Search

Abstract— Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes and released into the blood as high molecular weight multimeric glycoproteins weighing up to 20 million Daltons. Blood plasma metalloprotease ADAMTS13 cleaves ultra-large vWF multimers to smaller multimeric and oligomeric molecules. The vWF molecules attach to the sites of damage at the surface of arterioles and capillaries and unfold under conditions of shear stress. On the unfolded vWF molecule, the regions interacting with receptors on the platelet membrane are exposed. After binding to the vWF filaments, platelets are activated; platelets circulating in the vessels are additionally attached to them, leading to thrombus formation, blocking of microvessels, and cessation of bleeding. This review describes the history of the discovery of vWF, presents data on the mechanisms of vWF secretion and its structure, and characterizes the processes of vWF metabolism in the body under normal and pathological conditions.

Abstract Here, we propose a new approach for quantitative estimation of von Willebrand factor (vWF) exposed on the surface of endothelial cells (ECs) using the ARC1779 aptamer that interacts with the vWF A1 domain. To visualize complex formation between vWF and the aptamer, the latter was conjugated with the Cy5 fluorescent label. Cultured human umbilical vein endothelial cells (HUVEC) were stained with the ARC1779-Cy5 conjugate and imaged with a fluorescence microscope. The images were analyzed with the CellProfiler software. vWF released from the Weibel–Palade bodies was observed as bright dot-like structures of round and irregular shape, the number of which increased several times after HUVEC exposure to histamine or thrombin. Staining with ARC1779-Cy5 also revealed long filamentous vWF structures on the surface of activated HUVEC. vWF secretion by ECs is activated by the second messengers cAMP and Ca2+. There is evidence that hydrogen peroxide also acts as a second messenger in ECs. In addition, exogenous H2O2 formed in leukocytes can enter ECs. The aim of our study was to determine the effect of H2O2 on the vWF exposure at the surface of HUVEC using the proposed method. It was shown that hydrogen peroxide at concentration 100 µM, which is lower than the cytotoxicity threshold of H2O2 for cultured HUVEC, increased several times the number of dot-like structures and total amount of vWF exposed on plasma membrane of HUVEC, which suggest that H2O2 acts as a mediator that activates exocytosis of Weibel–Palade bodies and vWF secretion in the vascular endothelium during inflammation and upon elevated generation of endogenous reactive oxygen species in ECs.

The additional study of ancient volcanogenic massive sulfide deposits in various regions revealed microtextures, probably of biogenic origin, which could represent varieties of the shells of mineralized fauna. The new finds expand the list of sites containing relics of bioforms associated with hydrothermal vents of "black smokers".

The composition of microbial communities in rock samples, reservoir water, and enrichment cultures from subsurface horizons of an uranium deposit (Russia) was determined. The studied horizons were located in the zone of hindered water exchange at a depth of 513–544 m, characterized by moderate salinity (up to 15 g/L) of reservoir water and the presence of charry plant organic matter. The biodiversity of autochthonous subsurface prokaryotes was determined by high-throughput sequencing of the V4 region of the 16S rRNA gene. Bacterial phyla predominant in the rock samples were Firmicutes (24.2%), Fusobacteriota (23.0%), Proteobacteria (18.7%), Actinobacteriota (15.5%) and Bacteroidota (9.0%). The predominant bacterial phylum in the reservoir water was Proteobacteria (90.7%), including representatives of the genera Methylophaga, Porphyrobacter, Roseovarius, Pseudomonas, and Methylococcus. Sequencing of the internal transcribed spacer (ITS) revealed occurrence of lower fungi of the genera Mucor and Thamnidium (phylum Mucoromycota) and of the genus Penicillium (phylum Ascomycota) in the rock samples; members of these genera are known for their resistance to heavy metals and the ability to use complex organic substrates. The functional characteristics of bacterial communities of the rock and reservoir water samples, predicted by the iVicodak program and the KEGG database, showed that reservoir water bacteria had a higher potential ability to carry out the pathways of carbohydrate, nitrogen, and sulfur metabolism, degradation of xenobiotics, benzoate, polycyclic aromatic hydrocarbons and chlorinated organic compounds than the rock microbiota. Enrichment cultures of iron-reducing and sulfate-reducing bacteria and pure cultures of denitrifying bacteria of the genera Bacillus, Paenibacillus, and Acinetobacter were obtained. These results indicate the presence of a small but viable microbial community that can participate in the processes of transformations of carbon, nitrogen, sulfur, and metals in the subsurface horizon when water exchange is activated.

