Репозиторий Университета

© 2019 He et al. Current understanding of flagellum/cilium length regulation focuses on a few model organisms with flagella of uniform length. Leptomonas pyrrhocoris is a monoxenous trypanosomatid parasite of firebugs. When cultivated in vitro, L. pyrrhocoris duplicates every 4.2 ± 0.2 h, representing the shortest doubling time reported for trypanosomatids so far. Each L. pyrrhocoris cell starts its cell cycle with a single flagellum. A new flagellum is assembled de novo, while the old flagellum persists throughout the cell cycle. The flagella in an asynchronous L. pyrrhocoris population exhibited a vast length variation of ∼3 to 24 μm, casting doubt on the presence of a length regulation mechanism based on a single balance point between the assembly and disassembly rate in these cells. Through imaging of live L. pyrrhocoris cells, a rapid, partial disassembly of the existing, old flagellum is observed upon, if not prior to, the initial assembly of a new flagellum. Mathematical modeling demonstrated an inverse correlation between the flagellar growth rate and flagellar length and inferred the presence of distinct, cell cycle-dependent disassembly mechanisms with different rates. On the basis of these observations, we proposed a min-max model that could account for the vast flagellar length range observed for asynchronous L. pyrrhocoris. This model may also apply to other flagellated organisms with flagellar length variation. IMPORTANCE Current understanding of flagellum biogenesis during the cell cycle in trypanosomatids is limited to a few pathogenic species, including Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The most notable characteristics of trypanosomatid flagella studied so far are the extreme stability and lack of ciliary disassembly/absorption during the cell cycle. This is different from cilia in Chlamydomonas and mammalian cells, which undergo complete absorption prior to cell cycle initiation. In this study, we examined flagellum duplication during the cell cycle of Leptomonas pyrrhocoris. With the shortest duplication time documented for all Trypanosomatidae and its amenability to culture on agarose gel with limited mobility, we were able to image these cells through the cell cycle. Rapid, cell cycle-specific flagellum disassembly different from turnover was observed for the first time in trypanosomatids. Given the observed length-dependent growth rate and the presence of different disassembly mechanisms, we proposed a min-max model that can account for the flagellar length variation observed in L. pyrrhocoris.

© Copyright © 2019 Veremeyko, Yung, Dukhinova, Strekalova and Ponomarev. Twenty years ago, the scientific community exhibited relatively little interest in the study of microglial cells. However, recent technical and conceptual advances in this field have greatly increased interest in the basic biology of these cells within various neurodegenerative diseases, including multiple sclerosis, Alzheimer’s disease, and traumatic brain/spinal cord injuries. The main functions of these cells in the normal central nervous system (CNS) remain poorly understood, despite considerable elucidation of their roles in pathological conditions. Microglia populate the brain before birth and remain in close lifelong contact with CNS-resident cells under the influence of the local microenvironment. Within the CNS parenchyma, microglia actively interact with two main cell types, astrocytes and neurons, which produce many factors that affect microglia phenotypes in the normal CNS and during neuroinflammation. These factors include interleukin (IL)-34, macrophage colony-stimulating factor, transforming growth factor-β, and IL-4, which promote microglial expansion, survival, and differentiation to an anti-inflammatory phenotype in the normal CNS. Under inflammatory conditions, however, astrocytes produce several pro-inflammatory factors that contribute to microglial activation. The interactions of microglia with neurons in the normal and diseased CNS are especially intriguing. Microglia are known to interact actively with neurons by facilitating axonal pruning during development, while neurons provide specific factors that alter microglial phenotypes and functions. This review focuses mainly on the roles of soluble neuronal factors that affect microglial phenotypes and functions and the possible involvement of these factors in the pathology of neurodegenerative diseases.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The object of this contribution based on a systematic review of the literature is to examine to what degree the level of use and potency play a role in regulatory policies for alcohol, other psychoactive substances and gambling, and whether there is an evidence base for this role. Level of use is usually defined around a behavioural pattern of the user (for example, cigarettes smoked per day, or average ethanol use in grams per day), while potency is defined as a property or characteristic of the substance. For all substances examined (alcohol, tobacco, opioids, cannabis) and gambling, both dimensions were taken into consideration in the formulation of most regulatory policies. However, the associations between both dimensions and regulatory policies were not systematic, and not always based on evidence. Future improvements are suggested.

