Репозиторий Университета

© 2018 Elsevier B.V. Development of efficient biodegradable, environmentally responsive, biocompatible and non-toxic delivery system is needed for efficient gene delivery. As well known, properties of the vehicle are determined by the structure of carrier components. The aim of the current study was to estimate in vitro transfection efficacy of aliphatic di-, tri- and tetrapeptide-based cationic lipoplexes loaded with siRNA in function of a number of cationic groups using 2D (monolayer culture) and 3D (multicellular tumor spheroids) in vitro models. Physicochemical properties and cytotoxicity of the liposomes were found to be dependent upon a number of amino acid derivatives in an amphiphilic polar head. Uptake of liposomes loaded with nucleic acid (lipoplexes) and their localization in HEK293T cells was studied by confocal microscopy. The liposomes based on lipotripeptides had the highest transfection efficiency which was 20-fold higher than those fabricated from lipotetrapeptides.

© 2018 Elsevier Ltd  Rod cell membranes contain cholesterol-rich detergent-resistant membrane (DRM) rafts, which accumulate visual cascade proteins as well as proteins involved in regulation of phototransduction such as rhodopsin kinase and guanylate cyclases. Caveolin-1 is the major integral component of DRMs, possessing scaffolding and regulatory activities towards various signaling proteins. In this study, photoreceptor Ca 2+ -binding proteins recoverin, NCS1, GCAP1, and GCAP2, belonging to neuronal calcium sensor (NCS) family, were recognized as novel caveolin-1 interacting partners. All four NCS proteins co-fractionate with caveolin-1 in DRMs, isolated from illuminated bovine rod outer segments. According to pull-down assay, surface plasmon resonance spectroscopy and isothermal titration calorimetry data, they are capable of high-affinity binding to either N-terminal fragment of caveolin-1 (1–101), or its short scaffolding domain (81–101) via a novel structural site. In recoverin this site is localized in C-terminal domain in proximity to the third EF-hand motif and composed of aromatic amino acids conserved among NCS proteins. Remarkably, the binding of NCS proteins to caveolin-1 occurs only in the absence of calcium, which is in agreement with higher accessibility of the caveolin-1 binding site in their Ca 2+ -free forms. Consistently, the presence of caveolin-1 produces no effect on regulatory activity of Ca 2+ -saturated recoverin or NCS1 towards rhodopsin kinase, but upregulates GCAP2, which potentiates guanylate cyclase activity being in Ca 2+ -free conformation. In addition, the interaction with caveolin-1 decreases cooperativity and augments affinity of Ca2 + binding to recoverin apparently by facilitating exposure of its myristoyl group. We suggest that at low calcium NCS proteins are compartmentalized in photoreceptor rafts via binding to caveolin-1, which may enhance their activity or ensure their faster responses on Ca 2+ -signals thereby maintaining efficient phototransduction recovery and light adaptation.

© 2017 IEEE. The article analyzes the process of development of electronic industry in the USSR in the late 1950s and 1960-ies. It's based on documents of the CPSU Central Committee. The authors argue that in these years Soviet electronics were developing rapidly in military and research areas related to space exploration and nuclear energy. Gradual introduction of computers in civil engineering was stated at the same time. But USSR still conceded significantly United States in the growth of the computing machinery. However, in the 1960-ies ideas of universal computerization of the USSR and formation of communism on this basis appeared.

© 2017 IEEE. This paper describes the early period in the development of Soviet digital computers and R&D policy in this field (late 1940s - mid 1950s). The authors focus on the Soviet scientists and economic executives' awareness of the new types of computing machines, their initial application area - the Soviet Atomic Project, and the conditions in which the first computers were made. The Atomic Project leaders realized the value of the new machines but were planning to use only the limited number of them.