BACKGROUND: It is now known regulatory effect of gaseous mediators in many bodily functions. These mediators include nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S). However, detailed data on the regulatory role of each of these gasotransmitters (GTs) are still not sufficiently studied. OBJECTIVE: The aim of this study was to investigate on models of microrheological behaviour of intact red blood cells and their recovered ghosts of cellular responses to all three known gasotransmitters: NO, H2S, and CO. METHODS: In experiments with intact red blood cells (RBCs) and their recovered ghosts (filled with an isotonic solution of known viscosity), deformability (RBCD) and aggregation (RBCA) were recorded after incubation of cells with GT donors or stimulators of their endogenous synthesis. RESULTS: It was found that all three GT donors moderately increased the deformability of both intact RBCs and their recovered ghosts (by 5–10%, p

This article is devoted to the problem of working out of damping polymer materials which are effective in the wide temperature and frequency range. In the modern world, work is being carried out to create damping polymer composite materials (DPM) from which it is possible to manufacture protective elements and parts of engineering structures of reduced vibration excitability. Existing DPM have a narrow temperature range, within which effective vibration absorption is observed, moreover, most of them go through a vulcanization stage, which increases the cost of the final product, has a harmful effect on environment and allows limited recycling of waste. One of the ways to solve this problem is to replace traditional rubber vibration-absorbing materials with thermo-elastoplasts (TEP). The most promising polymer for TEP is ethylene vinyl acetate (EVA), which has high damping properties, oil resistance and relative incombustibility. In this regard, experimental studies were conducted to establish the patterns of influence of the type and concentration of structure-forming components (plasticizers, fillers, modifiers) on the dynamic mechanical properties of TEP based on EVA in order to develop a new DPM effective in a wide temperature range. The leading method to investigate this problem is a method of dynamic mechanical analysis which allows to get information about changes of mechanical characteristics under mechanical load and controlled temperature and frequency. With the help of detected patterns it was possible to determine type of plasticizer which significantly decreases glass temperature of EVA. The percentage ratio of EVA/plasticizer system is stated, and the type of plasticizer at which the maximum of mechanical losses takes over greater values is accordingly detected. It is revealed, that to work out DPM on EVA basis, which are effective in wide temperature range it is more preferable to add not less than 40 % on volume basis inert fillers, such as talc or mica with addition of 5-10 % of carbon as the hardening additive. The kind of resin improving damping properties and raising rigidity of composites on EVA basis is defined. On the basis of the research, a material was developed which has the following properties: the maximum value of tan δ is at least 0.45 at a temperature of plus 5�C (oscillation frequency 10 Hz); width of the temperature interval within which tan δ is not less than 0.3 from minus 40 to plus 50�С (oscillation frequency 10 Hz); conditional tensile strength of not less than 10 kg/cm2, cold resistance up to minus 50�C.

Study of the submicroscopic structure of oxide ores revealed their similarity to the present-day bacterial communities. It was shown that the structure of cobalt-bearing crusts and ferromanganese nodules is based on bacterial mats, which permits identifying them as stromatolites and oncolites. Data that support intense interaction between biofilms and the environment were found. Signs of formation of the mineral phase as a result of biochemical absorption and assimilation of iron and manganese by bacteria were observed.

In this paper we report on the application of dual-wavelength photodynamic therapy with a topical chlorin-based photosensitizer for treatment of Ramsay Hunt syndrome in a patient with HIV. Traditional treatment approach (combination of acyclovir and a glucocorticosteroid) failed to provide a significant outcome, while photodynamic therapy resulted in fast positive dynamics. No recurrence was observed in a 5-month-long follow-up.

Experimental studies on the effect of frequency and temperature on the dynamic mechanical properties of filled composites are studied poorly and require further research. The purpose of theresearch is to study the effect of heavy fillerbarite (BaSO4), on the dynamic characteristics of a highly filled composite based on butyl rubber, and to compare the efficiency of barite in the composite with similar light filler. The conclusions are made on the basis of a comparative analysis of the temperature-frequency dependences of the loss tangent and the storage modulusat various percentages of filler, obtained by the DMA method. It has been established that while increasing barite concentration the elasticity of the composite material decreases, the glass transition temperature shifts upwards, and the reverse occurs in the zone of highly elastic state of the composite: the higher the barite concentration, the higher the damping properties. The authors provided a rationale that the heavy filler shows the effect only in the highly elastic zone if compared with the light one. The article is of practical value for the development of new vibration insulation materials.

Erythrocytes change their micromechanical properties associated with membrane viscoelasticity when they perform the transport function. There is some evidence that this is due to the influence of signaling molecules, including such gasotransmitters as nitrogen oxide (NO) and hydrogen sulfide (H2S). The aim of this study was to investigate the changes in microrheology of human erythrocytes under the influence of donors and stimulants of endogenous formation of gasotransmitters. The erythrocyte deformability, assessed by the elongation index of erythrocytes (EIE), and aggregation parameters, the indices of aggregation of erythrocytes (IAE), of washed cells were recorded after their incubation with sodium nitroprusside (SNP); sodium hydrosulfide (NaHS), the donor of H2S; 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-l-one (ODQ), an inhibitor of soluble guanylate cyclase; L-arginine and N-nitroarginine methyl ester (L-NAME), a substrate and an inhibitor of NO synthase, respectively; and glibenclamide (GBC ), the blocker of ATP-sensitive potassium channels. In addition, the resealed ghosts of erythrocytes were prepared, incubated with the above compounds, and the change in their deformability was evaluated. EIE increased by 8–11% (p < 0.01) and IAE decreased by 11–26% (p < 0.01) after the incubation of erythrocytes with SNP and NaHS, respectively. L-arginine and SNP exerted similar microrheological effects, which were eliminated by L-NAME or ODQ. GBC caused an increase in EIE by 8% (p < 0.05); the effects of GBC and NaHS were not additive. Incubation of the erythrocyte ghosts with SNP, L-arginine and NaHS was accompanied by a moderate but significant increase in membrane elasticity (p < 0.05). The obtained results indicate that the donors and stimulators of gasotransmitters NO and H2S moderately increase deformability of erythrocytes and markedly reduce their aggregability. The experiments on the erythrocyte ghosts suggest the existence of a direct effect of gasotransmitters on the viscoelastic properties of the membrane of these cells, which is independent of cGMP.

