Genetic Peculiarities Research Articles

Selenium Biofortification of Allium Species

Allium species have great potential in the production of functional food via selenium biofortification. This review is devoted to the specificity of Allium plant biofortification with Se, including the genetic peculiarities, effect of the chemical form of the microelement, methods of supply, sulfur and AMF effects, and hormonal regulation. The biosynthesis of methylated Se amino acids and the beneficial effect of Se treatment on secondary metabolite accumulation and plant yield are discussed. Special attention is paid to the production of functional foods based on Allium plants enriched in different ways: bread with leek leaf powder, Allium microgreens and seedlings, and ‘Black garlic’ biofortified with Se. Further focus is provided to the high variability of Allium crop yield and quality under Se supply governed by genetic factors and environmental stresses, and to the need for plant growth technology optimization to obtain the predicted nutritional characteristics of the derived functional product with high anti-carcinogenic activity.

Home and Spread of Indo-European Tribes in the Light of Name Research

Today, large parts of Europe are populated by speakers of Indo-European languages. People have long wondered where they came from, where their original home was. Archeology has long been trusted to provide a solution to the problem. This has now been abandoned. Today there is a great deal of trust in the results of genetic research, which can certainly contribute to important findings. However, one should not forget an important aspect: when one looks for the speakers of Indo-European languages, one is not looking for specific material finds (devices, weapons, etc.) or for the carriers of certain genetic peculiarities, but for the speakers of languages. Their homeland and distribution can only be determined using linguistic methods. The languages alone are crucial. And at this point a scientific discipline that is based on languages comes into view: it is place name research. Place and river names are firmly anchored in the original region. They often pass on their names to changing populations and are therefore undoubtedly the most important witnesses to the history of peoples and languages. And another scientific discipline must be included: agricultural science, because early settlements were based on good and productive soils that enabled continuous settlement. With the help of geographical names and the distribution of Europe's good soils, the study determines the original settlements of the Slavs on the northern slope of the Carpathians, the Germanic tribes north of the Harz and those of the Celts on the western edge of the Carpathians. River names that can be assigned to Old European, i.e. Indo-European, hydronymy also show that old ones come from almost all settlement areas. There is evidence of connections to the Baltics and the Baltic languages. The Baltics are therefore the center of Indo-European names and there is no reason not to consider them as the starting area and home of Indo-European expansions. A homeland outside of Old European hydronymy, be it in southern Russia or in Asia Minor or in the Caucasus, as is often assumed today, especially on the basis of genetic studies, is excluded.

Pre-pregnancy training of women with early pregnancy loss and adenomyosis, taking into account folate cycle gene polymorphisms

Polymorphisms in folate cycle genes (methylene tetrahydrofolate reductase – MTHFR, methionine synthase reductase – MTRR and methionine synthase – MTR) and associated hyperhomocysteinemia and folate deficiency play an important role among multiple genetic causes early pregnancy loss.The results of studies examining the influence of polymorphic variants of the folate cycle genes in women with pregnancy losses are quite contradictory. It has been proven that prescribing folic acid preparations or in combination with other vitamins and trace elements at the stage of preparation for pregnancy and during pregnancy significantly reduces the risk of miscarriage and pregnancy loss, is an important prevention of defects in the development of the nervous system of the fetus and disorders of the autistic spectrum in newborns and children. Adenomyosis remains a complex and urgent problem in obstetrics and gynecology, as today there is convincing evidence of the negative impact of adenomyosis both on fertility and on the course and outcomes of pregnancy.The objective: to study the prevalence of folate cycle gene polymorphisms and to assess the effectiveness of vitamin-mineral complex use in the pre-gravid preparation taking into account the genetic peculiarities of folate metabolism in women with early pregnancy loss (EPL) and adenomyosis.Materials and methods. Data from the examination at the stage of pre-gravid preparation of 40 women with early pregnancy loss – EPL (5–13 weeks of gestation) and adenomyosis, which were included in the main group, and 34 women with adenomyosis without a history of EPL (control group) were analyzed.Resuts. In 73,5% of women of the control group, the C/C genotype of the MTHFR 677 C>T gene prevailed, in women with EPL and adenomyosis, a significant increase in the frequency (50%) of the heterozygous polymorphism for this C/T allele of the MTHFR 677 gene and a decrease in the frequency of detection of neutral A/A allele and increased frequency (80%) of MTHFR 1298 gene allele polymorphism (A/C and C/C). In women with EPL and adenomyosis, a significant increase in homocysteine (12,8±2,3мμmol/l) and a deficiency of folic acid (5,0±0,9 ng/ml) in blood serum compared to reference values were found.Conclusions. The use of vitamin-mineral complex, which includes betaine (200 mg), cystine (200 mg), zinc (10 mg), niacin (16 mg), folic acid (in the form of 5-MTHF-glucosamin – 400 mcg), vitamin B12 (in the form of methylcobalamin – 2.5 mcg), vitamin B6 (1.4 mg) and riboflavin (1.4 mg), 1 tablet 1-2 times a day for 3 months for the pre-gravid preparation leaded to significant decrease of homocysteine concentration, normalization of folic acid concentration. This formed favorable conditions for pregnancy course and for risk reduction of possible obstetrical complications.

