N A Kolchanov

Novosibirsk State University, Novo-Nikolaevsk, Novosibirsk, Russia

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Publications (302)342.39 Total impact

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    ABSTRACT: Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that their deposition on the total surface of the nasal cavity is higher in the mole vole than in a terrestrial rodent Mus musculus (mouse), but lower on the olfactory epithelium. In agreement with simulation results, we found a reduced accumulation of manganese in olfactory bulbs of mole voles in comparison with mice after the inhalation of nano-sized MnCl2 aerosols. We ruled out the possibility that this reduction is owing to a lower transportation from epithelium to brain in the mole vole as intranasal instillations of MnCl2 solution and hydrated nanoparticles of manganese oxide MnO · (H2O)x revealed similar uptake rates for both species. Together, we conclude that nasal geometry contributes to the protection of brain and lung from accumulation of air-dispersed particles in mole voles.
    Proceedings of the Royal Society B: Biological Sciences 10/2014; 281(1792). · 5.68 Impact Factor
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    ABSTRACT: We describe development and application of the new SNP–MED modular software system, designed to examine the influence of singlenucleotide polymorphisms (SNPs) on the function of genes associated with the risk of socially significant diseases. The SNP–MED system includes Genomics, Proteomics, and Gene Networks’ software components, and the Information Resource Database.
    Russian Journal of Genetics: Applied Research. 06/2014; 4(3):159-167.
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    ABSTRACT: Co-existence of bronchial asthma (BA) and tuberculosis (TB) is extremely uncommon (dystropic). We assume that this is caused by the interplay between genes involved into specific pathophysiological pathways that arrest simultaneous manifestation of BA and TB. Identification of common and specific genes may be important to determine the molecular genetic mechanisms leading to rare co-occurrence of these diseases and may contribute to the identification of susceptibility genes for each of these dystropic diseases. To address the issue, we propose a new methodological strategy that is based on reconstruction of associative networks that represent molecular relationships between proteins/genes associated with BA and TB, thus facilitating a better understanding of the biological context of antagonistic relationships between the diseases. The results of our study revealed a number of proteins/genes important for the development of both BA and TB.
    Immunogenetics 06/2014; · 2.89 Impact Factor
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    ABSTRACT: The TATA-binding protein (TBP) is a key part of the transcription complex of RNA polymerase II. Alone or as a part of the basal transcription factor TFIID, TBP binds the TATA box located in the core region of the TATA-containing promoters of class II genes. Previously, we studied the effects of single nucleotide polymorphisms (SNPs) on TBP/TATA-box interactions using gel retardation assay. It was demonstrated that most SNPs in the TATA boxes of some human gene promoters cause a 2- to 4-fold decrease in TBP/TATA affinity, which is associated with an increased risk of hereditary diseases, such as β thalassemias of diverse severity, hemophilia B Leyden, myocardial infarction, thrombophlebitis, lung cancer, etc. In this work, the process of TBP/TATA complex formation has been studied in real time by a stopped-flow technique using recombinant human TBP and duplexes, which were identical to the TATA box of the wild-type and a SNP-containing triosephosphate isomerase gene promoter and were fluorescently labeled by the Cy3/Cy5 FRET pair. It has been demonstrated for the first time that real-time binding of TBP to the TATA box of the TPI gene promoter is complete within 10 s and is described by a single-stage kinetic model. The complex formation of TBP with the wild-type TATA box occurs 5.5 times faster and the complex dissociation occurs 31 times slower compared with the SNPcontaining TATA box. Within the first seconds of the interaction, TBP binds to and simultaneously bends the TATA box. Importantly, the TATA box of the wild-type TPI gene promoter requires lower TBP concentrations compared to the TATA box containing the -24T → G SNP, which is associated with neurological and muscular disorders, cardiomyopathy, and other diseases.
    Acta naturae. 04/2014; 6(2):36-40.
