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Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors

Overview of attention for article published in Chemistry Central Journal, December 2011
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • Good Attention Score compared to outputs of the same age and source (75th percentile)

Mentioned by

blogs
1 blog
twitter
1 tweeter

Citations

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8 Dimensions

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5 Mendeley
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Title
Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors
Published in
Chemistry Central Journal, December 2011
DOI 10.1186/1752-153x-5-83
Pubmed ID
Authors

Terence Davis, Matthew C Dix, Michal J Rokicki, Amy JC Brook, Caroline S Widdowson, David Kipling, Mark C Bagley

Abstract

Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. However, interpretation of these data is problematical because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its preferred targets, it does show relatively low overall kinase selectivity. Several lines of data support a role for both p38 and JNK1/2 activation in the control of cellular proliferation and also the pathology of diseases of ageing, including type II diabetes, diseases to which Werner Syndrome individuals are prone, thus making the use of JNK inhibitors attractive as possible therapeutics. We have thus tested the effects of the widely used JNK inhibitor SP600125 on the proliferation and morphology of WS cells. In addition we synthesised and tested two recently described aminopyridine based inhibitors. SP600125 treatment resulted in the cessation of proliferation of WS cells and resulted in a senescent-like cellular phenotype that does not appear to be related to the inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD 6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular proliferation of immortalised WS cells, but no effect on the replicative lifespan of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially explain its effects on WS cells, since MK2 is known to be involved in regulating cellular morphology via HSP27 phosphorylation, and is thought to play a role in cell cycle arrest. These data suggest that total JNK1/2 activity does not play a substantial role in the proliferation control in WS cells.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 40%
Professor > Associate Professor 1 20%
Researcher 1 20%
Student > Postgraduate 1 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 2 40%
Chemistry 2 40%
Immunology and Microbiology 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 January 2012.
All research outputs
#1,807,249
of 12,429,455 outputs
Outputs from Chemistry Central Journal
#82
of 569 outputs
Outputs of similar age
#29,522
of 217,864 outputs
Outputs of similar age from Chemistry Central Journal
#18
of 90 outputs
Altmetric has tracked 12,429,455 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 569 research outputs from this source. They receive a mean Attention Score of 3.8. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 217,864 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 90 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.