Репозиторий Университета

© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Experimental Biology. Potato is the most economically important non-cereal food crop. Tuber formation in potato is regulated by phytohormones, cytokinins (CKs) in particular. The present work studied CK signal perception in potato. The sequenced potato genome of doubled monoploid Phureja was used for bioinformatic analysis and as a tool for identification of putative CK receptors from autotetraploid potato cv. Désirée. All basic elements of multistep phosphorelay required for CK signal transduction were identified in the Phureja genome, including three genes orthologous to three CK receptor genes (AHK 2-4) of Arabidopsis. As distinct from Phureja, autotetraploid potato contains at least two allelic isoforms of each receptor type. Putative receptor genes from Désirée plants were cloned, sequenced and expressed, and the main characteristics of encoded proteins were determined, in particular their consensus motifs, modelled structure, ligand-binding properties, and ability to transmit CK signals. In all studied aspects the predicted sensor histidine kinases met the requirements for genuine CK receptors. Expression of potato CK receptors was found to be organ-specific and sensitive to growth conditions, particularly to sucrose content. Our results provide a solid basis for further in-depth study of CK signaling system and biotechnological improvement of potato.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The activity of APHC2, a new polypeptide modulator of TRPV1 receptors that was isolated from Heteractis crispa, is studied. It was established that APHC2 possessed analgesic properties, did not disturb normal locomotor activity, and did not change body temperature and hemostasis of experimental animals. These attributes could be of great practical value for designing a new generation of efficacious analgesics. A brief increase of heart rate was observed during studies of the hemodynamic activity. Further investigation of the binding specifics of this polypeptide with TRPV1 receptors could open approaches to discovering other antagonists of these receptors.

© 2018, EDRA S.p.A. All rights reserved. Background. Asthma is a common childhood respiratory disease, affecting around 20% of Irish children. In other populations, vitamin D receptor (VDR) polymorphisms have been associated with asthma risk. We aimed to investigate the association between 2 VDR polymorphisms and uncontrolled paediatric asthma. Methods. 44 asthmatic children and 57 healthy volunteers were studied. The VDR TaqI gene variant in exon 9 (T/C) (rs731236) and ApaI (rs7975232) in intron 8 (C/T) were determined, using TaqMan® Assays. The lung function, serum 25-hydroxyvitamin D (25OHD) levels and other biomarkers of allergy, immunity, airway and systemic inflammation were assessed. Results. The distribution of T and C alleles and genotype frequencies differed significantly between asthmatics and controls for both polymorphisms (p < 0.05). A significant association was found between both TaqI (OR = 2.37, 95% CI (1.27 - 4.45), p = 0.007) and ApaI polymorphisms, and asthma risk (OR = 2.93, 95% CI (1.62 - 5.3), p = 0.0004). No association was observed between genotypes and 25OHD levels, lung function and other biomarkers, with the exception of Interleukin-10 (IL-10) and white blood cells count (WBC). IL-10 levels were lower in asthmatics with TC genotype for TaqI polymorphism (p < 0.01) and were higher in patients with TT genotype for ApaI (p < 0.01). WBC were higher in patients with TC and CC genotypes for TaqI (p < 0.05) and lower in TT genotype for ApaI (p < 0.05). Conclusion. TaqI and ApaI polymorphisms are associated with asthma in Irish children. Further studies are warranted to investigate the importance of decreased IL-10 levels in paediatric asthmatics with specific genotypes.

© 2018 Elsevier Ltd Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin–receptor interaction, we used 25 derivatives of potent cytokinin N6-benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis. The main in planta assay system was based on Arabidopsis double mutants retaining only one isoform of cytokinin receptors and harboring cytokinin-sensitive reporter gene. Classical cytokinin biotest with Amaranthus seedlings was used as an additional biotest. In parallel, the binding of ligands to individual cytokinin receptors was assessed in the in vitro test system. Quantitative comparison of results of different assays confirmed the partial similarity of ligand-binding properties of receptor isoforms. Substituents at positions 8 and 9 of adenine moiety, elongated linker up to 4 methylene units, and replacement of N6 by sulfur or oxygen have resulted in the suppression of cytokinin activity of the derivative toward all receptors. Introduction of a halogen into position 2 of adenine moiety, on the contrary, often increased the ligand activity, especially toward AHK3. Features both common and distinctive of cytokinin receptors in Arabidopsis and Amaranthus were revealed, highlighting species specificity of the cytokinin perception apparatus. Correlations between the extent to which a compound binds to a receptor in vitro and its ability to activate the same receptor in planta were evaluated for each AHK protein. Interaction patterns between individual receptors and ligands were rationalized by structure analysis and molecular docking in sensory modules of AHK receptors. The best correlation between docking scores and specific binding was observed for AHK3. In addition, receptor-specific ligands have been discovered with unique properties to predominantly activate or block distinct cytokinin receptors. These ligands are promising for practical application and as molecular tools in the study of the cytokinin perception by plant cells.

