Alcohol abuse poses an important challenge to public health and is associated with a shorter lifespan, numerous disorders, and social and economic problems. Methods to identify heavy drinkers are necessary for choosing the prevention and treatment strategies in medicine and are in demand in forensics. Alcohol consumption is often underestimated in self-reported data, and objective laboratory tests are therefore essential to employ in diagnosing chronic alcohol abuse and acute alcoholic excess. Carbohydrate-deficient transferrin (CDT) is one of the most specific biomarkers of alcohol abuse. CDT is a set of transferrin isoforms with a lower content of sialic acid residues and is found when glycosylation is impaired by ethanol metabolites. Oxidation of exogenous ethanol to acetaldehyde by alcohol dehydrogenase 1B (ADH1B) is a major pathway of ethanol metabolism. This study showed for the first time that carriers of the allele ADH1B*48His (rs1229984), which determines acetaldehyde production to higher concentrations, have greater CDT levels as compared with noncarriers, alcohol consumption being the same. The difference should be taken into account in medicine, forensics, and studies where Mendelian randomization with respect to the polymorphic locus rs1229984 is performed to address the effects of drinking alcohol.

The results of study of hypermethylation of promoters of the cell cycle genes (RASSF1A, p16/INK4A, p14/ARF, p53, ATM), antioxidant protection (GSTP1, SOD3), and estrogen receptor (ESR1) are summarized in individuals exposed to chronic or fractionated irradiation in the range of small and medium doses (101 people, 24–78 years old, liquidators of the accident at the Chernobyl nuclear power plant, and adult residents of territories contaminated with radionuclides at 135–688 kBq/m2), in the aspect of the relationship of these epigenetic modifications with the cytogenetic status of the individual. Multiple regression analysis showed that the frequency of both simple and complex exchange aberrations of the chromosomal type is associated with the methylation status of the complex of the studied genes (β = 0.504, p = 1.9E-7 and β = 0.349, p = 3.6E-4, respectively), but not with age (β = –0.122, p = 0.178 and β = 0.153, p = 0.109). In general, highly significant differences were demonstrated between groups of exposed individuals with different epigenetic status (number of hypermethylated genes) for all cytogenetic parameters considered, with the exception of chromatid-type aberrations (Kruskal–Wallis test: p = 2E-4 and p = 5E-8 for the total frequency of cytogenetic disorders and rearrangements of the chromosomal type, respectively). The level of cytogenetic disorders of the chromosomal type increases with an increase in the number of methylated genes in irradiated individuals. The data obtained may point to general patterns in the mechanisms of induction and preservation over the years of the considered genetic and epigenetic effects of radiation.

The dynamics of the composition of the populations of Adalia bipunctata L. in St. Petersburg and Yalta (Crimean Peninsula) for 4732 years has been studied. The proportion of black individuals in them decreased by almost 2 times. Comparison of the composition of populations with climatic features of habitats (average annual temperature) showed that the proportion of black individuals in the population negatively correlates with the average annual temperature of the previous year. The observed change in the composition of geographically remote populations is probably the effect of global warming.

