36 research outputs found
The Arabidopsis Framework Model version 2 predicts the organism-level effects of circadian clock gene mis-regulation
- Author
- Publication venue
- 'Oxford University Press (OUP)'
- Publication date
- 01/01/2022
- Field of study
Predicting a multicellular organism’s phenotype quantitatively from its genotype is challenging, as genetic effects must propagate across scales. Circadian clocks are intracellular regulators that control temporal gene expression patterns and hence metabolism, physiology and behaviour. Here we explain and predict canonical phenotypes of circadian timing in a multicellular, model organism. We used diverse metabolic and physiological data to combine and extend mathematical models of rhythmic gene expression, photoperiod-dependent flowering, elongation growth and starch metabolism within a Framework Model for the vegetative growth of Arabidopsis thaliana, sharing the model and data files in a structured, public resource. The calibrated model predicted the effect of altered circadian timing upon each particular phenotype in clock-mutant plants under standard laboratory conditions. Altered night-time metabolism of stored starch accounted for most of the decrease in whole-plant biomass, as previously proposed. Mobilisation of a secondary store of malate and fumarate was also mis-regulated, accounting for any remaining biomass defect. The three candidate mechanisms tested did not explain this organic acid accumulation. Our results link genotype through specific processes to higher-level phenotypes, formalising our understanding of a subtle, pleiotropic syndrome at the whole-organism level, and validating the systems approach to understand complex traits starting from intracellular circuits
Differential expression of VEGF-Axxx isoforms is critical for development of pulmonary fibrosis
- Author
- Publication venue
- 'American Thoracic Society'
- Publication date
- 28/06/2017
- Field of study
RATIONALE
Fibrosis after lung injury is related to poor outcome, and idiopathic pulmonary fibrosis (IPF) can be regarded as an exemplar. Vascular endothelial growth factor (VEGF)-A has been implicated in this context, but there are conflicting reports as to whether it is a contributory or protective factor. Differential splicing of the VEGF-A gene produces multiple functional isoforms including VEGF-Aa and VEGF-Ab, a member of the inhibitory family. To date there is no clear information on the role of VEGF-A in IPF.
OBJECTIVES
To establish VEGF-A isoform expression and functional effects in IPF.
METHODS
We used tissue sections, plasma, and lung fibroblasts from patients with IPF and control subjects. In a bleomycin-induced lung fibrosis model we used wild-type MMTV mice and a triple transgenic mouse SPC-rtTATetoCreLoxP-VEGF-Ato conditionally induce VEGF-A isoform deletion specifically in the alveolar type II (ATII) cells of adult mice.
MEASUREMENTS AND MAIN RESULTS
IPF and normal lung fibroblasts differentially expressed and responded to VEGF-Aa and VEGF-Ab in terms of proliferation and matrix expression. Increased VEGF-Ab was detected in plasma of progressing patients with IPF. In a mouse model of pulmonary fibrosis, ATII-specific deficiency of VEGF-A or constitutive overexpression of VEGF-Ab inhibited the development of pulmonary fibrosis, as did treatment with intraperitoneal delivery of VEGF-Ab to wild-type mice.
CONCLUSIONS
These results indicate that changes in the bioavailability of VEGF-A sourced from ATII cells, namely the ratio of VEGF-Aa to VEGF-Ab, are critical in development of pulmonary fibrosis and may be a paradigm for the regulation of tissue repair
Measurement of differential cross-sections of a top quark produced in association with a W boson at √s=13 TeV with ATLAS
- Author
- A. A. Affolder
- A. A. Alshehri
- A. A. E. Bannoura
- A. A. Elliot
- A. A. Grillo
- A. A. J. Lesage
- A. A. Minaenko
- A. A. O’Rourke
- A. A. Snesarev
- A. A. Solodkov
- A. A. Talyshev
- A. Aloisio
- A. Alonso
- A. Andreazza
- A. Angerami
- A. Annovi
- A. Antonov
- A. Artamonov
- A. Ashkenazi
- A. B. Fenyuk
- A. B. Kowalewska
- A. Bandyopadhyay
- A. Baroncelli
- A. Basalaev
- A. Bassalat
- A. Beddall
- A. Bellerive
- A. Bethani
- A. Betti
- A. Bingul
- A. Blue
- A. Bocci
- A. Borisov
- A. Boveia
- A. Brandt
- A. Bruni
- A. Buzatu
- A. C. König
- A. C. Martyniuk
- A. C. Schaffer
- A. C. Taylor
- A. Calandri
- A. Camplani
- A. Campoverde
- A. Catinaccio
- A. Cattai
- A. Cerri
- A. Cervelli
- A. Chafaq
- A. Chegwidden
- A. Cheplakov
- A. Chitan
- A. Chr. Dudder
- A. Ciocio
- A. Clark
- A. Coccaro
- A. Cortes-Gonzalez
- A. Cueto
- A. D. Pilkington
- A. D. Sherman
- A. Dattagupta
- A. De Benedetti
- A. De Maria
- A. De Salvo
- A. De Santo
- A. Dell’Acqua
- A. Demilly
- A. Dewhurst
- A. Di Ciaccio
- A. Di Girolamo
- A. Di Simone
- A. Dimitrievska
- A. Doria
- A. Dubreuil
- A. Ducourthial
- A. Dudarev
- A. Duperrin
- A. Durglishvili
- A. E. Baas
- A. E. Barton
- A. E. Bolz
- A. E. Dumitriu
- A. E. Kiryunin
- A. E. Lionti
- A. Ereditato
- A. Ezhilov
- A. F. Casha
- A. F. Saavedra
- A. F. Webb
- A. Farbin
- A. Farilla
- A. Favareto
- A. Ferrari
- A. Ferrer
- A. Filipčič
- A. Formica
- A. Forti
- A. G. Bogdanchikov
- A. G. Buckley
- A. G. Foster
- A. G. Goussiou
- A. G. Kharlamov
- A. G. Myagkov
- A. Gabrielli
- A. Gabrielli
- A. Gascon Bravo
- A. Gaudiello
- A. Glazov
- A. Gomes
- A. Gongadze
- A. Gorišek
- A. Grummer
- A. Haas
- A. Hadef
- A. Hamilton
- A. Hasib
- A. Held
- A. Hoecker
- A. Hostiuc
- A. Hoummada
- A. Hrynevich
- A. I. Etienvre
- A. I. Mincer
- A. J. Armbruster
- A. J. Barr
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- A. J. Bozson
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- A. J. Lankford
- A. J. Parker
- A. J. Taylor
- A. Jelinskas
- A. Jinaru
- A. Juste Rozas
- A. K. Ciftci
- A. K. Duncan
- A. K. Morley
- A. Kaczmarska
- A. Kaluza
- A. Kamenshchikov
- A. Kastanas
- A. Katre
- A. Khanov
- A. Khodinov
- A. Klimentov
- A. Knue
- A. Kobayashi
- A. Korn
- A. Kotwal
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- A. Kourkoumeli-Charalampidi
- A. Krasznahorkay
- A. Kugel
- A. Kupco
- A. L. Maslennikov
- A. L. Read
- A. La Rosa
- A. Lanza
- A. Lapertosa
- A. Liblong
- A. Limosani
- A. Lipniacka
- A. Lister
- A. Lleres
- A. Loesle
- A. Lopez Solis
- A. Lounis
- A. Lucotte
- A. M. Burger
- A. M. Cooper-Sarkar
- A. M. Henriques Correia
- A. M. Litke
- A. M. Nairz
- A. M. Sickles
- A. M. Soukharev
- A. M. Wang
- A. M. Wharton
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- A. Macchiolo
- A. Madsen
- A. Maio
- A. Mann
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- A. Mehta
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- A. Wolf
