Table of Contents
Tortricid moths; Leafrollers; Psylla and mealybugs; Fruit flies; etc In this review, issues related to the nature of iPSCs are discussed and different methods of iPSC production are described. Often, closed-cell foam is compressed around the lower stem and inserted into an opening in the aeroponic chamber, which decreases labor and expense; for larger plants, trellising is used to suspend the weight of vegetation and fruit. As a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells KG-1A human myeloblastic leukemia cells and U human histiocytic lymphoma cells , which are normally resistant to Ad5 infection. This site was developed to try to provide a "one-stop shopping" portal for air quality tools. A large part of nutrient management is record keeping. The details of the proteasomal degradation of MBP are still unclear.
Abysheva 1 , A. Katanugina 1 , D. Baholdin 1 , G. Yanus 1,2 , A. Togo 1 , V. Moiseyenko 1,3 , S. Maximov 1 , V. Semiglazov 1 , E. Petersburg 4 City Oncological Hospital, St. The epidemiology of hereditary breast-ovarian cancer in Russia has some specific features. In addition, there are two other recurrent BRCA1 alleles: 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.
Dementyeva 1,2 , S. ABSTRACT 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. Reshetnikov 1,4 , A. Kopylov 2,3,4 , A. 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.
Two quantitative parameters were used to describe the quadruplex structure: 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 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. 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.
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. These results indicate that the development of enzyme conjugates can be medically significant, as a promising approach for the creation of new drugs. KEYWORDS antioxidant therapy, superoxide dismutase, catalase, chondroitin sulfate, vascular wall, oxidative stress, hydrogen peroxide, bienzyme conjugate, platelets, ring arterial fragment, hemodynamics, vasoprotective activity.
Glushkov 1 , S. Filipenko 1,2 , V. Matveeva 1,2 , A. Bakulina 1 , V. Lunin 3 , M. 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 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.
Marshak 2 , D. Mukha 1 , A. The results presented allow for the consideration of the chromatin diminution as a mechanism of rDNA copy number regulation. Chernorizov 1 , V. ABSTRACT 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: 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.
Kovalyov 1 , M. Kovalyova 1 , K. Lisitskaya 1 , L. Eremina 1 , A. Ivanov 1 , E. Gerasimov 1 , E. Sadykhov 1 , N. Ulasova 2 , O. Sokolova 2 , I. Toropygin 3 , V. 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 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. Logunov 1 , I.
Gitlin 2 , M. Shmarov 1 , P. Adzhieva 1 , A. Moroz 1 , N. Kostyukova 1 , L. Burdelya 2 , B. Naroditsky 1 , A. Gintsburg 1 , A. The activation of PRR by specific, highly conserved pathogen-associated molecular patterns PAMPs induces numerous immune reactions related both to innate and adaptive immunity.
Makarycheva 1 , E. Tsareva 1,2 , M. Sudomoina 1,2 , O. Kulakova 1,2 , B. Titov 1,2 , O. Bykova 3 , N. Kuzenkova 3 , A. Boiko 2 , O. Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS.
We investigated the association and linkage with MS of the following immune-system genes polymorphisms: For this purpose we used the transmission disequilibrium test TDT.
The group investigated was comprised of nuclear families of Russian ethnicity, each consisting of an affected offspring and his nonaffected parents.
Suplatov 1,2 , V. However, numerous enzymes that derive from a common ancestor and have undergone substantial functional alterations during natural selection appear not to have a sequence similarity acceptable for a statistically reliable comparative analysis.
At the same time, their active site structures, in general, can be conserved, while other parts may largely differ. Therefore, it sounds both plausible and appealing to implement a comparative analysis of the most functionally important structural elements — the active site structures; that is, the amino acid residues involved in substrate binding and the catalytic mechanism.
A computer algorithm has been developed to create a library of enzyme active site structures based on the use of the PDB database, together with programs of structural analysis and identification of functionally important amino acid residues and cavities in the enzyme structure.
The insight has revealed a high structural similarity of catalytic site areas, including the conservative organization of a catalytic triad and oxyanion hole residues, despite the wide functional diversity among the remote homologues compared. Gusev 2 , O. Zaitseva 2 , E. Lazareva 1 , G.
Onishchenko 1 , E. Kuznetsova 3 , A. Tkachev 4 , A. Feofanov 1,5 , M. ABSTRACT Engineered nanoparticles ENPs are now being used in many sectors of industry; however, the impact of ENPs on the environment still requires further study, since their use, recycling, and accidental spill can result in the accumulation of nanoparticles in the atmosphere, soil, and water. Plants are an integral part of ecosystems; hence their interaction with ENPs is inevitable.
It is important to understand the consequences of this interaction and assess its potential effects. The present research is focused on studying the effects of the industrial material Taunit, containing multi-walled carbon nanotubes MWNTs , on plants, and testing of its ability to penetrate into plant cells and tissues.