Terapiya tamoksifenom u chasti pacientok s gormonochuvstvitel'nym rakom molochnoj zhelezy (GR+RMZH) privodit k uvelicheniyu tolshchiny endometriya. Dannye o vliyanii polimorfnyh variantov v gene CYP2D6, kodiruyushchem ferment CYP2D6 semejstva citohroma R450, na effektivnost' i bezopasnost' lecheniya tamoksifenom protivorechivy. Cel'yu prospektivnogo kogortnogo issledovaniya bylo izuchenie associacii polimorfizmov CYP2D6*3, *4, *6 s riskom razvitiya gipertrofii endometriya v processe ad"yuvantnoj terapii tamoksifenom po povodu GR+RMZH. V issledovanie vklyucheno 145 bol'nyh operabel'nym GR+RMZH, poluchavshih tamoksifen v dozirovke 20 mg v sutki peroral'no. Polimorfizmy CYP2D6*3, *4, *6 opredeleny metodom PCR v rezhime real'nogo vremeni. Provodili izmerenie tolshchiny endometriya ul'trazvukovym metodom cherez 3, 6 i 9 mesyacev gormonoterapii. V issledovanii pokazano, chto gipertrofiyu endometriya chashche nablyudali u bol'nyh bez al'ternativnyh allelej na etape 3 mesyacev nablyudeniya (40% po sravneniyu s 23,2% v gruppe «slabyh metabolizatorov»; r = 0,034). Metaanaliz vsekh periodov nablyudeniya pokazal, chto sredi «normal'nyh metabolizatorov» nablyudaetsya znachimo bolee vysokaya chastota sluchaev gipertrofii endometriya po sravneniyu so «slabymi metabolizatorami» (OSH = 1,88; 95%DI = 1,27–2,79; r = 0,002). Otsutstvie statisticheski znachimyh razlichij v pokazatelyah sostoyaniya endometriya mezhdu gruppami pacientok s razlichnym CYD2D6-genotipom v zavisimosti ot menopauzal'nogo statusa trebuyut provedeniya dopolnitel'nyh issledovanij.

Paraquat at a concentration of 0.01 mol/L induces intense luminescence of E. coli pSoxS-lux and E. coli pKatG-lux biosensors, which indicates the formation of the superoxide radical anion (О 2– ) and hydrogen peroxide (Н 2 О 2 ), respectively, in bacterial cells. At a paraquat concentration of 0.1 mol/L, the luminescence intensity of biosensors decreases, as does bacteria viability from 4 × 10 7 colony-forming units (CFU) in the control to 1 × 10 5 CFU in the experiment. When recalculating the luminescence intensity index per 1000 CFU, the expression of the superoxide dismutase gene increases sharply from 0.13 in the control to 4.36 and 119 conventional units at paraquat concentrations of 0.01 and 0.1 mol/L, respectively. The antioxidants (glutathione and N-acetylcysteine) reduce the concentration of free radicals generated by paraquat in cells and increase the bacterial viability. The method of gel electrophoresis reveals the DNA-damaging ability of paraquat at a concentration of 0.1 mol/L, reduced by antioxidants.

Hypermethylation of CpG islands in the promoter regions of four genes ( p53 , ATM , SOD3 , ESR1 ) was studied in blood leukocytes of irradiated humans (100 subjects: Chernobyl Nuclear Power Plant clean-up workers, nuclear specialists, residents of territories with radionuclide contamination) and 140 unirradiated subjects (control group) using methylation-sensitive polymerase chain reaction (PCR) assay. The obtained data significantly supplemented and allowed us to summarize results from several years of the study of radiation-induced hypermethylation in the gene promoters in various contingents of individuals exposed to chronic or fractionated radiation in a wide range of doses. The differential significance of age and radiation exposure in methylation of CpG islands in promoter regions of different genes was revealed, which is demonstrated by unidirectional effects observed in independent samples of irradiated individuals. The ROC curve analysis showed a high prognostic potential of consideration of detected epigenetic disorders as biomarkers of radiation exposure (AUC = 0.846 ± 0.015, p = 1.5E-48). Hypermethylation of the CpG islands in the RASSF1A and p14 / ARF genes depends on age, and epigenetic modification of the p16 / INK4A and GSTP1 loci is highly significantly associated with radiation exposure, which was verified on two test samples of the examined individuals. The revealed dose-dependent hypermethylation of the studied genes is indirectly confirmed by a positive associative relationship between the level of chromosomal aberrations and the frequency of methylated loci ( r = 0.604, p = 2.3E-11).