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- B. Martin dit Latour
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- Y. Tian
- Y. Tu
- Y. Unno
- Y. Wu
- Y. Yamaguchi
- Y. Yamazaki
- Y. Yang
- Y. Yasu
- Y. Zhang
- Y. Zhao
- Y. Zhou
- Y. Zhu
- Yu. A. Tikhonov
- Z. Barnovska-Blenessy
- Z. D. Greenwood
- Z. Dolezal
- Z. H. Citron
- Z. Hubacek
- Z. Idrissi
- Z. J. Grout
- Z. Jiang
- Z. Liang
- Z. M. Karpova
- Z. Marshall
- Z. Rurikova
- Z. Wang
- Z. Xi
- Z. Yan
- Z. Yang
- Z. Zhang
- Z. Zhao
- Z. Zinonos
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2018
- Field of study
The differential cross-section for the production of a W boson in association with a top quark is measured for several particle-level observables. The measurements are performed using 36.1fb−1 of pp collision data collected with the ATLAS detector at the LHC in 2015 and 2016. Differential cross-sections are measured in a fiducial phase space defined by the presence of two charged leptons and exactly one jet matched to a b-hadron, and are normalised with the fiducial cross-section. Results are found to be in good agreement with predictions from several Monte Carlo event generators
Recent Engagements with Adam Smith and the Scottish Enlightenment
- Author
- ---
- ---
- ---
- ---
- ---
- ---
- ?ule �zler
- ?ule �zler
- A M C Waterman
- A M C Waterman
- Aaron Garrett
- Aaron Garrett
- Adam Ferguson
- Alexander Broadie
- Alexander Broadie
- Alexander Gerard
- Alexander Sir
- Alexander Wilson
- Allan Ramsay
- Amartya Sen
- Amos Witztum
- Amos Witztum
- Archibald Davidson
- Arie Arnon
- Ashraf
- Brian Bonnyman
- Carmen Pagliari
- Christopher J Berry
- Christopher J Berry
- Christopher J Berry
- Christopher Martin
- Colin Maclaurin
- Craig Smith
- David B Wilson
- David Gregory
- David Norton
- David Raphael
- Dennis C Rasmussen
- Donald Rutherford
- Dugald Stewart
- Elias L Khalil
- Eric Schliesser
- Fonna Forman-Barzilai
- Fredrik Jonsson
- Gavin Kennedy
- George Campbell
- George Turnbull
- George Turnbull
- Harvey S James
- Henry Mackenzie
- Herbert Gintis
- Hiroshi Mizuta
- Hiroyuki Furuya
- Horst Recktenwald
- Hugh Blair
- Iain Mcdaniel
- Ian Ross
- Istvan Hont
- Jack Weinstein
- James Beattie
- James Buchan
- James Dunbar
- James Harris
- James Hutton
- James Konow
- James Watt
- Jaworski
- Jean-Louis Peaucelle
- Jeffrey T Young
- Jerry Evensky
- John Anderson
- John Gregory
- John Hope
- John Hunter
- John Keill
- John Millar
- John Playfair
- John Pringle
- John Robison
- John Salter
- John Sir
- John Stevenson
- John Walker
- Jonathan B Wight
- Joseph Black
- Julie Whittaker
- Karin Brown
- Keith A Bender
- Keith Tribe
- Knud Haakonssen
- Kwangsu Kim
- L Kiesling
- Leonidas Montes
- Lisa Herzog
- Lord Dundas
- Lord Kames
- Marco Iacoboni
- Maria Paganelli
- Maria Pia Paganelli
- Mark Collier
- Michael Perelman
- Nicholas T Phillipson
- Paul A Gabrinetti
- Paul J Zak
- Paul J Zak
- Paul Oslington
- Peter J Buckley
- Reinhard Schumacher
- Richard E Wagner
- Robert W Dimand
- Robert Wallace
- Roger Backhouse
- Roger L Emerson
- Ryan Hanley
- Samuel Fleischacker
- Samuel Fleischacker
- Sheila Dow
- Shinichi Nagao
- Shinji Nohara
- Shudong Chen
- Silvia Sebastiani
- Stephen J Mckenna
- T C Smout
- Terry Peach
- Thomas Reid
- Tony Aspromourgos
- Vernon L Smith
- Vernon L Smith
- Vivienne Brown
- Warren J Samuels
- William Cullen
- William Leechman
- William Robertson
- Yong-Sun Yang
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2015
- Field of study
Measurement of the inclusive and fiducial tt ¯ production cross-sections in the lepton+jets channel in pp collisions at s √ =8 TeV with the ATLAS detector
- Author
- A Buckley
- A. A. Affolder
- A. A. Alshehri
- A. A. E. Bannoura
- A. A. Elliot
- A. A. Grillo
- A. A. J. Lesage
- A. A. Komar
- A. A. Korol
- A. A. Minaenko
- A. A. O’Rourke
- A. A. Snesarev
- A. A. Solodkov
- A. A. Talyshev
- A. Aloisio
- A. Alonso
- A. Andreazza
- A. Angerami
- A. Annovi
- A. Antonov
- A. Artamonov
- A. Ashkenazi
- A. B. Fenyuk
- A. B. Kowalewska
- A. Bandyopadhyay
- A. Baroncelli
- A. Basalaev
- A. Bassalat
- A. Beddall
- A. Bellerive
- A. Bethani
- A. Betti
- A. Bingul
- A. Blue
- A. Bocci
- A. Borisov
- A. Boveia
- A. Brandt
- A. Bruni
- A. Buzatu
- A. C. Daniells
- A. C. König
- A. C. Martyniuk
- A. C. Schaffer
- A. C. Taylor
- A. Calandri
- A. Camplani
- A. Campoverde
- A. Catinaccio
- A. Cattai
- A. Cerri
- A. Cervelli
- A. Chafaq
- A. Chegwidden
- A. Cheplakov
- A. Chitan
- A. Chr. Dudder
- A. Ciocio
- A. Clark
- A. Coccaro
- A. Cortes-Gonzalez
- A. Cueto
- A. D. Pilkington
- A. D. Sherman
- A. Dattagupta
- A. De Benedetti
- A. De Maria
- A. De Salvo
- A. De Santo
- A. Dell’Acqua
- A. Demilly
- A. Dewhurst
- A. Di Ciaccio
- A. Di Girolamo
- A. Di Simone
- A. Dimitrievska
- A. Doria
- A. Dubreuil
- A. Ducourthial
- A. Dudarev
- A. Duperrin
- A. Durglishvili
- A. E. Baas
- A. E. Barton
- A. E. Bolz
- A. E. Dumitriu
- A. E. Kiryunin
- A. E. Lionti
- A. Ereditato
- A. Ezhilov
- A. F. Casha
- A. F. Saavedra
- A. F. Webb
- A. Farbin
- A. Farilla
- A. Favareto
- A. Ferrari
- A. Ferrer
- A. Filipčič
- A. Fischer
- A. Formica
- A. Forti
- A. G. Bogdanchikov
- A. G. Buckley
- A. G. Foster
- A. G. Goussiou
- A. G. Kharlamov
- A. G. Myagkov
- A. Gabrielli
- A. Gabrielli
- A. Gascon Bravo
- A. Gaudiello
- A. Glazov
- A. Gomes
- A. Gongadze
- A. Gorišek
- A. Grummer
- A. Haas
- A. Hadef
- A. Hamilton
- A. Hasib
- A. Held
- A. Hoecker
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- A. Hoummada
- A. Hrynevich
- A. I. Etienvre
- A. I. Mincer
- A. J. Armbruster
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- A. J. Beddall
- A. J. Bevan
- A. J. Bozson
- A. J. Brennan
- A. J. Chuinard
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- A. J. Lankford
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- A. J. Taylor
- A. Jelinskas
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- A. Juste Rozas
- A. K. Ciftci
- A. K. Duncan
- A. K. Kopp
- A. K. Morley
- A. Kaczmarska
- A. Kaluza
- A. Kamenshchikov
- A. Kastanas
- A. Katre
- A. Khanov
- A. Khodinov
- A. Klimentov
- A. Knue
- A. Kobayashi
- A. Korn
- A. Kotwal
- A. Koulouris
- A. Kourkoumeli-Charalampidi
- A. Krasznahorkay
- A. Kugel
- A. Kupco
- A. L. Maslennikov
- A. L. Read
- A. La Rosa
- A. Lanza
- A. Lapertosa
- A. Liblong
- A. Limosani
- A. Lipniacka
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- A. M. Henriques Correia
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- A. M. Zaitsev
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- A. Madsen
- A. Maio
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- A. Melzer
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- A. Montalbano