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    ABSTRACT: SNPs in ТАТА boxes are the cause of monogenic diseases, contribute to a large number of complex diseases, and have implications for human sensitivity to external and internal environmental signals. The aim of this work was to explore the kinetic characteristics of the formation of human ТВР complexes with ТАТА boxes, in which the SNPs are associated with β-thalassemias of diverse severity, immunosuppression, neurological disorders, etc. It has for the first time been demonstrated, using an electrophoretic mobility shift assay, that TBP interacts with SNP-containing ТАТА boxes with a significant (8-36-fold) decrease in TBP/ТАТА association rate constant (ka ) as compared with that in healthy people, a smaller decrease in dissociation rate constant (kd ) and changes in the half-lives of TBP/ТАТА complexes. Carriers of the -24G allele (rs 1800202T>G) in the TATA box of the triosephosphate isomerise gene promoter, associated with neurological and muscular disorders, were observed to have a 36-fold decrease in TBP/TATA association rate constant that are consistent with TPI deficiency shown for patients who carry this defective allele. The kinetic characteristics of TBP/ТАТА complexes obtained suggest that, at a molecular level, hereditary diseases are largely caused by changes in TBP/ТАТА association rates and these changes have a bearing on disease severity. This article is protected by copyright. All rights reserved.
    Human Mutation 02/2014; · 5.21 Impact Factor
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    ABSTRACT: The molecular mechanism of olfactory cognition is very complicated. Olfactory cognition is initiated by olfactory receptor proteins (odorant receptors), which are activated by olfactory stimuli (ligands). Olfactory receptors are the initial player in the signal transduction cascade producing a nerve impulse, which is transmitted to the brain. The sensitivity to a particular ligand depends on the expression level of multiple proteins involved in the process of olfactory cognition: olfactory receptor proteins, proteins that participate in signal transduction cascade, etc. The expression level of each gene is controlled by its regulatory regions, and especially, by the promoter [a region of DNA about 100-1000 base pairs long located upstream of the transcription start site (TSS)]. We analyzed single nucleotide polymorphisms using human whole-genome data from the 1000 Genomes Project and revealed an extremely high level of single nucleotide polymorphisms in promoter regions of olfactory receptor genes and HLA genes. We hypothesized that the high level of polymorphisms in olfactory receptor promoters was responsible for the diversity in regulatory mechanisms controlling the expression levels of olfactory receptor proteins. Such diversity of regulatory mechanisms may cause the great variability of olfactory cognition of numerous environmental olfactory stimuli perceived by human beings (air pollutants, human body odors, odors in culinary etc.). In turn, this variability may provide a wide range of emotional and behavioral reactions related to the vast variety of olfactory stimuli.
    Frontiers in Psychology 01/2014; 5:247. · 2.80 Impact Factor
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    ABSTRACT: As an RNA virus, hepatitis C virus (HCV) is able to rapidly acquire drug resistance, and for this reason the design of effective anti-HCV drugs is a real challenge. The HCV subgenomic replicon-containing cells are widely used for experimental studies of the HCV genome replication mechanisms, for drug testing in vitro and in studies of HCV drug resistance. The NS3/4A protease is essential for virus replication and, therefore, it is one of the most attractive targets for developing specific antiviral agents against HCV. We have developed a stochastic model of subgenomic HCV replicon replication, in which the emergence and selection of drug resistant mutant viral RNAs in replicon cells is taken into account. Incorporation into the model of key NS3 protease mutations leading to resistance to BILN-2061 (A156T, D168V, R155Q), VX-950 (A156S, A156T, T54A) and SCH 503034 (A156T, A156S, T54A) inhibitors allows us to describe the long term dynamics of the viral RNA suppression for various inhibitor concentrations. We theoretically showed that the observable difference between the viral RNA kinetics for different inhibitor concentrations can be explained by differences in the replication rate and inhibitor sensitivity of the mutant RNAs. The pre-existing mutants of the NS3 protease contribute more significantly to appearance of new resistant mutants during treatment with inhibitors than wild-type replicon. The model can be used to interpret the results of anti-HCV drug testing on replicon systems, as well as to estimate the efficacy of potential drugs and predict optimal schemes of their usage.
    PLoS ONE 01/2014; 9(3):e91502. · 3.73 Impact Factor
  • Russian Journal of Genetics: Applied Research. 12/2013; 17(4/1):686-704.
