Distance Learning of Foreign Languages for Students of Economic Specialties

The purpose of the present research is a comprehensive analysis of the process and results of distance learning of a foreign language (English) for students of economic specialties. The research methods are as follows: the analysis of modern opportunities for organizing distance learning; study of theoretical and methodological papers on the subject matter; method of experimental teaching of foreign languages with an emphasis on tactics of stimulating the personal and motivational sphere of students’ educational activities; development of author’s diagnostic models in order to reveal the dynamics of development of knowledge and practical skills in a foreign language of students of economic profile; qualitative and quantitative analysis of empirical data; statistical and mathematical interpretation of results, their functional analysis; method of generalization and abstraction. According to the data obtained, the hypothesis of the research has been confirmed. It lies in the fact that the students with higher indicators of motivation have shown higher results of academic achievements in mastering a foreign language

A Polymorphism in the Gene Encoding Heat Shock Factor 1 (HSF1) Increases the Risk of Type 2 Diabetes: A Pilot Study Supports a Role for Impaired Protein Folding in Disease Pathogenesis

The aim of this pilot study was to investigate whether polymorphisms in the gene encoding heat shock factor 1 (HSF1), a transcriptional activator of molecular chaperones, play a role in the development of type 2 diabetes (T2D). A total of 3229 unrelated individuals of Slavic origin, including 1569 T2D patients and 1660 age- and sex-matched healthy controls, were enrolled for the study. Five common single nucleotide polymorphisms (SNPs) of the HSF1 gene were genotyped using the MassArray-4 system. SNPs rs7838717 (p = 0.002) and rs3757971 (p = 0.005) showed an association with an increased risk of T2D in females with a body mass index ≥ 25 kg/m2. The rs7838717T-rs4279640T-rs3757971C and rs7838717T-rs4279640T-rs3757971T haplotypes were associated with increased and decreased disease risk in overweight or obese females, respectively. The associations were replicated as disease susceptibility genes in large cohorts from the UK Biobank (p = 0.008), DIAMANTE (p = 2.7 × 10−13), and DIAGRAM (p = 0.0004) consortiums. The functional annotation of the SNPs revealed that the rs7838717-T and rs3757971C alleles correlated with increased expression of the genes involved in unfolded protein response. The present study showed, for the first time, that genetic variation of HSF1 is associated with the risk of type 2 diabetes, supporting a role for impaired protein folding in disease pathogenesis

The Link between Type 2 Diabetes Mellitus and the Polymorphisms of Glutathione-Metabolizing Genes Suggests a New Hypothesis Explaining Disease Initiation and Progression

The present study investigated whether type 2 diabetes (T2D) is associated with polymorphisms of genes encoding glutathione-metabolizing enzymes such as glutathione synthetase (GSS) and gamma-glutamyl transferase 7 (GGT7). A total of 3198 unrelated Russian subjects including 1572 T2D patients and 1626 healthy subjects were enrolled. Single nucleotide polymorphisms (SNPs) of the GSS and GGT7 genes were genotyped using the MassArray-4 system. We found that the GSS and GGT7 gene polymorphisms alone and in combinations are associated with T2D risk regardless of sex, age, and body mass index, as well as correlated with plasma glutathione, hydrogen peroxide, and fasting blood glucose levels. Polymorphisms of GSS (rs13041792) and GGT7 (rs6119534 and rs11546155) genes were associated with the tissue-specific expression of genes involved in unfolded protein response and the regulation of proteostasis. Transcriptome-wide association analysis has shown that the pancreatic expression of some of these genes such as EDEM2, MYH7B, MAP1LC3A, and CPNE1 is linked to the genetic risk of T2D. A comprehensive analysis of the data allowed proposing a new hypothesis for the etiology of type 2 diabetes that endogenous glutathione deficiency might be a key condition responsible for the impaired folding of proinsulin which triggered an unfolded protein response, ultimately leading to beta-cell apoptosis and disease development

The Impact of Genetic Polymorphisms in Glutamate-Cysteine Ligase, a Key Enzyme of Glutathione Biosynthesis, on Ischemic Stroke Risk and Brain Infarct Size

The purpose of this pilot study was to explore whether polymorphisms in genes encoding the catalytic (GCLC) and modifier (GCLM) subunits of glutamate-cysteine ligase, a rate-limiting enzyme in glutathione synthesis, play a role in the development of ischemic stroke (IS) and the extent of brain damage. A total of 1288 unrelated Russians, including 600 IS patients and 688 age- and sex-matched healthy subjects, were enrolled for the study. Nine common single nucleotide polymorphisms (SNPs) of the GCLC and GCLM genes were genotyped using the MassArray-4 system. SNP rs2301022 of GCLM was strongly associated with a decreased risk of ischemic stroke regardless of sex and age (OR = 0.39, 95%CI 0.24–0.62, p GCLM possessed protective effects against ischemic stroke risk (p GCLC. The mbmdr method enabled identifying epistatic interactions of GCLC and GCLM gene polymorphisms with known IS susceptibility genes that, along with environmental risk factors, jointly contribute to the disease risk and brain infarct size. Understanding the impact of genes and environmental factors on glutathione metabolism will allow the development of effective strategies for the treatment of ischemic stroke and disease prevention