Genetic and Epigenetic Characteristics in Isolated Pancreatic Metastases of Clear-Cell Renal Cell Carcinoma.

Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC. The genetic and epigenetic causes of exclusive pancreatic involvement have not yet been investigated and are currently unknown. Conversely, according to the few available data in the literature, the following genetic and epigenetic peculiarities can already be identified as the cause of the protracted course: 1. high genetic stability of the tumour cell clones in both the primary tumour and the pancreatic metastases; 2. a low frequency of copy number variants associated with aggressiveness, such as 9p, 14q and 4q loss; 3. in the chromatin-modifying genes, a decreased rate of PAB1 (3%) and an increased rate of PBRM1 (77%) defects are seen, a profile associated with a favourable course; 4. an increased incidence of KDM5C mutations, which, in common with increased PBRM1 alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.

Phenotypic and Genomic Characterization of the Comune di Sicilia Goat: Towards the Conservation of an Endangered Local Breed.

The Comune di Sicilia, a local goat breed from Sicily (Italy), is currently undergoing recognition as a distinct breed. This study aims to characterize the population both phenotypically and genomically to advance its recognition process. A total of 78 subjects from two locations were enrolled, and their phenotypic data, including qualitative traits and morphometric measurements of adult animals, were recorded and statistically analyzed. The goats were genotyped using the Illumina 50 k Goat SNPchip, comparing them with 473 goats from 15 Italian breeds. Population structure, phylogenetic relationships, admixture, and genomic inbreeding were analyzed. Additionally, subjects with different morphological traits were compared using FST and runs of homozygosity, leading to the identification of potential candidate genes associated with anotia and wattle presence in goats. The Comune di Sicilia breed exhibited distinctive genomic and phenotypic features, setting it apart from other breeds in the same region. However, moderate variability, possibly influenced by selection practices, was also observed. To ensure the breed's preservation and prevent excessive inbreeding, a comprehensive approach considering both morphology and genomic background is recommended. This study contributes valuable insights into the genetic peculiarities of the Comune di Sicilia goat, supporting its recognition as a unique and valuable breed.

Оцінка генетичної мінливості племінних стад амурського сазана (Cyprinus rubrofuscus Lacépède, 1803)