Taunit has been found to stimulate the growth of roots and stems and cause an increase in peroxidase activity in Onobrychis arenaria seedlings. MWNTs from Taunit were detected in the cells and tissues of seedling roots and leaves, implying the ability of MWNTs to penetrate into roots and accumulate there, as well as their ability to be transported into seedling leaves.
Thus, the changes in the physiological parameters of plants are associated not only with MWNT adsorption on the root surface, as previously believed, but also with their penetration, uptake and accumulation in the plant cells and tissues.
Ovsepyan 4 , D. Panchenkov 1,3 , E. Telegin 4 , N. Zhigalova 1 , E. Golubev 2 , T. Sviridova 5 , S. Matskeplishvili 2 , K. Skryabin 1 , U. In this work, a minimally invasive method for simulating myocardial infarction in mice is described in the Russian Federation for the very first time; the procedure is carried out by ligation of the coronary heart artery or by controlled electrocoagulation.
As a part of the methodology, a series of anesthetic, microsurgical and revival protocols are designed, owing to which a decrease in the postoperational mortality from the initial ECG confirms the development of large-focal or surface myocardial infarction. Postmortal histological examination confirms the presence of necrosis foci in the heart muscles of Altogether, the medical data allow us to conclude that an adequate mouse model for myocardial infarction was generated.
A further study is focused on the standardization of the experimental procedure and the use of genetically modified mouse strains, with the purpose of finding the most efficient therapeutic approaches for this disease. The living cell is a relatively simple, but at the same time very sophisticated biological system. After the sequencing of the human genome, molecular physiology has endeavored to investigate the systems of cellular interactions at a completely new level based on knowledge of the spatial organization and functions of receptors, their ligands, and protein-protein interactions.
In recent years, the achievements in molecular physiology have centered on the study of sensor reception mechanisms and intercellular data transfer, as well as the immune system physiology, amongst other processes. Petrin 1 , S. Arutyunov 1 , V. Tsarev 1 , L. Akulenko 1 , A. Zorina 2 , D. Rebrikov 3,4 , A. Rubanovich 3,4 , S. Borinskaya 1,4 , N. ABSTRACT Gingivitis and periodontitis are chronic inflammatory diseases of the periodontal tissue in humans caused by both environmental and genetic factors.
The human cytokine genes that regulate the immune response may play an important role in the development of these chronic inflammatory diseases. The aim of this study is to analyze the allele status of eight human cytokine genes and to associate it with the inflammation of periodontal tissue in humans. A total of unrelated males of Russian origin were studied. The influence of genetic factors on gingivitis may contribute to the understanding of the mechanisms of interaction between genetic and environmental factors in periodontal conditions, and to the identification of risk groups for effective prevention and treatment.
ABSTRACT Semiconductor quantum dots QDs are a new class of fluorophores with unique physical and chemical properties, which allow to appreciably expand the possibilities for the current methods of fluorescent imaging and optical diagnostics.
Here we discuss the prospects of QD application for molecular diagnostics of tumors ranging from cancer-specific marker detection on microplates to non-invasive tumor imaging in vivo. We also point out the essential problems that require resolution in order to clinically promote QD, and we indicate innovative approaches to oncology which are implementable using QD.
ABSTRACT Progressive loss of the telomeric ends of chromosomes caused by the semi-conservative mechanism of DNA replication is an important timing mechanism which controls the number of cells doubling. Telomerase is an enzyme which elongates one chain of the telomeric DNA and compensates for its shortening during replication. Therefore, telomerase activity serves as a proliferation marker.
Telomerase activity is not detected in most somatic cells, with the exception of embryonic tissues, stem cells, and reproductive organs. This is the primary reason why assays regarding the development of telomerase activity have attracted the attention of researchers.
Telomerase activity testing may be useful in the search for telomerase inhibitors, which have the potential to be anti-cancer drugs. Moreover, telomerase activation may play a positive role in tissue regeneration; e. All telomerase activity detection assays can be divided into two large groups: The methods discussed in this review are suitable for testing telomerase activity in different samples: An adequate study of the disease requires essential understanding of the molecular fundamentals of the pathogenesis.
In the present study, the structure and dynamics of the recombinant peptide corresponding to the APP fragment, GlnLys, which comprises the APP transmembrane domain with an adjacent N-terminal juxtamembrane sequence, were determined in the membrane mimetic environment composed of detergent micelles using NMR spectroscopy. Alekseenko 1,2 , M. Zinovyeva 1 , T. Vinogradova 1 , E. It develops from pigment-forming cells melanocytes and results in a high number of lethal outcomes.