  • Parallel Computing Technologies; 10/2013
  • Doklady Biological Sciences 09/2013; 452(1):316-9.
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    ABSTRACT: The hepatitis C virus (HCV) belongs to Flaviviridae family and causes hazardous liver diseases leading frequently to cirrhosis and hepatocellular carcinoma. HCV is able to rapidly acquire drug resistance and for this reason there is currently no effective anti-HCV therapy in spite of appearance of new potential drugs. Mathematical models are relevant to predict the efficacy of potential drugs against virus or host targets. One of the promising targets for development of new drugs is the viral NS3 protease. Here we developed a stochastic model of the subgenomic HCV replicon replication in Huh-7 cells and in the presence of the NS3 protease inhibitors. Along with consideration of the stochastic nature of the subgenomic HCV replicon replication, the model takes into account the existence and generation of main NS3 protease drug resistant mutants, namely BILN-2061 (A156T, D168V, R155Q), VX-950 (A156S, A156T, T54A) and SCH-503034 (A156T, A156S, T54A). The model reproduces well the viral RNA kinetics in the cell from the moment of the subgenomic HCV replicon transfection to steady state, as well as the viral RNA suppression kinetics in the presence of NS3 protease inhibitors BILN-2061, VX-950 and SCH-503034. We showed that the resistant mutants should be taken into account for the correct description of biphasic kinetics of the viral RNA suppression. The mutants selected in the presence of different inhibitor concentrations have maximal replication capacity in the given inhibitor concentration range. Our model can be used to interpret the results of the new anti-HCV drug testing in replicon systems, as well as to predict the efficacy of new potential drugs and optimize the mode of their use.
    Biophysics 09/2013;
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    ABSTRACT: The CELLmicrocosmos PathwayIntegration (CmPI) was developed to support and visualize the subcellular localization prediction of protein-related data such as protein-interaction networks. From the start it was possible to manually analyze the localizations by using an interactive table. It was, however, quite complicated to compare and analyze the different localization results derived from data integration as well as text-mining-based databases. The current software release provides a new interactive visual workflow, the Subcellular Localization Charts. As an application case, a MUPP1-related protein-protein interaction network is localized and semi-automatically analyzed. It will be shown that the workflow was dramatically improved and simplified. In addition, it is now possible to use custom protein-related data by using the SBML format and get a view of predicted protein localizations mapped onto a virtual cell model.
    Journal of Bioinformatics and Computational Biology 02/2013; 11(1):1340005.
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    ABSTRACT: Plant hormone auxin is a key regulator of growth and development. Auxin affects gene expression through ARF transcription factors, which bind specifically auxin responsive elements (AuxREs). Auxin responsive genes usually have more than one AuxRE, for example, a widely used auxin sensor DR5 contains seven AuxREs. Auxin responsive regions of several plant genes have been studied using sets of transgenic constructions in which the activity of one or several AuxREs were abolished. Here we present the method for analysis of the datasets on promoter activity assays having promoter sequences, namely, number and sequences of AuxREs, altogether with their measured auxin induction level. The method for a reverse problem solution considers two extreme models of AuxRE cooperation. Additive model describes auxin induction level of a gene as a sum of the individual AuxREs impacts. Multiplicative model considers pure cooperation between the AuxREs, where the combined effect is the multiplication of the individual AuxRE impacts. The reverse problem solution allows estimating the impact of an individual AuxRE into the induction level and the model for their cooperation. For promoters of three genes belonging to different plant species we showed that the multiplicative model fits better than additive. The reverse problem solution also suggests repressive state of auxin responsive promoters before auxin induction. The developed method provides possibility to investigate AuxRE structure-activity relationship and may be used as the basis for a novel approach for AuxRE recognition.
    Journal of Bioinformatics and Computational Biology 02/2013; 11(1):1340011.
