To involvement the conformation of the adenine nucleotide translocase in opening the Tl+-induced permeability transition pore in Ca2+-loaded rat liver mitochondria

The conformation of adenine nucleotide translocase (ANT) has a profound impact in opening the mitochondrial permeability transition pore (MPTP) in the inner membrane. Fixing the ANT in 'c' conformation by phenylarsine oxide (PAO), tert-butylhydroperoxide (tBHP), and carboxyatractyloside as well as the interaction of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) with mitochondrial thiols markedly attenuated the ability of ADP to inhibit the MPTP opening. We earlier found (Korotkov and Saris, 2011) that calcium load of rat liver mitochondria in medium containing TINO3 and KNO3 stimulated the Tl+-induced MPTP opening in the inner mitochondrial membrane. The MPTP opening as well as followed increase in swelling, a drop in membrane potential (Delta Psi(mito)), and a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration were visibly enhanced in the presence of PAO, tBHP, DIDS, and carboxyatractyloside. However, these effects were markedly inhibited by ADP and membrane-penetrant hydrophobic thiol reagent, N-ethylmaleimide (NEM) which fix the ANT in 'm' conformation. Cyclosporine A additionally potentiated these effects of ADP and NEM. Our data suggest that conformational changes of the ANT may be directly involved in the opening of the Tl+-induced MPTP in the inner membrane of Ca2+-loaded rat liver mitochondria. Using the Tl+-induced MPTP model is discussed in terms finding new transition pore inhibitors and inducers among different chemical and natural compounds. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

MATHEMATICAL MODELING OF DIFFUSION PROCESSES OF MASS TRANSFER OF «FREE CALCIUM HYDROXIDE» DURING CORROSION OF CEMENT CONCRETES

The paper presents a mathematical model of mass transfer in the processes of corrosion of the first type of cement concrete at the level of phenomenological equations for a closed reservoir-liquid system. A step-by-step transition to the recording of the boundary value mass conduction problem in dimensionless coordinates is shown. The solutions of the boundary value mass conduction problem for the region of large and small values of Fourier numbers are obtained

Aspects of Serological Diagnostics of Listeriosis (Literature Review)

The review presents data on the antigenic structure and the current classification of epidemically significant serovariants of Listeria. Description of species-specific properties of serovariants of Listeria, which may be common for two or more species, and common antigens with staphylococci and typhoid and paratyphoid bacteria, are given. It has been shown that only the antigenic scheme of Listeria monocytogenes is of practical interest for medical microbiology. Importance of serotyping in the epidemiological analysis to determine the source of infections and ways of its spreading has been determined. Differences in the designation of serovariants in the diagnosis of listeriosis in medical practice are observed. High level of adaptive properties of Listeria, its ability to reproduce in an abiotic environment, including food, susceptibility of immunodeficient individuals, prevalence of food pathway of infection pose a significant danger of increased sickness rate with listeriosis. Serological diagnostics of Listeria has not been developed in detail, and the existing serological methods are aimed at identifying specific antibodies to listeria. Advantages of the serological method include: quick results and the possibility to study any biological material. Currently available serological methods have a number of disadvantages: low reliability of results and low specificity of the study. The most promising method for identification of a serological group of cultures, according to the world classification, is the multiplex PCR method, based on the correlation between the serogroup of an isolate and the presence of specific open reading frames in its genome

Arginase Inhibitor in the Pharmacological Correction of Endothelial Dysfunction

This paper is about a way of correction of endothelial dysfunction with the inhibitor of arginase: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction

Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile-onset cardiomyopathy

Recessively inherited variants in AARS2 (NM_020745.2) encoding mitochondrial alanyl-tRNA synthetase (mt-AlaRS) were first described in patients presenting with fatal infantile cardiomyopathy and multiple oxidative phosphorylation defects. To date, all described patients with AARS2-related fatal infantile cardiomyopathy are united by either a homozygous or compound heterozygous c.1774C>T (p.Arg592Trp) missense founder mutation that is absent in patients with other AARS2-related phenotypes. We describe the clinical, biochemical and molecular investigations of two unrelated boys presenting with fatal infantile cardiomyopathy, lactic acidosis and respiratory failure. Oxidative histochemistry showed cytochrome c oxidase-deficient fibres in skeletal and cardiac muscle. Biochemical studies showed markedly decreased activities of mitochondrial respiratory chain complexes I and IV with a mild decrease of complex III activity in skeletal and cardiac muscle. Using next-generation sequencing, we identified a c.1738C>T (p.Arg580Trp) AARS2 variant shared by both patients that was in trans with a loss-of-function heterozygous AARS2 variant; a c.1008dupT (p.Asp337*) nonsense variant or an intragenic deletion encompassing AARS2 exons 5-7. Interestingly, our patients did not harbour the p.Arg592Trp AARS2 founder mutation. In silico modelling of the p.Arg580Trp substitution suggested a deleterious impact on protein stability and folding. We confirmed markedly decreased mt-AlaRS protein levels in patient fibroblasts, skeletal and cardiac muscle, although mitochondrial protein synthesis defects were confined to skeletal and cardiac muscle. In vitro data showed that the p.Arg580Trp variant had a minimal effect on activation, aminoacylation or misaminoacylation activities relative to wild-type mt-AlaRS, demonstrating that instability of mt-AlaRS is the biological mechanism underlying the fatal cardiomyopathy phenotype in our patients.Peer reviewe

Detection of tick-borne pathogens in wild birds and their ticks in Western Siberia and high level of their mismatch

Abstract: The Tomsk region located in the south of Western Siberia is one of the most high-risk areas for tick-borne diseases due to elevated incidence of tick-borne encephalitis and Lyme disease in humans. Wild birds may be considered as one of the reservoirs for tick-borne pathogens and hosts for infected ticks. A high mobility of wild birds leads to unpredictable possibilities for the dissemination of tick-borne pathogens into new geographical regions. The primary goal of this study was to evaluate the prevalence of tick-borne pathogens in wild birds and ticks that feed on them as well as to determine the role of different species of birds in maintaining the tickborne infectious foci. We analysed the samples of 443 wild birds (60 species) and 378 ticks belonging to the genus Ixodes Latraille, 1795 collected from the wild birds, for detecting occurrence of eight tick-borne pathogens, the namely tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and species of Borrelia, Rickettsia, Ehrlichia, Anaplasma, Bartonella and Babesia Starcovici, 1893, using RT-PCR/or PCR and enzyme immunoassay. One or more tick-borne infection markers were detected in 43 species of birds. All markers were detected in samples collected from fieldfare Turdus pilaris Linnaeus, Blyth’s reed warbler Acrocephalus dumetorum Blyth, common redstart Phoenicurus phoenicurus (Linnaeus), and common chaffinch Fringilla coelebs Linnaeus. Although all pathogens have been identified in birds and ticks, we found that in the majority of cases (75.5%), there were mismatches of pathogens in birds and ticks collected from them. Wild birds and their ticks may play an extremely important role in the dissemination of tick-borne pathogens into different geographical regions

Determining the Smart University Infrastructure Development Level Based on Data Models

The paper presents applied research in the framework of solving determining the smart university infrastructure development level problem. Today, all digital transformation and transition to the digital economy concept and smart society development issues are very important. Education is the intellectual core of the digital transformation, the knowledge base, and the training center for the digital economy. Therefore, more attention should be paid to the creation and development of the smart university infrastructure. The purpose of the study is to develop criteria and models for determining the level of smart university infrastructure development. To describe the management of infrastructure level assessment, we propose to use adapted mathematical methods, structural analysis, and mathematical statistics methods. The study examines trends in the development of smart education, highlights the main elements of the smart university infrastructure (technological and organizational), and examines approaches to determining the level of its development based on data models. Taking into account the diversity and volume of quantitative and qualitative indicators of the smart university infrastructure, we propose to measure the level of the infrastructure using data models and Educational Data Mining tools. Universities can use got models when forming a development strategy or selecting funding directions, to reduce the time of digital transformation and transition to the optimal state of a smart university, to prepare for accreditation or to align the smart infrastructure of individual departments

