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The study of immune response and inflammation gene polymorphisms in a genogeographic context is relevant in the study of human populations. Here, in the indigenous populations of Siberia the frequencies of polymorphic variants -174G/C (rs1800795) and -572C/G (rs1800796) of the IL6 gene encoding the proinflammatory cytokine IL-6 were determined. For the first time, it was shown that the frequencies of the -174G and -572C alleles, which determine increased inflammatory response and are also associated with several diseases were statistically significantly higher in ethnic groups of Buryats, Teleuts, Yakuts, Dolgans and Tuvinians than in Russians living in Siberia. These values were in the intermediate position between those in the European and East-Asian groups. We hypothesize an adaptive role of these IL6 genetic variants in human settlement from Africa to the Eurasian continent. However, due to the departure from the traditional way of life and the increasing anthropogenic environmental pollution, the risk of diseases whose pathogenesis is based on inflammation in indigenous Siberian populations is likely increased.

Mycobacterium tuberculosis cells contain two apurinic/apyrimidinic (AP) endonucleases, endonuclease IV (MtbEnd) and exonuclease III (MtbXthA), the former playing a dominant role in protecting mycobacterial DNA from oxidative stress. Mycobacterial endonuclease IV substantially differs from its homologs found in Escherichia coli and other proteobacteria in a number of conserved positions important for DNA binding and AP site recognition. The M. tuberculosis end gene was cloned, and recombinant MtbEnd purified and characterized. The protein efficiently hydrolyzed DNA at the natural AP site and its 1'-deoxy analog in the presence of divalent cations, of which Ca^(2+), Mn^(2+), and Co^(2+) supported the highest activity. Exonuclease activity was not detected in MtbEnt preparations. The pH optimum was estimated at 7.0-8.0; the ionic strength optimum, at ~50 mM NaCl. Enzymatic activity of MtbEnd was suppressed in the presence of methoxyamine, a chemotherapeutic agent that modifies AP sites. Based on the results, MtbEnd was assumed to provide a possible target for new anti-tuberculosis drugs.

Compelling evidence demonstrates chromosome 8q24 as a prostate cancer susceptibility locus. In present work we studied whether the common variants of 8q24 region, rs6983267 and rs1447295, were associated with the sporadic prostate cancer risk in the Russian population. Polymorphisms were genotyped in 393 case and 384 control Russian Caucasian men from Siberia region. The A allele of rs1447295 was significantly associated with the risk of prostate cancer (OR[CI 95%] = 1.74 [1.26-2.4], p = 7.8 x 10(-4)). A common G-A haplotype for rs6983267 - rs1447295 also showed an association with prostate cancer risk in Russian population (OR[CI 95%] = 2.03 [1.1 - 3.75], p = 0.02). We performed a meta-analysis combining our results with previous studies to evaluate the association between studied SNPs and prostate cancer risk. Meta-analysis has strongly supported the association for these SNPs (p < 10(-6)). Accordingly our study confirms the association between chromosome 8q24 and prostate cancer risk.

Biodegradation of microbial linear polymers of hydroxyalkanoic acids (polyhydroxyalkanoates, PHAs) by soil microbiocoenoses of different structures has been studied during two field seasons in different weather conditions. This process was shown to be influenced by the polymer chemical composition, temperature, humidity, and the microbial soil component. The PHA degradation was accompanied by a decrease in the polymer molecular weight and an increase in the degree of crystallinity, indicating the preferential destruction of the amorphous phase compared to the crystalline one. The quantity of the true PHA destructors developing at the surface of the polymer samples was lower than the quantity of accompanying bacteria. The dominant PHA destructors under the test conditions were identified as bacteria of the genera Variovorax, Stenotrophomonas, Acinetobacter, Pseudomonas, Bacillus, and Xanthomonas and as micromycetes from Penicillium, Paecilomyces, Acremonium, Verticillium. and Zygosporium.

