Vol 2, No 1 (2010)


A Letter from the Editors

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Acta Naturae. 2010;2(1):1-1
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The "Molecular and Cell Biology" Program of the Presidium of the Russian Academyof Sciences as an Effective Format for the Support of Promising Scientific Research Groups

Sychev V.V.


There are various ways to finance science in Russia, both governmental and private. Financial support can range from tens of thousands of rubles up to several million in stipends and grants. One of the questions most often addressed to the heads of agencies or funds is about the level of transparency and objectivity when selecting groups which receive financial support. Few well-known financing organizations have avoided criticism regarding this issue. Nevertheless, there is one scientific financing program that has earned the right to be called one of the most transparent and objective programs of its kind. This is the "Molecular and Cell Biology" program of the Presidium of the Russian Academy of Sciences (RAS), which is commonly named the Georgiev program after its coordinator, RAS academy member Georgiy Georgiev. According to numerous specialists, this is the best program in our country.
Acta Naturae. 2010;2(1):6-9
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Federal Target Programs: Targeted Funding of Priorities in Science and Technology

Murav'eva M.A.


A federal target program (FTP) is one of the most important tools that the government has to create an innovative economy in Russia. In particular, the development of Russian science and technology is currently supported through the "Research and Development in Important Scientific and Technological Areas of Russia, 2007-2012" FTP. Currently, the main governmental client of the program, the Federal Agency for Science and Innovations, is being reorganized, and this FTP will be managed by the Ministry of Education and Science; the essence of the program, however, will not change. Top managers of the Federal Agency for Science and Innovations have told us about the program's structure and management.
Acta Naturae. 2010;2(1):10-14
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The Russian Foundation for Basic Research: Concern for the Future of the Largest Grant Fund

Sterligov I.A.


The Russian Foundation for Basic Research is the oldest and most highly regarded source of scientific grants in Russia. It was created by a presidential decree of Boris Yeltsin "On Urgent Measures for Conserving the Scientific and Technical Potential of the Russian Federation" in 1992. Among other lines of research, the foundation is an active supporter of life sciences, which receive approximately 20% of the available funds.
Acta Naturae. 2010;2(1):15-20
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Mechanisms of Gravitational Sensitivity of Osteogenic Precursor Cells

Buravkova L.B., Gershovich P.M., Gershovich J.G., Grigorev A.I.


This report is a detailed review of the current data on mechanic and gravitational sensitivity of osteoblasts and osteogenic precursor cells in vitro. It summarizes the numerous responses of cells with an osteoblastic phenotype and osteogenic precursor cells and especially their responses to the alteration of their mechanic or gravitational surroundings. The review also discusses the osteogenic cell’s pathways of signal transduction and the mechanisms of gravitational sensitivity. It was shown, that the earliest multipotent stromal precursor cells of an adult organism’s bone marrow can sense changes of intensity in a gravitational or mechanic field in model conditions, which may play a certain role in the development of osteopenia in microgravity.
Acta Naturae. 2010;2(1):28-35
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Selectivity of Enzymatic Conversion of Oligonucleotide Probes during Nucleotide Polymorphism Analysis of DN

Vinogradova O.A., Pyshnyi D.V.


The analysis of DNA nucleotide polymorphisms is one of the main goals of DNA diagnostics. DNA-dependent enzymes (DNA polymerases and DNA ligases) are widely used to enhance the sensitivity and reliability of systems intended for the detection of point mutations in genetic material. In this article, we have summarized the data on the selectiveness of DNA-dependent enzymes and on the structural factors in enzymes and DNA which influence the effectiveness of mismatch discrimination during enzymatic conversion of oligonucleotide probes on a DNA template. The data presented characterize the sensitivity of a series of DNA-dependent enzymes that are widely used in the detection of noncomplementary base pairs in nucleic acid substrate complexes. We have analyzed the spatial properties of the enzyme-substrate complexes. These properties are vital for the enzymatic reaction and the recognition of perfect DNA-substrates. We also discuss relevant approaches to increasing the selectivity of enzyme-dependent reactions. These approaches involve the use of modified oligonucleotide probes which “disturb” the native structure of the DNA-substrate complexes.
Acta Naturae. 2010;2(1):36-52
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Regulation of immunogen processing: signal sequences and their application for the new generation of DNA-vaccines

Starodubova E.S., Isaguliants M.G., Karpov V.L.


