[Genetic aspects of potato resistance to phytophthorosis]. / Генетические аспекты устойчивости картофеля к фитофторозу.

Phytophthora infestans Mont. de Bary is the main oomycete pathogen of cultivated crops in the family Solanaceae, especially potato (Solanum tuberosum). Because potato is the fourth most cultivated crop worldwide, its annual losses from late blight are tremendous. Studies of the basic mechanisms of interaction between potato and the late blight pathogen not only expand the fundamental knowledge in this area, but also open up new possibilities for regulating these interactions in order to increase resistance to the pathogen. The interaction of potato and the late blight pathogen can be considered from a genetic point of view, and it is interesting to consider both the response of the potato to the colonization process by P. infestans and the change in gene activity in late blight during plant infection. We can also investigate this process by changing the profile of secondary metabolites of the host and the pathogen. In addition to fundamental work in this area, applied work in the form of the development of new preparations for protecting potatoes is of no less importance. This review briefly describes the main stages of studies of potato resistance to late blight, starting almost from the first works. Much attention is paid to key works on changing the profile of secondary metabolites phytoalexins. A separate section is devoted to the description of both qualitative and quantitative characteristics of potato resistance to the late blight pathogen: their contribution to overall resistance, gene mapping, and regulation capabilities. Both types of traits are important for potato breeding: quantitative resistance due to R-genes is quickly overcome by the pathogen, while quantitative trait loci make it possible to create varieties with almost absolute resistance due to the pyramid of effective genes. The latest approaches in molecular biology make it possible to study translatomic profiles, which makes it possible to look at the interaction of potatoes and the late blight pathogen at a different angle. It has been shown that the process of potato colonization affects not only the activity of various genes and the profile of secondary metabolites: proteins-markers of the response to infection from potatoes have also been identified: they are pathogen-bound proteins and plastid carbonic anhydrase. On the part of P. infestans, fungal cellulose synthase proteins and haustorium-specific membrane protein were markers of infection. Thus, the review contains information on the most relevant complex studies of the genetic mechanisms of potato resistance to late blight.

[Ribosomal profiling as a tool for studying translation in plants: main results, problems and future prospects]. / Рибосомное профилирование как инструмент исследования трансляции у растений: основные итоги, проблемы и перспективы.

The expression of eukaryotic genes can be regulated at several stages, including the translation of mRNA. It is known that the structure of mRNA can affect both the efficiency of interaction with the translation apparatus in general and the choice of translation initiation sites. To study the translated fraction of the transcriptome, experimental methods of analysis were developed, the most informative of which is ribosomal profiling (RP, Ribo-seq). Originally developed for use in yeast systems, this method has been adapted for research in translation mechanisms in many plant species. This technology includes the isolation of the polysomal fraction and high-performance sequencing of a pool of mRNA fragments associated with ribosomes. Comparing the results of transcript coverage with reads obtained using the ribosome profiling with the transcriptional efficiency of genes allows the translation efficiency to be evaluated for each transcript. The exact positions of ribosomes determined on mRNA sequences allow determining the translation of open reading frames and switching between the translation of several reading frames - a phenomenon in which two or more overlapping frames are read from one mRNA and different proteins are synthesized. The advantage of this method is that it provides quantitative estimates of ribosome coverage of mRNA and can detect relatively rare translation events. Using this technology, it was possible to identify and classify plant genes by the type of regulation of their expression at the transcription, translation, or both levels. Features of the mRNA structure that affect translation levels have been revealed: the formation of G2 quadruplexes and the presence of specific motifs in the 5'-UTR region, GC content, the presence of alternative translation starts, and the influence of uORFs on the translation of downstream mORFs. In this review, we briefly reviewed the RP methodology and the prospects for its application to study the structural and functional organization and regulation of plant gene expression.

Effects of Gamma-Radiation on DNA Damage in Onion (Allium cepa L.) Seedlings.

The effect of γ-radiation on the level of nuclear DNA damage in onion seedlings (Allium-test) was studied using the comet assay. DNA breaks were first found in cells of onion seedlings exposed to low-dose radiation (≤ 0.1 Gy). Dose dependence of DNA damage parameters showed nonlinear behavior: a linear section in the low-dose region (below 0.1 Gy) and a dose-independent plateau in the dose range between 1 and 5 Gy. Thus, the comet assay can be used to estimate the biological effects of low-dose γ-radiation on Allium cepa seedlings.

[Apoptosis as the basic mechanism of cytotoxic action of ursolic and pomolic acids in glioma cells].

