42 research outputs found
Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome).
- Author
- C Preudhomme
- Colin G Steward
- Daniela T Pilz
- Dimitra Dafou
- F-Y Tsai
- Fiona C Connell
- Glen Brice
- Ines Martinez-Corral
- M Haugas
- M Khandekar
- Michael A Simpson
- ML Smith
- NP Rodrigues
- P Callier
- Peter Lunt
- Peter S Mortimer
- Pia Ostergaard
- Q Tong
- R Zheng
- Richard C Trembath
- Russell Keenan
- S Mansour
- S-J Zhang
- Sahar Mansour
- Sarah Smithson
- Shirley Hodgson
- Steve Jeffery
- T Pabst
- Taija Makinen
- Tatjana Kilo
- Victoria A Murday
- W-J Song
- Wesley J Woollard
- Publication venue
- NATURE PUBLISHING GROUP
- Publication date
- 01/09/2011
- Field of study
We report an allelic series of eight mutations in GATA2 underlying Emberger syndrome, an autosomal dominant primary lymphedema associated with a predisposition to acute myeloid leukemia. GATA2 is a transcription factor that plays an essential role in gene regulation during vascular development and hematopoietic differentiation. Our findings indicate that haploinsufficiency of GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in this syndrome
Prenatal Activation of Microglia Induces Delayed Impairment of Glutamatergic Synaptic Function
- Author
- A Barria
- A Peters
- A Rao
- A Roumier
- AL Ciaranello
- Alain Bessis
- Anne Roumier
- Antoine Triller
- AS Brown
- B Moghaddam
- Bernhard Baune
- C Hanus
- C Vicario-Abejon
- Catherine Béchade
- D Stellwagen
- DA Lewis
- DM Walsh
- E Tomasello
- E Tomasello
- EC Beattie
- Eleonore Réal
- GM Jonakait
- H Ashdown
- HM Golan
- I Dalmau
- IR Turnbull
- J Paloneva
- JA Hamerman
- Jean-Christophe Poncer
- JH Gilmore
- JJ Angevine
- K Ohmi
- K Takahashi
- L Shi
- L Shi
- M Megias
- N Spruston
- O Ganeshina
- O Ganeshina
- O Steward
- Olivier Pascual
- PH Patterson
- S Lei
- S Nataf
- S Rozen
- SEP Smith
- SH Fatemi
- Shirley Wakselman
- T Kaifu
- T Langmann
- TAGP Consortium
- U Meyer
- V Zujovic
- X Wang
- Publication venue
- Public Library of Science
- Publication date
- Field of study
BACKGROUND: Epidemiological studies have linked maternal infection during pregnancy to later development of neuropsychiatric disorders in the offspring. In mice, experimental inflammation during embryonic development impairs behavioral and cognitive performances in adulthood. Synaptic dysfunctions may be at the origin of cognitive impairments, however the link between prenatal inflammation and synaptic defects remains to be established. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that prenatal alteration of microglial function, including inflammation, induces delayed synaptic dysfunction in the adult. DAP12 is a microglial signaling protein expressed around birth, mutations of which in the human induces the Nasu-Hakola disease, characterized by early dementia. We presently report that synaptic excitatory currents in mice bearing a loss-of-function mutation in the DAP12 gene (DAP12(KI) mice) display enhanced relative contribution of AMPA. Furthermore, neurons from DAP12(KI) P0 pups cultured without microglia develop similar synaptic alterations, suggesting that a prenatal dysfunction of microglia may impact synaptic function in the adult. As we observed that DAP12(KI) microglia overexpress genes for IL1beta, IL6 and NOS2, which are inflammatory proteins, we analyzed the impact of a pharmacologically-induced prenatal inflammation on synaptic function. Maternal injection of lipopolysaccharides induced activation of microglia at birth and alteration of glutamatergic synapses in the adult offspring. Finally, neurons cultured from neonates born to inflamed mothers and cultured without microglia also displayed altered neuronal activity. CONCLUSION/SIGNIFICANCE: Our results demonstrate that prenatal inflammation is sufficient to induce synaptic alterations with delay. We propose that these alterations triggered by prenatal activation of microglia provide a cellular basis for the neuropsychiatric defects induced by prenatal inflammation
Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.