Immunization with naked genes (DNA-immunization) is a perspective modern approach to prophylactic as well as therapeutic vaccination against pathogens, as well as cancer and allergy. A panel of DNA immunogens has been developed, some are already in the clinical trials. However, the immunogenicity of DNA vaccines, specifically of those applied to humans, needs a considerable improvement. There are several approaches to increase DNA vaccine immunogenicity. One approach implies the modifications of the encoded immunogen that change its processing and presentation, and thus the overall pattern of anti-immunogen response. For this, eukaryotic expression vectors are constructed that encode the chimeric proteins composed of the immunogen and specialized targeting or signal sequences. The review describes a number of signals that if fused to immunogen, target it into the predefined subcellular compartments. The review gives examples of their application for DNA-immunization.
Acta Naturae. 2010;2(1):53-59
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Ecological Basis for Rational Phage Therapy

Letarov A.V., Golomidova A.K., Tarasyan K.K.


Understanding the mutual interactions of bacterial and phage populations in the environment of a human or animal body is essential in any attempt to influence these complex processes, particularly for rational phage therapy. Current knowledge on the impact of naturally occurring bacteriophages on the populations of their host bacteria, and their role in the homeostasis maintenance of a macro host, is still sketchy. The existing data suggest that different mechanisms stabilize phage-bacteria coexistence in different animal species or different body sites. The defining set of parameters governing phage infection includes specific physical, chemical, and biological conditions, such as pH, nutrient densities, host prevalence, relation to mucosa and other surfaces, the presence of phage inhibiting substances, etc. Phage therapy is also an ecological process that always implies three components that form a complex pattern of interactions: populations of the pathogen, the bacteriophages used as antibacterial agents, and the macroorganism. We present a review of contemporary data on natural bacteriophages occuring in human- and animal-body associated microbial communities, and analyze ecological and physiological considerations that determine the success of phage therapy in mammals.
Acta Naturae. 2010;2(1):60-71
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Calcium Signaling and Neurodegeneration

Bezprozvanny I.B.


Neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and spinocerebellar ataxias (SCA) are very important both for fundamental science and for practical medicine. Despite extensive research into the causes of these diseases, clinical researchers have had very limited progress and, as of now, there is still no cure for any of these diseases. One of the main obstacles in the way of creating treatments for these disorders is the fact that their etiology and pathophysiology still remain unclear. This paper reviews results that support the so-called “calcium hypothesis of neurodegenerative diseases.” The calcium hypothesis states that the atrophic and degenerative processes in the neurons of AD, PD, ALS, HD, and SCA patients are accompanied by alterations in calcium homeostasis. Moreover, the calcium hypothesis states that this deregulation of calcium signaling is one of the early-stage and key processes in the pathogenesis of these diseases. Based on the results we reviewed, we conclude that the calcium channels and other proteins involved in the neuronal calcium signaling system are potential drug targets for AD, PD, ALS, HD, and SCA therapy.
Acta Naturae. 2010;2(1):72-80
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A Novel High-resolving Method for Genomic PCR-fingerprinting of Enterobacteria

Isaeva A.S., Kulikov E.E., Tarasyan K.K., Letarov A.V.


We developed a novel PCR-fingerprinting system for differentiation of enterobacterial strains using a single oligonucleotide primer IS1tr that matches the inverted terminal repeats of the IS1 insertion element. Compared to widely used BOX-PCR and ribotyping methods, our system features higher resolution allowing differentiation of closely related isolates that appear identical in BOX-PCR and ribotyping but differ in their phage sensitivity. The IS1-profiling system is less sensitive to the quality of the material and equipment used. At the same time, BOX-PCR is more universal and suitable for bacterial strain grouping and reconstruction of the low-distance phylogeny. Thus, our system represents an important supplement to the existing set of tools for bacterial strain differentiation; it is particularly valuable for a detailed investigation of highly divergent and rapidly evolving natural bacterial populations and for studies on coliphage ecology. However, some isolates could not be reliably differentiated by IS1-PCR, because of the low number of bands in their patterns. For improvement of IS1-fingerprinting characteristics, we offer to modify the system by introducing the second primer TR8834 hybridizing to the sequence of a transposase gene that is widely spread in enterobacterial genomes.
Acta Naturae. 2010;2(1):82-87
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Tumoricidal Activity of RNase A and DNase I

Patutina O.A., Mironova N.L., Ryabchikova E.I., Popova N.A., Nikolin V.P., Kaledin V.I., Vlassov V.V., Zenkova M.A.


