus genome along with 13 other insect and 4 non-insect arthropod genomes. We generated a comprehensive collection of TFs and CPs across arthropods including 303 distinct types of domains in TFs and 139 in CPs. This, along with the availability of two hemipteran genomes, R. prolixus and Acyrthosiphon pisum, helped us identify possible determinants for their dramatic morphological and behavioral divergence. We identified five domain families (i.e. Pipsqueak, SAZ/MADF, THAP, FLYWCH and BED finger) as having undergone differential patterns of lineage-specific expansion in hemipterans or within hemipterans relative to other insects. These expansions appear to be at least in part driven by transposons, with the DNA-binding domains of transposases having provided the raw material for emergence of new TFs. Our analysis suggests that while R. prolixus probably retains a state closer to the ancestral hemipteran, A. pisum represents a highly derived state, with the emergence of asexual reproduction potentially favoring genome duplication and transposon expansion. Both hemipterans are predicted to possess active DNA methylation systems. However, in the course of their divergence, aphids seem to have expanded the ancestral hemipteran DNA methylation along with a distinctive linkage to the histone methylation system, as suggested by expansion of SET domain methylases, including those fused to methylated CpG recognition domains. Thus, differential use of DNA methylation and histone methylation might have played a role in emergence of polyphenism and cyclic parthenogenesis from the ancestral hemipteran. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Vidal, Newton M.; Grazziotin, Ana Laura; Iyer, Lakshminarayan M.; Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Vidal, Newton M.; Grazziotin, Ana Laura; Venancio, Thiago M.] Univ Estadual Norte Fluminense, Ctr Biociencias & Biotecnol, Lab Quim & Funcao Prot & Peptideos, Campos Dos Goytacazes, RJ, Brazil.
[Vidal, Newton M.; Venancio, Thiago M.] Inst Nacl Ciencia & Tecnol Entomol Mol, Rio De Janeiro, RJ, Brazil.
RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.; Venancio, TM (reprint author), Av Alberto Lamego 2000,5 Sala 217, BR-28013602 Campos Dos Goytacazes, RJ, Brazil.
EM nwvidal@gmail.com; analauragrazziotin@gmail.com;
lakshmin@ncbi.nlm.nih.gov; aravind@ncbi.nlm.nih.gov;
thiago.venancio@gmail.com
RI Venancio, Thiago/B-5003-2011
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq);
Intramural Research Program of National Library of Medicine at the
National Institutes of Health, USA; Institute Nacional de Ciencia e
Tecnologia em Entomologia Molecular (INCT-EM); CNPq; INCT-EM; FAPERJ
FX This work is supported by funds of: Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq); Intramural Research Program of National
Library of Medicine at the National Institutes of Health, USA, and;
Institute Nacional de Ciencia e Tecnologia em Entomologia Molecular
(INCT-EM). NMV is supported in part by CNPq. NMV was recipient of a
post-doctoral fellowship from INCT-EM. TMV is supported by INCT-EM, CNPq
and FAPERJ. TMV is a recipient of an established investigator fellowship
award from CNPq.
NR 91
TC 1
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U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
EI 1879-0240
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD FEB
PY 2016
VL 69
SI SI
BP 1
EP 13
DI 10.1016/j.ibmb.2015.07.001
PG 13
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA DE8PU
UT WOS:000370899600001
PM 26226651
ER
PT J
AU Fernandez-Medina, RD
Granzotto, A
Ribeiro, JM
Carareto, CMA
AF Fernandez-Medina, R. D.
Granzotto, A.
Ribeiro, J. M.
Carareto, C. M. A.
TI Transposition burst of mariner-like elements in the sequenced genome of
Rhodnius prolixus
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Transposable elements; Mariner family; Burst of transposition;
Speciation; Rhodnius prolixus
ID EUKARYOTIC TRANSPOSABLE ELEMENTS; DROSOPHILA-BUZZATII; CHAGAS-DISEASE;
COLONIZING POPULATIONS; ANOPHELES-GAMBIAE; FRUIT-FLY; OSVALDO;
EVOLUTION; DATABASE; TOOL
AB Transposable elements (TEs) are widespread in insect's genomes. However, there are wide differences in the proportion of the total DNA content occupied by these repetitive sequences in different species. We have analyzed the TEs present in R. prolixus (vector of the Chagas disease) and showed that 3.0% of this genome is occupied by Class II TEs, belonging mainly to the Tc1-mariner superfamily (1.65%) and MITEs (1.84%). Interestingly, most of this genomic content is due to the expansion of two subfamilies belonging to: irritans himar, a well characterized subfamily of mariners, and prolixus1, one of the two novel subfamilies here described. The high amount of sequences in these subfamilies suggests that bursts of transposition occurred during the life cycle of this family. In an attempt to characterize these elements, we performed an in silico analysis of the sequences corresponding to the DDD/E domain of the transposase gene. We performed an evolutionary analysis including network and Bayesian coalescent-based methods in order to infer the dynamics of the amplification, as well as to estimate the time of the bursts identified in these subfamilies. Given our data, we hypothesized that the TE expansions occurred around the time of speciation of R. prolixus around 1.4 mya. This suggestion lays on the "Transposon Model" of TE evolution, in which the members of a TE population that are replicative active are present at multiple loci in the genome, but their replicative potential varies, and of the "Life Cycle Model" that states that when present-day TEs have been involved in amplification bursts, they share an ancestral copy that dates back to this initial amplification. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Fernandez-Medina, R. D.] Fundacao Oswaldo Cruz, Programa Comp Cient, Av Brasil, BR-4365 Rio De Janeiro, Brazil.
[Granzotto, A.; Carareto, C. M. A.] Univ Estadual Paulista, UNESP, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil.
[Ribeiro, J. M.] NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Fernandez-Medina, RD (reprint author), Fundacao Oswaldo Cruz, Programa Comp Cient, Av Brasil, BR-4365 Rio De Janeiro, Brazil.
EM dfernandezmedina@gmail.com; adrianagranzotto@yahoo.com.br;
JRIBEIRO@niaid.nih.gov; carareto@ibilce.unesp.br
RI Carareto, Claudia/D-2814-2012;
OI Ribeiro, Jose/0000-0002-9107-0818
FU Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro
(CAPES/FAPERJ); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(FAPESP) [11/08820]; Intramural Research Program of the Division of
Intramural Research, National Institute of Allergy and Infectious
Diseases, National Institutes of Health [Z01 AI000810-17]; Conselho
Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
[304880/2009-4]
FX R.D.F.M. has a postdoctoral position supported by Fundacao de Amparo a
Pesquisa do Estado do Rio de Janeiro (CAPES/FAPERJ). A.G. was supported
by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP),
fellowship 11/08820. J.M.C.R. was supported by the Intramural Research
Program of the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health (Z01
AI000810-17) and C.M.A.C. was supported by Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq), Grant 304880/2009-4. We
thank Dr. Gonzalo B. Bello and Daiana Mir for helping with the Bayesian
Analyses.
