Vol 1, No 2 (2009)


Letter from the Editors

Gabibov A.G., Kochetkov S.N.
Acta Naturae. 2009;1(2):1-1
pages 1-1 views

The 50th Anniversary of the M. M. Shemyakin & Yu. A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Ivanov V.T.


Under the February 20, 1959, Resolution of the Presidium of the USSR Academy of Sciences, the Institute for Chemistry of Natural Products was founded within the Academy’s Chemical Sciences Division. The institution would go on to play an important part in the development of Russian physical and chemical biology. The founding of the Institute was brought about by the rapid developments in the chemistry of bioactive compounds, the natural products among them, and reflected the growing importance of this field in understanding the mechanisms of biological processes and in development of new medicinal preparations.
Acta Naturae. 2009;1(2):6-8
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In the Front Line of World Science

Zelenin A.V., Karpov V.L.


The creation and organization of the Institute of Molecular Biology (in its first six years it was called the Institute of Radiation and Physicochemical Biology, Academy of Sciences of the USSR) is forever connected with the name of Vladimir Alexandrovich Engelhardt, one of the most outstanding biochemists and molecular biologists of the 20th century. Vladimir Alexandrovich won broad fame and international acclaim as far back as the 1930s for discovering oxidative (respiratory) phosphorylation with the participation of ATP. In the beginning of the 1940s, Vladimir Alexandrovich earned fame again, when he and his wife Milicia Nikolaevna Lyubimova discovered the fermentation activity of myosin protein, which allowed him to suggest a theory about the combination of the structure and functions of biological compounds on the level of individual molecules. This scientific body of work became part of a goldmine of science, while Vladimir Alexandrovich began to be justifiably referred to as one of the founders of molecular biology in our country.
Acta Naturae. 2009;1(2):9-12
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Marine Natural Products: A Way to New Drugs

Stonik V.A.


The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural products are discussed herein.
Acta Naturae. 2009;1(2):15-25
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Influenza Virus Neuraminidase: Structure and Function

Shtyrya Y.A., Mochalova L.V., Bovin N.V.


The structure of the influenza virus neuraminidases, the spatial organization of their active site, the mechanism of carbohydrate chains desialylation by neuraminidase, and its role in the influenza virus function at different stages of the viral infectious cycle are considered in this review. Data on the neuraminidase substrate specificity and different approaches in studying the activity of this enzyme are summarized. In addition, data on neuraminidase inhibitors (as antivirals) are provided, along with considerations on the mechanisms of resistance of modern influenza viruses to those antivirals.
Acta Naturae. 2009;1(2):26-32
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Computer Modeling of the Structure and Spectra of Fluorescent Proteins

Nemukhin A.V., Grigorenko B.L., Savitsky A.P.


Fluorescent proteins from the family of green fluorescent proteins are intensively used as biomarkers in living systems. The chromophore group based on the hydroxybenzylidene-imidazoline molecule, which is formed in nature from three amino-acid residues inside the protein globule and well shielded from external media, is responsible for light absorption and fluorescence. Along with the intense experimental studies of the properties of fluorescent proteins and their chromophores by biochemical, X-ray, and spectroscopic tools, in recent years, computer modeling has been used to characterize their properties and spectra. We present in this review the most interesting results of the molecular modeling of the structural parameters and optical and vibrational spectra of the chromophorecontaining domains of fluorescent proteins by methods of quantum chemistry, molecular dynamics, and combined quantum-mechanical–molecular-mechanical approaches. The main emphasis is on the correlation of theoretical and experimental data and on the predictive power of modeling, which may be useful for creating new, efficient biomarkers.
Acta Naturae. 2009;1(2):33-43
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New Approaches for Cancer Treatment: Antitumor Drugs Based on gene-Targeted Nucleic Acids

Patutina O.A., Mironova N.L., Vlassov V.V., Zenkova M.A.


Currently, the main way to fight cancer is still chemotherapy. This method of treatment is at the height of its capacity, so, setting aside the need for further improvements in traditional treatments for neoplasia, it is vital to develop now approaches toward treating malignant tumors. This paper reviews innovational experimental approaches to treating malignant malformations based on the use of gene-targeted drugs, such as antisense oligonucleotides (asON), small interfering RN A (siRN A), ribozymes, and DNAzymes, which can all inhibit oncogene expression. The target genes for these drugs are thoroughly characterized, and the main results from pre-clinical and first-step clinical trials of these drugs are presented. It is shown that the gene-targeted oligonucleotides show considerable variations in their effect on tumor tissue, depending on the target gene in question. The effects range from slowing and stopping the proliferation of tumor cells to suppressing their invasive capabilities. Despite their similarity, not all the antisense drugs targeting the same region of the mRN A of the target-gene were equally effective. The result is determined by the combination of the drug type used and the region of the target-gene mRN A that it complements.
Acta Naturae. 2009;1(2):44-60
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Self-Renewalof Stem Cells

Terskikh V.V., Vorotelyak Y.A., Vasiliev A.V.