© Am J Case Rep, 2018.  Objective: Unusual setting of medical care Background: Noninvasive assessment of the fractional flow reserve (FFR) in patients with coronary artery disease plays an important role in determining the need for revascularization. It is particularly relevant for patients with a borderline stenoses and painless myocardial ischemia. Our article describes the first clinical experience in the Russian Federation of using an automated method of noninvasive assessment of the fractional flow reserve (FFR ct ) with a one-dimensional (1-D) mathematical model in a patient with painless myocardial ischemia. Case Report: A 58-year-old male patient who underwent stent implantation in the left circumflex coronary artery (LCX) due to an acute non-ST-elevation posterior myocardial infarction had borderline stenoses of the left anterior descending artery (LAD). After stent implantation, there were no relapse angina symptoms on drug treatment, and according to our examination guideline for patients with borderline stenoses, a treadmill test was performed. The test was positive; therefore, FFR assessment was recommended, with coronary multi-slice CT being performed. The following results were obtained: FFR ct LAD – 0.57; FFR ct LCX – 0.88. An invasive assessment of FFR was also performed as a reference standard and revealed: FFR LAD – 0.6; FFR LCX – 0.88, and simultaneously a LAD percutaneous coronary intervention (PCI) was performed. Three months later, the patient underwent a stress test, which revealed no evidence of induced ischemia. Conclusions: Our method of noninvasive assessment of FFR has shown encouraging results, but we believe that larger-scale studies are needed to establish it as common clinical practice.

© 2018 IEEE. The work is focused on the research of urea elimination possibilities out of the waste dialysis solution by its electro-oxidation on the surface of platinum group metals and carbon materials. The work includes findings of experimental tests of various electrode materials for the specific urea elimination rate in a model solution.

© 2018 IEEE. The paper presents an algorithm of system identification for implantable rotary blood pumps. The algorithm allows to build mathematical models in accordance with the quality metric introduced to assess the effectiveness of identification. The quality metric was set as an error of pump flow estimation. In the result the mathematical models were identified using experimental dataset for two different rotary blood pumps Sputnik. The identified model of Sputnik 1 characterizes by the mean error about 0.12 L on the control set, the identified model of updated pump-Sputnik 2-mean error about 0.14 L. The identified models intended for control of pump flow during in vitro trials.

© 2018 IEEE. In accordance with the results of the analysis of the current status of the medical industry in Russia, the methodical approach to the assessment of the feasibility of medical device creation project has been developed based on the calculation of the potential socio-economic impact of the implementation of medical devices by the cost of illness method, which includes the model and evaluation methodology and allows to make formalized quantitative assessment of the positive effect of the implementation of medical devices, to compare the potential impacts of the implementation of different medical devices being developed with the costs of the creation of medical device, as well as to prioritize medical device creation projects in the portfolio.

© 2018 Elsevier Ltd A number of imidazole-based acidic (χ(LA)≥0.6) ionic liquids (RmimCl-LA, where R = Et or Bu, LA = AlCl3, AlBr3, iBuAlCl2, FeCl3, GaCl3, and BBr3) has been synthesized and their activity in cationic polymerization of isobutylene has been assessed. Among different ionic liquids tested here, emimCl-AlCl3, emimCl-FeCl3 and emimCl-GaCl3 showed the best results in terms of monomer conversion, exo-olefin end group content and polydispersity. It was shown that reaction rate depended strongly on the rate of partial hydrolysis of corresponding ionic liquid and increased in the following order: emimCl-FeCl3<emimCl-GaCl3<emimCl-AlCl3. It was demonstrated that emimCl-FeCl3 is the most promising catalyst for the synthesis of HR PIB with desired low molecular weight (Mn < 2500 g mol−1) and polydispersity (Mw/Mn < 2.5) and high content of exo-olefin end groups (>85%). However, due to poor dispergation of emimCl-FeCl3 in n-hexane as well as its high stability toward hydrolysis, the catalyst aging and/or sonication of reaction mixture is required in order to provide acceptable polymerization rate.