The use of genetic constructs with the ability to specifically kill melanoma cells, but not normal cells, might increase the lifespan of patients, as well as improve their quality of life. One of the methods to achieve a selective impact for therapeutic genes on cancer cells is to utilize a transcriptional control mechanism using promoters that are specifically activated only in cancerous cells.
In this review, promoters of the genes that are preferentially expressed in melanoma cells are described. These promoters, and other highly melanoma-specific regulatory elements, reduce the unspecific expression of therapeutic genes in normal tissues. Moreover, cancer-specific promoters and their elements are advantageous for the development of universal anticancer drugs.
Examples of the use of double promoters that have a high potential as instruments in cancer gene therapy are also given in this review. Dykman 1 , N. ABSTRACT Functionalized gold nanoparticles with controlled geometrical and optical properties are the subject of intensive studies and biomedical applications, including genomics, biosensorics, immunoassays, clinical chemistry, laser phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and antigens, optical bioimaging and the monitoring of cells and tissues with the use of state-of-the-art detection systems.
This work will provide an overview of the recent advances and current challenges facing the biomedical application of gold nanoparticles of various sizes, shapes, and structures.
The review is focused on the application of gold nanoparticle conjugates in biomedical diagnostics and analytics, photothermal and photodynamic therapies, as a carrier for delivering target molecules, and on the immunological and toxicological properties. KEYWORDS gold nanoparticles; plasmon resonance; biosensors; biomedical diagnostics; photothermal and photodynamic therapy; targeted drug delivery; nanotoxicology.
Balanovsky 2,5 , A. Melnikov 3 , A. Lash-Zavada 3 , V. Tyazhelova 2 , V. Akhmetova 4 , O. Zhukova 2 , Yu. Shneider 2 , I. Borinskaya 2 , A. Marusin 1 , M. Spiridonova 1 , K. Simonova 1 , I. Khitrinskaya 1 , M.
Radzhabov 7 , A. Romanov 5 , O. Shtygasheva 8 , S. Balanovskaya 5 , A. Rybakova 3 , E. Khusnutdinova 4 , V. Puzyrev 1 , N. The degree of polymorphism and population diversity of microsatellite loci within the Power Plex system Promega in Russian populations; the distribution of alleles and genotypes within the populations of six cities and 11 ethnic groups of the Russian Federation; the levels of intra- and interpopulation genetic differentiation of population; genetic relations between populations; and the identification and forensic medical characteristics of the system of markers under study were determined.
Significant differences were revealed between the Russian populations and the U. A database of the allelic frequencies of 15 microsatellite loci that are used for DNA identification and forensic medical examination was created; the database has the potential of becoming the reference for performing forensic medical examinations in Russia. The spatial organization of genetic diversity over the panel of the STR markers that are used for DNA identification was revealed.
It represents the general regularities of geographical clusterization of human populations over various types of genetic markers. Samsonova 1,2 , K. Kudryashova 1 , A. ABSTRACT The antimicrobial peptide Ltc1-K and its derivates without one, two, then three N-terminal amino acid residues were studied based on the hypothesis backed by some experimental data that the hydrophobic N-terminal moiety of linear cationic antimicrobial peptides defines their haemolytic activity.
The synthesis of AICAR in Bacillus subtilis cells is controlled by the enzymes of purine biosynthesis; their genes constituting purine operon pur -operon. Reconstruction of purine metabolism in B. An insertion inactivating the gene purR that encodes the negative transcriptional regulator of the purine biosynthesis operon was introduced into the B.
Furthermore, the expression integrative vector carrying a strong promoter of the rpsF gene encoding the ribosomal protein S6 was designed. The modified purF and prs genes were inserted into the chromosome of the B. Extra amino acid residues are added to protein S6. The functional significance of these modifications has remained unclear. These modifications are not vital to the cells, and it is likely that they have regulatory functions.
This paper reviews all the known posttranslational modifications of ribosomal proteins in Escherichia coli. Certain enzymes responsible for the modifications and mechanisms of enzymatic reactions are also discussed. Various membrane-like media, partially those mimicking the conditions of multicomponent biological membranes, are used to study the structural and thermodynamic features that define the character of oligomerization of transmembrane helical segments.
The choice of the composition of the membrane-mimicking medium is conducted in an effort to obtain a biologically relevant conformation of the protein complex and a sample that would be stable enough to allow to perform a series of long-term experiments with its use.
However, a number of peculiarities place lipid bicelles closer to natural lipid bilayers in terms of their physical properties. Kulakov 1 , O. Boriskina 1 , D. ABSTRACT Periodontitis is a common disease that is considered to be a manifestation of the distortion of the ratio between the normal and conditionally pathogenic microflora of periodontal pockets. In this study, the ratio between the six most important periodontal pathogens and the total microflora of the periodontal pocket in healthy individuals and patients with varying severity of periodontitis was ascertained by quantitative real-time PCR.
