[Genotype-Specific Features of Cold-Induced Sweetening Process Regulation in Potato Varieties Nikulinsky, Symfonia, and Nevsky].

In this study, we performed expression analysis of genes associated with cold-induced sweetening in potato tubers: vacuolar invertase (Pain-1), sucrose synthase (SUS4), and invertase inhibitor (InvInh2). Potato varieties Nikulinsky, Symfonia, and Nevsky were used. All three varieties were found to accumulate sugars at low temperatures; the maximum accumulation of reducing sugars was observed at 4°C. It was found that the expression pattern of genes associated with cold-induced sweetening differs depending on the variety and storage duration. The increased expression of vacuolar invertase and its inhibitor is more pronounced at the beginning of storage period, whereas the increased expression of sucrose synthase is more pronounced after 3 months of storage. At early storage periods, high expression of invertase and low expression of inhibitor is observed in the Dutch variety Symfonia, and vice versa in the Russian varieties Nikulinsky and Nevsky. The involvement of the studied genes in the process of cold-induced sweetening is discussed.

Diversification of the Homoeologous Lr34 Sequences in Polyploid Wheat Species and Their Diploid Progenitors.

Allopolyploidization induces a multiple processes of genomic reorganization, including the structurally functional diversification of the homoeologous genes. An example of such diversification is the appearance of the Lr34 gene on chromosome 7D of bread wheat T. aestivum (BAD), the gene conferring durable, race non-specific protection against three fungal pathogens. In this study, we focused on the variability of a functionally critical region between exons 10-12 of Lr34 among diploid progenitors of wheat genomes and their respective polyploids. In the diploid A-genome species, two basic forms of the studied region have been revealed: (1) non-functional forms containing stop codons, or/and frameshifts (T. monococcum/T. urartu) and (2) forms with no such a mutations (T. boeoticum). The Lr34 sequence of T. urartu containing a TGA stop codon was inherited by the first tetraploid T. dicoccoides (BA), and then reorganized in some accessions of this species due to the insertion of an LTR retroelement in exon 10. Besides T. boeoticum, the second form of the Lr34 sequence is also characteristic of A. speltoides, which presumably donated this form to all polyploid descendants bearing B-genome. No differences were found between the D-genome-specific Lr34 sequences studied here and downloaded from databases, implying the highest level of conservation of the Lr34 predecessor throughout evolution. The sequence data were later used to construct phylograms, and apparent peculiarities in the evolution of the studied region of Lr34 genes discussed.

Role of Small Noncoding RNAs in Bacterial Metabolism.

The study of prokaryotic small RNAs is one of the most important directions in modern molecular biology. In the last decade, multiple short regulatory transcripts have been found in prokaryotes, and for some of them functional roles have been elucidated. Bacterial small RNAs are implicated in the regulation of transcription and translation, and they affect mRNA stability and gene expression via different mechanisms, including changes in mRNA conformation and interaction with proteins. Most small RNAs are expressed in response to external factors, and they help bacteria to adapt to changing environmental conditions. Bacterial infections of various origins remain a serious medical problem, despite significant progress in fighting them. Discovery of mechanisms that bacteria employ to survive in infected organisms and ways to block these mechanisms is promising for finding new treatments for bacterial infections. Regulation of pathogenesis with small RNAs is an attractive example of such mechanisms. This review considers the role of bacterial small RNAs in adaptation to stress conditions. We pay special attention to the role of small RNAs in Mycobacterium tuberculosis infection, in particular during establishment and maintenance of latent infection.

[Detection of genetic determinants that define the difference of near-isogenic Triticum aestivum L. Lines in photoperiodic sensitivity].

Identification of genetic determinants that define different degrees of line sensitivity to the photoperiod was conducted on material of near-isogenic lines of the soft hexaploid wheat Triticum aestivum L. using SSR markers and markers specific to the Vrn and Ppd genes. It was established that the Ppd-s line contains a dominant Ppd-Dla allele located on chromosome 2D. This allele is characterized by a vast deletion in the gene promoter region. For two other lines (Ppd-m and Ppd-w), introgression of the Ppd-B1 gene on chromosome 2B was shown from the parental Sonora variety, which is slightly sensitive to the length of the day; however, the previously described Ppd-Bla. 1 allele was not found. Another polymorphism that can cause weak photoperiodic sensitivity, an increased amount of the Ppd-B1 gene copies, was detected for these lines.

