Vol 2, No 4 (2010)


Letter from the Editors

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Acta Naturae. 2010;2(4):1-1
pages 1-1 views

Technology Platforms: Joining Forces, Establishing Dialogue

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The Russian government has begun creating a series of Technology Platforms (TPs). These platforms are meant to serve as a tool that should help close the gap between science and industry, encourage innovation at enterprises, and allow the government to focus its financial resources on the type of research and development that is of interest to business. The Ministry of Economic Development has issued a request for applications from initiators of TP development, and the government will determine the number of TPs based on the results of a selection process led by experts.
Acta Naturae. 2010;2(4):6-9
pages 6-9 views

National Technology Platforms: The European Experience

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The Ministry of Education of the Russian Federation has announced the start of the formation of national technology platforms to ensure coordinated development of innovation in key economic areas. The mechanism of the platforms is borrowed from that of the EU.
Acta Naturae. 2010;2(4):10-11
pages 10-11 views

Pharmaceutical Clusters: Remedy for Regional Economies

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The idea of pharmaceutical clusters is being actively pursued in Russia. Several projects have already been implemented, while others are in the pipeline. There are optimistic reports about regions setting up manufacturing, improving the level of education, and creating jobs, and about pharmaceutical companies receiving infrastructure and tax incentives. Is there reason to expect innovation with pharmaceutical clusters as well? That issue, along with others, was taken up at the International Forum "Innovative Drug Research and Development in Russia" organized by the Adam Smith Institute on November 17-18, 2010, in Moscow.
Acta Naturae. 2010;2(4):12-14
pages 12-14 views

Genomes, Populations and Diseases: Ethnic Genomics and Personalized Medicine

Stepanov V.A.


This review discusses the progress of ethnic genetics, the genetics of common diseases, and the concepts of personalized medicine. We show the relationship between the structure of genetic diversity in human populations and the varying frequencies of Mendelian and multifactor diseases. We also examine the population basis of pharmacogenetics and evaluate the effectiveness of pharmacotherapy, along with a review of new achievements and prospects in personalized genomics.
Acta Naturae. 2010;2(4):15-30
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Hereditary Breast-Ovarian Cancer Syndrome in Russia

Sokolenko A.P., Iyevleva A.G., Mitiushkina N.V., Suspitsin E.N., Preobrazhenskaya E.'., Kuligina E.S., Voskresenskiy D.A., Lobeiko O.S., Krylova N.Y., Gorodnova T.V., Buslov K.G., Bit-Sava E.M., Dolmatov G.D., Porhanova N.V., Polyakov I.S., Abysheva S.N., Katanugina A.S., Baholdin D.V., Yanus G.A., Togo A.V., Moiseyenko V.M., Maximov S.Y., Semiglazov V.F., Imyanitov E.N.


Hereditary breast-ovarian cancer syndrome contributes to as much as 5-7% of breast cancer (BC) and 10-15% of ovarian cancer (OC) incidence. Mutations in the “canonical” genes BRCA1 and BRCA2 occur in 20-30% of affected pedigrees. In addition to BRCA1 and BRCA2 mutations, germ-line lesions in the CHEK2, NBS1, and PALB2 genes also contribute to familial BC clustering. The epidemiology of hereditary breast-ovarian cancer in Russia has some specific features. The impact of the “founder” effect is surprisingly remarkable: a single mutation, BRCA1 5382insC, accounts for the vast majority of BRCA1 defects across the country. In addition, there are two other recurrent BRCA1 alleles: BRCA1 4153delA and BRCA1 185delAG. Besides BRCA1, in Russia breast cancer is often caused by germ-line alterations in the CHEK2 and NBS1 genes. In contrast to BRCA1 and BRCA2, the CHEK2 and NBS1 heterozygosity does not significantly increase the OC risk. Several Russian breast cancer clinics recently started to investigate the efficacy of cisplatin in the therapy of BRCA1-related cancers; initial results show a unique sensitivity of BRCA1 -associated tumours to this compound.
Acta Naturae. 2010;2(4):31-35
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Dosage Compensation of Sex Chromosome Genes in Eukaryotes

Dementyeva E.V., Zakian S.M.


Sex chromosome evolution is accompanied by significant divergence in morphology and gene content and results in most genes of one of the sex chromosomes being present in two dosages in one sex and in one dosage in the other. To eliminate the difference in the expression levels of these genes between sexes and to restore equal expression levels of the genes between sex chromosomes and autosomes, mechanisms of dosage compensation have appeared. Studies of three classical objects, Drosophila melanogaster, Caenorhabditis elegans, and mammals, have shown that dosage compensation of X-linked genes can be achieved through completely different chromosome-wide mechanisms. New data on sex chromosome gene expression demonstrating that many sex chromosome genes can be expressed at different levels in males and females were recently obtained from birds and butterflies. In this review, dosage compensation mechanisms in D. melanogaster, C. elegans, and mammals are considered and the data on sex chromosome gene expression in birds and butterflies, and their influence on our view of dosage compensation, are discussed.
Acta Naturae. 2010;2(4):36-43
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The Role of p66shc in Oxidative Stress and Apoptosis

Galimov E.R.


