A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness

While much progress has been made in understanding stem cell (SC) function, a complete description of the molecular mechanisms regulating SCs is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of SCs. We investigated the value of a novel meta-analysis of microarray gene expression in mouse SCs to aid the elucidation of regulatory mechanisms common to SCs and particular SC types.We added value to previously published microarray gene expression data by characterizing the promoter type likely to regulate transcription. Promoters of up-regulated genes in SCs were characterized in terms of alternative promoter (AP) usage and CpG-richness, with the aim of correlating features known to affect transcriptional control with SC function. We found that SCs have a higher proportion of up-regulated genes using CpG-rich promoters compared with the negative controls. Comparing subsets of SC type with the controls a slightly different story unfolds. The differences between the proliferating adult SCs and the embryonic SCs versus the negative controls are statistically significant. Whilst the difference between the quiescent adult SCs compared with the negative controls is not. On examination of AP usage, no difference was observed between SCs and the controls. However, comparing the subsets of SC type with the controls, the quiescent adult SCs are found to up-regulate a larger proportion of genes that have APs compared to the controls and the converse is true for the proliferating adult SCs and the embryonic SCs.These findings suggest that looking at features associated with control of transcription is a promising future approach for characterizing “stemness” and that further investigations of stemness could benefit from separate considerations of different SC states. For example, “proliferating-stemness” is shown here, in terms of promoter usage, to be distinct from “quiescent-stemness”

Multidrug-resistant gram-negative pathogens: the urgent need for 'old' polymyxins

Antibiotic resistance has presented a major health challenge in the world and many isolates of Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa become resistant to almost all current antibiotics. This chapter provides an overview on the mechanisms of antibiotic resistance in these Gram-negative pathogens and outlines the formidable problem of the genetics of bacterial resistance. Prevalent multidrug-resistance in Gram-negative bacteria underscores the need for optimizing the clinical use of the last-line polymyxins

beta-lactam antibiotic resistance in aerobic commensal fecal flora of newborns

Background: The purpose of the present paper was to prospectively determine the rate of beta-lactam antibiotic resistance in commensal fecal flora of newborns and the risk factors leading to this colonization