Reconstruction of bacterial transcription-coupled repair at single-molecule resolution

International audienc

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Chlamydia trachomatis Infection and Anti-Hsp60 Immunity: The Two Sides of the Coin

Chlamydia trachomatis (CT) infection is one of the most common causes of reproductive tract diseases and infertility. CT-Hsp60 is synthesized during infection and is released in the bloodstream. As a consequence, immune cells will produce anti-CT-Hsp60 antibodies. Hsp60, a ubiquitous and evolutionarily conserved chaperonin, is normally sequestered inside the cell, particularly into mitochondria. However, upon cell stress, as well as during carcinogenesis, the chaperonin becomes exposed on the cell surface (sf-Hsp60) and/or is secreted from cells into the extracellular space and circulation. Reports in the literature on circulating Hsp and anti-Hsp antibodies are in many cases short on details about Hsp60 concentrations, and about the specificity spectra of the antibodies, their titers, and their true, direct, pathogenetic effects. Thus, more studies are still needed to obtain a definitive picture on these matters. Nevertheless, the information already available indicates that the concurrence of persistent CT infection and appearance of sf-Hsp60 can promote an autoimmune aggression towards stressed cells and the development of diseases such as autoimmune arthritis, multiple sclerosis, atherosclerosis, vasculitis, diabetes, and thyroiditis, among others. At the same time, immunocomplexes composed of anti-CT-Hsp60 antibodies and circulating Hsp60 (both CT and human) may form deposits in several anatomical locations, e.g., at the glomerular basal membrane. The opposite side of the coin is that pre-tumor and tumor cells with sf-Hsp60 can be destroyed with participation of the anti-Hsp60 antibody, thus stopping cancer progression before it is even noticed by the patient or physician

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Bimodal structured bulk nanocrystalline Al-7.5Mg alloy

The microstructure, mechanical properties and deformation of bimodal structured nanocrystalline Al-7.5Mg alloy were investigated. Grain refinement was achieved by cryomilling of atomized Al-7.5Mg powders, and then cryomilled nanocrystalline powders blended with 15% and 30% unmilled coarse-grained powders were consolidated by hot isostatic pressing followed by extrusion to produce bulk nanocrystalline alloys. Bimodal bulk nanocrystalline Al-7.5Mg alloys, which were comprised of nanocrystalline grains separated by coarse-grain regions, show balanced mechanical properties of enhanced yield and ultimate strength and reasonable ductility and toughness compared to comparable conventional alloys and nanocrystalline metals

Bimodal microstructure and deformation of cryomilled bulk nanocrystalline Al-7.5Mg alloy

The microstructure, mechanical properties and deformation response of bimodal structured nanocrystalline Al-7.5Mg alloy were investigated. Grain refinement was achieved by cryomilling of atomized Al-7.5Mg powders, and then cryomilled nanocrystalline powders blended with 15 and 30% unmilled coarse-grained powders were consolidated by hot isostatic pressing followed by extrusion to produce bulk nanocrystalline alloys. Bimodal bulk nanocrystalline Al-7.5Mg alloys, which were comprised of nanocrystalline grains separated by coarse-grain regions, show balanced mechanical properties of enhanced yield and ultimate strength and reasonable ductility and toughness compared to comparable conventional alloys and nanocrystalline metals. The investigation of tensile and hardness test suggests unusual deformation mechanisms and interactions between ductile coarse-grain bands and nanocrystalline regions.close433

Effect Of Process Control Agent On The Microstructure And Mechanical Behavior Of An Aluminum And B4C Metal Matrix Composite

AA5083 and B4C powders were cryomilled in liquid nitrogen utilizing oleic, caprylic and stearic acids individually in order to determine the effect of each process control agent on the resultant microstructure and mechanical properties. The microstructure of the powders was examined and consolidated samples were mechanically tested in compression. Chemical analysis was performed to determine impurity concentrations of nitrogen, hydrogen and oxygen. Microstructural analysis of the powders revealed three types of agglomerates: composite powders of AA5083 with uniformly distributed B4C particulate, un-milled spherical AA5083 powder and deformed AA5083 powder. These three types of agglomerates were found in similar size and proportion regardless of the process control agent used. Nitrogen concentration correlates directly to the oxygen concentration in the sample. There was a slight increase in compressive strength with the increase in oxygen and nitrogen concentrations