An analysis of the system of breeding work in the pig industry of our country has been carried out. The scientifc and organizational factors that determine the improvement of breed and productive qualities of pigs have been analyzed. On the basis of many years of experimental data, selection practices obtained in the process of creating new breeding achievements, and using the scientifc results of the world science on genetics and animal breeding, proposals have been developed for a new system for assessing and improving the genetic potential of animal productivity based on modern achievements in genetics. In particular, a critical analysis was performed on the existing instructions for boning pigs, linear breeding, which does not meet the criteria of reality in the systematization of biological objects. The positive effect of breeding pigs in a closed mode in the form of a “line-population”, using such genetic markers as erythrocyte antigens, erythrocyte enzymes, lipoproteins, allowing intensifcation of the selection process, has been experimentally proved. When hogging pigs and developing breeding plans with a herd, it was proposed to use such selection and genetic parameters as heritability factors, phenotypic and genetic correlations, selective differential, selective effect, etc. for assessment of animals and prognostication of productivity. A system of continuous scoring of each selectable feature was developed, in contrast to the interval to the classes used in our country at the present time. A model of the selection index, taking into account the selection and economic signifcance of each of its components, has been proposed. Theoretical paths have been shown towards and experimental proof given to a relatively rapid transformation of breeds of animals bred in Russia to world-class productivity, as opposed to the constant import of breeding animals.

The article considers methods used for breeding and selection of mini-pigs in the ICG, SB RAS, the theoretical justifcation of these methods and the purposes for which they are used. We showed the genealogical structure of the herd and the contribution of inbreeding to the genetic similarity of modern representatives of genealogical lines and families with the founders of the breeding group. We characterized the phenotypic diversity of the ICG mini-pigs in colours, weight categories, types of growth and features of constitution. We listed measures supporting genetic diversity in the herd of the ICG mini-pigs. We explained the possibility of using similarity indices calculated by using portions of the ancestors’ blood (genome) for the selection of parental pairs and the evaluation of genetic consolidation of the herd. We showed that the average index of similarity between males and females, calculated by using portions of the ancestors’ blood, in the ICG minipigs is close to the limit value. It turned out that effective evaluation of the genetic potential of mini-pigs in growth rate and fnal size of individuals is only possible under the condition of a rich and full feeding of young animals. The time scale of estimation of growth of live weight of the ICG mini-pigs for three weight categories allocated in the selection group is presented. The types of growth and development of mini-pigs observed in the ICG breeding group and the type inherent to individuals in the small weight category are considered. We justifed the minimum live weight of a newborn piglet in the herd of the ICG mini-pigs. Values of optimal multiple pregnancy for the three categories of ICG mini-pig sows were calculated.

At present great attention is paid to studying genetic regulation of farm animal adaptations to environmental conditions. This problem is very important due to a wide expansion of highly productive cattle breeds created in Europe and North America. However, until the present no investigation of changing semen quality in bulls of imported breeds during their adaptations to environmental conditions of Western Siberia has been conducted. The aim of this study was to investigate semen quality peculiarities and the diversity of morphological sperm abnormalities in bulls of imported and local breeds kept in the environmental conditions of the southern part of Western Siberia. We determined sperm concentration, sperm count, and rate of sperm with progressive motility and percentage of morphologically normal spermatozoa. The rate of sperm abnormalities according to Blome’s classifcation was determined too. It was found that the mean values of sperm concentration, sperm motility and percentage of morphologically normal spermatozoa in the bulls investigated were similar to those in bulls kept in European countries. Inter­breed differences in these parameters were not found. However, bulls of the Red Danish, Angler, and Simmental breeds had a higher percentage of misshapen sperm head and pyriform sperm head than bulls of the Black­White breed. An inter­strain difference in sperm motility in bulls of the Black­White breed was observed. It was found that bulls of Reflection Sovereign 198998 strain had lover sperm motility than bulls of Wis Burke Ideal 1013415 strain. No inter­strain differences in sperm production, percentage of morphologically normal spermatozoa and rate of main sperm abnormalities were found. Thus, it has been found that the environmental conditions of the southern part of Western Siberia do not seriously affect the sperm production, sperm motility or percentage of morphologically normal spermatozoa in bulls. However, the increased rate of misshapen and pyriform sperm heads in the bulls of the foreign breeds points to a need to study sperm DNA fragmentation.