The goal of the present study was to define gene expression signatures that predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate set of candidate genes likely to be predictive a current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty four genes coding proteins belonging to following categories: ATP-dependent transport proteins, detoxification system proteins, reparation system proteins, tubulin and proteins responsible for its synthesis, cell cycle and apoptosis proteins were considered. Eight NSCLC cell lines (A549, Calul, H1299, H322, H358, H460, H292, and H23) were used in our study. For each NSCLC cell line a cisplatin and paclitaxel chemosensitivity as well as an expression level of 44 candidate genes were evaluated. To develop a chemosensitivity prediction model based on selected genes expression level a multiple regression analysis was performed. The model based on the expression level of 11 genes (TUBB3, TXR1, MRP5, MSH2, ERCC1, STMN, SMAC, FOLR1, PTPN14, HSPA2, GSTP1) allowed us to predict the paclitaxel cytotoxic concentration with high level of correlation (r = 0.91, p < 0.01). However, none model developed was able to reliably predict a sensitivity of the NSCLC cells to cisplatin.

The genes encoding of DNA ligases from the thermophilic archaeon Pyrococcus abyssi (PabDNA ligase) and Methanobacterium thermoautotrophicum (MthDNA ligase) were cloned and expressed in Escherichia coli. The activity of purified enzymes was studied by ligation of two oligonucleotides, one of which had preformed hairpin structure. In the used system the maximal output of reaction products for both DNA ligases was observed near 70 degrees C that is explained by substrate thermostability. At stoichiometric ratio of enzymes and substrate the output of a product reaches of plateau at 70-75% of theoretical ones. Investigated DNA ligases showed different thermostability. The half-time life of PabDNA ligase was about 60 min at 90 degrees C. MthDNA ligase was completely inactivated at this temperature during 10 min. Recombinant DNA ligases from P. abyssi and M. thermoautotrophicum possessed high stability during a storage at 4 degrees C.

The frequencies of the polymorphic gene variants MnSOD Ala9Val, GPX1 Pro198Leu, and GSTP1 Ile105 Val were estimated in female residents of Altai krai with breast cancer. The frequency distributions of the genotypes for all genes studied in both patients and control subjects fit the Hardy-Weinberg equilibrium. The estimated frequencies of the genotypes for the studied genes in the control group did not differ from those earlier reported for Caucasoid women living in Europe. The T(rs1050450) allele of the GPX1 gene was demonstrated to protect against sporadic breast cancer (OR = 0.74 (95% CI = 0.58-0.94), p = 0.012). Carriers of the genotype combination MnSOD CC + GPX1 CC were found to have a 1.6 times higher risk of sporadic breast cancer compared to the control group (OR = 1.59 (1.05-2.41), p = 0.0258). The polymorphic loci GSTP1 (rs1695) and MnSOD (rs4880) were not found to be significantly associated with the risk of familial or sporadic breast cancer.

Breast cancer is the most incident cancer among women. We investigated the role of polymorphisms of folate metabolizing genes MTHFR (C677T and A1298C), SHMT1 (C1420T) and MTHFD (G1258A) in genetic susceptibility to this type of cancer. We determined allele and genotype frequencies in case (850 women with sporadic form of breast cancer) and control (810 women) groups. None of these polymorphisms was significantly associated with breast cancer risk. To increase statistical power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. Meta-analysis also revealed no significant association of studied SNPs with breast cancer.

To define of possible mechanism of monoclonal antibody B2 interaction with haptens and peptide-mimotope of benzo[a]pyrene Fab-fragment structure was modeled. Antibody active centre structure was defined using docking with a number of different polyclic aromatic hydrocarbons. It was shown that active center of monoclonal antibody B2 composed of two binding pockets. Correlation was revealed between experimental and calculated data on relative free energies of monoclonal antibody B2 binding with different ligands. We found that synthetic peptide-mimotope of benzo[a]pyrene weakly competeswith benzo[a]pyrene conjugate in monoclonal antibody B2 binding. Immunization of mice with peptide-mimotope conjugate did not revealed antibodies to benzo[a]pyrene. To define structural features of peptide-mimotope of benzo[a]pyrene preliminary model of peptide-mimotope in the frame of pIII protein was calculated. It was shown that tryptophan located inside of peptide can be exhibited on a surface and accessible to antibody. Obtained modeling results could be applied for following optimizations ofbenzo[a]pyrene peptide-mimotope and active center of monoclonal antibody B2.

