GeneNet in 2005

The GeneNet system is designed for collection and analysis of the data on gene and metabolic networks, signal transduction pathways and kinetic characteristics of elementary processes. In the past 2 years, the GeneNet structure was considerably improved: (i) the current version of the database is now implemented using ORACLE9i; (ii) the capacities to describe the structure of the protein complexes and the interactions between the units are increased; (iii) two tables with kinetic constants and more detailed descriptions of certain reactions were added; and (iv) a module for kinetic modeling was supplemented. The current SRS release of the GeneNet database contains 37 graphical maps of gene networks, as well as descriptions of 1766 proteins, 1006 genes, 241 small molecules and 3254 relationships between gene network units, and 552 kinetic constants. Information distributed between 16 interlinked tables was obtained by annotating 1980 journal publications. SRS release of the GeneNet database, the graphical viewer and the modeling section are available at http://wwwmgs.bionet.nsc.ru/mgs/gnw/genenet/

Diagnostics of Microcirculatory Disorders in Children with Infectious Pathology

Laser Doppler flowmetry method (LDF) was used to examine children (43 patients with enteroviral infection, 34 patients with Astrakhan rickettsial fever, and 40 healthy controls). In addition, in view of LDF survey data, carried out was thermal assay and amplitude-frequency analysis of peripheral microcirculation predictors. Detected were incipient changes in microvasculature relative to microangiopathy

National increment of the concept of sustainable development: experience of the EEU states

One of these strategies is called the concept of sustainable development. Currently, there are several variants for this concept. The version of the concept formulated in United Nations documents is the most prevailing. A feature of the documents adopted in the EEU member states on sustainable growth is their programmatic nature. The implementation of the provisions enshrined requires the adoption of separate regulatory legal acts. This also holds true for organ

Models of the organization of the judicial system: the experience of Russia and foreign countries

This article provides an overview of the organization of the judiciary in various countries. Firstly, attention is drawn to the legislative framework on the basis of which the system of courts in a particular state is built. Secondly, the conclusion is drawn that there are three models of the organization of the judiciary: decen-tralized; moderately centralized; strongly centralized bathroom. Examples of states in which distinguished models of the organization of the judiciary operate are given. Particular attention is paid to the place of the Russian model in the classification of judicial systems according to the degree of centralization of the judiciar

Candidate SNP markers of social dominance, which may affect the affinity of the TATAbinding protein for human gene promoters

The following heuristic hypothesis has been proposed: if an excess of a protein in several animal organs was experimentally identified as physiological marker of increased aggressiveness and if a polymorphism (SNP) can cause superexpression of the human gene homologous of the animal gene encoding this protein, then this polymorphism can be a candidate SNP marker of social dominance, whereas a deficient expression corresponds to subordinate and vice versa. Within this hypothesis, we analyzed 21 human genes –ADORA2A, BDNF, CC2D1A, CC2D1B, ESR2, FEV, FOS, GH1, GLTSCR2, GRIN1, HTR1B, HTR1A, HTR2A, HTR2C, LGI4, LEP, MAOA, SLC17A7, SLC6A3, SNCA, TH – which represent the functions of proteins known as physiological markers of aggressive behavior in animals: hormones and their receptors, biosynthetic enzymes and receptors of neurotransmitters, transcription and neurotrophic factors. These proteins may play an important role in determining hierarchical relationships in social animals. Using our previously developed Web-service SNP_TATA_Comparator (http://beehive.bionet.nsc.ru/cgi-bin/mgs/tatascan/start.pl), we analyzed 381 SNPs within the region of [–70; –20] relative to the start protein-coding transcripts, which is the region of the all known TATA-binding protein (TBP) binding sites. We took them from the database dbSNP, v.147 As a result, we found 45 and 47 candidate SNP markers of dominance and submission, respectively (e. g., rs373600960 and rs747572588). Within the framework of the proposed heuristic hypotheses and database dbSNP v.147, we found statistically significant (α < 10-5) evidence of the effects of natural selection against the deficient expression of genes, which can affect the predisposition to dominate, as well as in favor of both subordination and domination behavior as a norm of reaction of aggressiveness (difference not significant: α > 0.35). The proposed hypothesis, the candidate SNP markers predicted and the observed regularities of effects of natural selection for the human genome are discussed in comparison with published data: whether they can have any relation to social dominance in human. It was concluded that these results require experimental verification

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

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

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

Candidate SNP-markers altering TBP binding affinity for promoters of the Y-linked genes CDY2A, SHOX, and ZFY are lowering many indexes of reproductive potential in men

Reproductive potential is the most important conditional indicator reflecting the ability of individuals in a population to reproduce, survive and develop under optimal environmental conditions. As for humans, the concept of reproductive potential can include the level of the individual’s mental and physical state, which allows them to reproduce healthy offspring when they reach social and physical maturity. Female reproductive potential has been investigated in great detail, whereas the male reproductive potential (MRP) has not received the equal amount of attention as yet. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of MRP. With our development named Web-service SNP_TATA_Z-tester, we examined in silico all 35 unannotated SNPs within 70-bp proximal promoters of the three Y-linked genes, CDY2A, SHOX and ZFY, which represent all types of human Y-chromosome genes, namely: unique, pseudo-autosomal, and human X-chromosome gene paralogs, respectively. As a result, we found 11 candidate SNP markers for MRP, which can significantly alter the TATA-binding protein (TBP) binding affinity for promoters of these genes. First of all, we selectively verified in vitro the values of the TBP-promoter affinity under this study, Pearson’s linear correlation between predicted and measured values of which were r = 0.94 (significance p < 0.005). Next, as a discussion, using keyword search tools of the PubMed database, we found clinically proven physiological markers of human pathologies, which correspond to a change in the expression of the genes carrying the candidate SNP markers predicted here. These were markers for spermatogenesis disorders (ZFY: rs1388535808 and rs996955491), for male maturation arrest (CDY2A: rs200670724) as well as for disproportionate short stature at Madelung deformity (e. g., SHOX: rs1452787381) and even for embryogenesis disorders (e. g., SHOX: rs28378830). This indicates a wide range of MRI indicators, alterations in which should be expected in the case of SNPs in the promoters of the human Y-chromosome genes and which can go far beyond changes in male fertility