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We have analyzed and compared the available experimental data (PDB) on the backbone geometry of the DNA in solution (NMR), in crystals (X-rays), and in complexes with proteins (X-rays and cryo-electron microscopy). The deoxyribose (pseudorotational angle τ0) and e/ζ (BI-BII transition in phosphates) flexibilities are practically the same in the four samples. The α/γ mobility is minimal in crystalline DNA: on the histograms, there is one canonical and one noncanonical t/t peak. The α/γ mobility increases in DNA solutions (three more noncanonical peaks) and is maximal in DNA-protein complexes (another additional peak). On a large amount of data, we have confirmed that the three main degrees of freedom of the sugar-phosphate backbone are "orthogonal": changes in any of the angles τ0, (ζ-e), and (γ-α) occur, as a rule, at a constant (usually canonical) value of any other. In the DNA-protein complexes, none of the geometrical parameters commonly used to distinguish the A and B forms of DNA, except for Zp and its simpler analog Zp', show an unambiguous correlation with τ0. Proteins, binding to DNA, in 59% of cases change the local shape of the helix up to the characteristic of the A-form without switching the deoxyribose conformation from south to north. However, we have found simple local characteristics of one nucleotide that correlate with the angles τ0 and (ζ-e). These are the angles C3'C1'N* and C4'C3'P(2), respectively. They are orthogonal in DNA-protein complexes exactly as the pair τ0 and (ζ-e). Most characteristics of DNA in complexes with proteins are the same in X-ray and in cryo-EM data, except for the histogram for the angle τ0. We offer a possible explanation for this difference. We also discuss the artifacts on the e/ζ histogram for DNA in solutions caused by the currently used NMR refinement protocols.

The influence of sizing compositions on the reinforcing properties of hydrated cellulose technical yarns has been investigated. The optimal mode of modification of hydrated cellulose yarns has been determined. The evaluation of the structural properties of the modified yarns has been carried out. The kinetic features of the modified yarns wetting by an epoxy oligomer have been studied.

The article presents the results of a study of synthesis and accumulation of heptyl in plants growing on soil contaminated with rocket fuel. The study was carried out under laboratory conditions of al-Farabi Kazakh National University. The results of the experiments confirmed that certain concentrations of a rocket fuel-heptyl (unsymmetrical dimethylhydrazine, UDMH) are not toxic for the crested wheatgrass, Agropyron pectiniforme Roem.et Schult., Kentucky bluegrass, Poa pratensis L., and tarragon, Artemisia terraе-albaе Krasch., although they can cause anatomical and morphological changes in the roots and leaves of plants grown on soil contaminated with UDMH. Changes in the morphological structure of plants under the influence of UDMH (in particular, in the outer tissue that protects the plant organs from drying out, temperature effects, mechanical damage and other adverse factors) can lead to an imbalance in water metabolism and gas exchange, a deterioration in the absorption and release of water, and the cessation of intake from the soil of both beneficial and harmful substances.

The strength and wettability of polyacrylonitrile technical cord and of hydrated cellulose and basalt technical threads, treated with organosilicon dressing agents, were evaluated. The modified threads show enhanced surface activity. The kinetic features of epoxy binder curing in the presence of the modified threads were studied. Introduction of the fibrous fillers under consideration improves the operation characteristics of the epoxy composites.

The effect of light and cadmium ions (Cd) on the morphophysiological characteristics and accumulation of low molecular weight phenolic antioxidants in the tea plant Camellia sinensis L. callus culture under their separate and combined action is studied. It was established that the light exposure and the cadmium intake separately led to a change in the morphophysiological characteristics of the culture, a decrease in its growth, and activation of the antioxidant system. It was noted that it was manifested in an increase in the total content of phenolic compounds, flavans, and proanthocyanidins (to a lesser extent) and did not depend on the activity of the phenolic metabolism key enzyme, L-phenylalanine ammoniac lyase. It was found that the cell response was more pronounced under the action of Cd than under the action of light. In some cases, these indicators correlated with the level of lipid peroxidation in callus cultures. It is shown that all changes were more pronounced under the combined action of light and Cd.

—Regulatory peptides have modulatory and integrative functions defining communication between different systems of the body. This review summarizes and systematizes the data on drugs created on the basis of peptide regulators. The therapeutic profiles of a wide range of oligopeptides are considered in various body systems: nervous, cardiovascular, digestive, immune, endocrine, etc. The data on various mechanisms of the polyfunctional physiological effect of peptide drugs are presented. These effects are, allosteric receptor modulations, directed transcriptome change, and induction of cascade processes. The innovative advantages of preparations of oligopeptide analogs are described.

To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters: the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events.