Identifcation of adaptive responses of breeding material, developed in different breeding centers, helps to purposefully correct these traits where it is necessary. Thus, 42 modern breeding lines from eight institutions of Russia and Kazakhstan were studied in comparison with the historical standard Bezenchukskaya 139 in trails of 16-17 and 18 KASIB-SDW (Kazakhstan-Siberian net for wheat improvement, spring durum wheat) in 2015–2017. Field experiments and yield measurements in each ecological cite were similar. To solve these tasks of the experiment, two-factor ANOVA, methods for adaptability assessment cluster analysis and principle component method were applied. As a result, it was established that 1) genotype and genotype – environment interaction (overall 15.8–23.5 % of total dispersion) had signifcant effect on yield variability; 2) genotype – environment interactions were of linear nature and had no destabilizing effect; 3) all the genotypes tested can be distributed in three clusters, the frst one for locally adapted varieties, the third for varieties of a wide areal, the second included genotypes with intermediate characteristics; 4) breeding centers of the Federal Altai Scientifc Centre of Agro-Biotechnologies and of the Research Institute of Agriculture of South-East produced predominantly varieties of local importance, the Samara Research Institute of Agriculture – varieties of wide area; 5) a stable trend of increased mean yield compared to historical standard Bezenchukskaya 139 over ecological sites was observed only for Samara varieties; 6) varieties of all the breeding centers had no stable difference from Bezenchukskaya 139 concerning stability and responsiveness, which can be explained by an incomplete breeding process for these parameters and confrms the importance of the KASIB program; 7) a trend of yield increase compared to Bezenchukskaya 139 under testing in defnite local environments had more stable parameters with the largest progress observed in the Altai Research Institute of Agriculture (135.4 and 163.2 % to Bezenchukskaya 139), which can be explained by a high efciency of breeding of locally adapted varieties in the breeding center.

VRN genes, determining wheat sensitivity to vernalization, are the main genetic system that defnes the duration of the entire growing period and the durations of the main organogenesis phases. To date, several alleles have been described for VRN-1 loci, and allele­specifc primers have been developed that allow rapid identifcation of allelic spectra in common wheat varieties and lines. The unequal influence of different alleles of VRN-1 loci on the duration of the growing period has also been shown; however, there is little information on the effect of the combination of different alleles on heading time. In developing genotypes having different alleles of dominant VRN genes on the base of the same genetic background, it is necessary to study the genetic effects of VRN genes on the duration of the growing season and the individual developmental phases, as well as on productivity. Most varieties presently grown in Russia carry the dominant alleles of two VRN-1 genes: Vrn-A1a and Vrn-B1a or Vrn-B1c; thus, the task was to create lines combining the dominant alleles of Vrn-A1a with Vrn-B1a and Vrn-B1c against the genetic background of the winter variety Bezostaya 1 (Bez1 Vrn-A1a/Vrn-B1a and Bez1 Vrn-A1a/Vrn-B1c). Homozygous plants were isolated in the F2 generation by using known allele­specifc primers for the Vrn-A1 and Vrn-B1 loci. The durations of the tillering–frst node period, which is the key stage determining growing duration, and the period from shoots to heading were signifcantly reduced in lines with a combination of two dominant alleles of VRN-1 loci compared to isogenic lines of Bezostaya 1 with the dominant alleles Vrn-B1a and Vrn-B1c. The duration of these developmental phases also decreased in the obtained lines as compared to the isogenic line containing the dominant Vrn-A1a allele, but the differences were not signifcant. No substantial differences were found in the duration of other growing phases in lines with two dominant alleles of the VRN-1 loci as compared to isogenic lines of Bezostaya 1.

Diversifcation of crop production in the Russian Federation could be partly achieved by the introduction and production of minor and underutilized crops. Green gram or mung bean (Vigna radiata (L.) R. Wilczek) and black gram or urd (V. mungo (L.) Hepper) are grain legume crops cultivated in limited areas in the Russian Federation. Meanwhile, green gram occupies about 8.5 % of the world production area under pulses (without soybean). It is cultivated mainly in countries of Southeast Asia, but production is expanding to the entire subtropical belt of the globe. In our country these crops can be successfully grown on irrigation in a number of regions in the southern area of the European part and the Russian Far East, where the temperatures during their vegetation are about 28–30 °C and always above 15 °C. The purpose of this paper is to summarize the world’s experience in breeding improvement of mung bean and urd as crops with promise for cultivation in certain soil and climatic zones of the Russian Federation. The world production, use of these high-protein crops, history and peculiarities of breeding, including in the USSR, are covered. To expand the production of both crops in the Russian Federation, their popularization and development of breeding are required. Basic requirements for modern varieties include resistance to biotic and abiotic stressors which can be introgressed from wild relatives. The great importance of both crops in the Asian countries led to the rapid development of molecular researches there. The genome of black gram has been fully sequenced, the genome of green gram has been partly sequenced. Some genes and QTL of adaptability traits have been marked and mapped in a number of wild species of the genus Vigna. The role of wild relatives in the breeding of crops concerned is discussed. In the world genebanks, signifcant genetic resources of mung bean and urd have been accumulated. All this creates prerequisites for the development of marker-assistant and genomic breeding.