[Sleep disorders and oncological diseases]. / Rasstroistva sna i onkologicheskie zabolevaniya.

The study of neurological symptoms and signs connected with neoplasms and antitumor therapy is relevant in the context of an increasing prevalence of cancer. The COVID-19 pandemic and social factors have increased the number of patients suffering from insomnia. Sleep disorders is an unfavorable prognostic factor for neoplasms. The review presents risk factors and mechanisms of sleep disturbance, their relationship with inflammation and dysfunction of the immune system in cancer. In particular, dysfunction of the melatonergic system is discussed as a risk factor for the development of insomnia and cancer. The relevance of developing measures aimed at the rehabilitation of patients in order to restore normal sleep, which plays a fundamental role in maintaining a person's mental and physical health, is emphasized.

The BLUP method in evaluation of breeding values of Russian spring wheat lines using micro- and macroelements in seeds.

Genomic selection is a technology that allows for the determination of the genetic value of varieties of agricultural plants and animal breeds, based on information about genotypes and phenotypes. The measured breeding value (BV) for varieties and breeds in relation to the target trait allows breeding stages to be thoroughly planned and the parent forms suitable for crossing to be chosen. In this work, the BLUP method was used to assess the breeding value of 149 Russian varieties and introgression lines (4 measurements for each variety or line, 596 phenotypic points) of spring wheat according to the content of seven chemical elements in the grain - K, Ca, Mg, Mn, Fe, Zn, Cu. The quality of the evaluation of breeding values was assessed using cross-validation, when the sample was randomly divided into five parts, one of which was chosen as a test population. The following average values of the Pearson correlation were obtained for predicting the concentration of trace elements: K - 0.67, Ca - 0.61, Mg - 0.4, Mn - 0.5, Fe - 0.38, Zn - 0.46, Cu - 0.48. Out of the 35 models studied, the p-value was below the nominal significant threshold (p-value < 0.05) for 28 models. For 11 models, the p-value was significant after correction for multiple testing (p-value < 0.001). For Ca and K, four out of five models and for Mn two out of five models had a p-value below the threshold adjusted for multiple testing. For 30 varieties that showed the best varietal values for Ca, K and Mn, the average breeding value was 296.43, 785.11 and 4.87 mg/kg higher, respectively, than the average breeding value of the population. The results obtained show the relevance of the application of genomic selection models even in such limited-size samples. The models for K, Ca and Mn are suitable for assessing the breeding value of Russian wheat varieties based on these characteristics.

Identification of QTLs associated with grain-filling duration and heading date in wheat.

An increase in genetic diversity of bread wheat caused by spring x winter forms leads to an alteration of genetic control of maturity time. Maturity time (MAT) is one of major yield components in wheat, which has two components: the heading date (HD) and grain-filling period (GFP). Using the Illumina Infinium 25k platform we analyzed the genetic control of the HD, GFP and MAT in the F2 and F2:3 populations from a cross between late-ripening spring/winter line 124-1 and spring wheat cultivar Novosibirskaya 31, possessing the same allelic composition of the VRN1 and PPD-D1 genes. The phenotypic evaluation of the populations studied was performed during three years. A total of 17 QTLs were mapped, out of which 4 QTLs for MAT or its components were confirmed over two years. Two common MAT and HD QTLs were identified on the 4A chromosome, and two loci controlling GFP and MAT were found on 6B chromosome. An environmentally stable HD QTL QHd.icg-7B.1 was associated with the FT-B1 gene having a non-synonymous polymorphism [G/C] in its coding region. A novel НD QTL was identified on 7D chromosome. QTL dissection allowed to propose putative genes for QMat.icg4-A and QMat.icg6-B, namely the SPL family gene (TraesCS4A02G359500) and the TCP transcription factor (TraesCS6B02G462100), respectively. The results of this study provide information for further investigation into wheat development.

Ligand-based virtual screening and biological evaluation of inhibitors of Mycobacterium tuberculosis H37Rv.

