Репозиторий Университета

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was assessment of gender differences in hair trace element content in English Thoroughbred horses (North Caucasus, Russia) using ICP-DRC-MS and calculation of the reference values. Trace element content in mane hair of 190 stallions and 94 mares (3–7 years old) bred in North Caucasus (Russia) was assessed using inductively coupled plasma mass spectrometry. Mane hair Co, Cr, Mn, Li, Si, and Sr levels in mares exceeded those in stallions by 77%, 63%, 64%, 42%, 39%, and 64%, respectively. Hair Fe and Si content was nearly twofold higher in female horses as compared to the males. Only hair Zn content was 5% higher in stallions as compared to mares. In addition, mares were characterized by 63%, 65%, 29%, and 40% higher levels of As, Pb, Sn, and Ni levels in hair as compared to the respective values in stallions. In turn, hair Al and Hg were more than twofold higher in mares than in stallions. The reference intervals of mane hair content (μg/g) for Co (0.006–0.143), Cr (0.028–0.551), Cu (4.17–6.84), Fe (10.11–442.2), I (0.026–3.69), Mn (0.551–12.55), Se (0.108–0.714), Zn (97.43–167), Li (0.011–0.709), Ni (0.060–0.589), Si (0.665–29.12), V (0.006–0.584), Al (1.98–168.5), As (0.006–0.127), Cd (0.002–0.033), B (0.494–16.13), Pb (0.018–0.436), Sn (0.002–0.144), Sr (1.0–9.46), and Hg (0.0018–0.017) in the total cohort of horses were estimated using the American Society for Veterinary Clinical Pathology Quality Assurance and Laboratory Standard Guidelines. The reference intervals were also estimated for stallions and mares bred in North Caucasus (Russia) and may be used for interpretation of the results of hair trace element analysis in horses.

© Copyright © 2019 Delfino, Porozov, Stepanov, Tamazian and Tozzini. Transitions between different conformational states are ubiquitous in proteins, being involved in signaling, catalysis, and other fundamental activities in cells. However, modeling those processes is extremely difficult, due to the need of efficiently exploring a vast conformational space in order to seek for the actual transition path for systems whose complexity is already high in the stable states. Here we report a strategy that simplifies this task attacking the complexity on several sides. We first apply a minimalist coarse-grained model to Calmodulin, based on an empirical force field with a partial structural bias, to explore the transition paths between the apo-closed state and the Ca-bound open state of the protein. We then select representative structures along the trajectory based on a structural clustering algorithm and build a cleaned-up trajectory with them. We finally compare this trajectory with that produced by the online tool MinActionPath, by minimizing the action integral using a harmonic network model, and with that obtained by the PROMPT morphing method, based on an optimal mass transportation-type approach including physical constraints. The comparison is performed both on the structural and energetic level, using the coarse-grained and the atomistic force fields upon reconstruction. Our analysis indicates that this method returns trajectories capable of exploring intermediate states with physical meaning, retaining a very low computational cost, which can allow systematic and extensive exploration of the multi-stable proteins transition pathways.