- Author
- A Diefenbach
- A Goios
- A Hodgkins
- A Kirby
- AD Ewing
- Adam Frankish
- AG Doran
- AL Rasmussen
- Anne Czechanski
- Anne Ferguson-Smith
- Anthony G. Doran
- B Paten
- B Yalcin
- B Yalcin
- Beiyuan Fu
- Benedict Paten
- Binnaz Yalcin
- C Durrant
- Charles Steward
- Chris J. Lelliott
- Clayton E. Mathews
- Cristina Sisu
- Darren W. Logan
- David J. Adams
- David Thybert
- Dent Earl
- Dirk-Dominik Dolle
- DM Church
- DR Schrider
- Duncan T. Odom
- ED Boyden
- EM Simpson
- ES Lander
- F Bauernfeind
- Fabio C. P. Navarro
- Fengtang Yang
- FY Ideraabdullah
- GA Churchill
- GA Churchill
- GA Taylor
- Glen Threadgold
- GTEx Consortium.
- H Mi
- H Zhang
- I Sastalla
- Ian T. Fiddes
- J Flint
- J Giordano
- J Harrow
- J Lilue
- JA Beck
- JA Weiner
- James Gilbert
- James Torrance
- Jane Loveland
- JE French
- Jennifer Harrow
- Jingtao Lilue
- JL Americo
- JL Levinsohn
- JM Mudge
- Joanna Collins
- Joel Armstrong
- Jonathan Flint
- Jonathan Wood
- JP Hunn
- JT Simpson
- K Boroviak
- Kerstin Howe
- KH Braunewell
- Kim Wong
- KL Svenson
- KM Monroe
- Lars Romoth
- Laura Reinholdt
- LD Shultz
- Leo Goodstadt
- Lesley Shirley
- LL Lanier
- LL Liebenauer
- LR Saraiva
- M Boniotto
- M Li
- M Stanke
- M Stremlau
- Marcela Sjoberg-Herrera
- Mario Stanke
- Mark Diekhans
- Mark Gerstein
- Mark Thomas
- Matt Dunn
- ME Dickinson
- Mike Quail
- Mikhail Kolmogorov
- MN Loviglio
- Monica Abrudan
- MT Ferris
- Naomi Park
- NH Putnam
- O Bustos
- O Keller
- P Broz
- Paul Flicek
- Paul Muir
- PD Dummer
- Petr Danecek
- Q Liu
- R Luo
- Richard Durbin
- Richard Mott
- Ruth Bennett
- S König
- Sarah Pelan
- SNP Kelada
- Son K. Pham
- SR Patierno
- Stefanie Nachtweide
- Stephan Collins
- T O’Sullivan
- TA Bell
- Thomas M. Keane
- TM Keane
- WC Skarnes
- William Chow
- Ximena Ibarra-Soria
- Y Cai
- Z Ye
- Z Zhang
- Publication venue
- Nat Genet
- Publication date
- 01/10/2018
- Field of study
We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development
Avant-garde and experimental music
- Author
- Abrahams
- Abrahams
- Abrahams
- Abrams
- Albright
- Aldrich
- Aldrich
- Allen
- Allen
- Alpert
- Altman
- Ammer
- Ancelet
- Anderson
- Anderson
- Appadurai
- Ardoin
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Armstrong
- Arvey
- Astley
- Atkins
- Attali
- Attridge
- Austin
- Averill
- Ayler
- Babbitt
- Babbitt
- Babington
- Babow
- Bachmann-Geiser
- Backus
- Badger
- Bailyn
- Baker
- Baker
- Ballard
- Bandel
- Banfield
- Banfield
- Banfield
- Barbour
- Barrios
- Barzun
- Bayard
- Bechet
- Becker
- Belden
- Benjamin
- Bennett
- Benser
- Benson
- Benson
- Berger
- Bergreen
- Berlin
- Berlin
- Bernard
- Bernstein
- Bernstein
- Billings
- Black Bear
- Blacking
- Blesh
- Blesh
- Bliss
- Block
- Block
- Block
- Block
- Block
- Block
- Bohlman
- Bohlman
- Bohlman
- Bolcom
- Bolcom
- Bolcom
- Bordman
- Bordman
- Bou-Khalil
- Boulez
- Bourassa-Trépanier
- Brackett
- Bradley
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- Burkholder
- Burkholder
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- Ziffrin
- Ziffrin
- Zimmermann
- Zimmermann
- Zwilich
- Publication venue
- 'Cambridge University Press (CUP)'
- Publication date
- 01/01/1998
- Field of study
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
- Abdusamad K.