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- A. P. Colijn
- A. Pacheco Pages
- A. Paramonov
- A. Petridis
- A. Peyaud
- A. Picazio
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- A. Policicchio
- A. Polini
- A. Pranko
- A. Puri
- A. Quadt
- A. R. Buzykaev
- A. R. Chomont
- A. R. Cukierman
- A. R. Stradling
- A. R. Weidberg
- A. Redelbach
- A. Reiss
- A. Rimoldi
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- A. Romaniouk
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- W-M. Yao
- W. A. Cribbs
- W. A. Leight
- W. Buttinger
- W. C. Fisher
- W. D. Breaden Madden
- W. Dabrowski
- W. Davey
- W. F. Mader
- W. Fedorko
- W. Guan
- W. Guo
- W. H. Hopkins
- W. J. Fawcett
- W. J. Johnson
- W. J. Murray
- W. K. Balunas
- W. K. Brooks
- W. K. Di Clemente
- W. Kozanecki
- W. Lampl
- W. Lavrijsen
- W. Liebig
- W. Lukas
- W. S. Chan
- W. Taylor
- W. Trischuk
- W. Van Den Wollenberg
- W. Vandelli
- W. Verkerke
- W. Wagner
- W. Walkowiak
- W. Wang
- W. Wang
- W. Wiedenmann
- W. Xu
- X. Chen
- X. Hoad
- X. Ju
- X. Lei
- X. Li
- X. Lou
- X. Ruan
- X. Sun
- X. T. Meng
- X. Wu
- X. Zhang
- X. Zhao
- X. Zhuang
- Y. A. Kurochkin
- Y. Abulaiti
- Y. Afik
- Y. Amaral Coutinho
- Y. Arai
- Y. Benhammou
- Y. C. Yap
- Y. Chen
- Y. Coadou
- Y. Du
- Y. Enari
- Y. F. Ryabov
- Y. Fang
- Y. Gao
- Y. Guo
- Y. H. Chiu
- Y. Hasegawa
- Y. Heng
- Y. Hernández Jiménez
- Y. Horii
- Y. Huang
- Y. Ikegami
- Y. Ilchenko
- Y. J. Lu
- Y. Jiang
- Y. K. Kim
- Y. Kataoka
- Y. Kulchitsky
- Y. L. Chan
- Y. L. Liu
- Y. Li
- Y. Liu
- Y. Ma
- Y. Makida
- Y. Minami
- Y. Minegishi
- Y. Ming
- Y. Nagasaka
- Y. Nakahama
- Y. Ninomiya
- Y. Noguchi
- Y. Okumura
- Y. Oren
- Y. P. Kulinich
- Y. Qin
- Y. Rodina
- Y. Rozen
- Y. S. Chow
- Y. S. Gao
- Y. S. Ng
- Y. Sakurai
- Y. Sano
- Y. Shen
- Y. Smirnov
- Y. Sugaya
- Y. Takubo
- Y. Tayalati
- Y. Tian
- Y. Tu
- Y. Unno
- Y. Wu
- Y. Yamaguchi
- Y. Yamazaki
- Y. Yang
- Y. Yasu
- Y. Zhang
- Y. Zhao
- Y. Zhou
- Y. Zhu
- Yu. A. Tikhonov
- Z. Barnovska-Blenessy
- Z. D. Greenwood
- Z. Dolezal
- Z. H. Citron
- Z. Hubacek
- Z. Idrissi
- Z. J. Grout
- Z. Jiang
- Z. Liang
- Z. M. Karpova
- Z. Marshall
- Z. Rurikova
- Z. Wang
- Z. Xi
- Z. Yan
- Z. Yang
- Z. Zhang
- Z. Zhao
- Z. Zinonos
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2017
- Field of study
The inclusive and fiducial tt ¯ production cross-sections are measured in the lepton+jets channel using 20.2 fb −1 of proton-proton collision data at a centre-of-mass energy of 8 TeV recorded with the ATLAS detector at the LHC. Major systematic uncertainties due to the modelling of the jet energy scale and b -tagging efficiency are constrained by separating selected events into three disjoint regions. In order to reduce systematic uncertainties in the most important background, the W+jets process is modelled using Z+jets events in a data-driven approach. The inclusive tt ¯ cross-section is measured with a precision of 5.7% to be σ inc (tt ¯ ) = 248.3 ± 0.7 (stat.) ± 13.4 (syst.) ± 4.7 (lumi.) pb, assuming a top-quark mass of 172.5 GeV. The result is in agreement with the Standard Model prediction. The cross-section is also measured in a phase space close to that of the selected data. The fiducial cross-section is σ fid (tt ¯ ) = 48.8 ± 0.1 (stat.) ± 2.0 (syst.) ± 0.9 (lumi.) pb with a precision of 4.5%
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
- Author
- Abdulkader Rita
- Abozaid Hanan S.
- Adab Peymané
- Adizie Tochukwu
- Adshead Rebecca
- Ahmad Yasmeen
- Ahmed Azeem A.
- Akil Mohammed
- Alavi Azita
- Alcorn Desmond
- Alexander Yvonne
- Alexander Yvonne
- Alexander Yvonne
- Allen Maggie
- Amarasena Roshan
- Amarasena Roshan I.
- Ambler Nick
- Amft Nicole
- Amft Nicole
- Amissah-Arthur Maame
- Amos Nicholson
- Anderson David
- Andres Mariano
- Andrews Jacqueline
- Arthur Catherine
- Ashton Simon
- Axford John
- Ayalew Yezenash
- Baburaj Krishnan
- Bacon Paul A.
- Baguley Elaine
- Ball Elisabeth
- Banik Snehashish
- Bari Syed F.
- Barone Francesca
- Barone Francesca
- Barton Anne
- Barton Anne
- Basu Neil
- Bateman James
- Bavakunji Riaz
- Bayley Rachel
- Beasley Marcus
- Bell Aubrey
- Bell Aubrey L.
- Birnbaum Julius
- Bombardieri M.
- Bombardieri Michele
- Bombardieri Michele
- Bombardieri Michele
- Bond Christine
- Bond Ursula
- Borg Frances
- Borg Frances A.
- Bosworth Ailsa
- Boulton John
- Bowman Simon
- Bowness Paul
- Bowness Paul
- Bowness Paul
- Braude Simon
- Brooksby Alan
- Brophy Sinead
- Brown Deborah
- Brown Nina
- Brown Sue J.
- Bruce Ian
- Bruce Ian
- Bruce Ian
- Bruce Ian
- Bruce Ian
- Buckley Chris
- Buckley Chris
- Buckley Chris
- Buckley Chris D.
- Bukhari Marwan
- Bukhari Marwan
- Bukhari Marwan
- Bullock Craig
- Bunn Diane
- Bunn Diane
- Bunning Rowena
- Bunning Rowena A. D.
- Bunning Rowena D.
- Calnan Michael
- Cardy Caroline M.
- Casey Matthew
- Caswell Richard
- Ceeraz Sabrina
- Chan Antoni
- Chana Jasroop K.
- Chapman Victoria
- Chen Liye
- Cheng K. K.
- Chitale Sarang
- Chitale Sarang
- Chiverton Neil
- Chiverton Neil
- Choy Ernest
- Choy Ernest H.
- Christidis Dimitrios
- Cloake Tom
- Cloake Tom
- Clunie Gavin
- Coady David
- Coady David
- Coady David
- Colaco Bernard
- Cole Zoe A.
- Coles Mark
- Collins Fraser
- Cooksey Roxanne
- Cooper Annie
- Cooper Cyrus
- Cooper Cyrus
- Cooper Nicola
- Cope Andrew
- Cordingley Lis
- Corrigall Valerie
- Coward Lucy
- Crawford Aileen
- Crilly Anne
- Cross Alison
- Cross Alison K.
- Crouch Carina
- Crozier Sarah R.
- Cumming Jo
- Curtis Elizabeth M.
- D'Cruz David
- Danda Debashish
- Daniel Priya
- Daniels Jodie
- Darroch James
- Dasgupta Bhaskar
- Dasgupta Bhaskar
- Dasgupta Bhaskar
- Davies Charlotte
- Davies David
- Davies Rebecca
- Davies Ursula M.
- Dent Caroline
- Devanny Ian
- Dey Ida D.
- Dhanjal Mandish
- Dhillon Veena
- DiCicco Maria
- Dixey Josh
- Dixey Josh
- Doherty Teresa
- Donnelly Simon P.
- Driscoll Paul C.
- Duncan G.
- Duncan Rosie
- Dunn Sara
- Dures Emma
- Edgar Suzanne
- Edmonds Sally
- Edwards Christopher J.
- Edwards Christopher J.
- Edwards Steven W.
- Ellis Benjamin
- Ellis Corrinne
- Else Sara
- Emery Paul
- Ennis H.
- Estrach Cristina
- Estrach Cristina
- Evans Bronwen
- Evans Hayley G.
- Evans Laura
- Eyre Tracey
- Fang Hong
- Farrow Luke
- Fattah Zozik
- Ferrell William R.
- Field Max
- Finlay Ron
- Fisher Roman
- Fleming S.
- Fletcher Debbie
- Fluess Elisa
- Foggo Heather
- Fortune F.
- Fu Bo
- Gainsborough Nicola
- Galloway James
- Galloway James
- Garner Rozeena
- Garza-Garcia Acely
- Gathany Tim
- Gayed Mary
- Gayed Mary
- Georgia Ntani
- Giles Ian
- Giles Ian
- Giles Ian
- Giles Joanna L.
- Godfrey Keith M.
- Goff Iain
- Golor G.
- Goodson Nicola J.
- Goodson Nicola J.
- Goodson Nicola J.
