Stress-strain state and loss of stability of anisotropic thermal coating under thermal shock

The deformation behavior of thermal barrier coatings has been investigated. The mechanism of occurring instabilities in such coatings based on their representation in the form of a plate located on an elastic foundation has been studied. Loss of stability manifests itself in the form of a doubly periodic system of intrusion and extrusion zones that is qualitatively consistent with the well-known experimental results. Typical features of stability loss and its dependence on the properties of conjugated materials have been investigated by the example of the thermal loading simulation of the copper specimen with a protective ceramic coating. The influence of the thermo-mechanical properties anisotropy of the coating material on the character of the emerging instability has been estimated

Predicting the severity of viral bronchiolitis in children

Acute viral bronchiolitis is one of the common causes of hospitalization and mortality, especially among children in the first year of life who have risk factors (prematurity, congenital heart defects, bronchopulmonary dysplasia, immunosuppression). As factors associated with the severe course of bronchiolitis, along with the traditional ones, single nucleotide polymorphisms of the genes of the immune response molecules can be considered.The aim. Based on the analysis of clinical, laboratory and molecular genetic parameters, to identify prognostic criteria for the severe course of acute viral bronchiolitis in children.Materials and methods. The study included 106 children with acute viral bronchiolitis (severe course – 34, mild course – 72), the etiology of which in 67.9 % was respiratory syncytial virus. Forty-seven anamnestic, clinical, traditional laboratory and molecular genetic parameters were assessed as prognostic criteria. Determination of SNP genes of cytokines IL-4 (C-589T), IL-10 (G-1082A), IL-10 (C-592A), IL-10 (C-819T), TNF-α (G-308A), IL-17A (G197A), IL-17F (His161Arg), TLR2-753ArgGln, TLR6-Ser249Pro in venous blood was carried out by the polymerase chain reaction method.Results. An additional criterion for the risk of developing a severe course of bronchiolitis can be the mutant genotype (AA) SNP of the IL-10 gene (C-592A), which was detected exclusively in the group of patients with severe bronchiolitis, increasing the risk of developing a severe disease by 16.11 times (OR = 16.11; 95 % CI: 0.81–121.22, p = 0.02) in conjunction with already established modifying factors: the presence of congenital heart disease, bronchopulmonary dysplasia, prematurity, birth weight < 1500 g. Based on a comprehensive assessment of the established risk factors, a method has been developed that allows calculate the likelihood of developing a severe course of acute viral bronchiolitis. Conclusion. The use of the developed prediction method will not only increase the likelihood of developing severe acute viral bronchiolitis in children, but also determine the priority group among children with predictors of severe viral bronchiolitis for priority immunoprophylaxis against RS-virus infection

Chlamydia pan-genomic analysis reveals balance between host adaptation and selective pressure to genome reduction

Background Chlamydia are ancient intracellular pathogens with reduced, though strikingly conserved genome. Despite their parasitic lifestyle and isolated intracellular environment, these bacteria managed to avoid accumulation of deleterious mutations leading to subsequent genome degradation characteristic for many parasitic bacteria. Results We report pan-genomic analysis of sixteen species from genus Chlamydia including identification and functional annotation of orthologous genes, and characterization of gene gains, losses, and rearrangements. We demonstrate the overall genome stability of these bacteria as indicated by a large fraction of common genes with conserved genomic locations. On the other hand, extreme evolvability is confined to several paralogous gene families such as polymorphic membrane proteins and phospholipase D, and likely is caused by the pressure from the host immune system. Conclusions This combination of a large, conserved core genome and a small, evolvable periphery likely reflect the balance between the selective pressure towards genome reduction and the need to adapt to escape from the host immunity

Роль полиморфизма генов некоторых молекул иммунного ответа в развитии острого вирус-индуцированного бронхиолита