It was ascertained that the relative content of Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythensis Bacteroides forsythus persistently develops in the total microflora of the periodontal pocket upon progressing periodontitis; this value is higher than that in the control group by more than two orders of magnitude upon a severe degree of chronic generalized periodontitis.
KEYWORDS ecosystem; habitat; periodontitis; periodontopathogenic microflora of periodontal pockets; quantitative polymerase chain reaction. However, after 20 min, the production of NO decreases; while the amplitude of Ca-signals remains high. Arkhipenko 1 , E. Petrova 1 , N. Nikitin 1 , A. Protopopova 2,3 , E. Dubrovin 3 , I. Yaminskii 2,3 , N. Rodionova 1 , O. Fedichev 1 , A. Vinnik 1 , J. Testa 3 , O. In vitro tests of the 14 top-rated ligands showed that compound Q12 displays the best ability to inhibit the proliferation of Dlx5 positive mouse lymphoma cells, which correlates with the down-regulation of c-myc expression.
Compound Q12 has low toxicity on normal human ovarian epithelial cells and mouse lymphoma cells with absent expression of Dlx5 , and can be used for further chemical optimization and for the development of novel, highly efficient cancer treatments. Gribova 1 , S. Tillib 2 , I. Shmarov 1 , D. Logunov 1 , L. Verkhovskaya 1 , B. ABSTRACT The present study is devoted to the feasibility of expressing the single-domain mini-antibody nanoantibody selected from the library of sequences of the variable domains of special single-stranded antibodies derived from an immunized camel, a gene of which was introduced into eukaryotic cells within a recombinant adenoviral vector.
A vector bearing the gene of a single-domain nanoantibody was obtained using the AdEasy Adenoviral Vector System Stratagene. This method of delivering the nanoantibody gene facilitates efficient expression of this gene and functional activity of the nanoantibody. The results obtained can be used to produce passive immunizing tools against pathogens or new-generation immunobiological antitoxic medication. Favorova 1 , E.
Goncharuk 1,2 , M. Mayzel 1 , D. Lesovoy 1 , V. Chupin 1 , E. Bocharov 1 , A. Arseniev 1 , M. FGFR3 plays an important role in human skeletal development. Mutations in this protein, including GlyArg or AlaGlu substitutions in the transmembrane TM region, can cause different disorders in bone development. The determination of the spatial structure of the FGFR3 TM domain in a normal protein and in a protein with single GlyArg and AlaGlu mutations is essential in order to understand the mechanisms that control dimerization and signal transduction by receptor tyrosine kinases.
The effective system of expression of eukaryotic genes in bacteria and the purification protocol for the production of milligram amounts of both normal TM fragments of FGFR3 and those with single pathogenic mutations GlyArg and AlaGlu, as well as their 15 N- and [ 15 N, 13 C]-isotope-labelled derivatives, were described.
The purification protocol involved immobilized metal affinity chromatography and cation- and anion-exchange chromatography, as well as the fusion protein cleavage with the light subunit of human enterokinase. Koliasnikov 1,2 , V. Egorov 2 , S. Lange 3 , R. ABSTRACT Recombinant immunoconjugates of marker enzymes with antigens or antibodies present considerably more advantages than those obtained by conventional methods of chemical synthesis; i.
Based on the pPICZ? B shuttle vector, we first managed to obtain a recombinant conjugate of key marker enzyme horseradish peroxidase HRP with Fab fragments of antibodies against atrazine.
The resulting genetic construction allows us to switch to any other antibody sequence, via the simple re-cloning of variable parts and an additional reporter enzyme.
Conjugates were successfully produced in the Pichia pastoris methylotrophic yeast expression system. The target activity of the conjugates both enzymatic and antigen-binding has been demonstrated by ELISA method. Dzyubenko 1,2 , D. Bagrov 1 , G. Maksimov 1 , S. Shram 2 , K. The present work describes an examination of the arrangement and mechanical properties of cytoskeleton of living astrocytes using atomic force microscopy AFM.
The experiments were performed with an organotypic culture of dorsal root ganglia DRG obtained from a chicken embryo. The cells were cultivated on a gelatinous substrate and showed strong adhesion. AFM allows one to observe cytoskeleton fibers, which are interpreted as actin filaments and microtubules. This assumption is supported by confocal microscopy fluorescence imaging of?
Thus, the data obtained indicate that AFM is a promising method to study neural cells cytoskeleton integrity and arrangement in in vitro models of neurodegeneration. Logunov 1 , D. Shchebliakov 1 , M. Shmarov 1 , E. Khodunova 3 , I. Galtseva 3 , R. Belousova 2 , B. As a result of the fiber modification, the adenovirus can efficiently deliver the genetic information to bone marrow leukocytes and the tumor blood cells KG-1A human myeloblastic leukemia cells and U human histiocytic lymphoma cells , which are normally resistant to Ad5 infection.