- Gordon Caroline
- Gordon Caroline
- Gordon Caroline
- Gorman Claire L.
- Greenbank Cathi
- Griffiths Bridget
- Griffiths Bridget
- Gullick Nicola J.
- Gullick Nicola J.
- Gupta Monica
- Haddock Gail
- Haddock Gail
- Hakim Alan J.
- Halsey John
- Han Chenglong
- Hands Rebecca
- Harper Lorraine
- Harris Claire L.
- Harta N.
- Harvey Nicholas C.
- Hashmi Tahir M.
- Hassan Ahmed I.
- Hassell Andrew
- Hayes Fiona
- Hayes Fiona
- Heaney Jonathan
- Heathfield Sarah
- Heron Louise
- Herrick Ariane
- Hewlett Sarah
- Hewlett Sarah
- Hickling M.
- Horan Michael
- Hsia Elizabeth
- Hughes Michael
- Hui Michelle
- Hull Richard
- Hull Richard G.
- Humby Frances
- Humphreys Jennifer
- Hunter John
- Hunter John
- Husain Muhammad J.
- Hutchinson David
- Hyrich Kimme
- Hyrich Kimme
- Ibrahim Ibrahim
- Inskip Hazel M.
- Ioannou John
- Ioannou Yiannis
- Iqbal Itrat
- Irvine Elizabeth
- Isaacs John
- Isenberg David
- Isenberg David
- Isenberg David
- Isenberg David
- Isenberg David
- Ismajli Mediola
- Jani Meghna
- Jani Meghna
- Jayaraj David M.
- Jayne David
- Jenkins Jessica
- Jennens Hannah
- Jiang C. Q.
- John Elizabeth
- Johnson Phil
- Jones Gareth T.
- Jones Gareth T.
- Jones Simon A.
- Jullion A.
- Kallankara Sathish
- Kate I.
- Kay Lesley
- Keeley Philip
- Keidel Sarah
- Kelly Sara
- Kelly Stephen
- Kendall David
- Kenu Ernest
- Kessler Benedikt M.
- Khamashta Munther
- Khattak Fazlihakim
- Kiely Patrick D.
- Kindness Kathy
- Kollnberger Simon
- Kollnberger Simon
- Kollnberger Simon
- Kretsos K.
- Kumar Kanta
- Kumar Namita
- Kuvikova Inna
- Lam T. H.
- Lane Peter
- Lanyon Peter
- Lanyon Peter
- Lanyon Peter
- Lawton Sally
- Le Maitre Christine
- Le Maitre Christine L.
- Le Maitre Christine L.
- Ledingham Jo
- Lendrem Dennis
- Leung Jansen
- Lewis Cathryn M.
- Lim Ken
- Ling Stephanie
- Lip Stefanie
- Little Jayne
- Littlewood Alison
- Lockhart John
- Loke Yoon
- Lovell Karina
- Low Audrey
- Lunt Mark
- Lunt Mark
- Lutalo Pamela M.
- Macfarlane Gary J.
- Macfarlane Gary J.
- Macfarlane Gary J.
- Macfarlane Matthew V.
- MacGregor Alex
- MacGregor Alex
- MacGregor Alex
- Mackie Sarah L.
- Macphie Elizabeth
- Mahadik Younis
- Mahendranath K. M.
- Main Wong Way
- Malaviya Anshuman P.
- Marks Jonathan
- Marroquin Osiris
- Mason Justin
- Mc Laughlin Maeve
- McBeth John
- McBeth John
- McBurney H.
- McHugh Kirsty
- McHugh Kirsty
- McHugh Neil
- McHugh Neil
- McHugh Neil
- McInnes Iain
- McInnes Ian
- McKenna Frank
- McKeogh John
- Mckew Jennifer R.
- McLaren John
- McLoughlin Yokemei
- Mehta Puja
- Mehta Puja
- Meldrum Gillian
- Mercer Louise
- Middleton Jim
- Millar Auleen M.
- Misra Ramnath
- Mitchell Adam
- Mitchell Sheryl
- Mobasheri Ali
- Moots Robert J.
- Moots Robert J.
- Moots Robert J.
- Morgan Anne
- Morgan Matthew
- Morris Marianne
- Mugford Miranda
- Mulvey Matthew
- Mulvey Matthew R.
- Murfitt Lucy
- Murphy Helen
- Murray-Brown William
- Mérida Angeles Acosta
- Nayar Saba
- Nayar Saba
- Nazeer Moideen Abdul
- Nelson-Piercy Catherine
- Newman W.
- Ng Nora
- Ng Wan-Fai
- Nicholl Karl
- Nikiphorou Elena
- Nikiphorou Elena
- Nowell Mari A.
- O'Connor Mortimer B.
- O'Neill Terence
- Ogunbambi Olabambo
- Oldroyd Alexander G.
- Oomatia Amin
- Oreffo Richard O.
- Osei-Bordom Daniel-Clement
- Osgood Louise
- Ostor Andrew J.
- Owens Martina
- Palmer Helen
- Parker Ben
- Parker Ben
- Parker Ben
- Patel Dipti
- Patel Yusuf
- Patil Pravin
- Paudyal Priya
- Paul Morgan B.
- Pauling John D.
- Payeli Sravan
- Pearce Fiona
- Pease Colin T.
- Pease Colin T.
- Pendleton Neil
- Pericleous Charis
- Pericleous Charis
- Perry Liz
- Petri Michelle
- Phelan Mark J.
- Phillips Ceri J.
- Phillips E.
- Phillips Kate L. E.
- Picarelli G.
- Pierangeli Silvia
- Pierangeli Silvia S.
- Pilling Claire
- Pitzalis C.
- Pitzalis Costantino
- Pitzalis Costantino
- Pitzalis Costantino
- Plant Darren
- Plant Darren
- Platt Philip N.
- Plevin Robin
- Pope Denise
- Popham Maria
- Price Elizabeth
- Price Elizabeth
- Price-Forbes Alec
- Priori R.
- Pushpakom S.
- Rahman Anisur
- Rahman Anisur
- Rahman Anisur
- Rankin Elizabeth
- Rao Chandini
- Ray David W.
- Raza Karim
- Rees Frances
- Regan Marian
- Regan Marian
- Reid David M.
- Renner Christoph
- Reynolds John A.
- Reynolds Piero
- Rhys-Dillon Brian
- Ridley Anna
- Robertson Calum
- Robinson Frances
- Robinson Sandra
- Robinson Siân M.
- Rooke Royston
- Rooney Madeleine
- Roskell S.
- Roussou Thalia
- Roussou Thalia
- Rump-Goodrich Lisa
- Russell M.
- Rutherford Michelle
- Ryan Sarah
- Rysnik Oliwia J.
- Sanderson Tessa
- Sayer Avan A.
- Scott David L.
- Scott Ian C.
- Segeda Iuliia
- Selvan Shilpa
- Semenova Olga
- Sensky T.
- Seoudi N.
- Severn Andrew
- Shah Preeti
- Sharp Charlotte A.
- Shastri Nilabh
- Shaw Jackie
- Shaw Jacqueline
- Shaw S.
- Sheldon Jo
- Shevchuk Sergii
- Siebert Stefan
- Siebert Stefan
- Simpson John
- Sivakumar Rajappa
- Skeoch Sarah
- Sofat Nidhi
- Solymossy Csilla
- Spandley A.
- Spector Tim
- Spencer Jo
- Srikanth Asha
- Steer Sophia
- Stewart Kirsty
- Stockton Marie
- Stone Michael
- Strand V.
- Sutcliffe Nurhan
- Sutton Emily J.
- Swan Joan
- Symmons Deborah
- Symmons Deborah
- Symmons Deborah
- Symmons Deborah
- Symmons Deborah
- Taams Leonie S.
- Tahir Hasan
- Tan Shaun
- Tandon Neeta
- Tappuni T.
- Tarelli Edward
- Taylor P.
- Taylor Peter
- Taylor Peter
- Teh Lee-Suan
- Thapper Muryum
- Thapper Muryum
- Thomas Huw B.
- Thompson Helen
- Timoshanko J.
- Tugnet Nicola
- Tysoe Carolyn
- Vadivelu Saravanan
- Valesini G.
- Vartoukian S.
- Varughese Sneha
- Venning Michael
- Verstappen Suzanne M.
- Viatte Sebastien
- Vincent Tonia
- Walker David
- Walker-Bone Karen
- Walker-Bone Karen
- Walsh David A.
- Wang Edward
- Watson Kath
- Watson Kath D.
- Watts Richard
- Weaver Dan
- West Louise
- West Lucy
- Wilkinson Mark
- Williams Anwen S.
- Williams Anwen S.
- Williams Emma L.
- Williams Frances M.