NR 70
TC 1
Z9 2
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
EI 1879-0240
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD FEB
PY 2016
VL 69
SI SI
BP 14
EP 24
DI 10.1016/j.ibmb.2015.09.003
PG 11
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA DE8PU
UT WOS:000370899600002
PM 26363296
ER
PT J
AU Meeks, HD
Song, HL
Michailidou, K
Bolla, MK
Dennis, J
Wang, Q
Barrowdale, D
Frost, D
McGuffog, L
Ellis, S
Feng, BJ
Buys, SS
Hopper, JL
Southey, MC
Tesoriero, A
James, PA
Bruinsma, F
Campbell, IG
Broeks, A
Schmidt, MK
Hogervorst, FBL
Beckman, MW
Fasching, PA
Fletcher, O
Johnson, N
Sawyer, EJ
Riboli, E
Banerjee, S
Menon, U
Tomlinson, I
Burwinkel, B
Hamann, U
Marme, F
Rudolph, A
Janavicius, R
Tihomirova, L
Tung, N
Garber, J
Cramer, D
Terry, KL
Poole, EM
Tworoger, SS
Dorfling, CM
van Rensburg, EJ
Godwin, AK
Guenel, P
Truong, T
Stoppa-Lyonnet, D
Damiola, F
Mazoyer, S
Sinilnikova, OM
Isaacs, C
Maugard, C
Bojesen, SE
Flyger, H
Gerdes, AM
Hansen, TVO
Jensen, A
Kjaer, SK
Hogdall, C
Hogdall, E
Pedersen, IS
Thomassen, M
Benitez, J
Gonzalez-Neira, A
Osorio, A
de la Hoya, M
Segura, PP
Diez, O
Lazaro, C
Brunet, J
Anton-Culver, H
Eunjung, L
John, EM
Neuhausen, SL
Ding, YC
Castillo, D
Weitzel, JN
Ganz, PA
Nussbaum, RL
Chan, SB
Karlan, BY
Lester, J
Wu, A
Gayther, S
Ramus, SJ
Sieh, W
Whittermore, AS
Monteiro, ANA
Phelan, CM
Terry, MB
Piedmonte, M
Offit, K
Robson, M
Levine, D
Moysich, KB
Cannioto, R
Olson, SH
Daly, MB
Nathanson, KL
Domchek, SM
Lu, KH
Liang, D
Hildebrant, MAT
Ness, R
Modugno, F
Pearce, L
Goodman, MT
Thompson, PJ
Brenner, H
Butterbach, K
Meindl, A
Hahnen, E
Wappenschmidt, B
Brauch, H
Bruning, T
Blomqvist, C
Khan, S
Nevanlinna, H
Pelttari, LM
Aittomaki, K
Butzow, R
Bogdanova, NV
Dork, T
Lindblom, A
Margolin, S
Rantala, J
Kosma, VM
Mannermaa, A
Lambrechts, D
Neven, P
Claes, KBM
Van Maerken, T
Chang-Claude, J
Flesch-Janys, D
Heitz, F
Varon-Mateeva, R
Peterlongo, P
Radice, P
Viel, A
Barile, M
Peissel, B
Manoukian, S
Montagna, M
Oliani, C
Peixoto, A
Teixeira, MR
Collavoli, A
Hallberg, E
Olson, JE
Goode, EL
Hart, SN
Shimelis, H
Cunningham, JM
Giles, GG
Milne, RL
Healey, S
Tucker, K
Haiman, CA
Henderson, BE
Goldberg, MS
Tischkowitz, M
Simard, J
Soucy, P
Eccles, DM
Le, N
Borresen-Dale, AL
Kristensen, V
Salvesen, HB
Bjorge, L
Bandera, EV
Risch, H
Zheng, W
Beeghly-Fadiel, A
Cai, H
Pylkas, K
Tollenaar, RAEM
van der Ouweland, AMW
Andrulis, IL
Knight, JA
Narod, S
Devilee, P
Winqvist, R
Figueroa, J
Greene, MH
Mai, PL
Loud, JT
Garcia-Closas, M
Schoemaker, MJ
Czene, K
Darabi, H
McNeish, I
Siddiquil, N
Glasspool, R
Kwong, A
Park, SK
Teo, SH
Yoon, SY
Matsuo, K
Hosono, S
Woo, YL
Gao, YT
Foretova, L
Singer, CF
Rappaport-Feurhauser, C
Friedman, E
Laitman, Y
Rennert, G
Imyanitov, EN
Hulick, PJ
Olopade, OI
Senter, L
Olah, E
Doherty, JA
Schildkraut, J
Koppert, LB
Kiemeney, LA
Massuger, LFAG
Cook, LS
Pejovic, T
Li, JM
Borg, A
Ouml;fverholm, A
Rossing, MA
Wentzensen, N
Henriksson, K
Cox, A
Cross, SS
Pasini, BJ
Shah, M
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
Gronwald, J
Agnarsson, BA
Kupryjanczyk, J
Moes-Sosnowska, J
Fostira, F
Konstantopoulou, I
Slager, S
Jones, M
Antoniou, AC
Berchuck, A
Swerdlow, A
Chenevix-Trench, G
Dunning, AM
Pharoah, PDP
Hall, P
Easton, DF
Couch, FJ
Spurdle, AB
Goldgar, DE
AF Meeks, Huong D.
Song, Honglin
Michailidou, Kyriaki
Bolla, Manjeet K.
Dennis, Joe
Wang, Qin
Barrowdale, Daniel
Frost, Debra
McGuffog, Lesley
Ellis, Steve
Feng, Bingjian
Buys, Saundra S.
Hopper, John L.
Southey, Melissa C.
Tesoriero, Andrea
James, Paul A.
Bruinsma, Fiona
Campbell, Ian G.
Broeks, Annegien
Schmidt, Marjanka K.
Hogervorst, Frans B. L.
Beckman, Matthias W.
Fasching, Peter A.
Fletcher, Olivia
Johnson, Nichola
Sawyer, Elinor J.
Riboli, Elio
Banerjee, Susana
Menon, Usha
Tomlinson, Ian
Burwinkel, Barbara
Hamann, Ute
Marme, Frederik
Rudolph, Anja
Janavicius, Ramunas
Tihomirova, Laima
Tung, Nadine
Garber, Judy
Cramer, Daniel
Terry, Kathryn L.
Poole, Elizabeth M.
Tworoger, Shelley S.
Dorfling, Cecilia M.
van Rensburg, Elizabeth J.
Godwin, Andrew K.
Guenel, Pascal
Truong, Therese
Stoppa-Lyonnet, Dominique
Damiola, Francesca
Mazoyer, Sylvie
Sinilnikova, Olga M.
Isaacs, Claudine
Maugard, Christine
Bojesen, Stig E.
Flyger, Henrik
Gerdes, Anne-Marie
Hansen, Thomas V. O.
Jensen, Allen
Kjaer, Susanne K.
Hogdall, Claus
Hogdall, Estrid
Pedersen, Inge Sokilde
Thomassen, Mads
Benitez, Javier
Gonzalez-Neira, Anna
Osorio, Ana
de la Hoya, Miguel
Perez Segura, Pedro
Diez, Orland
Lazaro, Conxi
Brunet, Joan
Anton-Culver, Hoda
Eunjung, Lee
John, Esther M.
Neuhausen, Susan L.
Ding, Yuan Chun
Castillo, Danielle
Weitzel, Jeffrey N.
Ganz, Patricia A.
Nussbaum, Robert L.
Chan, Salina B.
Karlan, Beth Y.
Lester, Jenny
Wu, Anna
Gayther, Simon
Ramus, Susan J.
Sieh, Weiva
Whittermore, Alice S.
Monteiro, Alvaro N. A.
Phelan, Catherine M.
Terry, Mary Beth
Piedmonte, Marion
Offit, Kenneth
Robson, Mark
Levine, Douglas
Moysich, Kirsten B.
Cannioto, Rikki
Olson, Sara H.
Daly, Mary B.
Nathanson, Katherine L.
Domchek, Susan M.
Lu, Karen H.
Liang, Dong
Hildebrant, Michelle A. T.
Ness, Roberta
Modugno, Francesmary
Pearce, Leigh
Goodman, Marc T.
Thompson, Pamela J.
Brenner, Hermann
Butterbach, Katja
Meindl, Alfons
Hahnen, Eric
Wappenschmidt, Barbara
Brauch, Hiltrud
Bruening, Thomas
Blomqvist, Carl
Khan, Sofia
Nevanlinna, Heli
Pelttari, Liisa M.