The expression of interleukin-2 in CAR-negative bone marrow leukocytes The fiber-modified adenovirus can be used as a vector for the efficient gene delivery of interleukin-2 to human normal and tumor hematopoietic cells.
Agapkina 1 , M. Inhibitors of HIV-1 integration have been under development for over 10 years; yet, only one integration inhibitor, raltegravir, has been approved for clinical use so far. Unfortunately, the clinical use of raltegravir results in the development of viral resistance among some patients. Several more HIV-1 integration inhibitors are undergoing clinical trials at the moment.
However, the structure and mechanism of action of those are similar to raltegravir, which results in the emergence of cross resistance with raltegravir. The present review is focused on the history of the development and clinical trials of raltegravir and its analogues, the problems connected with the emergence of viral resistance to integration inhibitors, and the prospect of their future clinical use.
ABSTRACT Deregulation of the expression of the genes that are involved in the control of the cell cycle impairs cellular differentiation and leads to cell death. This process can result in uncontrollable cell proliferation and, subsequently, cancer development. The obtained data indicate that the CCNB1 and PKC genes can be used as targets in the development of drugs for neuroblastoma treatment. Posukh 2 , N. Barashkov 3 , S. Fedorova 3 , F. Teryutin 3 , V.
Akhmetova 1 , I. Khidiyatova 1 , R. Khusainova 1 , S. Lobov 1 , E. The spectrum and prevalence of the GJB2 gene mutations are specific to populations of different ethnic origins.
The prevalence of the c. The haplotype analysis of chromosomes with the c. The peculiarities of the selection of escort aptamers are discussed in this review. The methods used in selection of escort aptamers via the SELEX technique are considered, including selection against isolated cell-surface proteins, cell fragments, living eukaryotic cells, and bacteria.
Particular attention is given to the design and chemical modification of escort aptamers. The different fields of application of escort aptamers are described, including the targeted delivery of siRNAs, nanoparticles, toxins, and photoagents, as well as the identification of specific cell markers and the detection or isolation of cells of a definite type.
The potential for the application of escort aptamers in the development of new therapeutic agents and diagnostic systems is also discussed. Mesenchymal stem cells MSCs are part of the most important population of adult stem cells. Bone marrow-derived MSCs have been believed to play the role of a source of cells for the renewal and repair of connective tissues, including bone, cartilage and adipose tissues.
Cells similar to bone marrow-derived MSCs have now been identified in all postnatal tissues. In our opinion, MSCs provide the connection between the blood-vascular, immune, endocrine, and nervous systems and tissue-specific stem cells in the body. Alekseeva 1,2,3 , S. Savin 2,3 , V. FDH consists of two identical subunits and contains neither prosthetic groups nor metal ions. This type of FDH was found in different microorganisms including pathogenic ones , such as bacteria, yeasts, fungi, and plants.
Formate dehydrogenase activity was first discovered as early as in in plant; however, until the past decade FDHs from plants had been considerably less studied than the enzymes from microorganisms. This review summarizes the recent results on studying the physiological role, properties, structure, and protein engineering of plant formate dehydrogenases.
Khramova 1 , M. L Semenova 1 , I. Saburina 2 , N. Nowadays, numerous protocols exist which provide a neural differentiation of the stem cells transplanted into the retina. However, questions concerning the functional replacement of the missing retinal neurons by transplanted cells thus far remain unanswered.
This technique enables a detailed characterization of cell behavior post-transplantation. MMSCs are also shown to form synapses up to 2. Following electrical stimulation 20V, 0. Shmigol 1 , V. Sysolyatina 2 , E. Nagurskaya 2 , S.
Ermolaeva 2 , A. The following is already known about MC Secondly, singlet oxygen can only be photogenerated by MC monomers. In the present work, we studied the effect of MC in the aggregated state on the rate of photosensitized inactivation of Staphylococcus aureus and Pseudomonas aeruginosa. To this end, bacteria either in MCcontaining distilled water or in a 0.
The results show that, in the presence of salt, the aggregation of MC greatly increases the efficiency of the MCphotosensitized inactivation of P. In the presence of salt, the rates of P. Our results suggest that a salt-induced photosensitization mechanism can switch from the singlet oxygen to the free-radical pathway.
Suzdaltseva 2 , K. Goryunov 1 , N. Kalinina 1 , V. Sysoeva 1 , V. Control of immune cell activation could be of significant benefit for regenerative medicine and the treatment of patients with autoimmune and degenerative diseases. It is a proven fact that MCSs multipotent mesenchymal stromal cells are capable of suppressing immune responses via the inhibition of dendritic cell maturation and via the restraining of the T, B, and NK cell function in the course of autoimmune diseases and various forms of inflammation.
