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In the modern world, global changes are taking place in all spheres of society, including economy, science, education and culture. In this regard, a detailed analysis and comprehension of ongoing processes become relevant to develop a specific strategy. In 2021, the Ministry of Science and Higher Education adopted the Order «On the approval of the nomenclature of scientific specialties for which scientific degrees are awarded ”; the nomenclature of scientific specialties was published, where specialty 05.25.03 «Library Science, Bibliography science and Bibliology» was not reflected (among pedagogical, historical, philological, technical sciences). This document came next to a draft nomenclature of scientific specialties (2020), which was widely discussed by the scientific community. The library community and representatives of university science carried out a number of activities aimed at changing the situation. The authors recreate the picture of forming and growing the profile scientific specialty, including its presentation in the nomenclature of scientific specialties for which scientific degrees are awarded since 1957; analyze statistic materials on post-graduate training of highly qualified scientific personnel and activity to defense dissertations in 1999–2020; generalize and assess the data, consider the problems and vectors of this specialty development to justify the inclusion of the specialty «Library Science, Bibliography Science and Bibliology» in the new nomenclature of scientific specialties to continue the training of highly qualified scientific personnel in graduate school, and to carry out specialized research. The article argues that the consequences of the ongoing reforms in science have led to transformations, slowing down the rotation of scientific personnel, extinguishing the activities of dissertation councils and scientific schools in library science, bibliography and bibliology in the regions and complicating the development of library and information science in general.

The pathogenesis of atherosclerosis and ischemic heart disease is associated with oxidative stress and mitochondrial dysfunction. Mitochondrial DNA encodes subunits of mitochondrial respiratory chain and is highly polymorphic in human populations. Mitochondrial DNA can be considered a candidate genetic locus for predisposition to cardiovascular diseases.Aim. To analyze the associations of the mitochondrial genome polymorphism and chronic heart failure in ischemic heart disease.Material and Methods. The study included two groups of individuals: patients with a combination of ischemic heart disease and chronic heart failure (n = 175) and a population sample of residents of Tomsk (n = 424). Percentages of patients with chronic heart failure of NYHA classes II, III, and IV were 37%, 50%, and 13%, respectively. All patients underwent echocardiographic examination; body mass index and the lipid fractions in blood serum were determined. The average was 55.4 years in patients and 47.6 years in the population sample. Polymorphism of mtDNA was studied by sequencing the hypervariable segment of D-loop of mtDNA and subsequent classification of mtDNA haplotypes into the known haplogroups. The mtDNA haplogroup frequencies were compared between the samples using the Chi-square test. The associations of genotype with quantitative trait variability were analyzed by variance analysis.Results. Male patients showed a higher frequency of haplogroup H compared to the population (45.86% in patients and 35.4% in population) and a higher total frequency of haplogroup H subgroups except the most frequent subgroup H1 (36.94% and 25.22%, respectively). The values of significance level (p-value) and odds ratio (OR) were determined as follows: p = 0.04; odds ratio OR = 1.55 (95% confidence interval (CI) 1.02–2.34) for haplogroup H as a whole; p = 0.02; OR = 1.74 (95% CI 1.12–2.70) for haplogroup H without subgroup H1. Analysis of quantitative traits revealed the associations of the same genetic marker (mtDNA haplogroup H) with the levels of high-density lipoproteins (p = 0.03) and triglycerides (p = 0.02) in blood serum of men in the population sample.Conclusion. The obtained results suggested that the most frequent European mtDNA haplogroup H may be a risk factor for the complications of ischemic heart disease in men.

A replicative analysis of associations with obesity of 53 polymorphic markers associated with the results of genome-wide studies with variability of the body mass index and/or obesity was performed. For the first time in the Russian population, an association with obesity of polymorphic markers rs3810291 of the ZC3H4 gene, rs12940622 of the RPTOR locus, rs1800437 of the GIPR gene, and rs13021737 located in the intergenic region of the genome is shown. Possible molecular mechanisms for the involvement of the studied genes in the pathogenesis of the disease are discussed.