© 2018 Igolkina, Porozov, Chizhevskaya and Andronov. Sandwich-like docking configurations of the heterodimeric complex of NFR5 and K1 Vicia sativa receptor-like kinases together with the putative ligand, Nod factor (NF) of Rhizobium leguminosarum bv. viciae, were modeled and two of the most probable configurations were assessed through the analysis of the mutual polymorphisms and conservatism. We carried out this analysis based on the hypothesis that in a contact zone of two docked components (proteins or ligands) the population polymorphism or conservatism is mutual, i.e., the variation in one component has a reflected variation in the other component. The population material of 30 wild-growing V. sativa (leaf pieces) was collected from a large field (uncultivated for the past 25-years) and pooled; form this pool, 100 randomly selected cloned fragments of NFR5 gene and 100 of K1 gene were sequenced by the Sanger method. Congruence between population trees of NFR5 and K1 haplotypes allowed us to select two respective haplotypes, build their 3D structures, and perform protein–protein docking. In a separate simulation, the protein-ligand docking between NFR5 and NF was carried out. We merged the results of the two docking experiments and extracted NFR5–NF–K1 complexes, in which NF was located within the cavity between two receptors. Molecular dynamics simulations indicated two out of six complexes as stable. Regions of mutual polymorphism in the contact zone of one complex overlapped with known NF structural variations produced by R. leguminosarum bv. viciae. A total of 74% of the contact zone of another complex contained mutually polymorphic and conservative areas. Common traits of the obtained two stable structures allowed us to hypothesize the functional role of three-domain structure of plant LysM-RLKs in their heteromers.

© The Author(s) 2018. Earlier studies have shown that combination of antibodies to S100 protein and to cannabinoid receptor type 1 in released-active form (Brizantin) may possess anxiolytic properties and decrease nicotine dependence. Released-active form of antibodies is a novel approach that permits to modify natural functions of the target molecule (antigen) under investigation. The aim of the present study was to evaluate the anxiolytic-like effect of Brizantin in the light–dark test in mice, according to its ability to influence the number of entries into the lit compartment and the total time spent there. Three doses of Brizantin (2.5, 5, and 10 mL/kg) were compared with diazepam (1 mg/kg), placebo, and vehicle control. Anxiolytic-like effect of the tested drug was shown to be dose dependent, with an increasing trend from 2.5 to 10 mL/kg. Brizantin in its highest dose significantly increased studied behavioral parameters, although its effect was less pronounced than that of the reference drug diazepam (1 mg/kg).

© 2017 Elsevier Inc. A wide range of methods are known to increase the prokaryotic intracellular recombinant proteins solubility, for instance, growth at low temperature, supplementation of culture media with “chemical chaperones” (proline, glycine-betaine, and trehalose), co-expression with chaperones or highly soluble fusion partners. As an alternative, we have introduced the polyglutamate tag, which, as it has been shown, increased the protein solubility and facilitated folding. In this study we evaluated the minimal quantity of high density negatively charged EEEEVE amino acid repeats (pGlu) necessary to switch the recombinant receptor-binding domain of human alpha-fetoprotein (rbdAFP) expression almost entirely from the inclusion bodies to the soluble cytoplasmic fraction in E. coli. For this purpose, genetic constructs based on pET vectors coding rbdAFP and containing from 1 to 4 additional EEEEVE repeats at the C-terminus have been prepared. It was found that 3 pGlu repeats is the minimal number, that leads to a complete shift of the expression to the soluble cytoplasmic fraction in E. coli SHuffle Express T7 while 4 repeats were required for that in E. coli BL21(DE3). The rbdAFP contained 4 pGlu repeats was purified making use of ion-exchange chromatography and characterized by circular dichroism and ability to bind and accumulate in AFP receptor positive cancer cells in order to check for the structural and specific activity alterations related to the additional polyanionic sequence introduction.

