Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis.

Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes a substantial socioeconomic burden. Under the influence of the proinflammatory milieu, synovial fibroblasts (SFs), the main effector cells in disease pathogenesis, become activated and hyperplastic, releasing proinflammatory factors and tissue-remodeling enzymes. This study shows that activated arthritic SFs from human patients and animal models express significant quantities of autotaxin (ATX; ENPP2), a lysophospholipase D that catalyzes the conversion of lysophosphatidylcholine to lysophosphatidic acid (LPA).

A critical role for gelsolin in ventilator-induced lung injury.

Mechanical ventilation, an essential life-support modality of patients with acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS), exerts its detrimental effects through largely unknown mechanisms. Gelsolin (GSN), an actin-binding protein and a substrate of caspase-3, was recently shown to play a major role in bleomycin- or lipopolysaccharide-induced lung injury. To dissect a possible role of GSN in the pathogenesis of ventilator-induced lung injury (VILI), genetically modified mice lacking GSN expression and wild-type controls underwent mechanical ventilation with high tidal volumes.

Development and application of versatile high density microarrays for genome-wide analysis of Streptomyces coelicolor: characterization of the HspR regulon.

Background: DNA microarrays are a key resource for global analysis of genome content, gene expression and the distribution of transcription factor binding sites. We describe the development and application of versatile high density ink-jet in situ-synthesized DNA arrays for the G+C rich bacterium Streptomyces coelicolor. High G+C content DNA probes often perform poorly on arrays, yielding either weak hybridization or non-specific signals.

Loss of the controlled localization of growth stage-specific cell-wall synthesis pleiotropically affects developmental gene expression in an ssgA mutant of Streptomyces coelicolor.

Members of the family of SsgA-like proteins (SALPs) are found exclusively in sporulating actinomycetes, and SsgA itself activates sporulation-specific cell division. We previously showed that SALPs play a chaperonin-like role in supporting the function of enzymes involved in peptidoglycan maintenance (PBPs and autolysins). Here we show that SsgA localizes dynamically during development, and most likely marks the sites where changes in local cell-wall morphogenesis are required, in particular septum formation and germination.

Analysis of gene expression in operons of Streptomyces coelicolor.

Background: Recent studies have shown that microarray-derived gene-expression data are useful for operon prediction. However, it is apparent that genes within an operon do not conform to the simple notion that they have equal levels of expression.

Results: To investigate the relative transcript levels of intra-operonic genes, we have used a Z-score approach to normalize the expression levels of all genes within an operon to expression of the first gene of that operon.

SsgA-like proteins determine the fate of peptidoglycan during sporulation of Streptomyces coelicolor.

During developmental cell division in sporulation-committed aerial hyphae of streptomycetes, up to a hundred septa are simultaneously produced, in close harmony with synchromous chromosome condensation and segregation. Several unique protein families are involved in the control of this process in actinomycetes, including that of the SsgA-like proteins (SALPs). Mutants for each of the individual SALP genes were obtained, and high-resolution and fluorescence imaging revealed that each plays an important and highly specific role in the control of the sporulation process, and their function relates to the build-up and degradation of septal and spore-wall peptidoglycan.

MILVA: an interactive tool for the exploration of multidimensional microarray data.

Motivation: Clustering techniques such as k-means and hierarchical clustering are commonly used to analyze DNA microarray derived gene expression data. However, the interactions between processes underlying the cell activity suggest that the complexity of the microarray data structure may not be fully represented with discrete clustering methods.

Results: A newly developed software tool called MILVA (microarray latent visualization and analysis) is presented here to investigate microarray data without separating gene expression profiles into discrete classes.

A bacterial hormone (the SCB1) directly controls the expression of a pathway-specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor.

Gamma-butyrolactone signalling molecules are produced by many Streptomyces species, and several have been shown to regulate antibiotic production. In Streptomyces coelicolor A3(2) at least one gamma-butyrolactone (SCB1) has been shown to stimulate antibiotic production, and genes encoding proteins that are involved in its synthesis (scbA) and binding (scbR) have been characterized. Expression of these genes is autoregulated by a complex mechanism involving the gamma-butyrolactone.