Haplotype associations of 894 DNA samples of elderly people from the Russian population of Tomsk were analyzed using 49 SNPs (single nucleotide polymorphisms). As the analyzed markers, SNPs were selected that showed an association with Alzheimer’s disease or variability of cognitive abilities in genome-wide association studies. As a result of the analysis, blocks on chromosomes 1, 2, 6, 8, 11, 19, and 20 were identified. Significant associations were shown, taking into account 50 000 permutations, for haplotypes localized on chromosomes 1 and 19 in the genes CR1 and APOE, APOC1, respectively. Our results confirm the role of the APOE and CR1 genes in the pathogenesis of Alzheimer’s disease in the Russian population.

The issues of library specialists’ competencies in the aspect of Federal State Educational Standards (GEF) are examined, the problems of determining competencies and their composition taking into account the requirements of the digital economy and the professional standard are identified. It is stated, that at present only lists of competencies of the Federal State Educational Standard are to be considered as the basic model of library specialists’ competencies. It is proposed to implement a number of special measures for to form the professional community’ consolidated position concerning the competences and their determination due to the type of the library and workers’ professional status.

A developed method of multiplex genotyping of polymorphic markers of genes associated with cognitive abilities and neuropsychiatric diseases is based on multilocus PCR and MALDI-TOF mass spectrometry of DNA molecules. The frequencies of 32 single-nucleotide markers localized in 24 genes are analyzed in a sample of elderly people from the Russian population of Tomsk. The data obtained are compared with data for populations from the 1000 Genomes Project.

Alzheimer’s disease (AD) is a neurodegenerative disorder, and represents the most common cause of dementia. In this study, we performed several different analyses to detect loci involved in development of the late onset AD in the Russian population. DNA samples from 472 unrelated subjects were genotyped for 63 SNPs using iPLEX Assay and real-time PCR. We identified five genetic loci that were significantly associated with LOAD risk for the Russian population (TOMM40 rs2075650, APOE rs429358 and rs769449, NECTIN rs6857, APOE ε4). The results of the analysis based on comparison of the haplotype frequencies showed two risk haplotypes and one protective haplotype. The GMDR analysis demonstrated three significant models as a result: a one-factor, a two-factor and a three-factor model. A protein–protein interaction network with three subnetworks was formed for the 24 proteins. Eight proteins with a large number of interactions are identified: APOE, SORL1, APOC1, CD33, CLU, TOMM40, CNTNAP2 and CACNA1C. The present study confirms the importance of the APOE-TOMM40 locus as the main risk locus of development and progress of LOAD in the Russian population. Association analysis and bioinformatics approaches detected interactions both at the association level of single SNPs and at the level of genes and proteins.

This article contains data on the frequencies of alleles, genotypes and haplotypes of the single nucleotide polymorphisms (SNPs) rs2279590 and rs1532278 in the CLU gene in a cohort of normal elderly from the Russian population. The SNPs have been reported to be associated with Alzheimer's disease and cognitive functions in genome-wide and candidate genes association studies. Cognitive performance in sample set was estimated by the Montreal Cognitive Assessment (MoCA). The frequencies of alleles, genotypes and haplotypes of two SNPs were calculated in 3 groups: total sample set, sample set with MoCA score less than 21 (the first quartile) and group with MoCA score more than 24 (the fourth quartile). Keywords: CLU, Cognitive performance, MoCa, Russian population, Elderly, Alzheimer's disease

Aim to study associations of polymorphic genetic variants of inflammatory response, endothelial function, lipid metabolism, and blood coagulation with impaired renal function in patients with ST elevation myocardial infarction (STEMI). Material and methods We enrolled in the study 171 patients admitted to the Kemerovo Cardiology Dispensary within 24 hours after onset of STEMI. All patients underwent genotype identification of 25 polymorphic variants of 18 major candidate genes for cardiovascular disease. Genotyping was performed with DNA chip SINKAR-1 (Institute of Medical Genetics and LLC "Genomic Diagnosis"). Glomerular filtration rate (GFR) was estimated using serum creatinine level measured at admission. Results Comparison of allelic and genotype frequencies of the studied polymorphisms revealed that angiotensin-converting enzyme (ACE) gene rs4291 was associated with decreased GFR: odds ratio (OR) for carriers of rare TT genotype was 2.31 [1.01-5.25], =0.043. Analysis of genotype combinations of ACE rs4343 polymorphism and hepatic lipase gene (LIPC) rs1800588 showed that AA genotype of rs4343 polymorphism in combination with CC genotype of rs1800588 polymorphism was associated with lowest risk of renal dysfunction, whereas GG and AG genotypes of ACE rs4343 in combination with TT and CT genotypes of LIPC rs1800588.

