Репозиторий Университета

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The review summarizes information on cyclopropane as an independent pharmacophore group and as a fragment for modification of pharmacological activity level of medicines used in practice. The advantages of a cyclopropane fragment over its bioisosteres are that, on the one hand, this fragment imposes conformational rigidity on the molecules of physiologically active compounds and, on the other hand, the replacement of acyclic terminal and “linker” groups with a cyclopropane fragment increases the metabolic stability of the target structures and extends the scope of their therapeutic action.

© 2018, Pleiades Publishing, Ltd. Genes encoding two three-finger toxins TFT-AF and TFT-VN, nucleotide sequences of which were earlier determined by cloning cDNA from venom glands of vipers Azemiops feae and Vipera nikolskii, respectively, were expressed for the first time in E. coli cells. The biological activity of these toxins was studied by electrophysiological techniques, calcium imaging, and radioligand analysis. It was shown for the first time that viper three-finger toxins are antagonists of nicotinic acetylcholine receptors of neuronal and muscle type.

© 2018, Pleiades Publishing, Inc. The article presents empirical data on the possible use of transcranial Doppler sonography as a method for the identification of functional specialization of hemispheres. We investigated intrahemispheric differences in the increase in blood flow velocity indicators during the performance of cognitive tasks with verbal and nonverbal stimuli in 20 healthy right-handed participants and 20 right-handed patients with local unilateral vascular brain lesions. We observed interhemispheric and intrahemispheric differences in blood flow velocity indicators between arteries during the performance of cognitive tasks with different variants of verbal stimuli in all participants. It has been found that one of the hemispheres plays a dominant role in verbal and nonverbal stimulus processing.

© 2017 The British Pharmacological Society Background and Purpose: Acid-sensing ion channels (ASICs) play an important role in synaptic plasticity and learning, as well as in nociception and mechanosensation. ASICs are involved in pain and in neurological and psychiatric diseases, but their therapeutic potential is limited by the lack of ligands activating them at physiological pH. Experimental Approach: We extracted, purified and determined the structure of a bisbenzylisoquinoline alkaloid, lindoldhamine, (LIN) from laurel leaves. Its effect on ASIC3 channels were characterized, using two-electrode voltage-clamp electrophysiological recordings from Xenopus laevis oocytes. Key Results: At pH 7.4 or higher, LIN activated a sustained, proton-independent, current through rat and human ASIC3 channels, but not rat ASIC1a or ASIC2a channels. LIN also potentiated proton-induced transient currents and promoted recovery from desensitization in human, but not rat, ASIC3 channels. Conclusions and Implications: We describe a novel ASIC subtype-specific agonist LIN, which induced proton-independent activation of human and rat ASIC3 channels at physiological pH. LIN also acts as a positive allosteric modulator of human, but not rat, ASIC3 channels. This unique, species-selective, ligand of ASIC3, opens new avenues in studies of ASIC structure and function, as well as providing new approaches to drug design.

© 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, Pediatria Ltd. All rights reserved. It is known that duration of postvaccinal immunity against viral hepatitis B is influenced by such factors as time of the last vaccination, immunization schedule, age, profession, the initial health state. Often there are difficulties in vaccinating children with recurrent respiratory diseases (RRD). Objective of the research – to evaluate the peculiarities of specific immunityformation after hepatitis B vaccination in children with RRD. Study materials and methods: authors performed a comparative prospective study to assess the level of postvaccinal immunity against viral hepatitis B in two comparison groups – healthy children and children with RRD aged 1–17 years. Blood was sampled for evaluation of anti-HBs and a protective level of protection for 18 months from the start of vaccination. Results: children with RRD had a delayed synthesis of antibodies for administration of hepatitis B vaccine first doses. The 3rd vaccine administration results in 100% seroconversion. One year after complete vaccination a marked decrease in anti-HBs occurs in such children, and the proportion of seronegative individuals among them is 40% compared to 10% among healthy individuals.

© 2018, Pleiades Publishing, Ltd. X-ray diffraction is used to determine the structure of a new 3-(benzo[d]oxazole-2-yl)-1-(2-(1,3,3- trimethylindoline-2-ylidene)ethylidene)naphthalene-2(1H)-one zinc chloride complex 1. It is demonstrated that the ligand molecule in complex 1 has a trans–trans–cis conformation in which the indoline nitrogen atom is oriented in the same direction as the chelate ring, which could promote an additional coordination with the complexing atom.