© 2019, The Author(s). Abstract: In 2014, the International Endohernia Society (IEHS) published the first international “Guidelines for laparoscopic treatment of ventral and incisional abdominal wall hernias.” Guidelines reflect the currently best available evidence in diagnostics and therapy and give recommendations to help surgeons to standardize their techniques and to improve their results. However, science is a dynamic field which is continuously developing. Therefore, guidelines require regular updates to keep pace with the evolving literature. Methods: For the development of the original guidelines, all relevant literature published up to year 2012 was analyzed using the ranking of the Oxford Centre for Evidence-Based Medicine. For the present update, all of the previous authors were asked to evaluate the literature published during the recent years from 2012 to 2017 and revise their statements and recommendations given in the initial guidelines accordingly. In two Consensus Conferences (October 2017 Beijing, March 2018 Cologne), the updates were presented, discussed, and confirmed. To avoid redundancy, only new statements or recommendations are included in this paper. Therefore, for full understanding both of the guidelines, the original and the current, must be read. In addition, the new developments in repair of abdominal wall hernias like surgical techniques within the abdominal wall, release operations (transversus muscle release, component separation), Botox application, and robot-assisted repair methods were included. Results: Due to an increase of the number of patients and further development of surgical techniques, repair of primary and secondary abdominal wall hernias attracts increasing interests of many surgeons. Whereas up to three decades ago hernia-related publications did not exceed 20 per year, currently this number is about 10-fold higher. Recent years are characterized by the advent of new techniques—minimal invasive techniques using robotics and laparoscopy, totally extraperitoneal repairs, novel myofascial release techniques for optimal closure of large defects, and Botox for relaxing the abdominal wall. Furthermore, a concomitant rectus diastasis was recognized as a significant risk factor for recurrence. Despite insufficient evidence with respect to these new techniques, it seemed to us necessary to include them in the update to stimulate surgeons to do research in these fields. Conclusion: Guidelines are recommendations based on best available evidence intended to help the surgeon to improve the quality of his daily work. However, science is a continuously evolving process, and as such guidelines should be updated about every 3 years. For a comprehensive reference, however, it is suggested to read both the initial guidelines published in 2014 together with the update. Moreover, the presented update includes also techniques which were not known 3 years before.

© 2019 The Author(s). Background: Trypanosomatids of the genus Leishmania are parasites of mammals or reptiles transmitted by bloodsucking dipterans. Many species of these flagellates cause important human diseases with clinical symptoms ranging from skin sores to life-threatening damage of visceral organs. The genus Leishmania contains four subgenera: Leishmania, Sauroleishmania, Viannia, and Mundinia. The last subgenus has been established recently and remains understudied, although Mundinia contains human-infecting species. In addition, it is interesting from the evolutionary viewpoint, representing the earliest branch within the genus and possibly with a different type of vector. Here we analyzed the genomes of L. (M.) martiniquensis, L. (M.) enriettii and L. (M.) macropodum to better understand the biology and evolution of these parasites. Results: All three genomes analyzed were approximately of the same size (~ 30 Mb) and similar to that of L. (Sauroleishmania) tarentolae, but smaller than those of the members of subgenera Leishmania and Viannia, or the genus Endotrypanum (~ 32 Mb). This difference was explained by domination of gene losses over gains and contractions over expansions at the Mundinia node, although only a few of these genes could be identified. The analysis predicts significant changes in the Mundinia cell surface architecture, with the most important ones relating to losses of LPG-modifying side chain galactosyltransferases and arabinosyltransferases, as well as β-amastins. Among other important changes were gene family contractions for the oxygen-sensing adenylate cyclases and FYVE zinc finger-containing proteins. Conclusions: We suggest that adaptation of Mundinia to different vectors and hosts has led to alternative host-parasite relationships and, thereby, made some proteins redundant. Thus, the evolution of genomes in the genus Leishmania and, in particular, in the subgenus Mundinia was mainly shaped by host (or vector) switches.

© 2019 Elsevier B.V. While research into the role of cathepsins has been progressing at an exponential pace over the years, research into their respective isoform proteins has been less frenetic. In view of the functional and biological potential of such protein isoforms in model systems for cancer during their initial discovery, much later they have offered a new direction in the field of cathepsin basic and applied research. Consequently, the analysis of such isoforms has laid strong foundations in revealing other important regulatory aspects of the cathepsin proteins in general. In this review article, we address these key aspects of cathepsin isoform proteins, with particular emphasis on how they have shaped what is now known in the context of nuclear cathepsin localization and what potential these hold as nuclear-based therapeutic targets in cancer.

