ACE and AGTR1 Polymorphisms in Pathogenesis of Human Left Ventricular Hypertrophy

The A2350G polymorphism of exon 17 of the angiotensin I-converting enzyme gene (ACE) and the A1166C polymorphism of the 3-untranslated region (3-UTR) of the angiotensin II type 1 receptor gene (AGTR1) were tested for association with left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) or arterial hypertension (AH) combined with diabetes mellitus type 2 (DM2). The patients with EH or AH + DM2 did not differ significantly in ACE or AGTR1 allele or genotype frequencies from healthy subjects. Both polymorphisms were associated with LVH in EH. AGTR1 allele 1166C was more frequent in patients with LVH than without (33.6 vs. 20.7%) and affected the left ventricular mass index (LVMI) in patients with EH (p = 0.007). The frequency of ACE allele 2350G in EH patients with LVH was 1.5 times higher, and that of genotype GG was 3.5 times higher, than in patients without LVH. LVMI differed significantly (p = 0.002) between patients with different ACE genotypes, being maximum in homozygotes GG and minimum in homozygotes AA. Thus, AGTR1 allele 1166C and ACE allele 2350G were identified as predisposing to LVH in EH. The two polymorphisms were not associated with the incidence or severity of LVH in patients with AH and DM2.     

Restriction polymorphism of the major noncoding region of mtDNA in the indigenous population of the TUVA republic]

Mitochondrial DNA sequence variation was examined in three rural populations of the indigenous inhabitants from the Tuva Republic. The frequencies of restriction sites within the D-loop region of mtDNA were determined. The three populations studied demonstrated similar patterns of mtDNA polymorphism. Like other Siberian populations, Tuvinians were characterized by high frequencies of the HaeIII 16517 and AspS9I (Cfr13I) 16516 restriction sites (about 75%). Moreover, in Tuvinians, a relatively low (71 to 81%) frequency of the KpnI 16129 restriction site was observed. The frequency of the mitotype differing from the Cambridge sequence by the HaeIII 16517 and KpnI 16129 sites in Tuvinians was higher than in Mongols and Russians. The features of mtDNA polymorphism point to the similarity between Tuvinians and other Siberian ethnic groups (Sel'kups in particular). This can be explained by the contribution of the Samoyed component, along with the Turkic and Mongoloid ones, to the formation of the Tuvinian ethnic group.     

Mechanisms of antimicrobial resistance and genetic relatedness among enterococci isolated from dogs and cats in the United States

Aims: In this study, mechanisms of antimicrobial resistance and genetic relatedness among resistant enterococci from dogs and cats in the United States were determined. Methods and Results: Enterococci resistant to chloramphenicol, ciprofloxacin, erythromycin, gentamicin, kanamycin, streptomycin, lincomycin, quinupristin/dalfopristin and tetracycline were screened for the presence of 15 antimicrobial resistance genes. Five tetracycline resistance genes [tet(M), tet(O), tet(L), tet(S) and tet(U)] were detected with tet(M) accounting for approx. 60% (130/216) of tetracycline resistance; erm(B) was also widely distributed among 96% (43/45) of the erythromycin‐resistant enterococci. Five aminoglycoside resistance genes were also detected among the kanamycin‐resistant isolates with the majority of isolates (25/36; 69%) containing aph(3′)‐IIIa. The bifunctional aminoglycoside resistance gene, aac(6′)‐Ie‐aph(2″)‐Ia, was detected in gentamicin‐resistant isolates and ant(6)‐Ia in streptomycin‐resistant isolates. The most common gene combination among enterococci from dogs (n = 11) was erm(B), aac(6′)‐Ie‐aph(2″)‐Ia, aph(3′)‐IIIa, tet(M), while tet(O), tet(L) were most common among cats (n = 18). Using pulsed‐field gel electrophoresis (PFGE), isolates clustered according to enterococcal species, source and antimicrobial gene content and indistinguishable patterns were observed for some isolates from dogs and cats. Conclusion: Enterococci from dogs and cats may be a source of antimicrobial resistance genes. Significance and Impact of the Study: Dogs and cats may act as reservoirs of antimicrobial resistance genes that can be transferred from pets to people. Although host‐specific ecovars of enterococcal species have been described, identical PFGE patterns suggest that enterococcal strains may be exchanged between these two animal species.     