The polymorphism of hordeins encoded by the Hrd A and Hrd B loci was studied using starch gel electrophoresis in 258 H. spontaneum accessions from 18 countries of North Africa, the Middle East, and Asia. A total of 225 variants of component blocks encoded by the Hrd A locus were identified, which were grouped into 16 families. Among the HRD A variants found in H. spontaneum, 33 variants (14.7%) were previously identified in H. vulgare. In wild barley, 308 variants encoded by the Hrd B locus were identified, which were grouped into 18 families of hordein component blocks. Among HRD B variants, 33 (10.7%) variants were also previously identified in cultivated barley. The families were considerably different in the number of block variants included in them, ranging from 4 (AVII) to 48 (AI) for HRD A and from 5 (BXI, BXIV) to 49 (BXIII) for HRD B. The mosaic structure and irregular frequency distribution patterns of HRD A and HRD B family variants in the studied H. spontaneum accessions were demonstrated. The highest diversity of component block variants in general and the largest number of "cultivated" HRD A and HRD B variants were found to be present in the H. spontaneum populations from Israel. Moreover, in wild barley accessions from Israel, all HRD A families and all HRD B families but one were identified. Taking into account these data, and the published data on genomic analysis, exome capture, and sequence analysis of the Btr1/btr1 and Btr2/btr2 genes in wild and cultivated barley, it was suggested that barley was first domesticated in northern Israel.

The estimation of hypermethylation of the cell cycle (RASSF1A, p16/INK4A, p14/ARF) and detoxification (GSTP1) gene promoters was carried out in blood leukocytes of humans exposed to radiation as a result of the Chernobyl accident (98 individuals: accident liquidators, 76 individuals; adult residents of the territories with radionuclide contamination, 135–688 kBq/m2, 22 individuals) depending on their cytogenetic status. The results of multiple regression analysis (“Frequency of aberrations ~ age + number of hypermethylated genes”) indicate a correlation of the total level of chromosomal type aberrations with the considered epigenetic disturbances (β = 0.256; р = 0.011), but not with age (β = –0.138; p = 0.165). The frequency of these cytogenetic disorders increases with an increase in the number of methylated loci. Thus, a positive association between the damages to the genome induced by radiation exposure in the range of small and medium doses (long time ago) and hypermethylation of promoters of the genes of the main protective systems of the cells was detected.

The DNA methylation profile can reflect both genetic features and exposure to the external factors that affect certain human traits, including behavioral characteristics and antisocial behavior in particular. To study an association of CpG methylation with aggressive behavior, the methylation level of 800K sites was determined in peripheral blood DNA samples from 122 men who have committed murder and 163 men of a control group. For 25 top CpG sites (p < 1E-22), the association with aggressive behavior was reproduced in the test sample and remained significant at the epigenome level after correction for concurrent factors (age, smoking status, and ethnicity). Phenotypes associated with the genes that correspond to the identified CpG sites include childhood adversity, smoking, alcohol abuse, and asthma, in agreement with published data on physical aggression-associated factors. The results contribute to understanding the biological basis of aggression and identifying biomarkers of aggressive behavior.

Hordein polymorphism in 2244 barley accessions was studied using starch gel electrophoresis. A total of 1197 old local accessions from 22 countries located in the main centers of barley diversity and the bordering regions, 428 varieties cultivated in the territory of the former Soviet Union and Russian Federation from 1929 to 2019, and 619 varieties from Europe, Asia, America, and Africa were analyzed. For the hordeins encoded by the Hrd A locus, 156 variants of blocks of components were identified; 271 variants were detected for the Hrd B locus; and 5 variants were detected for the Hrd F locus. On the basis of the published data on the molecular mechanisms of hordein polymorphism formation and analysis of artificial mutants at the hordein-coding loci, we identified groups, or families, of phenotypically similar component blocks among A- and B-hordein variants. For HRD A, 12 families (AI–AXII) were identified, and for HRG B, 17 families (BI–BXVII) were identified. The families differ significantly in the number of block variants: for HRD A, from 5 (AXII) to 60 (AI); for HRD B, from 3 (BXVII) to 41 (BXII). It is suggested that the families with the largest number of A- and B-hordein variants are the most ancient in domesticated barley. The mosaic structure and irregular distribution of frequencies of HRD A and HRD B family variants in local populations of different countries was shown. We suggested that the emergence of the HRD A and HRD B families was due to the spontaneous hybridization between H. vulgare and H. spontaneum during the spreading of domesticated barley. It is concluded that hordein polymorphism in domesticated barley resulted from spontaneous hybridization between the cultivated barley with a wild ancestor and accumulation of mutations in the genes at Hrd A and Hrd B loci in H. vulgare.