© 2019 by the authors. This paper reveals the mechanism of nanowelding a branched network of single-walled carbon nanotubes (SWCNTs) used as a framework for the formation of protein-polymer matrices with albumin, collagen, and chitosan. It is shown that the introduction of certain point defects into the structure of SWCNTs (single vacancy, double vacancy, Stone-Wales defect, and a mixed defect) allows us to obtain strong heating in defective regions as compared to ideal SWCNTs. The wavelengths at which absorption reaches 50% are determined. Non-uniform absorption of laser radiation along with inefficient heat removal in defective regions determines the formation of hot spots, in which nanowelding of SWCNTs is observed even at 0.36 nm between contacting surfaces. The regularities of formation of layered protein-polymer matrices and the features of their interaction with cell membrane are revealed. All studies are carried out in silico using high-precision quantum approaches.

© 2019 Wiley Periodicals, Inc. Background: Clinical measures and implant design innovation to improve primary osseointegration and reduce the bacterial contamination of the peri-implant area are intended to reduce the incidence of late inflammatory complications in dental implantation. Purpose: To study the effect of nanostructured coating and antiseptic sealant on the outcomes of dental implantation. Materials and methods: Ninety-six individuals were clinically supervised. In the first group (Screw Ti + sealant), a special antiseptic sealant matrix was used; the same sealant was used with nanocoated implants in the second group (Nanocoat + sealant), and the conventional treatment protocol was used in the control group (Screw Ti). Patients were evaluated longitudinally during treatment and rehabilitation phases with clinical examinations, radiography, periodontal pathogen detection, and patient experience surveys. Results: For patients who received a nanocoated implant and an antiseptic sealant (Nanocoat + sealant), relatively better hygienic indices were observed; there was less contamination with periodontal pathogens, bone density remained at the required level, and the overall results of treatment were better. Conclusions: Using a matrix for sealing the dental implant-abutment interface with a nanostructured surface provides reliable results regarding stable osseointegration and clinical and patient-reported outcomes of treatment success.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO.

© 2019 WILEY-VCH Verlag GmbH  &  Co. KGaA, Weinheim Nanoporous glassy polymers are perspective materials for the fabrication of gas separation membranes, especially for the application of gaseous hydrocarbon separation. However, the drawback of such materials is the pronounced physical aging resulting in the dramatic drop of gas transport properties due to relaxation of high-free-volume fraction in time. Herein, a novel and readily available group of such glassy polymers is reported based on 5-alkylnorbornenes. These polymers are easily synthesized from dicyclopentadiene and α-olefins by Diels-Alder reaction and vinyl (addition) polymerization of the formed cycloadducts in the presence of ([(η3-C3H5)PdCl]2/PCy3/Na+[B(3,5-(CF3)2C6H3)4]− catalyst. The obtained polymers display low-fraction free volume, stable gas permeability over time, and possess a unique feature for the glassy polymers—solubility controlled permeation of hydrocarbons and enhanced C4H10/CH4 selectivity.