© 2018 IOP Publishing Ltd. This study was aimed to design and characterise hybrid tissue-engineered constructs composed of osteoinducing polylactide-based scaffolds with multi-layered cellular biointerface for bone tissue reconstruction. Three-dimensional scaffolds with improved hydrophilic and osteoinducing properties were produced using the surface-selective laser sintering (SSLS) method. The designed scaffold pattern had dimensions of 8 ×8 ×2.5 mm and ladder-like pores (∼700 μm in width). Hyaluronic acid-coated polylactide microparticles (∼100 μm in diameter) were used as building blocks and water was used as the photosensitizer for SSLS followed by photocross-linking with Irgacure 2959 photoinitiator. Resulting scaffolds provided successful adhesion and expansion of human bone marrow mesenchymal stromal cells from a single-cell suspension. Induced calcium deposition by the cells associated with osteogenic differentiation was detected in 7-21 days of culturing in basal medium. The values were up to 60% higher on scaffolds produced at a higher prototyping speed under the experimental conditions. Innovative approach to graft the scaffolds with multi-layered cell sheets was proposed aiming to facilitate host tissue-implant integration. The sheets of murine MS-5 stromal cell line exhibited contiguous morphology and high viability in a modelled construct. Thus, the SSLS method proved to be effective in designing osteoinducing scaffolds suitable for the delivery of cell sheets.

© 2018, University of Kragujevac, Faculty of Science. All rights reserved. Two sets of reactants for modelling neurogenesis (SRMN) were developed based on the designed and tested genetic structures of lentiviral vectors. SRMN-1 contains the genetic construct LVV-GFAP-GCaMP3 and is intended for cellspecific transduction in astroglia cells. SRMN-2 contains the genetic construct LVV-PRSx8-TN-XXL and is intended for the phenotype-specific transduction in neurons. The present study examined SRMN-1 and SRMN-2 samples and assessed their efficiency in vitro and in vivo in Norvegicus rats. Specificity to particular cell types for all SRMN samples exceeded 97%. The number of induced signalling cascades was determined via activation of intracellular ingsignalling cascades in neurons and astrocytes (purinergic receptors and β-adrenoceptors). The results demonstrated dynamic recording of fluorescent signals and a two-fold increase in intensity after addition of the activator in all samples. The experimental SRMN samples revealed successful and stable transfection of catecholaminergic neurons and astrocytes, data on transfection efficiency, specificity of the developed genetic structures of SRMN, and calcium dynamics in transfected neurons and astrocytes.

© 2017, Springer Science+Business Media, LLC. The overview demonstrates how the use of only one physico-chemical approach, viz., the electron paramagnetic resonance method, allowed detection and identification of dinitrosyl iron complexes with thiol-containing ligands in various animal and bacterial cells. These complexes are formed in biological objects in the paramagnetic (electron paramagnetic resonance-active) mononuclear and diamagnetic (electron paramagnetic resonance-silent) binuclear forms and control the activity of nitrogen monoxide, one of the most universal regulators of metabolic processes in the organism. The analysis of electronic and spatial structures of dinitrosyl iron complex sheds additional light on the mechanism whereby dinitrosyl iron complex with thiol-containing ligands function in human and animal cells as donors of nitrogen monoxide and its ionized form, viz., nitrosonium ions (NO+).

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the biochemical composition of the tear film is a critical risk factor for the development of chronic perioperative dry eye syndrome, because increasing the duration of general anesthesia did not affect the dynamics of tear secretion recovery, but slowed down normalization of its structure and antioxidant activity in the post-anesthetic period.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Changes in the frequency characteristics of EEG alpha rhythm in during falling asleep were studied in three healthy individuals under conditions of long-term isolation (MARS-500 project). Falling asleep was preceded by enhanced alpha rhythm frequency. An inverse correlation between the duration of falling asleep and prevailing alpha rhythm frequency during active and relaxed wakefulness was revealed in the left hemisphere. These results demonstrate the principal possibility of predicting the duration of falling asleep by using alpha rhythm spectral analysis. It is assumed that the frequency of the alpha range spectral peak can be a marker of drowsiness and reflect the current need for sleep.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The composite Y14/siUTR, a complex consisting of cationic lipopeptide Y14 as an excipient and pharmaceutical substance of small interfering RNAtargeted against the UTR region of hepatitis C virus (siUTR), was investigated. The composite was intended to inhibit the hepatitis C virus replication cycle. The present work was aimed at developing pharmaceutical analytical methods for the components of this composite using HPLC-UV and UV spectroscopy.