Purpose. To study the genetic peculiarities of pedigree tocksof Amur carp and evaluate its genetic variability by analyzing distribution of alleles and genotypes by the specific protein systems and cytogenetic parameters. Methodology. Analysis of polymorphism of protein systems was performed using electrophoresis in polyacrylamide gel. As protein markers to evaluate the genetic structure of Amur carp stocks, the separation of allelic and genotypic frequencies by loci, which encode a number of fish blood proteins, were used: transferrin (TF), albumin (ALB) and esterase (EST, 3.1.1.1). Cytogenetic analysis was performed using the micronucleus test and analysis of apoptosisfrequencies. Collection and processing of biological material of fish as well as statistical processing of the obtained data was performed using generally accepted methods. Findings. A comprehensive analysis of the genetic structure of Amur carp from three farms in Ukraine was carried out by protein systems and cytogenetic markers. The results of the study showed that all pedigree groups of Amur carp were characterized by a deviation towards the predominance of heterozygotes (Fis = from –0.084 to –0.344). A minimal imbalance was observed in the group of carp from the farm “Karpatskyi Vodogray” LLC (Fis = –0.084). The maximum violation of the genetic balance was found in carp from the farm of JSC “Sumyrybhosp” (Fis = –0.308) and in the group from the experimental farm “Veliky Lyubin” (Fis = –0.344). In general, the analysis of the protein systems of fish blood showed a high level of heterogeneity of pedigree stocks of Amur carp from different farms in Ukraine. The analysis of frequencies of cytogenetic parameters of Amur carp from three fish farms showed that fish from fish farms of JSC “Sumyrybhosp” and PFE “Dzherelo” were characterized by a lower frequency of erythrocytes with micronuclei (EMN) (3.3±0.3 ‰), (3.2±0.3 ‰), lymphocytes with micronuclei (LMN) (2.1±0, 2 ‰), (1.9±0.2 ‰), and apoptosis (4.2±0.3‰), (4,3±0,3‰) compared to the group from fish farm “Karpatskyi Vodogray” LLC, where these values were as follows: EMN (4.7±0.3 ‰), LMN (2.4±0.2‰), apoptosis (5.6±0.4‰). These results indicates a lower level of destabilization of chromosomal apparatus of Amur carp from the fish farm JSC “Sumyrybhosp” at the time of the study. Originality. A comprehensive evaluation of the level of variability of the genetic structure of pedigree stocks of Amur carp from different regions of Ukraine was performed for the first time. Practical Value. Pedigree socksof Amur carp have important practical value in selective breeding work with carps, including works for obtaining hybrid lines to increase the resistance of breeding material. Keywords: Amur carp, genetic structure, locus, alleles, genotype, heterozygosity, micronucleus test, cytogenetic analysis.

Polymorphism of Saccharomyces cerevisiae Strains in DNA Metabolism Genes.

Baker's yeast, S. cerevisiae, is an excellent model organism exploited for molecular genetic studies of the mechanisms of genome stability in eukaryotes. Genetic peculiarities of commonly used yeast strains impact the processes of DNA replication, repair, and recombination (RRR). We compared the genomic DNA sequence variation of the five strains that are intensively used for RRR studies. We used yeast next-generation sequencing data to detect the extent and significance of variation in 183 RRR genes. We present a detailed analysis of the differences that were found even in closely related strains. Polymorphisms of common yeast strains should be considered when interpreting the outcomes of genome stability studies, especially in cases of discrepancies between laboratories describing the same phenomena.

Molecular profiling of male breast cancer by multigene panel testing: Implications for precision oncology.

Compared with breast cancer (BC) in women, BC in men is a rare disease with genetic and molecular peculiarities. Therapeutic approaches for male BC (MBC) are currently extrapolated from the clinical management of female BC, although the disease does not exactly overlap in males and females. Data on specific molecular biomarkers in MBC are lacking, cutting out male patients from more appropriate therapeutic strategies. Growing evidence indicates that Next Generation Sequencing (NGS) multigene panel testing can be used for the detection of predictive molecular biomarkers, including Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI). In this study, NGS multigene gene panel sequencing, targeting 1.94 Mb of the genome at 523 cancer-relevant genes (TruSight Oncology 500, Illumina), was used to identify and characterize somatic variants, Copy Number Variations (CNVs), TMB and MSI, in 15 Formalin-Fixed Paraffin-Embedded (FFPE) male breast cancer samples. A total of 40 pathogenic variants were detected in 24 genes. All MBC cases harbored at least one pathogenic variant. PIK3CA was the most frequently mutated gene, with six (40.0%) MBCs harboring targetable PIK3CA alterations. CNVs analysis showed copy number gains in 22 genes. No copy number losses were found. Specifically, 13 (86.7%) MBCs showed gene copy number gains. MYC was the most frequently amplified gene with eight (53.3%) MBCs showing a median fold-changes value of 1.9 (range 1.8-3.8). A median TMB value of 4.3 (range 0.8-12.3) mut/Mb was observed, with two (13%) MBCs showing high-TMB. The median percentage of MSI was 2.4% (range 0-17.6%), with two (13%) MBCs showing high-MSI. Overall, these results indicate that NGS multigene panel sequencing can provide a comprehensive molecular tumor profiling in MBC. The identification of targetable molecular alterations in more than 70% of MBCs suggests that the NGS approach may allow for the selection of MBC patients eligible for precision/targeted therapy.