© 2018 The Union. BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE : To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity. METHODS : TNFR1/2 levels on peripheral blood mononuclear cells (PBMCs) from 45 patients with aPTB and 150 healthy controls were analysed by flow cytometry using monoclonal antibodies and QuantiBRITE beads. Soluble TNFR1/2 and TNF-α in serum were measured using an enzyme-linked immunosorbent assay. RESULT S : TNFR1 expression in aPTB patients was increased in the main populations of immune cells. Patients who were Mycobacterium tuberculosis culturepositive on bronchoscopy had higher levels of the soluble forms of TNFR1 (sTNFR1) than M. tuberculosisnegative patients. CONCLUS ION: Active TB was shown to cause activation of different immune cell types by increasing TNFR1 expression on cells and reducing sTNFR1 expression compared with healthy controls. M. tuberculosis-positive patients with disseminated infection had the highest sTNFR1 serum level compared with other patients, but did not differ in receptor expression on PBMCs.

Physiology of breathing during sleep predisposes to the development or worsening of the respiratory disorders in patients with chronic obstructive pulmonary disease (COPD) even if waking respiratory function remains relatively normal. Physicians, who assess patient's state only during the day, in some cases can underestimate this problem. Respiratory abnormalities can provoke insomnia, which additionally affects patient's quality of life. Supplemental oxygen and pressure support ventilation improve blood gases during sleep, but in many cases, insomnia persists. In many cases, such patients need the treatment with hypnotics. Widely used drugs in insomnia are benzodiazepines. They are rather effective but can cause respiratory depression and respiratory failure in patients with COPD. Z-hypnotics are comparable to classical benzodiazepines but much more safe and rarely worsen respiratory parameters. Melatonin and melatonin receptor agonists, antihistamines, antidepressants and neuroleptics can be effective in some patients with insomnia, but insufficient data about their safety in case of respiratory pathology restrict the use of these drugs in patients with COPD. The orexin receptor antagonist suvorexant is a novel hypnotic with the potential benefits for patients with COPD because it strongly improves sleep but does not depress respiration and has a minimal negative impact on daytime cognitive function.

© 2018, Silicea-Poligraf. All rights reserved. The current population is characterized by a high prevalence of risk factors for the development of chronic kidney disease: hypertension, diabetes, obesity, metabolic syndrome, physical inactivity, smoking. The development of severe complications and a close connection with potentially fatal cardiovascular disorders make this disease a socially and economically significant problem. Treatment of chronic kidney disease in advanced stages belong to nephrologist duties. However, the success of preventive interventions depends on the time of their onset, which makes it relevant to identify the disease. The use of nephroprotective approaches by physicians of different specialties (general practitioners, cardiologists, gerontologists, nephrologists, endocrinologists) can significantly improve the prognosis of both those at risk of developing renal dysfunction and the existing disease. The review presents data on the clinical and laboratory efficacy of angiotensin-renin blocker use, as well as the combination of angiotensin II receptor blockers with calcium antagonists. Using the combination of the angiotensin II receptor blocker irbesartan and amlodipine as an example, we demonstrated the possibilities of nephroprotective therapy in patients with renal dysfunction.

© Russian Journal of Cardiology. Renin-angiotensin-aldosterone axis activation is an important mechanism of hypertension and its cardiovascular and renal complications. Angiotensin receptor blockers are considered among the first-choice antihypertensive drugs in Russia, European countries, and the USA. In addition to antihypertensive action, these drugs positively influence several components of the cardiovascular continuum and can be used for individualized management of high cardiovascular risk patients. The paper discusses the benefits of angiotensin receptor blockers use in patients with cardiovascular comorbidities. The paper includes a clinical case scenario revealing antihypertensive efficacy of telmisartan as an initial agent in a patient with high risk of cardiovascular events.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This article provides a short history of the creation of hypnotics, examines their mechanisms of action, and conducts a comparative analysis of the main groups of hypnotics such as barbiturates, benzodiazepines, "nonbenzodiazepine" benzodiazepine receptor agonists, melatonin receptor agonists, orexin receptor antagonists, histamine H1-receptor antagonists.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Current approaches to the search for new kappa-opioid receptor (κ-OR) agonists with potential analgesic activity are reviewed. Agents with peripheral activity and biased agonists are most promising for development. Signal events initiated by κ-OR activation are considered. Chemical structures of presently known κ-OR agonists are presented.