© 2018 by the authors. Composite fibers and films based on cellulose and betulin were spun for the first time from solutions in N-methylmorpholine-N-oxide using the dry-wet jet method. The rheological properties of the composite solutions did not reveal any fundamental difference from those of the cellulose solutions. Introduction of betulin into the cellulose matrix (up to 10%) led to a decrease in the mechanical properties of the obtained fibers. The structure of the composite fibers was analyzed using SEM and X-ray diffraction methods. It was shown that the introduction of an additive into the cellulose matrix led to a decrease in the structural ordering of the cellulose. Comparative studies of the antibacterial activity of the composite films on Escherichia coli (E. coli) were carried out. The antifungal activity of the composite films was estimated using the strain of the O-97 Trichoderma viride Pers ex Fr (Gause Institute of New Antibiotics, Moscow, Russia).

© 2018, Pleiades Publishing, Inc. Hemophilia A is a recessive X-linked hereditary disease, so its manifestation in women is extremely rare and can be a result of an asymmetric X-chromosome inactivation or, even more rarely, of a presence of mutations in both FVIII gene alleles. We conducted a mutation screening of the FVIII gene in two female patients with clinical hemophilia A manifestation in this study. One patient had a hereditary disease; the second one was diagnosed with acquired hemophilia A as an adult. Both patients carried the same missense mutation His2026Arg. The patient with the hereditary form of the disease also had previously known microinsertion c.4379_4380 insA (p.Asn1460Lys-fs*1). We found no additional aberrations by sequencing of all functionally significant parts of the factor VIII gene of the patient with acquired hemophilia but showed clear asymmetric inactivation of X-chromosomes. Therefore, one of the possible explanations for the emergence of the hemophilic syndrome in this case can be the delayed manifestation of the FVIII gene germline mutation owing to the enhancement of hematopoiesis clonality with age.

Copyright © 2018, Georg Thieme Verlag KG. All rights reserved. Thoracoplasty was invented for removing cavities between thoracic wall and remnant lung or mediastinum. It was initially used in cases of tuberculosis or unspecific infections, while currently it is used mainly for space problems after lobectomy/pneumonectomy. This article presents an overview of the historical and current techniques of this surgical procedure. Nowadays, thoracoplasty is rarely performed due to the low incidence of diseases for which this method is necessary. Therefore, this method has even been discredited. Furthermore, certain technical aspects of the thoracoplasty are not very well known because of the infrequent application of this procedure. Unfortunately, a look into the literature of thoracoplasty is not always usefull due to the biased views of advocates of different techniques such as Schede's thoracoplasty, Heller's Jalousie-Plastik, Alexander's extramusculoperiosteal thoracoplasty, Bjork's osteoplastic thoracoplasty, etc. Not to forget, there has always been a lack of research on the relevance and on the several techniques of thoracoplasty. The point is precise indication and correct execution of thoracoplasty as a final therapeutic option, which allows a safe and definitive solution of the space problem even in complex cases, without creating serious functional and cosmetic impairment for the patient. The main types of thoracoplasty are described in this article. Although the core principle of this operation remains unchanged, modern techniques are often cosmetically more considerable and less destructive, compared with techniques that were used in the past.

© 2018 Elsevier Ltd  Five lactam chemotypes amenable by the Castagnoli-Cushman reaction of imines and cyclic anhydrides have been investigated for their ability to activate p53 tumor suppressing transcription factor thus induce apoptosis in p53 + cancer cells. A virtual library of 1.07 million chemically diverse compounds based on these scaffolds was subjected to in silico screening first. The compounds displaying high docking score were visually prioritized to identify the best-fitting compounds, i. e. the ones which adequately mimic the interactions of clinical candidate inhibitor Nutlin-3a. These 38 compounds were synthesized and tested for apoptosis induction in p53 + H116 cancer cells to identify 9 potent apoptosis-inducers (two of them exceeding the activity of Nutlin-3a) which belonged to four different chemotypes. The activation of p53 involved in the proapoptotic activity observed was supported by effective induction of EGFP expression in human osteocarcinoma U2OS-pLV reporter cell line. Moreover, the two most potent apoptosis inducers displayed antiproliferative profile identical to several known advanced p53 activators: they inhibited the growth of p53 +/+ HCT116 cells in much lower concentration range compared to p53 −/− HCT116 cells.

© 2018 Sychev et al. Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.