GSTM1 and GSTT1 gene polymorphisms were studied in Shorians, Teleuts, and Caucasians of the Kemerovo region. It has been shown that distribution of homozygous deletions in the examined groups is significantly heterogeneous. The frequency of deletion genotypes and combinations of deletion in these genes was lower in Shorians and, Teleuts than in Caucasians.

Ribosomal protein L11 plays important role in ribosome, being involved in several steps in protein synthesis and also activates p53-dependent cell cycle arrest. Changes in the rpL11 levels might be implicated in cell cycle control and carcinogenesis. Therefore, the mechanism of regulation of rpL11 expression has increasing importance. Article presents research results of interaction of promotor elements of gene HRPL11 with proteins of nuclear extracts of cells of a various cell origin. Use oligonucleotide competitors containing known transcription factor-binding sites, and also polyclonal antibodies has shown, that transcription factor YY1 participates in regulation of a transcription of gene HRPL11 in all investigated cellular lines. Our data obtained from comparison of protein binding profiles using nuclear extracts from rapidly growth cells, normal cell lines and serum deprivation repressed cell allows us to consider of transcription factor YY1 as activator of HRPL11 gene transcription.

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.

The nucleotide sequence was established for the human ribosomal protein L11 gene (HRPL11). The gene (4583 bp) proved to consist of six exons and five introns. The structure of the HRPL11 promoter was shown to be typical for ribosomal protein genes of higher eukaryotes: the promoter lacks TATA or CAAT boxes and has a TATA-like element (ATAA, -24 ... -27) surrounded by GC-rich regions, the transcription start point is within an oligopyrimidine tract, and the 5'-untranslater region is short (26 bp). Proteins interacting with the HRPL11 promoter were identified by the electrophoretic mobility shift assay with oligonucleotide competitors containing known transcription factor-binding sites. The promoter regions were compared for the human genes for ribosomal proteins L11, L32, and S26.

The sequence of K-ras intron 2, which has been associated with lung tumor susceptibility in inbred mouse strains, was analyzed in susceptible strain GR and in resistant strains PT and UT. In the latter case, the intron had a tandem repeat of a 37-bp sequence with variant GC of its two single-nucleotide polymorphisms (SNPs), as earlier reported for resistant strains AKR, C57BL/c, and C3H/A. Strain GR did not differ in intron structure from susceptible strains A/He and ICR, having one copy of the 37-bp sequence with SNP variant CA. By gel retardation assay, a DNA probe corresponding to "susceptible" allele CA of K-ras region 278-307 formed an additional complex with nuclear proteins extracted from the lungs, as compared with probes corresponding to the "resistant" GC and "intermediate" CC alleles. With specific antibodies, the protein binding to the susceptible allele was identified as transcription factor GATA-6. Reverse transcription with subsequent multiplex PCR did not reveal a significant difference in K-ras expression for susceptible and resistant strains. The results suggest that SNPs of K-ras intron 2 do not affect the level of K-ras expression but do control the binding of GATA-6, which plays an important role in lung differentiation.

Expression of the proopiomelanocortin (POMC) gene in NISAG rats with inherited stress-induced arterial hypertension has been investigated by the reverse transcription-competitive PCR method. Normotensive rats of the inbred Wistar albino Glaxo (WAG) strain have been used as control. The effect of 3 h immobilization stress has been examined. The content of POMC mRNA in pituitaries of stressed NISAG rats exceeds that in non-stressed rats of the same strain by a factor of 2.4. Rats of the WAG strain do not demonstrate a significant increase in the level of POMC mRNA. In addition, the basIC transcription level of the POMC gene in NISAG rats is higher than in WAG ones.

o-Aminoazotoluene (OAT) suppressed more than twofold the glucocorticoid induction of tyrosine aminotransferase (TAT) in the liver of SWR mice, which are sensitive to the hepatocarcinogenic effect of OAT, but not in resistant AKR mice. The hormone- and DNA-binding activities of the glucocorticoid receptor (GR) were not affected in either line. The OAT-dependent suppression proved to be associated with a decrease in the DNA-binding activity of HNF3 in liver cell extracts. The content of the HNF3 mRNA did not change, suggesting a posttranscriptional effect of OAT.