MSCs can be isolated easily from almost every type of tissue or organ and subsequently expanded in vitro. These cells are self-renewable and can be differentiated into various cell types of mesenchymal lineage. The current review contains a collection and critical analysis of data regarding the molecular mechanisms responsible for cross-talk between immune cells and MSCs.
Some of these mechanisms can be used for the development of new practical approaches for the treatment of autoimmune diseases. Prokofjeva 1 , P. Spirin 1 , D. Yanvarev 1 , A. Ivanov 1 , M. Novikov 2 , O. Stepanov 1 , M. Gottikh 3 , S. Kochetkov 1 , B.
Fehse 4 , C. Stocking 5 , V. We have described in detail a system we designed that is based on lentiviral vectors Prokofjeva et. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form. Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing.
Tyulkina 1 , E. Skurat 1 , O. Frolova 2 , T. Komarova 2 , E. Karger 2 , I. The expression, based on the hybrid viral vectors, is genetically safe, since the systemic transport and formation of infective viral particles are blocked. The vectors can be used for the presentation of foreign peptides including epitopes of human pathogens on the surface of the VLP. The epitopes of the M2 influenza virus protein were not eliminated during the process of accumulation, polymerization and purification of chimeric VLP AltMV, providing evidence of the stability of chimeric VLP with C-terminal heterologous epitopes.
It is shown that TLRs play an essential role in the immune resistance of an organism to bacterial and viral infections. The binding of TLR to its own ligands results in the activation of several adapter molecules and kinases, inducing the activation of the main pro-inflammatory transcriptional factors, which in turn induce the activation of the main pro-inflammatory transcriptional factors.
This activation results in the development of both the innate immune response triggered by the enhanced expression of a number of pro-inflammatory cytokines and antimicrobial peptides and that of the adaptive immune response, via the activation of dendritic cells and enhancement of antigen presentation, etc. The ability of TLR agonists to bolster the immune reaction makes them promising for use in the therapy of infectious diseases and in the chemotherapy of malignant neoformations.
However, different TLR ligands may have either antitumor activity lipopolysaccharide, imiquimod, CpG or, conversely, could beef up the resistance of tumor cells to apoptosis, stimulating their proliferation under certain conditions lipopolysaccharide, lipopeptide. It has been shown that the TLR2-dependent signalling pathway in the myelomonocytic mouse leukaemia cell line WEHI-3B leads to the constitutive activation of the transcriptional factor NF-kB, suppression of apoptosis in tumor cells, and progression of myelomonocytic mouse leukaemia in vivo, upon the addition of TLR2 agonist synthetic lipopeptide Pam2CSK4 or following the infection of tumor cells with Mycoplasma arginini.
Khomutov 1 , S. Kochetkov 1 , S. Kotovskaya 2,3 , V. Levofloxacin the optically active form of ofloxacin is one of the most promising fluoroquinolone drugs, and its antibacterial activity is substantially higher than the activity of other drugs of the fluoroquinolone family. Earlier, in the Postovsky Institute of Organic Synthesis, UB RAS, an original method of levofloxacin synthesis was developed, and now the pilot batch of the drug is being prepared.
Bacterial DNA gyrase is a specific target of fluoroquinolones; hence, the study of the enzyme-drug interaction is of theoretical and practical importance. Moreover, the parameters of DNA gyrase inhibition may serve as a criterion for drug quality. Here, we present the results of studying the interaction of DNA gyrase with a number of fluoroquinolones and their analogs: The importance of two structural elements of the levofloxacin molecule for the efficiency of the inhibition is revealed.
The data obtained may be useful for the design of new drugs derived from levofloxacin. In mammals, the onset of mitosis is accompanied by the inhibition of rRNA synthesis, nucleolus disassembly, and the migration of pre-rRNA to the cytoplasm. However, the precise role of cytoplasmic pre-rRNA in mitosis remains unclear, and no comparative analysis of its different forms at consequent mitotic stages has thus far been performed.
The results reveal that all types of pre-rRNA appear in the cytoplasm at the beginning of mitosis, following the breakdown of the nucleolus and nuclear envelope. However, not all pre-rRNA are transported by chromosomes from maternal cells into daughter cells. At the end of mitosis, all types of pre-rRNA and 28S rRNA can be visualized in nucleolus-derived foci NDF , structures containing many proteins of mature nucleoli the appearance of which indicates the commencement of nucleologenesis.
Altogether, the results of this study strengthen the hypotheses that postulate that different forms of pre-rRNA may play various roles in mitosis, and that NDF can be involved in the maturation of pre-rRNA, remaining preserved in the cytoplasm of dividing cells.
Deyev 1 , D. Rzhevsky 2 , A. Berchatova 1 , O. Serova 1 , N. Popova 1 , A. Murashev 2 , A. The development of alkalosis under various pathological conditions poses an immediate threat to human life.