© 2019 The Authors This article is essentially a dataset necessary for analysing the taxation. The data analysis has allowed to determine the optimal taxation model, when the criteria of economic efficiency and equity are incompatible. The dataset has allowed the use of the method of successive concessions in tax optimization. The practical significance of the dataset lies in the ability to simultaneously improve the efficiency and equity in taxation. The dataset was obtained by using the method of expert estimates. A group of experts was asked to rank the taxes established by the Tax Code of the Russian Federation, in descending order of importance. Only strict rankings were allowed. The consistency of expert opinion was evaluated using the Kendall coefficient of concordance. The data set was supplemented with the expert ranking data of the basic principles of taxation, such as the principle of equity; the principle of certainty and accuracy of taxes; the principle of ease of tax collection for taxpayers; the principle of efficiency; the principle of commitment. The dataset can be used in the future to determine a rational amount of taxation depending on the established criteria.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Adiponectin is encoded by the ADIPOQ gene and participates in the pathogenesis of cardiovascular and metabolic diseases. The goal of the study was to assess associations of rs17300539, rs266729, rs182052, rs2241766, and rs17366743 single nucleotide polymorphisms (SNPs) of the ADIPOQ gene with concentrations of serum adiponectin and with coronary atherosclerosis and type 2 diabetes mellitus in 447 patients (316 men and 131 women) subjected to coronary angiography. SNPs of the ADIPOQ gene of the study participants were genotyped using real-time PCR. Multivariate linear regression adjusted for covariates revealed significant association between rs182052 SNP and serum adiponectin concentration (β= –0.11; 95% confidence interval (95%CI): – 0.19, –0.03; p = 0.016). Regression analysis revealed an increase in prevalence of unstable angina (OR (odds ratio) = 2.55; 95%CI 1.4–4.82; p = 0.018) and coronary artery disease (OR = 1.55; 95%CI 1.15– 2.09; p = 0.021) per copy of the rs182052 A allele. Prevalence of type 2 diabetes mellitus was higher in subjects with the rs182052 A allele (OR = 2.29; 95%CI 1.29-4.21; p = 0.024). Regression analysis of rs266729 showed that prevalence of unstable angina was increased (OR = 3.59; 95%CI 1.17–10.01; p = 0.045) in the subjects with the GG genotype and prevalence of coronary artery disease (CAD) was significantly increased (OR = 1.48; 95%CI 1.09–2.03; p = 0.045) per copy of the G allele. Haplotype analysis revealed that the subjects with the GCATT haplotype have lower adiponectin levels (β= – 0.15; p = 0.042) and higher prevalence of unstable angina (OR = 3.597; p = 0.007) compared with reference haplotype carriers. Thus, the results indicate that minor A allele of rs182052 of the ADIPOQ gene is significantly associated with a decrease in serum adiponectin levels, and two SNPs (rs182052 and rs266729) of the ADIPOQ gene are significantly associated with cardiovascular and metabolic diseases.

© 2019 Elsevier B.V. Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellular‑calcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm2, 100 mW/cm2, 500 mW/cm2, 1000 mW/cm2, 1500 mW/cm2, 2000 mW/cm2) irradiated with a “standard” (Gaussian fluence distribution) hand-piece or with a “flat-top” (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.

© 2019 Elsevier GmbH We report a case of severe babesiosis caused by the bovine pathogen Babesia divergens with the development of multisystem failure in a splenic host. Immunosuppression other than splenectomy can also predispose people to B. divergens. There was heavy multiple invasion of up to 14 parasites inside the erythrocyte, which had not been previously observed even in asplenic hosts. The piroplasm 18S rRNA sequence from our patient was identical B. divergens EU lineage with identity 99.5–100%.

© 2019 International Union of Crystallography. During a comprehensive study of a series of 2-(N-arylimino)coumarin-3-carboxamides with the aryl group substituted in the ortho-position by either a halogen atom, a methyl group or a methoxy group, the existence of three groups of isotypic crystal structures has been revealed. The similarity of crystal structures belonging to the same groups was confirmed by the analysis based on the comparison of pairwise interactions energies obtained from quantum chemical calculations. Group I includes unsubstituted, methyl-substituted and polymorphic modification 1 of fluoro-substituted 2-(N-arylimino)coumarin-3-carboxamide. Structures of polymorphic modification 2 of fluoro-substituted derivative, chloro-substituted and polymorphic modification 1 of bromo-substituted 2-(N-arylimino)coumarin-3-carboxamide may represent group II. Group III contains structures of polymorphic modification 2 of bromo-substituted derivative, iodine-and methoxy-substituted 2-(N-arylimino)coumarin-3-carboxamides. Structures of the same type group have extremely close parameters of the unit cell as well as those of molecular and crystal structures. But they are not identical. Polymorphic modifications of fluoro-and bromo-substituted 2-(N-arylimino)coumarin-3-carboxamides belong to different crystal types mainly due to different arrangement of basic structural motifs separated out using quantum chemical calculations.

