Effect of a Synthetic Organoselenium Compound on Post-Vaccination Immunopoiesis in the Red Bone Marrow and Cell Composition of Peripheral Blood of White Mice Vaccinated with Yersinia pestis EV.

We studied the effect of an experimental synthetic organoselenium compound 2,6-dipyridinium- 9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the cell composition of the red bone marrow and peripheral blood in white mice. The study drug co-administered with Yersinia pestis EV vaccine strain (103 CFU) potentiated maturation and migration of mature neutrophils from the bone marrow into the circulation. Reducing the dose of the live vaccine and the anti-inflammatory properties of the study drug made it possible to reduce the allergic reaction during the vaccination process.

Immunotropic Properties of an Experimental Synthetic Selenium-Organic Compound.

We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.

Effect of Synthetic Organoselenium Drug on the Degree of Pathological Changes in the Organs of White Mice Immunized with Tularemia and Brucellosis Vaccines.

We studied the effect of the organoselenium compound 2,6-dipyridinium-9-selenium-bicyclo[ 3,3,1]nonan dibromide (974zh) on the severity of pathological changes in the organs of experimental animals immunized with live tularemia and brucellosis vaccines. It was found that 974zh reduced reactogenicity of vaccines for experimental animals. Our findings indicate the prospects for further studies of the effects of 974zh on the functional state of experimental animals.

[The analysis of association between type 2 diabetes and polymorphic markers in the CDKAL1 gene and in the HHEX/IDE locus].

The increase in diabetes was noted at the turn of the 21st century. Patients with type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a multifactorial disease. It arises from adverse effects of environmental factors on the body of genetically susceptible peoples. According to modern concepts, T2DM is a polygenic disease. Each of the involved genes contributes to the risk of developing of this disease. In our study, the association between polymorphic genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were studied. Four hundred forty patients with type 2 diabetes and 264 healthy individuals without any signs of the disease were examined. The comparative analysis of distribution of genotypes and allele frequencies points to an association between polymorphic genetic markers rs7756992, rs9465871, and rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no statistically significant associations are found. On the basis of these data, we can conclude that the CDKAL1 gene is associated with development of T2DM. For the HHEX/IDE locus, such an association is absent.

[Association of the polymorphisms of the FTO, KCNJ11, SLC30A8 and CDKN2B genes with type 2 diabetes].

To study the association with diabetes mellitus type 2 we performed anal- ysis of the distribution of frequencies of alleles and genotypes of polymorphic markers of FTO, KCNJ11, SIC30A8 and CDKN2B genes. The study included groups of T2DM patients and unrelated controls of Russian origin. Analysis of the distribution of frequencies of alleles and genotypes of the polymorphic markers of KCNJ11, SLC30A8 and CDKN2B genes showed the presence of association with T2DM in Russian population, while for the FTO gene was not found statistically significant associations with type 2 diabetes. We can conclude that in Russian population main role in the development of type 2 diabetes play genes, affecting the level of syn- thesis and secretion of the insulin in beta-cells of the pancreas.

2-(Phenyl-selenon-yl)pyridine.

In the title compound, C11H9NO2Se, the pyridine and phenyl rings are almost perpendicular, with the dihedral angle between their mean planes being 79.16 (7)°. In the crystal, the mol-ecules pack so as to form ruffled sheets in the (110) plane connected by weak C-H⋯O inter-actions. In addition, there are weak π-π inter-actions between the mean planes of both the phenyl [centroid-centroid perpendicular distance of 3.591 (2) Šand slippage of 1.854 (2) Å] and pyridine rings [centroid-centroid perpendicular distance of 3.348 (2) Šand slippage of 1.854 (2) Å].

The carriage of risk variants of CDKAL1 impairs beta-cell function in both diabetic and non-diabetic patients and reduces response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel.