 Wheat stem rust caused by the biotrophic fungus Puccinia graminis f. sp. tritici is a dangerous disease that seriously damages the economics in many countries of the world. The review contains information about epidemics of wheat stem rust and causes of their emergence worldwide. Recently wheat stem rust epidemics have been recorded in the northern regions of Kazakhstan and on the territories adjacent to Omsk Region of Russia. It has been shown that severe wheat stem rust epidemics occur mainly due to the emergence of new virulent races of the disease agent and to growing susceptible wheat cultivars. New methods of studying the race composition of the fungus are described as well as the use of the previous and current differential sets for race determination of P. graminis f. sp. tritici. The results of developing molecular markers and assessing their effectiveness in studying stem rust races are presented. Wheat stem rust races dominant in major grain-growing countries of the globe and their typical peculiarities are described. The paper contains information on identifcation of race Ug99 and of its variations including data on areas of their dissemination and on their virulence to Sr-resistance genes. The existence and emergence of other races of the agent potentially dangerous for commercially important genes for stem rust resistance is also described. Currently in nature strongly virulent races of P. graminis f. sp. tritici are circulating with wide geographical coverage and their virulence is absolutely different from the virulence of race Ug99. Historical and modern data on studying the race composition of the pathogen in Kazakhstan are summarized. It is stated that the use of the old standard differential set and an incomplete North American system of race nomenclature in experiments prevents measuring similarity between Kazakhstani races and the worldwide known races of the pathogen. It has been shown that there is a need to continue studies on the intraspecies structure of the disease agent’s population in Kazakhstan with the use of the modern differential set, on determination of race composition and ways of emergence of new races potentially dangerous for commercial wheat varieties.

Pyrenophora tritici-repentis (Ptr) is the causative agent of tan spot, one of the yield limiting diseases of wheat, rapidly increasing in wheat growing countries including Kazakhstan. The aim of this study was the identifcation of wheat genotypes with resistance to Ptr race 1 and race 5 and their host­selective effectors (toxins) Ptr ToxA and Ptr ToxB. A common wheat collection of 41 accessions (38 experimental and 3 controls) was characterized using the molecular markers Xfcp623 and XBE444541, diagnostic for the Tsn1 and Tsc2 genes conferring sensitivity to fungal toxins. The coincidence of the marker XBE444541 with resistance to race 5 was 92.11 %, and with Ptr ToxB, 97.37 %. Genotyping results using the marker Xfcp623 confrmed the expected response to Ptr ToxA; the presence/absence of the marker Xfcp623 completely (100 %) coincided with sensitivity/resistance to race 1 and Ptr ToxA. This demonstrates the reliability of the diagnostic marker Xfcp623 for identifying wheat genotypes with resistance to the fungus and insensitivity to Ptr ToxA. The study of the reaction of wheat germplasm to the fungal inoculation and toxin infltration showed that out of 38 genotypes analyzed 30 (78 %) exhibited resistance to both race 1 and race 5, and insensitivity to toxins Ptr ToxA and ToxB. Of most signifcant interest are eight wheat genotypes that showed resistance/insensitivity both to the two races and two toxins. The results of phenotyping were reconfrmed by the molecular markers used in this study. Sensitivity to Ptr ToxB is not always correlated with susceptibility to race 5 and is dependent on the host’s genetic background of the wheat genotype, i. e. on a specifc wheat genotype. The results of the study are of interest for increasing the efciency of breeding based on the elimination of the genotypes with the dominant alleles Tsn1 and Tsc2 sensitive to the toxins Ptr ToxA and ToxB. The genotypes identifed will be used in wheat breeding for resistance to tan spot.