Isotope shifts of $$n = 1$$ and $$n = 2$$ levels and corresponding transitions in helium-like highly charged ions are calculated with high precision. The total value of the isotope shift is determined mainly by the sum of the field and mass shifts. The field shift is calculated by using the Dirac–Fock–Sturm method taking into account interaction of configurations. Quantum-electrodynamic corrections to this contribution are taken into account approximately by using the corresponding one-electron expressions. The mass shift is calculated both within the framework of the Breit approximation and by taking into account quantum-electrodynamic contributions that become substantial for heavy ions. In the case of thorium and uranium ions, corrections due to nuclear polarization and deformation are taken into account additionally.

The cryopreservation effi ciency of nucleated cells (NCs), in particular hematopoietic progenitor (HPCs) and cord blood (CB) cells was comprehensively assessed in protective mixtures, containing intracellular cryoprotectant dimethyl sulfoxide (DMSO) and antioxidant glutathione in different concentrations assessed immediately after thawing and further transfer to the in vitro conditions, simulating physiological ones. The use of 1 and 3 mM glutathione in cryoprotectant medium with 7.5 and 10% DMSO enabled preserving 85.9 and 91.2% of viable NCs and HPCs, respectively, immediately after thawing and 75–80% of viable NCs/HPCs after 1-hour incubation in the antioxidant-free Hank’s solution, which exceeded the control values. At the same time, the recovery and viability of NCs and HPCs after cryopreservation in 5% DMSO with 1mM or 3 mM glutathione were the same or even higher than those in 7.5 and 10% DMSO without glutathione. The NCs cryopreservation in the glutathione-containing solutions was esta-blished to reduce the number of DCF+ cells. The supplementation of 7.5% DMSO with 1 or 3 mM glutathione reduced the cell number with excess reactive oxygen species from 19% (in glutathione-free samples) to 11% (in glutathione-contained ones), even after transfer to the in vitro conditions, simulating physiological. Probl Cryobiol Cryomed 2020; 30(1): 058–067

The development of a specific inflammation in mice that had been infected by two influenza virus strains, A/chicken/Kurgan/5/2005 (H5N1) and A/Hamburg/2009 MA (H1N1), was studied. We investigated the effect of a non-toxic lipopolysaccharide from Rhodobacter capsulatus PG on the survival and body weight of the mice, production of IgG antibodies, and the induction of pro- and anti-inflammatory cytokines in blood serum. The administration of the R. capsulatus PG lipopolysaccharide was shown to induce interferon- synthesis, both in healthy and influenza A virus-infected mice, and to promote production of antiviral antibodies in the blood of the influenza-infected animals.

A numerical study has been conducted to investigate the onset and nonlinear regimes of Soret-induced convection of a mixture of dodecane, isobutylbenzene and tetralin at equal mass fraction proportions in a rectangular porous cavity with solid boundaries elongated in a horizontal direction and heated from below. The vertical boundaries of the cavity are insulated. The components of the mixture are representatives of the main groups of chemical compounds that make up the oil. The values of porosity and permeability of the medium were chosen close to the values of real media, such as sands, sandstones or limestone. The area of such configuration simulates a real hydrocarbon field. Due to the Soret effect, the light components of the mixture, dodecane and isobutylbenzene, which have positive separation ratios, accumulate in the hot region, and the heavy component of the mixture, tetralin, in the cold region. This leads to the onset of convection in the case of heating from below, which in natural conditions is ensured by the presence of a geothermal gradient. It has been found that at a certain value of the Rayleigh number a steady flow occurs in the cavity, which, with an increase in the Rayleigh number, is replaced by an oscillatory one. With a further increase in the Rayleigh number, irregular oscillations occur. In the considered interval of the Rayleigh numbers, several monotonic and oscillatory regimes characterized by different spatial scales (from one to ten vortexes) were found. The form of oscillations of instantaneous flow characteristics in oscillatory regimes has a complex shape. The monotonic flow regime with an asymmetric structure was revealed. The intervals of the Rayleigh numbers, in which the obtained regimes may exist, and the time dependences of the integral characteristics occurred in the process of formation of steady flows were determined. The effect of supercriticality on the flow structure and the concentration distribution of mixture components were studied.

