Inactivation of DNA-Binding Response Regulator Sak189 Abrogates β-Antigen Expression and Affects Virulence of Streptococcus agalactiae

BACKGROUND: Streptococcus agalactiae is able to colonize numerous tissues employing different mechanisms of gene regulation, particularly via two-component regulatory systems. These systems sense the environmental stimuli and regulate expression of the genes including virulence genes. Recently, the novel two-component regulatory system Sak188/Sak189 was identified. In S. agalactiae genome, it was adjacent to the bac gene encoding for beta-antigen, an important virulence factor. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the sak188 and sak189 genes were inactivated, and the functional role of Sak188/Sak189 two-component system in regulation of the beta-antigen expression was investigated. It was demonstrated that both transcription of bac gene and expression of encoded beta-antigen were controlled by Sak189 response regulator, but not Sak188 histidine kinase. It was also found that the regulation occurred at transcriptional level. Finally, insertional inactivation of sak189 gene, but not sak188 gene, significantly affected virulent properties of S. agalactiae. CONCLUSIONS/SIGNIFICANCE: Sak189 response regulator is necessary for activation of bac gene transcription. It also controls the virulent properties of S. agalactiae. Given that the primary functional role of Sak188/Sak189 two-component systems is a control of bac gene transcription, this system can be annotated as BgrR/S (bacgene regulatory system)

Epidemiological manifestations of tuberculosis infection in the Omsk region: dynamics and trends

Background. Tuberculosis (TB) infection remains relevant as one of the leading public health problems in Russia.The aim. To characterize the dynamics and trends of epidemiological manifestations of TB infection in the Omsk region.Materials and methods. An observational descriptive-evaluative epidemiological study was carried out in the Omsk region from 2009 to 2021. The data available in the Federal statistical observation forms NN 7, 8, and 33, and results of the bacteriological study of patients with respiratory TB were analyzed.Results. In the Omsk region, an improvement in the epidemiological situation was observed from 2009 to 2021. It was associated with a decrease in TB prevalence by 3.7 times (from 325.6 to 86.7), mortality – by 5.8 times (from 21.1 to 3.6), incidence – by 2.7 times (from 130.7 to 48.4 per 100,000). At the same time, proportion of microscopy/culture-positive patients infected with multidrug-resistant Mycobacterium tuberculosis strains increased from 9.2 to 29.8 % among all patients, and from 15.5 to 30.6 % among newly diagnosed patients. There was a trend towards an increase in the number of cases with primary extensive drug resistance of M. tuberculosis. The incidence of tuberculosis associated with HIV infection has increased 10 times and reached 15.6 per 100,000 population.Conclusions. In the Omsk region, there is a change in the structure of M. tuberculosis strains with a predominance of multiple and extensive drug resistance along with decrease in TB incidence and mortality. New approaches are needed to organize the system of epidemiological surveillance and control of TB infection

Theoretical analysis of magnetic coupling in sandwich clusters V_n(C_6H_6)_{n+1}

The mechanism of ferromagnetism stability in sandwich clusters V$_n$(C$_6$H$_6$)$_{n+1}$ has been studied by first-principles calculation and model analysis. It is found that each of the three types of bonds between V and benzene (Bz) plays different roles. V 3d$_{z^2}$ orbital, extending along the molecular axis, is weakly hybridized with Bz's HOMO-1 orbital to form the $\sigma$-bond. It is quite localized and singly occupied, which contributes 1$\mu_B$ to the magnetic moment but little to the magnetic coupling of neighboring V magnetic moments. The in-plane d$_{x^2-y^2}$, d$_{xy}$ orbitals are hybridized with the LUMO of Bz and constitute the $\delta$-bond. This hybridization is medium and crucial to the magnetic coupling though the $\delta$ states have no net contribution to the total magnetic moment. d$_{xz}$, d$_{yz}$ and HOMO of Bz form a quite strong $\pi$-bond to hold the molecular structure but they are inactive in magnetism because their energy levels are far away from the Fermi level. Based on the results of first-principles calculation, we point out that the ferromagnetism stability is closely related with the mechanism proposed by Kanamori and Terakura [J. Kanamori and K. Terakura, J. Phys. Soc. Jpn. 70, 1433 (2001)]. However, the presence of edge Bz's in the cluster introduces an important modification. A simple model is constructed to explain the essence of the physical picture.Comment: 16 pages, 7 figure