Novel antimycobacterial compounds are needed to expand the existing toolbox of therapeutic agents, which sometimes fail to be effective. In our study we extracted, filtered, and aggregated the diverse data on antimycobacterial activity of chemical compounds from the ChEMBL database version 24.1. These training sets were used to create the classification and regression models with PASS and GUSAR software. The IOC chemical library consisting of approximately 200,000 chemical compounds was screened using these (Q)SAR models to select novel compounds potentially having antimycobacterial activity. The QikProp tool (Schrödinger) was used to predict ADME properties and find compounds with acceptable ADME profiles. As a result, 20 chemical compounds were selected for further biological evaluation, of which 13 were the Schiff bases of isoniazid. To diversify the set of selected compounds we applied substructure filtering and selected an additional 10 compounds, none of which were Schiff bases of isoniazid. Thirty compounds selected using virtual screening were biologically evaluated in a REMA assay against the M. tuberculosis strain H37Rv. Twelve compounds demonstrated MIC below 20 µM (ranging from 2.17 to 16.67 µM) and 18 compounds demonstrated substantially higher MIC values. The discovered antimycobacterial agents represent different chemical classes.

A study of the influence of the T2DL.2DS-2SS translocation and the 5S(5D) substitution from Aegilops speltoides on breeding-valuable traits of common wheat.

The use of the gene pool of wild relatives for expanding the genetic diversity of common wheat is an important task of breeding programs. However, the practical application of common wheat lines with alien genetic material is constrained by the lack of information on chromosomal rearrangements and the negative impact of the transferred material on agronomically important traits. This research is aimed at studying 14 introgression lines with the T2DL.2DS-2SS translocation and the 5S(5D) substitution from Aegilops speltoides obtained from crossing common wheat varieties (Aurora, Krasnodarskaya 99, Nika Kubani) with the genome-substituted form Avrodes (BBAASS). Hybrid lines with different combinations of T2DL.2DS-2SS and T1BL.1RS translocations and 5S(5D) substitution were characterized by resistance to leaf and yellow rusts, productivity components and technological qualities of grain. The assessment of the varieties' resistance to rust diseases showed that Krasnodarskaya 99, Nika Kubani and the Aurora variety, which is a carrier of the T1BL.1RS translocation, are highly susceptible to diseases, while the presence of the T2DL.2DS-2SS translocation and the 5S(5D) substitution, both together and separately, provides resistance to fungal pathogens. The analysis of the lines using markers designed for known resistance genes of Ae. speltoides did not reveal the presence of the Lr28, Lr35 and Lr51 genes in the lines. The results suggest that the genetic material of Ae. speltoides transferred to chromosomes 2D and 5D contains new resistance genes. To determine the effect of the T2DL.2DS-2SS translocation and the 5S(5D) substitution on the productivity and technological qualities of grain, the lines were assessed by weight of 1000 grains, grain weight and number of ears per 1 m2, by protein and gluten content, gluten quality and general baking evaluation. A positive effect was determined upon the weight of 1000 grains, protein and gluten content. There were no significant differences in other characteristics. The T2DL.2DS-2SS translocation and the 5S(5D) substitution did not have a negative effect on the productivity and technological quality of grain, and are of interest for breeding practice.

Diversification of the duplicated F3h genes in Triticeae.

The F3h gene encodes the flavonoid synthesis enzyme flavanone 3-hydroxylase. Unlike most plant genomes, the bread wheat (Triticum aestivum L.) B genome has two, rather than just one F3h copy. The paralogous F3h-B2 sequence was isolated by PCR and shown to be transcribed, but its predicted polypeptide differed from the typical F3H sequence at a number of the conserved residues associated with its putative substrate-binding sites. The F3h-B2 promoter region was highly divergent from that of F3h-B1, and the transcriptional profiles of the two genes were distinct. Among a panel of 95 Triticeae accessions, representing 24 species, an F3h-2 copy was only detected within those carrying a B, S, G, or an R genome. Analysis of the coding sequence divergence suggested that a small segmental duplication occurred early in the evolution of the Triticeae tribe. The duplicated F3h copy appears to have acquired a novel function in the progenitor of the closely related B, G, and S genomes, as well as in the R genome. In other Triticeae genomes, the F3h-2 paralog may have been lost following pseudogenization.

The effect of two differentially expressed wheat VRN-B1 alleles on the heading time is associated with structural variation in the first intron.