A group of patients with ischemic heart disease and myocardial infarction (N = 156) and a reference population sample (N = 300) were genotyped for 58 single nucleotide polymorphisms (SNPs) in the genes involved in extracellular matrix function and collagen metabolism or associated with cardiovascular diseases and atherosclerotic plaque stability. Genotyping was performed by mass-spectrometry with two multiplex sets of 27 and 31 SNPs. The study revealed different genetic composition of predisposition to cardiovascular disease continuum (CVDC) syntropy (patients with concomitant conditions: hypercholesterolemia, hypertension, and type-II diabetes mellitus, N = 96) and to isolated myocardial infarction (without these conditions, N = 60). Only the KIAA1462 gene (rs3739998) showed associations with both CVDC syntropy (OR = 1.71; 95% CI 1.19-2.45; р = 0.003) and isolated infarction (OR = 1.58; 95% CI 1.05-2.40; р = 0.028). Isolated myocardial infarction was also associated with LIG1 (rs20579) (OR = 2.08; 95% CI 1.06-4.17; р = 0.028) and ADAMDEC1 (rs3765124) (OR = 1.63; 95% CI 1.07-2.50; р = 0.020). CVDC syntropy was associated with CDKN2BAS1 (rs1333049) (OR = 1.48; 95% CI 1.03-2.12; р = 0.029) and APOA2 (rs5082) (OR = 1.47; 95% CI 1.02-2.11; р = 0.035). So, genes involved in fibrogenesis contribute to predisposition to the myocardial infarction as well. Isolated myocardial infarction and CVDC syntropy can be considered as pathogenetically different cardiovascular conditions, with different genes that contribute to the susceptibility.

To estimate the association of rs11218343 in the sortilin-related receptor 1 (SORL1) gene with cognitive performance in the elderly and with Alzheimer's disease (AD) in the Russian population.A sample included 586 elderly people (mean age 70.9±5.7 years) without AD diagnosis and 100 patients with late-onset AD (mean age 72.1±7.8 years) from the Tomsk population. SORL1 rs11218343 was genotyped using PCR and MALDI-TOF mass spectrometry. Cognitive performance in the sample of elderly without AD was assessed by Montreal Cognitive Assessment (MoCA) test.Allele frequencies of the SORL1 polymorphism were not significantly different between the elderly without AD and AD patients. However mean MoCA score in the carriers of the rare allele (19.00±6.61) was significantly lower than in homozygotes for the common variant (22.25±3.89) (F=4.97; p=0.026).The rare variant in SORL1 gene previously associated with AD in genome-wide association studies and meta-analyses was associated with lower total МоСА scores in the random sample of elderly people that suggests declined cognitive functions in the carriers of this variant in elderly.Цель исследования. Изучение связи rs11218343 гена сортилинподобного рецептора 1 (SORL1) с показателями состояния когнитивных функций у пожилых людей из российской популяции с диагнозом 'болезнь Альцгеймера' (БА) и без такового. Материал и методы. Выборка включала 586 пожилых пациентов (средний возраст 70,9±5,7 года) без БА и 100 пациентов с поздним началом БА (средний возраст 72,1±7,8 года) из популяции Томска. Генотипирование rs11218343 гена SORL1 проводили с помощью ПЦР и масс-спектрометрии. Нейропсихологическое тестирование проводили по Монреальской шкале оценки когнитивных функций (МоСА). Результаты. Частота аллелей rs11218343 гена SORL1 в изученных группах обследованных не достигала степени статистической достоверности. Однако средние значения общего балла по МоСА в контрольной выборке пожилых пациентов (без БА) у носителей редких аллелей отличались (были ниже) от гомозигот с частыми их вариантами (19,00±6,61 и 22,25±3,89; р0,026). Заключение. Редкий вариант в гене SORL1 связан с низкими показателями МоСА, о чем свидетельствует снижение когнитивных функций у носителей редкого аллеля в пожилом возрасте.