The aim of our research was to study the influence of hydrogen peroxide on the exocytosis of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVEC). We have found that H2O2 at a non-toxic concentration (100 μM) increases the amount of vWF secreted by HUVEC by 43 ± 14% over control (p < 0.03) and elevates total exposition of vWF on cell surface by 89 ± 5% (p < 0.01). Analysis of immunofluorescent images of HUVEC with CellProfiler program revealed that the average number of antigen positive structures on the single cell surface increases from 11.4 ± 0.16 in control up to 17.5 ± 0.21 after incubation with H2O2 (p < 0.01). vWF is exposed on the cell surface as dots with the average sizes around 1–3 μm. H2O2 causes an increase in the number of these dots and the appearence of the strings of vWF which are absent in control HUVEC. It is suggested that H2O2 may serve as a messenger which stimulates vWF exocytosis.

Albumin is known to be able to cleave ether bonds in organophosphates (OPs). Amino acids responsible for esterase and pseudo-esterase albumin activity towards OPs are not yet finally identified. Presumably, Sudlow’s site I with the Tyr150 residue shows a “true” esterase activity, while Sudlow’s II site with the Tyr411 residue—a pseudo-esterase one. Both human (HSA) and bovine (BSA) serum albumins were used in in vitro studies of albumin (pseudo)esterase activity towards OPs. There is a body of evidence that the efficiency of interaction of different xenobiotics differs for these two proteins. Using paraoxon as an example, the aim of this study was to conduct an in silico study of the OP interaction with the previously identified potential sites of HSA and BSA (pseudo)esterase activity, to estimate the possibility of enzymatic reactions at these sites, to comparatively analyze these proteins from the evolutionary viewpoint, and to assess the possibility of extrapolating the experimental data obtained on BSA to a human organism. Molecular docking of paraoxon into the sites of HSA and BSA potential (pseudo)esterase activity has been performed. Conformational changes occurring in the resultant complexes with time have been studied by molecular dynamics simulation. It has been shown that Sudlow’s site II is less liable to evolutionary changes. Binding of modulators at other sites is not required for productive sorption of OPs and the phosphorylation reaction at Sudlow’s site II. It has been concluded that simi lar results for HSA and BSA could be expected for the irreversible binding of OPs at Sudlow’s site II. Since Sudlow’s site I is less conservative, diff erent binding efficiency could be expected for rigid molecules or optically active compounds. Both for HSA and BSA, productive binding of OPs at Sudlow’s site I is possible only after changes in the albumin molecule structure induced by binding of modulators at other sites.

Hydrogen peroxide at concentrations below cytotoxic ones causes an increase in the cytoplasmic calcium concentration in human umbilical vein endothelial cells as a result of calcium release from intracellular stores. Two-pore calcium channel blocker trans-NED19 partially suppresses the increase in the level of calcium ions in the cells in response to the addition of hydrogen peroxide. The staining of endothelial cells with the fluorescent stereoisomer cis-NED19 and LysoTracker confirmed the localization of two-pore calcium channels in lysosomes and endolysosomal vesicles.

The article deals with the problem of creating vibration damping polymeric materials with high damping properties in a wide temperature range. The purpose of the article is to study physical-mechanical properties of composites based on ethylene-vinyl acetate by adding various modifiers in the form of resins. The main method to investigate this problem is the method of dynamic mechanical analysis, which makes possible to obtain viscoelastic properties of polymeric materials under the influence of an oscillating load at various temperatures and oscillation frequencies. Due to the established experimental dependencies, the authors have determined the type of resin, which improves the damping properties and increases the stiffness of the composites based on ethylene-vinyl acetate. Moreover, the authors have defined the limit of working capacity of composites with resins at negative temperatures.

This research is devoted to the actual problem of the development of damping polymer materials which are effective in a wide range of temperatures and having satisfactory strength characteristics. There are many works devoted to the study of dynamic mechanical properties of filled composites, but most do not take into account the influence of plasticizer on the strength properties of the polymer, as they change its characteristics for the worse. In this respect, the study and comparison of the mechanical properties of the polymer base with the introduction of different types and concentrations of plasticizers is an urgent task. According to the received regularities it was possible to define the type, concentration and boundaries of the polarity of the plasticizer, which reduces the strength characteristics of ethylene-vinyl acetate to a lesser degree.

Oxide ores of the global ocean — cobalt-rich crusts and ferromanganese nodules are of bacterial origin and identified as stromatolites and onkolites. Pillar structure of ferromanganese stromatolites and festoon-shaped structures of onkolites represent the bacterial mats, formed by interbedding of fossilized bacterial biofilms. The appearance of ore-forming types of procaryotic family and their evolution are defined by major biosphere events. On the case study of the ferromanganese nodules of Magellanic mountains and cobalt-rich crusts of the province of the Clarion-Clipperton, the main stages of the evolution of structural forms of bacterial communities have been revealed. It has been shown that the change of phases happened due to the influence of major tectonic, volcanic and other geological events.