Aittomaeki, Kristiina
Butzow, Ralf
Bogdanova, Natalia V.
Doerk, Thilo
Lindblom, Annika
Margolin, Sara
Rantala, Johanna
Kosma, Veli-Matti
Mannermaa, Arto
Lambrechts, Diether
Neven, Patrick
Claes, Kathleen B. M.
Van Maerken, Tom
Chang-Claude, Jenny
Flesch-Janys, Dieter
Heitz, Florian
Varon-Mateeva, Raymonda
Peterlongo, Paolo
Radice, Paolo
Viel, Alessandra
Barile, Monica
Peissel, Bernard
Manoukian, Siranoush
Montagna, Marco
Oliani, Cristina
Peixoto, Ana
Teixeira, Manuel R.
Collavoli, Anita
Hallberg, Emily
Olson, Janet E.
Goode, Ellen L.
Hart, Steven N.
Shimelis, Hermela
Cunningham, Julie M.
Giles, Graham G.
Milne, Roger L.
Healey, Sue
Tucker, Kathy
Haiman, Christopher A.
Henderson, Brian E.
Goldberg, Mark S.
Tischkowitz, Marc
Simard, Jacques
Soucy, Penny
Eccles, Diana M.
Le, Nhu
Borresen-Dale, Anne-Lise
Kristensen, Vessela
Salvesen, Helga B.
Bjorge, Line
Bandera, Elisa V.
Risch, Harvey
Zheng, Wei
Beeghly-Fadiel, Alicia
Cai, Hui
Pylkas, Katri
Tollenaar, Robert A. E. M.
van der Ouweland, Ans M. W.
Andrulis, Irene L.
Knight, Julia A.
Narod, Steven
Devilee, Peter
Winqvist, Robert
Figueroa, Jonine
Greene, Mark H.
Mai, Phuong L.
Loud, Jennifer T.
Garcia-Closas, Montserrat
Schoemaker, Minouk J.
Czene, Kamila
Darabi, Hatef
McNeish, Iain
Siddiquil, Nadeem
Glasspool, Rosalind
Kwong, Ava
Park, Sue K.
Teo, Soo Hwang
Yoon, Sook-Yee
Matsuo, Keitaro
Hosono, Satoyo
Woo, Yin Ling
Gao, Yu-Tang
Foretova, Lenka
Singer, Christian F.
Rappaport-Feurhauser, Christine
Friedman, Eitan
Laitman, Yael
Rennert, Gad
Imyanitov, Evgeny N.
Hulick, Peter J.
Olopade, Olufunmilayo I.
Senter, Leigha
Olah, Edith
Doherty, Jennifer A.
Schildkraut, Joellen
Koppert, Linetta B.
Kiemeney, Lambertus A.
Massuger, Leon F. A. G.
Cook, Linda S.
Pejovic, Tanja
Li, Jingmei
Borg, Ake
Ofverholm, Anna
Rossing, Mary Anne
Wentzensen, Nicolas
Henriksson, Karin
Cox, Angela
Cross, Simon S.
Pasini, Barbara J.
Shah, Mitul
Kabisch, Maria
Torres, Diana
Jakubowska, Anna
Lubinski, Jan
Gronwald, Jacek
Agnarsson, Bjarni A.
Kupryjanczyk, Jolanta
Moes-Sosnowska, Joanna
Fostira, Florentia
Konstantopoulou, Irene
Slager, Susan
Jones, Michael
Antoniou, Antonis C.
Berchuck, Andrew
Swerdlow, Anthony
Chenevix-Trench, Georgia
Dunning, Alison M.
Pharoah, Paul D. P.
Hall, Per
Easton, Douglas F.
Couch, Fergus J.
Spurdle, Amanda B.
Goldgar, David E.
CA EMBRACE
kConFab Investigators
Australia Ovarian Canc Study Grp
HEBON
GEMO Study Collaborators
OCGN
PRostate Canc Assoc Grp
TI BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate,
and Ovarian Cancers
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GERM-LINE MUTATION; PANCREATIC-CANCER;
SUSCEPTIBILITY GENE; DNA RECOMBINATION; ESTROGEN-RECEPTOR;
FAMILY-HISTORY; FANCONI-ANEMIA; LOCI; CONSORTIUM
AB Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers.
Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.
Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed.
Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.
C1 [Meeks, Huong D.; Goldgar, David E.] Univ Utah, Huntsman Canc Inst, Canc Control & Populat Sci, Salt Lake City, UT USA.
[Song, Honglin; Pasini, Barbara J.; Shah, Mitul; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Barrowdale, Daniel; Frost, Debra; McGuffog, Lesley; Ellis, Steve; Antoniou, Antonis C.; Pharoah, Paul D. P.; Easton, Douglas F.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Feng, Bingjian; Goldgar, David E.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA.
[Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Hopper, John L.; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Tesoriero, Andrea] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[kConFab Investigators] KConFab Kathleen Cuningham Consortium Res Familia, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[James, Paul A.] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia.
[James, Paul A.] Univ Melbourne, Dept Oncol, Melbourne, Vic, Australia.
[Bruinsma, Fiona; Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Campbell, Ian G.] Univ Melbourne, Peter MacCallum Canc Ctr, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
[Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
[Australia Ovarian Canc Study Grp] Peter MacCallum Canc Inst, East Melbourne, Vic, Australia.
[Broeks, Annegien; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands.
[HEBON] Netherlands Canc Inst, Hereditary Breast & Ovarian Canc Res Grp Netherla, Coordinating Ctr, Amsterdam, Netherlands.
[Beckman, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Comprehens Canc Ctr Erlangen EMN, Univ Hosp Erlangen, Dept Gynaecol & Ostetr, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Fletcher, Olivia; Johnson, Nichola; Swerdlow, Anthony] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Sawyer, Elinor J.] Guys Hosp, Kings Coll London, Div Canc Studies, Res Oncol, London SE1 9RT, England.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Banerjee, Susana] Royal Marsden NHS Fdn Trust, London, England.
[Menon, Usha] Univ Coll London Elizabeth Garrett Anderson EGA, Inst Womens Hlth, Womens Canc, London, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Burwinkel, Barbara] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Hamann, Ute; Kabisch, Maria; Torres, Diana] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Vilnius, Lithuania.
[Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
[Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA.
[Cramer, Daniel; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 75 Francis St, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.; Spurdle, Amanda B.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.; Spurdle, Amanda B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave, Boston, MA 02115 USA.
[Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Guenel, Pascal; Truong, Therese] Natl Inst Hlth & Med Res, Ctr Res Epidemiol & Populat Hlth CESP, Environm Epidemiol Canc, INSERM,U1018, Villejuif, France.
[Guenel, Pascal; Truong, Therese] Univ Paris Sud, Villejuif, France.
[GEMO Study Collaborators] UNICANCER Genet Grp, GEMO Study Natl Canc Genet Network, Paris, France.
[Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France.
[Stoppa-Lyonnet, Dominique] INSERM, U830, Inst Curie, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.] Univ Lyon, Ctr Rech Cancerol Lyon, INSERM,U1052, CNRS UMR 5286, Lyon, France.
[Sinilnikova, Olga M.] Hosp Civils Pyon, Ctr Leon Berard, Unite Mixte Genet Constitutionelle Canc Frequents, Lyon, France.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel, Lab Diagnost Genet, Hop Civil, Strasbourg, France.
[Maugard, Christine] Hop Univ Strasbourg, CHRU Nouvel, Serv Oncohematol, Hop Civil, Strasbourg, France.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark.
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[Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark.
