14 research outputs found

    Characteristic of the snow cover for the Western Siberia territory

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    The warming for the Siberian territory has more rapid growth, than for Northern Hemisphere, in general. The purpose of the work is the description of characteristics of a snow cover for the south-east territory of the Western Siberia, which is great importance for many branches of the economy of Siberia. Date of appearance of snow cover, duration of a steady snow cover, thickness were analyzed in present research. The presented results are: the increase in duration of the presence the snow cover is revealed. The reason is the increase in amount of precipitation during the winter period

    Changing Vectors of International Cooperation of Russian Universities in the New Geopolitical Situation

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    Introduction. With the implementation of state policy aimed at integrating the Russian higher education into the world educational system, universities internationalization has been intensively developing in recent decades. However, the unprecedented sanction pressure of unfriendly countries (starting in 2022) affected universities international activity prompting them to search for new foreign partners. The purpose of the research was to study the vectors of Russian universities’ international activity under transformation in the current geopolitical situation. The analysis of new geography and forms of international cooperation in the educational, scientific, cultural and humanitarian spheres was of specific interest. Materials and Methods. The method of content analysis was employed to study the news on international activity, posted on the websites of leading Russian universities, government authorities and specialized organizations. The results of this analysis were mapped (the mapping method was used). The method of substantive analysis of news reports was used to obtain a characterization of the forms of international cooperation. Statistical data were analyzed in the article by means of quantitative methods. The methods of substantive analysis, systematization and classification of information contained in theoretical sources, normative-legal acts, information and analytical materials were used. Results. A set of sanction restrictions on the internationalization of Russian universities is characterized. Diagrammatic maps of the new geography of their international cooperation are presented. They indicate the growth of international contacts with universities in the CIS countries, Asia, Africa and Latin America against the backdrop of the decreased contacts with Western countries. Discussion and Conclusion. The expansion of international cooperation between Russian universities geography can help minimize risks of sanction pressure, as well as open up new opportunities for the long-term international partnership development and the formation of new world scientific and educational superiority centers. The article can be useful for universities in Russia for forming their international strategy in the new geopolitical conditions

    A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

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    Regulation of the microecological state of the lower parts of the female reproductive tract with vitamins

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    Aim. To study the changes in the microecology of the vagina under the influence of ascorbic acid, α-tocopherol, and retinol acetate.Materials and methods. The number of vaginal lactobacilli and opportunistic bacteria, the concentrations of IL1β, raIL1, INFγ, TGFβ1, lactoferrin and sIgA in vaginal fluids of women with deficiency of ascorbic acid (n = 35) or retinol acetate (n = 35) or α-tocopherol (n = 35) were assessed before and after intravaginal application of these vitamins. The obtained data were compared with those of healthy women without vitamin deficiency (n = 15).Results. An association between deficiency of α-tocopherol, retinol acetate and ascorbic acid with a deficiency of lactoflora, a high frequency of bacterial vaginosis and candidiasis, and proinflammatory changes of the parameters of mucosal immunity has been found. A normalizing effect of all vitamins on the lactoflora of the vagina was identified. The severity of this effect decreased in the following order: α-tocopherol → retinol acetate → ascorbic acid. Retinol acetate caused the increase, while ascorbate and tocopherol caused the reduction in the number of opportunistic microorganisms. The effect of ascorbate was pronounced, but short-term, while the effect of tocopherol was less pronounced, but long-lasting. The use of vitamins affected the condition of mucosal immunity in different directions: ascorbic acid caused an increase in pro-inflammatory changes; on the contrary, α-tocopherol and retinol acetate caused anti-inflammatory changes.Conclusion. Our data on the effects of α-tocopherol, retinol acetate, and ascorbic acid on the microecological state of the vaginal biotope suggest that these vitamins may be considered as regulatory factors for both host cells and microsymbionts

    Chemo-Enzymatic Synthesis and Biological Evaluation of 5,6-Disubstituted Benzimidazole Ribo- and 2 '-Deoxyribonucleosides

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    A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic bases showed good substrate activity for PNP and the ribo- and 2-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-d- ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-d- ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2- deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cytotoxicity. © Georg Thieme Verlag Stuttgart New York.status: publishe

    Multi-Enzymatic Cascades in the Synthesis of Modified Nucleosides: Comparison of the Thermophilic and Mesophilic Pathways