The currently existing terms “apoptotic index” and “apoptotic potential” are insufficient for the adequate qualitative evaluation and analysis of the proapoptotic activity of chemical agents within the wide range of therapeutic and toxic doses. Herein we introduce a new concept of cytotoxic power as an alternative to these terms related to apoptosis and other types of cell death on the basis of experimental data of hydrogen peroxide cytotoxic activity towards the human umbilical vein endothelial cells (HUVEC). We also propose an algorithm for computing cytotoxic power. Correlations between the percentage of early apoptotic and late apoptotic/necrotic cells and the expression or concentration of endothelial markers such as CD143, CD309, von Willebrand factor, phosphatase PTEN, have been revealed.

Hydrogen peroxide, formed in the endothelium, acts as a factor contributing to the relaxation of blood vessels. The reason for this vasodilatory effect could be modulation by H2O2 of calcium metabolism, since mobilization of calcium ions in endothelial cells is a trigger of endothelium-dependent relaxation. The aim of this work was to investigate the influence of H2O2 on the effects of Ca2+-mobilizing agonists in human umbilical vein endothelial cells (HUVEC). We have found that H2O2 in concentration range 10-100 μM increases the rise of [Ca2+]i induced by 5-hydroxytryptamine (5-HT) and carbachol and does not affect the calcium signals of ATP, agonist of type 1 protease-activated receptor SFLLRN, histamine and bradykinin. Using specific agonists of 5-HT1B and 5-HT2B receptors CGS12066B and BW723C86, we have demonstrated that H2O2 potentiates the effects mediated by these types of 5-HT receptors. Potentiation of the effect of BW723C86 can be produced by the induction of endogenous oxidative stress in HUVEC. We have shown that the activation of 5-HT2B receptor by BW723C86 causes production of reactive oxygen species (ROS). Inhibitor of NADPH oxidases VAS2870 suppressed formation of ROS and partially inhibited [Ca2+]i rise induced by BW723C86. Thus, it can be assumed that vasorelaxation induced by endogenous H2O2 in endothelial cells partially occurs due to the potentiation of the agonist-induced calcium signaling.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Poisoning by organophosphates (OPs) takes one of the leading places in the total number of exotoxicoses. Detoxication of OPs at the first stage of the poison entering the body could be achieved with the help of DNA- or RNA-aptamers, which are able to bind poisons in the bloodstream. The aim of the research was to develop an approach to rational in silico design of aptamers for OPs based on the example of paraoxon. From the published sequence of an aptamer binding organophosphorus pesticides, its threedimensional model has been constructed. The most probable binding site for paraoxon was determined by molecular docking and molecular dynamics (MD) methods. Then the nucleotides of the binding site were mutated consequently and the values of free binding energy have been calculated using MD trajectories and MM-PBSA approach. On the basis of the energy values, two sequences that bind paraoxon most efficiently have been selected. The value of free binding energy of paraoxon with peripheral anionic site of acetylcholinesterase (AChE) has been calculated as well. It has been revealed that the aptamers found bind paraoxon more effectively than AChE. The peculiarities of paraoxon interaction with the aptamers nucleotides have been analyzed. The possibility of improving in silico approach for aptamer selection is discussed.

In recent years, a series of investigations has been devoted to a possibility of using crystals based on CdTe with addition of magnesium (Mg), selenium (Se), or manganese (Mn) for X and gamma radiation detectors. In the literature there are contradictory data with respect to the segregation of Mg in (Cd,Mg)Te and Se in Cd(Te,Se) and to the possibility of obtaining materials with a homogeneous composition without grains and twins. We have wide technological possibilities of preparing crystals and investigating some of their properties. Thus, we performed crystallizations of (Cd,Mg)Te, Cd(Te,Se), (Cd,Mn)(Te,Se), and (Cd,Mn)Te compounds. The aim of our studies was to check whether any of the investigated materials may be easily obtained by the Low Pressure Bridgman (LPB) method in the form of large, homogeneous, high resistivity single crystals with as few as possible twins, subgrains, and tellurium inclusions. The crystallization processes were performed by using the LPB method. The elements used: Cd, Te, Mn, Mg, and Se were of the highest purity available at that time. In order to obtain reliable conclusions the crystallization processes were carried out under identical technological conditions. The details of our technological method and the results of the investigation of physical properties of the samples are presented below.

Non-curing sealants have a complex composition consisting of a mixture of polymers, plasticizers, extenders, adhesive additives, various special purpose additives (pigments, biocides, fire-retardants), and therefore the optimization of their compositions to improve the physical and mechanical and technological characteristics is rather complicated. This article demonstrates the experimental results of physical and mechanical properties such as penetration, strength, density, adhesion to metal and concrete, water absorption, and elongation of sealants on the basis of butyl-rubber and EPDM, depending on filler type and volume. The basic regularities of the nature influence and fillers on the physical and mechanical and technological characteristics of sealants are revealed. We’ve identified the ultimate proportion of fillers when the sealants meet the required specifications. The research results are the recommendations on the selection and optimization of the filler content of the sealant composition.