© 2018, Pleiades Publishing, Ltd. The identification of factors that determine the structure and rate of mortality is a topical complex task requiring unification of efforts of medical science and social disciplines. The authors contribute to its solution through a comparative study of mortality indicators in two Russian megalopolises—Moscow and St. Petersburg. Analyzing statistical data, they form several hypotheses that help explain the significant differences in the mortality rates of the two cities. The focus is not only on the socioeconomic and climatic features of Moscow and St. Petersburg but also on the state of the financial and resource support of the health care systems of these cities. The results obtained are only the first step, but a necessary one, toward an adequate system of measures to decrease mortality, implying subsequent studies on the significance of each of the factors considered.

© 2018, Pleiades Publishing, Ltd. Pyridoxine derivatives, 3-hydroxy-2-methylpyridine-4- and -5-carbohydrazides, were synthesized according to optimized known procedures, and a method for the synthesis of 5-(hydroxymethyl)-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-6-carbohydrazide was developed. The hydroxymethyl groups in positions 5 and 6 of 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine showed different reactivities, and only the 6-hydroxymethyl group was selectively oxidized to aldehyde under mild conditions. The lactone ring in 5,6-dihydrofuro[3,4-b]pyridin-7(5H)-one was found to be stable to nucleophiles. The synthesized hydrazides showed no antimycobacterial activity.

© 2018, Pleiades Publishing, Ltd. Metal and metal oxide nanoparticles are considered a basis for the development of antibacterial agents of new generation. Dental drugs are among the promising fields of their application. Experimental samples are obtained and microbiological studies are carried out with the dental plaque microflora and aqueous solutions of Fe3O4, SnO, ZnO, Ag, and Cu nanoparticles 10–100 nm in size and with a mass concentration of 1.53–10.12 mg/L. The study of the effect of colloid solutions on the culture of dental plaque microflora shows that the antibacterial properties predominantly depend on the chemical composition of the particles of the dispersed phase. Dispersed systems containing magnetite with an initial concentration of 2.11 mg/L, as well as silver (2.39 mg/L), copper (2.07 mg/L), and zinc oxide (7.03 mg/L), prove to be the most efficient ones. The results of this study may be used to develop promising mouth rinse and other antibacterial drugs based on aqueous solutions of metal and metal oxide nanoparticles.

© 2018 The Author(s). Published by S. Karger AG, Basel.  Background/Aims: Endothelial-mesenchymal transition (EndMT) has been shown to take part in the generation and progression of diverse diseases, involving a series of changes leading to a loss of their endothelial characteristics and an acquirement of properties typical of mesenchymal cells. Low-intensity pulsed ultrasound (LIPUS) is a new therapeutic option that has been successfully used in fracture healing. However, whether LIPUS can inhibit oxidative stress-induced endothelial cell damages through inhibiting EndMT remained unknown. This study aimed to investigate the protective effects of LIPUS against oxidative stress-induced endothelial cell damages and the underlying mechanisms. Methods: EndMT was induced by H 2 O 2 (100 μm for seven days). Human aortic endothelial cells (HAECs) were exposed to H 2 O 2 with or without LIPUS treatment for seven days. The expression of EndMT markers (CD31, VE-cadherin, FSP1 and α-SMA) were analyzed. The levels of total and phosphorylated PI3K and AKT proteins were detected by Western Blot analysis. Cell chemotaxis was determined by wound healing and transwell assay. Results: LIPUS relieved EndMT by decreasing ROS accumulation and increasing activation of the PI3K signaling cascade. LIPUS alleviated the migration of EndMT-derived mesenchymal-like cells through reducing extracellular matrix (ECM) deposition that is associated with matrix metallopeptidase (MMP) proteolytic activity and collagen production. Conclusion: LIPUS produces cytoprotective effects against oxidative injuries to endothelial cells through suppressing the oxidative stress-induced EndMT, activating the PI3K/AKT pathway under oxidative stress, and limiting cell migration and excessive ECM deposition.

