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Institution

Medical Research Council

GovernmentLondon, United Kingdom
About: Medical Research Council is a government organization based out in London, United Kingdom. It is known for research contribution in the topics: Population & Malaria. The organization has 16430 authors who have published 19150 publications receiving 1475494 citations.


Papers
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Journal ArticleDOI
TL;DR: Pivotal roles for Met in development and cancer have been established: Met controls cell migration and growth in embryogenesis; it also controls growth, invasion and metastasis in cancer cells; and activating Met mutations predispose to human cancer.
Abstract: Hepatocyte growth factor/scatter factor and its receptor, the tyrosine kinase Met, arose late in evolution and are unique to vertebrates In spite of this, Met uses molecules such as Gab1 — homologues of which are present in Caenorhabditis elegans and Drosophila melanogaster — for downstream signalling Pivotal roles for Met in development and cancer have been established: Met controls cell migration and growth in embryogenesis; it also controls growth, invasion and metastasis in cancer cells; and activating Met mutations predispose to human cancer

2,468 citations

Journal ArticleDOI
21 Mar 2008-Science
TL;DR: The evidence suggests a pathophysiological link between TDP-43 and ALS, and neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.

2,425 citations

Journal ArticleDOI
27 Feb 2009-Science
TL;DR: A missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6, is identified, which suggests that a common mechanism may underlie motor neuron degeneration.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is familial in 10% of cases. We have identified a missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6. In a survey of 197 familial ALS index cases, we identified two further missense mutations in eight families. Postmortem analysis of three cases with FUS mutations showed FUS-immunoreactive cytoplasmic inclusions and predominantly lower motor neuron degeneration. Cellular expression studies revealed aberrant localization of mutant FUS protein. FUS is involved in the regulation of transcription and RNA splicing and transport, and it has functional homology to another ALS gene, TARDBP, which suggests that a common mechanism may underlie motor neuron degeneration.

2,373 citations

Journal ArticleDOI
TL;DR: Approaches used for drug repurposing (also known as drug repositioning) are presented, the challenges faced by the repurpose community are discussed, and innovative ways by which these challenges could be addressed are recommended to help realize the full potential of drugRepurposing.
Abstract: Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.

2,365 citations

Journal ArticleDOI
Eugenia E. Calle1, Clark W. Heath1, R. J. Coates2, Jonathan M. Liff2  +191 moreInstitutions (45)
TL;DR: Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast cancer diagnosed in women using HRT and associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body- mass index.

2,343 citations


Authors

Showing all 16441 results

NameH-indexPapersCitations
Shizuo Akira2611308320561
Trevor W. Robbins2311137164437
Richard A. Flavell2311328205119
George Davey Smith2242540248373
Nicholas J. Wareham2121657204896
Cyrus Cooper2041869206782
Martin White1962038232387
Frank E. Speizer193636135891
Michael Rutter188676151592
Richard Peto183683231434
Terrie E. Moffitt182594150609
Kay-Tee Khaw1741389138782
Chris D. Frith173524130472
Phillip A. Sharp172614117126
Avshalom Caspi170524113583
Network Information
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20236
20229
2021262
2020243
2019231
2018309