We present the results of the numerical investigation of the Soret-induced convection in a ternary liquid mixture consisting of dodecane, isobutylbenzene and tetralin, taken in equal portions. The mixture is placed into a square porous cavity with rigid impermeable boundaries heated from below. The lateral boundaries are adiabatic. The problem under consideration is a model of natural hydrocarbon reservoir with porous medium, and the components of mixture are representatives of the main groups of chemical compounds comprising oil. Due to the thermodiffusion effect, dodecane and isobutylbenzene as the lighter components of this mixture with positive separation ratios are accumulated in the warmer domain of the cavity, and the heavy component, tetralin, is accumulated in the colder domain, which may lead to the development of convection. The calculations are performed for the parameters of porous medium close to the real parameters of oil fields and temperature gradient that correspond to geothermal gradient. They provide data on the temporal evolution of the characteristics of the flow and component separation. We also analyze the onset and development of single-vortex and two-vortex instability modes with the growth of the Rayleigh number $$Ra_{\mathrm{{por}}}$$ . It is found that at a certain value of the supercriticality, the stationary flow regime is replaced by the oscillatory regime. At even higher values of the Rayleigh number, the chaotic oscillations take place. The transitions between single-vortex and two-vortex flows are also observed. For porosity equal to 0.1, the two oscillatory regimes at different oscillation amplitudes are excited. With the porosity growth, the region of the existence of the oscillatory regimes becomes narrower.

The paper presents the results of modeling convection in the layered structure of a hydrocarbon field. A horizontally elongated rectangular cavity of a porous medium, which consists of two layers with equal porosity and different constant permeabilities, is considered. The cavity is filled with a homogeneous ternary hydrocarbon mixture. The problem is solved within the framework of the Darcy-Boussinesq model, taking into account thermal diffusion. Data on convective regimes and distribution of mixture components were obtained in cases when the ratio of the permeabilities of the lower and upper layers is greater or lower than unity.

Outer membrane vesicles (OMVs), produced by nonpathogenic Gram-negative bacteria, have potentially useful biotechnological applications in extraterrestrial extreme environments. However, their biological effects under the impact of various stressors have to be elucidated for safety reasons. In the spaceflight experiment, model biofilm kombucha microbial community (KMC) samples, in which Komagataeibacter intermedius was a dominant community-member, were exposed under simulated Martian factors (i.e., pressure, atmosphere, and UV-illumination) outside the International Space Station (ISS) for 1.5 years. In this study, we have determined that OMVs from post-flight K. intermedius displayed changes in membrane composition, depending on the location of the samples and some other factors. Membrane lipids such as sterols, fatty acids (FAs), and phospholipids (PLs) were modulated under the Mars-like stressors, and saturated FAs, as well as both short-chain saturated and trans FAs, appeared in the membranes of OMVs shed by both post-UV-illuminated and "dark" bacteria. The relative content of zwitterionic and anionic PLs changed, producing a change in surface properties of outer membranes, thereby resulting in a loss of interaction capability with polynucleotides. The changed composition of membranes promoted a bigger OMV size, which correlated with changes of OMV fitness. Biochemical characterization of the membrane-associated enzymes revealed an increase in their activity (DNAse, dehydrogenase) compared to wild type. Other functional membrane-associated capabilities of OMVs (e.g., proton accumulation, interaction with linear DNA, or synaptosomes) were also altered after exposure to the spaceflight stressors. Despite alterations in membranes, vesicles did not acquire endotoxicity, cytotoxicity, and neurotoxicity. Altogether, our results show that OMVs, originating from rationally selected nonpathogenic Gram-negative bacteria, can be considered as candidates in the design of postbiotics or edible mucosal vaccines for in situ production in extreme environment. Furthermore, these OMVs could also be used as promising delivery vectors for applications in Astromedicine.

