Mutual antagonistic relationship between prostaglandin E(2) and IFN-gamma: Implications for rheumatoid arthritis.

Prostaglandin E(2) (PGE(2)) is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE(2), acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE(2), we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes (FLS).

Gene expression profiling in patients with chronic obstructive pulmonary disease and lung cancer.

Rationale: Chronic obstructive lung disease (COPD) is a common and disabling lung disease for which there are few therapeutic options.

Objectives: We reasoned that gene expression profiling of COPD lungs could reveal previously unidentified disease pathways.

Methods: Forty-eight human lung samples were obtained from tissue resected from five nonsmokers, 21 GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0, 9 GOLD stage 1, 10 GOLD stage 2, and 3 GOLD stage 3 patients.

Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma.

Overexpression of Gob-5 has previously been linked to goblet cell metaplasia and mucin overproduction in both in vitro and in vivo model systems. In this study, Gob-5 knockout mice were generated and their phenotype was evaluated in two established preclinical models of allergic asthma. We sought to determine whether the Gob-5-null animals could produce less mucus in response to allergic challenge, and whether this would have any impact on reducing goblet cell metaplasia and airway inflammation.

oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes.

Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective.

Genomic conflict settled in favour of the species rather than the gene at extreme GC percentage values.

Wada and colleagues have shown that, whether prokaryotic or eukaryotic, each gene has a "homostabilising propensity" to adopt a relatively uniform GC percentage (GC%). Accordingly, each gene can be viewed as a "microisochore" occupying a discrete GC% niche of relatively uniform base composition amongst its fellow genes. Although first, second and third codon positions usually differ in GC%, each position tends to maintain a uniform, gene-specific GC% value.

Comparison of responses by bacteriophages and bacteria to pressures on the base composition of open reading frames.

Differences in the base composition of genomes can occur because of GC pressure, purine-loading pressure (AG pressure) and RNY pressure, for which there are possible functional explanations, and because of the more abstract pressures exerted by individual bases. The graphical approach of Muto and Osawa was used to analyse how bacteriophages and bacteria balance potentially conflicting pressures on their genomes. Phages generally respond to AG pressure by increasing A while keeping T constant, and by decreasing C while keeping G constant.