Forms of chemical elements migration in underground waters of the river Katun basin in its average current

The characteristic of chemical elements condition in underground waters of the river katun basin (mountainous altai) is shown; the main forms of migration of chemical macro- and microelements are allocated: na+, mg2+, ca2+, mn2+, fe2+, pb2+, сu2+, zn2+. statistical calculations, which purpose was confirmation of results of complex-formation process modeling, are carried ou

Trends of the major porin gene (ompF) evolution

OmpF is one of the major general porins of Enterobacteriaceae that belongs to the first line of bacterial defense and interactions with the biotic as well as abiotic environments. Porins are surface exposed and their structures strongly reflect the history of multiple interactions with the environmental challenges. Unfortunately, little is known on diversity of porin genes of Enterobacteriaceae and the genus Yersinia especially. We analyzed the sequences of the ompF gene from 73 Yersinia strains covering 14 known species. The phylogenetic analysis placed most of the Yersinia strains in the same line assigned by 16S rDNA-gyrB tree. Very high congruence in the tree topologies was observed for Y. enterocolitica, Y. kristensenii, Y. ruckeri, indicating that intragenic recombination in these species had no effect on the ompF gene. A significant level of intra- and interspecies recombination was found for Y. aleksiciae, Y. intermedia and Y. mollaretii. Our analysis shows that the ompF gene of Yersinia has evolved with nonrandom mutational rate under purifying selection. However, several surface loops in the OmpF porin contain positively selected sites, which very likely reflect adaptive diversification Yersinia to their ecological niches. To our knowledge, this is a first investigation of diversity of the porin gene covering the whole genus of the family Enterobacteriaceae. This study demonstrates that recombination and positive selection both contribute to evolution of ompF, but the relative contribution of these evolutionary forces are different among Yersinia species

The effects of SN Ps in the regions of positioning RNA polymerase II on the TBP/promoter affinity in the genes of human circadian clock

Genetic variability in the genes of circadian clock is manifested as the phenotypic variability of physiological functions and behavior as well as disorders of the function of not only the clock but also other systems, leading to the development of a pathologies. We analyzed the influence of SNPs localized in the [–70, –20] region from the transcription start site of the gene on TBP / promoter affinity in two groups of genes that are components of the system of human circadian clock. The first group comprises the genes of the circadian oscillator core (11 genes); the second, the genes of the nearest regulatory environment of the circadian oscillator (21 genes). A group for comparison included genes with another function (31 genes). The SNP_TATA_Comparator web service was used for prediction of the effect of SNPs in the regions of positioning of RNA polymerase II on the dissociation constant for TBP / promoter. It was shown that the number of SNP markers reducing the TBP / promoter affinity in the first group of genes significantly lower than the number of SNP markers increasing affinity (α < 10–3). The reverse was true of the comparison group: SNP markers reduced TBP / promoter affinity to a significantly greater extent than the SNP marker increased affinity (α < 10–6). This property may be a characteristic feature of genes  of the circadian oscillator. These predictions are important for identification of candidate SNP markers of various pathologies associated with the dysfunction of circadian clock genes for further testing them in experimental and clinical studies, as well as for verification of mathematical models of the circadian oscillator

Biomedical and candidate SN P markers of chronopathologies can significantly change affinity of ТАТА -binding protein for human gene promoters

Computational analysis of millions of unannotated SNPs from the 1000 Genomes Project may speed up the search for biomedical SNP markers. We combined the analysis of SNPs in the binding sites of ТАТА - binding protein (ТВР) using a previously described W eb service (http://beehive.bionet.nsc.ru/cgi-bin/mgs/ tatascan/start.pl) with a keyword search for biochemicalmarkers of chronopathologies, which correspond to clinical manifestations of these SNPs. In the [–70; –20] region of promoters of 14 human genes (location of proven binding sites of ТВР), we found 32 known and candidate SNP markers of circadian- rhythm disturbances, including rs17231520 and rs569033466 (both: risk of chronopathologies in liver); rs35036378 (behavioral chronoaberrations); rs549858786 (rheumatoid arthritis with a chronoaberration of IL1B expression); rs563207167, rs11557611, and rs5505 (all three: chronopathologies of the tumor – host balance, blood pressure, and the reproductive system); rs1143627 (bipolar disorder with circadian dependence of diagnosis and treatment); rs16887226 and rs544850971 (both: lowered resistance to endotoxins because of the imbalance between the circadian and immune systems); rs367732974 and rs549591993 (both: circadian dependence of heart attacks); rs563763767 (circadian dependence of myocardial infarction); rs2276109 and rs572527200 (both: circadian dependence of asthma attacks); rs34223104, rs563558831, and rs10168 (circadian optima of treatment with methotrexate and cyclophosphamide); and rs397509430, rs33980857,rs34598529, rs33931746, rs33981098, rs34500389, rs63750953, rs281864525, rs35518301, and rs34166473 (all: neurosensory hearing loss and restless legs syndrome). For these SNPs, we evaluated α (significance) of changes in the affinity of ТВР for promoters, where increased affinity corresponds to overexpression of the genes, and decreased affinity to deficient expression (Z-test). Verification of these 32 SNP markers according to clinical standards and protocols may advance the field of predictive preventive personalized medicine