The development of type 2 diabetes mellitus (DM2) is accompanied by disturbances in lipid metabolism. These include the increase in serum levels of atherogenic fractions of very low-density (VLDL) and low-density lipoproteins (LDL), total cholesterol, triglycerides and apo B. In contrast, the level of antiatherogenic high density lipoproteins (HDL) and the content of apolipoprotein A-I (apoA-I) decreased. To study the effect of the observed metabolic changes on insulin secretion in vitro, we used the islets of Langerhans isolated from the rat pancreas. It has been found that incubation of the islets in the presence of serum of the obese patients and patients with decompensated DM2 leads to a decrease in insulin secretion by 2.4 and 5.0 times, respectively. On the contrary, the addition of HDL to the incubation medium increased the insulin secretion by 3.4 times. A similar effect was observed in the presence of apoA-I, the main protein component of HDL. In the presence of apoA-I, the extracellular activity of matrix metalloproteinases (MMPs) demonstrated a 10-fold increase. The addition of LDL and VLDL to the islets did not change the secretion of insulin and activity of MMP. Our results testify to the important role of HDL and apoA-I in regulation of the insulin secretion by b-cells and the activity of MMPs in the islets of Langerhans.Razvitie sakharnogo diabeta (SD) 2 tipa soprovozhdaetsia narusheniem lipidnogo obmena. Na éto ukazyvaet vozrastanie v syvorotke krovi kontsentratsii aterogennykh fraktsiĭ lipoproteinov ochen' nizkoĭ (LPONP) i nizkoĭ plotnosti (LPNP), triglitseridov i apolipoproteina V. Naprotiv, uroven' antiaterogennykh lipoproteinov vysokoĭ plotnosti (LPVP) i apolipoproteina A-I (apoA-I) u étikh bol'nykh snizhaetsia. Dlia izucheniia vliianiia obnaruzhennykh metabolicheskikh izmeneniĭ na sekretsiiu insulina in vitro my proveli issledovaniia na ostrovkakh Langergansa, izolirovannykh iz podzheludochnoĭ zhelezy krys. Ustanovleno, chto inkubatsiia ostrovkov v prisutstvii syvorotki bol'nykh ozhireniem i bol'nykh SD 2 tipa v stadii dekompensatsii privodit k snizheniiu sekretsii insulina v 2,4 i 5,0 raz, sootvetstvenno. Dobavlenie v inkubatsionnuiu sredu LPVP, naprotiv, soprovozhdaetsia vozrastaniem sekretsii insulina v 3,4 raza. Podobnyĭ éffekt obnaruzhen v prisutstvii apoA-I, kotoryĭ iavliaetsia osnovnym belkovym komponentom LPVP. Pod vliianiem apoA-I takzhe znachitel'no vozrastala (v 10 raz) vnekletochnaia aktivnost' matriksnykh metalloproteinaz (MMP). Pri dobavlenii k ostrovkam LPONP i LPNP sekretsiia insulina i aktivnost' MMP ne izmenialas'. Poluchennye rezul'taty svidetel'stvuiut o tom, chto LPVP i apoA-I iavliaiutsia vazhnymi faktorami, reguliruiushchimi sekretsiiu insulina b-kletkami i aktivnost' MMP v ostrovkakh Langergansa.

The ability of physiological (1α,25-dihydroxyvitamin D3, retinoic acid) and non-physiological (various LPS) agents and their combinations to influence the direction of promonocytic THP-1 cell differentiation was studied. The differentiating activity of the agents was evaluated by the expression and the ratio of surface receptors (TLR4, CD11b, and CD14) as well as by the change in THP-1 cell phagocytic activity of different degree of differentiation by Flow cytometry. The THP-1 cell differentiation by VD3 was shown to lead probably to the formation of classical monocytes. Summarizing we can conclude that VD3 induces the THP-1 cells differentiation with the formation of classical monocytes and the sequence of 1α, 25-dihydroxyvitamin D3 and non-toxic LPS R. capsulatus PG causes the THP-1 cells differentiation with the formation of inflammatory or intermediate monocytes.

In patients with type 2 diabetes mellitus, serum activities of MMP-2 and MMP-7 were substantially decreased in comparison with apparently healthy individuals. At the decompensation stage, along with the increased content of glucose and glycated hemoglobin, a pronounced (3-fold) increase in proinsulin concentration was observed. On the contrary, MMP activity and C-peptide concentration decreased at this stage. The ratio of proinsulin concentration to MMP activity at the stages of diabetes mellitus compensation and subcompensation was approximately 1:50, while at the stage of decompensation it was 1:12. Thus, the ratio of these blood serum parameters can be used as an additional diagnostic marker of diabetes decompensation and severity of its complications.

We have derived effective potentials of Na+ and Cl— ions in implicit water at temperatures from 273 to 340 K and concentrations between 0,3 and 1 M. We divide the potentials into two parts: slowly decreasing Coulomb function and solvation energy. The primary dependence of the effective potentials on the parameters proved to be in the dependence on them of the dielectric constant. Slight temperature dependence of the solvation is present for the pairs Na+ — Na+ and Na+ — Cl— only.

The coarse-grained model of polyethylene and alkanes (the united-atom model, in which each CH2 group is represented by a single bead) was proposed several decades ago. It is widely applied in molecular dynamics simulations. For different tasks, the models with different geometrical and force parameters are used. Until now, it was thought that the coarse-grained model of polyethylene cannot reproduce the orthorhombic crystalline phase, which is typical of this polymer. In the present study, we analyze the simplest coarse-grained model of polyethylene. In this model, the Lennard-Jones potential (6–12) is adopted for van der Waals interactions between the beads of different chains. Of the bonded interactions, only the “valence” bonds between beads and the “bond” and “torsion” angles are taken into account, whereas the cross terms between them are disregarded. We consider the model variation in which the bead (the force center with the mass of a CH2 group) is displaced from the center of the carbon atom and all the interactions, both bonded and nonbonded, are defined by the positions of these beads. For this model, we find the area of geometrical parameters (the displacement value and the van der Waals radius of the bead) in which all the three known crystalline phases of polyethylene are at equilibrium at low temperatures. We choose the force field constants for the model so that its oscillation spectrum reproduces the low-frequency part of the inelastic neutron scattering spectrum of the orthorhombic polyethylene. It proved to be that this choice can be made unambiguously. We compare the dispersion curves in the terahertz range with experimental data on the Raman scattering and infrared spectroscopy, and discuss the advantages and disadvantages of the analyzed simplest coarse model.