On chromosome 6q22.3, a cluster of single-nucleotide polymorphisms located in intron 5 of the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1) gene were shown to confer susceptibility to type 2 diabetes in multiple ethnic groups. The diabetogenic role of CDKAL1 variants is suggested to consist in lower insulin secretion probably due to the insufficient inhibition of the CDK5 activity. In this study, we assessed the association of several SNPs of CDKAL1 with T2D in 772 Russian affected patients and 773 normoglycemic controls using a Taqman-based allelic discrimination assay. We showed association of the minor allele C of rs10946398 (Odds Ratio (OR) = 1.21, 95% CI = 1.04-1.4, P = 0.016), allele C of rs7754840 (OR = 1.18, 95% CI = 1.01-1.37, P = 0.038), and allele G of rs7756992 (OR = 1.21, 95% CI = 1.04-1.42, P = 0.017) with higher diabetes risk thereby replicating the predisposing role of CDKAL1 in etiology of T2D. These alleles contribute to three haplotypes (CCA, CGG, and CCG) related to higher diabetes risk (OR = 1.48, 2.12, and 1.95). Combinations of these haplotypes between each other form the group of high-risk haplogenotypes whose carriers had decreased HOMA-ß compared to other CDKAL1 variants in both diabetic (38.6 ± 19.3 vs. 48.2 ± 21.2, P(adjusted) = 0.019-0.044) and non-diabetic (91.8 ± 42.1 vs. 108 ± 47.2, P(adjusted) = 0.0054-0.01) patients. The carriage of the risk haplogenotypes of CDKAL1 was associated with reduced response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel. These data suggest that CDKAL1 is involved in the pathogenesis of T2D through impaired beta-cell function.

[Polymorphic markers TCF7L2 rs12255372 and SLC30A8 rs13266634 confer susceptibility to type 2 diabetes in a Russian population].

Genes 7CF7L2 and SLC30A8, encoding transcription factor-4 and transmembrane zinc transporter-8, respectively, play an important role in the regulation of development, proliferation, and pancreatic beta cell function. In the present study we examined polymorphic markers of genes rs12255372 [NT_03359.12:g33557428G --> T] of 7CF7L2 gene and rs13266634 [NP_776250.2:p.R325W] of SLC30A8 in groups of Russians with type 2 diabetes (T2D) (n = 588) and healthy normoglycemic controles (n = 597). Significant association of allele T(rs12255372) and allele R (rs13266634) with a higher risk of T2D development has been found (OR = 1.37 and 1.22, respectively). Adjustment for the effect of potential nongenetic risk factors resulted in a further increase in the OR values, from 1.54 (P = 0.24) to 1.89 (P = 0.046) for homozygous carriers of the T allele and from 1.29 (P = 0.035) to 1.35 (P = 0.019) in the individuals homozygous for the R allele. The patients homozygous for predisposing allele T (rs12255372) or R (rs13266634) had significantly lower insulin concentrations in the blood 2 h after glucose tolerance test (GTT) as well as lower values of HOMA-beta, beta cell homeostasis indicator compared to the carriers of other genotypes. Thus, we have shown that the rs12255372 and rs13266634 markers are independent genetic T2D risk factors in a Russian population.

Genetic variations in the pancreatic ATP-sensitive potassium channel, beta-cell dysfunction, and susceptibility to type 2 diabetes.

The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by beta-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P=0.023) and 2.41 (P=1.95 x 10(-5))], respectively. Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A+A/G (P=0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-beta value characterizing the beta-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0+/-46.9) then for other genotypes (HOMA-beta = 85.6+/-45.5 for A/A+A/G, P=0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.

[Feasibility of decreasing the adhesive activity of Corynebacterium diphtheriae by biopolymers of natural origin]. / Izuchenie vozmozhnosti snizheniia adgezivnoi aktivnosti Corynebacterium diphtheriae biopolimerami prirodnogo proiskhozhdneiia.

Possible decreasing of the Corynebacterium diphtheriae adhesive activity by natural biopolymers was studied. It was shown that the strains of C.diphtheriae circulating on the Primorye Territory had middle, low or minimal adhesive activity. Natural biopolymers were found to decrease the adhesive properties of C.diphtheriae. The results of the study are promising for further investigation of natural biopolymers as agents preventing C.diphtheriae colonization on the stomatopharynx mucosa.

[Effects of low-intensity electromagnetic radiation of extremely high frequency on the animal body within the framework of total low-dose x-ray irradiation]. / Vozdeistvie nizkointensivnogo élektromagnitnogo izlucheniia v diapazone kraine vysokikh chastot na zhivotnyi organizm na fone obshchego rentgenovskogo oblucheniia v malykh dozakh.

Effect of low-intensive electromagnetic radiation of extremely high frequency (EMR EHF) on the rats, subjected to the low-dose X-ray irradiation (6.192 mC/rg) was investigated. Content of glial fibrillary acidic protein as well as glucose content and activity of glutamate dehydrogenase and malate dehydrogenase was studied. It was shown than EMR EHF modifies the X-ray irradiation effect: filament GFAP concentration in brain and glucose content in serum were restored. The authors suggest central nervous system participation in realization of EMR EHF effects on the organism.

