Репозиторий Университета

© 2018 Elsevier Ltd The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically converted to fibrin, which self-assembles to form double-stranded protofibrils. When reaching a critical length, these intermediate species aggregate laterally to transform into fibers arranged into branched fibrin network. We combined multiscale modeling in silico with atomic force microscopy (AFM) imaging to reconstruct complete atomic models of double-stranded fibrin protofibrils with γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions—all important structural determinants not resolved crystallographically. Structures of fibrin oligomers and protofibrils containing up to 19 monomers were successfully validated by quantitative comparison with high-resolution AFM images. We characterized the protofibril twisting, bending, kinking, and reversibility of A:a knob-hole bonds, and calculated hydrodynamic parameters of fibrin oligomers. Atomic structures of protofibrils provide a basis to understand mechanisms of early stages of fibrin polymerization. Zhmurov et al. used 27 relevant crystal structures to computationally reconstruct the full-atomic models of fibrin oligomers and protofibrils, which correlate with high-resolution atomic force microscopy images. The structures contain much valuable information for understanding the early stages of fibrin polymerization.

© 2018 IOP Publishing Ltd. The integration of energy harvesting and energy storage in a single device both enables the conversion of ambient energy into electricity and provides a sustainable power source for various electronic devices and systems. On the other hand, mechanical flexibility, coupled with optical transparency of the energy storage devices, is required for many applications, ranging from self-powered rolled-up displays to wearable optoelectronic devices. We integrate a piezoelectric poly(vinylidene-trifluoroethylene) (P(VDF-TrFE)) film into a flexible supercapacitor system to harvest and store the energy. The asymmetric output characteristics of the piezoelectric P(VDF-TrFE) film under mechanical impacts results in effective charging of the supercapacitors. The integrated piezo-supercapacitor exhibits a specific capacitance of 50 F g-1. The open-circuit voltage of the flexible and transparent supercapacitor reached 500 mV within 20 s during the mechanical action. Our hybridized energy harvesting and storage device can be further extended to provide a sustainable power source for various types of sensors integrated into wearable units.

© 2018 Contemporary Clinical Dentistry | Published by Wolters Kluwer - Medknow. Background: The success of endodontic treatment depends on the knowledge of root canal system. The root canals have complex morphology and wide individual variations. The aim of this study was to evaluate the root canal morphology of the maxillary first molars among residents of the Moscow region using cone-beam computed tomography (CBCT) scanning. Materials and Methods: Three hundred CBCT images of patients aged 20-70 years old were analyzed to study the root canal system (the number of canals and the configuration according to Vertucci's classification) of the maxillary first molars. The prevalence of a second mesiobuccal (MB2) in the mesiobuccal root (MB) was recorded in each age group. Results: three separated roots of the maxillary first molar were observed in 100% of cases. MB2 canals were found in 59.8% of cases. A second distobuccal canal was observed in 0.5% of cases. The canal morphology in the MB root was 40.2% in Type I, 22.4% in Type II, and 37.3% in Type IV. Conclusion: The prevalence of MB2 canals was 59.8%, and the most common canal morphology was Vertucci's Type I. Using CBCT scanning is a useful technique to evaluate and analyze the root canal system.