ДЕЯКІ РЕАКЦІЇ N-{3-[(АРИЛ-1-СУЛФОНІЛ)ІМІНО]-6-ОКСОЦИКЛОГЕКСА-1,4-ДІЄН-1-ІЛ}БЕНЗАМІДІВ

N-{3-[(Aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamides have been synthesized by the reaction of the corresponding N-(4-oxocyclohexa-2,5-diene-1-ylidene)arylsulfonamides with N-chloramides with a ratio of reagents 1:2 in a solution of propan-2-one in the presence of triethylamine. The products of addition of hydrogen halides with the entry of halogen atoms in position 4 or 5 of the quinoid ring have been obtained as a result of hydrochlorination and hydrobromination of N-{3-[(aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-diene-1-yl}benzamides. The possibility of hydrohalogenation and thiocyanation of these benzamides is determined by a steric factor. The presence of bulk substituents in the quinoid ring does not allow the introduction of a halogen atom in the 2 position of the quinoid ring. The product of aromatization of the quinoid cycle, N-{2-hydroxy-3,4-dimethyl-5-[(4-methylbenzene-1-sulfonyl)amino]phenyl}-4-methylbenzamide, was only obtained as a result of the action of hydrogen halides on 4-methyl-N-{4,5-dimethyl-3-[(4-methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamide. The thiocyanate ion addition product was obtained only for 4-chloro-N-{4-methyl-3-[(4-methylbenzene-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamide, which has a free ortho-position relative to the carbonyl carbon of the quinoid ring. The activities Insulysin inhibitor, CTGF expression inhibitor, Glutamyl endopeptidase II inhibitor, Transcription factor STAT3 inhibitor are possible for the products of hydrohalogenation and thiocyanation of N-{3-[(aryl-1-sulfonyl)imino]-6-oxocyclohexa-1,4-dienе-1-yl}benzamides.N-{3-[(Арил-1-сульфонил)имино]-6-оксоциклогекса-1,4-диен-1-ил}бензамиды синтезированы по реакции соответствующих N-(4-оксоциклогекса-2,5-диен-1-илиден)арилсульфонамидов с N-хлорамидами с соотношением реагентов 1:2 в растворе пропан-2-она в присутствии триэтиламина. В результате гидрохлорирования и гидробромирования N-{3-[(арил-1-сулфонил)имино]-6-оксоциклогекса-1,4-диен-1-ил}бензамидов получены продукты присоединения галогеноводородов с вхождением атомов галогена в положение 4 или 5 хиноидного ядра. Возможность гидрогалогенирования и роданирования данных бензамидов определяется стерическим фактором. Наличие объемных заместителей в хиноидном ядре не позволяет ввести атом галогена во 2 положение хиноидного ядра – в результате действия галогеноводородов на 4-метил-N-{4,5-диметил-3-[(4-метилбензен-1-сульфонил)имино]-6-оксоциклогекса-1,4-диен-1-ил}бенза-мид получен только продукт ароматизации хиноидного цикла – N-{2-гидрокси-3,4-диметил-5-[(4-метилбензен-1-сульфонил)амино]фенил}-4-метилбензамид. Продукт присоединения тиоцианат-иона получен только для 4-хлор-N-{4-метил-3-[(4-метилбензен-1-сульфонил)имино]-6-оксоциклогекса-1,4-диен-1-ил}бензамида, который имеет свободное орто-положение по отношению к карбонильному атому углерода хиноидного ядра. Для продуктов гидрогалогенирования и роданирования N-{3-[(арилсулфонил)имино]-6-оксоциклогекса-1,4-диен-1-ил}бензамидов возможно проявление активностей Insulysin inhibitor, CTGF expression inhibitor, Glutamyl endopeptidase II inhibitor, Transcription factor STAT3 inhibitor.N-{3-[(Арил-1-сульфоніл)іміно]-6-оксоциклогекса-1,4-дієн-1-іл}бензаміди синтезовано за реакцією відповідних N-(4-оксоциклогекса-2,5-дієн-1-іліден)арилсульфонамідів з N-хлорамідами зі співвідношенням реагентів 1:2 у розчині пропан-2-ону за присутності триетиламіну. В результаті гідрохлорування і гідробромування N-{3-[(арил-1-сулфоніл)іміно]-6-оксоциклогекса-1,4-дієн-1-іл}бензамідів отримано продукти 1,4- та 6,3-приєднання галогеноводнів зі входженням атомів галогену у положення 3 або 4 хіноїдного ядра. Можливість перебігу гідрогалогенування і роданування даних бензамідів визначається стеричним фактором. Наявність об’ємних замісників в хіноїдному ядрі не дозволяє ввести атом галогену у 6 положення хіноїдного ядра – в результаті дії галогеноводнів на 4-метил-N-{4,5-диметил-3-[(4-метилбензен-1-сульфоніл)іміно]-6-оксоциклогекса-1,4-дієн-1-іл}бензамід отримано тільки продукт ароматизації хіноїдного циклу – N-{2-гідрокси-3,4-диметил-5-[(4-метилбензен-1-сульфоніл)аміно]феніл}-4-метилбензамід. Продукт приєднання тіоціанат-іону отримано тільки для 4-хлор-N-{4-метил-3-[(4-метилбензен-1-сульфоніл)іміно]-6-оксоциклогекса-1,4-дієн-1-іл}бензаміду, який має вільне орто-положення по відношенню до карбонільного атому Карбону хіноїдного ядра. Для продуктів гідрогалогенування і роданування N-{3-[(арилсулфоніл)іміно]-6-оксоциклогекса-1,4-дієн-1-іл}бензамідів можливий прояв активностей Insulysin inhibitor, CTGF expression inhibitor, Glutamyl endopeptidase II inhibitor, Transcription factor STAT3 inhibitor