The paper evaluated the efficiency of N-acetyl-L-cysteine (AC) antioxidant for cryopreservation of human cord blood nucleated cells (CBNCs) with various concentrations of endocellular cryoprotectant dimethyl sulfoxide (DMSO). It has been found that rise in DMSO concentration (from 2.5 and 5 up to 7.5% and 10%) and exposure time of the CBNCs suspension with cryoprotectant (from 15 to 30 min and longer) resulted in a significant increase in the amount of cells with excess reactive oxygen species (ROS) (from (7.5 ± 0.8)% at 5% DMSO and 15-min incubation to (28.9 ± 3.2)% with 10% DMSO and 60 min incubation), decrease in their viability and preservation rate. Supplementing 10 mM AC to the cryopreservation medium led to a reduction in the amount of cells with excess ROS and rise of their preservation rate and viability at the stage of equilibration with cryoprotectant, as well as after freeze-thawing of CBNCs suspension. Maximum effect was achieved after AC supplementing to the media with 7.5 and 10% DMSO concentrations. We proved that the use of antioxidant contributed to the rise in preservation rate and viability of CBNCs if cryoprotectant concentration and exposure time with it were optimal.Probl Cryobiol Cryomed 2016; 26(4): 295–307.

Objective. To study the efficacy and use of baclofen (Baclosan) for stabilizing remission in patients with alcoholism. Materials and methods. A total of 32 patients with alcoholism were randomized to two groups. Patients of group 1 (16 patients) received baclofen (50 mg/day) for three months; patients of group 2 received a placebo of identical appearance. All patients were required to attend the clinic every week for monitoring of remission (alcohol consumption) and assessment of the levels of alcohol attraction (craving), affective disorders (depression and anxiety), and γ-glutamyltransferase (GGT) activity, and for monitoring of compliance with medication (urine riboflavin). Alcohol consumption was monitored by retrospective analysis and assay of GGT. Anxiety was evaluated using the Hamilton and Spielberger scales. Depression was assessed on the Montgomery-Asberg Depression Scale. Alcohol cravings were assessed using obsessive-compulsive, Pennsylvania, and visual analog scales. Overall assessment of treatment efficacy was obtained using the Clinical Global Impression scale. The study followed a double-blind design. Results and conclusions. No significant difference in measures of the efficacy of stabilizing remission was seen between the baclofen and placebo groups in patients with alcoholism (probably due to insufficiently large cohort sizes). Measures of holding patients in remission and of alcohol consumption in the baclofen group were somewhat better than in the placebo group; between-group differences in these measures approached statistical significance, pointing to a greater efficacy for baclofen than placebo in alcoholism. Baclofen did not show any significant difference from placebo in terms of the number of side effects (adverse events) and effects on liver enzyme activity, which is evidence for its good tolerance and safety in this contingent of patients. The authors take the view that evidence-based conclusions regarding The efficacy of baclofen in the treatment of alcoholism require further studies in patients using larger cohorts.

Summary The paper is dedicated to the possibility of carbonate reservoir properties prediction with the use of results of seismic inversion. Authors propose improved method of seismic inversion which implicates use of results of genetic inversion as trend for rising of low-frequency model accuracy. Also the method supposes signal changing over time. As the result final acoustic impedance cube gets higher quality. Resulted cube was used as trend for reservoir properties modeling goals and final prediction was better than prediction obtained without trend. Method was prepared in the context of one oil field and was in further tested on another field and final results were satisfying too.

Precise calculations of the isotope shifts in berylliumlike thorium and uranium ions are presented. The main contributions to the field and mass shifts are calculated within the framework of the Dirac-Coulomb-Breit Hamiltonian employing the configuration-interaction Dirac-Fock-Sturm method. These calculations include the relativistic, electron-electron correlation, and Breit-interaction effects. The QED, nuclear deformation, and nuclear polarization corrections are also evaluated., Comment: 11 pages, 2 tables

Analysis of the carbon isotopic composition in aryl carotenoid derivatives, including isorenieratene, in bitumen from domanikoid rocks of the sections cropping out along the Chut River revealed that they contain anomalously heavy carbon, which is determined by the formation of these compounds from green sulfur bacteria of the family Chlorobiaceae. These bacteria use the peculiar process of carbon fixing as HCO3− in the reversed tricarboxilic acid cycle. The fact of hydrosulfuric contamination of the photic water layer in the Domanik basin is confirmed by the plurality of data. Anoxity in shelf water of the middle Frasnian Timan–Pechora basin is evident from lithological features such as, for example, lamination of some rocks and mass death of the fauna.

