Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

Developing consistent data and methods to measure the public health impacts of ambient air quality for Environmental Public Health Tracking: progress to date and future directions

Environmental Public Health Tracking (EPHT) staff at the state and national levels are developing nationally consistent data and methods to estimate the impact of ozone and fine particulate matter on hospitalizations for asthma and myocardial infarction. Pilot projects have demonstrated the feasibility of pooling state hospitalization data and linking these data to The United States Environmental Protection Agency (EPA) statistically based ambient air estimates for ozone and fine particulates. Tools were developed to perform case-crossover analyses to estimate concentration–response (C-R) functions. A weakness of analyzing one state at a time is that the effects are relatively small compared to their confidence intervals. The EPHT program will explore ways to statistically combine the results of peer-reviewed analyses from across the country to provide more robust C-R functions and health impact estimates at the local level. One challenge will be to routinely share data for these types of analyses at fine geographic and temporal scales without disclosing confidential information. Another challenge will be to develop C-R estimates which take into account time, space, or other relevant effect modifiers

Совершенствование технологии сооружения подводных переходов трубопроводов проложенных методом горизонтально-направленного бурения

Цель работы – разработка рекомендаций по применению технологии прокладки трубопроводов методом горизонтально-направленного бурения с применением защитного устройства. В процессе исследования проводились сравнительная характеристика существующих методов бестраншейной прокладки трубопроводов, расчет основных характеристик подводного перехода, подбор защитного устройства, исследование напряженно-деформированного состояния трубопровода с помощью конечно-элементного моделирования в программном комплексе Ansys. В результате исследования подобраны оптимальные параметры подводного перехода, методом конечно-элементного моделирования в программном комплексе Ansys определено напряженно-деформированнон состояние трубопровода с защитным устройством и без него.The purpose of the work is to develop recommendations for the application of pipeline laying technology by the method of horizontal directional drilling using a protective device. In the process of the research, the existing methods of trenchless pipeline laying, the calculation of the main characteristics of the underwater crossing, the selection of the protective device, the study of the stress-strain state of the pipeline using finite element modeling in the software complex Ansys were compared. As a result of the research, optimal parameters of the underwater transition were selected, the finite element method in the software complex Ansys determined the stress-strain state of the pipeline with the protective device and without it

Prediction of first matrix cracking in micro/nanohybrid brittle matrix composites

The classical Aveston-Cooper-Kelly shear-lag model for predicting the first matrix cracking strength in a brittle matrix composite is extended to the case of a hybrid brittle matrix composite containing both micro-scale and nano-scale fibers. First, closed-form solutions for the stresses in the two types of fibers and the matrix are derived. These are then used along with an energy analysis to predict the matrix cracking stress as a function of relevant material parameters. The analysis is applied to a typical Nicalon-SiC/CVI-SiC ceramic matrix composite containing additional nanofibers, for a wide range of nanofiber properties. A few volume percent of small diameter, moderate-stiffness nanofibers is predicted to provide significant strengthening and reduced crack opening while maintaining acceptable post-cracking fiber stresses. Various issues in the design of such micro/nanohybrid composites are then discussed. (C) 2010 Elsevier Ltd. All rights reserved

Study of the formation, evolution, and dissolution of interfacial defects in silicon wafer bonding

International audienceInterface defects formed during the wafer bonding process upon annealing have been studied. Based on the hydrogen diffusion in SiO2 and the stability of the bubbles at the bonding interface, models of the growth and further dissolution of the defects are presented. Considering the hydrogen diffusion through the interfacial oxide, diffusion coefficients and activation energy (Ea=0.25 eV) are obtained. It has been shown that the defect dissolution is driven by the exodiffusion of the hydrogen toward the silicon substrates

Caractérisation des émissions produites par les lampes fluo-compactes à basse consommation d'énergie dans la perspective de l'exposition des personnes

National audienc

Integration of buried insulators with high thermal conductivity in SOI MOSFETs: thermal properties and short channel effects

International audienc

Integration of high thermal conductivity buried insulators in SOI MOSFETs

International audienc