Marginal screening (MS) is the computationally simple and commonly used for the dimension reduction procedures. In it, a linear model is constructed for several top predictors, chosen according to the absolute value of marginal correlations with the dependent variable. Importantly, when kpredictors out of mprimary covariates are selected, the standard regression analysis may yield false-positive results if m>> k(Freedman's paradox). In this work, we provide analytical expressions describing null distribution of the test statistics for model selection via MS. Using the theory of order statistics, we show that under MS, the common F-statistic is distributed as a mean of ktop variables out of mindependent random variables having a 21χdistribution. Based on this finding, we estimated critical p-values for multiple regression models after MS, comparisons with which of those obtained in real studies will help researchers to avoid false-positive result. Analytical solutions obtained in the work are implemented in a free Excel spreadsheet program.

Dioxins and dioxin-like compounds are persistent organic pollutants (POPs) and technogenic ecotoxicants, the most dangerous of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A peculiar feature of the considered genotoxicants that distinguishes them from other POPs is hormone-like activity, which is realized through binding to a special cellular protein, the Aryl hydrocarbon Receptor (AhR). In the present study, the phenomenological aspects of DNA methylation changes induced by dioxins and dioxin-like compounds and revealed in the studies in vitro and in vivo are considered. In animal models, multigenerational and transgenerational effects of dioxin-induced locus-specific DNA methylation changes and their association with reproductive dysfunctions and congenital malformations were firmly established. The importance of investigations of the long-term epigenetic consequences of human exposure to dioxins and the potential value of such studies for preventive diagnostics of somatic and reproductive pathologies are discussed.

In 2017, a group of the leading mathematical statisticians published a paper-manifesto having an extremely simple sense: the common critical level of p-values should be decreased by an order of magnitude (0.005 instead of 0.05) (Benjamin, et al., 2017). In this review, the arguments of proponents and opponents of this proposal are discussed. Moreover, the problems related to the "reproducibility crisis" of the scientific results are considered. The corresponding argumentation cannot be understood without consideration of the fundamentals of the theory of statistical derivation. In this connection, the precise sense of some concepts, such as p-value, the Bayes factor, and the minimum a posteriori probability of the zero hypothesis are discussed in the review. This is made mainly with the examples related to the comparison of frequencies. It was shown that, when using p-values, particular attention should be paid to the comparison of low frequencies on the highly abundant samples. Some practical recommendations on application of the Bayes analysis are given.

It has been shown for the first time that preliminary incubation of bacteria in a medium containing deuterium oxide (D2O) at concentrations of 2.5 to 10% leads to an increase in recA expression induced by hydrogen peroxide at concentrations of 2.2–8.8 mmol/L. The induction of recA in deuterated and non-deuterated (control) cultures was compared using a biosensor based on the E. coli strain K12 MG1655 (pRecA-lux), where luminescence occurs as a result of recA promoter activation in response to DNA damage caused by H2O2. The most effective D2O concentrations were 5.0 and 7.5%. To explain the phenomenon, expression of the catalase gene was studied in deuterated and non-deuterated cultures of E. coli K12 MG1655 (pKatG-lux) biosensor. The luminescence of this biosensor results from activation of the katG promoter in response to an increase in the concentration of H2O2 in the cell. It was found that D2O downregulated katG expression, which can lead to H2O2 accumulation, and, as a consequence, to an increase in the level of DNA damage as seen by an increase in recA expression.