The concept of syntropic diseases was proposed at the beginning of the last century to emphasize the phenomenon of nonrandom co-occurrence of human disorders. Common genes underlying specific syntropic diseases were called syntropic genes. The application of this concept to contemporary genomic studies will facilitate the understanding of the molecular basis of complex diseases, provide future direction for discovering new targets for therapy and prognosis, and may even lead to the reassessment of disease classification for the practice of more precise personalized medicine. With the acceptance of the syntropic genes theory, new genetic tests, focused on markers pointing to a set of pathogenetically linked diseases rather than to a single nosology, can be developed.

In contrast to the modest progress made in the interpretation and clinical application of genomic data, genotyping technologies have experienced great progress. Genotyping costs are progressively decreasing making individual genotyping more commonly available. Financial availability of individual genome analysis and the strong desire of many people to know about their individual genomic characteristics, promotes the marketing of genetic tests of variable predictive value directly to the public. A survey of 2000 Russian respondents revealed very positive attitudes and beliefs towards these genetic developments: 85% of surveyed individuals would like to have their genetic risk for avoidable diseases estimated, and 89% responded stating that they would try to change their lifestyle by giving up bad habits, following a recommended diet or taking medications if a high risk of disease was identified. It is believed that with time, validated genetic information will find its rightful place in medicine, by supplementing phenotypic clinical data with validated genetic interpretations.

Cognitive performance is an important endophenotype for various neurodegenerative and neuropsychiatric traits. In the present study two genetic variants in the leucine-zipper protein (LUZP2) and the F-box 40 protein (FBXO40) genes, previously reported to be genome-wide significant for Alzheimer’s diseases and schizophrenia, were examined for an association with cognitive abilities in normal elderly from the Russian population. Rs1021261 in the LUZP2 and rs3772130 in the FBXO40 were genotyped by multiplex PCR and MALDI-TOF mass spectrometry in a sample of 708 normal elderly subjects tested for cognitive performance using the Montreal Cognitive Assessment (MoCA). Association of genetic variability with the MoCA scores was estimated by parametric and nonparametric analysis of variance and by the frequency comparison between upper and lower quartiles of MoCA distribution. Significantly higher frequency of “TT” genotype of rs1021261 in the LUZP2 gene as well as “A” allele and “AA” genotype of rs3772130 in the FBXO40 gene was found in a subsample of individuals with the MoCA score less than 20 comparing to the fourth quartile’s subsample (MoCA > 25). The data of the present study suggests that genetic variability in the LUZP2 and FBXO40 loci associated with neurodegenerative and neuropsychiatric diseases is also contributed to the normal variability in cognitive performance in the elderly.

We performed an association analysis for the mtDNA major common variants and haplogroups with incidence of myocardial infarction and essential prognostic characteristics in patients. A comparison of patients (N = 406) and control groups (N = 183) uncovered a higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p = 0.033). Patients with early infarction (before age of 55 in men) had a higher frequency of 16189C variant, compared to patients who endured first infarction at age older than 55 (24.1% vs. 12.5%; p = 0.008). In addition, haplogroup U2e was only detected in the subgroup with early infarction (4.4%; p = 0.004). Haplogroup U5 was less frequent in patients with early infarction (5.1% vs. 15.4%; p = 0.002). Observations during a 1-year follow-up uncovered that patients with recurring cardiovascular incidents had higher frequency of haplogroup H1 (20%, versus 4.5% in patients without complications, p = 0.002) and variant 16189C (30% versus 13.5%; p = 0.018). Haplogroup U5 was more frequent in the subgroup of patients with lower (

The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians.