P66shc is a gene that regulates the level of reactive oxygen species (ROS), apoptosis induction, and lifespan in mammals. Mice knocked out for p66shc have a lifespan ~30% longer and demonstrate an enhanced resistance to oxidative stress and age-related pathologies such as hypercholesterolemia, ischemia, and hyperglycemia. In this respect, p66shc is a promising pharmacological target for the treatment of age-related diseases. In this review, an attempt has been made to survey and put to a critical analysis data concerning the involvement of p66shc in the different signaling pathways that regulate oxidative stress and apoptosis.
Acta Naturae. 2010;2(4):44-51
pages 44-51 views

Chromatin Diminution Process Regulates rRNA Gene Copy Number in Freshwater Copepods

Zagoskin M.V., Marshak T.L., Mukha D.V., Grishanin A.K.


The results of quantitative PCR (qPCR) presented in the paper clearly demonstrate that the sixteenfold genome reduction in Cyclops kolensis during chromatin diminution (from 15.3 pg to 0.98 pg) results in a dramatic decrease in ribosomal RNA gene copy numbers in the genome of a somatic cell line by more than two orders of magnitude. The results presented allow for the consideration of the chromatin diminution as a mechanism of rDNA copy number regulation.
Acta Naturae. 2010;2(4):52-57
pages 52-57 views

Association Study of Xenobiotic Detoxication and Repair Genes with Malignant Brain Tumors in Children

Salnikova L.E., Zelinskaya N.I., Belopolskaya O.B., Aslanyan M.M., Rubanovich A.V.


This study presents the results of research on DNA polymorphism in children with malignant brain tumors (172 patients, 183 in the control group). Genotyping was performed using an allele-specific tetraprimer reaction for the genes of the first (CYP1A1 (2 sites)) and second phases of xenobiotic detoxication (GSTM1, GSTT1, GSTP1, GSTM3), DNA repair genes XRCC1, XPD (2 sites), OGG1, as well as NOS1 and MTHFR. The increased risk of disease is associated with a minor variant of CYP1A1 (606G) (p = 0.009; OR = 1.50) and a deletion variant of GSTT1, (p = 0.013, OR = 1.96). Maximum disease risk was observed in carriers of double deletions in GSTT1-GSTM1 (p = 0.017, OR = 2.42). The obtained results are discussed in reference to literary data on the risk of malignant brain tumor formation in children and adults.
Acta Naturae. 2010;2(4):58-65
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Modeling of the Full-Size 3D Structure of Human Chaperone Hsp70 and Study of Its Interdomain Interactions

Chernorizov K.A., Švedas V.K.


Hsp70 is a chaperone protein that participates in the folding of de novo synthesized proteins, protection of the hydrophobic regions of denaturated proteins, the regulation of apoptosis, the immune response, and several other cellular processes. Despite the large number of publications devoted to the functioning and structure of Hsp70, a reliable full-size 3D structure of this protein remains currently unavailable. Several probable full-size models of human Hsp70 have been constructed based on the structures of individual domains and their components from different organisms and using molecular modeling methodology. The stability of the obtained structures was studied using molecular dynamics. As a result of such an analysis, the most adequate model was selected. The model was built on the basis of Hsp70 elements from Bos Taurus and Caenorhabditis elegans. Using the method of steered molecular dynamics, the key salt bridges responsible for the interdomain interactions were identified: Arg171: Glu516 and Arg416: Glu218. Based on the performed molecular modeling, the scheme of the mechanism triggering ATP hydrolysis and leading to the separation of ATPase and the substrate-binding domains was proposed.
Acta Naturae. 2010;2(4):66-71
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Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

Reshetnikov R.V., Kopylov A.M., Golovin A.V.


The present work is devoted to the analysis of the G-quadruplex DNA structure using the bioinformatics method. The interest towards quadruplex DNAs is determined by their involvement in the functioning of telomeres and onco-promoters as well as by the possibility to create on their basis aptamers and nanostructures. Here, we present an algorithm for a general analysis of the polymorphism of the G-quadruplex structure from the data bank PDB using original parameters. 74 structures were grouped according to the following parameters: the number of DNA strands, the number of G-quartets, and the location and orientation of the connecting loops. Two quantitative parameters were used to describe the quadruplex structure: the twist angle between two adjacent quartets (analogous to that for the complementary pair in the duplex DNA) and the quartet planarity (an original parameter). The distribution patterns of these values are specific for each group of quadruplex structures and are dependent upon the type of connecting loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel quadruplex was used as a comparison template. The lateral loops introduce the strongest distortion into the structure of quadruplexes: the values of the twist angles are the lowest and are not typical for the other quadruplex groups. The loops of the diagonal type introduce much weaker deformation into quadruplexes; the structures with propeller loops are characterized by the optimum geometry of G-quartets. Hence, the correlation between the twist angle and the tension in the structure of quadruplex DNA is revealed.
Acta Naturae. 2010;2(4):72-81
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Biopharmacology of Enzyme Conjugates: Vasoprotective Activity of Supramolecular Superoxide Dismutase-Chondroitin Sulfate-Catalase Derivative

Maksimenko A.V., Vavaev A.V., Bouryachkovskaya L.I., Mokh V.P., Uchitel I.A., Lakomkin V.L., Kapelko V.I., Tischenko E.G.


