Whole genome comparative analysis of four Georgian grape cultivars.

Grapevine is the one of the most important fruit species in the world. Comparative genome sequencing of grape cultivars is very important for the interpretation of the grape genome and understanding its evolution. The genomes of four Georgian grape cultivars-Chkhaveri, Saperavi, Meskhetian green, and Rkatsiteli, belonging to different haplogroups, were resequenced. The shotgun genomic libraries of grape cultivars were sequenced on an Illumina HiSeq. Pinot Noir nuclear, mitochondrial, and chloroplast DNA were used as reference. Mitochondrial DNA of Chkhaveri closely matches that of the reference Pinot noir mitochondrial DNA, with the exception of 16 SNPs found in the Chkhaveri mitochondrial DNA. The number of SNPs in mitochondrial DNA from Saperavi, Meskhetian green, and Rkatsiteli was 764, 702, and 822, respectively. Nuclear DNA differs from the reference by 1,800,675 nt in Chkhaveri, 1,063,063 nt in Meskhetian green, 2,174,995 in Saperavi, and 5,011,513 in Rkatsiteli. Unlike mtDNA Pinot noir, chromosomal DNA is closer to the Meskhetian green than to other cultivars. Substantial differences in the number of SNPs in mitochondrial and nuclear DNA of Chkhaveri and Pinot noir cultivars are explained by backcrossing or introgression of their wild predecessors before or during the process of domestication. Annotation of chromosomal DNA of Georgian grape cultivars by MEGANTE, a web-based annotation system, shows 66,745 predicted genes (Chkhaveri-17,409; Saperavi-17,021; Meskhetian green-18,355; and Rkatsiteli-13,960). Among them, 106 predicted genes and 43 pseudogenes of terpene synthase genes were found in chromosomes 12, 18 random (18R), and 19. Four novel TPS genes not present in reference Pinot noir DNA were detected. Two of them-germacrene A synthase (Chromosome 18R) and (-) germacrene D synthase (Chromosome 19) can be identified as putatively full-length proteins. This work performs the first attempt of the comparative whole genome analysis of different haplogroups of Vitis vinifera cultivars. Based on complete nuclear and mitochondrial DNA sequence analysis, hypothetical phylogeny scheme of formation of grape cultivars is presented.

A COMPUTER MODELING STUDY OF BINDING PROPERTIES OF CHIRAL NUCLEOPEPTIDE FOR BIOMEDICAL APPLICATIONS.

Nucleopeptides often show interesting properties of molecular binding that render them good candidates for development of innovative drugs for anticancer and antiviral therapies. In this work we present results of computer modeling of interactions between the molecules of hexathymine nucleopeptide (T6) and poly rA RNA (A18). The results of geometry optimization calculated using Hyperchem software and our own computer program for molecular docking show that molecules establish stable complexes due to the complementary-nucleobase interaction and the electrostatic interaction between the negative phosphate group of poly rA and the positively-charged residues present in the cationic nucleopeptide structure. Computer modeling makes it possible to find the optimal binding configuration of the molecules of a nucleopeptide and poly rA RNA and to estimate the binding energy between the molecules.

Environmental safety risk research.

Pilot epidemiology survey has been conducted with the aim to study the effect of occupational factors on workers in the Zestafoni Manganese Processing Plant. Overall 102 workers have been surveyed. They were selected from the list circulating in the plant ambulance. Selected workers have been surveyed through a standard questionnaire. The survey revealed that prevalence of such diseases as Radiculitis, hypertension, bronchitis, gastritis, and ulcer, ocular and nasal-pharyngeal diseases are high among the workers of the Zestafoni Processing Plant. Study results have shown direct correlation between development of diseases and distance residence from the plant. Prevalence of hypertension, ocular and nasal-pharyngeal diseases, bronchitis was higher among workers lived within distance of 2-5 kilometers from the plant. Positive correlation revealed between length of job and prevalence of bronchitis, ocular diseases, Radiculitis, hypertension, cardiac diseases and gastritis. Among plant workers revealed high prevalence of symptoms characterized the central nervous system disorders such as sleep disorder, insomnia, backache, walking disorders. The results proven correlation between occupational factors and diseases and different symptoms.