© 2018 Ima-Press Publishing House. All Rights Reserved. Objective: to investigate the effectiveness of cognitive and motor training as an additional method to basic therapy in patients with Alzheimer's disease (AD) and vascular cognitive impairment (VCI). Patients and methods: The investigation enrolled 41 patients (15 women and 26 men; mean age. 73.59±6.3 years), including 32 patients with AD (mean age 74.94±5.15 years) and 9 patients with VCI (mean age, 72.31±4.98 years). Cognitive impairment (CI) corresponded to mild dementia in 15 patients (5 women and 10 men; mean age 74.6±2.8 years) and to moderate dementia in 29 (10 women and 19 men; mean age 72.1±3.2 years). The patients were randomly assigned to individual, group, and mixed (individual and then group) cognitive training groups. Quantitative scales were used to assess changes in CI and emotional and behavioral disorders after 1.5, 3, and 6 months of therapy. Results and discussion: During cognitive and motor training, all the groups showed a significant decrease in the severity of CI (p < 0.05), depression, anxiety, and apathy. The effectiveness of the training was further influenced by the severity of concomitant cardiovascular disease, the degree of apathy, adherence to the training, and the early initiation of basic symptomatic therapy. The greatest positive changes in anxiety and depressive disorders were noted in the patients receiving group cognitive and motor training. Conclusion: The results of the investigation allow group cognitive and motor training to be recommended as a mainstay in the therapy of patients with CI concurrent with emotional disorders.

© 2018 Izdatel'stvo Meditsina. All rights reserved. NMDA receptor modulators are a new class of antidepressants with rapid onset of action and lasting antidepressant effect. These drugs increase BDNF level in CNS and adult hippocampal neurogenesis, which events are in common for both NMDA receptor modulators and classical antidepressants. However, unlike classical antidepressants, drugs of this new group produce no direct influence on the monoaminergic system, but regulate the neuroplasticity in the prefrontal cortex and hippocampus via modulation of the glutamatergic neurotransmission. Clinical tests of ketamine and rapastinel confirmed the rapid onset of action and the continuation of stable antidepressant effect (upon single administration per 7 days) for both usual and treatment-resistant forms of depression.

© Saint Petersburg Pasteur Institute. All rights reserved. The aim of the present systematic literature review is to summarize data on the role of TLRs in maintaining homeostasis of the female genitals, in maintaining the physiological development of pregnancy, provision of anti-infective resistance in pregnant women with intrauterine infection. The review substantiates the importance of TLRs of female genitals as a necessary and determining factor in the reaction to various changes in the environment, and also responsible for changes in metabolic, structural, or energy, in the maintenance of anti-infective resistance and homeostasis. As universal regulators of vital activity of organism TLRs in conjunction with other receptors of innate immunity provide maintaining the general reactivity and anti-infective resistance at the physiological level. In physiologically developing pregnancy in a background of immunosuppression in response to pregnancy TLRs during contact with infectious and non-infectious pathogens stimulate the production of nonspecific adaptive immunity factors (defensins, cathelicidins, histatines, etc.), which together with the non-specific innate factors lysozyme, complement, properdin, etc. support anti-infective resistance of the female genitals at a high level at the beginning of the infectious process. Possible violations of the development of pregnancy may be accompanied by changes in the response of TLRs to infectious and non-infectious factors until hyper-reaction, excessive inflammation or apoptosis, which requires adequate management of pregnancy. Was established the significance of the influence of pathogens of infectious and noninfectious origin in intrauterine infection indirectly through TLRs in the homeostasis of the organism, on the formation of breaches in anti-infective resistance at the organism and community level the identification of new pathophysiological and immunological pathogenetic mechanisms of development of pathological processes. IUI is a penetration of microorganisms into the tissues of fetus and it's infection. The inhibition of the functional activity of TLRs is accompanied by the direct effect of the pathogen on the tissues, and during hyper-reaction of TLRs to pathogens revealed a pronounced inflammatory response in the fetus. The level of expression of TLRs correlates directly with the severity of the process that can be considered as early markers of infection. Depending on the nature of the pathogen an increased expression of one or the other TLRs is observed. Explained the lack of symptoms, the possibility of atypical manifestations, the asymptomatic course of infection.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review article considers the modern notions about glucocorticoid hormones. Particular attention is paid to their molecular mechanisms of action, with emphasis on the importance of studying new compounds of the group of selective modulators of glucocorticoid receptors.