Bienzyme conjugate was obtained by the covalent connection of superoxide dismutase with catalase through endothelial glycocalyx glycosaminoglycan - chondroitin sulfate (SOD-CHS-CAT). This SOD-CHS-CAT conjugate has vasoprotective activity in respect to platelet interactions, tonus of the ring arterial fragment of a rat blood vessel, as well as normalization of hemodynamic parameters in rats and rabbits in conditions of oxidative stress caused by the administration of hydrogen peroxide. The SOD-CHS-CAT conjugate had antiplatelet potential due to its antiaggregation action manifested through the combination of enzyme activities and an acquired supramolecular structure. The influence on arterial fragment tonus was equivalent for SOD and CAT in native and conjugated form. Blood pressure and heart rate were significant and effectively normalized with SOD-CHS-CAT conjugate in rats and rabbits (after hydrogen peroxide administration as a perturbance stimulus). We have discovered the possibility of using the antioxidant bienzyme conjugate in chronic prophylaxis. It is important for a real development of the oral form of the SOD-CHS-CAT conjugate. These results indicate that the development of enzyme conjugates can be medically significant, as a promising approach for the creation of new drugs.
Acta Naturae. 2010;2(4):82-94
pages 82-94 views

Prostate Cancer Proteomics" Database

Shishkin S.S., Kovalyov L.I., Kovalyova M.A., Lisitskaya K.V., Eremina L.S., Ivanov A.V., Gerasimov E.V., Sadykhov E.G., Ulasova N.Y., Sokolova O.S., Toropygin I.Y., Popov V.O.


A database of Prostate Cancer Proteomics has been created by using the results of a proteomic study of human prostate carcinoma and benign hyperplasia tissues, and of some human-cultured cell lines (PCP, http://ef.inbi.ras.ru). PCP consists of 7 interrelated modules, each containing four levels of proteomic and biomedical data on the proteins in corresponding tissues or cells. The first data level, onto which each module is based, is a 2DE proteomic reference map where proteins separated by 2D electrophoresis, and subsequently identified by mass-spectrometry, are marked. The results of proteomic experiments form the second data level. The third level contains protein data from published articles and existing databases. The fourth level is formed with direct Internet links to the information on corresponding proteins in the NCBI and UniProt databases. PCP contains data on 359 proteins in total, including 17 potential biomarkers of prostate cancer, particularly AGR2, annexins, S100 proteins, PRO2675, and PRO2044. The database will be useful in a wide range of applications, including studies of molecular mechanisms of the aetiology and pathogenesis of prostate diseases, finding new diagnostic markers, etc.
Acta Naturae. 2010;2(4):95-104
pages 95-104 views

A Novel Approach to the Development of Anticarcinogenic Vaccines

Glushkov A.N., Apalko S.V., Filipenko M.L., Matveeva V.A., Bakulina A.Y., Lunin V.G., Kostyanko M.V.


Human exposure to chemical carcinogens is an important etiological factor in cancer diseases. In this article, we will discuss a new approach to the development of anticarcinogenic vaccines. The main task in our research was to select a benzo[a]pyrene immunomimetic peptide considered as a hapten-specific component. For this purpose, we synthesized carcinogen-protein conjugates and prepared mono- and polyclonal antibodies to benzo[a]pyrene. Phage display technology was used to select the benzo[a]pyrene immunomimetic peptide, followed by an evaluation of the immunological properties of the obtained peptide. The obtained benzo[a]pyrene immunomimetic peptide could only simulate chemical carcinogens in the frame of the pIII protein. As a result, we prepared a recombinant protein composed of the benzo[a]pyrene immunomimetic peptide and pIII-encoding sequences. Using ELISA, we demonstrated that the recombinant protein specifically interacts with the anti-benzo[a]pyrene monoclonal antibody (mAB B2). Using molecular modeling, we predicted the 3-D structure of the mAB B2 active center and analyzed the characteristics of its interaction with different polycyclic aromatic hydrocarbons, as well as with the benzo[a]pyrene immunomimetic peptide. Thus, a comprehensive analysis of the results of the obtainment of hapten-specific components of anticarcinogenic vaccines allowed us to outline a strategy for future development in this direction.
Acta Naturae. 2010;2(4):105-111
pages 105-111 views

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