Osidak M.S.,Imtek Ltd |
Osidak E.O.,Gamaleya Institute of Epidemiology and Microbiology |
Akhmanova M.A.,Imtek Ltd |
Domogatsky S.P.,Imtek Ltd |
Current Pharmaceutical Design | Year: 2015
The ability of a human artery to pass through 150 million liters of blood sustaining 2 billion pulsations of blood pressure with minor deterioration depends on unique construction of the arterial wall. Viscoelastic properties of this construction enable to re-seal the occuring damages apparently without direct immediate participance of the constituent cells. Collagen structures are considered to be the elements that determine the mechanoelastic properties of the wall in parallel with elastin responsible for elasticity and resilience. Collagen scaffold architecture is the function-dependent dynamic arrangement of a dozen different collagen types composing three distinct interacting forms inside the extracellular matrix of the wall. Tightly packed molecules of collagen types I, III, V provide high tensile strength along collagen fibrils but toughness of the collagen scaffold as a whole depends on molecular bonds between distinct fibrils. Apart of other macromolecules in the extracellular matrix (ECM), collagen-specific interlinks involve microfilaments of collagen type VI, meshwork-organized collagen type VIII, and FACIT collagen type XIV. Basement membrane collagen types IV, XV, XVIII and cell-associated collagen XIII enable transmission of mechanical signals between cells and whole artery matrix. Collagen scaffold undergoes continuous remodeling by decomposition promoted with MMPs and reconstitution from newly produced collagen molecules. Pulsatile stress-strain load modulates both collagen synthesis and MMP-dependent collagen degradation. In this way the ECM structure becomes adoptive to mechanical challenges. The mechanoelastic properties of the arterial wall are changed in atherosclerosis concomitantly with collagen turnover both type-specific and dependent on the structure. Improving the feedback could be another approach to restore sufficient blood circulation. © 2015 Bentham Science Publishers.
Kulibin A.Y.,Russian Academy of Sciences |
Malolina E.A.,Gamaleya Institute of Epidemiology and Microbiology
Reproduction | Year: 2016
Adult mammalian Sertoli cells (SCs) have been considered to be quiescent terminal differentiated cells for many years, but recently, proliferation of adult SCs was demonstrated in vitro and in vivo. We further examined mouse SC behavior in culture and found that there are two populations of adult SCs. The first population is SCs from seminiferous tubules that hardly proliferate in vitro. The second population is small and consists of SCs with atypical nuclear morphology from the terminal segments of seminiferous tubules, a transitional zone (TZ). TZ SCs multiply in culture and form colonies, display mixture of mature and immature SC characteristics, and generate cord-like structures in a collagen matrix. The specific features of TZ SCs are ACTA2 expression in vitro and DMRT1 low levels in vivo and in vitro. Although the in vivo function of TZ SCs still remains unclear, this finding has significant implications for our understanding of SC differentiation and functioning in adult mammals. © 2016 Society for Reproduction and Fertility.
Ilyina T.S.,Gamaleya Institute of Epidemiology and Microbiology
Molecular Genetics, Microbiology and Virology | Year: 2015
Filamentous bacteriophages of the genus Inovirus (Inoviridae) infect a number of gram-negative, and some gram-positive, bacteria. This review discusses contemporary data on the role of filamentous bacteriophages in the virulence and evolution of known pathogenic bacteria, such as V. cholerae, Yersinia pestis, Neisseria meningitides, Escherichia coli O18: K1: H7, Pseudomonas aruginosa, and some pathogens of cultivars. © 2015, Allerton Press, Inc.
Ershova A.S.,Gamaleya Institute of Epidemiology and Microbiology |
Karyagina A.S.,Gamaleya Institute of Epidemiology and Microbiology |
Vasiliev M.O.,Gamaleya Institute of Epidemiology and Microbiology |
Lyashchuk A.M.,Gamaleya Institute of Epidemiology and Microbiology |
And 3 more authors.