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. Since the 1990s, when it was demonstrated by Hammel and others that liver fibrosis is reversible, researchers and physicians actively search for new antifibrotic therapies. In recent years, knowledge of liver fibrosis pathophysiology has greatly advanced and new cellular and molecular mechanisms were described. The cells that determine extracellular matrix components distribution are myofibroblasts, but their origin is diverse. They can be activated hepatic stellate cells (HSCs), portal fibroblasts (PF), or circulating mesenchymal stem cells of the bone marrow. Among large number of substrates to inhibit activation, to inhibit proliferation of myofibroblasts, and to induce their apoptosis we, chose curcumin and gliotoxin. Primarily, in the current work, we optimized the explantation culture method for isolation of hepatic myofibroblasts and received two different cultures—myofibroblasts of HSC and PF origin. Exposition of 50 μM curcumin and 0.1 μM gliotoxin was the most optimal; we observed suppression of hepatic myofibroblast activation and inhibition of their proliferation. These results extend the current knowledge of the cells within the liver fibrogenic populations and prove inhibitory influence of biologically active substances (curcumin and gliotoxin) on portal myofibroblasts.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The liposomal form of silibinin was obtained, and its antihepatotoxic activity in mice was studied using a model of acute toxic hepatitis caused by injection of carbon tetrachloride or paracetamol. It was shown that the use of the drug in therapy or prevention regimens leads to normalization of levels of transaminases and total protein in the blood of experimental animals. The results of the study showed that liposomal silibinin when administered intravenously shows a more pronounced hepatoprotective effect compared to intragastric administration of free silibinin. Thus, the effectiveness of the therapeutic action of silibinin can be significantly increased by using its liposomal form. Liposomal drug, in contrast to native silibinin, can be injected directly into the blood that significantly increases its bioavailability.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Issues pertaining to determination of the pharmacokinetic parameters of calcium preparations are examined using their comparative bioavailability as an example. Pharmacokinetic parameters of calcium such as area under the concentration—time curve (AUC) and maximum concentration (Cmax) are calculated considering the background calcium contents in volunteers. Calcium excretion with urine is assessed as clearance of creatinine, a calcium elimination factor. The dynamics of the content of parathormone (PTH), the main hormone regulating calcium homeostasis, are studied. The results can be used to plan clinical trials for assessing the pharmacokinetics of drug analogs of endogenous compounds.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The levels of pollution by heavy metals and arsenic in top soil layers and medicinal plant raw materials in Voronezh Region were studied using Urtica dioica and Plantago major leaves as examples. The analyses were carried out using atomic absorption spectrometry on a graphite-furnace MGA-915MD spectrometer. Samples were collected from districts with different anthropogenic impacts across the whole region. Leaves of P. major characteristically had the highest coefficients of accumulation from the soil for Cd, As, and Ni. Leaves of U. dioica typically had high accumulation coefficients for Ni.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Solid dispersions (SDs) of indomethacin with polyethylene glycol 1500 (PEG-1500) were studied to determine their effect on indomethacin solubility. Production of SDs increased the solubility and dissolution rate of indomethacin in H2O. The solubility and dissolution rate of indomethacin from SDs increased by 1.8 – 2.2 and 3.1 – 4.4 times, respectively. Indomethacin became less crystalline and then amorphous during preparation of the SDs. Dissolution of the SDs solubilized indomethacin and formed colloidal solutions.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Objective: The article studies state-of-the art physical therapeutic techniques as a high degree of relevance to minimize invalidation and improve quality of life for patients with dental osteosarcoma. Materials and Methods: A randomized controlled clinical trial was conducted in 21 patients with osteogenic sarcoma of mandible (C41.1). There were 10 patients in the experimental group and 11 patients in the control group. Results: A comprehensive treatment and rehabilitation program for patients with osteosarcoma of mandible was developed. The first part of the program comprised 3 basic phases: preop chemotherapy, surgery, and postop rehabilitation. The surgical treatment further included resection of an affected part of the mandible and primary repair of the defect with jaw fragments and an autoimplant joined together with the help of positioning devices. The postop rehabilitation included postop chemotherapy and mesodiencephalic modulation (MDM). The second part of the program comprised preop examination, modeling, using stereolytic 3-dimensional models of the mandible, corrective surgeries, including implantation into the auto-implantda fragment of patient’s fibula, and building of a removable titanium alloy–based denture. MDM sessions were administered after each invasive intervention. Conclusions: Higher psychological and physical well-being was observed in the experimental group as compared with the control group (P, 0.01) in 2 weeks after the first surgery and 2 months after scheduled corrective surgeries, which finished in denture installation.

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

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

© 2017, Springer Science+Business Media, LLC, part of Springer Nature. We need to take into complex assessment a set of influencing factors of drinking water safety. This raises the task of developing an integrated methodology assessing the safety of drinking water that reaches the consumers. For the integrated assessment of the safety of drinking water, the method of clustering was chosen, namely, the neural network method of Kohonen self-organizing maps. Zones were separated by the method of cluster neural network analysis. The zones are characterized by different content of metal cations in drinking water, levels of carcinogenic and non-carcinogenic risk to the health of the child population, and the probability of the receipt of metal cations with potable water to consumers.