Voltage-dependent gating underlies loss of ENaC function in Pseudohypoaldosteronism type 1

Here we explore the mechanism and associated structure-function implications of loss of function for epithelial Na⁺ channel (ENaC) containing a pseudohypoaldosteronism type 1 (PHA-1)-causing missense point mutation. As expected, human ENaC that contained subunits harboring PHA-1-causing substitutions within an absolutely conserved, cytosolic Gly residue (e.g., βG37S) had significantly less activity. Unexpectedly, though, such substitution also results in voltage sensitivity with greater activity at hyperpolarizing potentials. This is a consequence of voltage-dependent changes in the single-channel open probability and is not species- or subunit-dependent. Voltage sensitivity in PHA-1 mutants stems from the disruption of critical structure, rather than the development of new properties resulting from the introduction of novel side chains. Residues near the conserved His-Gly sequence of G95 in α-mENaC are particularly important for voltage sensing. Although substitution of I93 in α-mENaC results in voltage sensing, it also slows the activation and deactivation kinetics enough to enable capture of the dynamic changes in single-channel open probability that account for changes in macroscopic activity. This provides definitive proof of the mechanism that underlies loss of function. In addition, the voltage dependence of ENaC with PHA-1 substitutions is akin to that which results from substitution of a critical, interfacial Trp residue conserved at the intracellular base of TM1 (e.g., W112 in α-mENaC). Dynamic interactions between similarly positioned His and Trp residues are essential for gating and the girdle-like structure that lines the intracellular mouth of the M2 proton channel. The similar residues in ENaC may serve a shared function, suggesting the possibility of an intracellular girdle just below the mouth of the ENaC pore.     

Genetic demographic study of Shors in Tashtagolskiĭ district of the Kemerovo region: changes in the marriage migration structure

The changes in the marriage structure with respect to the age at marriage, ethnicity, and spouses' birthplaces during the period of time corresponding to two generations have been analyzed in the rural population of Shors of Tashtagolskii raion of Kemerovo oblast. In general, the Shor population had a high assortative marriage rate with respect to these parameters in the period studied, although there was a temporary tendency towards its decrease. The ages of marriage for both the male and the female Shor populations in the years 2000-2005 were significantly older than in 1940-1945 and 1970-1975. The age-assortative marriage rate was r = = 0.60 in 1940-1945, r = 0.73 in 1970-1975, and r = 0.66 in 2000-2005. The birthplace-assortative marriage rate decreased from 79.63% in 1970-1975 to 70.64% in 2000-2005. The ethnic assortative marriage rate of Shors steadily decreased during the time interval studied; it was 96.92, 89.95, and 80.98% in 1940-1945, 1970-1975, and 2000-2005, respectively, for the total rural population of Tashtagolskii raion.     

Effect of individual peculiarities on formation of preference of ethanol in female and male Wistar rats

Individual characteristics of animal behavior can serve a prognostic parameter of predisposition to use of alcohol. The goal of the work was to study dynamics of formation of preference of alcohol at early stages in the process of forced alcoholization in male and female rats as well as the accompanying changes in behavior parameters. For 3 months, the rats were submitted to the forced alcoholization with 10 % ethanol. Each week the rats were tested in the "two-glass trial". Individual peculiarities of all animals were evaluated prior to, after 6 weeks, and after the end of the experiment with aid of the "open field test" and "Suok-test". Results showed that the male rats demonstrating by the end of the experiment the significantly higher level of the alcohol preference, at the initial stages of the forced alcoholization demonstrated the significantly lower preference as compared with the remaining ones. These rats also showed the lower levels of the motor and exploratory activities before alcoholization as compared with control. On the contrary, the individuals that by the end of the experiment did not differ from control by the level of the alcohol preference demonstrated prior to alcoholization in the "Suok-test" the higher anxiety level. In female groups, no statistically significant differences were observed both in parameters of the motor and exploratory activities and in the anxiety level in both tests. Thus, in male rats, the prognostic parameter predicting formation of the abuse can serve the degree of alcohol preference at the initial stages.     