The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.

The effect of the modification parameters on the structure and properties of polyacrylonitrile technical filament (PAN-TF) used to reinforce an epoxide matrix was studied. It was found that treatment of PAN-TF with aqueous solutions of hydrated Cu(II) sulfate could produce modified reinforcing fillers for which the physicomechanical properties tended to increase. The operating properties of composites with the studied PAN-TF were evaluated.

Transitions between the B and A forms of a short DNA double helix (12 base pairs) at different salt concentrations in an aqueous solution have been studied by the molecular dynamics method in the framework of a coarse-grained model with explicit ions but without friction. It has been shown that the A-DNA, stable at high salt concentrations, is a dynamic conglomerate of the molecule and the ions coming from the solution into the deep major groove and then leaving it. In such a short helix, in the model without friction, even at low salt concentrations, transitions from B-DNA to A-DNA and back are frequent and fast. Stable ADNA (without transitions to B-DNA) forms at salt concentrations greater than 0.45 mol/L.

The purpose of the study is to obtain a durable and cheap road-building material based on ash, reinforced with mineral astringent. Within the framework of the research, the optimal dosages of binders were searched for, the characteristics of the strength of mixture of ash with sludge and ash with cement were also determined. A comparative analysis of the economic efficiency between using a mixture of ash from the incineration of sewage sludge, reinforced with nepheline sludge, and traditional road building materials was carried out. The results of the study of mixtures of ash with mineral binders, such as nepheline sludge and cement, show that the obtained materials have high strength indicators and high indicators of the modulus of elasticity. They can be attributed to strength grades from M20 to M100. The developed building material (ash mixed with binders (nepheline sludge, cement)) could replace a similar building material in the technology of road construction, because if this mixture is taken in optimal dosages, it will be more profitable in the process of use, both from the point of physical and mechanical views, and point of view of economic indicators.

Human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) may be a valuable source for cell therapy and regenerative medicine. In this study, the potential of DNA methyltransferases (DNMT) inhibitors Decitabine, Zebularine, RG108 alone or combined with Zebularine and p53 inhibitor Pifithrin-α to induce cardiomyogenic differentiation of AF-MSCs was investigated. Differentiation into cardiomyocyte-like cells initiation was indicated with all agents by changes in the cell phenotype, upregulation of the relative expression of the main cardiac genes (NKX2-5, TNNT2, MYH6, and DES) as well as of cardiac ion channels genes (sodium, calcium, and potassium) as determined by reverse-transcription quantitative polymerase chain reaction and the increase in Connexin43 levels as detected from Western blot and immunofluorescence data. Cellular energetics and mitochondrial function in induced cells were assessed using Seahorse analyzer and revealed the initiation of AF-MSCs metabolic transformation into cardiomyocyte-like cells. All used inducers were nontoxic to AF-MSCs, arrested cell cycle at the G0/G1 phase, and upregulated p53 and p21 expression. The relative expression of miR-34a and miR-145 that are related to cell cycle regulation was also observed. Furthermore, the evaluated levels of chromatin remodeling proteins enhancer of zeste homolog 2, suppressor of zeste 12 protein homolog, DNMT1, histone deacetylase 1 (HDAC1), HDAC2, and heterochromatin protein 1α, as well as the rate of activating histone modifications, exhibited rearrangements of chromatin after the induction of cardiomyogenic differentiation. In conclusion, we demonstrated that all explored DNMT and p53 inhibitors initiated cardiomyogenesis-related alterations in AF-MSCs through rather similar mechanisms but to a different extent providing useful insights for the future research and potential applications of AF-MSCs.

In the framework of the ‘sugar’ coarse-grained DNA model [N.A. Kovaleva, I.P. Koroleva (Kikot), M.A. Mazo, Journal of Molecular Modeling 23(2):66 (2017), https://doi.org/10.1007/s00894-017-3209-z], we study the transition between B and A forms of a short DNA molecule (12 base pairs) when the concentration of salt changes. The model exploits the explicit ions and implicit water representation and allows to separately change the friction of the ions and of the DNA molecule. We compare the behavior of the system for different values of friction which proved to not affect the order of the transition, but allowed to determine the roles of the DNA and the ions in the behavior of the conglomerate. We find the order (the first) and the point of the transition (0.316 M) in the case of ‘inviscid’ water (zero friction for both the ions and the DNA, the NVE ensemble). The helix consisting of 12 bp (more than thousand atoms) proved to exhibit the features of small systems. Namely, even at low salt concentrations, one can observe the jumps from B-DNA to A-DNA and back. We analyse the structure of the A-DNA and find the reasons for such a behavior.