Albumin is known as being able to cleave ester bonds in organophosphates (OP) and serve as a major means of OP detoxification due to its large amount in the blood serum. Most of in vivo toxicological studies are conducted on rodents, mice and rats. To adequately extrapolate results of ligand/albumin interaction studies to a human organism, it is necessary to carry out a comparative analysis of the rat (RSA) and human (HSA) albumin structure by in silico methods. X-ray diffraction analysis of RSA has not been done as yet, and the RSA structure is still undetermined. The aim of this study was to build a three-dimensional (3D) model of RSA by homology modeling. As templates, 14 RSA homologs were selected from the Protein Data Bank. A 3D model of the RSA molecule was built using the RSA primary sequence and 3D models of the selected templates. The 3D model geometry was improved by the energy minimization method. The quality of the model was evaluated by 9 parameters. According to this evaluation, in 97% of protein structures from the comparative dataset these parameters were worse than in the obtained model. It was concluded that this model is suitable for further research, specifically, for in silico studies of the RSA/OP interaction and comparative evolutionary analysis of RSA and HSA.

Bacterial mats, formed by successively accumulating biofilms, are the main constructive component of the oxide ferromanganese ores on the oceanic floor. The coordinated behavior of the bacterial colonies in the biofilms controlled the growth of the stromatolites and onkolites structures. Biofilms of the stromatolite bacterial mats represent the microbial community, with the thread bacteria forming a poiygonal network that determines a piliar structure of the crusts. Bacterial mats in nodules are festoon-shaped. Biofilms in festoons intensely interact with the environment, assimilating petrogenic components and consuming the sedimentary material.

It is known that albumin can break the ester bonds in organophosphorus compounds (OPs). Amino acids responsible for esterase and pseudoesterase activity of albumin towards OPs are still not determined. It is assumed that Sudlow’s site I with residue Tyr150 exhibits the “true” esterase activity; and Sudlow’s site II containing residue Tyr411, a pseudoesterase one. Binding of fatty acids to albumin affects the efficiency of its interaction with xenobiotics; however, the effect of fatty acids on the interaction of albumin with OPs was not studied. The purpose of this work was to study the interaction of OPs with potential sites of albumin enzymatic activity and to examine the effect of fatty acids on the efficiency of such interaction using the molecular modeling methods by the example of paraoxon, a known inhibitor of acetylcholinesterase, and oleic acid. The structures of the protein complexes with paraoxon and oleic acid were determined by the molecular docking procedure; the conformational changes were calculated by the molecular dynamics method. It has been shown that sorption of oleic acid in one of the fatty acid-binding sites leads to the conformational changes in Sudlow’s sites I and II due to a “reversal” of the side chains of Arg410 and Arg257 residues by 90°. It has been found that this change in geometry reduces the affinity of Sudlow’s site I and increases the Sudlow’s site II affinity to paraoxon. The amino acid residue Ser193, which was previously identified as a site of possible albumin esterase activity, is not able to bind paraoxon efficiently. It is assumed that its activity can be affected by the interaction of the oleic acid molecules with other fatty acid-binding sites. It is hypothesized that the lesser toxicity of paraoxon compared to soman may be associated not only with its lower inhibitory activity against cholinesterases, but also with the increased affinity of paraoxon to albumin. It was concluded that albumin may serve as an alternative means of OP detoxification.

Enzymatic activities of three types of serum albumin—rat, bovine and human—were analyzed comparatively using a mathematical model. Kinetic and equilibrium constants of carboxylesterase and paraoxonase activities of albumin in Sudlow’s sites I and II were determined. The effects of specific ligands, ibuprofen and warfarin, on enzyme kinetics in these sites were studied. Ibuprofen was found to have an inhibitory effect both on carboxylesterase and paraoxonase albumin activities, whereas warfarin specifically inhibited only carboxylesterase albumin activity.

The remote effects of acute poisoning with organophosphates (OPs) are poorly studied, and the experimental models used often disregard species-related traits. Here we compare two toxicological models, both with rats as the model animal and paraoxon (POX) as the model OP, which were applied to study the dynamics of biochemical indices over 3 months after acute poisoning. Blood plasma carboxylesterase (CE) was preliminary inhibited with paraoxon or 2-(o-crezyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP). As was expected, the most sensitive biochemical index within the first hours and days after OP poisoning was blood acetylcholinesterase (AChE) activity: it decreased by almost an order of magnitude in all experimental animal groups 3 h after poisoning. Changes in the parameters of carbohydrate and fat metabolism (triglyceride, free fatty acid, d -3-hydroxybutyrate, cholesterol, and glycerol levels) were detected at different time points after poisoning. Significant changes in a number of biochemical markers were found in positive control relative to negative control rats.

The analysis of the submicroscopic textures of the cobaltiferous crusts from the Magellan Seamounts has shown that biofilms−ferromanganese stromatolite builders absorb petrogenic components (SiO2, Al2O3, P2O5, etc.) from the environment and use them for the formation of a columnar structure.

Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) isolated from rat aorta and on aorta contraction. To address this issue, the NAADP structural analogue and inhibitor of TPCs, NED 19, was applied. We have demonstrated a high degree of colocalization of the fluorescent signals of cis-NED 19 and endolysosmal probe LysoTracker in SMCs. Both cis- or trans-NED 19 inhibited the rise of [Ca2+]i in SMCs induced by 100 &mu, M NE by 50&ndash, 60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 &mu, M, respectively. The inhibition by NED 19 stereoisomers of the effects of AngII, AVP, and 5-HT was much weaker. Both forms of NED 19 caused relaxation of aortic rings preconstricted by NE, with relative potency of cis-NED 19 several times higher than that of trans-NED 19. Inhibition by cis-NED 19 of NE-induced contraction was maintained after intensive washing and slowly reversed within an hour of incubation. Cis- and trans-NED 19 did not cause decrease in the force of aorta contraction in response to Ang II and AVP, and only slightly relaxed aorta preconstricted by 5-HT and by KCl. Suppression of TPC1 in SMCs with siRNA caused a 40% decrease in [Ca2+]i in response to NE, whereas siRNA against TPC2 did not change NE calcium signaling. These data suggest that TPC1 is involved in the NE-stimulated [Ca2+]i rise in SMCs. Inhibition of TPC1 activity by NED 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.

We examine two kinds of volume defects in CdTe-based compounds grown from the melt: cadmium and tellurium inclusions. We have determined their chemical composition by energy-dispersive X-ray spectroscopy and their internal morphology by infrared transmission microscopy. The tellurium inclusions are spheroidal/polyhedral, while the cadmium ones appear star-like. The core size of both the tellurium and the cadmium inclusions is 5–8 μm. Cadmium inclusions cause micro cracks so that they create star-like defects the size of which is about ten times bigger than the inclusions themselves. Each pair of branches in the star-shaped defect we associate with the three easy-cleavage planes (1 1 0) of the zinc blende structure. Using Pockels imaging we have investigated how tellurium and cadmium inclusions influence the electric field distribution in CdTe compounds, which is an important issue for nuclear detectors. Only tellurium inclusions distributed along a continuous plane have an impact on the internal electric field. Neither the separated tellurium inclusions nor the separated cadmium inclusions influence the internal electric field. Crystals of (Cd,Mn)(Te,Se) have a high concentration (104–105 cm−3) of both types of inclusions. In (Cd,Mg)Te there are numerous twin boundaries decorated with tellurium inclusions. Among the studied compounds, (Cd,Mn)Te has the highest quality.

Scandium is introduced into bulk SiC during the physical vapor transport (PVT) growth. SiC crystals grown with different Sc contents (from 0.5 wt% up to 2.5 wt%, added to the SiC source material) are studied. Magnetic properties of SiC doped with scandium during the PVT growth are reported for the first time. The presence of antiferromagnetic interactions between magnetic moments of Sc ions is concluded from the temperature dependence of magnetic susceptibility. Detailed PL spectra of 4H-/6H-SiC:B and 4H-/6H-SiC:Sc crystals are presented. A new energy level of 35–37 meV is found on SiC:Sc samples and its possible assignment to a complex defect, consisting of nitrogen donor and scandium acceptor, is proposed.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. In blood vessels, serotonin 5-HT2B receptors mainly mediate relaxation, although their activation by the selective agonist BW723C86 is known to exert contraction of aorta in deoxycorticosterone acetate (DOCA)-salt and N(omega)-nitro-L-arginine (L-NAME) hypertensive rats [Russel et al., 2002; Banes et al., 2003] and in mice with type 2 diabetes [Nelson et al., 2012]. The unmasking effect on vasoconstriction can be caused by a shift in the balance of tyrosine phosphorylation in smooth muscle cells (SMC) due to oxidative stress induced inhibition of protein tyrosine phosphatases (PTP). We have demonstrated that BW723C86 which does not cause contraction of rat aorta and mesenteric artery rings, evoked a vasoconstrictor effect in the presence of PTP inhibitors sodium orthovanadate (Na3VO4) or BVT948. BW723C86 induced a weak rise of [Ca2+]i in the SMC isolated from rat aorta; however, after pre-incubation with Na3VO4 the response to BW723C86 increased more than 5-fold. This effect was diminished by protein tyrosine kinase (PTK) inhibitor genistein, inhibitor of Src-family kinases PP2, inhibitor of NADPH-oxidase VAS2870 and completely suppressed by N-acetylcysteine and 5-HT2B receptor antagonist RS127445. Using fluorescent probe DCFH-DA we have shown that Na3VO4 induces oxidative stress in SMC. In the presence of Na3VO4 BW723C86 considerably increased formation of reactive oxygen species while alone had no appreciable effect on DCFH oxidation. We suggest that oxidative stress causes inhibition of PTP and unmasking of 5-HT2B receptors functional activity.

open access article Endothelium is a community of endothelial cells (ECs), which line the blood and lymphatic vessels, thus forming an interface between the tissues and the blood or lympha. This strategic position of endothelium infers its indispensable functional role in controlling vasoregulation, haemostasis, and inflammation. The state of endothelium is simultaneously the cause and effect of many diseases, and this is coupled with modifications of endothelial phenotype represented by markers and with biochemical profile of blood represented by biomarkers. In this paper, we briefly review data on the functional role of endothelium, give definitions of endothelial markers and biomarkers, touch on the methodological approaches for revealing biomarkers, present an implicit role of endothelium in some toxicological mechanistic studies, and survey the role of reactive oxygen species (ROS) in modulation of endothelial status.

open access article The albumin molecule, in contrast to many other plasma proteins, is not covered with a carbohydrate moiety and can bind and transport various molecules of endogenous and exogenous origin. The enzymatic activity of albumin, the existence of which many scientists perceive skeptically, is much less studied. In toxicology, understanding the mechanistic interactions of organophosphates with albumin is a special problem, and its solution could help in the development of new types of antidotes. In the present work, the history of the issue is briefly examined, then our in silico data on the interaction of human serum albumin with soman, as well as comparative in silico data of human and bovine serum albumin activities in relation to paraoxon, are presented. Information is given on the substrate specificity of albumin and we consider the possibility of its affiliation to certain classes in the nomenclature of enzymes.