Nucleic Acids Research | Year: 2012
Prokaryotic restriction-modification (R-M) systems defend the host cell from the invasion of a foreign DNA. They comprise two enzymatic activities: specific DNA cleavage activity and DNA methylation activity preventing cleavage. Typically, these activities are provided by two separate enzymes: a DNA methyltransferase (MTase) and a restriction endonuclease (RE). In the absence of a corresponding MTase, an RE of Type II R-M system is highly toxic for the cell. Genes of the R-M system are linked in the genome in the vast majority of annotated cases. There are only a few reported cases in which the genes of MTase and RE from one R-M system are not linked. Nevertheless, a few hundreds solitary RE genes are present in the Restriction Enzyme Database (http://rebase.neb.com) annotations. Using the comparative genomic approach, we analysed 272 solitary RE genes. For 57 solitary RE genes we predicted corresponding MTase genes located distantly in a genome. Of the 272 solitary RE genes, 99 are likely to be fragments of RE genes. Various explanations for the existence of the remaining 116 solitary RE genes are also discussed. © 2012 The Author(s).
Ilyina T.S.,Gamaleya Institute of Epidemiology and Microbiology
Molecular Genetics, Microbiology and Virology | Year: 2012
The recently discovered method of horizontal distribution of bacterial genes with ISCR atypical insertion sequences is reviewed using the example of drug-resistance genes. The mechanism of transposition of such elements including rolling circle replication, formation of autonomous nonreplicable circular structures, and homologous recombination provides mobilization of any section of the adjacent DNA. ISCR elements represent a more powerful gene mobilization system than transposons and integrons and provide formation of groups of mobile genes, including antibiotic resistance genes of pathogenic bacteria. The structure and functions of ISCR elements are discussed together with their similarity and dissimilarity to IS91-like elements and their role in emergence of blocks of multiple antibiotic resistance genes and their contribution to evolution of bacteria and plasmids. © 2012 Allerton Press, Inc.
Voronina A.L.,Gamaleya Institute of Epidemiology and Microbiology
Molekuliarnaia genetika, mikrobiologiia i virusologiia | Year: 2013
88 cultures of microorganisms referred to the Burkholderia cepacia complex (Bcc) during initial identification were analyzed by multilocus sequencing (Multilocus Sequence Typing, MLST). 13 genotypes (sequence type, ST) were detected, 9 of them (708, 709, 710, 711, 712, 714, 727, 728, 729) were identified for the first time. Two new alleles for the gene trpB (357, 358), one of the genes atpD (306) and gltB (352) were detected and registered. It was found that strains of 2 genotypes (711, 712) belong to the species B. multivorans, 1 (ST102) - B. contaminans, 1 (ST51) - B. stabilis, 1 (ST729) - B. vietnamiensis. Most strains of the sample, representing 8 genotypes (208, 241, 728, 727, 708, 709, 710, 714), belong to the species B. cenocepacia. Identified genotypes differ in the global spread of the world: 4 genotype (51, 102, 208, 241) have intercontinental distribution, 1 (712) - intra. It is shown that strains causing nosocomial infections, in most cases refer to genotypes 728 and 708. Epidemiologically significant in respect of patients with cystic fibrosis should recognize genotype 709, detected in strains isolated from patients in seven federal districts (FD) of Russia. The Bcc strains of genotypes 241 (B. cenocepacia) and 729 (B. vietnamiensis) were isolated from the patients of the Far Eastern FD. They are not typical for other FD Russia. The possibility of concomitant infection in cystic fibrosis patient with two genotypes 709 - epidemiologically significant and 708 - nosocomial, was indicated. The long-termpersistence of a single genotype strain in the organism of patients with cystic fibrosis was demonstrated as for Bcc species B. cenocepacia (ST 709), so for B. multivorans (ST712). The possibility of transferring the strain Bcc, typical for nosocomial environment to patient with cystic fibrosis at surgery was observed.
Kryuchkova P.,RAS Engelhardt Institute of Molecular Biology |
Grishin A.,Gamaleya Institute of Epidemiology and Microbiology |
Eliseev B.,RAS Engelhardt Institute of Molecular Biology |
Karyagina A.,Gamaleya Institute of Epidemiology and Microbiology |
And 2 more authors.