- Williams Mark
- Williams Mark R.
- Wilson Anthony
- Wilson Gillian
- Wilson Jo
- Win Maw Win
- Woby Steve
- Wong-Baeza Isabel
- Wood Elizabeth F.
- Worthington J.
- Worthington Jane
- Wright Helen L.
- Wright Stephen A.
- Yates Max
- Yee Chee-Seng
- Young Adam
- Young Adam
- Young Stephen
- Young Stephen P.
- Zaki Awal
- Zeef Leo
- Zoma Asad
- Publication venue
- Publication date
- 02/08/2017
- Field of study
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
- Author
- Adlard Julian
- Ahmed Munaza
- Aich Anshul
- Aitman Tim
- Alachkar Hana
- Alle Hana Lango
- Allsup David
- Almeida-King Jeff
- Ambrose J. C.
- Amin Aliya S.
- Ancliff Philip
- Antrobus Richard
- Armstrong Ruth
- Arno Gavin
- Arumugam P.
- Ashford Sofie
- Astle William
- Attwood Anthony
- Babbs Chris
- Bakchoul Tamam
- Bariana Tadbir
- Barwell Julian
- Bennett David
- Bentley David
- Bevers R.
- Bierzynska Agnieszka
- Biss Tina
- Bleda M.
- Bleda Marta
- Boardman-Pretty F.
- Bogaard Harm
- Bourne Christian
- Boustred C. R.
- Boyce Sara
- Bradley John
- Breen Gerome
- Brennan Paul
- Brewer Carole
- Brittain H.
- Brod Naomi Clements
- Brown M. A.
- Brown Matthew
- Browning Michael
- Buchan Rachel
- Buckland Matthew
- Bueser Teofila
- Burns Siobhan
- Burren Oliver
- Calleja Paul
- Carr-White Gerald
- Carss Keren
- Casey Ruth
- Caulfield M. J.
- Caulfield Mark
- Cebola Inês
- Chambers Jennifer
- Chambers Jenny
- Chambers John
- Chan G. C.
- Chan Melanie M. Y.
- Cheng Floria
- Chinnery Patrick F.
- Christian Martin
- Church Colin
- Coghlan Gerry
- Colby Elizabeth
- Cole Trevor
- Collins Janine
- Collins Peter
- Colombo Camilla
- Condliffe Robin
- Cook Stuart
- Cook Terry
- Cooley Sharon
- Cooper Nichola
- Corris Paul
- Crisp-Hihn Abigail
- Curry Nicola
- Danesino Cesare
- Daniels Matthew
- Daugherty Louise
- Davis John
- Deevi Sri V. V.
- Dent Timothy
- Dewhurst Eleanor
- Dixon Peter
- Dixon Peter H.
- Donnelly Jennifer
- Downes Kate
- Drazyk Anna
- Drewe Elizabeth
- Dutt Tina
- Edgar David
- Edwards Karen
- Egner William
- Erber Wendy
- Erwood Marie
- Estiu Maria C.
- Estiu Maria Cecilia
- Evans Dafydd Gareth
- Evans Gillian
- Everington Tamara
- Eyries Mélanie
- Favier Remi
- Fletcher Debra
- Fowler T.
- Fox James
- Frary Amy
- French Courtney
- Freson Kathleen
- Frontini Mattia
- Gale Daniel
- Gale Daniel P.
- Gall Henning
- Geary Michael
- Geoghegan Claire
- Gerighty Terry
- Ghio Stefano
- Ghofrani Hossein-Ardeschir
- Gibbs Simon
- Giess A.
- Gilmour Kimberley
- Girerd Barbara
- Goddard Sarah
- Gomez Keith
- Gordins Pavels
- Gosal David
- Grassi Luigi
- Greene Daniel
- Greenhalgh Lynn
- Greinacher Andreas
- Gresele Paolo
- Griffiths Philip
- Grigoriadou Sofia
- Grocock Russell
- Grozeva Detelina
- Gräf Stefan
- Hackett Scott
- Hadinnapola Charaka
- Hague William
- Hague William M.
- Haimel Matthias
- Hall Matthew
- Hamblin A.
- Hanson Helen
- Harkness Kirsty
- Harper Andrew
- Harris Claire
- Hart Daniel
- Hassan Ahamad
- Hayman Grant
- Henderson Alex
- Henderson S.
- Hoffmann Jonathan
- Horvath Rita
- Houweling Arjan
- Howard Luke
- Hu Fengyuan
- Hubbard T. J. P.
- Hudson Gavin
- Hughes Joseph
- Huissoon Aarnoud
- Humbert Marc
- Humphray Sean
- Hunter Sarah
- Hurles Matthew
- Izatt Louise
- Jackson R.
- James Roger
- Johnson Sally
- Jolles Stephen
- Jolley Jennifer
- Jones L. J.
- Jurkute Neringa
- Kasanicki Mary
- Kasperaviciute D.
- Kayikci M.
- Kazkaz Hanadi
- Kazmi Rashid
- Kelleher Peter
- Kiely David
- Kingston Nathalie
- Klima Robert
- Kostadima Myrto
- Kousathanas A.
- Kovacs Gabor
- Koziell Ania
- Kreuzhuber Roman
- Kuijpers Taco
- Kumar Ajith
- Kumararatne Dinakantha
- Kuria Manju
- Laffa Michael
- Lahnstein L.
- Lalloo Fiona
- Lamber Michele
- Lawrie Allan
- Layton Mark
- Leigh S. E. A.
- Lentaigne Claire
- Leong I. U. S.
- Levine Adam
- Levine Adam P.
- Linger Rachel
- Longhurst Hilary
- Lopez F. J.
- Louka Eleni
- Madan Bella
- Maher Eamonn
- Maimaris Jesmeen
- Maleady-Crowe F.
- Mangles Sarah
- Mapeta Rutendo
- Marchbank Kevin
- Marks Stephen
- Markus Hugh S.
- Marschall Hanns-Ulrich
- Marshall Andrew
- Martin Jennifer
- Mathias Mary
- Matthews Emma
- Maude Hannah
- Maxwell Heather
- McAlinden Paul
- McCarthy Mark
- McEntagart M.
- Meacham Stuart
- Mead Adam
- Megy Karyn
- Mehta Sarju
- Michaelides Michel
- Millar Carolyn
- Minneci F.
- Mitchell Alice L.
- Moledina Shahin
- Montani David
- Moor Tony
- Morrell Nicholas
- Moutsianas L.
- Mozere Monika
- Mueller M.
- Muir Keith
- Mumford Andrew
- Murugaesu N.
- Need A. C.
- Newnham Michael
- Nicolaides Kypros
- Noordegraaf Anton Vonk
- O'Donovan P.
- O'Sullivan Jennifer
- Obaji Samya
- Odhams C. A.
- Okoli Steven
- Olschewski Andrea
- Olschewski Horst
- Ong Kai Ren
- Ormondroy Elizabeth
- Ouwehan Willem
- Papadi Sofia
- Park Soo-Mi
- Parry David
- Patch C.
- Paterson Joan
- Peacock Andrew
- Peden John
- Peerlinck Kathelijne
- Penkett Christopher
- Pepke-Zaba Joanna
- Pereira M. B.
- Perez-Gil D.
- Petersen Romina
- Pullinger J.
- Pyle Angela
- Rahim T.
- Rankin Stuart
- Rao Anupama
- Raymond F. Lucy
- Rayner-Matthew Paula
- Rees Christine
- Rendon A.
- Rendon Augusto
- Renton Tara
- Rice Andrew
- Richardson Sylvia
- Richter Alex
- Roberts Irene
- Rogers T.
- Ross Robert MacKenzie
- Roughley Catherine
- Roy Noemi
- Sadeghi-Alavijeh Omid
- Saleem Moin
- Samani Nilesh
- Sanchis-Juan Alba
- Sargur Ravishankar
- Satchell Simon
- Savage K.
- Savic Sinisa
- Sawant K.
- Scelsi Laura
- Schulman Sol
- Scott R. H.
- Scully Marie
- Searle Claire
- Seeger Werner
- Sewell Carrock
- Seyres Denis
- Shapiro Susie
- Sharmardina Olga
- Shtoyerman Rakefet
- Sibson Keith
- Siddiq A.
- Side Lucy
- Sieghart A.
- Simeoni Ilenia
- Simpson Michael
- Sivapalaratnam Suthesh
- Skytte Anne-Bine
- Smith Katherine
- Smith Kenneth G. C.
- Smith S. C.
- Snape Katie
- Sosinsky A.
- Soubrier Florent
- Staines Simon
- Staples Emily
- Stark Hannah
- Stephens Jonathan
- Stirrups Kathleen
- Stock Sophie
- Stuckey A.