Disease resistance is an important characteristic for each variety of potato, and the search for pathogen resistance markers is one of the primary tasks of plant breeding. Higher plants possess a wide spectrum of enzymes catalyzing the hydrolysis of nucleic acids; it is believed that protection against pathogens is the most probable function of the enzymes. RNases are actively involved in several immune systems of higher plants, for example, systemic acquired resistance (SAR) and genetic silencing, hence RNase activity in plant leaves, as a relatively easily measured parameter, can serve as a good marker for the selection of pathogen resistant varieties. We have analyzed sixteen varieties of potatoes permitted for use on the territory of the Russian Federation and tested the correlation of the level of variety­specifc ribonuclease (RNase) activity with such economically valuable traits as maturity and resistance to viruses, late blight and common scab. In general, the level of RNase activity was variety­specifc, which was confrmed by very small values of average squared error for the majority of tested varieties. We have detected a statistically signifcant positive correlation of RNase activity in potato leaves with increased resistance of varieties to phytopathogenic viruses, a negative correlation with resistance to scab and an absence of a signifcant connection with maturity and resistance to late blight, regardless of the organ affected by the oomycete. Thus, the level of RNase activity in potato leaves can be used as a selective marker for resistance to viruses, while varieties with increased RNase activity should be avoided when selecting resistance to scab.

Intracranial aneurysm (IA) is a complex disease resulting in subarachnoid hemorrhage (SAH) due to a rupture. The average worldwide prevalence of this disease is about 2–5 %, with 50 % of them ending in death or neurological disorders of varying severity, with a high probability of recurrence of hemorrhage during the frst half of the year after rupture. Subarachnoid hemorrhage is annually registered in at least 18 thousand people in Russia. Associations of polymorphic variants rs594942 and rs11603042 of the VEGFB gene in intracranial aneurysm development in the Volga-Ural region of the Russian Federation with the presence of the symptom complex of undifferentiated connective tissue dysplasia (uDST) and arterial hypertension (AH) were investigated. The C* allele rs594942 and rs11603042 of the VEGFB gene is a marker of an increased risk of IA as a whole (p = 0.025; χ2 = 5.052; OR = 1.32) in women as a whole (p = 0.001; χ2 = 10.124; OR = 1.70) and in comorbid state with uDCT (p = 0.002; χ2 = 9.501; OR = 2.34) and AG (p = 0.006; χ2 = 7.385; OR = 2.109). We found that the genotype *C*C of locus rs594942 of the VEGFB gene is a marker of an increased risk of intracranial aneurysm in general (p = 0.017; χ2 = 5.702; OR = 1.49) and among women in general (p = 0.0005; χ2 = 12.078; OR = 2.25) and with the symptomatic complex uCTD (p = 0.007; χ2 = 7.173; OR = 2.67) and AH (p = 0.010; χ2 = 6.471; OR = 2.51). We have obtained new results on the role of polymorphic variants of the VEGFB gene in the formation of intracranial aneurysm, taking into account the presence of the symptom complex uDCT and AH among the residents of the Volga-Ural region of Russia. A burdened comorbid background and the presence of undifferentiated connective tissue dysplasia and arterial hypertension can contribute to an increased risk of intracranial aneurysm, as evidenced by the results of our study.

The review is devoted to the consideration of genetic determination and pathophysiology of one of the forms of hypertensive disease known as low-renin hypertension. At frst glance, the development of low-renin hypertension is “unnatural”, as renin, as a key enzyme of the renin-angiotensin system, which plays an important role in the development of hypertensive disease, is suppressed in low-renin hypertension. At the same time, the most important drugs actual in the treatment of hypertensive disease belong to the renin-angiotensin system blockers. This contradiction was resolved by a study of genetic and pathophysiological mechanisms of hypertension in some groups of patients with characteristic symptoms bringing these people together. Genetic studies of some recent decades using both family analysis and modern molecular genetic technologies have revealed the main mechanisms underlying low-renin hypertension, which can be classifed as certain syndromes with well-defned genetic and clinical features. These syndromes include cases of sporadically occurring somatic mutations in the cells of the adrenal cortex, which begin to produce aldosterone in increased amounts. Also, several oligogenic forms of low-renin hypertension were studied, some of which are associated with the hyperproduction of aldosterone, but in the others the development of low-renin hypertension was associated with mutations of genes involved in regulation of the functioning of the kidney ion channels. The discovery of some types of arterial hypertension with known mechanisms of their development is of paramount importance for medicine, as it allows for targeted efective therapy and in some cases for achieving a complete cure. However, the main contingent of patients with low-renin hypertension belongs to cases with unexplained etiology, as their development is associated with polygenic systems and with a signifcant influence of numerous environmental factors. The study of genetic and physiological mechanisms of various forms of low-renin arterial hypertension provides a good example of how penetration into the intimate mechanisms of the blood pressure regulation in each personal case makes it possible to identify some specifc syndromes and establish its fnal causes. It seems that progress in understanding the causes and mechanisms of essential hypertension lies along this way.