We have performed association analysis for mtDNA most common variants and haplogroups with myocardial infarction and some prognostic characteristics in patients. Comparison of patients (N=406) and controls (N=183) has shown higher frequency of HV0 haplogroup in patients (6.9% vs. 2.2%; p=0.033). Patients with early infarction (before age 55), comparing to patiens older than 55 and the first infarction, had higher frequency of 16189C variant (24.1 vs. 12.5%; p=0.008); also, haplogroup U2e was registered only in the subgroup with early infarction (4.4%; p=0.004). On the other side, haplogroup U5 was less frequent in the patients with early infarction (5.1% vs. 15.4%; p=0.002). The patients with recurring cardiovascular incidents during one year follow-up had higher frequency of haplogroup H1 (20% versus 4.5% in the patients without complications, p=0.002) and variant 16189C (30% versus 13.5%; p=0.018). Haplogroup U5 was more frequent in the group of patients with left ventricular ejection fraction less than 40%: 17.1% comparing to 8.2% in the group with ejection fraction>40%; p=0.034. The results suggest that mtDNA polymorphism contributes to coronary atherosclerosis. The associations could be explained by the polymorphism effect on oxidative phosphorylation and reactive oxygen production in mitochondria.

Recently, genetic markers rs10503253 and rs2616984 in the CUB and Sushi multiple domains-1 (CSMD1) gene have been reported to be associated with schizophrenia and cognitive functions in genome-wide association studies. We examined the associations of the above SNPs with cognitive performance evaluated by the Montreal Cognitive Assessment (MoCA) tool in a cohort of the normal elderly from the Russian population. Significant association of rs2616984 genotypes with the MoCA scores was found using nonparametric analysis. No association of rs10503253 with MoCA scores was observed using both parametric and nonparametric statistics. Significant combined effect of two-locus CSMD1 genotypes on MoCA scores was demonstrated by median test. Allele “A” and genotype “AA” of rs2616984 were significantly associated with the lower MoCA scores in comparison of 1st and 4th quartiles of MoCA total score distribution. The results suggest that genetic variants in CSMD1 gene are likely a part of genetic component of cognitive performance in the elderly.

Ru-containing catalysts on hyper-cross-linked polystyrene (MN 270) and its functionalized analogs (MN 100 and MN 500) are used in the hydrolytic hydrogenation of cellulose for the first time. The texture characteristics of the polymer supports and the catalysts are determined via low-temperature nitrogen adsorption. Experiments on converting cellulose into polyols are performed in a 50 cm3 steel reactor in subcritical water at 245°C, a partial pressure of hydrogen of 6 MPa, and a stirrer velocity of 600 rpm. The morphological parameters of the supports correlate with the activity of the catalysts. The 1.0% Ru/HPS MN 270 catalyst displays the highest activity. The total yield of sorbitol and mannitol is 50% on average at a cellulose conversion of 85%, which is comparable to the figures for more complex and expensive catalysts. The parameters of cellulose conversion can be further optimized and the proposed catalysts improved to develop a highly effective procedure for processing cellulose biomass into raw materials for chemical synthesis and the production of second-generation biofuels.

The distribution of the allele and genotype frequency for the TOMM40 gene polymorphic variants rs741780, rs157580, rs1160985, rs2075650, and rs8106922 was analyzed in a sampling of ethnic Russians from the city of Kemerovo. The study of the structure of linkage disequilibrium in terms of five studied polymorphic variants showed the presence ofa haplotype block 2 Kb in length, which includes three polymorphic variants, i.e., rs741780, rs1160985, and rs8106922. The differences in the frequencies of alleles and genotypes in terms of the polymorphic rs2075650 and rs157580 variants between ethnic Russians from the city of Kemerovo and other European populations were detected. It was discovered that polymorphic variants of TOMM40 rs741780, rs1160985, and rs8106922 are associated with serum triglyceride concentrations. In men, the polymorphic variant rs2075650 is associated with low-density lipoprotein cholesterol levels. In women, the polymorphic variant rs741780 is associated with diastolic blood pressure levels.