Lipid-Associated GWAS Loci Predict Antiatherogenic Effects of Rosuvastatin in Patients with Coronary Artery Disease

We have shown that lipid-associated loci discovered by genome-wide association studies (GWAS) have pleiotropic effects on lipid metabolism, carotid intima-media thickness (CIMT), and CAD risk. Here, we investigated the impact of lipid-associated GWAS loci on the efficacy of rosuvastatin therapy in terms of changes in plasma lipid levels and CIMT. The study comprised 116 CAD patients with hypercholesterolemia. CIMT, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were measured at baseline and after 6 and 12 months of follow-up, respectively. Genotyping of fifteen lipid-associated GWAS loci was performed by the MassArray-4 System. Linear regression analysis adjusted for sex, age, body mass index, and rosuvastatin dose was used to estimate the phenotypic effects of polymorphisms, and p-values were calculated through adaptive permutation tests by the PLINK software, v1.9. Over one-year rosuvastatin therapy, a decrease in CIMT was linked to rs1689800, rs4846914, rs12328675, rs55730499, rs9987289, rs11220463, rs16942887, and rs881844 polymorphisms (Pperm < 0.05). TC change was associated with rs55730499, rs11220463, and rs6065906; LDL-C change was linked to the rs55730499, rs1689800, and rs16942887 polymorphisms; and TG change was linked to polymorphisms rs838880 and rs1883025 (Pperm < 0.05). In conclusion, polymorphisms rs1689800, rs55730499, rs11220463, and rs16942887 were found to be predictive markers for multiple antiatherogenic effects of rosuvastatin in CAD patients

The Joint Link of the rs1051730 and rs1902341 Polymorphisms and Cigarette Smoking to Peripheral Artery Disease and Atherosclerotic Lesions of Different Arterial Beds

Genome-wide association studies (GWAS) have discovered numerous single nucleotide polymorphisms (SNP) contributing to peripheral artery disease (PAD), but their joint effects with risk factors like cigarette smoking (CS) on disease susceptibility have not been systematically investigated. The present study looked into whether CS mediates the effects of GWAS loci on the development of PAD and atherosclerotic lesions in different arterial beds. DNA samples from 1263 unrelated individuals of Slavic origin including 620 PAD patients and 643 healthy subjects were genotyped by the MassArray-4 system for rs1051730, rs10134584, rs1902341, rs10129758 which are known as PAD-associated GWAS loci. The rs1051730 polymorphism was strongly associated with an increased risk of PAD (p = 5.1 × 10−6), whereas rs1902341 did not show an association with disease risk. The rs1051730 polymorphism was associated with increased plasma levels of LDL cholesterol (p = 0.001), and conferred a greater risk of PAD in cigarette smokers than in nonsmokers (p < 0.01). Interestingly, the rs1902341T allele was associated with an increased risk of PAD in smokers and a decreased disease risk in nonsmokers. SNPs and CS were both linked to unilateral and/or bilateral atherosclerotic lesions of peripheral vessels, as well as the abdominal aorta, coronary, and cerebral arteries. The studied polymorphisms exert pleiotropic and cigarette smoking-mediated effects on atherosclerotic lesions of different arterial beds

Comprehensive Statistical and Bioinformatics Analysis in the Deciphering of Putative Mechanisms by Which Lipid-Associated GWAS Loci Contribute to Coronary Artery Disease

The study was designed to evaluate putative mechanisms by which lipid-associated loci identified by genome-wide association studies (GWAS) are involved in the molecular pathogenesis of coronary artery disease (CAD) using a comprehensive statistical and bioinformatics analysis. A total of 1700 unrelated individuals of Slavic origin from the Central Russia, including 991 CAD patients and 709 healthy controls were examined. Sixteen lipid-associated GWAS loci were selected from European studies and genotyped using the MassArray-4 system. The polymorphisms were associated with plasma lipids such as total cholesterol (rs12328675, rs4846914, rs55730499, and rs838880), LDL-cholesterol (rs3764261, rs55730499, rs1689800, and rs838880), HDL-cholesterol (rs3764261) as well as carotid intima-media thickness/CIMT (rs12328675, rs11220463, and rs1689800). Polymorphisms such as rs4420638 of APOC1 (p = 0.009), rs55730499 of LPA (p = 0.0007), rs3136441 of F2 (p PLTP (p = 0.002) showed significant associations with the risk of CAD, regardless of sex, age, and body mass index. A majority of the observed associations were successfully replicated in large independent cohorts. Bioinformatics analysis allowed establishing (1) phenotype-specific and shared epistatic gene–gene and gene–smoking interactions contributing to all studied cardiovascular phenotypes; (2) lipid-associated GWAS loci might be allele-specific binding sites for transcription factors from gene regulatory networks controlling multifaceted molecular mechanisms of atherosclerosis