Despite the advances in medicine, about 4 million children under the age of 6 months die annually around the world due to infection, which is 450 deaths per hour (UNISEF, 2009). The degree of development of the immune system of children born in time is determined by many factors, including the immunogenetic similarity or difference of mother and fetus organisms, which, in turn, is due to the genotypes of mating pairs, as well as the selection of surrogate mothers during in vitro fertilization. From our review of the literature, it follows that immunogenetic interactions of mother and fetus organisms, which occur at all stages of pre- and postnatal development, have a signifcant effect on the resistance of offspring to infections and allergens. Before implantation, the mother’s immune responses are formed under the influence of semen fluid antigens, leukocytes and cytokines, as well as under the influence of the genes of the major histocompatibility complex, which are expressed in embryos at the stage of two cells. After implantation, transplacental transfer of immunoglobulins and immunocompetent cells becomes of immunomodulating importance. It is important to emphasize that, although substances with a high molecular weight usually do not pass through the placenta, this rule does not apply to immunoglobulin G (IgG), which, with a molecular weight of about 160 kDa, overcomes the transplacental barrier due to binding to the fetal Fc receptor. The level of IgG in newborns usually correlates with the level of maternal antibodies. During the period of natural feeding, the immune protection of newborns is provided by the mechanisms of innate immunity and the factors of humoral immunity of mothers. It has been shown that immunoglobulins from the milk of many animal species are transferred through the neonatal intestinal epithelium to the blood. Since breast milk contains large amounts of various immunoactive components, including proteins, cytokines, hormones, immunoglobulins, exosomes containing micro-RNA, and viable immune cells, the immunomodulating effects of breast milk persist even after elimination of maternal immunoglobulins from the blood of the offspring, up to maturation. Analysis of a large body of experimental data shows that the study of mechanisms of “motherfetus” and “mother-newborn” interactions are the basis of a knowledge base needed to fnd means of life-long directed modulation of the descendants’ immune status.

Generation of induced pluripotent stem (iPS) cells expanded possibilities of pluripotency and early development studies. Generation of order Carnivora iPS cells from dog (Canis lupus familiaris), snow leopard (Panthera uncia), and American mink (Neovison vison) was previously reported. The aim of the current study was to examine conditions of pinniped fbroblast reprogramming. Pinnipeds are representatives of the suborder Caniformia sharing conservative genomes. There are several ways to deliver reprogramming transcription factors: RNA, proteins, plasmids, viral vectors etc. The most effective delivery systems for mouse and human cells are based on viral vectors. We compared a lentiviral vector which integrates into the genome and a Sendai virus­based vector, CytoTune EmGFP Sendai Fluorescence Reporter. The main advantage of Sendai virus­based vectors is that they do not integrate into the genome. We performed delivery of genetic constructions carrying fluorescent proteins to fbroblasts of seven Pinnipeds: northern fur seal (Callorhinus ursinus), Steller sea lion (Eumetopias jubatus), walrus (Odobenus rosmarus), bearded seal (Erignathus barbatus), Baikal seal (Pusa sibirica), ringed seal (Phoca hispida), and spotted seal (Phoca largha). We also transduced American mink (N. vison), human (Homo sapiens), and mouse (Mus musculus) fbroblasts as a control. We showed that the Sendai virus­based transduction system provides transgene expression one­two orders of magnitude higher than the lentiviral system at a comparable multiplicity of infection. Also, transgene expression after Sendai virus­based transduction is quite stable and changes only slightly at day four compared to day two. These data allow us to suggest that Sendai virus­based vectors are preferable for generation of Pinniped iPS cells.

Human induced pluripotent stem (hiPS) cells are a powerful tool for biomedical research. The ability to create patient-specifc pluripotent cells and their subsequent differentiation into any somatic cell type makes hiPS cells a valuable object for creating in vitro models of human diseases, screening drugs and a future source of cells for regenerative medicine. To realize entirely a potential of hiPScells, effective and precise methods for their genome editing are needed. The CRISPR/Cas9 system is the most widely used method for introducing site-specifc double-stranded breaks into DNA. It allows genes of interest to be knocked out with high efciency. However, knock-in into the target site of the genome is a much more difcult task. Moreover, many researchers have noted a low efciency of introducing target constructs into the hiPS cells’ genome. In this review, I attempt to describe the currently known information regarding the matter of increasing efciency of targeted insertions into hiPS cells’ genome. Here I will describe the most effective strategies for designing the donor template for homology-directed repair, methods to manipulate the double-strand break repair pathways introduced by a nuclease, including control of CRISPR/Cas9 delivery time. A low survival rate of hiPS cells following genome editing experiments is another difculty on the way towards successful knock-in, and here several highly effective approaches addressing it are proposed. Finally, I describe the most promising strategies, one-step reprogramming and genome editing, which allows gene-modifed integration-free hiPS cells to be efciently generated directly from somatic cells.