Методические основы развития материального обеспечения войск (сил) за пределами Российской Федерации

Purpose of the study. The main purpose of this research is to develop a methodological basis for material support of groups of troops (forces) on the territory of a foreign state in a military conflict.Materials and methods. The following methods are used: a systematic approach to the study and development of methodological foundations to improve the efficiency of material support of troops (forces) outside the Russian Federation; methods of economic analysis, analytical, statistical, logical, linguistic and graphical methods; applied general scientific and specific methods of substantiation of the concept: abstraction and concretization, historical and logical, as well as methods of graphic and mathematical modeling, factor analysis.Results. The technique of development of material support of group of troops (forces) operating in the territory of the foreign state in the conditions of the military conflict is developed. Factors of influence on the process of formation and management of the assortment of commercial and household support for a group of troops (forces) operating outside the Russian Federation are systematized. Exogenous and endogenous factors of formation of parameters of trade and household (sales and service) network of the divisions providing grouping of troops (forces) in the territory of the foreign state are offered. The assortment policy of divisions of material support of the contingent of troops (forces) operating in the territory of the foreign state as the systematized set of the purposes, tasks and the main directions of formation of the trade and household range planned by the management of this group and staff of logistics of Armed Forces of the Russian Federation is defined.Conclusion. Material support activities require consideration of the principles and conceptual frameworks that determine their sustainability and effectiveness. The initial stage of formation and development of system of material support of the military personnel outside the Russian Federation, dynamism of external factors of the environment of providing divisions and high degree of commercial risk (for all subjects of process of commodity circulation), demand continuous tracking or dynamic adequate decisions in the sphere of operational management of implementation of strategy of development of material support regarding formation of assortment policy.Цель исследования. Основная цель данного научного исследования заключается в том, чтобы разработать методические основы материального обеспечения группировки войск (сил) на территории иностранного государства в условиях военного конфликта.Материалы и методы. Использованы: системный подход к обоснованию и разработке методических основ, обеспечивающих повышение эффективности материального обеспечения войск (сил) за пределами Российской Федерации; методы экономического анализа, аналитические, статистические, логические, лингвистические и графические методы; применены общенаучные и специфические методы обоснования концепции: абстрагирование и конкретизация, историко-логический, а также приемы графического и математического моделирования, факторного, анализа.Результаты. Разработана Методика развития материального обеспечения группировки войск (сил), действующей на территории иностранного государства в условиях военного конфликта. Систематизированы факторы влияния на процесс формирования и управления ассортиментом торгово-бытового обеспечения группировки войск (сил), действующей за пределами Российской Федерации. Предложены экзогенные и эндогенные факторы формирования параметров торгово-бытовой (сбытовой и сервисной) сети подразделений, обеспечивающих группировку войск (сил) на территории иностранного государства. Определена ассортиментная политику подразделений материального обеспечения контингента войск (сил), действующую на территории иностранного государства, как систематизированная совокупность целей, задач и основных направлений формирования торгово-бытового ассортимента, планируемых руководством данной группировки и Штабом материально-технического обеспечения Вооруженных Сил Российской Федерации.Заключение. Деятельность по организации материального обеспечения требует учета принципов и концептуальных основ, определяющих ее устойчивость и эффективность. Начальный этап становления и развития системы материального обеспечения военнослужащих за пределами Российской Федерации, динамизм внешних факторов окружения обеспечивающих подразделений и высокая степень коммерческого риска (для всех субъектов процесса товародвижения), требуют постоянного отслеживания или динамичных адекватных решений в сфере оперативного управления реализацией стратегии развития материального обеспечения в части формирования ассортиментной политики

Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine

<p>Abstract</p> <p>Background</p> <p>A persistent increase of tuberculosis cases has recently been noted in the Ukraine. The reported incidence of drug-resistant isolates of <it>M. tuberculosis </it>is growing steadily; however, data on the genetic variation of isolates of <it>M. tuberculosis </it>circulating in northern Ukraine and on the spectrum and frequency of occurrence of mutations determining resistance to the principal anti-tuberculosis drugs isoniazid and rifampicin have not yet been reported.</p> <p>Methods</p> <p>Isolates of <it>M. tuberculosis </it>from 98 tuberculosis patients living in Kharkiv Oblast (Ukraine) were analyzed using VNTR- and RFLP-IS6110-typing methods. Mutations associated with resistance to rifampicin and isoniazid were detected by RFLP-PCR methods, and also confirmed by sequencing.</p> <p>Results</p> <p>We identified 75 different genetic profiles. Thirty four (34%) isolates belonged to the Beijing genotype and 23 (23%) isolates belonged to the LAM family. A cluster of isolates belonging to the LAM family had significant genetic heterogeneity, indicating that this family had an ancient distribution and circulation in this geographical region. Moreover, we found a significant percentage of the isolates (36%) belonged to as yet unidentified families of <it>M. tuberculosis </it>or had individual non-clustering genotypes. Mutations conferring rifampicin and isoniazid resistance were detected in 49% and 54% isolates, respectively. Mutations in codon 531 of the <it>rpoB </it>gene and codon 315 of the <it>katG </it>gene were predominant among drug-resistant isolates. An association was found for belonging to the LAM strain family and having multiple drug resistance (R = 0.27, p = 0.0059) and also for the presence of a mutation in codon 531 of the <it>rpoB </it>gene and belonging to the Beijing strain family (R = 0.2, p = 0.04).</p> <p>Conclusions</p> <p>Transmission of drug-resistant isolates seems to contribute to the spread of resistant TB in this oblast. The Beijing genotype and LAM genotype should be seen as a major cause of drug resistant TB in this region.</p

Genetic diversity of Mycobacterium tuberculosis in Peru and exploration of phylogenetic associations with drug resistance.

BACKGROUND: There is limited available data on the strain diversity of M tuberculosis in Peru, though there may be interesting lessons to learn from a setting where multidrug resistant TB has emerged as a major problem despite an apparently well-functioning DOTS control programme. METHODS: Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community-based patients and 241 hospital-based HIV co-infected patients with pulmonary tuberculosis in Lima, Peru. Phylogenetic and epidemiologic analyses permitted identification of clusters and exploration of spoligotype associations with drug resistance. RESULTS: Mean patient age was 31.9 years, 63% were male and 30.4% were known to be HIV+. Rifampicin mono-resistance, isoniazid mono-resistance and multidrug resistance (MDR) were identified in 4.7%, 8.7% and 17.3% of strains respectively. Of 794 strains from 794 patients there were 149 different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498 strains (62.7%) were clustered in the nine most common spoligotypes: 16.4% SIT 50 (clade H3), 12.3% SIT 53 (clade T1), 8.3% SIT 33 (LAM3), 7.4% SIT 42 (LAM9), 5.5% SIT 1 (Beijing), 3.9% SIT 47 (H1), 3.0% SIT 222 (clade unknown), 3.0% SIT1355 (LAM), and 2.8% SIT 92 (X3). Amongst HIV-negative community-based TB patients no associations were seen between drug resistance and specific spoligotypes; in contrast HIV-associated MDRTB, but not isoniazid or rifampicin mono-resistance, was associated with SIT42 and SIT53 strains. CONCLUSION: Two spoligotypes were associated with MDR particularly amongst patients with HIV. The MDR-HIV association was significantly reduced after controlling for SIT42 and SIT53 status; residual confounding may explain the remaining apparent association. These data are suggestive of a prolonged, clonal, hospital-based outbreak of MDR disease amongst HIV patients but do not support a hypothesis of strain-specific propensity for the acquisition of resistance-conferring mutations