Diversity of the vegetation cover of the zone of potential influence of the Nizhneboguchanskaya HPP (Lower Angara region)

Active economic development of the Lower Angara zone requires the creation of a scientific basis for long-term monitoring of the state of natural ecosystems. The paper gives an assessment of the diversity of vegetation cover in the zone of potential influence of the Nizhneboguchanskaya HPP. An analysis of its typological structure on a landscape-ecological basis is given. The results of the DCA ordination and the interpretation of the leading axes of variation demonstrated the presence of four distinct groups of forest types that form ecological series according to the leading factors - the richness and hydrothermal regimes of soils. The dendrogram of forest types in the study area reflects the floristic integrity of the identified groups of forest types and the floristic relationships between them

Mechanism of Heterogeneous Alkaline Deacetylation of Chitin: A Review

This review provides an analysis of experimental results on the study of alkaline heterogeneous deacetylation of chitin obtained by the authors and also published in the literature. A detailed analysis of the reaction kinetics was carried out considering the influence of numerous factors: reaction reversibility, crystallinity and porosity of chitin, changes in chitin morphology during washing, alkali concentration, diffusion of hydroxide ions, and hydration of reacting particles. A mechanism for the chitin deacetylation reaction is proposed, taking into account its kinetic features in which the decisive role is assigned to the effects of hydration. It has been shown that the rate of chitin deacetylation increases with a decrease in the degree of hydration of hydroxide ions in a concentrated alkali solution. When the alkali concentration is less than the limit of complete hydration, the reaction practically does not occur. Hypotheses have been put forward to explain the decrease in the rate of the reaction in the second flat portion of the kinetic curve. The first hypothesis is the formation of “free” water, leading to the hydration of chitin molecules and a decrease in the reaction rate. The second hypothesis postulates the formation of a stable amide anion of chitosan, which prevents the nucleophilic attack of the chitin macromolecule by hydroxide ions