We measured the level of VRN-B1 transcripts within near-isogenic lines of Triticum aestivum cultivar 'Bezostaya 1' carrying two VRN-B1 alleles from cultivars 'Saratovskaya 29' and 'Diamant 2' (VRN-B1c and VRN-B1a, respectively). Both lines have similar kinetics of VRN-B1 transcript accumulation at the third to fifth leaf stages. However, quantitative PCR analysis at the third leaf stage showed that the VRN-B1c allele was transcribed 10 times faster than the VRN-B1a allele. The F1 hybrid between the lines is more similar to the line carrying the VRN-B1a allele with regard to the level of VRN-B1 transcription. The difference in the transcript levels of the VRN-B1 alleles appears to be due to the previously identified structural changes in the first intron of VRN-B1c (deletion of 0.8 kb and duplication of 0.4 kb) as compared with VRN-B1a, as no other differences were revealed in the present study. We suggested that the first intron structural changes in the VRN-B1c allele as compared with VRN-B1a result in a higher level of VRN-B1 transcripts and an earlier heading time. We confirmed that the expression of the dominant VRN-1 gene induces transcription of the recessive homoeoalleles, coupled with the reduction of the transcript level of a flowering repressor VRN-2.

[Epigenetic regulation of expression of vernalization genes].

We reviewed the mechanisms of epigenetic regulation of vernalization genes of plants which control the transition to the generative stage, depending on the low temperatures. Based on the example of FLC-gene of Arabidopsis, the involvement of the PR2 repression complex and non-coding RNAs in these mechanisms has been shown. On the basis of our own and other data, the authors suggest a similar mechanism of regulation of Vrn-1 gene of cereals.

[A comparative genetic and cytogenetic mapping of wheat chromosome 5B using introgression lines].

The genetic map of chromosome 5B has been constructed by using microsatellite (SSR) analysis of 381 plants from the F2 population produced by cross of the Chinese Spring (CS) and Renan cultivars. Initially, 180 SSR markers for the common wheat 5B chromosome have been used for analysis of these cultivars. The 32 markers able to detect polymorphism between these cultivars have been located on the genetic map of chromosome 5B. Cytogenetic mapping has involved a set of CS 5B chromosome deletion lines. Totally, 51 SSR markers have been located in ten regions (deletion bins) of this chromosome by SSR analysis of these deletion lines. Five genes--TaCBFIIIc-B10, Vrn--B1, Chi--B1, Skr, and Ph1--have been integrated into the cytogenetic map of chromosome 5B using the markers either specific of or tightly linked to the genes in question. Com- parison of the genetic and cytogenetic maps suggests that recombination is suppressed in the pericentromeric region of chromosome 5B, especially in the short arm segment. The 18 markers localized to deletion bins 5BL16-0.79-1.00 and 5BL8-0.66-0.79 have been used to analyze common wheat introgression lines L842, L5366-180, L73/00i, and L21-4, carrying fragments of alien genomes in the terminal region of 5B long arm. L5366-180 and L842 lines carry a fragment of the Triticum timopheevii 5GL chromosome, while L73/00i ? L21-4 lines, a fragment of the Aegilopsspeltoides 5SL chromosome. As has been shown, the translocated fragments in these four lines are of different lengths, allowing bin 5BL18-0.66-0.79 to be divided into three shorter regions. The utility of wheat introgression lines carrying alien translocations for increasing the resolution of cytogenetic mapping is discussed.

[Comparative Characteristic of Triticum aestivum/Triticum durum and Triticum aestivum/Triticum dicoccum hybrid lines by genomic composition and resistance to fungal diseases under different environmental conditions].

The genetic diversity of common wheat hybrid lines Triticum aestivum/Triticum durum and Triticum aestivum/Triticum dicoccum (2n = 42, F(6-7)) using chromosome-specific microsatellite (SSR) markers and C-staining of chromosomes was studied. Cluster analysis of data obtained by 42 SSR markers indicated that the hybrid lines can be broken into three groups according to their origin. There were two cases of complete genetic similarity between lines 183(2)-2/184(1)-6 and-208-3/213-1, which were obtained using common wheat as the parental plants. In cross combinations, when the stabilization of the nuclear genome of hexaploid lines occurred against a background of the cytoplasmic genome of tetraploid wheats, there was a high level of divergence between sister lines, in some cases exceeding 50%. The evaluation of the degree of susceptibility of the lines to powdery mildew, leaf and stem rust, and septoria leafblotch was performed under different environmental conditions. It was shown that resistance to powdery mildew and leaf rust significantly depended on the region where assays were conducted. An evaluation of the field data showed that he lines 195-3, 196-1, and 221-1 with T. durum genetic material displayed complex resistance to fungal pathogens in Western Siberia and the Republic of Belarus. For lines 195-3 and 196-1, one shows a possible contribution of chromosomes 4B and 5B in the formation of complex resistance to diseases. Hybrid lines with complex resistance can be used to expand the genetic diversity of modern common wheat cultivars for genes of immunity.