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    ABSTRACT: Human genome sequencing has resulted in a great body of data, including a stunningly large number of single nucleotide polymorphisms (SNPs) with unknown phenotypic manifestations. Identification and comprehensive analysis of regulatory SNPs in human gene promoters will help quantify the effects of these SNPs on human health. Based on our experimental and computer-aided study of SNPs in TATA boxes and the use of literature data, we have derived an equation for TBP/TATA equilibrium binding in three successive steps: TATA-binding protein (TBP) sliding along DNA due to their nonspecific affinity for each other ↔ recognition of the TATA box ↔ stabilization of the TBP/TATA complex. Using this equation, we have analyzed TATA boxes containing SNPs associated with human diseases and made in silico predictions of changes in TBP/TATA affinity. An electrophoretic mobility shift assay (EMSA)-based experimental study performed under the most standardized conditions demonstrates that the experimentally measured values are highly correlated with the predicted values: the coefficient of linear correlation, r, was 0.822 at a significance level of α<10(-7) for equilibrium K(D) values, (-ln K(D)), and 0.785 at a significance level of α<10(-3) for changes in equilibrium K(D) (δ) due to SNPs in the TATA boxes ([Formula: see text]). It has been demonstrated that the SNPs associated with increased risk of human diseases such as α-, β- and δ-thalassemia, myocardial infarction and thrombophlebitis, changes in immune response, amyotrophic lateral sclerosis, lung cancer and hemophilia B Leyden cause 2-4-fold changes in TBP/TATA affinity in most cases. The results obtained strongly suggest that the TBP/TATA equilibrium binding equation derived can be used for analysis of TATA-box sequences and identification of SNPs with a potential of being functionally important.
    PLoS ONE 01/2013; 8(2):e54626. · 3.73 Impact Factor
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    ABSTRACT: Mature microRNAs (miRNAs) are small endogenous non-coding RNAs 18-25 nt in length. They program the RNA Induced Silencing Complex (RISC) to make it inhibit either messenger RNAs or promoter DNAs. We have found that the mean abundance of miRNAs in Arabidopsis is correlated with the abundance of DRYD tetranucleotides near the 3'-end and the abundance of WRHB tetranucleotides in the center of the miRNA sequence. Based on this correlation, we have estimated miRNA abundances in seven organs of this plant, namely: inflorescences, stems, siliques, seedlings, roots, cauline, and rosette leaves. We have also found that the mean affinity of miRNAs for two proteins in the Argonaute family (Ago2 and Ago3) in man is correlated with the abundance of YRHB tetranucleotides near the 3'-end and that the preference of miRNAs for Ago2 is correlated with the abundance of RHHK tetranucleotides in the center of the miRNA sequence. This allowed us to obtain statistically significant estimates of miRNA abundances in human embryonic kidney cells, HEK293T. These findings in relation to two taxonomically distant entities (man and Arabidopsis) fit one another like pieces of a jigsaw puzzle, which allowed us to heuristically generalize them and state that the miRNA abundance in the human brain may be determined by the abundance of YRHB and RHHK tetranucleotides in these miRNAs.
    Frontiers in Genetics 01/2013; 4:122.
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    ABSTRACT: Approaches are considered for the search for novel sources of non-food, renewable raw materials for third-generation biofuel production, namely, microalgae strains inhabiting natural systems of Western Siberia. This regional biodiversity survey is of great interest in connection with the vast habitat areal and the limited research on the properties of microalgae. During the work, a number of strains was isolated; one of them, Chlorella spp. A1125, has the necessary characteristics for cultivation in a pilot photobioreactor, including a maximum lipid productivity of 0.081 g/L (23% of the dry cell weight) with growth in minimal media. The strain is characterized by the content of both saturated fatty acids C16:0 (25%) and unsaturated fatty acids C16:2 (16%) and C18:2 (27%), making it a promising candidate for the third-generation biofuel production.
    Russian Journal of Genetics: Applied Research. 01/2013; 3(6).
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    ABSTRACT: Based on original measurements of the frequencies of guanine (G) damage in DNA by ultraviolet (UV) laser light with a wavelength of 193 nm, we found that these frequencies depended on the local nucleotide environment of G. This is the first study to demonstrate the reliability of forecasting the frequency of UV damage of G by the sequence of a known DNA on the basis of this sequence using an independent control.