[Chronic persistent infections of anterior segment of eye: clinico-laboratory aspects].

AIM: Improvement of therapy of chronic ophthalmic infectious diseases during assessment of functioning of different arms of immune system. MATERIALS AND METHODS: Three hundred and fifty patients with chronic red-eye syndrome were tested by immunofluorescence assay on the presence of antigens of herpesviruses, adenoviruses and Chlamydia in samples from conjunctiva. Expression of 11 cytokines' genes was measured in peripheral blood mononuclear cells by reverse transcription polymerase chain reaction. Production of IFN-alpha and IFN-gamma, levels of serum and spontaneously produced interferon as well as level of susceptibility to the range of immunomodulating preparations were measured during study of interferon status in whole blood cells. Study of parameters of cytokine, interferon and immune statuses was performed in 70 patients. Counts of T- and B-lymphocytes, T-helpers, NK-cells as well as level of circulating immune complexes were measured during study of immune status. RESULTS: Antigens of herpes simplex virus and adenoviruses were detected in samples from conjunctiva in 27% (95 persons) and 36% (126 persons) of patients respectively. Enhanced level of expression of several cytokines (IL-2, IL-4) in studied patients compared with healthy volunteers was observed. Expression levels of IL-12 and TNF-alpha mRNAs were, in opposite, in 2 - 3 times lower. Disorder of IFN-alpha and IFN-gamma synthesis on post-transciption level was observed in 60 - 90% of patients. Decrease of absolute numbers of total T-lymphocytes and T-helpers as well as increase of absolute number of NK-cells was noted in 20%, 25%, and 27% of patients respectively. CONCLUSION: Assignment of individually oriented antiviral, antibacterial and immunomodulating therapy allowed to mitigate intensity of clinical symptoms in 30 -60% of patients with chronic persistent infections of anterior segment of eye.

[Conformational transitions in myosin cross-bridges during the mechanochemical act]. / O konformatsionnykh perekhodakh v miozinovykh mostikakh v protsesse me khanokhimicheskogo akta.

The investigations of the molecular bases of muscle contraction posed the following question: in which part of the myosin cross-bridge, the head or the fibrillar part, the conformational changes occur that lead to the generation of force. The paper deals with experimental and theoretical data that are in some way related to the solution of this question. Based on the analysis of recent data, an alternative pattern of ATP hydrolysis-coupled structural alternations in the myosin bridge during the mechanochemical act is proposed.

[Superspiralized alpha-spiral. 1. Distribution of nonpolar residues in the hydrophobic core]. / Superspiralizovannaia alpha-spiral'. 1. Raspredelenie nepoliarnykh ostatkov v gidrofobnom stvole.

Distribution of nonpolar residues in the hydrophobic core (a and d positions) of fibrillar proteins in the form of alpha-helical coiled-coil has been studied. It was shown that concentration of large nonpolar residues (Phe, Trp) in a and d positions would not stabilize this structure; amino acids with smaller nonpolar side chains (Leu, Ala, Val, Ile, Met) are preferable, and Leu is the most preferred amino acid in the hydrophobic core; nonpolar residues with branching at the C beta atom (Val, Ile) prefer the a to the d position. The results obtained show that the distribution of nonpolar residues in the a and d positions of the alpha-helical coiled-coil cannot be only accounted for hydrophobic interactions between nonpolar residues of adjacent helices in the considered structure.

[Superspiralized alpha-spiral. 2. Conformational analysis of a model fragment of the dual-chain parallel superspiralized alpha-spiral]. / Superspiralizovannaia alpha-spiral'. 2. Konformatsionnyi analiz model'nogo framenta dvukhtsepochechnoi parallel'noi superspiralizovannoi superspiralizovannoi alpha-spirali.