[Jensen, Allen; Kjaer, Susanne K.; Hogdall, Estrid] Danish Canc Soc, Dept Virus Lifestyle & Genes, Res Ctr, Copenhagen, Denmark.
[Kjaer, Susanne K.; Hogdall, Claus] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark.
[Benitez, Javier; Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Human Genotyping Unit CEGEN, Madrid, Spain.
[Benitez, Javier; Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[de la Hoya, Miguel] IdISSC Inst Invest Sanitaria Hosp Clin San Carlos, Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain.
[Perez Segura, Pedro] IdISSC, Hosp Clin San Carlos, Dept Oncol, Madrid, Spain.
[Diez, Orland] Univ Hosp Vall dHebron, VHIO, Oncogenet Grp, Barcelona, Spain.
[Diez, Orland] Univ Autonoma Barcelona, E-08193 Barcelona, Spain.
[Lazaro, Conxi] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain.
[Brunet, Joan] Catalan Inst Oncol, IDIBGI Inst Invest Biomed Girona, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain.
[Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Dept Epidemiol, Irvine, CA 92717 USA.
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[Rennert, Gad] B Rappaport Fac Med, Haifa, Israel.
[Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg, Russia.
[Hulick, Peter J.] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA.
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[Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Gynaecol, NL-6525 ED Nijmegen, Netherlands.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
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[Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden.
[Ofverholm, Anna] Sahlgrens Univ Hosp, Dept Clin Genet, Gothenburg, Sweden.
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[Cox, Angela] Univ Sheffield, Sheffield Canc Res Dept Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
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RP Goldgar, DE (reprint author), Univ Utah, Sch Med, Huntsman Canc Inst, Dept Dermatol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA.
EM david.goldgar@hsc.utah.edu
RI Teixeira, Manuel/E-4885-2011; Li, Jingmei/I-2904-2012; Teo,
Soo-hwang/H-2353-2014; Bruning, Thomas/G-8120-2015; Andrulis,
Irene/E-7267-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011;
Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; Osorio,
Ana/I-4324-2014; Woo, Yin Ling/B-5198-2010; Dork, Thilo/J-8620-2012;
Knight, Julia/A-6843-2012; Zheng, Wei/O-3351-2013; Bjorge,
Line/C-1307-2017; salvesen, Helga/C-1187-2017; manoukian,
siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017;
OI Teixeira, Manuel/0000-0002-4896-5982; Li, Jingmei/0000-0001-8587-7511;
Bruning, Thomas/0000-0001-9560-5464; Gronwald,
Jacek/0000-0002-3643-2871; Brenner, Hermann/0000-0002-6129-1572; Osorio,
Ana/0000-0001-8124-3984; Woo, Yin Ling/0000-0003-1742-1066; Zheng,
Wei/0000-0003-1226-070X; Bjorge, Line/0000-0002-0240-2770; salvesen,
Helga/0000-0002-4438-8831; manoukian, siranoush/0000-0002-6034-7562;
Peissel, Bernard/0000-0001-9233-3571; Glasspool,
Rosalind/0000-0002-5000-1680; Schoemaker, Minouk/0000-0001-8403-2234;
Cox, Angela/0000-0002-5138-1099; Ramus, Susan/0000-0003-0005-7798;
Barrowdale, Daniel/0000-0003-1661-3939; Khan, Sofia/0000-0003-4185-8882;
Brunet, Joan/0000-0003-1945-3512; Dunning, Alison
Margaret/0000-0001-6651-7166
FU Government of Canada through Genome Canada; Canadian Institutes of
Health Research; Ministere de l'Economie, de l'Innovation et des
Exportations du Quebec through Genome Quebec; National Health and
Medical Research Council (NHMRC) Senior Research Fellowship; Australian
NHMRC Project [1010719]; National Institutes of Health (NIH) [CA128978,
CA116167]; NIH specialized program of research excellence in breast
cancer [P50 CA116201]; Breast Cancer Research Foundation; Consortium of
Investigators of Modifiers of BRCA1/2 (CIMBA) data management and
analysis through Cancer Research-UK grant [C12292/A11174]; Cancer
Research UK [C1287/A10118, C1287/A12014, C1287/A 10710, C12292/ A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/ A10692, C8197/A16565];
European Community's Seventh Framework Programme [223175
(HEALTH-F2-2009-223175)]; European Union COST programme [BM0606];
Ovarian Cancer Research Fund [PPD/RPCI.07]; US National Cancer Institute
Genetic Associations and Mechanisms in Oncology (GAME-ON) Post-Genome
Wide Association Study (GWAS) Initiative [U19-CA148112]; Wellcome Trust
[076113]; European Community's Seventh Framework Programme (COGS)
[223175 (HEALTH-F2-2009-223175)]; National Institutes of Health
[CA128978]; Post-Cancer GWAS initiative (GAME-ON initiative) [1U19
CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence
[W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for
the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for
the Cure; Breast Cancer Research Foundation,; Ovarian Cancer Research
Fund
FX This work was supported by the Government of Canada through Genome
Canada and the Canadian Institutes of Health Research and the Ministere
de l'Economie, de l'Innovation et des Exportations du Quebec through
Genome Quebec.; Amanda Spurdle is supported by a National Health and
Medical Research Council (NHMRC) Senior Research Fellowship, and aspects
of this research were funded by Australian NHMRC Project grant ID
#1010719. This work was also supported in part by National Institutes of
Health (NIH) grants CA128978 and CA116167, an NIH specialized program of
research excellence in breast cancer to the Mayo Clinic (P50 CA116201),
and the Breast Cancer Research Foundation. The The Consortium of
Investigators of Modifiers of BRCA1/2 (CIMBA) data management and
analysis is funded through Cancer Research-UK grant C12292/A11174.
Breast Cancer Association Consortium (BCAC) data management was funded
by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the
European Community's Seventh Framework Programme under grant agreement
223175 (HEALTH-F2-2009-223175). BCAC meetings have been funded by the
European Union COST programme (BM0606). Ovarian Cancer Association
Consortium (OCAC) is supported by a grant from the Ovarian Cancer
Research Fund thanks to donations by the family and friends of Kathryn
Sladek Smith (PPD/RPCI.07). The scientific development and funding for
this project were in part supported by the US National Cancer Institute
Genetic Associations and Mechanisms in Oncology (GAME-ON) Post-Genome
Wide Association Study (GWAS) Initiative (U19-CA148112). This study made
use of data generated by the Wellcome Trust Case Control consortium. A
full list of the investigators who contributed to the generation of the
data is available at http://www.wtccc.org.uk/. Funding for the project
was provided by the Wellcome Trust under award 076113. The results
published here are in part based upon data generated by the Cancer
Genome Atlas Pilot Project established by the National Cancer Institute
and National Human Genome Research Institute.; Funding for the iCOGS
infrastructure came from: the European Community's Seventh Framework
Programme under grant agreement no 223175 (HEALTH-F2-2009-223175)
(COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/ A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/ A10692, C8197/A16565),
the National Institutes of Health (CA128978) and Post-Cancer GWAS
initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON
initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian
Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks
of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer
Research Foundation, and the Ovarian Cancer Research Fund.
NR 54
TC 1
Z9 1
U1 6
U2 21
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD FEB
PY 2016
VL 108
IS 2
AR djv315
DI 10.1093/jnci/djv315
PG 10
WC Oncology
SC Oncology
GA DF2EP
UT WOS:000371153900007
ER
PT J
AU Wentzensen, N
Fetterman, B
Castle, P
Schiffman, M
Wood, S
Tokugawa, D
Bodelon, C
Poitras, N
Lorey, T
Kinney, W
AF Wentzensen, Nicolas
Fetterman, Barbara
Castle, Philip
Schiffman, Mark
Wood, Shannon
Tokugawa, Diane
Bodelon, Clara
Poitras, Nancy
Lorey, Tom
Kinney, Walter
TI RE: p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in
HPV-Positive Women RESPONSE
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID CANCER
C1 [Wentzensen, Nicolas; Schiffman, Mark; Wood, Shannon; Bodelon, Clara] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Fetterman, Barbara; Tokugawa, Diane; Poitras, Nancy; Lorey, Tom] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA USA.