[Efficacy of Mexidol in the correction of postcovid syndrome in patients with chronic cerebrovascular diseases]. / Effektivnost' preparata Meksidol v korrektsii postkovidnogo sindroma u patsientov s khronicheskimi tserebrovaskulyarnymi zabolevaniyami.

OBJECTIVE: To evaluate the effectiveness of sequential therapy with Mexidol and Mexidol FORTE 250 in the correction of postcovoid syndrome (PKS) in patients with chronic cerebrovascular diseases (CVD). MATERIAL AND METHODS: The analysis of the results of examination and treatment of 110 patients with CVD who underwent COVID-19 was carried out. Patients of the main group (OH, n=55) received Mexidol (5 ml IV drip for 14 days, followed by the transition to the tablet form of Mexidol FORTE 250 1 table 3 times/day for 2 months); 55 patients of the comparison group (GS) did not receive antioxidants. All patients included in the study were conducted MRI examination and extensive neuropsychological testing. RESULTS: There was a significant improvement in the state of cognitive functions, regression of symptoms of asthenia, improvement of night sleep in patients with OG. The differences were statistically significant both in comparison with the baseline level and the HS. CONCLUSION: The administration of the drug does not require age-related dose adjustment and is well combined with basic therapy. The recommended regimen for the use of Mexidol: 14 days of 5 ml i/v or i/m, then taking the drug Mexidol FORTE 250 at a dose of 1 table 3 times/day for 2 months.

GBS-DP: a bioinformatics pipeline for processing data coming from genotyping by sequencing.

The development of next-generation sequencing technologies has provided new opportunities for genotyping various organisms, including plants. Genotyping by sequencing (GBS) is used to identify genetic variability more rapidly, and is more cost-effective than whole-genome sequencing. GBS has demonstrated its reliability and flexibility for a number of plant species and populations. It has been applied to genetic mapping, molecular marker discovery, genomic selection, genetic diversity studies, variety identification, conservation biology and evolutionary studies. However, reduction in sequencing time and cost has led to the need to develop efficient bioinformatics analyses for an ever-expanding amount of sequenced data. Bioinformatics pipelines for GBS data analysis serve the purpose. Due to the similarity of data processing steps, existing pipelines are mainly characterised by a combination of software packages specifically selected either to process data for certain organisms or to process data from any organisms. However, despite the usage of efficient software packages, these pipelines have some disadvantages. For example, there is a lack of process automation (in some pipelines, each step must be started manually), which significantly reduces the performance of the analysis. In the majority of pipelines, there is no possibility of automatic installation of all necessary software packages; for most of them, it is also impossible to switch off unnecessary or completed steps. In the present work, we have developed a GBS-DP bioinformatics pipeline for GBS data analysis. The pipeline can be applied for various species. The pipeline is implemented using the Snakemake workflow engine. This implementation allows fully automating the process of calculation and installation of the necessary software packages. Our pipeline is able to perform analysis of large datasets (more than 400 samples).

[The impact of Ty3-gypsy group retrotransposon Lila on D-genome specificity of wheat Triticum aestivum L].