[Modular evolution of Bsp-repeats: formation of subrepeats and monomers preceded the divergence of four species of Canidae]. / Blochnaia évoliutsiia Bsp-povtorov: formirovanie subpovtorov i monomerov predshestvovalo raskhozhdeniiu chetyrekh vidov Canidae.

Determination of two nucleotide sequences of satellite-like DNA (Bsp-repeats) segments from the raccoon-like dog genome and analysis of these and three other homologous sequences from distantly related genomes of Canidae (silver fox, domestic dog, and gray fox) show that all these DNA fragments consist of five types of subrepeats (A, B, C, D, and E) and two types of monomers-ACB and ACED. Raccoon-like dog repeated segment of 1620 bp is composed of both type of monomers: ACBACED. Different monomers of the same type could be distinguished by subtypes of subrepeats. Building of a cladogram of 18 subrepeats and analysis of the structures of monomers and higher-order repeated units allowed us to reveal probable evolution events which have determined the hierarchical order in Bsp-repeat organization. Approximate periods of time for these evolution events were calculated from the number of substitutions per branch. Five main types of subrepeats and two types of monomers have been generated and propagated through several steps before divergence of the main phylogenetic trees of Canidae. Combinatorial variability appears to play a fundamental role in forming the hierarchical layers in Bsp-repeats structure.

[State of nonpulmonary tuberculosis care in West Siberia]. / Sostoianie vnelegochnoi sluzhby v Zapadnoi Sibiri.

Basic epidemiologic parameters in relation to extrapulmonary tuberculosis were analysed in 6 regions of West Siberia as well as the state of the material-technical base of extrapulmonary service in these areas. Despite a general reduction of the revealed incidence and morbidity of extrapulmonary tuberculosis, the true incidence persists at a high level with predominance of advanced forms of the process. One of the causes of this situation is insufficient material-technical support of extrapulmonary tuberculosis service in West Siberia.

Species- and tissue-specific transcription of complex, highly repeated satellite-like Bsp elements in the fox genome.

We have studied the transcription of highly repeated satellite-like Bsp elements containing the potential promoter boxes for RNA polymerase III in the genomes of adult silver and arctic foxes. The Bsp repeat transcripts were abundant enough to be detected by Northern blot and semiquantitative dot blot hybridizations, and the majority were found in the nuclear RNA fraction from arctic fox kidneys. Weak hybridization signals were revealed with the cytoplasmic RNA preparation from silver fox kidneys and with the nuclear RNA fraction from arctic fox liver, and their intensity was intermediate with the total RNA from arctic fox brain. Taken together, the data suggest possible genomic interspersion of some Bsp repeats in these two representatives of Canidae. The observed species-and tissue-specificity of the transcription of Bsp repeats suggests that they may potentially accomplish regulatory functions in the fox genomes.

[Species-specific features of the distribution of restriction sites in Bsp-repeats of Canidae genome]. / Vidospetsificheskie osobennosti raspredeleniia restriktsionnykh saitov v Bsp-povtorakh genomov Canidae.

Differences and similarities of the Bsp-repeats' organization in fox, dog, polar fox and raccoon dog genomes were studied. Specificity of Bsp-repeats to the Canidae family was demonstrated. The repeats are mainly organized in large clusters in all species studied. The species-specific features in restriction patterns were revealed for all five genomes, in spite of high intragenomic polymorphism exhibited in each case. This suggests that certain unique sets of structural versions of Bsp-repeats were fixed in canid genomes by amplification during the process of speciation. Fox and polar fox exhibited the highest similarity in restriction patterns of Bsp-repeats. Raccoon dog pattern is most unusual among others: its distinguishable character is the absence of large multimeric series. The EcoRI hydrolysate of raccoon dog Bsp-repeats consists mainly of one band corresponding to 1600 bp. These are in accordance with phylogenetic relations between canids.

[Heterogeneity of the Canidae Bsp-repeats family: discovery of the EcoRI subfamily]. / Geterogennost; semeistva Bsp-povtorov Canidae: obnaruzhenie EcoRI-podsemeistva.