Pentacyclic triterpene acids are of great interest as compounds that exhibit selective cytotoxicity against malignant tumor cells. If earlier studies were carried out mainly in cancer cells of epithelial origin, in the present work the cytotoxic effect of ursolic and pomolic acids on the primary and permanent glioma cell lines was analyzed. Both compounds are toxic to oncotransformed cells and induce apoptosis in U-87 MG line. Using molecular docking, it has been shown that Akt1 and MDM2 may be potential targets of the studied triterpene acids. It has been suggested that ursolic and pomolic acids induce apoptosis in glioma cells through inhibition of the PI3K/Akt signaling pathway, and they can be considered as potentially promising agents for the treatment of glioblastoma.

Genotoxicity assessment of low-level doses of gamma radiation with the SOS chromotest and the Ames test.

This is the first study to present data on the genotoxicity of low γ-irradiation doses for E. coli and S. typhimurium cells obtained using the SOS chromotest and the Ames test. The most pronounced effect was recorded in the first 24 h of γ-irradiation. After 72 h in the Ames test and after 96 h in the SOS chromotest, a significant effect of γ-irradiation on bacterial cells was detected. The absence of genotoxicity at the later stages can be explained by the adaptation of bacterial cells to the conditions of exposure. The findings allow the bacterial test system to be used for studying the effects of low doses at the early stages of exposure to radiation.

[Genotoxic and Mutagenic Properties of Synthetic Betulinic and Betulonic Acids].

Synthesis of betulinic acid was performed from the birch bark extract (Betula pendula). Betulonic acid was intermediate of the synthesis. Both acids were isolated with purity 95%. Genotoxicity and mutagenicity of obtained compounds were analyzed by Ames test and SOS chromotest, none of these properties have been detected.

[Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene.

Influence of Antioxidant SkQ1 on Accumulation of Mitochondrial DNA Deletions in the Hippocampus of Senescence-Accelerated OXYS Rats.

Reduction of efficiency of oxidative phosphorylation associated with aging and the development of neurodegenerative diseases including Alzheimer's disease is thought to be linked to the accumulation of deletions in mitochondrial DNA (ΔmtDNA), which are seen as a marker of oxidative damage. Recently, we have shown that mitochondria-targeted antioxidant SkQ1 (10-(6'-plastoquinonyl)decyltriphenylphosphonium) can slow the development of signs of Alzheimer's disease in senescence-accelerated OXYS rats. The purpose of this study was to explore the relationship between the development of neurodegenerative changes in the brain of OXYS rats and changes in the amount of mtDNA and the 4834-bp mitochondrial DNA deletion (ΔmtDNA4834) as well as the effect of SkQ1. We studied the relative amount of mtDNA and ΔmtDNA4834 in the hippocampus of OXYS and Wistar (control) rats at ages of 1, 2, 6, 10, and 20 days and 3, 6, and 24 months. During the period crucial for manifestation of the signs of accelerated aging of OXYS rats (from 1.5 to 3 months of age), we evaluated the effects of administration of SkQ1 (250 nmol/kg) and vitamin E (670 mmol/kg, reference treatment) on the amount of mtDNA and ΔmtDNA4834 and on the formation of the behavioral feature of accelerated senescence in OXYS rats - passive type of behavior in the open field test. In OXYS rats, the level of ΔmtDNA4834 in the hippocampus is increased compared to the Wistar rats, especially at the stage of completion of brain development in the postnatal period. This level remains elevated not only at the stages preceding the manifestation of the signs of accelerated brain aging and the development of pathological changes linked to Alzheimer's disease, but also during their progression. However, at age of 24 months, there were no detectable differences between the two strains. SkQ1 treatment reduced the level of ΔmtDNA4834 in the hippocampus of Wistar and OXYS rats and slowed the formation of passive behavior in OXYS rats. These results support the possible use of SkQ1 for prophylaxis of brain aging.

Analysis of mitochondrial DNA somatic mutations in OXYS and Wistar strain rats.

Rats of the OXYS strain are sensitive to oxidative stress and serve as a biological model of premature aging. We have compared spectra of somatic mutations in a control region of mtDNA from the liver of the OXYS rat strain and of Wistar rats as a control. The majority of nucleotide substitutions in the mutation spectra were represented by transitions: 94 and 97% in the OXYS and Wistar rats, respectively. It was shown that 40% of somatic mutations in the control region of mtDNA from Wistar rats were significantly consistent with the model of dislocation mutagenesis. No statistical support for this model was found for mutations in the control region of mtDNA from OXYS rats. The mutation frequency in the ETAS section was higher in the OXYS strain rats than in Wistar rats. These results suggest different mechanisms of mutagenesis in the two rat strains under study.