Understanding the physiological mechanisms of alkalosis compensation may stimulate the development of new therapeutic approaches and new drugs for treatment. It was previously shown that the orphan insulin receptor-related receptor IRR is activated by mildly alkaline media. In this study, we analyzed mutant mice with targeted inactivation of the insrr gene encoding IRR, and revealed their phenotype related to disorders of the acid-base equilibrium. Higher concentrations of bicarbonate and CO 2 were found in the blood of insrr knockout mice in response to metabolic alkalosis.
Semenov 1 , E. Kuligina 1 , O. Koval 1 , I. Rabinov 1 , Y. Trifonova 1 , E. Eremina 2 , F. Urnov 3 , V. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics.
Telomerase maintains the stability of the genome in eukaryotic cells by replicating chromosomal ends. The structural and functional investigation of the telomerase complex is significantly restricted due to difficulties connected with the isolation of its main catalytic subunit in recombinant form.
Herein, we describe a method developed for the isolation of the recombinant telomerase reverse transcriptase from thermotolerant yeast Hansenula polymorpha.
The difference could presumably be attributed to the differences in the biochemical composition of the cell plasma membrane. As a result of the heating of HeLa cells, the zeta potential shifted towards more negative voltages by 4. An increase in the zeta potential correlated with an increase in the content of phosphatidylserine on the cell surface, which is considered to be an early marker of apoptosis.
The DLS technique was also used to study the interactions between the cells and membranotropic polymers, such as polycations and nonionogenic Pluronic L Velsher 1,2 , A.
Byakhov 1,2 , T. Duditskaya 1,2 , D. ABSTRACT Presented herein is a clinical study comprising 48 patients 42 men and 6 women of working age 40—70 years , all of whom are suffering from locally advanced oropharyngeal cancer. A modern approach is applied to treat these patients, i. The use of gefitinib causes an antitumor effect in Egorova 1 , A. Ramonova 1 , S. Bogorodski 2 , V. Popov 2 , I. Agapov 1,3 , M. ABSTRACT Biodegradable polylactide microparticles with encapsulated cytotoxic protein viscumin were obtained via the ultrasound-assisted supercritical fluid technique.
The time course of viscumin release from microparticles was studied using an immunoenzyme test system with anti-viscumin monoclonal antibodies. It was found that Importantly, the method of ultrasonic dry supercritical fluid encapsulation failed to alter both the cytotoxic potency and the immunochemical properties of the encapsulated viscumin.
Thus, this procedure can be used to generate biodegradable polylactide microparticles with encapsulated bioactive substances. Borinskaya 1 , Zh. Kozhekbaeva 1 , A. Zalesov 1,2 , E. Olseeva 3 , A. Maksimov 4 , S. Kutsev 5 , M. Garaev 6 , A. Rubanovich 1 , N. However, data relating to the protective effect for CCR5del32 heterozygous individuals have been contradictory.
The frequency of the CCR5del32 allele in population control cohorts was compared with that of a group of children 27 Kalmyks and 50 Russians infected by G-subtype HIV-1 in a nosocomial outbreak. The frequency of the CCR5del32 allele was shown to be lower among the infected children in comparison with that of the control group; however, the difference was small and statistically insignificant.
Similar results were obtained in a number of earlier studies. The insignificance of the small differences could be a result of one of two reasons. In this case, there would be no differences even if the infected cohort is enlarged. Prior to this study, no data of the type or any conclusions had been published for Caucasians.
The features of the meta-analysis influencing the threshold level and the statistical validity of the effects are being discussed. Solopova 1 , L. Pozdnyakova 1 , N.
Varlamov 1 , M. Bokov 1 , E. Yagudin 2 , P. However, the mechanisms of this interference remain poorly understood. We studied the conformation of angiotensins 1, 2 and 3, which are produced naturally in a sequential fashion from a precursor protein angiotensinogen and contain an identical peptide core structure.
Using the example of angiotensins 1, 2 and 3, it was shown that similar amino acid sequences may have significant conformational differences in various molecules. In order to assess the conformational changes, we developed a panel of high-affinity mouse monoclonal antibodies against angiotensins 1, 2 and 3 and studied their cross-reactivity in indirect and competitive ELISAs.
It was found that the conformations of inactive angiotensin1 and the corresponding fragment of angiotensinogen are similar; the same is true for the conformations of active angiotensins 2 and 3, whereas the conformations of homologous fragments in the active and inactive angiotensins differ significantly.
Volodina 2 , E. Sebentsova 1 , N. Glazova 1 , D. Manchenko 2 , L. Inozemtseva 1 , O. Dolotov 1 , L. Andreeva 1 , N. Kamensky 2 , N. ABSTRACT Adverse experience during the early postnatal period induces negative alterations in physiological and neurobiological functions, resulting in long-term disorder in animal behavior.
