N A Kolchanov

Institute of Cytology and Genetics, Novo-Nikolaevsk, Novosibirsk, Russia

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Publications (258)247.91 Total impact

  • Doklady Biochemistry and Biophysics 05/2015; 462(1):176-80. DOI:10.1134/S1607672915030102 · 0.37 Impact Factor
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    ABSTRACT: The review describes integrated experimental and computer approaches to the investigation of the mechanisms of transcriptional regulation of the organization of eukaryotic genes and transcription regulatory regions. These include (a) an analysis of the factors affecting the affinity of TBP (TATA-binding protein) for the TATA box; (b) research on the patterns of chromatin mark distributions and their role in the regulation of gene expression; (c) a study of 3D chromatin organization; (d) an estimation of the effects of polymorphisms on gene expression via high-resolution Chip-seq and DNase-seq techniques. It was demonstrated that integrated experimental and computer approaches are very important for the current understanding of transcription regulatory mechanisms and the structural and functional organization of the regulatory regions controlling transcription.
    Genetika 04/2015; 51(4):409-29. · 0.37 Impact Factor
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    ABSTRACT: The review describes combined experimental and computational approaches to the investigation of the mechanisms of transcriptional regulation of eukaryotic genes and organization of transcription regulatory regions. These include (a) an analysis of the factors affecting the affinity of TBP (TATA-binding protein) for the TATA box; (b) research on the patterns of chromatin mark distributions and their role in the regulation of gene expression; (c) a study of 3D chromatin organization; (d) an estimation of the effects of polymorphisms on gene expression via high-resolution ChIP-seq and DNase-seq techniques. It was demonstrated that combined experimental and computational approaches are very important for the current understanding of transcription regulatory mechanisms and the structural and functional organization of the regulatory regions controlling transcription.
    Russian Journal of Genetics 04/2015; 51(4):334-352. DOI:10.1134/S1022795415040067 · 0.41 Impact Factor
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    ABSTRACT: Terahertz (THz) radiation was proposed recently for use in various applications, including medical imaging and security scanners. However, there are concerns regarding the possible biological effects of non-ionising electromagnetic radiation in the THz range on cells. Human embryonic stem cells (hESCs) are extremely sensitive to environmental stimuli, and we therefore utilised this cell model to investigate the non-thermal effects of THz irradiation. We studied DNA damage and transcriptome responses in hESCs exposed to narrow-band THz radiation (2.3 THz) under strict temperature control. The transcription of approximately 1% of genes was subtly increased following THz irradiation. Functional annotation enrichment analysis of differentially expressed genes revealed 15 functional classes, which were mostly related to mitochondria. Terahertz irradiation did not induce the formation of γH2AX foci or structural chromosomal aberrations in hESCs. We did not observe any effect on the mitotic index or morphology of the hESCs following THz exposure.
    Scientific Reports 01/2015; 5. DOI:10.1038/srep07749 · 5.58 Impact Factor
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    ABSTRACT: The adaptation of subterranean rodents, which dig passages with their front teeth, to underground life presumes the formation of protection mechanisms against inhaling dust particles of different size when digging. One such mechanism can be a specific pattern of air-flow organization in the nasal cavity. To verify this assumption, we conducted a comparative study of the geometry and aerodynamics of nasal passages of a typical representative of subterranean rodents, the mole vole, and a representative of ground rodents, the house mouse. Numerical modeling of air flows and the deposition of micro- and nanoparticle aerosols indicate that sedimentation of model particles over the whole surface of the nasal cavity is higher in the mole vole than in the house mouse, while, on the contrary, particle deposition on the surface of the olfactory epithelium is much less in the burrowing rodent as compared to the ground rodent. The adaptive significance of the latter was substantiated by an experimental study on the inflow of hydrated manganese oxide MnO · (H2O) x and Mn ion nanoparticles from the nasal cavity into brain. It has been shown with use of magnetic resonance tomography (MRT) that there is no difference between the studied species with respect to the inflow of particles or ions by the olfactory bulb when they are introduced intranasally. Meanwhile, when inhaling a nanoparticle aerosol of MnCl2, the Mn deposition in the house mouse’s olfactory bulbs significantly exceeds that in the mole vole’s bulbs. Thus, the morphology of nasal passages as a factor determining the aerodynamics of upper respiratory tract ensures more efficient protection of both the lungs and brain against inhaled aerosols for burrowing rodents than for ground ones.
    01/2015; 5(1):36-45. DOI:10.1134/S2079086415010065
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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). DOI:10.1098/rspb.2014.0919 · 5.29 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. DOI:10.1134/S2079059714030034
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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. · 0.87 Impact Factor
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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 11/2013; 3(6). DOI:10.1134/S2079059713060075