- Suntharalingam Jay
- Swietlik Emilia
- Syngelaki Argyro
- Tait R. Campbell
- Talks Kate
- Tan Rhea
- Tanguy M.
- Taylor Tavares A. L.
- Thaventhiran James
- Themistocleous Andreas
- Thomas E. R. A.
- Thomas Moira
- Thompson S. R.
- Thomson Kate
- Thorsell Malin
- Thrasher Adrian
- Thys Chantal
- Tischkowitz Marc
- Titterton Catherine
- Toh Cheng-Hock
- Toshner Mark
- Traylor Matthew
- Treacy Carmen
- Trembath Richard
- Tucci A.
- Tuna Salih
- Turek Wojciech
- Turro Ernest
- Vale Tom
- Van Geet Chris
- Van Zuydam Natalie
- Vazquez-Lopez Marta
- von Ziegenweidt Julie
- Waisfisz Quintin
- Walker Suellen
- Ware James
- Watkins Hugh
- Watt Christopher
- Webster Andrew
- Wei Wei
- Welch Steven
- Welland M. J.
- Wessels Julie
- Westbury Sarah
- Westwood John-Paul
- Wharton John
- Whitehorn Deborah
- Whitworth James
- Wilkins Martin R.
- Williams E.
- Williamson Catherine
- Witkowska K.
- Wong Edwin
- Wood Nicholas
- Wood S. M.
- Wood Yvette
- Woods Geoff
- Woodward Emma
- Wort Stephen
- Worth Austen
- Yates Katherine
- Yong Patrick
- Young Tim
- Yu Ping
- Yu-Wai-Man Patrick
- Zhang Jun
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 17/08/2022
- Field of study
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
- Author
- Abassi Yama
- Abelin Jennifer G
- Abolhalaj Milad
- Abraham Tara S
- Adam Ammar
- Adams David
- Adams Homer
- Adams Sarah F
- Adamus Tomasz
- Addepalli Murali
- Addepalli Murali
- Adjei Alex A
- Agapova Larissa
- Agarwala Sanjiv
- Ager Casey
- Aggarwal Charu
- Agnello Giulia
- Agudo Judith
- Aguilar Ethan G
- Aguilera Todd
- Ahamadi Malidi
- Ahn Yong-Oon
- Ahrens Eric T
- Aizer Ayal
- Ajina Reham
- Akerley Wallace
- Al-Muftah Mariam
- Albershardt Tina C
- Albershardt Tina C
- Albrekt Ann-Sofie
- Alekar Shilpa
- Alemany Ramon
- Alemany Ramon
- Alexander Brian
- Allbritton Omaira
- Allen Clint T
- Alley Evan W
- Allison James
- Allison James
- Allison James
- Alston Tesha
- Alt Jürgen
- Alters Susan
- Amatulli Michael
- Anand Snjezana
- Anand Snjezana
- Anand Snjezana
- Anderson Clark
- Anderson Mark
- Andersson Bengt
- Andre Pascale
- Andtbacka Robert H I
- Andtbacka Robert H I
- Angiuoli Sam
- Ansari Tameem
- Anthony Scott
- Antonarakis Emmanuel S
- Antonia Scott J
- Anwar Firoz
- Aquino-Michaels Keston
- Archer Jacob F
- Arina Ainhoa
- Armand Philippe
- Armenta Paul
- Armet Caroline M
- Arnoux Thomas
- Ascarateil Stephane
- Askmyr David
- Atkins Michael
- Atkins Michael B
- Atkinson Victoria
- Au Katrina
- Autio Karen A
- Awad Mark
- Bagarazzi Mark
- Bai Dina
- Baia Gilson
- Baird Jason
- Bajaj Anshika
- Balatoni Timea
- Balboni Tracy
- Balch Leslie
- Bang Andrew
- Bao Riyue
- Bao Yangyi
- Bao Yangyi
- Barakat David
- Barberi Theresa
- Barker Christopher A
- Barnea Eytan
- Barras David
- Bartkowiak Todd
- Bartlett David
- Bartlett David
- Bartlett David
- Bartlett David
- Barton Sunjay M
- Barve Minal
- Bauer Todd
- Bauer Todd W
- Bauman Julie
- Baumgaertner Petra
- Bauml Joshua
- Beceren-Braun Figen
- Beck Kristen
- Becker Annette
- Beckers Johannes
- Beckett Michael A
- Bedognetti Davide
- Bedognetti Davide
- Bedognetti Davide
- Bell Bryan
- Bell Charles J M
- Bell Peter
- Beltran Pedro
- Bender Lewis H
- Bender Steven
- Bennett Mark K
- Benz Steven
- Bera Tapan
- Berglund Peter
- Berglund Peter
- Berkey Sara
- Bernatchez Chantale
- Berry John S
- Berzofsky Jay A
- Bhardwaj Nina
- Bian Zhen
- Bianco Alberto
- Biediger Ronald J
- Bifulco Carlo
- Bigley Alison
- Bingham Patrick
- Biniszkiewicz Detlev M
- Bischoff Helge
- Blake Zoe
- Blake Zoe
- Blakely Collin
- Blazar Bruce R
- Blogowski Wojciech
- Bloom Anja C
- Boehm Jesse
- Bokovanov Vladimir
- Bommareddy Praveen K
- Bommareddy Praveen K
- Bommareddy Praveen K
- Bommareddy Praveen K
- Booth Jamie
- Bornschlegl Svetlana
- Bose Nandita
- Bossenmaier Birgit
- Boughorbel Sabri
- Boyer Jean
- Bramante Simona
- Branstetter Daniel
- Brech Dorothee
- Brenin David
- Broaddus V. C
- Brockstedt Dirk G
- Brockstedt Dirk G
- Brody Joshua
- Bronson Roderick
- Brooks Alan
- Brooks Alan D
- Broucek Joseph
- Brown Alice
- Brown Brian
- Brown Brittany
- Brown Gail L
- Brown Sheila
- Bruce Jeffrey N
- Brunet Laura R
- Bruno Tullia C
- Bryan Jennifer
- Bryant Richard
- Buchbinder Elizabeth
- Bucsek Mark
- Budhu Sadna
- Budhu Sadna
- Budkowska Marta
- Bueno Raphael
- Buettner Florian
- Buettner Nico
- Bullock Kim
- Bullock Kim
- Burova Elena
- Burrill Joel
- Bussler Holm
- Butterfield Lisa H
- Butterfield Lisa H
- Byrne-Steele Miranda
- Cagney Daniel
- Calderon Hugo
- Callahan Margaret K
- Campesato Luis F
- Campogan Dwayne
- Cao Felicia
- Capasso Cristian
- Capasso Cristian
- Caplazi Patrick
- Cappuccini Federica
- Carcaboso Angel M
- Carlino Matteo S
- Carpi Sara
- Carrasco Ruben
- Carrera Diego A
- Carrero Rosa M S
- Carson Dennis A
- Castellini Laura
- Cathomas Richard
- Cauvin Annick
- Cauwenberghs Sandra
- Caux Christophe
- Cebon Jonathan S
- Ceccarelli Michele
- Celis Esteban
- Cerignoli Fabio
- Cerullo Vincenzo
- Cerullo Vincenzo
- Cervera-Carrascón Víctor
- Cesareni Gianni
- Cha John
- Cha John
- Cha John
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- Chan Chanty
- Chan Ivan
- Chan Leo
- Chan Timothy A
- Chang Alfred E
- Chang Alfred E
- Chang Joe
- Chang Nancy N
- Chang Thomas
- Chanuc Fabien
- Chapelin Fanny
- Chaplin Jenny
- Chappel Scott C
- Charych Deborah H
- Charych Deborah H
- Chaudhuri Amitabha
- Chaussabel Damien
- Chen Ada
- Chen Ada
- Chen Gang
- Chen Jason
- Chen Jason
- Chen Xiaomu
- Chen Xin
- Chen Xiufen
- Chen Yu
- Chen Yu
- Chenchik Alex
- Chheda Zinal
- Chiang Eugene
- Chikina Maria
- Chittenden Thomas
- Chiu Hsiling
- Cho Charles
- Chongyung Fang
- Chou Margaret
- Choueiri Toni K
- Choy Carmen
- Clark Joseph I
- Clavijo Paul E
- Clifton Guy T
- Clynes Raphael
- Cobbold Mark
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- Coder Brandon
- Coffman Robert L
- Cohen Cyrille
- Cohen Ezra E W
- Cohen Roger
- Colen Rivka
- Colevas A. D
- Collins Natalie
- Colrain Jillian
- Coltharp Carla
- Concha-Benavente Fernando
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- Conwell Darwin
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- Corrales Leticia P
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- Coukos George
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- Coussens Lisa M
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- Craggs Graham
- Craig Andrew
- Crittenden Marka
- Cron Kyle R
- Cronstein Bruce N
- Crooks James
- Crosby Andrea
- Crosignani Stefano
- Crowder Robert
- Cruickshank Scott
- Csuka Orsolya
- Curbishley Stuart
- Curiel Tyler
- Curran Emily
- Curran Michael
- Curti Brendan
- Curti Brendan
- Da Costa Andre
- Dai Fu
- Dai Jie
- Dai Peihong
- Dalgleish Angus
- Dalvie Deepak
- Daniels Gregory A
- Daud Adil
- David Justin M
- Davies Bronwyn
- de Boisferon Marc H
- de Groot Patricia
- de Gruijl Tanja
- De Henau Olivier
- de Leon Laura
- De Maeseneire Coraline
- De Sanctis Francesco
- de Silva Suresh
- Deacon Donna
- Deacon Donna H
- DeBenedette Mark
- DeBenedette Mark
- Declerck Paul
- Decock Julie
- Decock Julie
- DeFalco Jeff
- Dela Cruz Filemon
- Delgoffe Greg
- Delgoffe Greg M
- Delgoffe Greg M
- Delgoffe Greg M
- Delogu Lucia
- Delorenzi Mauro
- Demaria Sandra
- Demaria Sandra
- Deng Liang
- Deng Weiwen
- Deng Wentao
- Denies Sofie
- Denis Caroline
- Desbien Anthony L
- deVries Michele
- Dhupkar Pooja
- Diab Adi
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- Dimberg Anna