© Copyright © 2019 Krasil’nikova, Surin, Sorokina, Fisenko, Boyarkin, Balyasin, Demchenko, Pomytkin and Pinelis. Glutamate excitotoxicity is implicated in the pathogenesis of numerous diseases, such as stroke, traumatic brain injury, and Alzheimer’s disease, for which insulin resistance is a concomitant condition, and intranasal insulin treatment is believed to be a promising therapy. Excitotoxicity is initiated primarily by the sustained stimulation of ionotropic glutamate receptors and leads to a rise in intracellular Ca2+ ([Ca2+]i), followed by a cascade of intracellular events, such as delayed calcium deregulation (DCD), mitochondrial depolarization, adenosine triphosphate (ATP) depletion that collectively end in cell death. Therefore, cross-talk between insulin and glutamate signaling in excitotoxicity is of particular interest for research. In the present study, we investigated the effects of short-term insulin exposure on the dynamics of [Ca2+]i and mitochondrial potential in cultured rat cortical neurons during glutamate excitotoxicity. We found that insulin ameliorated the glutamate-evoked rise of [Ca2+]i and prevented the onset of DCD, the postulated point-of-no-return in excitotoxicity. Additionally, insulin significantly improved the glutamate-induced drop in mitochondrial potential, ATP depletion, and depletion of brain-derived neurotrophic factor (BDNF), which is a critical neuroprotector in excitotoxicity. Also, insulin improved oxygen consumption rates, maximal respiration, and spare respiratory capacity in neurons exposed to glutamate, as well as the viability of cells in the MTT assay. In conclusion, the short-term insulin exposure in our experiments was evidently a protective treatment against excitotoxicity, in a sharp contrast to chronic insulin exposure causal to neuronal insulin resistance, the adverse factor in excitotoxicity.

© 2019, Pleiades Publishing, Ltd. Abstract: Histone-like protein HU is a dimeric nucleoid-associated protein (NAP). HU is the most conserved NAP. It binds nonspecifically to duplex DNA with a preference for targeting nicked and bent DNA. HU limits the architecture of the bacterial nucleoid and its deletion is lethal for Bacillus subtilis and Mycoplasma genitalium which do not contain other NAPs. E. coli lacking HU is viable but has numerous growth defects. The effects of the HU protein on gene expression is known from microarray analysis and HU regulons were identified. In HU-deficient E. coli, absence of this DNA architectural protein causes a disorder in gene regulation; on the other hand, E. coli growth under standard conditions is almost unaltered in the absence of HU. To understand how the bacterium confronts the chromosomal disorder, we performed proteome analysis to compare protein abundances in cells containing the HU protein or not. Comparison of the proteomic profile of wild-type and HU-deficient E. coli shows how the altered gene expression influences the protein content. We show that proteome profile changes are very similar to the gene expression profile changes in HU-deficient E. coli. Several exceptions show that proteome studies are very important.

© 2018 John Wiley  &  Sons, Ltd. Distribution of blood flow in myocardium is a key determinant of the localization and severity of myocardial ischemia under impaired coronary perfusion conditions. Previous studies have extensively demonstrated the transmural difference of ischemic vulnerability. However, it remains incompletely understood how transmural myocardial flow is regulated under in vivo conditions. In the present study, a computational model of the coronary circulation was developed to quantitatively evaluate the sensitivity of transmural flow distribution to various cardiovascular and hemodynamic factors. The model was further incorporated with the flow autoregulatory mechanism to simulate the regulation of myocardial flow in the presence of coronary artery stenosis. Numerical tests demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim), and coronary perfusion pressure (Pper) were the major determinant factors for transmural flow distribution (evaluated by the subendocardial-to-subepicardial (endo/epi) flow ratio) and that the flow autoregulatory mechanism played an important compensatory role in preserving subendocardial perfusion against reduced Pper. Further analysis for HR variation-induced hemodynamic changes revealed that the rise in endo/epi flow ratio accompanying HR decrease was attributable not only to the prolongation of cardiac diastole relative to systole, but more predominantly to the fall in Pim. Moreover, it was found that Pim and Pper interfered with each other with respect to their influence on transmural flow distribution. These results demonstrate the interactive effects of various cardiovascular and hemodynamic factors on transmural myocardial flow, highlighting the importance of taking into account patient-specific conditions in the explanation of clinical observations.