The calcineurin signaling pathway plays a crucial role in the heart remodeling of a different nature, in the development of left ventricular dilatation, and in the progression of heart failure. Components of the calcineurin pathway are involved in the regulation of cardiomyocyte hypertrophy, angiogenesis, and apoptosis. In this study, quantitative expression profiles were determined for major calcineurin pathway genes PPP3CA, PPP3R1, PPP3CB, GATA4, and NFATC4 in the myocardium of the right atrium auricle in patients with ischemic heart disease who underwent different types of surgery depending on the severity of clinical symptoms as follows: surgical reconstruction of left ventricle (LV) geometry (post-infarction aneurysm) or coronary artery bypass grafting (unaltered LV morphology). In patients with sizable post-infarction LV dilatation (n = 21), the expression levels of calcineurin catalytic subunit genes PPP3CA and PPP3CB were 1.3 and 1.6 times lower (p = 0.018 and 0.023, respectively) than in patients with unaltered heart shape (n = 34). The differences in expression levels of PPP3R1, which encodes calcineurin regulatory subunit B and levels of GATA4 and NFATC4, which encode transcription factors, were not significant. Thus, decreased PPP3CA and PPP3CB expression in the atrial myocardium may be a marker of significant post-infarction LV remodeling. The further investigation of the relationship between expression levels of calcineurin pathway genes and the degree of myocardial damage may provide useful insights for predicting adverse events in cardiosurgical treatment of patients with post-infarction heart remodeling.

To study the relationship between polymorphous G-1082A (rs3024491) and C-592A (rs1800872) variants of the IL10 gene and multifocal atherosclerosis (MFA) in patients with acute coronary syndrome (ACS) without segment ST elevation.Genotypes of polymorphous G-1082A (rs3024491) and C-592A (rs1800872) variants of the IL10 gene were determined in 178 patients. Interleukin-10 (IL-10) level was measured in 93 of them using solid-phase immunoenzymatic assay. All patients underwent visualization of coronary and peripheral arteries.C-592A (rs1800872) polymorphism ofthe IL10 gene tended to be associated with type 2 diabetes mellitus in the carriers of the CC (gg) genotype and with elevated concentration of high density lipoproteins and reduced intima-media thickness in the carriers of the AA (tt) genotype. The frequency of MFA in the carriers of different genotypes of rs1800872 polymorphism was practically identical while the CA(gt) genotype was associated with more severe manifestations of atherosclerosis and AA(tt) genotype with lower frequency of peripheral artery stenosis. Patients with AA(tt) genotype of rs1800872 polymorphism had higher IL-10 levels. No relationship between rs3024491 polymorphism of IL10 gene, blood IL-10 level, clinical risk factors, and MFA was documented.CC (gg) genotype of C-592A (rs1800872) polymorphism of the IL10 gene in patients with acute coronary syndrome (ACS) without segment ST elevation was associated with type 2 diabetes mellitus while the AA(tt) genotype of the same polymorphism with elevated concentration of high density lipoproteins, reduced intima-media thickness, low frequency of peripheral artery stenosis, and increased IL-10 production. CA (gt) genotype of rs1800872 polymorphism of the IL10 gene was associated with MFA.

In this study we genotyped polymorphism Thr12Ser (rs1937) in TFAM gene in two groups: patients with coronary artery disease and control group (people from Tomsk population). For genotyping was used restriction fragment length polymorphism. We have found significant higher genotype CC frequency in men with coronary artery disease — 4.52% compared with control men — 0.45% (χ2 = 6.315; р = 0.043; OR = 10.45). Thus genotype CC is associated with coronary artery disease in men fromTomsk population.

In this study, we genotyped polymorphism in GPX1 Pro198→Leu (C→T) rs 1050450 in four groups, i.e., patients with coronary artery disease, people who lived a long time (over 90 years), people who died early (before 55 years) from cardiovascular disease, and the Russian population as a control group. We have found a significant higher T-allele frequency in men with coronary artery disease, i.e., 34.84% (χ2 = 5.228, p = 0.022; OR =1.46), and in men who died early from cardiovascular diseases, 38.16% (χ2 = 6.461, p = 0.011; OR = 1.69) compared to men in the control group, 26.8%. Moreover, a significantly higher genotype TT frequency has been shown in patients with coronary artery disease and myocardial infarction before age 50, which is 19.44% compared to the control group, which was 7.28% (χ2 = 9.55, p = 0.002). The TT frequency in individuals who lived a long time (4.39%) was the lowest and differed significantly from the group with coronary artery disease, which was 12.79% (χ2 = 8.07, p = 0.0045), and from the subgroup with coronary artery disease with myocardial infarction before age 50, which was 19.44% (χ2 = 14.49, p = 0.0001). Thus, our results indicate that the TT allele (Leu) of GPX1 Pro198→Leu (C > T) polymorphism is unfavorable for successful aging; it leads to predisposition to coronary artery disease, early myocardial infarction (before age 50), and early death (before age 55).