In our work the antitumor and antimetastatic activities of RNase A and DNase I were studied using two murine models of pulmonary (Lewis lung carcinoma) and liver (hepatoma A-1) metastases. We found that intramuscular administration of RNase A at the dose range of 0.1-50 μg/kg retarded the primary tumor growth by 20-40%, and this effect disappeared with the increase in RNase A dose over 0.5 mg/kg. DNase I showed no effect on the primary tumor growth. The intramuscular administration of RNase A (0.35-7 μg/kg) or DNase I (0.02-2.3 mg/kg) resulted in a considerable decrease in the metastasis number into the lungs of animals with Lewis lung carcinoma and a decrease of the hepatic index of animals with hepatoma 1A. A histological analysis of the organs occupied by metastases revealed that the administration of RNase A and DNase I induced metastasis pathomorphism as manifested by the destruction of oncocytes, an increase in necrosis and apoptosis foci in metastases, and mononuclear infiltration. Our data indicated that RNase A and DNase I are highly promising as supplementary therapeutics for the treatment of metastasizing tumors.
Acta Naturae. 2010;2(1):88-93
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Penicillin Acylase-Catalyzed Effective and Stereoselective Acylation of 1-phenylethylamine in Aqueous Medium using Non-Activated Acyl Donor

Guranda D.T., Ushakov G.A., Svedas V.K.


Until recently the biocatalytic preparation of enantiomerically pure amines was based on stereoselective acyl transfer in an organic medium using activated acyl donors. The possibility of performing an effective and enantioselective enzymatic acylation of amines in an aqueous medium without using activated acyl donors was demonstrated for the first time as the example of direct condensation of phenylacetic acid and racemic 1-phenylethylamine. Direct condensation of the acid and the amine took place at mild reaction conditions with a high initial rate (3.3 μmole/(l∙h)), degree of conversion (80% acylation of active amine enantiomer), and enantioselectivity (enantiomeric excess of the product was more than 95%). The suggested approach has remarkable advantages compared to enzymatic reactions in organic media and is of practical value for the biocatalytic preparation of enantiomerically pure compounds at mild conditions using readily available reagents.
Acta Naturae. 2010;2(1):94-96
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Assessment of Formate Dehydrogenase Stress Stability in vivo using Inactivation by Hydrogen Peroxide

Savin S.S., Tishkov V.I.


Kinetic studies on hydrogen peroxide-induced inactivation of mutant formate dehydrogenase from Pseudomonas sp. 101 (PseFDH Cys255Ala) suggest a simple bimolecular mechanism for enzyme reaction with the inactivation agent. In the excess of hydrogen peroxide, the decrease in enzyme activity follows first-order kinetics. Therefore, the first-order effective inactivation kinetic constants determined for various FDH forms at a constant H 2O 2 concentration can be used as a quantitative measure of the enzyme stability. It was shown that two cysteine residues located in the active site formate- and coenzyme-binding domains (Cysl45 and Cys255, respectively) make similar contributions to the enzyme stability, while the contribution of Cys354 is insignificant. The inactivation kinetics of wild-type PseFDH, mutant PseFDH Cysl45Ser/Cys255Ala, and FDH produced under stress conditions by bacterium Staphylococcus aureus, higher plants Arabidopsis thaliana, and soya Glycine max, was studied. It was found that the stress-induced FDHs are at least 20 times more stable than the nonstress-induced PseFDH from Pseudomonas sp. 101 grown on methanol.
Acta Naturae. 2010;2(1):97-101
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Changes in the Proteasome Pool during Malignant Transformation of Mouse Liver Cells

Astakhova T.M., Delone G.V., Lyupina Y.V., Abramova E.B., Uryvaeva I.V., Sharova N.P.