The astrophysics of nanohertz gravitational waves

Pulsar timing array (PTA) collaborations in North America, Australia, and Europe, have been exploiting the exquisite timing precision of millisecond pulsars over decades of observations to search for correlated timing deviations induced by gravitational waves (GWs). PTAs are sensitive to the frequency band ranging just below 1 nanohertz to a few tens of microhertz. The discovery space of this band is potentially rich with populations of inspiraling supermassive black hole binaries, decaying cosmic string networks, relic post-inflation GWs, and even non-GW imprints of axionic dark matter. This article aims to provide an understanding of the exciting open science questions in cosmology, galaxy evolution, and fundamental physics that will be addressed by the detection and study of GWs through PTAs. The focus of the article is on providing an understanding of the mechanisms by which PTAs can address specific questions in these fields, and to outline some of the subtleties and difficulties in each case. The material included is weighted most heavily toward the questions which we expect will be answered in the near-term with PTAs; however, we have made efforts to include most currently anticipated applications of nanohertz GWs

AN EXPERIMENTAL STUDY OF THE EFFECT OF RARE POLYMORPHISMS OF HUMAN HBB, HBD AND F9 PROMOTER TATA BOXES ON THE KINETICS OF INTERACTION WITH THE TATA-BINDING PROTEIN

Human genes HBB, HBD and F9 belong to the hematopoiesis system. The deficiency or excess of these genes’ products is the cause of hereditary thalassemias of various severity and haemophilia B Leyden. Previously, it was shown that a number of annotated single-nucleotide polymorphisms of TATA boxes of these genes associated with the occurrence of ß- and δ-thalassemia affect the interaction with the TATAbinding protein, the interaction changing proportionally with the change in the number of gene products. In the present work, we investigate the effect of rare not annotated single-nucleotide polymorphisms (SNPs) of TATA boxes of these genes with an unknown manifestation on the TATA-binding protein interaction. To study the kinetic characteristics of TBP/TATA complex formation in vitro, doublestranded oligodeoxynucleotides identical to the TATA-containing portions of the promoters of the HBB, HBD and F9 genes (“normal” and minor alleles) and recombinant human TBP were used. It was shown that the TATA-box SNP of –25A > C (rs281864525) and the deletion of the –25AA (rs63750953) TATA-box of the β-globin gene have the same effect on the TBP/TATA affinity, which decreases 3-folds in both cases. However, the effect of these substitutions on the rate of the TBP/TATA complex formation is significantly different: SNP –25A > C decreases the rate 5-fold, and the deletion decreases the rate more than 7-fold. The influence of substitutions on the strength of the TBP/TATA complexes has a different effect. If in the case of SNP –25A > C the strength of the complexes increases 1.8-fold, then in the case of the –25AA deletion, the strength of the complexes increases 2.4-fold, even though the affinity of the TATAbinding protein to the TATA box decreases. A comparison of experimental values of affinity (KD) of the TBP/T complexes of “normal” and minor alleles with the predicted has shown that data correlate well with each other. The coefficient of linear correlation r = 0.94 (α < 0.0001). A comprehensive approach to the study of rare polymorphisms may lead to the identification of the most sensitive markers of orphan diseases, which will contribute to the development of reliable and rapid methods for their diagnosis and treatment

Prediction and verification of the influence of the rs367781716 SN P on the interaction of ТАТА -binding protein with the promoter of the human АВСА9 gene

