An extracytoplasmic function (ECF) sigma/anti-sigma factor system regulates hypochlorous acid resistance and impacts expression of the type IV secretion system in Brucella melitensis

The intracellular bacterial pathogen Brucella causes persistent infections in various mammalian species. To survive and replicate within macrophages, these bacteria must be able to withstand oxidative stresses and express the type IV secretion system (T4SS) to evade host immune responses. The extracytoplasmic function (ECF) sigma factor system is a major signal transduction mechanism in bacteria that senses environmental cues and responds by regulating gene expression. In this study, we defined an ECF σ bcrS and its cognate anti-σ factor abcS in Brucella melitensis M28 by conserved domain analysis and a protein interaction assay. BcrS directly activates an adjacent operon, bcrXQP, that encodes a methionine-rich peptide and a putative methionine sulfoxide reductase system, whereas AbcS is a negative regulator of bcrS and bcrXQP. The bcrS/abcS and bcrXQP operons can be induced by hypochlorous acid and contribute to hypochlorous acid resistance in vitro. Next, RNA sequencing analysis and genome-wide recognition sequence search identified the regulons of BcrS and AbcS. Interestingly, we found that BcrS positively influences T4SS expression in an AbcS-dependent manner and that AbcS also affects T4SS expression independently of BcrS. Last, we demonstrate that abcS is required for the maintenance of persistent infection while bcrS is dispensable in a mouse infection model. Collectively, we conclude that BcrS and AbcS influence expression of multiple genes responsible for Brucella virulence traits. Importance Brucella is a notorious intracellular pathogen that induces chronic infections in animals and humans. To survive and replicate within macrophages, these bacteria require a capacity to withstand oxidative stresses and to express the type IV secretion system (T4SS) to combat host immune responses. In this study, we characterized an extracytoplasmic function (ECF) sigma/anti-sigma factor system that regulates resistance to reactive chlorine species and T4SS expression, thereby establishing a potential link between two crucial virulence traits of Brucella. Furthermore, the anti-sigma factor AbcS contributes to Brucella persistent infection of mice. Thus, this work provides novel insights into Brucella virulence regulation as well as a potential drug target for fighting Brucella infections.

Expression of tissue factor and tissue factor pathway inhibitors during ovulation in rats: a relevance to the ovarian hyperstimulation syndrome

Background Blood coagulation has been associated with ovulation and female infertility. In this study, the expression of the tissue factor system was examined during ovulation in immature rats; the correlation between tissue factor and ovarian hyperstimulation syndrome (OHSS) was evaluated both in rats and human follicular fluids. Methods Ovaries were obtained at various times after human chorionic gonadotropin (hCG) injection to investigate the expression of tissue factor system. Expression levels of ovarian tissue factor, tissue factor pathway inhibitor (Tfpi)-1 and Tfpi-2 genes and proteins were determined by real-time quantitative polymerase chain reaction (qPCR), and Western blot and immunofluorescence analyses, respectively. Expression levels of tissue factor system were also investigated in ovaries of OHSS-induced rats and in follicular fluid of infertile women. Results The expression of tissue factor in the preovulatory follicles was stimulated by hCG, reaching a maximum at 6 h. Tissue factor was expressed in the oocytes and the preovulatory follicles. Tfpi-2 mRNA levels were mainly increased by hCG in the granulosa cells whereas the mRNA levels of Tfpi-1 were decreased by hCG. Human CG-stimulated tissue factor expression was inhibited by the progesterone receptor antagonist. The increase in Tfpi-2 expression by hCG was decreased by the proliferator-activated receptor γ (PPARγ) antagonist. Decreased expression of the tissue factor was detected in OHSS-induced rats. Interestingly, the tissue factor concentrations in the follicular fluids of women undergoing in vitro fertilization were correlated with pregnancy but not with OHSS. Conclusions Collectively, the results indicate that tissue factor and Tfpi-2 expression is stimulated during the ovulatory process in rats; moreover, a correlation exists between the levels of tissue factor and OHSS in rats but not in humans.

Studying the profitability of the mining farm's operations

Subject. The article examines the profitability of the mining farm. Objectives. I determine what aspects the mining farm’s profitability should be analyzed, and articulate my own technique for analyzing, untapping the room for the profitability growth on the analyzable mining farm. Methods. To make my suggestions reasonable, reliable and substantiate them, I use the comprehensive approach to studying the profitability of the mining farm, general and special methods of research, such as the retrospective, systems and functional-structural analysis, observation, classification, instrumental techniques for grouping, sampling, comparison and generalization, factor analysis. Results. The study is the first to present the structural-logic model of the factor system of profitability of the mining farm. I assessed factors that influenced the profitability, found bottle necks and aspects to focus on in order to improve the performance of the mining farm. Conclusions and Relevance. Business entities that are residents at the Belarus Part of High Technology and have mining farms can use the proposed technique, which are of applied nature.

THE VIABILITY AS AN EMERGENT PROPERTY OF SELF-ORGANIZING SYSTEMS

The necessity of a man-machine system considering as a self-organizing one is shown. The most significant difficulty in such a system is the study of its emergent properties. The paper focuses on viability as an emergent property of the system. The concepts of hardiness, human factor, system resources, biosystem were considered. It allowed proposing the viability’s concept of a self-organizing system based on biomimetics principles. The roadmap of convergent research and analysis of the man-machine system’s viability is presented. The convergent approach to the self-organizing system’s viability is realised in the proposed roadmap.