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Inertial microfluidics has emerged recently as a promising tool for high-throughput manipulation of particles and cells for a wide range of flow cytometric tasks including cell separation/filtration, cell counting, and mechanical phenotyping. Inertial focusing is profoundly reliant on the cross-sectional shape of channel and its impacts on not only the shear field but also the wall-effect lift force near the wall region. In this study, particle focusing dynamics inside trapezoidal straight microchannels was first studied systematically for a broad range of channel Re number (20 OpenSPiltSPi Re OpenSPiltSPi 800). The altered axial velocity profile and consequently new shear force arrangement led to a cross-lateral movement of equilibration toward the longer side wall when the rectangular straight channel was changed to a trapezoid; however, the lateral focusing started to move backward toward the middle and the shorter side wall, depending on particle clogging ratio, channel aspect ratio, and slope of slanted wall, as the channel Reynolds number further increased (Re CloseSPigtSPi 50). Remarkably, an almost complete transition of major focusing from the longer side wall to the shorter side wall was found for large-sized particles of clogging ratio K ~ 0.9 (K = a/Hmin) when Re increased noticeably to ~ 650. Finally, based on our findings, a trapezoidal straight channel along with a bifurcation was designed and applied for continuous filtration of a broad range of particle size (0.3 OpenSPiltSPi K OpenSPiltSPi 1) exiting through the longer wall outlet with ~ 99% efficiency (Re OpenSPiltSPi 100).

© 2017, Springer Science+Business Media New York. Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay. Our results indicated that hMSCA-CM improved cell viability, reduced nuclear fragmentation, attenuated the production of reactive oxygen species, and preserved mitochondrial membrane potential and ultrastructural parameters. In addition, hMSCA-CM upregulated neuroglobin in T98G cells and the genetic silencing of this protein prevented the protective action of hMSCA-CM on damaged cells, suggesting that neuroglobin is mediating, at least in part, the protective effect of hMSCA-CM. Overall, this evidence suggests that the use of hMSCA-CM is a promising therapeutic strategy for the protection of astrocytic cells in central nervous system (CNS) pathologies.

© 2017 This work is aimed at exhaustive and detailed study of chemical, physical and physico-chemical characteristics of NO-containing gas flow (NO-CGF) generated by a plasma-chemical generator of Plason device, which has been used in medical practice for more than 15 years for effectively healing wound and inflammatory conditions with exogenous nitric oxide (NO-therapy). Data was obtained on spatial structure of the gas flow, and values of its local parameters in axial and radial directions, such as nitric oxide content, velocity, temperature and mass flow density of nitric oxide, providing altogether the effectiveness of treatment by the exogenous NO-therapy method, were determined experimentally and by computations. It was demonstrated that plasma-chemical synthesis of NO from atmospheric air in a low direct current (DC) arc provides a high mass flow of nitric oxide at the level of 1.6–1.8 mg/s, while in the area of impact of NO-CGF on the biological tissue, on its axis, NO content is 400–600 ppm, flow velocity about 5 m/s, nitric oxide mass flow density 0.25–0.40 mg/(s·cm2), temperature 40-60 °C. Tendencies were determined for designing new devices for further experimental biological and medical research in the field of NO-therapy: lowering the temperature of NO-CGF to ambient temperature will enable variation, in experiments, of the affecting flow parameters in a wide range up to their maximum values: NO content up to 2000 ppm, velocity up to 20 m/s, nitric oxide mass flow density up to 2.5 mg/(s·cm2).

© 2018 Wiley-VCH Verlag GmbH  &  Co. KGaA, Weinheim The rational design of broad-spectrum antivirals requires data on antiviral activity of compounds against multiple viruses, which are often not available. We have developed a panel of (+)ssRNA viruses composed of Enterovirus and Flavivirus genera members allowing to study these activity spectra. Antiviral activity profiling of a set of nucleoside analogues revealed N4-hydroxycytidine as an efficient inhibitor of replication of coxsackieviruses and other enteroviruses, but ineffective against tick-borne encephalitis virus. Furano[2, 3-d]pyrimidine nucleosides with n-pentyl or n-hexyl tails showed selective inhibition of Enterovirus A representatives. 5-(Tetradec-1-yn-1-yl)-uridine showed selective inhibition of tick-borne encephalitis virus at the micromolar level.