The aim of the present work was to study the long-lasting effects of chronic neonatal stress in white rats and to estimate the possibility of their correction using Semax, an analogue of ACTH fragment 4— Early neonatal isolation was used as a model of early-life stress.
Rat pups were separated from their mothers and littermates for 5 h daily during postnatal days 1— The pups of the control group were left undisturbed with the dams. The other animals received intranasal vehicle injections daily at the same time points. It was shown that neonatal isolation leads to a delay in physical development, metabolic disturbances, and a decrease in the corticosterone stress response in white rats.
These changes were observed during the first two months of life. Semax administration weakened the influence of neonatal isolation on the animals, body weight , reduced metabolic dysfunction, and led to an increase in stress-induced corticosterone release to the control values.
So the chronic intranasal administration of Semax after termination of the neonatal isolation procedure diminishes the negative effects of neonatal stress. Orlova 1,2 , S. Kovnir 1,2 , I. Yuriev 2 , A. Gabibov 1 , A. Development of a biosimilar recombinant FVIII requires the creation of a highly productive clonal cell line and generation of monoclonal antibodies suitable for affinity purification of the product.
Methotrexate-driven transgene amplification of genetic cassettes that code full-length and truncated variants of FVIII under the control of the CMV promoter was studied. The transgene amplification procedure was sufficient for a twofold increase of the expression level in the transfected cells pool and subsequent selection of the clonal line, stably producing truncated FVIII at the level of 0.
The producer cell line and monoclonal antibodies obtained are sufficient for the development of upstream and downstream processes of biosimilar FVIII production.
ABSTRACT In this paper, we shall consider the main evolutionary stages that occurred within the field of physicochemical biology during the 20th century, following the determination of the tertiary structure of DNA by Watson and Crick and the subsequent successes in the X-ray structural analysis of biopolymers. KEYWORDS DNA structure; enzyme active sites; unstructured proteins; dynamics of biochemical processes; single molecule studies of enzymatic processes and biopolymer tertiary structure formation.
Malyavko 1 , Yu. Naraikina 3 , M. The telomere length specifies the number of divisions a cell can undergo before it finally dies i. For example, telomerase is activated in embryonic cell lines and the telomere length is maintained at a constant level; therefore, these cells have an unlimited fission potential.
Stem cells are characterized by a lower telomerase activity, which enables only partial compensation for the shortening of telomeres. Somatic cells are usually characterized by the absence of telomerase activity. Telomere shortening leads to the attainment of the Hayflick limit, the transition of cells to a state of senescence. The cells subsequently enter a state of crisis, accompanied by massive cell death. The surviving cells become cancer cells, which are capable both of dividing indefinitely and maintaining telomere length usually with the aid of telomerase.
Aggregate stability is an indicator of organic matter content, biological activity, and nutrient cycling in soil. Generally, the particles in small aggregates mm. These large aggregates are more sensitive to management effects on organic matter, serving as a better indicator of changes in soil quality. Greater amounts of stable aggregates suggest better soil quality.
When the proportion of large to small aggregates increases, soil quality generally increases. Stable aggregates can also provide a large range in pore space, including small pores within and large pores between aggregates.
Pore space is essential for air and water entry into soil, and for air, water, nutrient, and biota movement within soil. Large pores associated with large, stable aggregates favor high infiltration rates and appropriate aeration for plant growth.
Pore space also provides zones of weakness for root growth and penetration. Surface crusts and filled pores occur in weakly aggregated soils. Surface crusts prevent infiltration and promote erosion; filled pores lower water-holding and air-exchange capacity and increase bulk density, diminishing the conditions for root growth. Specific problems that might be caused by poor function: Aggregate stability is critical for infiltration, root growth, and resistance to water and wind erosion.
Unstable aggregates disintegrate during rainstorms. Dispersed soil particles fill surface pores and a hard physical crust can develop when the soil dries. Infiltration is reduced, which can result in increased runoff and water erosion, and reduced water available in the soil for plant growth. A physical crust can also restrict seedling emergence. Wind normally detaches only loosely held particles on the soil surface, but as blowing soil particles are accelerated by the wind they hit bare soil with sufficient energy to break additional particles loose from weakly aggregated soil.
This action increases the number of particles that can be picked up by the wind and abrade a physically-unprotected soil surface. What you can do: You can improve the aggregate stability of your soil by increasing levels of organic matter or applying specialized chemical compounds, such as anionic polyacrylamide PAM.
Practices that keep soil covered physically protect it from erosive forces that disrupt aggregation, while also building organic matter. Any practice that increases soil organic matter, and consequently biological activity, improves aggregate stability.
However, it can take several growing seasons or years for significant organic matter gains.