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    Doklady Biological Sciences 09/2013; 452(1):316-9. DOI:10.1134/S0012496613050104
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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; DOI:10.1134/S0006350913050059
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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 regimen of their use. Key words: hepatitis C virus, subgenomic HCV replicon, mathematical modeling, stochastic model, drug resistant mutants, NS3 protease inhibitors, drug efficacy
    BIOPHYSICS 06/2013; 58(5):758-774.
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    ABSTRACT: The incidence of allergic diseases in the 20th century has rapidly increased. Currently, many people in industrial countries suffer from allergies, which makes analysis of the allergenic properties of proteins an urgent problem. Earlier, it was assumed that the allergenicity of proteins depends on their size, enzymatic properties, homology to human proteins, etc. However, no analysis of the relationship between the allergenicity of proteins and the habitat of the organisms producing them has been conducted as of yet. We have predicted the allergenic proteins from proteomes of more than 500 species of microorganisms. It is shown that the number of allergenic proteins in the proteomes of microorganisms is significantly related to their pathogenicity, habitats, ambient temperature conditions, and oxygen demands of these microorganisms.
    Russian Journal of Genetics: Applied Research 05/2013; 3(3). DOI:10.1134/S2079059713030027
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    ABSTRACT: Embryo morphodynamics at early developmental stages of Arabidopsis thaliana has been studied. A pipeline has been elaborated from confocal microscopy and tissue 3D reconstruction to cell-lineage tracing and numerical simulation of growing embryo mechanics. Tentative results of its use are presented.
    Russian Journal of Genetics: Applied Research 05/2013; 3(3). DOI:10.1134/S207905971303009X
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    T. I. Merkulova · E. A. Ananko · E. V. Ignatieva · N. A. Kolchanov
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    ABSTRACT: The key aspects of transcription regulation in multicellular organisms were discussed in the paper, including characteristics of promoters, transcription factor binding sites and composite elements. The functional roles of transcriptional regulators (GTFs and transcription factors) were described together with mechanisms, which regulate its activity. The importance of DNA-encoded nucleosome organization and chromatin modifications for the process of transcription regulation have been declared. Also the significance of mechanisms which regulate activity of transcription factors within Gene Networks have been stressed. In light of recent data transcriptional regulatory codes of a eukaryotic genome were discussed.
    Russian Journal of Genetics 01/2013; 49(1). DOI:10.1134/S1022795413010079 · 0.41 Impact Factor
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    ABSTRACT: (translation of original Russian publication.)
    Doklady Biological Sciences 01/2013; 452:316-319. DOI:10.7868/S0869565213280268
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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. DOI:10.1134/S1607672912060038 · 0.37 Impact Factor
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    ABSTRACT: Development of plant embryo beginning from the very early stages is not fully studied yet. For example, detailed description of dynamics of cellular composition of embryo, and the cells growth are unknown. Herein we propose a quantitative description of the early Arabidopsis thaliana development. The description is quantitative with respect to cell shapes, division planes, dynamics though time lapse data are not available. We have designed three algorithms. The first one is devoted to 3D reconstruction from stacks of confocal images. The second algorithm builds a tree representation of the embryo. Each node of the tree corresponds to a set of related cells and each branch points towards a daughter cell. This representation is based on topological and geometrical rules applied on the 3D reconstructions. The third algorithm is devoted to embryos comparisons. Considering two embryos at different stages of development and their associated tree representations we propose to plug the younger embryo inside the older one. This is realized by tree explorations from the root. Results: 3D geometrical models of early stages of Arabidopsis embry development were constructed in meshes representation. Different features such as volumes, neighboring structure have been computed. For several embryos, the history of divisions has been reconstructed.Growth rates could be inferred from the plug-in of embryos. Conlusion: From a collection of Arabidopsis embryos observed iconfocal microscopy quantitative data such as volumes can be analyzed. Despite the fact that no time lapse is available dynamics information could be inferred. At least several rounds of divisions can be guess. Of course variability should be addressed and the plug-in algorithm we propose can be helpful. The 4D information we got can now be used for designing models for biomechanics and transport phenomena evaluation during early plant embryo development.

Publication Stats

3k Citations
247.91 Total Impact Points

Institutions

  • 1983–2015
    • Institute of Cytology and Genetics
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 2006–2014
    • Novosibirsk State University
      • Department of Natural Sciences
      Novo-Nikolaevsk, Novosibirsk, Russia
  • 1991–2013
    • Russian Academy of Sciences
      • Institute of Cytology and Genetics, Siberian Branch
      Moskva, Moscow, Russia
  • 2007
    • Institute of Computational Mathematics and Mathematical Geophysics SB RAS
      Novo-Nikolaevsk, Novosibirsk, Russia