The high-throughput sequencing project “1 000 Genomes” made it possible to catalog and utilize genetic loci and single nucleotide polymorphisms (SNPs) in medicine. Analysis of SNP markers (significantly frequent differences of individual genomes of patients from the reference human genome) allows physicians to optimize treatment. On the other hand, tens of millions of unannotated SNPs correspond to a gigantic number of false positive (false negative) candidate SNP markers that are selected by computer methods for comparison of their frequency in patients with that in healthy people. This approach contributes to undervaluation of clinically relevant SNPs and to unnecessary computational expenses (on verification of neutral SNPs). Preclinical empirical verification of possible candidate SNP markers may eliminate neutral SNPs from the dataset. In the present study, we found, using the SNP_TATA_Comparator web service, the unannotated SNP rs367781716: the substitution of ancestral T (health) with minor C at position –37 before the transcription initiation site of the АВСА9 gene. This SNP significantly reduces affinity of TATAbinding protein (TBP) for this gene’s promoter and corresponds to a deficiency (low protein level) of the АВСА9 gene product (the transporter ATP-binding cassette A9) in patients with the –37C allele. For preclinical empirical verification of rs367781716, we used an electrophoretic mobility shift assay (EMSA) to measure the rates of formation (ka) and decay (kd) of the complexes of TBP with an oligonucleotide matching either allele –37C or –37T of the АВСА9 gene. We found that the rate of formation (ka) of the TBP/TATA complex for the minor allele is 2.4-fold lower than that for the ancestral allele. We calculated the empirical value of the change in the equilibrium constant of dissociation (KD = kd /ka), which characterizes binding affinity of TBP for a promoter containing the ТАТА box. This empirical value matched the value predicted by SNP_ТАТА _Comparator within the margin of error of the measurements and calculations. We also determined the half-life and Gibbs free energy of the complex of TBP with the АВСА9 promoter. Possible phenotypic manifestations of the candidate SNP marker rs367781716 are discussed

МИОЦЕНОВЫЙ И ДЕВОНСКИЙ МАГМАТИЗМ В СОЧЛЕНЕНИИ ТУВИНО-МОНГОЛЬСКОГО МАССИВА И СИБИРСКОГО КРАТОНА: ОБЩИЙ КОМПОНЕНТ МАНТИЙНЫХ ИСТОЧНИКОВ И ЕГО ПРОИСХОЖДЕНИЕ

Devonian dikes of the Urik-Belaya and Shagayte-Gol-Urik zones and Miocene lavas of the Urik volcanic field are spatially associated with each other at the structural junction between the Neoproterozoic Tuva-Mongolian massif and Siberian craton. The former dike belt is represented by basalts and basaltic andesites of tholeiitic series and the latter one by trachybasalts, trachyandesitic basalts of moderately alkaline series and trachybasalts, phonotephrites of highly alkaline one. The Urik volcanic field is composed of trachybasalts and trachyandesitic basalts of moderately alkaline series. A partial similarity between magmatic series of different age is found in terms of major oxides, trace elements, and Sr, Pb isotopes. The common component corrected for age was defined through its converging mixing trends with those of the lithospheric mantle and crust. The component identification was a basis for deciphering the nature of isotopic and geochemical heterogeneity of evolved magmatic sources. It was inferred that the common component characterizes either a modified (depleted) reservoir of the lower mantle or, more likely, a local region of the convecting asthenospheric mantle that underlies the Tuva-Mongolian massif. The latter interpretation assumes the formation of a locally convecting asthenosphere in the middle Neoproterozoic, along with the development of the Oka zone at the massif, and puts constrains on later sufficient processing of the asthenosphere due to rising plumes or subducting slabs.В структурном сочленении неопротерозойского Тувино-Монгольского массива с Сибирским кратоном пространственно совмещены между собой девонские дайки Урик-Бельского и Шагайтэ-Гол-Урикского поясов и миоценовые лавы Урикского вулканического поля. Первый дайковый пояс представлен базальтами-андезибазальтами толеитовой серии, второй – трахибазальтами-трахиандезибазальтами умереннощелочной серии с локальным распространением трахибазальтов-фонотефритов серии повышенной щелочности. Урикское вулканическое поле образуют трахибазальты-трахиандезибазальты умереннощелочной серии. Выявлено частичное сходство концентраций петрогенных оксидов, микроэлементов и изотопных отношений стронция и свинца разновозрастных магматических серий. С поправкой на возраст определен общий компонент магматических расплавов по сходящимся трендам его смешения с компонентами мантийной части литосферы и коры. Идентификация компонента послужила основой для расшифровки характера изотопно-геохимической гетерогенности разновозрастных магматических источников. Сделан вывод о том, что общий компонент характеризует либо модифицированный (обедненный) нижнемантийный резервуар, либо, что более вероятно, локальную область конвектирующей астеносферной мантии, подстилающей Тувино-Монгольский массив. В последней интерпретации допускается образование локального конвектирующего объема астеносферы в середине неопротерозоя, одновременно с заложением и развитием Окинской зоны массива, и накладываются ограничения на последующие существенные преобразования астеносферы под влиянием поднятия плюмового или погружения слэбового материала