Asymmetric division is one of the most fundamental characteristics of adult stem cells , which ensures one daughter cell maintains stem cell status and the other daughter cell becomes committed to differentiation. New data emerged recently that allow us to conclude that asymmetric division has another important aspect: it enables self-maintenance of stem cells.
Acta Naturae. 2009;1(2):61-65
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Covalent Binding Antibodies Suppress Advanced glycation: On the Innate Tier of Adaptive Immunity

Shcheglova T., Makker S.P., Tramontano A.


Non-enzymatic protein glycation is a source of metabolic stress that contributes to cytotoxicity and tissue damage. Hyperglycemia has been linked to elevation of advanced glycation endproducts, which mediate much of the vascular pathology leading to diabetic complications. Enhanced glycation of immunoglobulins and their accelerated vascular clearance is proposed as a natural mechanism to intercept alternative advanced glycation endproducts, thereby mitigating microvascular disease. We reported that antibodies against the glycoprotein KLH have elevated reactivity for glycopeptides from diabetic serum. These reactions are mediated by covalent binding between antibody light chains and carbonyl groups of glycated peptides. Diabetic animals that were immunized to induce reactive antibodies had attenuated diabetic nephropathy, which correlated with reduced levels of circulating and kidney-bound glycation products. Molecular analysis of antibody glycation revealed the preferential modification of light chains bearing germline-encoded lambda V regions. We previously noted that antibody fragments carrying V regions in the germline configuration are selected from a human Fv library by covalent binding to a reactive organophosphorus ester. These Fv fragments were specifically modified at light chain V region residues, which map to the combining site at the interface between light and heavy chains. These findings suggest that covalent binding is an innate property of antibodies, which may be encoded in the genome for specific physiological purposes. This hypothesis is discussed in context with current knowledge of the natural antibodies that recognize altered self molecules and the catalytic autoantibodies found in autoimmune disease.
Acta Naturae. 2009;1(2):66-72
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M. tuberculosis gene Expression during Transition to the “Non-Culturable” State

Salina E.G., Mollenkopf H.J., Kaufmann S.H., Kaprelyants A.S.


We analyzed the gene expression profile under specific conditions during reversible transition of M. tuberculosis cells to the “non-culturable” (NC ) state in a prolonged stationary phase. More than 500 genes were differentially regulated, while 238 genes were upregulated over all time points during NC cell formation. Approximately a quarter of these upregulated genes belong to insertion and phage sequences indicating a possible high intensity of genome modification processes taking place under transition to the NC state. Besides the high proportion of hypothetical/conserved hypothetical genes in the cohort of upregulated genes, there was a significant number of genes belonging to intermediary metabolism, respiration, information pathways, cell wall and cell processes, and genes encoding regulatory proteins. We conclude that NC cell formation is an active process involved in the regulation of many genes of different pathways. A more detailed analysis of the experimental data will help to understand the precise molecular mechanisms of dormancy/latency/persistence of M. tuberculosis in the future. The list of upregulated genes obtained in this study includes many genes found to be upregulated in other models of M. tuberculosis persistence. Thirteen upregulated genes, which are common for different models, can be considered as potential targets for the development of new anti-tuberculosis drugs directed mainly against latent tuberculosis.
Acta Naturae. 2009;1(2):73-77
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Relative Comparison of Catalytic Characteristics of human Foamy Virus and hIV-1 Integrases

Knyazhanskaya E.S., Smolov M.A., Kondrashina O.V., Gottikh M.B.


Due to their ability to integrate into the host cell’s genome, retroviruses represent an optimal basis for the creation of gene therapy vectors. The integration reaction is carried out by a viral enzyme integrase: thus, a detailed research of this enzyme is required. In this work, the catalytic properties of human foamy virus integrase were studied. This virus belongs to the Retroviridae family. The dissociation constant was determined, together with the kinetics of integrase catalytic activity. The data obtained were compared to those for the human immunodeficiency virus integrase and a considerable similarity in the activity of the two enzymes was observed.
Acta Naturae. 2009;1(2):78-80
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Telomerase Complex from Yeast Saccharomyces cerevisiae Contains a Biotinylated Component

Shcherbakova D.M., Zvereva M.I., Dontsova O.A.


Telomerase adds telomeric repeats to single-stranded DNA at the ends of the chromosomes. This enzyme is a ribonucleoprotein complex. Telomerase from yeast Saccharomyces cerevisiae consists of TLC1 RN A, which serves as a template for the synthesis of telomeric repeats, telomerase reverse transcriptase Est2p, and a number of accessory proteins (Est1p, Est3p, Ku70/Ku80, and Sm-complex). We found that the yeast telomerase complex contains a biotinylated component. The telomerase fraction containing biotinylated protein is active in vitro and constitutes a small part of the total amount of active telomerase isolated from cells. We speculate about the nature of the biotinylated component.
Acta Naturae. 2009;1(2):81-85
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A Comparison of Target gene Silencing using Synthetically Modified siRNA and shRNA That Express Recombinant Lentiviral Vectors

Spirin P.V., Baskaran D., Rubtsov P.M., Zenkova M.A., Vlassov V.V., Chernolovskaya E.L., Prassolov V.S.