Ethnic and Geographical Aspects of the Prevalence of the Polymorphic Variants of Genes Associated with Tuberculosis

Specificity of the structure of gene pools of different ethno-territorial groups of the human population can underlie the epidemiological features of the spread of tuberculosis (TB) and the structure of the genetic component of the susceptibility to the disease. The variability of 62 genetic variants potentially associated with the risk of the development of TB in the Russian population of the city of Tomsk has been studied and the differentiation of various ethno-territorial groups of the world by these markers has been assessed. The studied sample comprised 445 Russian residents of the city of Tomsk without bronchopulmonary pathology. For comparison, the data on the variability of the genetic markers of interest in 26 populations from the 1000 Genomes Project was involved. In the Tomsk population, only the ancestral allele was found for seven of the 58 SNPs studied; the allele frequencies for 36 markers were within the limits of the values seen in other European populations; for 12 SNPs, the observed frequencies were closer to populations with a significant Mongoloid component. By the total of the SNPs, the Tomsk population, despite the geographical distance from the rest of the European populations, did not differ from them (in genetic distances and G_st statistics), although it had some features of the gene pool. Intergroup differentiation of the world populations by these SNPs reflects mainly interracial differences. The greatest differences in the genetic structure between the studied populations were seen for the markers localized in intergenic regions. Statistically significant differences were found when comparing the levels of the average expected heterozygosity between groups of “L4 carrier populations” of mycobacteria and “non-L4” populations, which indicates the impact of the prevalence of different pathogenic lineages of M. tuberculosis on the formation of population specificity of the allelic frequencies.     

Sequence of the <Emphasis Type="Italic">mrjp3</Emphasis> Microsatellite Locus in Honeybees of Different Origin

The sequencing of the nucleotide sequences of the mrjp3 repetitive region (mrjp3 microsatellite locus) in Siberian honeybees was carried out. A high similarity of the studied nucleotide sequences (≥99% identity) with reference sequences was observed, which indicates a high conservation of the mrjp3 repetitive region in different Apis mellifera subspecies.     

Methanol and ethanol utilization in methylotrophic yeast Pichia pinus wild-type and mutant strains

In the wild-type strain of methylotrophic yeast Pichia pinus diauxic growth is observed during cultivation in medium containing a mixture of methanol and ethanol: firstly, slow phase of ethanol utilization is revealed and, secondly, a fast phase of methanol consumption is shown. Diauxic growth is observed also in ecr1 mutant, impaired in ethanol-induced catabolite repression of methylotrophic metabolism enzymes, but the order of utilization of the alcohols is inverted in this mutant. Such succession of alcohols utilization in both strains correlates well with the sequence of synthesis of microbody enzymes which catalyze key reactions of C₁- and C₂-metabolism. On the contrary, simultaneous utilization of methanol and ethanol from the mixture, as well as synchronous synthesis of both peroxisomal and glyoxisomal enzymes is observed in adh1 mutant which has reduced alcohol dehydrogenase activity. The strong differences between the wild-type strain and adh1 mutant were observed also in the kinetics of specific activity changes for C₁-metabolizing enzymes, localized in cytosol. In the wild-type strain during growth on methanol and ethanol mixture such changes correlate with the sequence of alcohol utilization. At the same time, in adh1 mutant the activities of formaldehyde dehydrogenase and formate dehydrogenase during the growth on the alcohols mixture are as high as during growth on methanol only, but the activity of dihydroxyacetone kinase is as low as under the growth on ethanol and is lower than on methanol.