Independent work of students in distance learning

The elaboration of the course task in the remote training of the students is aimed at assisting their preparation for the examination and enhancing their interest to the application of the theoretical knowledge. The usage of the materials and the methodical instructions for its elaboration could help the revealing of the creative potential of each trainee. The article demonstrates an original approach to the complex solution of a given professional taskРазработка курса задачи в дистанционном обучении студентов направлена на оказание помощи их подготовку к экзамену и повышения их интереса к применению теоретических знаний. Использование материалов и методических указаний для его разработки может помочь раскрытию творческого потенциала каждого обучающегося. Статья демонстрирует оригинальный подход к комплексному решению данной профессиональной задач

Issues when learning technical subjects via the MOODLE platform

The resources of the electronic learning platform are undoubtedly useful and convenient for students’ education. Using „Moodle“ platform when learning technical subjects requires more caution due to the fact that some of the tasks to be performed need to be carried out under real conditions and in direct contact with teachersРесурсы в платформе электронного обучения, несомненно, полезны и удобны для обучения студентов. Использование платформы Moodle для обучения технической дисциплине требует некоторой осторожности, учитывая, что некоторые задачи должны быть выполнены в реальном выражении и в непосредственном контакте с лекторам

Pro-autophagic signal induction by bacterial pore-forming toxins

Pore-forming toxins (PFT) comprise a large, structurally heterogeneous group of bacterial protein toxins. Nucleated target cells mount complex responses which allow them to survive moderate membrane damage by PFT. Autophagy has recently been implicated in responses to various PFT, but how this process is triggered is not known, and the significance of the phenomenon is not understood. Here, we show that S. aureus α-toxin, Vibrio cholerae cytolysin, streptolysin O and E. coli haemolysin activate two pathways leading to autophagy. The first pathway is triggered via AMP-activated protein kinase (AMPK). AMPK is a major energy sensor which induces autophagy by inhibiting the target of rapamycin complex 1 (TORC1) in response to a drop of the cellular ATP/AMP-ratio, as is also observed in response to membrane perforation. The second pathway is activated by the conserved eIF2α-kinase GCN2, which causes global translational arrest and promotes autophagy in response to starvation. The latter could be accounted for by impaired amino acid transport into target cells. Notably, PKR, an eIF2α-kinase which has been implicated in autophagy induction during viral infection, was also activated upon membrane perforation, and evidence was obtained that phosphorylation of eIF2α is required for the accumulation of autophagosomes in α-toxin-treated cells. Treatment with 3-methyl-adenine inhibited autophagy and disrupted the ability of cells to recover from sublethal attack by S. aureus α-toxin. We propose that PFT induce pro-autophagic signals through membrane perforation–dependent nutrient and energy depletion, and that an important function of autophagy in this context is to maintain metabolic homoeostasis

Programmed Cellular Necrosis Mediated by the Pore-Forming α-Toxin from Clostridium septicum

Programmed necrosis is a mechanism of cell death that has been described for neuronal excitotoxicity and ischemia/reperfusion injury, but has not been extensively studied in the context of exposure to bacterial exotoxins. The α-toxin of Clostridium septicum is a β-barrel pore-forming toxin and a potent cytotoxin; however, the mechanism by which it induces cell death has not been elucidated in detail. We report that α-toxin formed Ca2+-permeable pores in murine myoblast cells, leading to an increase in intracellular Ca2+ levels. This Ca2+ influx did not induce apoptosis, as has been described for other small pore-forming toxins, but a cascade of events consistent with programmed necrosis. Ca2+ influx was associated with calpain activation and release of cathepsins from lysosomes. We also observed deregulation of mitochondrial activity, leading to increased ROS levels, and dramatically reduced levels of ATP. Finally, the immunostimulatory histone binding protein HMGB1 was found to be released from the nuclei of α-toxin-treated cells. Collectively, these data show that α-toxin initiates a multifaceted necrotic cell death response that is consistent with its essential role in C. septicum-mediated myonecrosis and sepsis. We postulate that cellular intoxication with pore-forming toxins may be a major mechanism by which programmed necrosis is induced

Regulation of Hemolysin Expression and Virulence of Staphylococcus aureus by a Serine/Threonine Kinase and Phosphatase

Exotoxins, including the hemolysins known as the alpha (α) and beta (β) toxins, play an important role in the pathogenesis of Staphylococcus aureus infections. A random transposon library was screened for S. aureus mutants exhibiting altered hemolysin expression compared to wild type. Transposon insertions in 72 genes resulting in increased or decreased hemolysin expression were identified. Mutations inactivating a putative cyclic di-GMP synthetase and a serine/threonine phosphatase (Stp1) were found to reduce hemolysin expression, and mutations in genes encoding a two component regulator PhoR, LysR family transcriptional regulator, purine biosynthetic enzymes and a serine/threonine kinase (Stk1) increased expression. Transcription of the hla gene encoding α toxin was decreased in a Δstp1 mutant strain and increased in a Δstk1 strain. Microarray analysis of a Δstk1 mutant revealed increased transcription of additional exotoxins. A Δstp1 strain is severely attenuated for virulence in mice and elicits less inflammation and IL-6 production than the Δstk1 strain. In vivo phosphopeptide enrichment and mass spectrometric analysis revealed that threonine phosphorylated peptides corresponding to Stk1, DNA binding histone like protein (HU), serine-aspartate rich fibrinogen/bone sialoprotein binding protein (SdrE) and a hypothetical protein (NWMN_1123) were present in the wild type and not in the Δstk1 mutant. Collectively, these studies suggest that Stk1 mediated phosphorylation of HU, SrdE and NWMN_1123 affects S. aureus gene expression and virulence

The Eurasian Economic Union: integration without liberalisation?

The Eurasian Economic Union (EaEU) came into being in 2015 with the ostensible goal of increasing integration among its member states. An implicit assumption behind this goal was to further trade liberalisation, at least within the bloc, as a means to promote additional trade. This paper assesses the development of the EaEU against this promise. Going beyond an analysis of the dynamics of mutual trade, the main focus of this paper is to understand the EaEU’s institutional processes, examining if the commitments and framework put in place by the EaEU could actually contribute to trade liberalisation. Focusing on the trade policies at the level of the EaEU and the political economy of protectionism, our assessment is not favourable. In particular, the charge that the EaEU remains a geopolitical rather than economic project rings true, as trade liberalisation has been halting in individual member states and across the bloc as a whole. This reality is further illustrated in the external trade policies of the Union, most prominently in trade agreements concluded with Vietnam, Iran, Singapore and Serbia, and relations with other major trade partners. The paper argues that, in line with often overlooked theoretical predictions, the institutional framework of the EaEU is not robust enough to ensure that integration processes actually deliver on their stated objectives