RN A interference is an efficient natural mechanism of gene expression modulation on the post translation level that was revealed both in higher animal and plant eukaryotes and in lower level eukaryotes and viruses. At present RN A interference is used as a powerful instrument in research of the functional activity of the genes, and with the help of this instrument findings have been obtained that are of significant importance for many areas of fundamental biology. At the same time, developments are under way in many world laboratories aimed at creating new-generation therapeutic means able to treat inherited, malignant and inflectional diseases of different aetiology based on the usage of the interfering RN As. One of the major problems of these researches is the retrieval of the efficient techniques able to deliver the interfering RN As into the target cells. At present for the introduction of the interfering RN As into the cells transfection and transduction are used with the help of the viral vectors that direct the shRN A synthesis in the cells, which are the predecessors of the corresponding siRN As. In the article findings are given of the comparison the efficiency of the oncogene AML1-ET O suppression with the help of lipofection of the synthetic siRN A and also while using the lentiviral vector which directs the shRN A synthesis – the anti AML1- ET O siРНК predecessor.
Acta Naturae. 2009;1(2):86-90
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Derivation and Characterization of human Induced Pluripotent Stem Cells

Shutova M.V., Bogomazova A.N., Lagarkova M.A., Kiselev S.L.


Cell biology is one of the most rapidly developing branches in modern biology. The most interesting stages in early embryonic development for cell biology are those when a large number of cells are pluripotent. Inner-cell mass of blastocyst can be cultivated in vitro, and these cells are called embryonic stem cells. They are able to differentiate into different types of cells and tissues. But the greatest interest for practical application is the return (reprogramming) of adult cells into the pluripotent state. In our study for the first time induced pluripotent cells were derived from human umbilical vein endothelial cells by genetic reprogramming. We showed that these cells are similar to embryonic stem cells in their morphology, function, and molecular level. We are the first to show that reprogramming sufficiently changes X-chromosome chromatin state, which is normally inactive in female endothelial cells, towards its activation, providing evidence that endothelial cells are reprogrammed at an epigenetic level.
Acta Naturae. 2009;1(2):91-92
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Influence of pub gene Expression on Differentiation of Mouse Embryonic Stem Cells into Derivatives of Ecto-, Meso-, and Endoderm in vitro

Novosadova E.V., Manuilova E.S., Arsenieva E.L., Lebedev A.N., Khaidarova N.V., Tarantul V.Z., Grivennikov I.A.


The influence of low and high pub gene expression on the initial stages of the differentiation of mouse embryonic stem cells into derivatives of ecto-, meso-, and endoderm in vitro was investigated. As follows from the results of a RT -PCR analysis, the expression of the vimentin, somatostatin, GATA 4, and GATA 6 genes, being the markers of endodermal differentiation, does not vary in both the cells with high pub gene expression and the cells with low pub gene expression, as well as in the corresponding control lines. The cells with high pub gene expression are characterized by an increase in the expression of mesodermal differentiation gene-markers ( trI card, trI skel, c-kit, and IL-7), whereas the cells with low pub gene expression are specified by a decrease in their expression. According to the analyses carried out, the reverse is characteristic of the expression of ectodermal differentiation gene-markers ( nestin, β- III tubulin, gfap, and th). Expression of these genes decreases in cell lines with high pub gene expression, whereas their expression increases with the decrease in pub gene expression. Hence, it is suggested that the variations in the pub gene expression in the embryonic stem cells influence significantly the mesodermal and ectodermal differentiation of these cells.
Acta Naturae. 2009;1(2):93-97
pages 93-97 views

Cell Phenotypes in human Amniotic Fluid

Davydova D.A., Vorotelyak E.A., Smirnova Y.A., Zinovieva R.D., Romanov Y.A., Kabaeva N.V., Terskikh V.V., Vasiliev A.V.


Stem cells capable of long-term proliferation and differentiation into different cell types may be a promising source of cells for regenerative medicine. Recently, much attention has been paid to fetal stem cells, among which are cells from amniotic fluid (AF). We have isolated amniotic stem cells from 3 AF samples. Flow cytometry, RT -PCR and immunohistochemistry have shown that these cells express mesenchymal (CD90, CD73, CD105, CD13, CD29, CD44, and CD146), neural (β 3-tubulin, Nestin, and Pax6), epithelial (keratin 19 and p63) markers and also markers of pluripotency ( Oct4, Nanog, and Rex-1). Transplantation of the cells to nude mice does not lead to tumor formation. Thus, putative stem/progenitor cells from AF are capable of long-term proliferation in vitro and the profile of gene expression led us to speculate that they have greater differentiation potential than mesenchymal stem cells and may be useful for cell therapy.
Acta Naturae. 2009;1(2):98-103
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Acta Naturae. 2009;1(2):104-104
pages 104-104 views

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