© 2018 Dynasty Publishing House. All rights reserved. The objective: The purpose of the study is to establish the role of infection with herpes simplex viruses type I and II in the pathogenesis of urogenital infection in pregnant women. Patients and methods: 89 patients of I, II trimester gestation, aged 18 to 35 years (average age of 27.5 ± 5.6 years) were examined. The design of the research and the methodology of verification of the UGI pathogens of pregnant women are presented in previously published materials. The establishment of character of pregnancy course (urgent delivery, premature birth, termination of pregnancy and mis-carriage), the presence or absence of infection and/or clinical manifestations of infectious and inflam-matory diseases, as well as evaluating the gene expression of TLR-2, TLR-3, TLR-4, TLR-8 (in relative units - RU) was conducted according to manuals. Results: It is established, that in UGI in pregnant combined viral-bacterial infection is registered. Viral component of UGI pathogens in pregnant women is presented by the association of viruses from the Herpesviridae family - herpes simplex viruses, Cytomega-lovirus, Epstein-Bar virus. Against the background of polyfactorial mechanisms of the pathogenesis of abortion, extra maximum activation of gene expression of TLR (22-23 RU or more) additional external factors, for example, infections can be an aggravating pathogenetic factor of miscarriage. Reduced expression of genes of TLR2, TLR4, TLR3 and TLR8 in the mucous membrane of the cervical canal in UGI of pregnant women in infection with herpes simplex virus due to the oppressive effect of pregnancy on the reaction of TLR, combined with the immunodepressive effect of the virus itself. With the violation of cellular part of immuno-logical reactivity of the body under the influence of adverse endogenous and exogenous factors on the process of pregnancy is activated the infectious process caused by the bacte-rial-viral pathogens association, which is accompanied by hyper reaction and increased reaction from the expression of genes of TLR, determines the pathological development of pregnancy. It is established that in the UGI of pregnant gene expression levels of TLR2-21.2 and above, TLR4-23.0 and above, TLR8 - 26.0 and above (the level of gene expression of TLR8 above 28 is the predictor of the onset of abortion and miscarriage) testify to the acute infectious process with the clinical manifestations of the UGI, and also indicates the possible interruption of pregnancy and miscarriage; levels of gene expression of TLR2 below 21.2, TLR4 below 23.0, TLR8 below 26.0, in-dicated a decrease in the severity of the infectious process and its chronicity, as well as the possibility of direct microbial damage to the tissues of UGT, placenta, and fetus. Conclusion: Verified in preg-nant women in 61% of cases clinical manifestations of the infectious process are necessarily associated with the verification of the association of herpes simplex viruses I and II type - triggers of infectious process deterioration, determining the prognosis and outcome of the development of the UGI in preg-nant.

© 2018 Ima-Press Publishing House. All rights reservbed. Dementia develops as a result of continuous long-term progression of less severe cognitive impairment (CI). Social and psychological methods (neurocognitive stimulation and neurocognitive training) are the mainstay of treatment for dementia. At the moment, there are no drugs both to cure dementia and to stop the degeneration of nerve tissue. Modern pharmacotherapy for dementia aims to maintain cognitive functions in the patient for as long as possible and to slow down disability, thus ensuring higher living standards. CI therapy most often consists of compensation for cognitive defect. Among the whole variety of pharmacological agents, the effective drugs to treat dementia are only two groups, such as acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. Atypical neuroleptics are employed for the treatment of psychotic disorders; antidepressants from a group of selective serotonin reuptake inhibitors are for depression. Cognitive behavioral therapy and cognitive stimulation deserve special attention. A high educational level and physical, social, and intellectual and activities can prevent dementia.

© 2018 Media Sphera Publishing Group. All rights reserved. A review deals with the problem of chronic kidney disease (CKD) from the position of a physician and cardiologist. The epidemiology of the disease was discussed both abroad and in Russia, including the most up-to-date data. In Russia CKD markers were detected in 49.4% of hypertensives. Authors describe risk factors and mechanisms of CKD at the most important pathogenetic conditions: hypertension, diabetes and obesity. The current classification and methods for calculating the glomerular filtration rate are given. The review disclose a paradigm of the renal continuum and its relation to cardiovascular diseases. It is well known fact that the final causes of the death of patients with CKD, as a rule, are cardiovascular complications. Based on the literature data, the necessity and expediency of screening for renal dysfunction is justified. In the example of use of an angiotensin receptor blocker II - irbesartan nephroprotective demonstrated possibilities of intervention in patients with renal dysfunction of varying severity.