[Castle, Philip] Global Coalit Cerv Canc, Arlington, VA USA.
[Castle, Philip] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD FEB
PY 2016
VL 108
IS 2
AR djv390
DI 10.1093/jnci/djv390
PG 2
WC Oncology
SC Oncology
GA DF2EP
UT WOS:000371153900023
ER
PT J
AU DeGrazia, D
AF DeGrazia, David
TI Modal Personhood and Moral Status: A Reply to Kagan's Proposal
SO JOURNAL OF APPLIED PHILOSOPHY
LA English
DT Editorial Material
AB Kagan argues that human beings who are neither persons nor even potential persons if their impairment is independent of genetic constitution are modal persons: individuals who might have been persons. Moreover, he proposes a view according to which both (actual) personhood and modal personhood are sufficient for counting more, morally, than nonhuman animals. In response to this proposal, I raise one relatively minor concern about Kagan's reasoning that he judges too quickly that insentient beings can have interests before engaging the appeal to modal personhood. I challenge the thesis that modal personhood is relevant to one's moral status, first, by way of analogy to a kicker who misses a field goal though he might have made it; second, by casting doubt on implications for two impaired infants (only one of whom might have been a person); and, finally, by examining implications for dogs who would count as modal persons when genetic enhancements are capable of transforming them into persons.
C1 [DeGrazia, David] George Washington Univ, Dept Philosophy, 801 22nd St NW, Washington, DC 20052 USA.
[DeGrazia, David] NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
RP DeGrazia, D (reprint author), George Washington Univ, Dept Philosophy, 801 22nd St NW, Washington, DC 20052 USA.; DeGrazia, D (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM ddd@gwu.edu
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0264-3758
EI 1468-5930
J9 J APPL PHILOS
JI J. Appl. Philos.
PD FEB
PY 2016
VL 33
IS 1
BP 22
EP 25
DI 10.1111/japp.12166
PG 4
WC Ethics; Philosophy
SC Social Sciences - Other Topics; Philosophy
GA DE6EU
UT WOS:000370727300002
ER
PT J
AU Matelski, L
Van de Water, J
AF Matelski, Lauren
Van de Water, Judy
TI Risk factors in autism: Thinking outside the brain
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Review
DE Autism; Gene-environment; Immune dysfunction; Risk; Maternal factors
ID MATERNAL IMMUNE ACTIVATION; SPECTRUM DISORDERS; AUTOIMMUNE-DISEASES;
CHILDHOOD AUTISM; FETAL-BRAIN; GASTROINTESTINAL SYMPTOMS; INFLAMMATORY
CYTOKINES; ENVIRONMENTAL-FACTORS; RHESUS-MONKEY; GLUTEN-FREE
AB Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in 68 in the United States. This has prompted the search for possible explanations, and has even resulted in some controversy regarding the "true" prevalence of autism. ASD are influenced by a variety of genetic, environmental, and possibly immunological factors that act during critical periods to alter key developmental processes. This can affect multiple systems and manifests as the social and behavioral deficits that define these disorders. The interaction of environmental exposures in the context of an individual's genetic susceptibilities manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder. This has also made it very difficult to elucidate underlying genes and exposure profiles, but progress is being made in this area. Some pharmaceutical drugs, toxicants, and metabolic and nutritional factors have been identified in epidemiological studies as increasing autism risk, especially during the prenatal period. Immunologic risk factors, including maternal infection during pregnancy, autoantibodies to fetal brain proteins, and familial autoimmune disease, have consistently been observed across multiple studies, as have immune abnormalities in individuals with ASD. Mechanistic research using animal models and patient-derived stem cells will help researchers to understand the complex etiology of these neurodevelopmental disorders, which will lead to more effective therapies and preventative strategies. Proposed therapies that need more investigation include special diets, probiotics, immune modulation, oxytocin, and personalized pharmacogenomic targets. The ongoing search for biomarkers and better treatments will result in earlier identification of ASD and provide much needed help and relief for afflicted families. (C) 2015 Published by Elsevier Ltd.
C1 [Matelski, Lauren; Van de Water, Judy] Univ Calif Davis, Dept Internal Med, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA.
[Matelski, Lauren; Van de Water, Judy] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA.
[Matelski, Lauren; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA.
RP Van de Water, J (reprint author), Univ Calif Davis, Dept Internal Med, Div Rheumatol Allergy & Clin Immunol, 451 E Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA.
EM javandewater@ucdavis.edu
FU NIEHS Ceniter for Children's Environmental Health and Environmental
Protection Agency (EPA) [2P01ES011269-11, 83543201]; NIEHS
[R01ES015359]; NICHD [U54HD079125]
FX This study was funded by the NIEHS Ceniter for Children's Environmental
Health and Environmental Protection Agency (EPA) grants
(2P01ES011269-11, 83543201 respectively), the NIEHS-funded CHARGE study
(R01ES015359), and the NICHD funded IDDRC 054 (U54HD079125). We also
thank the staff of the CHARGE study, and families involved in this
research.
NR 91
TC 12
Z9 12
U1 14
U2 44
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD FEB
PY 2016
VL 67
BP 1
EP 7
DI 10.1016/j.jaut.2015.11.003
PG 7
WC Immunology
SC Immunology
GA DE8KM
UT WOS:000370884900001
PM 26725748
ER
PT J
AU Agre, P
Bertozzi, C
Bissell, M
Campbell, KP
Cummings, RD
Desai, UR
Estes, M
Flotte, T
Fogleman, G
Gage, F
Ginsburg, D
Gordon, JI
Hart, G
Hascall, V
Kiessling, L
Kornfeld, S
Lowe, J
Magnani, J
Mahal, LK
Medzhitov, R
Roberts, RJ
Sackstein, R
Sarkar, R
Schnaar, R
Schwartz, N
Varki, A
Walt, D
Weissman, I
AF Agre, Peter
Bertozzi, Carolyn
Bissell, Mina
Campbell, Kevin P.
Cummings, Richard D.
Desai, Umesh R.
Estes, Mary
Flotte, Terence
Fogleman, Guy
Gage, Fred
Ginsburg, David
Gordon, Jeffrey I.
Hart, Gerald
Hascall, Vincent
Kiessling, Laura
Kornfeld, Stuart
Lowe, John
Magnani, John
Mahal, Lara K.
Medzhitov, Ruslan
Roberts, Richard J.
Sackstein, Robert
Sarkar, Rita
Schnaar, Ronald
Schwartz, Nancy
Varki, Ajit
Walt, David
Weissman, Irving
TI Training the next generation of biomedical investigators in
glycosciences
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
AB This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. The group was deliberately composed not only of individuals with a current research emphasis in the glycosciences, but also of many experts from other fields, who evinced a strong interest in being involved in the discussions. The original goal was to discuss the value of creating centers of excellence for training the next generation of biomedical investigators in the glycosciences. A broader theme that emerged was the urgent need to bring the glycosciences back into the mainstream of biology by integrating relevant education into the curricula of medical, graduate, and postgraduate training programs, thus generating a critical sustainable workforce that can advance the much-needed translation of glycosciences into a more complete understanding of biology and the enhanced practice of medicine.
C1 [Agre, Peter] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Bertozzi, Carolyn] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
[Bissell, Mina] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Biol Syst & Engn, Berkeley, CA 94720 USA.