To estimate the role of nonbonded interactions in the folding of the hydrophobic core of a two-stranded parallel alpha-helical coiled-coil, a conformational analysis was carried out for the model fragment: [formula: see text] with a 2-fold symmetry axis running between the parallel helices, where X denotes nonpolar residues Ala, Leu, Val, Ile, Met, Phe, Tyr, Trp. For every residue X, the energy of interaction between two helices and the complete conformational energy, were mapped as functions of (R, nu 0) where R is radius of coiled coil and nu 0 is the angle that determines orientation of two helices relatively to each other. It was shown that when Phe, Tyr, Ile and Val were located in the d position of repeating heptapeptide, there appeared certain steric restrictions. The obtained results allow one to explain certain peculiarities in the distribution of nonpolar residues in coiled-coil structure in fibrous proteins, i.e., a high percentage of Leu in the hydrophobic core of these structures; preference of a position for Val and Ile compared to d position, and a rare occurrence of Phe in d position.

[Transitions of the left poly-L-proline II helix-right alpha helix type in the regions of myosin subfragment S2 of cross-striated muscle as a possible conformational basis for a mechanical-chemical act]. / Perekhody tipa levaia spiral' poli-L-prolin II-pravaia alpha-spiral' v uchastkakh subfragmenta S2 miozina poperechnopolosatoi myshtsy kak vozmozhnaia konformatsionnaia osnova mekhano-khimicheskogo akta.

Local conformational states of fibrous fragments of myosin molecules from striated muscle have been studied. Analysis of the amino acid sequences of the rat embryonic skeletal muscle myosin heavy chain and the nematode myosin heavy chain have been performed with the aim to estimate the influence of electrostatic interactions on secondary structure stability of these fragments. The heterogeneity of stability of alpha-helical conformation along the fibrous fragment have been found on the basis of estimation of interaction between side group charges and between side group charges and main chain charges. Periodically located short sections have been found in the N-terminal half of the myosin rod where clusters of Asp and Glu destabilize alpha-helical structure being ionized. Changes of the distribution of charges near the latter sections bring about conformational transitions from left-handed polyproline II helix to right alpha-helix or vice versa. The new scheme of orientation of fibrous part of the cross-bridge in relation to the thick filament for various stages of muscle contraction process suggests asynchronous character of transitions in the different sites. It may be proposed that existence of alteration left- and right-helical fragments in N-terminal half of fibrous part of heavy myosin chain determines zigzag form of this part of myosin molecule in resting muscle. A model of the cross-bridge movement in the course of ATP hydrolysis has been suggested.

[Prospects for realizing a structure of the spiral-turn-spiral type in a "zinc finger"]. / O vozmozhnosti realizatsii u "tsinkovogo pal'chika" struktury tipa spiral'-izgib-spiral'.

The realization of two models for Zn-finger structure--DNA-binding domain was estimated by taking into account the geometric and energetic requirements of polypeptide chain folding. The following structures were taken as models: antiparallel beta-structure and helix-turn-helix motif. The latter hasn't been considered earlier as the possible structure for Zn-finger. The preference was given to the above-mentioned models on the base of the available experimental data. It was shown that the helix-turn-helix motif for which the angle between axes of alpha-helices doesn't exceed 40 degrees cannot be excluded from the list of the assumed models for Zn-finger. There is a suggestion that the helix-turn-helix motif is likely to be characteristic for the majority of DNA-binding domains in proteins.

[Cyclic conformation of parallel polypeptide chains closed by cross bridges]. / O konformatsiiakh polipeptidnykh parallel'nykh tsepei, zamknutykh v tsikl poperechnymi mostikami.

The method of possible conformations calculations for cyclic structures, formed by two (or more) identical parallel polypeptide chains, closed by cross bridges has been elaborated. The algorithm is necessary for rigorous conformational analysis of cyclic regions in immunoglobulin, fibronectin and myosin.

[Two possible conformations of the repetitive site of the immunoglobulin G3 hinge region]. / O dvukh vozmozhnykh konformatsiiakh povtoriaiushcheisia chasti sharnirnogo uchastka immunoglobulina G3.

Conformational analysis of immunoglobulin G3 (IgG3) hinge region repeating part was performed. In approximation of backbone regular conformations for the case of C2 symmetry (the symmetry axis is perpendicular to S-S bridges and passes through their midpoint) on the basis of total analysis of ring geometry possibilities and estimation of steric conditions, the existence of two conformations with n = 3 (3(10) helix type and polyproline II type) was inferred. A possible role of these conformations in the immunoglobulin functioning was discussed.