SiC crystals grown by a Physical Vapor Transport (PVT) method in the presence of varying Ce impurity contents (from 0.1 wt% up to 2.5 wt%) added to SiC source material are investigated. The presence of the cerium vapor in the growth atmosphere is confirmed by X-ray photoelectron spectroscopy measurements. Different electrical properties of SiC crystals are obtained while use was made of non-oxide (CeSi 2 ) or oxide (CeO 2 ) sources of Ce impurity. The impact of cerium on low concentrations of boron atoms in bulk SiC is reported. Presence of Ce in the vapor stabilizes the growth of the 4H-SiC polytype.

Thrombin acts on mammalian cells through the specific, so-called protease-activated receptors (PARs). The thrombin action is mediated via three out of four known types of these receptors—PAR1,3,4. Mammalian thrombin receptors, apart from performance of other functions, control cardiac and vascular contractility. It is not known whether receptors of such kind exist in invertebrate animals. In the present work we have showed for the first time that thrombin in the concentration range of 0.01–1 units/ml increases amplitude of contractions of the isolated heart ventricle of the edible snail Helix pomatia. Its effect is reproduced by peptide ligands of receptors PAR1 and PAR4 that have sequences Ser-Phe-Leu-Leu-Arg-Asn (SFLLRN) and Glu-Tyr-Pro-Gly-Lys-Phe (QYPGKF), respectively. A potent activator of cardiac contractility of H. pomatia is serotonin. A comparative study of the mechanisms of action of serotonin and thrombin on the edible snail heart was carried out. cAMP participates in transduction of signal from serotonin receptors. On the membrane preparation from the H. pomatia heart, it was shown that thrombin and peptide ligands PAR1 and PAR4, unlike serotonin, did not increase adenylyl cyclase activity. Thus, mechanism of activation of cardiac contractility of H. pomatia by thrombin differs from that of serotonin. It is suggested that molluscs have receptors homologous to protease-activated mammalian receptors.

Simulation of the thermal state of continuous-cast slabs permits comparative analysis of two cooling systems: the periphery-center system; and remote control of the pipe positions. These systems differ in the distribution of cooling over the ingot width. The results of numerical experiments are presented. In the periphery-center system, which is in wide global use, the edges of the slab are overcooled in some cases. Accordingly, it is better to organize slab cooling by means of pipes distributed diagonally over the height with sprayers that ensure coverage of the edges. Quantitative characteristics are proposed for the effectiveness of cooling in terms of the formation of precipitates (nitrides and carbonitrides of aluminum and alloying elements) that might weaken the grain boundaries.

Comparative study of the effect of calmodulin inhibitors trifluoperazine, W-12, and W-13 and the TRPV1 channel blocker capsazepine on receptor-dependent calcium metabolism in smooth muscle cells of the rat aorta and on the contraction of the isolated rat aorta was performed. Trifluoperazine almost completely abolishes an increase in free cytoplasmic calcium concentration in smooth muscle cells isolated from the rat aorta and smooth muscle cells of the A7r5 line in response to serotonin and does not affect cellular reaction to vasopressin and angiotensin II. W-12 and W-13 also do not attenuate responses to vasopressin and angiotensin II and reduces by two times free cytoplasmic calcium concentration elevation in response to serotonin. The efficiency of calcium metabolism suppression by calmodulin inhibitors correlates with the degree of inhibition of the aorta contractile response to serotonin. It was demonstrated that the inhibitory action of calmodulin antagonists on calcium metabolism in smooth muscle cells and the contractility of the isolated rat aorta during the activation of serotonin vasoconstrictive receptors are realized by a TRPV1-independent mechanism. It was demonstrated in experiments in vivo that trifluoperazine does not influence hypotensive reaction in rats (normally observed in response to intravenous serotonin injection), but removes the hypertensive effect of this neurotransmitter in rats after chronic introduction of dexamethasone. The results obtained confirm the hypothesis (that we previously stated) about the direct involvement of calmodulin in signal transmission from vasoconstrictive serotonin receptors.

Modern data concerning expression, localization, biophysical properties, involvement in calcium regulation, and physiological functions of TRP and Orai channels in skeletal muscle cells are analyzed. In skeletal muscles TRPC1/2/3/4/5/6/7, TRPV2/4, TRPM2/7 and Orai1/3 channels are expressed. Activities of TRPC1/3 and TRPV4 facilitate maximal muscle contraction during tetanus. Orai1 channels provide recovery of intracellular calcium stores and are obligatory for proliferation of myoblasts and differentiation of skeletal muscles. TRPC1 knockout results in alterations of the development of skeletal muscles. Enhanced calcium influx via the channels is supposed to be a pathogenic factor of myodystrophy.