[Campbell, Kevin P.] Univ Iowa, Howard Hughes Med Inst, Dept Mol Physiol & Biophys Neurol & Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Cummings, Richard D.] Beth Israel Deaconess Med Ctr, Dept Surg, Harvard Med Sch, Boston, MA 02215 USA.
[Desai, Umesh R.] Virginia Commonwealth Univ, Dept Med Chem, Richmond, VA 23298 USA.
[Desai, Umesh R.] Virginia Commonwealth Univ, Inst Struct Biol Drug Discovery & Dev, Richmond, VA USA.
[Estes, Mary] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Flotte, Terence] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA.
[Fogleman, Guy] FASEB, Bethesda, MD USA.
[Gage, Fred] Salk Inst far Biol Studies, Lab Genet LOG G, La Jolla, CA USA.
[Ginsburg, David] Univ Michigan, Dept Internal Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Ginsburg, David] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Gordon, Jeffrey I.] Washington Univ, Ctr Genome Sci & Syst Biol, St Louis, MO USA.
[Hart, Gerald] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA.
[Hascall, Vincent] Cleveland Clin Fdn, Dept Bioengn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Kiessling, Laura] Univ Wisconsin, Dept Chem, 1101 Univ Ave, Madison, WI 53706 USA.
[Kornfeld, Stuart] Washington Univ, Dept Med, St Louis, MO USA.
[Lowe, John] Genentech Inc, Dept Pathol Res, San Francisco, CA USA.
[Magnani, John] GlycoMimet, Rockville, MD USA.
[Mahal, Lara K.] NYU, Dept Chem, Inst Biomed Chem, New York, NY USA.
[Medzhitov, Ruslan] Yale Univ, Dept Immunobiol, New Haven, CT USA.
[Roberts, Richard J.] New England Biolabs Inc, Ipswich, MA USA.
[Sackstein, Robert] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol & Med, Boston, MA 02115 USA.
[Sarkar, Rita] NHLBI, Div Blood Dis & Resources, Bethesda, MD USA.
[Schnaar, Ronald] Johns Hopkins Univ, Dept Pharmacol & Neurosci, Baltimore, MD USA.
[Schwartz, Nancy] Univ Chicago, Dept Pediat & Biochem & Mol Biol, Chicago, IL 60637 USA.
[Varki, Ajit] Univ Calif San Diego, Dept Med, San Diego, CA USA.
[Varki, Ajit; Walt, David] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA USA.
[Walt, David] Tufts Univ, Dept Chem, Tufts Inst Innovat, Medford, MA 02155 USA.
[Weissman, Irving] Stanford Univ, Ludwig Ctr Canc Stem Cell Res, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
RP Varki, A (reprint author), Univ Calif San Diego, Dept Med, BRF2,Room 4126,9500 Gilman Dr,MC 0687, La Jolla, CA 92093 USA.; Varki, A (reprint author), Dept Cellular & Mol Med, BRF2,Room 4126,9500 Gilman Dr,MC 0687, La Jolla, CA 92093 USA.; Schnaar, R (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol, 725 N Wolfe St,318 Wood Basic Sci Bldg, Baltimore, MD 21205 USA.; Schnaar, R (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, 725 N Wolfe St,318 Wood Basic Sci Bldg, Baltimore, MD 21205 USA.
EM schnaar@jhu.edu; alvarki@ucsd.edu
RI Schnaar, Ronald/S-8967-2016;
OI Schnaar, Ronald/0000-0002-7701-5484; Desai, Umesh/0000-0002-1976-6597;
Roberts, Richard/0000-0002-4348-0169
FU NHLBI NIH HHS [P01 HL107146, P01 HL107150, P01 HL107151]; NINDS NIH HHS
[U54 NS053672]
NR 1
TC 2
Z9 2
U1 5
U2 14
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2016
VL 126
IS 2
BP 405
EP 408
DI 10.1172/JCI85905
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DE5NI
UT WOS:000370677300001
PM 26829621
ER
PT J
AU Maldarelli, F
AF Maldarelli, Frank
TI The role of HIV integration in viral persistence: no more whistling past
the proviral graveyard
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; VIRUS TYPE-1 VIREMIA;
LATENT RESERVOIR; RALTEGRAVIR INTENSIFICATION; LOW-LEVEL; INSERTIONAL
MUTAGENESIS; SITE SELECTION; INFECTED-CELLS; IN-VIVO
AB A substantial research effort has been directed to identifying strategies to eradicate or control HIV infection without a requirement for combination antiretroviral therapy (cART). A number of obstacles prevent HIV eradication, including low-level viral persistence during cART, long-term persistence of HIV-infected cells, and latent infection of resting CD4(+) T cells. Mechanisms of persistence remain uncertain, but integration of the provirus into the host genome represents a central event in replication and pathogenesis of all retroviruses, including HIV. Analysis of HIV proviruses in CD4(+) lymphocytes from individuals after prolonged cART revealed that a substantial proportion of the infected cells that persist have undergone clonal expansion and frequently have proviruses integrated in genes associated with regulation of cell growth. These data suggest that integration may influence persistence and clonal expansion of HIV-infected cells after cART is introduced, and these processes may represent key mechanisms for HIV persistence. Determining the diversity of host genes with integrants in HIV-infected cells that persist for prolonged periods may yield useful information regarding pathways by which infected cells persist for prolonged periods. Moreover, many integrants are defective, and new studies are required to characterize the role of clonal expansion in the persistence of replication-competent HIV.
C1 [Maldarelli, Frank] NCI, Clin Retrovirol Sect, HIV Dynam & Replicat Program, NIH, Frederick, MD 21701 USA.
RP Maldarelli, F (reprint author), NCI, Clin Retrovirol Sect, HIV Dynam & Replicat Program, NIH,Frederick Natl Canc Lab, Bldg 535,Room 108E,1050 Boyles St, Frederick, MD 21701 USA.
EM fmalli@mailnih.gov
FU NIH Bench-to-Bedside Program
FX I am grateful to the study participants who contributed to research
described and to F.R. Simonetti, S.H. Hughes, J. Coffin, J. Mellors,
M.F. Kearney, W. Shao, X. Wu, T. Uldrick, R. Yarchoan, C. Lane, M.
Polis, and J. Kovacs for insightful discussions. This work was supported
in part by the NIH Bench-to-Bedside Program.
NR 133
TC 2
Z9 2
U1 2
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2016
VL 126
IS 2
BP 438
EP 447
DI 10.1172/JCI80564
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DE5NI
UT WOS:000370677300006
PM 26829624
ER
PT J
AU Roychoudhuri, R
Eil, RL
Clever, D
Klebanoff, CA
Sukumar, M
Grant, FM
Yu, ZY
Mehta, G
Liu, H
Jin, P
Ji, Y
Palmer, DC
Pan, JH
Chichura, A
Crompton, JG
Patel, SJ
Stroncek, D
Wang, E
Marincola, FM
Okkenhaug, K
Gattinoni, L
Restifo, NP
AF Roychoudhuri, Rahul
Eil, Robert L.
Clever, David
Klebanoff, Christopher A.
Sukumar, Madhusudhanan
Grant, Francis M.
Yu, Zhiya
Mehta, Gautam
Liu, Hui
Jin, Ping
Ji, Yun
Palmer, Douglas C.
Pan, Jenny H.
Chichura, Anna
Crompton, Joseph G.
Patel, Shashank J.
Stroncek, David
Wang, Ena
Marincola, Francesco M.
Okkenhaug, Klaus
Gattinoni, Luca
Restifo, Nicholas P.
