Biomedical subjects

Richard Pearson

Publications and source records attributed to Richard Pearson.

3 recordsLinked to original sources

PubMed2006

Recruitment of TFIIH to the HIV LTR is a rate-limiting step in the emergence of HIV from latency.

Latently infected cells rapidly initiate HIV transcription after exposure to signals that induce NF-kappaB. To investigate the role of TFIIH during HIV reactivation in vivo, we developed a population of Jurkat cells containing integrated, but transcriptionally silent, HIV proviruses. Surprisingly, the HIV promoter in unactivated Jurkat T cells is partially occupied and carries Mediator containing the CDK8 repressive module, TFIID and RNAP II that is hypophosphorylated and confined to the promoter region. Significantly, the promoter is devoid of TFIIH. Upon stimulation of the cells by TNF-alpha, NF-kappaB and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost. Detailed time courses show that the levels of TFIIH at the promoter fluctuate in parallel with NF-kappaB recruitment to the promoter. Similarly, recombinant p65 activates HIV transcription in vitro and stimulates phosphorylation of the RNAP II CTD by the CDK7 kinase module of TFIIH. We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency.

Gene Expression Regulation, Viral↗

PubMed2005

Expression of stress response protein glucose regulated protein-78 mediated by c-Myb.

Glucose regulated protein-78, GRP78 has been implicated in the protection of tumor cells from cytotoxic damage and apoptosis. When protein profiles of colon cell lines were investigated we found remarkably high GRP78 expression in two cell lines. These cell lines express elevated levels of the transcription factor c-Myb due to genomic amplification of the c-myb locus and we hypothesized that c-Myb regulates GRP78 expression in colon cancer cells. The promoters of human and murine GRP78 and the related family member GRP94 were examined and potential c-Myb binding sites were identified and characterized. DNA binding studies with recombinant c-Myb and nuclear extracts together with ChIP assays on colon cell lines validated these sites. Endogenous GRP78 expression was further induced in these colon cells in response to Thapsigargin treatment, a potent inducer of the unfolded protein response. Transactivation studies with the human GRP78 promoter in colon cell lines showed reporter activity was dependent upon the presence of a conserved c-Myb binding site independent of sequences associated with the unfolded protein response. Finally, over-expression of c-Myb induced the endogenous GRP78 gene. These data suggest that amplification of c-myb in tumor cells may lead to robust GRP78 gene induction, which may in turn assist cells in survival under conditions of oxygen deprivation and nutrient stress.

Amino Acid Sequence↗

PubMed2004

Recruiting and developing an effective workforce in the British NHS.

The British NHS faces major challenges recruiting, motivating and retaining staff in a period of sustained growth and change. This paper examines the prevalence of skill shortages and organisations' coping strategies, as well the factors that motivate staff in the workplace and in the NHS in particular. It argues that the evidence base for informed policy-making needs radical improvement. It then considers a number of approaches to pay that are being used or suggested to attract, motivate and retain staff. These include performance pay, team pay and local pay determination, as well as considering broader factors such as morale and staff development. The paper then draws together some conclusions for policy-makers. These argue that better evidence is needed as to what is happening in the public sector labour market in order to frame appropriate responses and that thorough evaluation of policy initiatives is necessary to establish their utility before their widespread implementation.

Employment↗