© 2018. ASERS Publishing. All rights reserved. The paper understands cross-border natural resources as a totality of characteristics of local ecological systems, which can act as regulators of human’s life space. Authors state that uniqueness of this phenomenon is defined by the fact that all natural resources act as a single system of planet scale. The problem distinguished in the paper is based on the fact that in the period of ecological systems and natural resources development a little attention is paid to cross-border management on the part of nations they belong to. The research subject is an indicator of stability and quality of management of cross-border natural resources in the aspect of their even existing and carrying out of their functions. Scientific novelty of the research is that it’s proved for the first time that each ecological system has s number of parameters, one of which shows how much it resistant to human impact. The system of providing biodiversity is one of such parameters. In the paper the legal characteristics of the issue are identified with the actual state of interstate cooperation and the opportunity of its expansion within the already existing interstate formation is determined. The example of such formation is European Union. The areas of further research can be defined as an expansion of specified cooperation of Asian and South American continent.

© 2018 Russian Association of Endocrinologists. All rights reserved. The development of effective methods of obesity treatment with the goal of preventing many associated diseases is among the priorities of modern biomedical research. In 2016 glucagon-like peptide-1 analog (GLP-1) liraglutide 3 mg (Saxenda®) was approved in the Russian Federation for the treatment of obesity. This review presents literature data on the effects of GLP-1 and liraglutide on appetite and body weight as well as an analysis of the effectiveness and safety of drug Saxenda based on the results of major clinical trials.

© 2018 Bulletin of Siberian Medicine. All rights reserved. The aim of the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs. Materials and methods. 157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods. Results. It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance. Conclusion. Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.

© 2018 Nutritec. All rights reserved. Specialized sports nutrition is one of the most important factors in the extension of the functional potential of athletes, providing adaptive resistance to physical stress, which determines the high physical performance and prolongs athletic longevity of the athletes. The study involved 30 skiers-racers (the average age of 19.5±1.8 years). 12 skiers of the main group within 21 days consumed a specialized food product, obtained on the basis of fermented milk whey containing amino acids, several vitamins, minerals and trace elements, live culture of lactic acid bacteria: L. lactis, L. thermophilus, L. bulgaricus (1.2 × 10s CFU/cm3). The control group consisted of 18 skiers, those taking the placebo (food starch of the same consistency). After a course of product intake, blood level of hemoglobin increased by 6%, of leukocytes - by 10% due to an increase in the number of granulocytes by 32%, and segmented neutrophils by 16% (p<0.05), there was a tendency to increase the number of red blood cells by 7% with a significant decrease in lymphocyte count by 19%. Erythrocyte sedimentation rate in blood of the skiers from the comparison group increased by 41% (p<0.05), while in the athletes of the main group it decreased by 16% (p>0.05). After product intake it has been established by the method of laser Dopplerflowmetry that there was a tendency to increase blood perfusion by 15%, a statistically reliable increase in the flux by 53%, which is based on the improvement of the internal mechanisms of microcirculation regulation. According to the mathematical analysis of cardiac rhythm, centralization of regulation decreased while the activity of an autonomous mechanism for controlling the work of the heart increased. The revealed functional changes ensured an increase of absolute (by 31%, p<0.05) and relative (by 33%, p<0.05) physical performance and aerobic endurance of skiers, contributed to the improvement of short-Term memory. The conclusion is made about the expediency of the intake of the specialized food product to enhance the adaptive capacity of athletes under the influence of systematic physical loads.

© 2018 Ima-Press Publishing House. All rights reserved. The paper analyzes the concepts of personality profiles and demonstrates the possibility of applying this approach to comparatively assessing the psychological characteristics of patients with essential arterial hypertension (EAH). It sets forth the fundamentals of the concepts by F. Alexander, H.F. Dunbar, M. Friedman, and R. Rosenman, which emphasize the importance of emotional, personal, and behavioral factors for the etiology and pathogenesis of EAH and analyzes in detail the psychological study of the characteristics of the so-called type D (distressed) personality that is characterized by a combination of the predominance of negative emotions, social isolation, and inability to regulate these factors. The authors present the results of their own empirical study of personal characteristics (through the Cattel's 16 personality factors questionnaire) in patients with office hypertension (OH) versus those with classical EAH and healthy individuals. OH patients are shown to be significantly less sociable, less emotionally stable, more overwrought and shy, and more prone to self-control and feelings of guilt. The experimental psychological study (by simulating of emotional stress and by using the modified variant of the procedure developed by S. Rosenzweig to examine frustration reactions) has revealed that the patients with OH tend to experience the most intense negative sthenic emotions and they significantly more frequently resort to repression of these emotions. The findings prove that the EAH group is e heterogeneous and confirm the assumption that OH patients show negative affectivity and lower social activity.