This work is an analysis of the layered structure of ferromanganese concretions (FMC) from the Clarion-Clipperton ore province and Co-rich manganese from guyots of the Magellan seamounts, study of microtextures, detection and interpretation of accessory minerals, which allowed us to establish that the formation of deposits of oxide ores, was accompanied by active intraplate volcanism and the formation of sulfide structures, such as black smokers.

The expression levels of inositol-1,4,5-trisphosphate receptors (InsP3R) and cytoplasmic free calcium concentration ([Ca2+]c) changes in response to ATP in cultured skeletal myoblasts C2C12, in myoblasts at different stages of differentiation into myotubes, and in differentiated multinucleated myotubes have been determined. Using reverse transcription and real-time polymerase chain reaction we have shown that during differentiation of myoblasts into myotubes the expression of all three InsP3R increased 2–2.5-fold and at all stages of differentiation the expression levels of InsP3R2 and InsP3R3 were nearly equal to each other and 1.5–2 times higher than the expression level of InsP3R1. The kinetics of calcium signal in myotubes is characterized by higher maximal [Ca2+]c rise and more prolonged second phase in comparison with myoblasts. The data obtained provide evidence in favor of the increasing role of InsP3-dependent calcium mobilization at the first stages of skeletal muscles maturation.

The C60 fullerite has been Ca-intercalated under high pressure up to 240 kbar induced by a pressure shock wave. Magnetometric measurements have revealed superconductivity of the as-prepared sample at 9.9 K. The sample relaxed under normal conditions in the helium atmosphere has exhibited traces of superconductivity with the onset at T = 30 K.

Shock-wave pressure treatment up to 65 GPa has been applied to samples representing powdered mixtures of calcium and calcium phosphate in 1:1 volume ratio. Magnetometric measurements have revealed superconductivity of the samples at 50 K. By means of X-ray powder diffraction and magnetometric measurements, it has been found that superconductivity observed in the samples corresponds to instability at ambient pressure and room temperature of the phase/s formed in the samples during their shock-wave pressure treatment.

Expression of channel protein Orai-1 has been demonstrated in cultured skeletal myoblasts and myotubes. In order to evaluate its functional role in Ca2+ transport in these cells we used small interfering RNA (siRNA) targeted against mRNA coding for Orai-1. Optimal conditions for the effective transfection of myoblasts and myotubes were found. In experiments using myotubes from an mdx cell line we have shown that inactivation of mRNA coding Orai-1 results in complete suppression of 45Ca2+ entry induced by thapsigargin, an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase. The data obtained indicate that Orai-1 is involved in store-activated Ca2+ entry into skeletal myotubes.

Organosulfur compounds (OSC) are widely present in our bodies and the natural environment. There are two principal groups of vegetables that contain OSC with special properties. Garlic, onion, shallot, leek, and chives are well-known representatives of the Allium genus (family Amaryllidaceae) that contain S-alk(en)yl- l -cysteine sulfoxides. Cabbage, cauliflower, Brussels sprouts, and kale are representatives of the Brassica genus, and rucola (rocket salad) is representative of the Eruca genus of the mustard or cruciferous family (Brassicaceae), which contain S-methyl cysteine- l -sulfoxide. OSC as nutraceutical agents not only can serve as direct antioxidants trapping electrons but also can have nonantioxidant effects, such as antiplatelet, fibrinolytic, anti-inflammatory, immunomodulatory, and antiaging actions. These properties of OSC are useful in the prophylaxis and treatment of various pathological states, such as cardiovascular diseases, cancer, neurodegenerative disorders, and diabetes; they have antibacterial, antiviral, and some other activities. Theories have emerged that explain these properties of OSC by their correction of redox-sensing and redox-signaling properties.

A study of electrophysical and thermodynamic properties of C60 single crystals under step shock loading has been carried out. The increase and the following reduction in specific electroconductivity of C60 fullerite single crystals at step shock compression up to pressure 30 GPa have been measured. The equations of state for face centred cubic (fcc) C60 fullerite as well as for two-dimensional polymer C60 and for three-dimensional polymer C60 (3D-C60) were constructed. The pressure–temperature states of C60 fullerite were calculated at step shock compression up to pressure 30 GPa and temperature 550 K. The X-ray diffraction studies of shock-recovered samples reveal a mixture of fcc C60 and a X-ray amorphous component of fullerite C60. The start of the formation of the X-ray amorphous component occurs at a pressure P m≈ 19.8 GPa and a temperature T m≈ 520 K. At pressures exceeding P m and temperatures exceeding T m, the shock compressed fullerite consist of a two-phase mixture of fcc C60 fullerite and an X...

Zn 1-x Mn x Te crystals (0 ≤ x ≤ 0.30) have been grown by the high pressure Bridgman technique. The free exciton energy of Zn 1-x Mn x Te was determined from the photoluminescence and reflectance measurements in the temperature range from 1.7 to 270 K. The magneto-photoluminescence and magneto-reflectance were studied at T= 1.7 K and in magnetic fields up to 6 T. The magnetization of Zn 1-x Mn x Te was calculated from the giant Zeeman effect. It was found that there is an efficient energy transfer channel from the photo-excited carriers into the Mn 2+ ions by spin-flip scattering processes. It allows one to change the spin temperature of the Mn 2+ subsystem and consequently to control its magnetization by tuning laser excitation density. The magnetization of the Zn 1-x Mn x Te can be changed by 60% of its maximum value.