[New promising antioxidants based on 2,6-dimethylphenol].

Three new sulfur-containing derivatives of 2,6-dimethylphenol were synthesized. Their antioxidative activity, mutagenicity, and genotoxicity were examined by bacterial tests and by calculating the dominant lethal mutations in murine embryonic cells. It was shown that all the compounds synthesized have a marked antioxidative effect and no genotoxic or mutagenic properties. One of the antioxidants, 4-(3-dodecylthiopropyl)-2,6-dimethylphenol, increases the survival of cells of both the wild-type Escherichia coli strain and bacterial strains defective in the genes of repair enzymes and has a more distinct antioxidative effect than the classic antioxidants alpha-tocopherol and trolox, increasing the survival of cells devoid of repair enzymes.

Oxidation of guanine in liver and lung DNA of prematurely aging OXYS rats.

Immunofluorescence assay was applied for determination of 8-oxoguanine (8-oxoG) in DNA. The 8-oxoG content in liver and lung DNA of 2- and 18-month-old Wistar rats was compared with that of prematurely aging OXYS rats. It was shown that for rats of both strains, 8-oxoG content in lung DNA compared with liver DNA was 1.7-2.0-fold and 1.3-1.7-fold higher for 2- and 18-month-old rats, respectively. However, the degree of oxidative damage in liver DNA of OXYS rats was 2.4- (p < 0.01) and 1.5-fold (p < 0.05) higher for 2- and 18-month-old animals, respectively, than that in liver DNA of Wistar rats. Oxidation of guanine in lung DNA of OXYS rats was 2- (p < 0.01) and 1.7-fold (p < 0.05) higher for 2- and 18-month-old animals, respectively, than that in lung DNA of Wistar rats. The data indicate that elevated DNA oxidative damage in various organs of OXYS rats may be an important factor of accelerated aging and progression of age-related diseases--cataract, macular dystrophy, hypertension, osteoporosis, cognitive and behavioral dysfunctions, and also lung and liver pathologies.

[Age-related changes in protein and lipid oxidation in the liver of prematurely aging rats OXYS]. / Vozrastnye izmeneniia okislennosti belkov i lipidov v pecheni prezhdevremenno stareiushchikh krys OXYS.

Age-dependent variations in products of lipid peroxidation products (LPO) and oxidative damage of proteins have been studied in the liver mitochondria and microsomes of premature aging OXYS rats. Characteristics of oxidative processes in OXYS rats were compared with parameters in Wistar rats. Changes in lipid peroxidation products content and oxidative damage of proteins in rat liver mitochondria and microsomes of both strains rats were nonlinear and had opposite direction during the first year of life. The level of protein oxidative damage in OXYS rat liver mitochondria and cytosol was higher than in Wistar at 12 months. The content of primary and end lipid peroxidation products in OXYS rat liver microsomes was significantly decreased in 12 months, but content of conjugated dienes was increased in mitochondria.

[Use of mirtilene forte and adrusen zinco for correction of oxidative lesions in mitochondria in rats OXYS with inherited hyperproduction of free radicals]. / Primenenie mirtilene forte i adruzena tsinco dlia korrektsii okislitel'nykh povrezhdenii mitokhondrii krys OXYS s vrozhdennoi sposobnost'iu k radikaloobrazovaniiu.

A long-term uptake of a diet supplemented with Mirtilene Forte (Vaccinum myrtillus extract) or Adrusen Zinco (a vitamin E complex with zinc, copper, selenium and omega-3 polyunsturated fatty acid) improved the functional state of liver mitochondria in OXYS rat strain. Adrusen Zinco sharply decreases the level of protein and lipid oxidation products. Possible mechanisms of the drug action are considered in relationship with their antioxidant properties.

[Molecular mechanisms of the initiation of complete and mosaic mutations]. / Molekuliarnye mekhanizmy vozniknoveniia polnykh i mozaichnykh mutatsii.

To study the molecular basis of the origin of complete and mosaic mutants, pBR322 plasmid with one- or two-stranded DNA damage was constructed by limited chemical modification of the plasmid DNA. Damage of one strand of DNA resulted in induction of mosaic mutants. Data were obtained indicating that complete mutations arise as a result of damage of two strands in the region of the mutagenized gene.