The sequences of two mitochondrial 16S RNA gene fragments (137- and 174-bp in size) were determined in nine grasshopper species belonging to three Acrididae subfamilies. Phylogenetic reconstruction was performed using the sequences of twelve grasshopper species and the cricket Acheta domesticus sequence as an outgroup (some data were purchased from the GeneBank Data Library (NCBI). In the phylogenetic tree, the Acridinae and Locustinae formed compact groups. Annexpected position of Celes scalozubovi (Locustinae) within the subfamily Acridinae indicated its vague phylogeny. The Catantopinae species lied close to the base of the Acridinae. Almost all branches of phylogenetic trees were strongly (55-100%) supported by bootstrap analysis.

The susceptibility of the ICR, DD/He and CC57/BR mice to urethane-induced lung tumors was analyzed in comparison with the A/He (highly susceptible) and AKR (resistant) lines of mice. Allelic variants of the K-Ras gene intron 2 in these lines have been determined. Susceptibility of the ICR mice was similar to that of the A mice, and intron 2 of the K-Ras ICR gene carried the 37-bp deletion analogous to that described in the A/He line. The DD mice intron 2 also contained the deletion, but despite the presence of the "susceptible" K-Ras allele, the DD/He mice were resistant to urethane induction of lung tumors. The CC57BR line carried the deletion and demonstrated relatively high susceptibility. Our findings indicate that the K-Ras gene may be important in the chemical induction of lung tumors.

The allele frequencies of a tetranucleotide repeat in intron 6 of the lipoprotein lipase gene (humLPL) were analyzed in 95 people from Novosibirsk. Genotype frequencies were shown to conform to the Hardy-Weinberg equilibrium. The allele frequency distribution of the tested hypervariable loci in the Novosibirsk population did not differ significantly from that in the Austrian population.

A search for DNA markers of hereditary arterial hypertension in ISIAH rats was performed by means of contemporary molecular genetic approaches. The backcross rat population used for the analyses was derived from a cross of the Wistar x ISIAH F1 progeny with the Wistar rats. Hybridization of the HaeIII-digested DNA samples with the (CAC)5 microsatellite probe revealed cosegregation of the basal arterial pressure value with the 4.8-kb polymorphic DNA fragment. Examination of the DNA polymorphism by means of polymerase chain reaction with arbitrary primers showed an association of the 700-bp polymorphic DNA fragment with the increase of arterial blood pressure under conditions of emotional stress.

Gene HRPS26 encoding the S26 human ribosomal protein has been sequenced. Gene HRPS26 consists of four exons and three introns. Its size is 2027 bp; the size of its mRNA is 438 nucleotides. As most of the genes of ribosomal proteins of vertebrates, the HRPS26 gene has a short first exon, which corresponds to the 5'-untranslated region of mRNA; the origin of transcription is located in the polypyrimidine tract. The functional activity of the cloned HRPS26 promoter region has been confirmed by transcription of hybrid plasmids in HeLa cells.

The possibility of using oligonucleotides from MER1 family repeats as PCR primers for the amplification of human genome DNA fragments was studied. The recommended oligonucleotide primers were chosen by computer analysis of the data base of the EMBL (release 37.0) nucleotide sequences. Use of one of the oligonucleotides was shown to allow specific human DNA amplification to be carried out.

The metabolism of juvenile hormone (JH) in imagos of two Drosophila species (D. virilis and D. melanogaster) was studied in the normal state and after short-term heat stress. Females of both species respond to stress by a decrease in the activity of JH esterase. This decrease is realized through a decrease in the amount of protein. JH metabolism in males does not change after heat stress. Genetic analysis of differences in the activity of DPF-resistant JH esterase in stress-sensitive and stress-resistant strains of D. virilis was performed. The differences are controlled by one autosomal gene.