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    A comparative study of the possibilities of using ribokinase → phosphopentomutase → nucleoside phosphorylase cascades in the synthesis of modified nucleosides was carried out. Recombinant phosphopentomutase from Thermus thermophilus HB27 was obtained for the first time: a strain producing a soluble form of the enzyme was created, and a method for its isolation and chromatographic purification was developed. It was shown that cascade syntheses of modified nucleosides can be carried out both by the mesophilic and thermophilic routes from D-pentoses: ribose, 2-deoxyribose, arabinose, xylose, and 2-deoxy-2-fluoroarabinose. The efficiency of 2-chloradenine nucleoside synthesis decreases in the following order: Rib (92), dRib (74), Ara (66), F-Ara (8), and Xyl (2%) in 30 min for mesophilic enzymes. For thermophilic enzymes: Rib (76), dRib (62), Ara (32), F-Ara (<1), and Xyl (2%) in 30 min. Upon incubation of the reaction mixtures for a day, the amounts of 2-chloroadenine riboside (thermophilic cascade), 2-deoxyribosides (both cascades), and arabinoside (mesophilic cascade) decreased roughly by half. The conversion of the base to 2-fluoroarabinosides and xylosides continued to increase in both cases and reached 20-40%. Four nucleosides were quantitatively produced by a cascade of enzymes from D-ribose and D-arabinose. The ribosides of 8-azaguanine (thermophilic cascade) and allopurinol (mesophilic cascade) were synthesized. For the first time, D-arabinosides of 2-chloro-6-methoxypurine and 2-fluoro-6-methoxypurine were synthesized using the mesophilic cascade. Despite the relatively small difference in temperatures when performing the cascade reactions (50 and 80 °C), the rate of product formation in the reactions with Escherichia coli enzymes was significantly higher. E. coli enzymes also provided a higher content of the target products in the reaction mixture. Therefore, they are more appropriate for use in the polyenzymatic synthesis of modified nucleosides

    New Biocides Based on <i>N</i><sup>4</sup>-Alkylcytidines: Effects on Microorganisms and Application for the Protection of Cultural Heritage Objects of Painting

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    The rapid increase in the antibiotic resistance of microorganisms, capable of causing diseases in humans as destroying cultural heritage sites, is a great challenge for modern science. In this regard, it is necessary to develop fundamentally novel and highly active compounds. In this study, a series of N4-alkylcytidines, including 5- and 6-methylcytidine derivatives, with extended alkyl substituents, were obtained in order to develop a new generation of antibacterial and antifungal biocides based on nucleoside derivatives. It has been shown that N4-alkyl 5- or 6-methylcytidines effectively inhibit the growth of molds, isolated from the paintings in the halls of the Ancient Russian Paintings of the State Tretyakov Gallery, Russia, Moscow. The novel compounds showed activity similar to antiseptics commonly used to protect works of art, such as benzalkonium chloride, to which a number of microorganisms have acquired resistance. It was also shown that the activity of N4-alkylcytidines is comparable to that of some antibiotics used in medicine to fight Gram-positive bacteria, including resistant strains of Staphylococcus aureus and Mycobacterium smegmatis. N4-dodecyl-5- and 6-methylcytidines turned out to be the best. This compound seems promising for expanding the palette of antiseptics used in painting, since quite often the destruction of painting materials is caused by joint fungi and bacteria infection

    Enzymatic Transglycosylation Features in Synthesis of 8-Aza-7-Deazapurine Fleximer Nucleosides by Recombinant <i>E. coli</i> PNP: Synthesis and Structure Determination of Minor Products

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    Enzymatic transglycosylation of the fleximer base 4-(4-aminopyridine-3-yl)-1H-pyrazole using recombinant E. coli purine nucleoside phosphorylase (PNP) resulted in the formation of “non-typical” minor products of the reaction. In addition to “typical” N1-pyrazole nucleosides, a 4-imino-pyridinium riboside and a N1-pyridinium-N1-pyrazole bis-ribose derivative were formed. N1-Pyrazole 2′-deoxyribonucleosides and a N1-pyridinium-N1-pyrazole bis-2′-deoxyriboside were formed. But 4-imino-pyridinium deoxyriboside was not formed in the reaction mixture. The role of thermodynamic parameters of key intermediates in the formation of reaction products was elucidated. To determine the mechanism of binding and activation of heterocyclic substrates in the E. coli PNP active site, molecular modeling of the fleximer base and reaction products in the enzyme active site was carried out. As for N1-pyridinium riboside, there are two possible locations for it in the PNP active site. The presence of a relatively large space in the area of amino acid residues Phe159, Val178, and Asp204 allows the ribose residue to fit into that space, and the heterocyclic base can occupy a position that is suitable for subsequent glycosylation. Perhaps it is this “upside down” arrangement that promotes secondary glycosylation and the formation of minor bis-riboside products
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