© Copyright © 2019 Klochkov, Pukhov, Afanasieva, Neganova, Ananiev, Avila-Rodriguez, Tarasov and Aliev. Natural sesquiterpene lactones which contain an exocyclic methylene group in the β-position of the lactone ring react readily with N-nucleophiles. When studying the reaction of the natural epoxyalantolactone with the primary amines we demonstrate the formation of a new heterocyclic system—the hydrogenated benzo[g]furo[4,3,2-cd]indol-3(1H)-one. Spectral data on the characteristics of the synthesized compounds are presented. The data on the reaction mechanisms and its applicability for the preparation are discussed.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. WWP2 is an E3 ubiquitin ligase that differentially regulates the contextual tumour suppressor/progressor TGFβ signalling pathway by alternate isoform expression. WWP2 isoforms select signal transducer Smad2/3 or inhibitor Smad7 substrates for degradation through different compositions of protein-protein interactionWWdomains. The WW4 domain-containing WWP2-C induces Smad7 turnover in vivo and positively regulates the metastatic epithelial-mesenchymal transition programme. This activity and the overexpression of these isoforms in human cancers make them candidates for therapeutic intervention. Here, we use NMR spectroscopy to solve the solution structure of the WWP2 WW4 domain and observe the binding characteristics of Smad7 substrate peptide. We also reveal that WW4 has an enhanced affinity for a Smad7 peptide phosphorylated at serine 206 adjacent to the PPxY motif. Using the same approach, we show that the WW3 domain also binds Smad7 and has significantly enhanced Smad7 binding affinity when expressed in tandem with the WW4 domain. Furthermore, and relevant to these biophysical findings, we present evidence for a novel WWP2 isoform (WWP2C-DHECT) comprising WW3-WW4 tandem domains and a truncated HECT domain that can inhibit TGFβ signalling pathway activity, providing a further layer of complexity and feedback to the WWP2 regulatory apparatus. Collectively, our data reveal a structural platform for Smad substrate selection by WWP2 isoform WW domains that may be significant in the context of WWP2 isoform switching linked to tumorigenesis.

Heart failure is a complex syndrome whose phenotypic presentation and disease progression depends on a complex network of adaptive and maladaptive responses. One of these responses is the endothelial release of NRG (neuregulin)-1-a paracrine growth factor activating ErbB2 (erythroblastic leukemia viral oncogene homolog B2), ErbB3, and ErbB4 receptor tyrosine kinases on various targets cells. NRG-1 features a multitasking profile tuning regenerative, inflammatory, fibrotic, and metabolic processes. Here, we review the activities of NRG-1 on different cell types and organs and their implication for heart failure progression and its comorbidities. Although, in general, effects of NRG-1 in heart failure are compensatory and beneficial, translation into therapies remains unaccomplished both because of the complexity of the underlying pathways and because of the challenges in the development of therapeutics (proteins, peptides, small molecules, and RNA-based therapies) for tyrosine kinase receptors. Here, we give an overview of the complexity to be faced and how it may be tackled.

© 2019 Elsevier B.V. This study demonstrates a hollow structure constructed by Au nanoparticles decorated on the surface of the In2O3 hollow nanospheres. This structure is prepared via calcination of solid organic precursors and in-situ reduction of Au nanoparticles on the metal oxide surface. The In2O3 hollow nanospheres are with the diameter of ˜200 nm and the shell thickness of 30 nm, while the Au nanoparticles on the surface of In2O3 hollow spheres are with the size of ˜10 nm. XPS indicates that the Au modification can increase the deficient oxygen vacancy ratio, and the presence of the positive Au ions (Auδ+) in the composites helps to trap the electrons and further improve the sensing performance. The gas sensing tests indicate that the Au decorated In2O3 hollow nanocomposites show excellent sensitivity (26.3 of 100 ppm) and selectivity toward 1-butylamine at the optimized temperature of 340 °C. The decoration of Au nanoparticles can lower the optimized working temperature and shorten the response/recovery times. The enhanced sensing mechanism can be attributed to electronic and chemical sensitization. The decoration of Au nanoparticles on the In2O3 surface can cause the Schottky barrier at the interface. The existence of positive Au ions can boost the barrier by trapping extra electrons. These results tender the promising hollow structure for sensing organic amine vapor in field-based use.