Multiple forms of proteasomes regulate cellular processes by destroying proteins or forming the peptides involved in those processes. Various pathologies, including carcinogenesis, are related to changes in functioning the proteasome forms. In this study, we looked at the changes in the pool of liver proteasomes during nodular regenerative hyperplasia and formation of adenoma and hepatocellular carcinoma in mice treated with Dipin, followed by partial liver resection. The relative content of various proteasome forms was determined using Western blot analysis. The chymotrypsin-like activity of proteasomes was assessed from the hydrolysis of the commercial Suc-LLVY-AMC substrate. It was found that changes in the proteasome pool appeared already during the formation of diffuse nodules, the changes being the increased expression of the X(β5) constitutive subunit and the LMP7(β5i) and LMP2(β1i) immune subunits, accompanied by the increase of the total proteasome pool and the decrease in the chymotrypsin-like activity. These changes were more pronounced in hepatocellular carcinoma. The content of the total proteasome pool and the LMP2(β1i) immune subunit and the chymotrypsin-like activity in adenoma were intermediate compared to those in the samples of liver with diffuse nodules and carcinoma. In addition, the level of the Rpt6 subunit present in the 19S proteasome activator was increased in carcinoma. Our results indicate that nodular regenerative hyperplasia and adenomatosis may be stages preceding carcinogenesis. We also conclude that there is a need to find signalling pathways that change the expression of various proteasome subunits during carcinogenesis. The l9S proteasome activator, which is overexpressed in malignant tumours, can be a promising target for the development of new anticancer drugs.
Acta Naturae. 2010;2(1):102-107
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New 5-Modified Pyrimidine Nucleoside Inhibitors of Mycobacterial Growth

Alexandrova L.A., Shmalenyuk E.R., Kochetkov S.N., Erokhin V.V., Smirnova T.G., Andreevskaia S.N., Chernousova L.N.


The WHO has declared tuberculosis (TB) a global health emergency. Therefore, there is an urgent need to discover and develop new anti-TB drugs. Here we report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of Mycobacterium tuberculosis growth in vitro. A series of 2'-deoxy-, 3'-azido-2',3'-dideoxy-, and 3'-amino-2',3'-dideoxypyrimidine nucleoside analogues bearing lengthy flexible alkyloxymethyl substituents exhibited marked inhibitory activity against M tuberculosis in vitro. 5-Dodecyloxymethyl-2'-deoxyuridine was found to be a potent inhibitor of M. tuberculosis propagation in vitro. In contrast, monophosphates of the tested nucleosides were devoid of antimycobacterial activity. This new class of inhibitors seems to be a promising chemotherapeutic agent against TB and merits further studies.
Acta Naturae. 2010;2(1):108-110
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Induction of a Protective Heterosubtypic Immune Response Against the Influenza Virus by Using Recombinant Adenoviral Vectors Expressing Hemagglutinin of the Influenza H5 Virus

Shmarov M.M., Sedova E.S., Verkhovskaya L.V., Rudneva I.A., Bogacheva E.A., Barykova Y.A., Shcherbinin D.N., Lysenko A.A., Tutykhina I.L., Logunov D.Y., Smirnov Y.A., Naroditsky B.S., Gintsburg A.L.


Influenza viruses are characterized by a high degree of antigenic variability, which causes the annual emergence of flu epidemics and irregularly timed pandemics caused by viruses with new antigenic and biological traits. Novel approaches to vaccination can help circumvent this problem. One of these new methods incorporates genetic vaccines based on adenoviral vectors. Recombinant adenoviral vectors which contain hemagglutinin-encoding genes from avian H5N1 and H5N2 (Ad-HA5-1 and Ad-HA5-2) influenza viruses were obtained using the AdEasy Adenoviral Vector System (Stratagene). Laboratory mice received a double intranasal vaccination with Ad-HA5-1 and Ad-HA5-2. This study demonstrates that immunization with recombinant adenoviruses bearing the Н5 influenza virus hemagglutinin gene induces a immune response which protect immunized mice from a lethal dose of the H5 influenza virus. Moreover, it also protects the host from a lethal dose of H1 virus, which belongs to the same clade as H5, but does not confer protection from the subtype H3 influenza virus, which belongs to a different clade. Our data allow us to conclude that adenoviral vectors may become a universal platform for obtaining vaccines against seasonal and pandemic strains of the influenza virus.
Acta Naturae. 2010;2(1):111-118
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Guidelines for Authors

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Acta Naturae. 2010;2(1):120-120
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