TI The transcription factor BACH2 promotes tumor immunosuppression
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID REGULATORY T-CELLS; REPRESSOR BACH2; RISK LOCI; HOMEOSTASIS; DISEASE;
MICE; METAANALYSIS; EFFECTOR; PROGRAMS; CANCER
AB The immune system has a powerful ability to recognize and kill cancer cells, but its function is often suppressed within tumors, preventing clearance of disease. Functionally diverse innate and adaptive cellular lineages either drive or constrain immune reactions within tumors. The transcription factor (TF) BACH2 regulates the differentiation of multiple innate and adaptive cellular lineages, but its role in controlling tumor immunity has not been elucidated. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. However, augmented tumor clearance in the absence of Bach2 was dependent upon the adaptive immune system. Analysis of tumor-infiltrating lymphocytes from Bach2-deficient mice revealed high frequencies of rapidly proliferating effector CD4(+) and CD8(+) T cells that expressed the inflammatory cytokine IFN-gamma. Effector T cell activation coincided with a reduction in the frequency of intratumoral Foxp3(+) Tregs. Mechanistically, BACH2 promoted tumor immunosuppression through Treg-mediated inhibition of intratumoral CD8(+) T cells and IFN-gamma. These findings demonstrate that BACH2 is a key component of the molecular program of tumor immunosuppression and identify therapeutic targets for the reversal of immunosuppression in cancer.
C1 [Roychoudhuri, Rahul; Eil, Robert L.; Clever, David; Klebanoff, Christopher A.; Sukumar, Madhusudhanan; Yu, Zhiya; Mehta, Gautam; Ji, Yun; Palmer, Douglas C.; Pan, Jenny H.; Chichura, Anna; Crompton, Joseph G.; Patel, Shashank J.; Gattinoni, Luca; Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
[Roychoudhuri, Rahul; Grant, Francis M.; Okkenhaug, Klaus] Babraham Inst, Babraham Res Campus, Cambridge CB22 3AT, England.
[Liu, Hui; Jin, Ping; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar.
RP Roychoudhuri, R (reprint author), Babraham Inst, Babraham Res Campus, Cambridge CB22 3AT, England.; Restifo, NP (reprint author), NCI, Rm 3W-5762,Bld 10-CRC, Bethesda, MD 20892 USA.
EM rahul.roychoudhuri@babraham.ac.uk; restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Roychoudhuri,
Rahul/A-7442-2010;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Roychoudhuri, Rahul/0000-0002-5392-1853; Mehta,
Gautam/0000-0002-8009-6430; Okkenhaug, Klaus/0000-0002-9432-4051
FU Intramural Research Program of the US National Cancer Institute [ZIA
BC010763]; UK Biotechnology and Biological Sciences Research Council
[BB/N007794/1]; Sir Henry Dale Fellowship - Wellcome Trust
[105663/Z/14/Z]; Sir Henry Dale Fellowship - Royal Society
[105663/Z/14/Z]; Tiens Charitable Foundation; NIH Center for
Regenerative Medicine; Milstein Family Foundation
FX This research was supported by the Intramural Research Program of the US
National Cancer Institute (ZIA BC010763) and the UK Biotechnology and
Biological Sciences Research Council (grant BB/N007794/1). R.
Roychoudhuri is supported by a Sir Henry Dale Fellowship, jointly funded
by the Wellcome Trust and the Royal Society (grant 105663/Z/14/Z). The
research was also supported by the Tiens Charitable Foundation, the NIH
Center for Regenerative Medicine, and the Milstein Family Foundation.
NR 25
TC 5
Z9 5
U1 1
U2 5
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2016
VL 126
IS 2
BP 599
EP 604
DI 10.1172/JCI82884
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DE5NI
UT WOS:000370677300021
PM 26731475
ER
PT J
AU Cui, CY
Sima, J
Yin, MZ
Michel, M
Kunisada, M
Schlessinger, D
AF Cui, Chang-Yi
Sima, Jian
Yin, Mingzhu
Michel, Marc
Kunisada, Makoto
Schlessinger, David
TI Identification of potassium and chloride channels in eccrine sweat
glands
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Letter
DE Hypohidrosis; Ectodermal dysplasia; FoxA1; Best2; Nkcc1
ID TRANSPORT; SECRETION; REVEALS; ROLES
C1 [Cui, Chang-Yi; Sima, Jian; Yin, Mingzhu; Michel, Marc; Schlessinger, David] NIA, Genet Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
[Kunisada, Makoto] Kobe Univ, Grad Sch Med, Div Dermatol, Dept Internal Related, Kobe, Hyogo 657, Japan.
RP Cui, CY (reprint author), NIA, Genet Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM cuic@mail.nih.gov
FU Intramural NIH HHS
NR 10
TC 2
Z9 2
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD FEB
PY 2016
VL 81
IS 2
BP 129
EP 131
DI 10.1016/j.jdermsci.2015.11.001
PG 3
WC Dermatology
SC Dermatology
GA DE9UT
UT WOS:000370985600009
PM 26627722
ER
PT J
AU Groen, IIA
Ghebreab, S
Lamme, VAF
Scholte, HS
AF Groen, Iris I. A.
Ghebreab, Sennay
Lamme, Victor A. F.
Scholte, H. Steven
TI The time course of natural scene perception with reduced attention
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE attention; natural scenes; electro-encephalography/event-related
potential; image statistics
ID COARSE-TO-FINE; PERIPHERAL-VISION; IMAGE STATISTICS;
HEMISPHERIC-DIFFERENCES; OBJECT RECOGNITION; REQUIRES ATTENTION;
SPATIAL-FREQUENCY; NEURAL MECHANISMS; TEMPORAL CORTEX; VISUAL SCENES
AB Attention is thought to impose an informational bottleneck on vision by selecting particular information from visual scenes for enhanced processing. Behavioral evidence suggests, however, that some scene information is extracted even when attention is directed elsewhere. Here, we investigated the neural correlates of this ability by examining how attention affects electrophysiological markers of scene perception. In two electro-encephalography (EEG) experiments, human subjects categorized real-world scenes as manmade or natural (full attention condition) or performed tasks on unrelated stimuli in the center or periphery of the scenes (reduced attention conditions). Scene processing was examined in two ways: traditional trial averaging was used to assess the presence of a categorical manmade/natural distinction in event-related potentials, whereas single-trial analyses assessed whether EEG activity was modulated by scene statistics that are diagnostic of naturalness of individual scenes. The results indicated that evoked activity up to 250 ms was unaffected by reduced attention, showing intact categorical differences between manmade and natural scenes and strong modulations of single-trial activity by scene statistics in all conditions. Thus initial processing of both categorical and individual scene information remained intact with reduced attention. Importantly, however, attention did have profound effects on later evoked activity; full attention on the scene resulted in prolonged manmade/natural differences, increased neural sensitivity to scene statistics, and enhanced scene memory. These results show that initial processing of real-world scene information is intact with diminished attention but that the depth of processing of this information does depend on attention.
C1 [Groen, Iris I. A.; Ghebreab, Sennay; Lamme, Victor A. F.; Scholte, H. Steven] Univ Amsterdam, Dept Brain & Cognit, Amsterdam Brain & Cognit Ctr, Amsterdam, Netherlands.
[Ghebreab, Sennay] Univ Amsterdam, Inst Informat, Intelligent Syst Lab Amsterdam, Amsterdam, Netherlands.
RP Groen, IIA (reprint author), NIMH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM iris.groen@nih.gov
RI Groen, Iris/A-1462-2017
OI Groen, Iris/0000-0002-5536-6128
FU European Research Council; Dutch national public-private research
program COMMIT
FX This work is part of the Research Priority Program "Brain & Cognition"
at the University of Amsterdam and was supported by an Advanced
Investigator Grant from the European Research Council to V. A. F. Lamme
and the Dutch national public-private research program COMMIT to S.
