Том 60, № 10 (2024)

This work is an analytical review dedicated to the search for driver mechanisms of epigenetic changes in atherosclerosis pathogenesis. The disease affects the cardiovascular system in the adult population, mainly the elderly and senile. Atherosclerosis is accompanied by progressive deposition of cholesterol and lipoproteins in vessels intima with inflammation, narrowing of the lumen and impaired blood supply to tissues and organs. These processes are characterized by changes in the expression of CACNA1C, GABBR2, TCF7L2, DCK, NRP1, PBX1, FANCC, CCDC88C, TCF12, ABLIM1 genes. Prevention of atherosclerosis is physical activity, the mechanisms of which are not fully understood. Experimental models have shown that regular training not only has a protective effect on the development of atherosclerosis, but also inhibits the progression of an already developed disease with a decrease in vascular stenosis, an increase in the concentration of collagen and elastin and matrix metalloproteinases in plaques. These results have been confirmed by clinical studies. The purpose of this review was to systematize the accumulated results on the causes of epigenetic changes, including those under the influence of regular training, causing changes in the expression of specific microRNAs in atherosclerosis. It was found that physical exercise in Apo-/- mice increases the expression of miR-126 and miR-146a (inhibiting the TLR4 and TRAF genes), miR-20a (affecting PTEN), miR-492 (suppressing RETN gene mRNA). Clinical studies have shown an increase in the levels of miR-146a, miR-126, miR-142-5p, miR-424-5p and a decrease in the transcription of miR-15a-5p, miR-93-5p, miR-451 under the influence of aerobic training. It has been suggested that the drivers of epigenetic changes in atherosclerosis are transposons pathologically activated during aging, the transcription of which can change under the influence of physical training, which is accompanied by impaired expression of long non-coding RNAs and microRNAs derived from transposons. Analysis of the literature data allowed us to identify 36 such microRNAs, 25 of which showed identical changes in levels during aging and atherosclerosis.

Sugar transporters play an important role in regulating the long-distance sucrose transport from source to sink organs. The main sucrose absorber in woody plants is developing wood. Thus, sucrose transport, regulated by SUT, SWEET, and MST gene families, will determine the formation of woody biomass. Based on silver birch (Betula pendula var. pendula Roth) genomic data, we identified and analyze encoding sugar transporters in Betula pendula. We conducted BLAST-search, phylogenetic, structural analysis and analysis of cis-acting elements of sugar transporter genes and determined their chromosomal localization. We were able to identify and characterize 3 genes of the SUT family, 10 SWEET genes and 36 MST genes, which have a typical number of functional and transmembrane domains for the family. It was shown that silver birch contains a smaller number of sugar transporters genes compared to A. thaliana, which is probably because of the apoplastic type of terminal phloem loading in Arabidopsis, while in silver birch phloem loading is carried out predominantly symplastically. The results obtained may be useful for further study of the participation of sucrose transporters in various biosynthetic processes in woody plants and provide a basis for various biotechnological manipulations.

Cysteine-rich peptides play an important role in the plant defense system. The aim of the present work was to search in silico for genes encoding antimicrobial and signaling peptides in the genome of Thinopyrum elongatum (Host) D.R. Dewey (2n = 14, EE) − a wild grass species with high resistance to pathogens and abiotic stress. Bioinformatic analysis revealed 154 new genes of antimicrobial and signaling peptide precursors belonging to 9 families in Th. elongatum genome. Introns were detected in a number of cysteine-rich peptide genes. The structure of peptide precursors and localization of peptide genes in wheat chromosomes were determined. The greatest similarity of the sequences of Th. elongatum peptides with homologous peptides of plants of the genera Triticum and Aegilops was shown, which confirms the cytogenetic data on the relatedness of genome E with genome D and similar genomes. The results obtained contribute to the characterization of molecular components of the immune system of Th. elongatum and will serve as a basis for further studies of resistance mechanisms, as well as for scientifically justified practical use of this species as a resistance donor in wheat breeding.

The first data on the population genetic structure of the D. cristata Sars, 1862 and D. longiremis Sars, 1862 species (Anomopoda: Daphniidae) from the water bodies of North Eurasia are present. The variability of the 12S gene fragment of the mtDNA for these taxa belonging to subgenus Daphnia (Daphnia) O.F. Müller, 1776 (Crustacea: Cladocera) in this region is studied, and the phylogenetic analysis performed. The genealogical relationships between haplotypes of the D. cristata and D. longiremis species and their geographical distribution are shown. Our new data allow us to suggest a recent rapid spatial expansion for D. cristata during the Late Pleistocene and Early-Middle Holocene periods. According to the results of the study, the distribution zones of D. cristata and D. longiremis species are separated in the latitudinal direction with the zone of their contact in Central Yakutia. Our results provide convincing evidence for the influence of ice ages and interglacial on the formation of modern genetic diversity and the phylogeographic structure of D. cristata and D. longiremis.