This article proposes the establishment of a United States–Israel Longitudinal Database for Healthy Aging and Preclinical Dementia as a prototype model for the eventual creation of an international database. It is envisioned that such a comprehensive international database, as a shared research resource, will provide the foundation for a systems approach to solve the dual public health problems of: (1) Early detection of individuals at an elevated risk of developing Alzheimer's disease, and (2) Developing interventions to delay onset of, or prevent, chronic brain disorders later in life.

Many new genetic tests for common multifactorial disorders are becoming available to individuals, including direct-to-consumer genotyping services. Typically, studies of public attitudes reveal a high level of interest for individual genotyping. In a Russian urban population, 85% of 2000 respondents answered positively to a question about their own willingness to undergo predictive genetic testing for preventable health conditions. Gender, age and health status significantly influenced response. Multivariate discriminant analyses revealed that wanting to know about probable future diseases, readiness to improve lifestyles and an interest in learning about individual genome characteristics are the most important predictors for wanting to be tested. Along with the high level of interest, highly overestimated expectations were encountered in many studies. With the low predictive abilities of currently available genetic tests for common disorders, proper interpretation of the data and genetic counseling are essential. There is a need for prospective validation of genetic panels for risk assessments, and for efforts to measure the effects of genetic information disclosure and how this information might contribute to lifestyle changes.

Aims: To study the frequency distribution of cytochrome P450 (CYP) functional genetic variants in five Eurasian populations from the territory of Siberia in Russia. Materials & Methods: Unrelated healthy Tuvinians, Buryats, Altaians, Yakuts and Russians (n = 87–88) were genotyped for CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3 and CYP3A5*6. Standard pairwise genetic distances, locus-specific and global Fst statistics were calculated. Results: CYP allele and genotype frequencies demonstrated significant variability. Overall, the degree of between-population variance displayed by CYP SNPs was lower than that recorded from neutral short tandem repeats and Aluinsertion polymorphism, indicating evolutionary conservation of CYP polymorphisms. CYP-based genetic distances were well correlated with the geographic distances across populations (r = 0.822, p = 0.008). Conclusions: Although the tested variants were present in the neighboring, yet secluded, populations at the expected range of frequencies, the observed frequencies were significantly variable across Eurasian populations, indicating potential relevance to clinical decision making. The appropriate class, dose and treatment regimen that lead to optimal therapeutic safety and efficacy are presumed to be governed, at least partially, by genetic determinants. Thus, it is expected that, in the future, genetic markers will serve as diagnostics, informing and guiding clinical decision making. Based on this principle, pharmacogenetic research is aimed at identifying individuals who are expected to benefit from a certain pharmacotherapy, while dramatically reducing the suffering and costs associated with adverse drug reactions (ADRs). Indeed, it has been stated that most of the commonly used drugs are effective in only 25–60% of patients, and more than 2 million cases of ADRs occur

The idea of the pseudoperturbation method is due to Gavurin [1], who applied the pseudoperturbation operator to improve estimates of simple eigenvalues and eigenelements of self-adjoint operators on a Hilbert space. Later, his post-graduate student Kuhnert [2] solved this problem for non‐self-adjoint operators. The further development of the pseudoperturbation method is due to Loginov, Rakhimov, and Sidorov, who refined multiple eigenvalues, eigenvectors, and generalized Jordan elements of operator functions linear with respect to a spectral parameter on Banach spaces. The pseudoperturbation operator constructed in [3] did not make it possible to use generalized Jordan chains (GJCs) of adjoint operator functions, and in the general case, the problem remained unsolved. In 2003 [4], pseudoperturbation operators of two forms were suggested, which symmetrically used the generalized Jordan structure of the direct and adjoint operator functions to refine multiple eigenvalues and generalized Jordan elements of the eigenvalue problem in Banach spaces linear with respect to a spectral parameter. Linearization by using matrix operators makes it possible to apply the idea of the pseudoperturbation method to the case of a polynomial and an analytic dependence of the operator function under consideration on a spectral parameter [5, 6]. This paper considers various applications of the pseudoperturbation method. 1. STATEMENT OF THE PROBLEM In Banach spaces E 1 and E 2 , we consider the eigenvalue problem