Genetic Peculiarities, Gold-Containing Volcanogenic Deposits of the Non-Ferrous Metals of the Paleoisland-Arc Structures of the Lesser Caucasus and East Pontides according to Gas-Fluid Inclusions Data and Isotopic Investigations

The geological settings of deposits exploration in Turkey, Azerbaijan, Armenia and Georgia have been determined in the article. Most of them can be related to the Kuroko type and they are differed by ore accumulation nature

Оценка риска нарушения состояния гепатобилиарной системы у работников производства бутилового каучука с учетом анализа полиморфного варианта rs1052133 гена OGG1

Contemporary petrochemical productions maintain strict control over contents of adverse chemicals in workplace air. Despite that, the chemical factor remains one of the major harmful occupational factors and can produce adverse effects on workers’ health by increasing, among other things, risks of general somatic diseases. Given that, prevention of chronic non-communicable diseases in workers employed at chemical productions remains a vital challenge for occupational medicine. A way to tackle it is to timely detect risk groups relying on, among other things, analysis of workers’ genetic peculiarities. This article presents a study with 140 volunteers participating in it; they had basic occupations required at contemporary butyl rubber production. It was conducted within a periodical medical examination that involved using up-to-date hygienic, clinical-laboratory and genetic methods. The study included hygienic assessment of the chemical factor at the analyzed production, examination of hematologic and biochemical blood indicators, identification of workers’ genetic status as per the rs1052133 polymorphic variant of the OGG1 gene and the severity of DNA breaks. The study revealed adverse effects produced by the chemical factors on health of workers with basic occupations based on deviations in biochemical blood indicators obtained by tests that included indicator enzyme identification, and DNA damage. Following the study results, a risk group was created as per the state of the hepatobiliary system. To preserve workers’ health, it is necessary to implement certain preventive measures that include providing safe working conditions as regards the chemical factor, timely detection of risk groups and rehabilitation activities.

Assessing risks of functional disorders of hepatobiliary system in workers employed at butyl rubber production allowing for analysis of the ogg1 gene polymorphic variant rs1052133

Contemporary petrochemical productions maintain strict control over contents of adverse chemicals in workplace air. Despite that, the chemical factor remains one of the major harmful occupational factors and can produce adverse effects on workers’ health by increasing, among other things, risks of general somatic diseases. Given that, prevention of chronic non-communicable diseases in workers employed at chemical productions remains a vital challenge for occupational medicine. A way to tackle it is to timely detect risk groups relying on, among other things, analysis of workers’ genetic peculiarities. This article presents a study with 140 volunteers participating in it; they had basic occupations required at contemporary butyl rubber production. It was conducted within a periodical medical examination that involved using up-to-date hygienic, clinical-laboratory and genetic methods. The study included hygienic assessment of the chemical factor at the analyzed production, examination of hematologic and biochemical blood indicators, identification of workers’ genetic status as per the rs1052133 polymorphic variant of the OGG1 gene and the severity of DNA breaks. The study revealed adverse effects produced by the chemical factors on health of workers with basic occupations based on deviations in biochemical blood indicators obtained by tests that included indicator enzyme identification, and DNA damage. Following the study results, a risk group was created as per the state of the hepatobiliary system. To preserve workers’ health, it is necessary to implement certain preventive measures that include providing safe working conditions as regards the chemical factor, timely detection of risk groups and rehabilitation activities.

Species Diversity in the Fusarium solani (Neocosmospora) Complex and Their Pathogenicity for Plants and Humans

The Fusarium solani species complex is a large group of soil saprotrophs with a broad adaptive potential, which allows the fungi to exist under various conditions and to parasitize on different hosts. The review analyzes the modern data concerning the genetic peculiarities of species from this complex by the example of F. solani f. sp. pisi and generalizes the data on the most widespread species pathogenic for both plants and humans. The enhanced resistance of the F. solani species complex to the most of modern antifungal agents and the need for novel therapeutic agents against fusariosis has been considered.