A 1600 bp EcoRI fragment was cloned from genome of raccoon dog. The structure obtained is homologous to the Canidae Bsp-repeats family. Comparative blot hybridization of the EcoRI fragment and BamHI repeat from fox genome with restricted hydrolysates of the total of raccoon dog and fox DNAs revealed differences both in structure and genomic organization between these two Bsp-repeats versions. Evidently, the EcoRI fragment contains a sequence lacking from the BamHI fragment of the fox Bsp-repeats. Quantitative differences in contents of two Bsp versions in various canid genomes were revealed as well. The EcoRI version is most abundant in raccoon dog genome, while the BamHI fox version is most representative in polar fox genome. With other species studied, quantitative differences in version contents are not so dramatic, and the EcoRI fragment is always present in lower copy numbers. The discovery of the EcoRI subfamily of the Bsp-repeats is in accordance with the "library hypothesis" advanced by Salser in 1976. Connection of the Bsp-repeats' evolution with centric fusions and breaks characteristic of karyotype evolution of canids is being discussed. Comparative study of cloned EcoRI and BamHI fragments of Bsp-repeats in cytogenetical and molecular aspects may be useful, when investigating the role of tandem repeats in large chromosome rearrangements.

[Features of the structure and evolution of complex tandemly organized Bsp-repeats in the fox genome. II. Tissue-specific and recombinant BamHI-dimer sites]. / Osobennosti struktury i évoliutsii slozhnykh tandemno organizovannykh Bsp-povtorob genoma lisitsy. II. Tkanespetsificheskie i rekombinatsionnye saity BamHI-dimera.

The complex structure of the clustered Bsp-repeats in fox genome seems to have evolved throughout a long period of time as a result of multiplication, recombination and divergence events. The sequence of the subrepeat (SR) approximately 245 b.p long is the basic substructure for the hierarchically arranged Bam HI-repeat 1468 b.p. long. The monomer consists of 3 SRs with a 43-59% homology. A dimer is composed of 2 monomers with a 93% homology. Amplification of the Bsp-repeats during evolution seems to have occurred at least twice: first--on the SR ancestral form level, second--on the monomer level. Despite profound divergence, there are still conservative regions in SRs with sequences homologous to known functional sites in eukaryotes. However qualitative and quantitative composition of most functional motifs is stringently individual in every SR. The performed analysis revealed that throughout evolution SRs acquired significant amount of motifs homologous to promoter and enhancer regions in tissue-specific genes and virus regulatory regions. Functional motifs in separate SRs are being differently grouped. Most inducible motifs are located in the III and II subrepeats, putative promoters--in the II one; elements participating both in transcriptional and replicational processes--mainly in the I subrepeat. A few ensembles of functional motifs remotely resemble extended regulatory regions of some tissue-specific genes. The monomers are potentially capable of ensuring diverse aspects of transcriptional regulation. As a whole, motifs of the 3 SRs are potentially capable of regulating the RNA synthesis periodicity with respect to the cellular cycle, activation and repression of genetical material in response to signals from the environment (AP-1, AP-2, AP-4, T-antigen, etc) and temporal ("octamers") etc. Apart from the BamHI-dimer, a few homologues fragments were isolated from fox genome and sequenced. Some of them were rearranged with respect to the BamHI-dimer. Inversion locally alters the composition of motifs and the sequence acquires new functional potential. Thus, the analysis of the emergence and development of Bsp-repeat structural variations allows us to consider repetitive DNA sequences as an ideal material in constructing multiprofile regulatory sequences.

[Features of the structure and evolution of complex, tandemly organized Bsp-repeats in the fox genome. I. Structure and internal organization of the BamHI-dimer]. / Osobennosti struktury i évoliutsii slozhnykh, tandemno organizovannykh, Bsp-povtorov genoma lisitsy. I. STruktura i vnutrenniaia organizatsiia BamHI-dimera.

A 1468 b.p. DNA BamHI-fragment homologous to the Bsp-repeat was isolated from the fox genome and sequenced. This fragment is an hierarchically arranged dimer. Its 734 b.p.-monomers consist of three subrepeats (SR), each 245 b.p. long, abundant with overlapping imperfect tandem repeats which in turn are rich in short direct related repeats (each 4-7 b.p. in size). The latters are mainly composed of AG, TG dinucleotides and their complements CT, CA. All subrepeats in the BamHI-dimer are flanked by motifs homologous to Jeffreys' sites. At certain points the sites are doubled. The above data allow to assume that the Bsp-repeat complex structure is likely to have developed throughout long multi-step evolution of relatively simple DNA sequences which had emerged de novo. Single substitutions, small inserts and deletions, multiple duplication and recombination events seem to have most contributed to the evolution of the Bsp-repeats. Single substitutions in SRs with respect to the consensus are not equally distributed along their length. A wave-like pattern of this distribution is the evidence for non-random character of mutations accumulation. A correspondence was noted between conservative regions in SR and the presence therein of functional motifs homologous to the binding sites of already known regulatory proteins.