Probability Theory in Statistical Physics, Percolation, and Other Random Topics: The Work of C. Newman

In the introduction to this volume, we discuss some of the highlights of the research career of Chuck Newman. This introduction is divided into two main sections, the first covering Chuck's work in statistical mechanics and the second his work in percolation theory, continuum scaling limits, and related topics.Comment: 38 pages (including many references), introduction to Festschrift in honor of C.M. Newma

Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens

© 2015, Springer-Verlag Berlin Heidelberg. The rapid unchecked rise in antibiotic resistance over the last few decades has led to an increased focus on the need for alternative therapeutic strategies for the treatment and clinical management of microbial infections. In particular, small molecules that can suppress microbial virulence systems independent of any impact on growth are receiving increased attention. Quorum sensing (QS) is a cell-to-cell signalling communication system that controls the virulence behaviour of a broad spectrum of bacterial pathogens. QS systems have been proposed as an effective target, particularly as they control biofilm formation in pathogens, a key driver of antibiotic ineffectiveness. In this study, we identified coumarin, a natural plant phenolic compound, as a novel QS inhibitor, with potent anti-virulence activity in a broad spectrum of pathogens. Using a range of biosensor systems, coumarin was active against short, medium and long chain N-acyl-homoserine lactones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key virulence systems were studied in the nosocomial pathogen Pseudomonas aeruginosa. Consistent with suppression of QS, coumarin inhibited biofilm, the production of phenazines and swarming motility in this organism potentially linked to reduced expression of the rhlI and pqsA quorum sensing genes. Furthermore, coumarin significantly inhibited biofilm formation and protease activity in other bacterial pathogens and inhibited bioluminescence in Aliivibrio fischeri. In light of these findings, coumarin would appear to have potential as a novel quorum sensing inhibitor with a broad spectrum of action

Pro-Inflammatory Mediation of Myoblast Proliferation

Skeletal muscle satellite cell function is largely dictated by the surrounding environment following injury. Immune cell infiltration dominates the extracellular space in the injured area, resulting in increased cytokine concentrations. While increased pro-inflammatory cytokine expression has been previously established in the first 3 days following injury, less is known about the time course of cytokine expression and the specific mechanisms of cytokine induced myoblast function. Therefore, the expression of IL-1b and IL-6 at several time points following injury, and their effects on myoblast proliferation, were examined. In order to do this, skeletal muscle was injured using barium chloride in mice and tissue was collected 1, 5, 10, and 28 days following injury. Mechanisms of cytokine induced proliferation were determined in cell culture using both primary and C2C12 myoblasts. It was found that there is a ,20-fold increase in IL-1b (p#0.05) and IL-6 (p = 0.06) expression 5 days following injury. IL-1b increased proliferation of both primary and C2C12 cells ,25%. IL-1b stimulation also resulted in increased NF-kB activity, likely contributing to the increased proliferation. These data demonstrate for the first time that IL-1b alone can increase the mitogenic activity of primary skeletal muscle satellite cells and offer insight into the mechanisms dictating satellite cell function following injury