Biomedical subjects

James Hartley

Publications and source records attributed to James Hartley.

5 recordsLinked to original sources

PubMed2005

Cardiac glycosides inhibit TNF-alpha/NF-kappaB signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor.

Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-alpha/NF-kappaB signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-alpha-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-kappaB and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event.

Blotting, Western↗

PubMed2005

Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic.

Preferential binding of ligands to Grb2 SH2 domains in beta-bend conformations has made peptide cyclization a logical means of effecting affinity enhancement. This is based on the concept that constraint of open-chain sequences to bend geometries may reduce entropy penalties of binding. The current study extends this approach by undertaking ring-closing metathesis (RCM) macrocyclization between i and i+3 residues through a process involving allylglycines and beta-vinyl-functionalized residues. Ring closure in this fashion results in minimal macrocyclic tetrapeptide mimetics. The predominant effects of such macrocyclization on Grb2 SH2 domain binding affinity were increases in rates of association (from 7- to 16-fold) relative to an open-chain congener, while decreases in dissociation rates were less pronounced (approximately 2-fold). The significant increases in association rates were consistent with pre-ordering of solution conformations to near those required for binding. Data from NMR experiments and molecular modeling simulations were used to interpret the binding results. An understanding of the conformational consequences of such i to i+3 ring closure may facilitate its application to other systems where bend geometries are desired.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Current findings from research on structured abstracts.

BACKGROUND: Structured abstracts were introduced into medical research journals in the mid 1980s. Since then they have been widely used in this and other contexts. AIM: The aim of this paper is to summarize the main findings from research on structured abstracts and to discuss the limitations of some aspects of this research. METHOD: A narrative literature review of all of the relevant papers known to the author was conducted. RESULTS: Structured abstracts are typically longer than traditional ones, but they are also judged to be more informative and accessible. Authors and readers also judge them to be more useful than traditional abstracts. However, not all studies use "real-life" published examples from different authors in their work, and more work needs to be done in some cases. CONCLUSIONS: The findings generally support the notion that structured abstracts can be profitably introduced into research journals. Some arguments for this, however, have more research support than others.

Abstracting and Indexing↗

PubMed2004

Down with "op. cit.".

Explore the source record for details and available documents.

Abstracting and Indexing↗

PubMed2002

Style and substance in psychology: are influential articles more readable than less influential ones?

The results from four studies are reported separately to test the idea that influential articles in psychology will be more readable than less influential ones. This idea is upheld when the papers involved are ones that have been highly rated by fellow colleagues (Studies 1 and 2) but it is not supported when the papers involved are highly-cited journal articles (Studies 3 and 4).

History, 20th Century↗