The aim of research: To investigate the genetic polymorphism of immune response molecules (TNFα-308G> A (rs1800629), IL4-589C>T (rs2243250), IL10-592C> A (rs1800872), IL10-819C> T (rs1800871), IL10-1082G>A (rs1800896), IL-17A-197G> A (rs2275913), IL- 17F-161His> Arg (rs763780), TLR-2-753Arg>Gln (rs5743708), TLR-6-249Ser>Pro (rs5743810) and assess their prognostic value in the development of acute virus-induced bronchiolitis.Materials and methods. The study included children of the first year of life, whose average age was 4.2 ± 3.7 months. The main group consisted of 106 patients with moderate and severe acute viral bronchiolitis, more often associated with respiratory syncytial virus (56.6%). The control group consisted of 100 healthy children of the same age who had no signs of acute respiratory infection at the time of examination and did not receive passive immunoprophylaxis of respiratory syncytial infection. Genotyping was performed using the polymerase chain reaction method. The analysis of the results included the compliance with the Hardy-Weinberg law, the χ 2 test, the relative chance, and its 95% confidence interval. To assess the distribution of the claimed gene polymorphisms and their alleles, we used the general (χ2 test, df =2) and multiplicative (χ2 test, df =1) inheritance models.Results. It was revealed that the risk of developing acute viral bronchiolitis is increased compared to the healthy population in carriers of the following genotypes: CC, ST gene IL10-819C> T (rs1800871), GG, AA gene IL-17A-197G> A (rs2275913), HisHis gene IL-17F-161His> Arg (rs763780), SerSer, SerPro gene TLR-6-249Ser> Pro (rs5743810), GG gene TNF-α-308G>A (rs1800629). The TT genotype of the IL10-819C>T (rs1800871) gene is associated with a high risk of developing bacterial complications (pneumonia) in viral bronchiolitis. Carriers of genotypes AA, CC of the IL10-592C> A (rs1800872) gene have an increased likelihood of a severe course of viral bronchiolitis.Conclusion. Genetic analysis of gene polymorphism IL10-592C> A (rs1800872), IL10-819C> T (rs1800871), IL-17A-197G> A (rs2275913), IL-17F-161His> Arg (rs763780), TLR-6-249Ser> Pro (rs5743810), TNF-α-308 G>A (rs1800629) can be used as a personalized developmental criterion acute virus-induced bronchiolitis in children, determining the severity of its course and the likelihood of complications.Цель: исследовать генетический полиморфизм молекул иммунного ответа (TNFα-308G>A (rs1800629), IL4-589C>T (rs2243250), IL10-592C>A (rs1800872), IL10-819C>T (rs1800871), IL10-1082G>A (rs1800896), IL-17A-197G>A (rs2275913), IL-17F-161His>Arg (rs763780), TLR2-753 Arg>Gln (rs5743708), TLR-6-249 Ser>Pro (rs5743810) и оценить их прогностическое значение в развитии острого вирус-индуцированного бронхиолита.Материалы и методы. В исследование включены дети первого года жизни, средний возраст которых составил 4,2±3,7 месяца. Основная группа – 106 пациентов с острым вирусным бронхиолитом средней и тяжелой степени тяжести, чаще ассоциированным с респираторно-синцитиальным вирусом (56,6%). Группа контроля – 100 здоровых детей аналогичного возраста, не имевших признаков острой респираторной инфекции на момент обследования и не получавших пассивную иммунопрофилактику респираторно-синцитиальной инфекции. Генотипирование проведено методом полимеразной цепной реакции. Анализ результатов включал соответствие закону Харди – Вайнберга, χ2-тест, относительный шанс и его 95% доверительный интервал. Для оценки распределения заявленных полиморфизмов генов и их аллелей использовали общую (χ2-тест, df=2) и мультипликативную (χ2-тест, df=1) модели наследования.Результаты. Выявлено, что риск развития острого вирусного бронхиолита повышен по сравнению со здоровой популяцией у носителей следующих генотипов: СС, СТ гена IL10-819C>T (rs1800871), GG, АА гена IL-17A-197G>A (rs2275913), HisHis гена IL-17F-161His>Arg (rs763780), SerSer, SerPro гена TLR-6-249Ser>Pro (rs5743810), GG гена TNF-α-308G>A (rs1800629). Генотип ТТ гена IL10-819C>T (rs1800871) ассоциирован с высоким риском развития бактериальных осложнений (пневмонии) при вирусном бронхиолите. Носители генотипов АА, СС гена IL10-592C>A (rs1800872) имеют повышенную вероятность тяжелого течения вирусного бронхиолита.Заключение. Генетический анализ полиморфизма генов IL10-592C>A (rs1800872), IL10-819C>T (rs1800871), IL-17A-197G>A (rs2275913), IL-17F-161His>Arg (rs763780), TLR-6-249Ser>Pro (rs5743810), TNF-α-308G>A (rs1800629) может использоваться в качестве персонифицированного критерия развития острого вирус-индуцированного бронхиолита у детей, определения тяжести его течения и вероятности формирования осложнений

Cmr is a redox-responsive regulator of DosR that contributes to M. tuberculosis virulence.

Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression. The DosR regulon is thought to be involved in establishing latent tuberculosis infections in response to hypoxia and nitric oxide. Accordingly, DNA-binding by Cmr was severely impaired by nitrosation. A cmr mutant was better able to survive a nitrosative stress challenge but was attenuated in a mouse aerosol infection model. The complemented mutant exhibited a ∼2-fold increase in cmr expression, which led to increased sensitivity to nitrosative stress. This, and the inability to restore wild-type behaviour in the infection model, suggests that precise regulation of the cmr locus, which is associated with Region of Difference 150 in hypervirulent Beijing strains of Mtb, is important for TB pathogenesis

Phage therapy in antibiotic resistant pneumonia: immunomodulation or redistribution?

Our report concerns the observations made during the treatment of pneumonia with individually selected bacteriophages in HCAI patients on mechanical ventilation. 19 patients on mechanical ventilation whose condition was complicated by antibiotic-resistant pneumonia were examined. The treatment of patients was supplemented with phage therapy, bacteriophages were selected individually for each patient, taking into account the microbial etiology of the disease (Pseudomonas aeruginosa, Кlebsiella pneumoniae, Acinetobacter baumanii). Immunophenotyping of blood lymphocytes was carried out using 2-3-parameter flow cytometry. The functional activity of blood leukocytes was assessed by their ability to produce IFNα and IFNγ during cultivation. The level of interferons production in supernatants collected after cultivation was quantitatively evaluated both by their concentration (ELISA, reagents from “Vector-Best-Europe”, Russia) and by their biological activity. Statistical processing of the results was carried out using the Statistica 6 program according to the nonparametric Mann-Whitney U-test. In the course of successful phage therapy with individually selected bacteriophages overcoming of lymphopenia (if there was one) and an increase in both the number and functional activity of peripheral blood lymphocytes in all patients with pneumonia observed are noted. The relationship between the microbial load (mono- or mixed infection, the number of CFU pathogens of pneumonia, the need for repeated courses of phage therapy) and the degree of deficiency in one or another subpopulation of lymphocytes was not detected. Activation of the immune system achieved after one course of phage therapy was maintained for at least 3 weeks after phage administration was discontinued

Extraction of MO from Model Solutions for Processing Nickel-Aluminum-Cobalt Catalysts

A method of extraction extraction of molybdenum from AMC catalysts has been developed. The kinetics of the extraction process was studied. As well as the effect of soda concentration and temperature dependence on the degree of molybdenum extraction

REDD1 Protects Osteoblast Cells from Gamma Radiation-Induced Premature Senescence

Radiotherapy is commonly used for cancer treatment. However, it often results in side effects due to radiation damage in normal tissue, such as bone marrow (BM) failure. Adult hematopoietic stem and progenitor cells (HSPC) reside in BM next to the endosteal bone surface, which is lined primarily by hematopoietic niche osteoblastic cells. Osteoblasts are relatively more radiation-resistant than HSPCs, but the mechanisms are not well understood. In the present study, we demonstrated that the stress response gene REDD1 (regulated in development and DNA damage responses 1) was highly expressed in human osteoblast cell line (hFOB) cells after γ irradiation. Knockdown of REDD1 with siRNA resulted in a decrease in hFOB cell numbers, whereas transfection of PCMV6-AC-GFP-REDD1 plasmid DNA into hFOB cells inhibited mammalian target of rapamycin (mTOR) and p21 expression and protected these cells from radiation-induced premature senescence (PS). The PS in irradiated hFOB cells were characterized by significant inhibition of clonogenicity, activation of senescence biomarker SA-β-gal, and the senescence-associated cytokine secretory phenotype (SASP) after 4 or 8 Gy irradiation. Immunoprecipitation assays demonstrated that the stress response proteins p53 and nuclear factor κ B (NFkB) interacted with REDD1 in hFOB cells. Knockdown of NFkB or p53 gene dramatically suppressed REDD1 protein expression in these cells, indicating that REDD1 was regulated by both factors. Our data demonstrated that REDD1 is a protective factor in radiation-induced osteoblast cell premature senescence