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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TL;DR: Signaling by protein kinase B to Forkhead proteins can account for the ability of insulin to regulate glucose-6-phosphatase promoter activity via the IRU and that other mechanisms that are independent of the IRUs also are important in mediating effects of in insulin on glucose- 6-ph phosphatase gene expression.
346 citations
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TL;DR: It is reported that the p38 MAPK pathway is required for normal skeletogenesis in mice, and an in vivo function for p38beta is revealed and it is established that MAPK signaling is essential for bone formation in vivo.
Abstract: Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member–encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteoblast differentiation. Among the MAPK kinase kinase (MAP3K) family, we identified TGF-β–activated kinase 1 (TAK1; also known as MAP3K7) as the critical activator upstream of p38 in osteoblasts. Osteoblast-specific deletion of Tak1 resulted in clavicular hypoplasia and delayed fontanelle fusion, a phenotype similar to the cleidocranial dysplasia observed in humans haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2). Mechanistic analysis revealed that the TAK1–MKK3/6–p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38β and establish that MAPK signaling is essential for bone formation in vivo. These results also suggest that selective p38β agonists may represent attractive therapeutic agents to prevent bone loss associated with osteoporosis and aging.
345 citations
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TL;DR: It is shown that AMPK directly phosphorylates eEF2 kinase, and the major site of phosphorylation as Ser-398 in a regulatory domain of eEF1 kinase is identified, which may provide a key link between cellular energy status and the inhibition of protein synthesis, a major consumer of metabolic energy.
345 citations
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TL;DR: Two types of mathematical model are presented which describe the invasion of host tissue by tumour cells and one of them enables one to model migration and invasion at the level of individual cells and hence it is possible to examine the implications of metastatic spread.
Abstract: In this paper we present two types of mathematical model which describe the invasion of host tissue by tumour cells. In the models, we focus on three key variables implicated in the invasion process, namely, tumour cells, host tissue (extracellular matrix) and matrix-degradative enzymes associated with the tumour cells. The first model focusses on the macro-scale structure (cell population level) and considers the tumour as a single mass. The mathematical model consists of a system of partial differential equations describing the production and/or activation of degradative enzymes by the tumour cells, the degradation of the matrix and the migratory response of the tumour cells. Numerical simulations are presented in one and two space dimensions and compared qualitatively with experimental and clinical observations. The second type of model focusses on the micro-scale (individual cell) level and uses a discrete technique developed in previous models of angiogenesis. This technique enables one to model migration and invasion at the level of individual cells and hence it is possible to examine the implications of metastatic spread. Finally, the results of the models are compared with actual clinical observations and the implications of the model for improved surgical treatment of patients are considered.
344 citations
Authors
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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 |