The role of the gene bcl-2 conferring resistance to apoptosis in the activation of the cellular senescence program induced by the histone deacetylase inhibitor (HDACi) sodium butyrate (NaBut) has been studied in transformed rat fibroblasts. The work was carried out in the rat embryo fibroblast cell line transformed by the oncogenes E1A, cHa-Ras, and bcl-2 (ERasBcl cells) resistant to apoptosis. The parent line of E1A-and cHa-Ras-transformed cells (ERas cells) was used as a control. It has been shown that NaBut suppresses the proliferation of ERasBcl cells to a much lesser extent than do the control ERas cells, in spite of the delay in cell cycle progression in the G1 phase for both lines. NaBut-induced hypertrophy is less marked in ERasBcl cells than in ERas cells due to the lower level of activation of the mTORC1 complex controlling protein synthesis and ribosome biogenesis. The activation of mTORC1 was assessed from the phosphorylation of its targets: ribosomal protein S6 and the inhibitor of translation initiation factor eIF4E (4E-BP1). Investigation of the dynamics of the level of one of the major markers of autophagosome formation (protein LC3) has shown the transient character of NaBut-induced accumulation of lipid-bound form LC3-II marking autophagosome membranes in bcl-2-expressing transformants in contrast to the ERas line. In addition, in ERasBcl cells there was no activation of the senescence-associated β-galactosidase (the marker for senescent cells). The results obtained suggest that the high level of expression of bcl-2, which blocks apoptotic cell death, prevents the implementation of the NaBut-induced tumor-suppressive cellular senescence program.

Results of a science-based analysis of ante-mortem trepanation carried out by Scythian Age surgeons of Gorny Altai (4th–3rd centuries BC) are presented. Inductively coupled plasma-mass spectrometry, energy dispersive X-ray fluorescent analysis using synchrotron radiation, and magnetic resonance tomography were supplemented by micro- wear experiments. All trepanations were performed by scraping and included two stages. The bone tissue around the holes reveals high concentrations of copper and tin but no traces of iron or arsenic, suggesting that surgical instruments were made of tin bronze. A knife, experimentally manufactured of copper, tin, and zinc alloy and shaped like knives used by Southern Siberian nomads, was successfully used to perform trepanation on a cadaver.

The optimum modification parameters for cellulose-hydrate fibers finished with solutions of AGM-9 and Duron OS 3151 preparations were determined. The properties of the modified cellulose-hydrate fibers were studied. The adhesive properties of the modified fibers were evaluated. It was found that modification helped to increase the strength and adhesive characteristics of the fibrous filler, which could be recommended for preparing an epoxide composite.

A key regulator of cellular senescence, mTORC1 complex, is a target of many signaling cascades, including Ras/Raf/MEK/ERK cascade. In this paper, we investigated the role of the MEK/ERK branch of this cascade in the process of cellular senescence induced by sodium butyrate (NaBut), a histone deacetylase inhibitor (HDACI), in transformed rat-embryo fibroblasts. Suppression of MEK/ERK activity by inhibitor PD0325901 did not prevent activation of mTORC1 complex induced by NaBut treatment. Inhibition of MEK/ERK increased mTORC1 activity and activated mTORC2 complex. Activation of mTOR-containing complexes was accompanied by reorganization of the actin cytoskeleton (formation of actin stress fibers) and the appearance of cellular senescence markers. In contrast to NaBut-induced senescence, no protein accumulation was observed, probably due to increased activity of the degradation processes. Furthermore, senescence induction under suppression of MEK/ERK drastically decreased the cell viability, Thus, NaBut-induced senescence upon suppressed activity of the MEK/ERK branch of MAP kinase cascade has a more pronounced tumor-suppressing effect that is manifested by activation of both mTOR complexes, reorganization of the actin cytoskeleton and protein degradation.