The variability of potentially important functional polymorphic variants rs2069705 (5'UTR of the IFNG gene), rs17880053 (near 5'UTR of the IFNGR2), rs11126176 (LOC100287361 pseudogene), and rs804271 (near 5'UTR of the NEIL2 gene) was characterized in representatives of four ethnic groups living in the Siberian region. These ethnic groups included three indigenous Mongoloid ethnic groups (Yakuts, the residents of the Republic of Sakha (Yakutia), Tuvinians from the Republic of Tuva, and Buryats from the Republic Buryatia) and the alien Russian population. All of the examined variants were polymorphic. The frequency of the rs2069705 allele C in Russians was 0.5833, while it was in a range from 0.7842 to 0.8967 in representatives of the indigenous populations. The frequency of rs17880053 deletion was 0.8073 in Russians and from 0.4474 to 0.5521 in the indigenous ethnic groups. The frequency of the rs11126176 allele A was equal to 0.5398 in Russians but was recorded with lower frequencies in indigenous ethnic groups (from 0.2722 to 0.4551). The frequency of the rs804271 allele Gwas 0.5215 in Russians and from 0.2527 to 0.4022 indigenous ethnic groups. With respect to the genotype structure, the alien Russian population was considerably distanced from indigenous Mongoloid populations. Specifically, the genetic distance was 0.0742 between Russians and Yakuts, 0.1365 between Russians and Tuvinians, and 0.1433 between Russians and Buryats. Among the Mongoloid indigenous ethnic groups of Siberia, Tuvinians and Yakuts were the most distant from each other (0.0262). The genetic distance was equal to 0.0151 between Yakuts and Buryats and 0.0127 between Buryats and Tuvinians.

Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non–random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the “My Gene” genomic service (www.i–gene.ru). An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype “IHD only,” including those in the APOB, CD226, NKX2–5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the “IHD and AH” phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the “IHD only” and “IHD and AH” phenotypes: rs4765623 in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic rs6501455, were identified for the “IHD and AH” phenotype and a combination of several diseases (syntropy); there were no common genetic markers for the “syntropy” and “IHD only” phenotypes. Classificatory analysis of the relationships between the associated genes and metabolic pathways revealed that lipid–metabolizing genes are involved in the development of all three CVC variants, whereas immunity-response genes are specific to the “IHD only” phenotype. The study demonstrated that comorbidity presents additional challenges in association studies of disease predisposition, since the genetic profile of combined forms of pathology can be markedly different from those for isolated “single” forms of a disease.

To comparatively study the diagnostic capabilities of positron emission tomography (PET) with various tumorotropic radiopharmaceuticals (TRPs) in detecting malignant brain gliomas (BG) and estimating their degree.One hundred and fourteen patients, including 47 with histologically verified glioblastoma multiforme (GBM), 27 with anaplastic astrocytoma (AA), 23 with benign astrocytoma (BA), and 17 with postoperative cysts, were examined. PET was performed using TRPs: 18F-fluorodesoxyglucose (18F-FDG), 11C-sodium butyrate (11C-SB), 11C-L-methionine (11C-MET), and 11C-choline (11C-COL).Malignant gliomas (GBM and AA) were clearly visualized by PET using 11C-MET, 11C-CHOL, and 11C-SB. 18F-FDG PET visualization of tumors was difficult because of increased RP accumulation in the cerebral cortex. WHO grades II-III gliomas were completely visualized by 11C-MET PET. Only some tumors were clearly displayed by PET with 11C-CHOL and 11C-SB. The accumulation indices (AI) obtained by 11C-CHOL PET in patients with malignant gliomas were, on average, 4.0- and 5.5-fold higher than those by 11C-MET and 11C-SB PET, respectively. Significant differences (p0.001) in AI obtained by "C-CHOL ("C-CHOL-AI) PET were first established between the patients with GBM (WHO grade IV) and those with AA (WHO grade III).11C-CHOL PET is the most sensitive method to identify gliomas and estimate their grade. The advantage of 11C-MET PET is the possible imaging of the entire volume of viable tumor tissue.