- Ding Yueyun
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- Dobkin Julie
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- Dolegowska Barbara
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- Doman Thompson
- Dominguez George
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- Dubensky Thomas W
- Dudimah Duafalia
- Duff Susan
- Dumontet Charles
- Dunai Cordelia
- Dunai Cordelia
- Dutcher Janice P
- Duttagupta Priyanka
- Duvvuri Uma
- Dyson Mike
- D’Apuzzo Massimo
- Ebner Peggy
- Edwards Robert
- Edwards Robert P
- Edwards Robert P
- Eickhoff Jens
- Eisenhower Mary
- El Alaoui Meddy
- El Alaoui Said
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- Emerling Daniel
- Eng Charis
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- English Jessie
- Enstrom Amanda
- Eremeev Artem
- Eriksson Emma
- Eriksson Emma
- Eriksson Emma
- Ertelt Kathleen
- Eswarappa Rajesh
- Evans Elizabeth
- Evans Kathy
- Facciabene Andrea
- Facciabene Andrea
- Facciabene Andrea
- Facciponte John
- Facciponte John
- Falchook Gerald
- Fantini Massimo
- Fantini Massimo
- Fantini Massimo
- Farkas Emil
- Farren Matthew
- Faustman Denise
- Fa’ak Faisal
- Fa’ak Faisal
- Femel Julia
- Feng JunLi
- Feng Yan
- Feng Zipei
- Feola Sara
- Fernandez Christian
- Fernando Ingrid
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- Fesenkova Valentyna
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- Foster Rosemary
- Fotin-Mleczek Mariola
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- Francica Brian
- Francis Julie-Ann
- Frangou Costa
- Franklin Marilyn
- Franklin Wilbur
- Frascaro Federica
- Fraser Kathryn
- Frederix Kim
- Freimark Bruce
- Freimark Bruce
- Freimark Bruce
- Frey Alan
- Fridman Leticia
- Friedman Alan
- Friedman David
- Fromm George
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- Fu Yichun
- Fu Yichun
- Fuertes Marraco Silvia A
- Fugle Caroline W
- Fuhrmann Steven
- Fukaya Satoshi
- Fulton Noreen
- Fuoco Claudia
- Fusciello Manlio
- Fuseri Nicolas
- Gabitzsch Elizabeth
- Gabrail Nashat
- Gabrilovich Dmitry
- Gajewski Thomas
- Gajewski Thomas F
- Gajewski Thomas F
- Gajewski Thomas F
- Gajewski Thomas F
- Gajewski Thomas F
- Gajewski Thomas F
- Galeassi Nadejda
- Gamble Alicia
- Gamble Alicia
- Gameiro Sofia
- Gameiro Sofia R
- Gandhi Anita
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- Gardai Shyra J
- Gardner Kellie
- Gartrell Robyn
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- Gasmi Billel
- Gastineau Dennis A
- Gaughan Elizabeth
- Gauthier Audrey
- Gauthier Kelsey S
- Geissler Michael
- Gergel Ivan
- Geukens Nick
- Gfeller David
- Ghadially Hormas
- Ghamsari Lila
- Ghandi Leena
- Ghisoli Maurizio
- Giaccia Amato
- Gibney Geoffrey
- Giffin Louise
- Gillies Stephen D
- Giri Sanjeev
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- Glickman Laura H
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- Godwin John
- Gomes Bruno
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- Gooding William
- Gooding William
- Goodman Reid
- Gopal Ajay
- Gordon Keith
- Gordon Nancy
- Gottschalk Stephen
- Gough Michael
- Gowda Nagaraj
- Goyal Sharad
- Graff Jeremy
- Graham Charles
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- Greenberg Norman
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- Griesinger Frank
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- Grose Mark
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- Grossenbacher Steven K
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- Karpathy Roberta
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- Kohlhapp Frederick
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- Kraus Manfred
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- Krishnan Monica
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- Lazo Suzan
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- Lemmens Edward E
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- Lepone Lauren
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- Leshem Jasmin
- Lesinski Gregory B
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- Lessey-Morillon Elizabeth
- Letai Anthony
- Letellier Marie-Claire
- Levy Laurent
- Levy Ronald
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- Li Jin
- Li Qiao
- Li Qiao
- Li Weiqun
- Li Wenlin
- Li Yanxia
- Li Yanyun
- Li Yanyun
- Li Zihai
- Liang Xiaoling
- Lieber Andre
- Lifke Alexander
- Lifke Valeria
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- Lipson Evan
- Liszkay Gabriella
- Litton Jennifer
- Liu Bei
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- Liu Glenn
- Liu Hao
- Liu Hongtao
- Liu Linying
- Liu Matt
- Liu Shouchun
- Liu Shouchun
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- Liu Weiqun
- Liu Xiu-fen
- Liu Yuan
- Liu Zhuqing
- Liu Zhuqing
- Lo Kin-Ming
- Loibner Hans
- Long Georgina V
- Longo Dan
- Loriaux Marc
- Loskog Angelica
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- Lossos Izidore S
- Lowe David
- Loya Matthew
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- Lu Shanhong
- Lu Shanhong
- Lu Yan
- Lu Yan
- Lu Yan
- Ludwig Dale
- Ludwug Thomas
- Luke Jason
- Lum Lawrence G
- Lund Amanda W
- Lundberg Kristina
- Lykov Maxim
- López Fernando
- MacDonald Andrew
- MacDonald Cameron
- MacDonald Douglas
- Mace Thomas
- Mace Thomas
- Mace Thomas
- MacKinnon Andy
- MacKinnon Andy
- Maegley Karen
- Magee Michael S
- Magnani John L
- Makarov Vladimir
- Makhanov Michael
- Makhijani Neil
- Makkouk Amani
- Malaker Stacy A
- Malaker Stacy A
- Mallon Zach
- Mallow Crystal
- Malnassy Gregory
- Mandloi Nitin
- Mangin Eric
- Mangrolia Drishty
- Manguso Robert
- Manieri Nicholas
- Manning Luisa
- Manning-Bog Amy
- Manoharan Malini
- Manro Jason
- Mansfield David
- Marabelle Aurelien
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- Marelli Bo
- Marguier Gisele
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- Maric Dragan
- Marillier Reece
- Marincola Francesco
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- Marks Douglas
- Marron Thomas U
- Marshall Netonia
- Martin Allison
- Martins Beatriz
- Mason Sean
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- Xu Chunxiao
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- Yadav Mahesh
- Yagiz Kader
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- Yan Jian
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- Yao Shiyin
- Ye Yun-bin
- Yin Catherine
- Ylösmäki Erkko
- Ylösmäki Erkko
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- Young Kristina
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- Young Steve W
- Young Steve W
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- Yu Huakui
- Yu Ling
- Yu Naichen
- Zafar Sadia
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zalevsky Jonathan
- Zappasodi Roberta
- Zappasodi Roberta
- Zauderer Maurice
- Zeh Herbert
- Zelenetz Andrew D
- Zeng Weiping
- Zeng Xue
- Zha Yuanyuan
- Zhang Danhui
- Zhang Jing
- Zhang Ping
- Zhang Qifang
- Zhang Shannon S
- Zhang Theresa
- Zhang Winter
- Zhang Yanping
- Zhao Fei
- Zhao Leyna
- Zhao Xingli
- Zheng Lianxing
- Zheng Wenxin
- Zheng Xianxian
- Zheng Yi
- Zhong Hong
- Zhou Li
- Zhou Xiangjun
- Zippelius Alfred
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zloza Andrew
- Zou Jun
- Zuba-Surma Ewa
- Zubkova Olga
- Zureikat Amer
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2016
- Field of study
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.
