Institution
University of Dundee
Education•Dundee, United Kingdom•
About: University of Dundee is a education organization based out in Dundee, United Kingdom. It is known for research contribution in the topics: Population & Protein kinase A. The organization has 19258 authors who have published 39640 publications receiving 1919433 citations. The organization is also known as: Universitas Dundensis & Dundee University.
Papers published on a yearly basis
Papers
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University of Dundee1, Texas Biomedical Research Institute2, Wellcome Trust Centre for Human Genetics3, National Institute for Health Research4, University of Oxford5, South London and Maudsley NHS Foundation Trust6, King's College London7, Princess Alexandra Hospital8, University of Queensland9, University College London10, University of London11, Trinity College, Dublin12, Cardiff University13, Wellcome Trust14, Wellcome Trust Sanger Institute15, Queen Mary University of London16, Leicester Royal Infirmary17, St George's, University of London18, University of Cambridge19, University of Leicester20, Glenfield Hospital21, University of Edinburgh22, Peninsula College of Medicine and Dentistry23, University of Exeter24, Ninewells Hospital25
TL;DR: It is concluded that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to meetformin.
Abstract: Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 × 10(-9), odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin.
362 citations
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TL;DR: It is reported that HSP27 like alphaB-crystallin is associated with glial fibrillary acidic protein and vimentin intermediate filament networks in unstressed U373MG astrocytoma cells, suggesting that one of the major functions of the association of small heat shock proteins with intermediate filaments is to help manage the interactions that occur between filaments in their cellular networks.
Abstract: HSP27 and alphaB-crystallin are both members of the small heat shock protein family. alphaB-crystalllin has been proposed to modulate intermediate filaments and recently a mutation in alphaB-crystallin has been identified as the genetic basis of desmin related myopathy. This disease is characterised in its pathology by aggregates of intermediate filaments associated with alphaB-crystallin. Here we report that HSP27 like alphaB-crystallin is associated with glial fibrillary acidic protein and vimentin intermediate filament networks in unstressed U373MG astrocytoma cells. HSP27 is also associated with keratin filaments in MCF7 cells, indicating that this association is not restricted to a particular intermediate filament type. The association of sHSPs with both the soluble and filamentous intermediate filament fractions of U373 cells was demonstrated biochemically. Heat shock or drug treatments induced a co-collapse of intermediate filaments and associated small heat shock proteins. These data show that the presence of HSP27 or alphaB-crystallin could not prevent filament collapse and suggest that the purpose of this association is more than just filament binding. Indeed, in U373MG cells the intermediate filament association with small heat shock proteins is similar to that observed for another protein chaperone, HSC70. In order to discern the effect of different chaperone classes on intermediate filament network formation and maintenance, several in vitro assays were assessed. Of these, falling ball viscometry revealed a specific activity of small heat shock proteins compared to HSC70 that was apparently inactive in this assay. Intermediate filaments form a gel in the absence of small heat shock proteins. In contrast, inclusion of alphaB-crystallin or HSP27 prevented gel formation but not filament assembly. The transient transfection of GFAP into MCF7 cells was used to show that the induction of a completely separate network of intermediate filaments resulted in the specific association of the endogenous HSP27 with these new GFAP filaments. These data lead us to propose that one of the major functions of the association of small heat shock proteins with intermediate filaments is to help manage the interactions that occur between filaments in their cellular networks. This is achieved by protecting filaments against those non-covalent interactions that result when they come into very close proximity as seen from the viscosity experiments and which have the potential to induce intermediate filament aggregation as seen in some disease pathologies.
362 citations
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TL;DR: The cornea demonstrates considerable stiffening with age with the behavior closely fitting an exponential power function typical of collagenous tissue.
Abstract: Purpose: The aim of this study was to determine the stress-strain behavior of corneal tissue and how the behavior was affected by age. Methods: Human corneal specimens ranging in age between 50 and 95 years were tested under inflation conditions to determine their stress-strain behavior. The corneas were subjected to two load rates that represent dynamic and static loading conditions. The pressure-deformation results were analyzed using shell theory to derive the stress-strain behavior. Results: The corneas demonstrated clear nonlinear behavior with an initial low stiffness stage and a final high stiffness stage. The transition between the two stages coincided with intraocular pressures between 12 and 20 mmHg. There was a considerable increase in stiffness associated with both age and load rate. Equations were derived to describe the nonlinear stress-strain relationship of corneal tissue for any age between 50 and 95 years, and these equations are presented in a form suitable for use in numerical simulati...
362 citations
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TL;DR: In this paper, the characteristics of an insulated-gate field effect transistor made from amorphous silicon (a-Si) deposited in a glow discharge are discussed, and it is suggested that the a-Si device could be applied with advantage in an addressable matrix of a liquid-crystal display panel.
Abstract: The characteristics of an insulated-gate field-effect transistor made from amorphous silicon (a-Si) deposited in a glow discharge are discussed. It is suggested that the a-Si device could be applied with advantage in an addressable matrix of a liquid-crystal display panel.
362 citations
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TL;DR: 2A functions in all the eukaryotic systems tested to date and has already been applied, with great success, to a broad range of biotechnological applications: from plant metabolome engineering to the expression of T-cell receptor complexes, monoclonal antibodies or heterodimeric cytokines in animals.
362 citations
Authors
Showing all 19404 results
Name | H-index | Papers | Citations |
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Matthias Mann | 221 | 887 | 230213 |
Mark I. McCarthy | 200 | 1028 | 187898 |
Stefan Schreiber | 178 | 1233 | 138528 |
Kenneth C. Anderson | 178 | 1138 | 126072 |
Masayuki Yamamoto | 171 | 1576 | 123028 |
Salvador Moncada | 164 | 495 | 138030 |
Jorge E. Cortes | 163 | 2784 | 124154 |
Andrew P. McMahon | 162 | 415 | 90650 |
Philip Cohen | 154 | 555 | 110856 |
Dirk Inzé | 149 | 647 | 74468 |
Andrew T. Hattersley | 146 | 768 | 106949 |
Antonio Lanzavecchia | 145 | 408 | 100065 |
Kim Nasmyth | 142 | 294 | 59231 |
David Price | 138 | 1687 | 93535 |
Dario R. Alessi | 136 | 354 | 74753 |