© 2017 Elsevier B.V. A novel ternary intermetallic germanide CeIrGe2 has been studied by means of x-ray diffraction, magnetization, specific heat and electrical resistivity measurements, performed in wide ranges of temperature and external magnetic fields. The compound crystallizes in an orthorhombic structure of the CeNiSi2-type (space group Cmcm). It exhibits a Kondo lattice behavior and orders antiferromagnetically at 4 K.

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered.

© The Author(s) 2017. Modeling tools provide a valuable support for DNA origami design. However, current solutions have limited application for conformational analysis of the designs. In this work we present a tool for a thorough study of DNA origami structure and dynamics. The tool is based on a novel coarse-grained model dedicated to geometry optimization and conformational analysis of DNA origami. We explored the ability of the model to predict dynamic behavior, global shapes, and fine details of two single-layer systems designed in hexagonal and square lattices using atomic force microscopy, Förster resonance energy transfer spectroscopy, and all-atom molecular dynamic simulations for validation of the results. We also examined the performance of the model for multilayer systems by simulation of DNA origami with published cryo-electron microscopy and atomic force microscopy structures. A good agreement between the simulated and experimental data makes the model suitable for conformational analysis of DNA origami objects. The tool is available at http://vsb.fbb.msu.ru/cosm as a web-service and as a standalone version.

© 2018 Elsevier Ltd The use of materials based on protein-polymer compositions is a promising method for solving a number of problems in biotechnology and medicine. In our work, we produced multilayer nanofilms based on 4th generation (G4) pyridylphenylene dendrimers with fully pyridine-based periphery containing a protein component. For dairy beta- and kappa-caseins, alpha-lactalbumin, recombinant sheep prion protein, lysozyme, trypsin, and alpha-chymotrypsin the ability to integrate into self-organizing structures about 230–710 nm thick, measured by atomic force microscopy, was found. The formation of nanofilms is dependent on the protein/dendrimer ratio in the initial solution. At the same time, the nanofilms are resistant to pH changes, and the action of detergents. We demonstrated that trypsin and chymotrypsin incorporated into the nanofilms still conserved proteolytic activities and were stable for at least 3 weeks. We have also conducted in silico molecular modeling of the G4 dendrimer interactions with lysozyme. Spatial structure of the dendrimer-protein complex was predicted and most probable variant remained almost intact under 100 ns molecular dynamics simulation conditions. We believe that dendrimer-protein systems are promising tools for possible applications in the development of new stable biomaterials and biosensors.

© 2018 Tkacheva et al. Background: Geriatric syndromes (GSs) are common in older adults and have a significant effect on their quality of life, disability, and use of health care resources. Few studies have assessed the prevalence of GSs in Russia. The aim of this study is to assess the prevalence of GSs among older adults living in the community in Moscow. Methods: A cross-sectional study was conducted in four community clinics in Moscow. A total of 1,220 patients completed a screening questionnaire, and 356 of them also underwent a comprehensive geriatric assessment (CGA). Results: The mean age of the 1,220 participants was 74.9±6.1 years; 75.5% were women. Based on the questionnaire, 58.3% reported visual or hearing impairment, 58.2% cognitive impairment, 46% mood disorder, 42% difficulty walking, 28.3% urinary incontinence, 21.3% traumatic falls (over the previous year), and 12.2% weight loss. The mean number of GSs per patient was 2.9±1.5. Based on CGA, a decline in Instrumental Activity of Daily Living score was identified in 34.8% of the patients, a risk of malnutrition (Mini-Nutritional Assessment score, 17–23.5) in 25.8%, probable cognitive impairment (Mini-Mental State Examination score <25) in 8.6%, and symptoms of depression (15-item Geriatric Depression Scale score >5) in 36.2%. On the whole, patients demonstrated good mobility (average walking speed, 1±0.2 m/s) and hand grip strength (23.9±6.4 kg in women and 39.1±8.3 kg in men), but poor balance (only 39.4% were able to maintain their balance on one leg for 10 s or more). Conclusion: The results of this study demonstrate a high prevalence of GSs among community-dwelling people aged 65 years and older in Moscow. The results provide a better understanding of the needs of older adults in Russia and can facilitate planning for medical and social assistance for this population.