The modifcation of crop genomes employing functional components of the microbial CRISPR/Cas immune system is a rapidly developing area of applied research. Site-directed plant genome modifcation by this technology involves the construction of Cas endonuclease- and guide-RNA-encoding vectors, delivery of the plasmid DNA into plant cells, processing of the chosen genomic target site by the corresponding gene products and regeneration of plants from modifed cells. The utilization of this technology in local breeding programs is mainly limited by the typically strong genotype dependence of gene transfer and in vitro regeneration procedures, which holds particularly true in cereals. In the present study, an evaluation of in vitro regeneration efciency of immature embryos of ten Siberian barley cultivars revealed that only one of these is on a par with the experimental standard cultivar Golden Promise. This cultivar, namely cv. Aley, was consequently chosen for further experiments on site-directed mutagenesis in leaf mesophyll protoplasts. Two genes controlling hulled vs naked (Nud) and two-rowed vs six-rowed barley (Vrs1) were used as targets to be modifed via polyethyleneglycol-mediated cellular uptake of guide-RNA/Cas9-encoding plasmid DNA. Deep-sequencing of amplicons obtained from protoplast genomic DNA revealed that 6 to 22 percent of the target sites were mutated. The detected modifcations comprised deletions in all three target sites and of various sizes, whereas insertions were observed in only one of the target genes (Vrs1) and were confned to the size of 1 nucleotide. This study demonstrates the possibility of site-directed genome modifcation in Siberian barley. Further steps in technology advancement will require the development of protocols with reduced genotype dependence in terms of both the gene transfer to totipotent cells and the subsequent plant regeneration originating from such cells.

Glioblastoma is a highly lethal brain cancer. Virotherapy with the use of oncolytic viruses has since recently been regarded as a promising approach for the clinic treatment of human glioblastomas. The purpose of this work was to perform a primary evaluation of the Zika virus as a potential oncolytic agent against glioblastomas. In vitro experiments showed that the Zika virus strain MR 766 is able to selectively infect and lyse neoplastic cells of the human glioblastoma cell line U87 MG. The selectivity index (SI, the ratio of infectious titer for tumor cells to titer on normal untransformed cells) was 2·102. The selectivity of the replicative activity of Zika virus in relation to U87 MG glioblastoma cells was additionally confrmed by indirect immunofluorescence. Using the model of immunodefcient SCID mice with subcutaneous xenografts of human glioblastoma U87 MG, a strong antitumor activity of the Zika virus under a course (daily for 4 days) of intratumoral administration of 5·105 TCID50 of Zika virus was shown. Treatment with Zika virus resulted in more than a 10­fold reduction in mean volumes of tumors. The tumor growth inhibition index was 92.63 %. Recurrences (metastases) of tumor re­growth were not registered within 64 days of observation. This result demonstrated the prospect of further in­depth studies of the Zika virus as a potential oncolytic agent against human glioblastomas.

The external drosophila mechanoreceptors, residing on the head and body of imago, are represented by bristles of different sizes (macrochaetes and microchaetes). Macrochaetes are arranged in the species-specifc bristle pattern, where each of them is strictly positioned. The bristle pattern is formed starting from its prototype (prepattern) in the imaginal disc. The position specifcity of future mechanoreceptors is determined by local expression of two proneural genes, achaete (ac) and scute (sc) belonging to the AS-C complex, in response to the action of certain factors, referred to as prepattern factors, nonuniformly distributed in the ectoderm of imaginal discs. The topography of their total distribution defnes the bristle prepattern. Thus, the full-fledged adult bristle pattern is the result of interaction of two systems – the prepattern and the system responding to prepattern, i. e., the achaete and scute genes. A considerable volume of miscellaneous experimental data related to various aspects in development of the bristle pattern has been so far accumulated; however, any formalized and detailed representation of the molecular genetic interaction of the prepattern factors with both each other and the achaete-scute genes is yet absent. This review systematizes the available data on the regular patterns of this interaction and shows that local expression of these genes is determined by hierarchical two-level control system comprising both direct and indirect regulators of their activities. A generalized scheme of the system containing the functional interactions of its components is proposed. The structural organization and principles of operation of the hierarchical molecular genetic system enabling the local expression of ASC genes and the resulting formation of ordered bristle pattern are described.