- Abernethy K.
- Aboelela H.
- Abouzaid M.
- Abraham M.
- Abraham T.
- Abrams J.
- Abu H.
- Abu-Arafeh A.
- Acton C.
- Adam F.
- Adam M.
- Adams C.
- Adams C.
- Adams D.
- Adams L.
- Addo A.
- Adedeji O.
- Adegoke K.
- Adewunmi E.
- Adeyemo T.
- Agbeko R.
- Aggarwal S.
- Ahmad S.
- Ahmed A.
- Ahmed I.
- Ahmed M.
- Ahmed R.
- Ahmed R.
- Ainsworth M.
- Ajmi A.
- Akili S.
- Al Aaraj A.
- Al Balushi A.
- Al-Asadi A.
- Al-Khalil M.
- Al-Ramadhani B.
- Al-Saadi Z.
- Al-Shahi Salman R.
- Al-Sheklly B.
- Albert P.
- Alegria A.
- Alexander A.
- Alexander P.
- Alhabsha O.
- Ali M.
- Ali M.
- Aliberti E.
- Alin J.
- Aliyuda F.
- Alkhudhayri A.
- Allan N.
- Allanson A.
- Allen E.
- Allen L.
- Alshaer I.
- Altaf S.
- Amezaga M.
- Amin A.
- Amit B.
- Anand A.
- Anantapatnaikuni S.
- Anderson L.
- Anderson M.
- Anderson M.
- Anderson N.
- Anderson R.
- Andrews A.
- Ang A.
- Anguvaa L.
- Aniruddhan K.
- Antonina Z.
- Araujo M.
- Archer A.
- Archer S.
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- Publication venue
- Springer Science and Business Media LLC
- Publication date
- 31/01/2024
- Field of study
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
- Author
- Abbas M.
- Abdul Rasheed A.
- Abdul A.
- Abdul-Kadir R.
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- Central Coordinating Office (for the RECOVERY Collaborative Group)
- Century H.
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- Health records (for the RECOVERY Collaborative Group)
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- Publication venue
- Nature Publishing Group
- Publication date
- Field of study
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia
- Author
- Publication venue
- 'American Society of Hematology'
- Publication date
- 17/11/2011
- Field of study
Hydroxyurea has been shown to be efficacious for the treatment of sickle cell anemia (SCA), primarily through the induction of fetal hemoglobin (HbF). However, the exact mechanisms by which hydroxyurea can induce HbF remain incompletely defined, although direct transcriptional effects and altered cell cycle kinetics have been proposed. In this study, we investigated potential epigenetic and alternative molecular mechanisms of hydroxyurea- mediated HbF induction by examining methylation patterns within the Gγ -globin promoter and miRNA expression within primary CD71+ erythrocytes of patients with SCA, both at baseline before beginning hydroxyurea therapy and after reaching maximum tolerated dose (MTD). Using both cross-sectional analysis and paired-sample analysis, we found that the highly methylated Gγ-globin promoter was inversely correlated to baseline HbF levels, but only slightly altered by hydroxyurea treatment. Conversely, expression of several specific miRNAs was significantly increased after hydroxyurea treatment, and expression of miR-26b and miR-151-3p were both associated with HbF levels at MTD. The significant associations identified in these studies suggest that methylation may be important for regulation of baseline HbF, but not after hydroxyurea treatment, whereas changes in miRNAexpression may be associated with hydroxyurea-mediated HbF induction. This study was registered at ClinicalTrials. gov (NCT00305175). © 2011 by The American Society of Hematology
The Roles of LAT in Platelet Signaling Induced by Collagen, TxA2, or ADP
- Author
- Publication venue
- 'Elsevier BV'
- Publication date
- Field of study
Students' Sociological Grouping Preferences of Learning Styles
- Author
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
Prolonged Bleeding Time With Defective Platelet Filopodia Formation in the Wistar Furth Rat
- Author
- Publication venue
- 'American Society of Hematology'
- Publication date
- Field of study