Vitamin D has immunomodulatory properties, which influence the immune system through a number of mechanisms, including the activation of dendritic cells (DCs). Langerhans cells (LCs) are dendritic cells in epidermis and belong to the skin immune system. DCs are professional antigen-presenting cells playing a major role in the induction of immune responses by activating native T-cells. In literature, there are no reports regarding the influence of vitamin D on DCs in patients with metabolic syndrome (MS). Thus, the aim of this study is to explore potential immunomodulatory activity of vitamin D on LCs in case of metabolic syndrome. In this study, we have conducted an analysis on a group of patients, both male and female, diagnosed with metabolic syndrome between the age of 40 and 55. Patients’ clinical examinations, measurement of blood pressure, and waist circumference were conducted. Blood biochemical analyses (cholesterol, HDL, LDL, vitamin D level, etc.) were also determined. Full-thickness circular 4-mm Punch biopsies were taken from 49 patients. Specimens were stained with haematoxylin and eosin, as well as immunohistochemistry using a transmembrane CD1a Langerhans’ cells marker was parformed by DakoCytomation EnVision method. The average age of patients is 43 years, and mean waist circumference is 95 cm. Total cholesterol is 5.5 mmol/l, LDL is 2.3 mmol/l, and average 25-hydroxyvitamin D is 27.0 ng/ml. In the skin conditioned with MS and low vitamin D level, evidence of perivascular accumulation of LCs in papillary dermis is observed, as well as a diffusion of mild interstitial cluster of LCs in some cases. In epidermis activity, the amount and filling of Birbeck’s granules is changed in cases of 25-hydroxyvitamin D deficiency. In patients with low 25-hydroxyvitamin D level, an average LC quantity in one field of vision is higher in comparison to those who have normal amount of 25-hydroxyvitamin D. Therefore, it is necessary to further investigate vitamin D activity on LCs in cases of metabolic syndrome in order to determine interactions with lymphocytes, plasma cells, and mast cells as a part of the skin immune system.

The role of JNK1,2 stress kinases in the regulation of premature senescence stimulated by sodium butyrate (NaB), a histone deacetylase inhibitor, has been studied. It was found that NaB did not block the cell cycle in E1A+cHa-ras transformants selected from embryonic mouse fibroblasts with jnk1,2 stress-kinase gene knockout (mERasJNK−/− cells). Even long-term (five days) NaB treatment did not block cell cycle distribution or cell proliferation, nor did it induce cellular hypertrophy or activate SA-β-galactosidase activity, a senescence marker. The data show that JNK stress kinases are involved in senescence induced in E1A+cHa-ras mouse transformants by NaB. It is possible to suggest that JNK1,2 have tumor suppressor properties because the process of senescence, which prevents tumor cell proliferation, does not occur if they are absent.

The role of p38α stress-kinase in the regulation of the premature senescence program induced by the histone deacetylase inhibitor sodium butyrate (NaB) was studied in rodent transformed cell lines. The study was carried out on E1A+cHa-ras transformants obtained from mouse embryonic fibroblasts null for the Mapk14 gene encoding p38α stress-kinase (the mERasp38−/− cell line), or for the PPM1D gene encoding the Wip1 phosphatase (the mERas Wip1−/− cell line), whose absence led to constitutive activation of p38α kinase. It was found that after NaB treatment both cell lines completely stopped proliferation due to irreversible G1/S cell cycle arrest. In both lines a marker of senescence appeared—the activity of β-galactosidase (SA-β-Gal). As well, treatment of the cells with NaB for several days led to morphological cell changes, such as partial readjustment of the actin cytoskeleton, spreading on the substrate, and heterochromatin focus formation (SAHF) in the senescent cell nuclei. These data allow us to suggest that, in the absence of functionally active p38α kinase, the NaB-induced irreversible process of cellular senescence may occur via alternative pathways for downregulation of the cell cycle.

The effect of treatment with various chemical modifiers on the physicomechanical properties of polyacrylonitrile (PAN) fibers was studied. The structures of the finished reinforcing systems were analyzed. The hardening kinetics of an epoxide binder in the presence of the modified fibrous systems were studied. It was found that modification of PAN filament improved the mechanical properties of epoxide composites based on it.

We have studied the role of the stress kinases p38 and JNK1,2 in premature senescence induced by sodium butyrate (NaBut), a histone deacetylase inhibitor, in mouse embryonic fibroblasts transformed by E1A+cHa-Ras oncogenes. It was found that transformants from p38 knockout cells are able to implement NaBut-induced senescence exhibited by cell cycle arrest, inhibition of proliferation, hypertrophic changes associated with mTORC1 activation and SA-β-galactosidase activity. In jnk1,2 knockouts, the NaButinduced senescence program was inhibited. NaBut-induced senescence in p38 knockouts closely correlates with mTORC1 activation shown by inhibiting mTORC1 with rapamycin. In jnk1,2 knockouts, mTORC1 complex is not activated. We believe that JNK1,2 kinases are required for mTORC1 activation and exhibition of premature senescence markers induced by NaBut in E1A+cHa-Ras transformants.

A new coarse-grained model of the DNA molecule has been proposed, which was elaborated on the basis of its all-atomic model analysis. The model has been shown to rather well reproduce the DNA structure under low and room temperatures. The Young’s and torsion moduli calculated using the coarse-grained model are in close agreement with experimental data and the theoretical results of other authors. The model can be used for DNA fragments of several hundreds base pairs for rather long time scales (of the order of μs) and for simulating their interactions with other structures.