Donors of ultra-earliness for spring common wheat breeding

Knowledge of productivity and genetic control of the rate of ultra-early lines development will facilitate their use in breeding of common wheat Tritium aestivum L. for high adaptive capacity. The research focused on ultra-early lines Rico (k-65588), Rimax (k-67257) (progeny of F3 Rico × ‘Max’, k-57181), Fori 1-8 line series (progeny of F4 ‘Photon’ × Rico) and Rifor 1-13 (progeny of F7-8 Rico × ‘Forlani Roberto’), as well as on the accessions ‘Photon’ (k-55696) and ‘Forlani Roberto’ (k-42641). The varieties ‘Leningradskaya 6’ (k-64900) and ‘Leningradskaya 97’ (k-62935) were used as standards in VIR, and ‘Chelyaba 2’ (k-64379) was used in Сhelyabinsk ARI. The alleles of Vrn and Ppd genes were identified by PCR using the published allele-specific primers. Responses to vernalization (30 days at 3°C) and to a short 12-hour day were determined according to the VIR guidelines. The ultra-earliness of common wheat lines is associated with the presence of dominant alleles Vrn-A1, Vrn-B1, Vrn-D1, Ppd-B1, Ppd-D1, and possibly Eps. The shortest emergence-to-heading period at two experimental locations was noted for Rico (39.9 ± 1.49 days), which is 14.8 ± 1.22 days earlier than the development of region-adapted varieties. The Rico genotype contains Vrn-A1, Vrn-B1, Vrn-D1, Ppd-B1 and Ppd-D1. In the Rimax genotype, different alleles of the Ppd-D1 and Vrn-B1 genes were found, possibly being a result of recombination processes in Rico × ‘Max’ hybrids. Under a short photoperiod (12 hours), the Rico and Rimax genes can interact in a cumulative polymeric mode, which is not the case in long-day environments. Unlike other Rifor lines, Rifor 4 and Rifor 5, as well as ‘Forlani Roberto’, have a recessive vrn-A1a allele. However, Rifor 4 and Rifor 5 do not respond to vernalization, while ‘Forlani Roberto’ is responsive to this factor. The absence of response to vernalization in Rifor 4 and Rifor 5 possessing the recessive vrn-A1a allele is possibly provided by a complex of modifier genes along with the dominant Vrn-D1 gene, which was formed during recombination in F7-8 Rico × ‘Forlani Roberto’ hybrids. Recombinants of spring common wheat, combining ultra-earliness and relatively high ear productivity, have been identified. Grain yield per 1 m2 of new ultra-early lines in some years can reach 90% of that of the ‘Leningradskaya 97’. It is expedient to use ultra-early lines as donors of high-rate development in common wheat breeding, considering genetic peculiarities of the source lines.

Single Cell RNA-Seq of Extranodal Marginal Zone Lymphoma (MZL) Identifies Site-Specific and Shared Features in Both B and T Cell Components