© 2018 Elsevier GmbH Background: The non-healing wound is a characteristic clinical sign in recessive dystrophic epidermolysis bullosa (RDEB). Methods: Six patients with recessive dystrophic epidermolysis bullosa were injected with suspension of allogeneic fibroblasts into erosion margins. Erosions (>1 month old) with surface area between 2 cm2 and 28 cm2 were selected for treatment. The patients were administered with 1 mL suspension of allogeneic fibroblasts with concentration 5 × 106 cells/ml, 10 × 106 cells/ml and 20 × 106 cells/ml. Paired erosions were injected with vehicle solution alone. All erosions were assessed for healing rate and biopsied at baseline and at two weeks after treatment. Immunofluorescence antigen mapping (IFM) was performed to detect C7 expression. Results: An increase of healing rate was detected 14 days after fibroblasts and vehicle alone injections, in some cases with complete erosion closure. The results of the IFM in patients treated with allogeneic fibroblasts and vehicle solution demonstrated the increase of collagen VII expression in dermo-epidermal junction, more intensive in patients injected with 20 × 106 cells/ml. Conclusions: Intradermal administration of allogeneic fibroblasts is a safe and effective method of treatment of non-healing wounds in recessive dystrophic epidermolysis bullosa.

© 2018 The Authors There are several pitfalls associated with research based on transgenic mice. Here, we describe our interpretation and analysis of mTORC1 activation in growth plate chondrocytes and compare these to a recent publication (Yan et al., Nature Communications 2016, 7:11151). Both laboratories employed TSC1-floxed mice crossed with collagen type 2-driven Cre (Col2-Cre), but drew substantially different conclusions. It was reported that activation of mechanistic target of rapamycin complex 1 (mTORC1) via Tsc1 ablation promotes the hypertrophy of growth plate chondrocytes, whereas we observe only disorganization in the resting zone, with no effect on chondrocyte hypertrophy or proliferation. Here, we present our data and discuss the differences in comparison to the earlier phenotypic characterization of TSC1 ablation in cartilage. Importantly, we detect Col2-Cre activity in non-cartilaginous tissues (including the brain) and discuss it in relation to other studies reporting non-cartilaginous expression of collagen alpha(1) II. Altogether, we conclude that mouse phenotypes following genetic ablation using Col2-Cre should be interpreted with care. We also conclude that activation of mTORC1 by TSC1 ablation in postnatal chondrocytes with inducible Col2-Cre (Col2-CreERt) leads to disorganization of the resting zone but causes no changes in chondrocyte proliferation or differentiation.

© 2018 Elsevier B.V. Recombination is a common event in RNA viruses; however, in the rabies virus there have been only a few reports of isolated recombination events. Comprehensive analysis found traces of recent recombination events within Arctic, Arctic-like and Africa 1b rabies virus groups, as well as recombination between distinct lyssaviruses. Recombination breakpoints were not linked to gene boundaries and could be detected all over the genome. However, there was no evidence that recombination is an important factor in the genetic variability of the rabies virus. It is therefore likely that recombination in the rabies virus is limited by ecological factors (e.g., rare co-circulation of distinguishable lineages and a narrow window for productive coinfection in most carnivore hosts), rather than molecular barriers (e.g., incompatibility of genome fragments).

© 2018. ASERS Publishing. All rights reserved. The paper understands cross-border natural resources as a totality of characteristics of local ecological systems, which can act as regulators of human’s life space. Authors state that uniqueness of this phenomenon is defined by the fact that all natural resources act as a single system of planet scale. The problem distinguished in the paper is based on the fact that in the period of ecological systems and natural resources development a little attention is paid to cross-border management on the part of nations they belong to. The research subject is an indicator of stability and quality of management of cross-border natural resources in the aspect of their even existing and carrying out of their functions. Scientific novelty of the research is that it’s proved for the first time that each ecological system has s number of parameters, one of which shows how much it resistant to human impact. The system of providing biodiversity is one of such parameters. In the paper the legal characteristics of the issue are identified with the actual state of interstate cooperation and the opportunity of its expansion within the already existing interstate formation is determined. The example of such formation is European Union. The areas of further research can be defined as an expansion of specified cooperation of Asian and South American continent.

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

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

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. Oxidative kidney injury was compared in newborn and adult rats under conditions of ischemia/reperfusion and in experimental model of systemic inflammation induced by endotoxin (LPS of bacterial cell wall) administration. Oxidative stress in the kidney accompanied both experimental models, but despite similar oxidative tissue damage, kidney dysfunction in neonates was less pronounced than in adult animals. It was found that neonatal kidney has a more potent regenerative potential with higher level of cell proliferation than adult kidney, where the level proliferating cell antigen (PCNA) increased only on day 2 after ischemia/reperfusion. The pathological process in the neonatal kidney developed against the background of active cell proliferation, and, as a result, proliferating cells could almost immediately replace the damaged structures. In the adult kidney, regeneration of the renal tissue was activated only after significant loss of functional nephrons and impairment of renal function.