Ghebreab.
NR 87
TC 6
Z9 6
U1 9
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB 1
PY 2016
VL 115
IS 2
BP 931
EP 946
DI 10.1152/jn.00896.2015
PG 16
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA DF2EW
UT WOS:000371154800029
PM 26609116
ER
PT J
AU Chao, BN
Baldwin, WH
Healey, JF
Parker, ET
Shafer-Weaver, K
Cox, C
Jiang, P
Kanellopoulou, C
Lollar, P
Meeks, SL
Lenardo, MJ
AF Chao, B. N.
Baldwin, W. H.
Healey, J. F.
Parker, E. T.
Shafer-Weaver, K.
Cox, C.
Jiang, P.
Kanellopoulou, C.
Lollar, P.
Meeks, S. L.
Lenardo, M. J.
TI Characterization of a genetically engineered mouse model of hemophilia A
with complete deletion of the F8 gene
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Animal model; blood coagulation factor inhibitors; factor VIII;
hemophilia A; knockout mouse
ID FACTOR-VIII GENE; MURINE FACTOR-VIII; INHIBITOR DEVELOPMENT; TARGETED
DISRUPTION; DOMAIN ANTIBODIES; ENDOTHELIAL-CELLS; IMMUNE-RESPONSE;
CLASS-II; MICE; MUTATION
AB Essentials
Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region.F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will aid in studying FVIII inhibitor formation.
Summary
Background The most important complication in hemophilia A treatment is the development of inhibitory anti-Factor VIII (FVIII) antibodies in patients after FVIII therapy. Patients with severe hemophilia who express no endogenous FVIII (i.e. cross-reacting material, CRM) have the greatest incidence of inhibitor formation. However, current mouse models of severe hemophilia A produce low levels of truncated FVIII. The lack of a corresponding mouse model hampers the study of inhibitor formation in the complete absence of FVIII protein.
Objectives We aimed to generate and characterize a novel mouse model of severe hemophilia A (designated the F8(TKO) strain) lacking the complete coding sequence of F8 and any FVIII CRM.
Methods Mice were created on a C57BL/6 background using Cre-Lox recombination and characterized using in vivo bleeding assays, measurement of FVIII activity by coagulation and chromogenic assays, and anti-FVIII antibody production using ELISA.
Results All F8 exonic coding regions were deleted from the genome and no F8 mRNA was detected in F8(TKO) mice. The bleeding phenotype of F8(TKO) mice was comparable to E16 mice by measurements of factor activity and tail snip assay. Similar levels of anti-FVIII antibody titers after recombinant FVIII injections were observed between F8(TKO) and E16 mice.
Conclusions We describe a new C57BL/6 mouse model for severe hemophilia A patients lacking CRM. These mice can be directly bred to the many C57BL/6 strains of genetically engineered mice, which is valuable for studying the impact of a wide variety of genes on FVIII inhibitor formation on a defined genetic background.
C1 [Chao, B. N.; Shafer-Weaver, K.; Jiang, P.; Kanellopoulou, C.; Lenardo, M. J.] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Baldwin, W. H.; Healey, J. F.; Parker, E. T.; Cox, C.; Lollar, P.; Meeks, S. L.] Emory Univ, Dept Pediat, Aflac Canc & Blood Disorders Ctr, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
RP Lenardo, MJ (reprint author), NIH, Bldg 10,Room 11D14,10 Ctr Dr, Bethesda, MD 20814 USA.
EM Lenardo@nih.gov
FU National Institutes of Health [U54 HL112309, K08 HL102262]; Hemophilia
of Georgia, Inc.; NIAID, NIH
FX S. L. Meeks was supported by National Institutes of Health grants U54
HL112309 and K08 HL102262 and Hemophilia of Georgia, Inc. P. L. was
supported by National Institutes of Health grants U54 HL112309 and
Hemophilia of Georgia, Inc. This work was also supported by the
Intramural Research Program of NIAID, NIH.
NR 42
TC 1
Z9 1
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD FEB
PY 2016
VL 14
IS 2
BP 346
EP 355
DI 10.1111/jth.13202
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DE5GM
UT WOS:000370659400016
PM 26588198
ER
PT J
AU Aflaki, E
Borger, DK
Moaven, N
Stubblefield, BK
Rogers, SA
Patnaik, S
Westbroek, W
Sullivan, P
Fujiwara, H
Lopez, G
Goldstein, DS
Ory, DS
Marugan, J
Sidransky, E
AF Aflaki, Elma
Borger, Daniel K.
Moaven, Nima
Stubblefield, Barbara K.
Rogers, Steven A.
Patnaik, Samarjit
Westbroek, Wendy
Sullivan, Patricia
Fujiwara, Hideji
Lopez, Grisel
Goldstein, David S.
Ory, Daniel S.
Marugan, Juan
Sidransky, Ellen
TI IPSC-derived dopaminergic neurons from patients with Gaucher disease and
Parldnsonism demonstrate the potential of a new glucocerebrosidase
chaperone
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 12th Annual WORLD Symposium
CY FEB 29-MAR 04, 2016
CL San Diego, CA
C1 [Aflaki, Elma; Borger, Daniel K.; Moaven, Nima; Stubblefield, Barbara K.; Westbroek, Wendy; Lopez, Grisel] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rogers, Steven A.] Univ Kansas, Specialized Chem Ctr, Lawrence, KS 66045 USA.
[Patnaik, Samarjit] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
[Sullivan, Patricia; Goldstein, David S.] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Fujiwara, Hideji; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr 5, St Louis, MO USA.
[Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2016
VL 117
IS 2
MA 4
BP S15
EP S15
DI 10.1016/j.ymgme.2015.12.162
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA DE8LS
UT WOS:000370888100005
ER
PT J
AU Jiang, XT
Sidhu, R
Dietzen, DJ
Farhat, NY
Porter, FD
Schaffer, JE
Ory, DS
AF Jiang, Xuntian
Sidhu, Rohini
Dietzen, Dennis J.
Farhat, Nicole Yanjanin
Porter, Forbes D.
Schaffer, Jean E.
Ory, Daniel S.
TI Improved diagnostics for Niemann-Pick disease type C based on a novel
bile acid biomarker
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 12th Annual WORLD Symposium
CY FEB 29-MAR 04, 2016
CL San Diego, CA
C1 [Jiang, Xuntian; Sidhu, Rohini; Dietzen, Dennis J.; Schaffer, Jean E.; Ory, Daniel S.] Washington Univ, St Louis, MO USA.
[Farhat, Nicole Yanjanin; Porter, Forbes D.] NIH, Bldg 10, Bethesda, MD 20892 USA.
RI Sidhu, Rohini/G-3547-2012
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2016
VL 117
IS 2
MA 147
BP S62
EP S62
DI 10.1016/j.ymgme.2015.12.305
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA DE8LS
UT WOS:000370888100148
ER
PT J
AU Latour, YL
Thomas, SE
Allende, ML
Proia, RL
Tifft, CJ
AF Latour, Yvonne L.
Thomas, Sarah E.
Allende, Maria L.
Proia, Richard L.
Tifft, Cynthia J.
TI Development of isogenic human cerebral organoids with beta-galactosidase
deficiency
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 12th Annual WORLD Symposium
CY FEB 29-MAR 04, 2016
CL San Diego, CA
C1 [Latour, Yvonne L.; Thomas, Sarah E.; Allende, Maria L.; Proia, Richard L.; Tifft, Cynthia J.] NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2016
VL 117
IS 2
MA 172
BP S70
EP S71
DI 10.1016/j.ymgme.2015.12.330
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA DE8LS
UT WOS:000370888100173
ER
EF