Nucleic Acids Research | Year: 2013
Release factor eRF1 plays a key role in the termination of protein synthesis in eukaryotes. The eRF1 consists of three domains (N, M and C) that perform unique roles in termination. Previous studies of eRF1 point mutants and standard/variant code eRF1 chimeras unequivocally demonstrated a direct involvement of the highly conserved N-domain motifs (NIKS, YxCxxxF and GTx) in stop codon recognition. In the current study, we extend this work by investigating the role of the 41 invariant and conserved N-domain residues in stop codon decoding by human eRF1. Using a combination of the conservative and non-conservative amino acid substitutions, we measured the functional activity of 80 mutant eRF1s in an in vitro reconstituted eukaryotic translation system and selected 15 amino acid residues essential for recognition of different stop codon nucleotides. Furthermore, toe-print analyses provide evidence of a conformational rearrangement of ribosomal complexes that occurs during binding of eRF1 to messenger RNA and reflects stop codon decoding activity of eRF1. Based on our experimental data and molecular modelling of the N-domain at the ribosomal A site, we propose a two-step model of stop codon decoding in the eukaryotic ribosome. © 2013 The Author(s).
Noskov A.N.,Gamaleya Institute of Epidemiology and Microbiology
Russian Journal of Bioorganic Chemistry | Year: 2013
AB5 toxins are poreforming protein complexes, which destroy eukaryotic target cells through ADP-ribosylation or N-glycosylation of intracellular enzyme complexes by A1 subunits. In this paradigm, B subunit pentamer interacts with the target-cell receptors and forms a pore in the cell membrane. Then receptor-mediated endocytosis is induced, and A subunit is translocated into the cytosol. In the present article, we propose a new model of A1 subunit translocation as a globular structure. It is based on those endosome properties that present it as a phospholipid bilayer "ball" with 3D structure as opposed to planar "unfolding- folding" 2D model. Furthermore, the proposed model accounts for membrane phospholipid physical and chemical properties and the activity of membrane-bound K+/Na+ - and H+ - ATPases. A subunit translocation (together with the B subunit) from the endosome to the cytosol is driven by the proton potential difference generated by H+-ATPases. This is followed by the reduction of A 1-A2 disulphide bond by intracellular enzymes, and subunits B and A2 return back into the endosome, where they are destroyed by endosomal/lysosomal proteases; the membrane pore is closed. Endosome integrates into the cellular membrane (endosome recycling), and membrane-bound enzymatic complexes (ATPases and others) return back to their initial position. The proposed model of receptor-mediated endocytosis is a universal mechanism of membrane reparation and translocation of effector toxin subunits or any other poreforming proteins into the target cell. © Pleiades Publishing, Ltd., 2013.
Kirsanov D.D.,Gamaleya Institute of Epidemiology and Microbiology |
Zanegina O.N.,Moscow State University |
Aksianov E.A.,Moscow State University |
Spirin S.A.,RAS Engelhardt Institute of Molecular Biology |
And 2 more authors.
Nucleic Acids Research | Year: 2013
The Nucleic acid - Protein Interaction DataBase (http://npidb.belozersky. msu.ru/) contains information derived from structures of DNA-protein and RNA-protein complexes extracted from the Protein Data Bank (3846 complexes in October 2012). It provides a web interface and a set of tools for extracting biologically meaningful characteristics of nucleoprotein complexes. The content of the database is updated weekly. The current version of the Nucleic acid - Protein Interaction DataBase is an upgrade of the version published in 2007. The improvements include a new web interface, new tools for calculation of intermolecular interactions, a classification of SCOP families that contains DNA-binding protein domains and data on conserved water molecules on the DNA-protein interface. © The Author(s) 2012.
Ospelnikova T.P.,Gamaleya Institute of Epidemiology and Microbiology
Voprosy Virusologii | Year: 2013
The role of interferon in influenza and herpes infections, general patterns of the Interferon system in these diseases, the identification of interferon deficiency, the possibility of their correction with the immune active drugs, including interferon inducers combining antiviral immunomodulatory interferon effects with etiopathogenic corrective mode of action, are discussed. Clinical values of faster recovery confirm the suitability of their application in the immunocompromised patients.