Tuberculosis outcomes related to the Mycobacterium tuberculosis genotype

Mycobacterium tuberculosis strains of different phylogenetic lineages and genetic families differ in biological properties that determine, to some extent, epidemiological features and clinical manifestation in tuberculosis (TB) patients.The aim of the study was to assess the risk of an adverse outcome of the disease in TB patients caused by various M. tuberculosis genotypes.Materials and methods. A total of 425 patients with respiratory TB were enrolled in this study. They were registered at phthisiatric facilities in the Omsk region from March 2015 to June 2017 period and included: males — 73.1%, mean age 39.9 years, females — 26.9%, mean age 42.0 years. M. tuberculosis culture and drug susceptibility testing and DNA extraction were performed in accordance with standard methods. Strains were assigned to the M. tuberculosis Beijing genotype and its epidemiologically relevant clusters B0/W148 and 94-32 by PCR based detection of specific markers. Non-Beijing strains were subjected to spoligotyping.Results. We found that 66.5% isolates belonged to the Beijing genotype, 12.8% — to LAM, 10.1% — to T, and 4.7% — to the Ural genotype. Multi-drug resistance (MDR) to anti-TB drugs was observed in 195 M. tuberculosis strains (45.9%). Moreover, Beijing genotype was more often isolated from patients with MDR-TB infection (PR = 2.09 (95% CI 1.6–2.74) and TB infection associated with HIV infection (PR = 1.14 (95% CI 1.01–1.31). Lethal outcome was double higher in patients infected with Beijing vs. non-Beijing strains, 28.6% vs. 14.0% (PR = 2.03; 95% CI 1.3–3.17). The risk factors were identified as follows: young age 18–44 years (RR = 1.7; 95% CI 1.18–2.7), co-morbidity with HIV (RR = 5.0; 95% CI 3.39–7.45), multiple (RR = 1.7; 95% CI 1.14–2.55) and extensive drug resistance (RR = 2.57; 95% CI 1.35–4.92), and association with the Beijing genotype (RR = 2.0, 95% CI 1.3–3.17).Conclusion. M. tuberculosis spread in the Omsk region is characterised by significant prevalence of the Beijing genotype, associated with multiple and extensive drug resistance. A significant association of adverse clinical outcomes and various factors, including association with the Beijing genotype, requires development of new approaches in the fight against tuberculosis

Magnonic Weyl states in Cu2OSeO3

The multiferroic ferrimagnet Cu$_2$OSeO$_3$ with a chiral crystal structure attracted a lot of recent attention due to the emergence of magnetic skyrmion order in this material. Here, the topological properties of its magnon excitations are systematically investigated by linear spin-wave theory and inelastic neutron scattering. When considering Heisenberg exchange interactions only, two degenerate Weyl magnon nodes with topological charges $\pm$2 are observed at high-symmetry points. Each Weyl point splits into two as the symmetry of the system is further reduced by including into consideration the nearest-neighbor Dzyaloshinsky-Moriya interaction, crucial for obtaining an accurate fit to the experimental spin-wave spectrum. The predicted topological properties are verified by surface state and Chern number analysis. Additionally, we predict that a measurable thermal Hall conductivity can be associated with the emergence of the Weyl points, the position of which can be tuned by changing the crystal symmetry of the material

Water Ozonation with Copper Catalyst for Organic Pollutants Removal

This work presents high-porous honeycomb copper catalyst for organic pollutants removal from water during the ozonation process. This catalyst demonstrates high efficiency in removing target compounds (oxalic and benzoic acids and methylene blue), appropriate stability and resistance to abrasion. Copper catalyst behavior in the ozonation process was investigated. It was found that under ozonation conditions reversible В  oxidation/reduction of the copper surface layer takes place. In contact with ozone, copper surface can easily be oxidized resulting in formation of copper oxides. As expected, it leads to decomposition of organic substances during ozonation and reduction of copper catalyst surface layer. Copper (II) oxide was also found to be an active catalyst in oxidation of organic pollutants with ozone, but it is not appropriate to use bulk CuO because of its low abrasion resistance. Copper (II) ions that form due to dissolution of catalyst surface layer with participation of the acidic medium in the ozonation process were detected. Pollutants removal efficiency at different pH values was also studied. It was found that catalytic removal of organic pollutants takes place at low pH, as compared to low efficiency of hydroxyl-radical formation at the acidic pH. A possible scheme for organic pollutants removal during ozonation with copper catalyst was proposed