The purpose of the study is to identify and analyze patterns of the diurnal dynamics of the expression of genes that differ in the shape of the curve. It can be expected that the similarity of the patterns of daily expression (shape of the curve) of genes is a reflection of the synchronization of gene expression by common external and internal signals or participation in similar biological processes. Different signals that have daily dynamics (light, activity, nutrition, stress, temperature, etc.) can affect different levels of expression regulation, which can be manifested in various forms of patterns of daily gene expression. In our research, we used experimental data on gene expression at the level of translation (ribosome profling) in the liver and kidney of a mouse (GSE67305 and GSE81283). To identify genes with a daily rhythm of expression, we used a oneway analysis of variance. To identify similar­in­shape curves of the daily dynamics of gene expression, we propose an approach based on cluster analysis. The distance between the genes was calculated by aligning the phases and fnding the maximum cross­correlation between the patterns of the daily expression of these genes by the cyclic shift. This approach allowed us to identify genes that have not only expression patterns with a single maximum (sinusoidal, asymmetrical, shifted to the left or right, pulsed), but also complex composite signals with several extremes. As a result, the groups of genes united by the similarity of the shape of the daily expression curve without regard to their phase characteristics were identifed. GO enrichment analysis of groups of genes with sharply different patterns of daily expression (sinusoidal and pulsed) in the mouse kidneys and liver showed that the group of genes with a sinusoidal pattern was more associated with regulation of circadian rhythm and metabolism. The group of genes with a pulsed pattern is largely associated with the protective functions of the organism, which require the quick response. Thus, our studies have confrmed the effectiveness of the proposed approach to the analysis of the diurnal dynamics of gene expression. The identifed dynamic patterns of diurnal expression are important for the further study of complex circadian regulation, synchronization and interaction of biological processes with diurnal dynamics in mammals.

Selection by means of genetic markers is a promising approach to the eradication of infectious diseases in farm animals, especially in the absence of effective methods of treatment and prevention. Bovine leukemia virus (BLV) is spread throughout the world and represents one of the biggest problems for the livestock production and food security in Russia. However, recent genome-wide association studies have shown that sensitivity/resistance to BLV is polygenic. The aim of this study was to create a catalog of cattle genes and genes of other mammalian species involved in the pathogenesis of BLV-induced infection and to perform gene prioritization using bioinformatics methods. Based on manually collected information from a range of open sources, a total of 446 genes were included in the catalog of cattle genes and genes of other mammals involved in the pathogenesis of BLV-induced infection. The following criteria were used to prioritize 446 genes from the catalog: (1) the gene is associated with leukemia according to a genome-wide association study; (2) the gene is associated with leukemia according to a case-control study; (3) the role of the gene in leukemia development has been studied using knockout mice; (4) protein-protein interactions exist between the gene-encoded protein and either viral particles or individual viral proteins; (5) the gene is annotated with Gene Ontology terms that are overrepresented for a given list of genes; (6) the gene participates in biological pathways from the KEGG or REACTOME databases, which are over-represented for a given list of genes; (7) the protein encoded by the gene has a high number of protein-protein interactions with proteins encoded by other genes from the catalog. Based on each criterion, a rank was assigned to each gene. Then the ranks were summarized and an overall rank was determined. Prioritization of 446 candidate genes allowed us to identify 5 genes of interest (TNF, LTB, BOLA-DQA1, BOLA-DRB3, ATF2), which can affect the sensitivity/resistance of cattle to leukemia.

Traditionally, studies of the neurobiology of learning and memory focus on the circuitry that interfaces between sensory inputs and behavioral outputs, such as the amygdala and cerebellum. However, evidence is accumulating that some forms of learning can in fact drive stimulus­specifc changes very early in sensory systems, including not only primary sensory cortices but also precortical structures and even the peripheral sensory organs themselves. In this study, we investigated the effect of olfactory associative training on the functional activity of olfactory epithelium neurons in response to an indifferent stimulus (orange oil). It was found that such a peripheral structure of the olfactory system of adult mice as the olfactory epithelium (OE) demonstrates experience­dependent plasticity. In our experiment, associative learning led to changes in the patterns of OE cell activation in response to orange oil in comparison with the control group and animals that were given odor without reinforcement. To interpret the results obtained, we compared the distribution of MRI contrast across the zones of OE in response to a conditioned odor in trained animals and in control animals that were given orange oil at three concentrations: original (used for conditioning), 4­fold higher and 4­fold lower. Since the OE activation patterns obtained coincided in the group of trained animals and controls, which were stimulated with orange oil at the 4­fold higher concentration, it can be concluded that associative conditioning increased the sensitivity of the OE to the conditioned stimulus. The observed increase in OE response to orange oil may be the result of neurogenesis, i. e. the maturation of new olfactory neurons responsive to this stimulus, or the consequence of an increase in individual sensitivity of each OE neuron. Based on data of MRI contrast accumulation in mouse OE, the sensory plasticity way in learning­induced increase in sensitivity of OE to conditioned stimulus is more possible. Thus, the sensory plasticity of the OE plays a signifcant role in the formation of the neuronal response to the provision of an initially indifferent odor and is part of the adaptive responses to the environmental changing.