    Doklady Biochemistry and Biophysics 12/2012; 447(1):267-72. · 0.32 Impact Factor
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    ABSTRACT: Leaf pubescence (hairiness) in wheat plays an important biological role in adaptation to the environment. However, this trait has always been methodologically difficult to phenotype. An important step forward has been taken with the use of computer technologies. Computer analysis of a photomicrograph of a transverse fold line of a leaf is proposed for quantitative evaluation of wheat leaf pubescence. The image-processing algorithm is implemented in the LHDetect2 software program accessible as a Web service at http://wheatdb.org/lhdetect2 . The results demonstrate that the proposed method is rapid, adequately assesses leaf pubescence density and the length distribution of trichomes and the data obtained using this method are significantly correlated with the density of trichomes on the leaf surface. Thus, the proposed method is efficient for high-throughput analysis of leaf pubescence morphology in cereal genetic collections and mapping populations.
    Planta 09/2012; · 3.35 Impact Factor
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    ABSTRACT: MicroRNA (hereafter, miRNA) genes have an important role in the transcriptional regulation of protein-coding genes, modulation of embryonic development, differentiation of embryonic stem cells, tissue formation and other processes. In this paper, we present an integrated study of the fastest evolving miRNAs in Homo neanderthalensis and Homo denisova, whose genomes have recently been sequenced. It has been demonstrated by the analysis of the functions of genes targeted by these miRNAs and changes in the secondary structures of their precursors that mutations in miRNA genes may have played a major role in the evolution of H. neanderthalensis and H. denisova, especially in the development and function of their brains.
    Archaeology Ethnology and Anthropology of Eurasia 09/2012; 40(3):22–30.
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    ABSTRACT: Elongation efficiency index (EEI) was suggested earlier to estimate gene expression efficiency by nucleotide context of coding sequence in unicellular organisms. We have analyzed association between EEI and nucleosome formation potential (NFP) in 5' regulatory regions upstream translation initiation site (TIS) from two yeast species. Theoretical estimations of NFP based on DNA sequence were obtained by Recon method. Experimental estimation of nucleosome occupancy was obtained by high-throughput sequencing data of nucleosomal DNA in Saccharomyces cerevisiae . For the sample of all genes correlation coefficient was calculated between two vectors: vector of NFP values for fixed position relative to TIS and vector of EEI values. Profiles of correlation coefficients of NFP and EEI were counted in (-600; +600) regions relative to TIS for gene sequences extracted from GenBank. We found regions of strong negative dependence between NFP and EEI for all genes as well as for 10% highly expressed genes in Schizosaccharomyces pombe (10% of EEI-highest genes). At the same time, we found positive dependence between NFP and EEI for all genes and for low expressed genes in S. cerevisiae (10% of EEI-lowest genes). The association between NFP and EEI could be explained by evolutionary selection of context characteristics of nucleotide sequences for gene expression optimization.
    Journal of biomolecular structure & dynamics 07/2012; · 4.99 Impact Factor

Publication Stats

3k Citations
342.39 Total Impact Points

Institutions

  • 2007–2014
    • Novosibirsk State University
      • • Chair of Informational Biology
      • • Department of Natural Sciences
      Novo-Nikolaevsk, Novosibirsk, Russia
    • Institute of Chemical Biology and Fundamental Medicine
      • Institute of Cytology and Genetics
      Novo-Nikolaevsk, Novosibirsk, Russia
    • Institute for System Dynamics and Control Theory of Siberian Branch of Russian Academy of Sciences (ISDCT SB RAS)
      Irkutsk, Irkutsk, Russia
  • 1984–2013
    • Russian Academy of Sciences
      • Institute of Cytology and Genetics, Siberian Branch
      Moskva, Moscow, Russia
  • 1983–2010
    • Institute of Cytology and Genetics
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 2001
    • RIKEN
      Вако, Saitama, Japan
  • 1999
    • Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук
      Moskva, Moscow, Russia
  • 1996
    • National Research Council
      • Institute of Biomedical Technologies ITB
      Roma, Latium, Italy