- Author
- Ahmed Munaza
- Aitken Stuart
- Aitman Timothy
- Akawi Nadia
- Al Turki Saeed
- Alachkar Hana
- Ali Sonia
- Allen Hana Lango
- Allen Louise
- Allsup David
- Alvi Mohsan
- Ambegaonkar Gautum
- Ambridge Kirsty
- Anderson Carl
- Anderson Julie
- Anjum Uruj
- Anney Richard
- Antony Dinu
- Antrobus Richard
- Archer Hayley
- Armstrong Ruth
- Armstrong Ruth
- Arno Gavin
- Artigas Maria Soler
- Arumugakani Gururaj
- Ashford Sofie
- Astle William
- Attwood Antony
- Austin Steve
- Awada Jana
- Ayub Muhammad
- Bacchelli Chiara
- Bakchoul Tamam
- Balasubramaniam Senduran
- Balasubramanian Meena
- Banka Siddharth
- Baralle Diana
- Bariana Tadbir K.
- Barnicoat Angela
- Barrett Daniel M.
- Barrett Jeffrey C.
- Barrett Jeffrey C.
- Barroso Inês
- Batstone Paul
- Baty David
- Baxendale Helen
- Bayzetinova Tanya
- Beales Phil
- Bennett Chris
- Bennett David
- Bentham Jamie
- Berg Jonathan
- Bernhard Birgitta
- Bethune Claire
- Bevan A. Paul
- Bhattacharya Shoumo
- Bibi Shahnaz
- Birney Ewan
- Bitner-Glindzicz Maria
- Bitner-Glindzicz Maria
- Blackwood Douglas
- Blair Edward
- Bleda Marta
- Blyth Moira
- Bobrow Martin
- Bochukova Elena
- Boggard Harm
- Bohanna David
- Bolton Patrick
- Bolton-Maggs Paula
- Booth Claire
- Bounds Rebecca
- Bourdon Louise
- Bourn David
- Boustred Chris
- Bradley John R.
- Bradley Lisa
- Brady Angela
- Brady Angie
- Breen Gerome
- Brent Simon
- Brewer Carole
- Brown Matthew
- Browning Michael
- Brunstrom Kate
- Bryant Emily
- Bryson Christine
- Bunyan David J.
- Burn John
- Burns Siobhan
- Calissano Mattia
- Calleja Paul
- Canham Natalie
- Canham Natalie
- Carmichael Jenny
- Carss Keren
- Carss Keren
- Carss Keren J.
- Carvill Gemma L.
- Castle Bruce
- Caulfield Mark
- Chalmers Elizabeth
- Chandler Kate
- Chandra Anita
- Chatterjee Krishna
- Chatzimichali Elena
- Chen Lu
- Chinnery Patrick
- Chitre Manali
- Church Colin
- Ciampi Antonio
- Cilliers Deirdre
- Cirak Sebhattin
- Clapham Peter
- Clarke Angus
- Clasper Susan
- Clayton Stephen
- Clayton-Smith Jill
- Clayton-Smith Jill
- Clement Emma
- Clement Gail
- Clements-Brod Naomi
- Clowes Virginia
- Clowes Virginia
- Coates Andrea
- Coates Guy
- Coghlan Gerry
- Cole Trevor
- Colgiu Irina
- Collier David
- Collins Amanda
- Collins Peter
- Collinson Morag N.
- Connell Fiona
- Cooper Nichola
- Cooper Nicola
- Cosgrove Catherine
- Cox Helen
- Cox Tony
- Craddock Nick
- Creaser-Myers Amanda
- Cresswell Lara
- Crooks Lucy
- Cross Gareth
- Cross J. Helen
- Crow Yanick
- Curran Sarah
- Curtis David
- D?Alessandro Mariella
- Dabir Tabib
- DaCosta Rosa
- Daly Allan
- Daugherty Louise
- Davidson Rosemarie
- Davies Sally
- Davies Sophie
- Davis John
- Day Ian N.M.
- Day-Williams Aaron
- de Vries Dylan
- De Vries Minka
- Dean John
- Debelle Geoff D.
- Deegan Patrick
- Deevi Sri V.V.
- Deshpande Charu
- Deshpande Charu
- Devlin Gemma
- Devlin Lisa
- Dewhurst Eleanor
- Dixit Abhijit
- Dobbie Angus
- Doffinger Rainer
- Donaldson Alan
- Donnai Dian
- Donnelly Carina
- Donnelly Deirdre
- Dormand Natalie
- Douglas Angela
- Douzgou Sofia
- Down Thomas
- Drewe Elizabeth
- Du Yuanping
- Duncan Alexis
- Dunham Ian
- Eason Jacqueline
- Edgar David
- Edkins Sarah
- Egner William
- Ellard Sian
- Ellis Ian
- Ellis Peter
- Elmslie Frances
- Erber Wendy N.
- Erwood Marie
- Evans David
- Evans Karenza
- Everest Sarah
- Everington Tamara
- Faroogi Sadaf
- Fatemifar Ghazaleh
- Favier Remi
- Fendick Tina
- Firth Helen
- Firth Helen V.
- Fisher Richard
- Fitzgerald Tomas W.
- FitzPatrick David R.
- Fitzpatrick David R.
- Fletcher Debra
- Flicek Paul
- Flinter Frances
- Flinter Frances
- Flyod James
- Foley A. Reghan
- Foulds Nicola
- Fox James C.
- Franklin Christopher S.
- Frary Amy
- Freson Kathleen
- Fry Andrew
- Fryer Alan
- Furie Bruce
- Furnell Abigail
- Futema Marta
- Gale Daniel
- Gallagher Louise
- Gardham Alice
- Gardiner Carol
- Gattens Michael
- Gaunt Lorraine
- Geihs Matthias
- Geschwind Daniel
- Ghali Neeti
- Ghali Neeti
- Ghataorhe Pavandeep K.
- Ghurye Rohit
- Gibbons Richard
- Gibbs Simon
- Gill Harinder
- Gilmour Kimberley
- Gissen Paul
- Goddard Sarah
- Gomez Keith
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- Gorman Kathleen M.
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- Kumar V. K. Ajith
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- Kurian Manju A.
- Lachance Genevieve
- Lachlan Katherine
- Laffan Michael A.
- Lam Wayne
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- Tachmazidou Ionna
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- Vandersteen Anthony
- Varghese Vinod
- Vasudevan Pradeep
- Veltman Marijke
- Vijayarangakannan Parthiban
- Vijayarangakannan Parthiban
- Visscher Peter M.
- Vogt Julie
- Vogt Julie
- von Ziegenweldt Julie
- Vonk Noordegraaf Anton
- Wain Louise V.
- Wakeling Emma
- Wakeling Emma
- Wallwark Sarah
- Walters James T.R.
- Wang Guangbiao
- Wang Jun
- Wang Yu
- Wanjiku Ivy
- Ward Kirsten
- Warner Timothy Q.
- Wassmer Evangeline
- Wassmer Evangeline
- Waters Jonathon
- Watkins Hugh
- Weber Astrid
- Webster Andrew
- Welch Steve
- Wellesley Diana
- Westbury Sarah
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- Wheeler Elanor
- Whiteford Margo
- Whitehorn Deborah
- Whyte Tamieka
- Widaa Sara
- Wilcox Sarah
- Wilkins Martin
- Wilkinson Emily
- Willcocks Lisa
- Williams Denise
- Williams Hywel
- Williams Nicola
- Williamson Catherine
- Williamson Kathleen A.
- Wilson Crispian
- Wilson Louise
- Wong Kim
- Woods Geoff
- Woods Geoffrey
- Wort John
- Wragg Christopher
- Wright Caroline F.
- Wright Michael
- Xu ChangJiang
- Yang Jian
- Yates Laura
- Yau Michael
- Yeatman Nigel
- Yong Patrick
- Young Tim
- Yu Ping
- Zhang Fend
- Zhang Pingbo
- Publication venue
- AJHG
- Publication date
- 01/01/2019
- Field of study
The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)
Active and Inactive Urinary Kallikrein in Man: Effects of Diuresis and Antidiuresis
- Publication venue
- 'Portland Press Ltd.'
- Publication date
- Field of study