The number of people with inflammatory bowel disease (IBD) is constantly increasing worldwide. The main factors that have effects on the etiology of the disease are genetic, environmental and immunological. However, the mechanism of disease development and effective treatment of IBD have not yet been found. Animal models help address these problems. The most popular model is considered to be transgenic models in which individual genes are knocked out. One of such models for the study of IBD are mice with a null mutation of the Muc2 gene encoding the Mucin-2 protein, which is involved in the formation of a protective mucin layer in the small and large intestine. Some of transcription factors that change the expression of intestinal genes are involved in the development of IBD and colorectal cancer. One of such transcription factors is “zinc fnger” domain-containing protein Kaiso which is able to bind to methylated DNA. In this study, we assessed the role of Kaiso in the development of intestinal inflammation using the experimental model of C57BL/6Muc2-/-Kaiso-/-. We have shown that mice with impaired intestinal barrier function that develop processes similar to human IBD also develop inflammatory responses, such as increased expression of Il1, Tnf and Il17a genes. The defciency of the Kaiso transcription factor in Mucin-2 knockout mice causes a decrease in the expression level of only the Cox2 and Tff3 genes. Perhaps a decline in the expression of the gene encoding cyclooxygenase-2 can lead to a decrease in the expression of the antibacterial factor Trefoil factor 3. However, in the experimental model of IBD, Kaiso protein did not play a signifcant role in the regulation of pro-inflammatory cytokines of tumor necrosis factor and interleukins 1 and 17.

The relevance of studies of adult neurogenesis is evident in connection with the potential use of these new neurons to replace neurons lost in the process of life. Despite considerable efforts, little is known about the fnal fate of these cells, the functional signifcance of their connections and the regulation of their development. It is known that physical activity signifcantly increases the number of fssile progenitors, the precursors of new neurons in the dentate gyrus of the hippocampus. The existing immunohistochemical methods for labeling new neurons do not allow tracing the temporal dynamics of changes in the volume of brain structures in the same animal, induced by external impacts, such as voluntary exercise. This makes it an urgent task to develop and improve methods for long­term control of changes that occur in the adult hippocampus due to the induction of neurogenesis. The main purpose of this work was to non­invasively track, by using magnetic resonance imaging (MRI), the temporal dynamics of changes in the volume of the hippocampus in the same animals that had voluntary physical activity. It was found that voluntary exercise did not change the total volume of the mouse hippocampus. However, the difference in the volume ratio between the right and left parts of the hippocampus was signifcantly lower compared with the control group. The reconstruction and analysis of protein­protein interactions that ensure the survival of a large number of new neurons and their integration into existing neural networks in the hippocampus have been carried out. The proposed approach allows the non­invasive registration of changes in the ratio of the volumes of these paired brain structures.

One of the crucial elements contributing to the adaptation of organisms to unfavorable environmental conditions is the reaction of stress. The study of its genetic control and role in adaptation to unfavorable conditions are of special interest. The juvenile hormone (JH) acts as a gonadotropic hormone in adult insects controlling the development of the ovaries, inducing vitellogenesis and oviposition. It was shown that a decrease in JH degradation in individuals reacting to adverse conditions by stress reaction (R­individuals) causes delay in egg laying and seems to allow the population to “wait out” the unfavorable conditions, thereby contributing to the adaptation at the population level. However, monitoring natural populations of D. melanogaster for the capability of stress reaction demonstrated that they have a high percentage of individuals incapable of it (NR­individuals). The study of reproductive characteristics of R­ and NR­individuals showed that under normal conditions R­individuals have the advantage of procreating offspring. Under unfavorable conditions, if the stressor is intense enough, NR­individuals die, but if its intensity is low, then they, unlike R­individuals, continue to produce offspring. Based on these data, it was hypothesized that the balance of R­ and NR­alleles in the population ensures its adaptation under frequent stresses of low intensity. To verify the hypothesis by an experiment, the ftness characteristics (lifespan, fecundity) of the R and NR lines of D. virilis were studied under normal conditions and under regular heat stress of various frequency.