An analysis of the primary structure of BAC clone 112D20 T. aestivum, that contains D-genome specific Ty3-gypsy-retrotransposon Lila is presented. PCR analysis of nulli-tetrasomic and deletion lines of T. aestivum allowed to localize this BAC clone in the distal region of the long arm of chromosome 5D. Characteristic feature of BAC clone 112D20 is a high concentration of Ty3-gypsy-retrotransposons (61.7%), and low content of the genes (1.2%). Only a single open reading frame was revealed homologous to an unknown gene of Ae. tauschii. Specific to the D-genome Ty3-gypsy-retrotransposon Lila in the BAC clone 112D20 is 14 kb in length and contains unequal in size long terminal repeats. The data of in situ hybridization and PCR analysis of different Triticeae species suggest that this retroelement was amplified within the ancestral species of Ae. tauschii, the donor D-genome. The suggested time of amplification based on estimation of insertion time of Lila 112D20 is 1.7 million years, which corresponds to the formation of the first allopolyploid forms of wheat. Based on comparison with the previously obtained data, it is concluded that the amplification ofretroelements specific to each genome of wheat took place during formation of the diploid progenitors of these genomes.

[Construction and study of leaf rust-resistant common wheat lines with translocations of Aegilops speltoides Tausch].

Genotyping was performed for the leaf rust-resistant line 73/00i (Triticum aestivum x Aegilops speltoides). Fluorescence in situ hybridization (FISH) with probes Spelt1 and pSc119.2 in combination with microsatellite analysis were used to determine the locations and sizes of the Ae. speltoides genetic fragments integrated into the line genome. Translocations were identified in the long arms of chromosomes 5B and 6B and in the short arm of chromosome 1B. The Spelt1 and pSc119.2 molecular cytological markers made it possible to rapidly establish lines with single translocation in the long arms of chromosomes 5B and 6B. The line carrying the T5BS x 5BL-5SL translocation was highly resistant to leaf rust, and the lines carrying the T6BS x 6BL-6SL translocation displayed moderate resistance. The translocations differed in chromosomal location from known leaf resistance genes transferred into common wheat from Ae. speltoides. Hence, it was assumed that new genes were introduced into the common wheat genome from Ae. speltoides. The locus that determined high resistance to leaf rust and was transferred into the common wheat genome from the long arm of Ae. speltoides chromosome 5S by the T5BS x 5BL-5SL translocation was preliminarily designated as LrAsp5.

32Starch metabolism in potato Solanum tuberosum L.

Starch is a major storage carbohydrate in plants. It is an important source of calories in the human and animal diet. Also, it is widely used in various industries. Native starch consists of water-insoluble semicrystalline granules formed by natural glucose polymers amylose and amylopectin. The physicochemical properties of starch are determined by the amylose:amylopectin ratio in the granule and degrees of their polymerization and phosphorylation. Potato Solanum tuberosum L. is one of the main starch-producing crops. Growing industrial needs necessitate the breeding of plant varieties with increased starch content and specified starch properties. This task demands detailed information on starch metabolism in the producing plant. It is a complex process, requiring the orchestrated work of many enzymes, transporter and targeting proteins, transcription factors, and other regulators. Two types of starch are recognized with regard to their biological functions. Transitory starch is synthesized in chloroplasts of photosynthetic organs and degraded in the absence of light, providing carbohydrates for cell needs. Storage starch is synthesized and stored in amyloplasts of storage organs: grains and tubers. The main enzymatic reactions of starch biosynthesis and degradation, as well as carbohydrate transport and metabolism, are well known in the case of transitory starch of the model plant Arabidopsis thaliana. Less is known about features of starch metabolism in storage organs, in particular, potato tubers. Several issues remain obscure: the roles of enzyme isoforms and different regulatory factors in tissues at various plant developmental stages and under different environmental conditions; alternative enzymatic processes; targeting and transport proteins. In this review, the key enzymatic reactions of plant carbohydrate metabolism, transitory and storage starch biosynthesis, and starch degradation are discussed, and features specific for potato are outlined. Attention is also paid to the known regulatory factors affecting starch metabolism.

Infections, Pandemics, and Sleep Disorders.

Studies of the neurological symptoms and signs associated with the acute and late phases of infectious diseases are important in pandemic conditions. The novel coronavirus infection (COVID-19) pandemic has increased the number of patients with sleeplessness, this being an adverse prognostic factor for infections. This review addresses the factors and mechanisms of sleep impairments and their relationship with inflammation and immune system dysfunction in infectious diseases. In particular, impairments to the functioning of the melatoninergic system are discussed as the cause of sleeplessness during pandemics. The relevance of developing measures for rehabilitating patients, particularly use of Sonnovan to restore normal sleep, which plays a fundamental role in supporting people's mental and physical health, is emphasized.