The distribution of alleles highly specific to Europeans in the Koryak gene pool, which formed as a result of intensive interethnic admixture in the Northern Priokhotie, characterized by the prevailing genetic contribution from males of Eastern European origin, was analyzed. The loci rs16891982 (SLC45A2 gene), rs1426654 (SLC24A5 gene), rs1408799 (TYRP1 gene), rs1076563 (DRD2 gene), rs3827760 (EDAR gene), and rs1448485 (OCA2 gene), which are mainly associated with the pigmentation system, were selected for analysis. High heterogeneity was found in the frequency of European-specific alleles, ranging from 1.4% for the variant rs1076563-C of the DRD2 gene to 14.7% for the variant rs1426654-A of the SLC24A5 gene. The reasons for the uneven influx of European-specific alleles into the Koryak gene pool are discussed. It is possible that the formation of genetic structure of modern Koryaks under intensive interethnic admixture was accompanied by the influence of natural selection on some parts of the genome.

Metastasis to the lymph nodes is one of the most important factors in the poor prognosis of patients with breast cancer; the five-year survival rate for metastatic breast cancer is less than 30%. DNA methylation occurs in the early stages of the development of cancer, and also plays an important role in the development of lymphatic metastases and can serve as a diagnostic and prognostic marker of malignant tumors, including breast cancer. The lncRNA genes GAS5, HOTAIR, HOTAIRM1, SSTR5-AS1, presumably hypermethylated in breast cancer and associated with epithelial-mesenchymal transition and metastasis, were bioinformatically selected. Quantitative methyl-specific PCR showed a statistically significant increase in the methylation level of these lncRNA genes in breast tumors compared to the paired norm. Hypermethylation of the HOTAIRM1 and SSTR5-AS1 genes in breast cancer was identified for the first time. Using statistical analysis, positive correlations were established between methylation levels for the GAS5-HOTAIR and SSTR5-AS1-HOTAIRM1 pairs. The result of co-methylation of GAS5 and HOTAIR in breast cancer is consistent with the bioinformatically predicted (using enrichment analysis and the ncPath database) participation of these lncRNAs in the regulation of common signaling pathways and biological processes. The level of methylation of the lncRNA genes HOTAIRM1 and SSTR5-AS1 is associated with indicators of breast cancer progression (stage of the tumor process, tumor size, presence of metastases in the lymph nodes). A model has been proposed for assessing the risk of developing lymphogenous metastases depending on the level of methylation of the HOTAIRM1 gene. Thus, data were obtained on lncRNAs GAS5, HOTAIR, HOTAIRM1 and SSTR5-AS1 and hypermethylation of their genes as factors in the development and progression of metastatic breast cancer.

The emergence of antibiotic resistance in microorganisms, including mycobacteria, poses a serious problem in modern medicine, reducing treatment effectiveness. In the modern world, there is considerable discussion about the influence of minimal selective concentrations of antibiotics (MSC), which are significantly lower than classical minimal inhibitory concentrations (MIC), on the emergence of antibacterial resistance. It is assumed that such microconcentrations may act as an additional mechanism for selecting drug-resistant strains, which is particularly relevant due to the accumulation of antibiotic concentrations in the environment as a result of human activity. In the context of mycobacteria, understanding the processes of induction of resistance to antibiotics at the MSC level is especially important for the development of effective treatment strategies and control of the spread of drug resistance. The aim of this study was to investigate the induction of the natural drug resistance system in mycobacteria under the influence of concentrations significantly lower than standard MIC and not affecting cell growth. The resistance of Mycobacterium smegmatis mc2 155 to one of the main antibiotics used in medical practice, bedaquiline, was analyzed during induction by tetracycline, ofloxacin, and kanamycin. It was established that one of the mechanisms influencing the change in sensitivity of the M. smegmatis mc2 155 strain during induction by microconcentrations of tetracycline is the antibiotic efflux system – MmpS5-Mmpl5.

Dopaminergic neurons control behavior, memory, and locomotion, and the causal relationship of their dysfunction to neurodegenerative diseases and aging has drawn attention to investigating the involvement of dopaminergic neurons in the regulation of lifespan. The highly conserved serine-threonine protein kinase GSK3 (Glycogen Syntase Kinase 3), one of the most important multifunctional cellular enzymes in higher organisms, which in Drosophila melanogaster is encoded by the shaggy gene, plays an important role in the function of dopaminergic neurons. This paper provides the first evidence that altering shaggy expression levels in just a few clusters of dopaminergic neurons can affect lifespan. This effect can be either negative or positive and depends on sex. The data obtained may serve as a basis for further search for targeted cell-specific factors regulating the rate of aging, as well as for the development of highly specific approaches to the therapy of neurodegenerative diseases.