Сandidate SNP-markers of rheumatoid arthritis that can significantly alter the affinity of the TATA-binding protein for human gene promoters

Rheumatoid polyarthritis (RA) is an autoimmune disease with autoantibodies, including antibodies to citrullant antigens and proinflammatory cytokines, such as TNF-α and IL-6, which are involved in the induction of chronic synovitis, bone erosion, followed by deformity. Immunopathogenesis is based on the mechanisms of the breakdown of immune tolerance to its own antigens, which is characterized by an increase in the activity of T-effector cells, causing RA symptomatology. At the same time, against the background of such increased activity of effector lymphocytes, a decrease in the activity of a number of regulatory cells, including regulatory T-cells (Treg) and myeloid suppressor cells, is recorded. There is reason to say that it is the change in the activity of suppressor cells that is the leading element in RA pathogenesis. That is why only periods of weakening (remission) of RA are spoken of. According to the more powerful female immune system compared to the male one, the risk of developing RA in women is thrice as high, this risk decreases during breastfeeding and grows during pregnancy as well as after menopause in proportion to the level of sex hormones. It is believed that 50 % of the risk of developing RA depends on the conditions and lifestyle, while the remaining 50 % is dependent on genetic predisposition. That is why, RA fits the main idea of postgenomic predictive-preventive personalized medicine that is to give a chance to those who would like to reduce his/her risk of diseases by bringing his/her conditions and lifestyle in line with the data on his/her genome sequenced. This is very important, since doctors consider RA as one of the most frequent causes of disability. Using the Web service SNP_TATA_Z-tester (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan_fox/start.pl), 227 variants of single nucleotide polymorphism (SNP) of the human gene promoters were studied. As a result, 43 candidate SNP markers for RA that can alter the affinity of the TATA-binding protein (TBP) for the promoters of these genes were predicted

AN INTEGRATED INFORMATION SYSTEM ON BIORESOURCE COLLECTIONS OF THE FASO OF RUSSIA

Biological collections play a huge role in studying biological diversity as systematic storages of biological materials in all combinations and forms. Collection materials have generally been formed over hundreds of years and may describe a vast number of samples counted by billions. Great efforts are made to preserve these materials, as well as to obtain more and more samples. The Russian Federation occupies a huge land area, has a long coastline and huge natural resources, a variety of natural and ecological zones. In this regard, its territory is unique from the viewpoint of biodiversity and development of biological collections. Currently, a large number of collections are being developed in Russia, but there are a number of problems associated, first of all, with the lack of an integrated information resource on bioresource collections (BRC). In order to support the development of scientific infrastructure, the Federal Agency for Scientific Organizations (FASO of Russia) has been working on the development of unified approaches to the use of existing bioresource collections and the establishment of the integrated information system. The paper presents an information portal designed to provide uniform methods of work for all BRC organizations of the FASO of Russia: input, storage, updating and differentiated access to specific information about storage units and their characteristics. The information system “Bioresource Collections of Scientific Organizations” (IS BRC) has been developed as a Web­portal (www.biores.cytogen.ru) integrating databases on bioresource collections of the FASO of Russia and graphical user interface. Access control to the databases integrated into the IS BRC is performed through authorized program access for viewing records, their creation and editing on the basis of REST technology. The graphical user interface (GUI) provides the following features in accordance with the access rights: authorized access to the BRC database; viewing BRC database records; editing BRC database records; creating and deleting BRC database records; statistical data analysis in the BRC database; generation of summary reports on the BRC database; export of records content in PDF/RTF/JSON format. The graphical user interface was implemented using the DRUPAL 7.0 toolkit. Architecturally, the portal is concerned as a central node with a series of modules communicating through the unified interfaces. In this way, we solve the problem of connecting new data sources (collection databases) implemented in different DBMS. Given the fact that currently many organizations support access to the catalogues of their collections independently, the portal also provides external links to these Web resources. At the same time, some information on collections is stored within the BRC databases of the FASO of Russia’s portal in unified formats. The portal contains the following functional sections: the home page containing general information on bioresource collections, the catalog of collections, individual pages for each particular collection with a short description (information about curators, statistical information about the number of storage units in the collection and the number of publications, as well as a link to the catalog of storage units of this BRC). Currently the portal contains more than 13 thousand entities of 65 bioresource collections organizations of the FASO of Russia. It is still being extended