Background. Extranodal MZL of MALT type (MALT lymphomas) represents 5-8% of all human B-cell lymphomas can occur at any anatomical site. We and others have previously highlighted the genetic, biological and clinical peculiarities of this tumor, differences due in part to the diverse primary sites of disease. Almost by definition, the cellular composition of MALT lymphomas can be very heterogenous, encompassing small B cells resembling MZ cells, monocytoid cells, and small lymphocytes, in addition to scattered immunoblasts, centroblast-like cells and plasma cells. This issue and the possible presence of anatomical site-specific nonmalignant cell biopsies make single cell (sc) RNA-Seq ideal for studying MALT lymphomas. scRNA-Seq has the potential to provide detailed information on the transcriptome of non-neoplastic cells and give insight on the heterogeneity of the lymphoma cell population. Methods. Cells were analyzed with the 10× Chromium Chip and the Single Cell 3′ Reagent Kit v3. Libraries were run on an Illumina Nextseq 500. A minimum of 50'000 reads per cell were sequenced. FASTQ files were mapped to human reference genome (HG38) using the cellranger pipeline. Data went through quality control and downstream analysis in R (v3.6.1) using Seurat (v3.0). Cell clusters were generated with the FindNeighbors/FindClusters functions and cells annotated with a mixed approach considering known biomarkers and unsupervised computational methods (celldex, SingleR). Non-linear dimensional reduction (UMAP) was used to visualize clustering results and Monocle 2.0 for pseudo-time analysis. Results. ScRNA-seq was performed on pulmonary (n=2), gastric and parotid (n=1, each one) MZLs. Publicly available data for a second parotid case were included in the analyses. A total of ~19K cells passed QC with a median of 1,368 detected genes per cell. Each specimen contained mostly B cells (median 76%; range 49-85%), followed by T cells (median 21%; 12-47%), plasma cells (median 2%; 1.6-2.7%), epithelial and myeloid cells (median <=1%). Each sample contained both neoplastic B cells (median percentage 49%; range 8-79%), defined as those bearing a monoclonality for κ (n.=4) or λ (n.=1), and normal B cells (median 26%; 6-41%). The latter mainly comprised naïve and memory B cells. When we merged the five cases together, neoplastic B cells had highly patient-specific profiles, whereas nonmalignant B cells and plasma cells shared similar gene expression profiles across different cases. CD4+T cells also showed patient specific-signatures, while CD8+ cells co-clustered, indicating a more homogenous phenotype across patients. Transcripts expressed across MZL cells were enriched for IRF4 and BCL6 targets, genes higher in splenic MZL vs normal spleen, genes expressed in memory B cells, plasma cells, ABC-DLBCL with high STAT3, and in OxPhos DLBCL. Examples of genes expressed in MZL cells vs normal B cells were PAX5 and CXCR4 (pulmonary MZLs), TNFRSF1B and KRAS in parotid MZL, PIK3CD in gastric MZL. SPIBand SOX5, among other genes, showed high expression levels in malignant cells from all individuals compared to the other cells. MZL cells showed high inter- and intra-tumoral heterogeneous expression of potential therapeutic targets (for example, MS4A1/CD20, CD19, BCL2, MCL1). Pseudo-temporal analysis identified a main trajectory that ordered naïve B cells and healthy memory B cells to plasma cells, while the differentiation toward malignant B cells was inferred as a distinct branch. Analysis of immune-related ligand-receptor (L-R) pair interactions showed that most of the B cell subclusters provided costimulatory signals to CD4+ or CD8+ T cells via CD22-PTPRC interactions. Another suggestive costimulatory interaction occurred through CD70-CD27, involving malignant B cells, CD4+, CD8+ cells and also Tregs. Regarding coinhibitory pairs, the CD86-CTLA4 axis was frequently identified between CD4+/Tregs subclusters and malignant B cells but not between non-malignant B and T cells. Conclusions. scRNA-Seq highlighted peculiar inter- and intra-tumoral behaviors of B and T cells in MALT lymphomas. The results indicate that although each anatomical site can have a different molecular portrait, common gene expression programs are found in malignant cell populations of MALT as well as in cells of the tumor microenvironment. Acknowledgments: supported by Barletta foundation and EASI-Genomics.

Clinical and molecular genetic parallels of steroid resistance of acantholytic pemphigus

The problem of pharmacological resistance is becoming a challenge for doctors of all specialties, especially for people suffering from severe chronic diseases, which lead to disability and death consequences, which are patients on acantholytic pemphigus (AP), who have to take system glucocorticosteroids (SGCS) for a long term. Among the existing hypotheses of formation of steroid resistance (SR) is perspective study of genetic factors, which are one of the main mechanisms of occurrence of resistance and can be connected with the alleles polymorphism of gene of multidrug resistance (MDR1). The increased expression of this gene leads to the acceleration of the elimation of drugs from cells. The study of molecular genetic peculiarities of SR in patients with AP has not been carried out until now. Thus, the study of polymorphism of MDR1 gene in patients with AP is relevant. The aim. Study the frequency of polymorphism of marker C3435T in gene MDR1 in the relationship with clinical and anamnestic peculiarities of the AP course. Materials and methods. Under the supervision were 33 patients on the AP aged from 29 to 73 years, treated in the dermatological department of the SE "IDV NAMS of Ukraine". The buccal epithelium obtained by scraping mucosa of the oral cavity was examined. The polymorphism of the C3435T marker in the MDR1 gene was determined by the PCR method. The clinical and anamnestic features of patients on AP were evaluated on a specially developed scale. Discussion. The results of the study showed clinical-anamnestic signs of lack of sensitivity to SGCS, which correlated with the results of MDR1 gene expression. The presence in patients with AP in the CT haplotype of the T allele gives reason to classify the group of patients with AP with an index of resistance (IR) as SGCS 7.3 ± 0.6 as a risk group for the development of SR. Conclusion. According to the results of the study in patients with AP, the correlation of clinical-anamnestic signs of SR with the results of gene expression was established MDR

SARS, MERS and COVID-19-Associated Renal Pathology

Coronaviruses are a large group of RNA viruses, the most notable representatives of which are SARS-CoV, MERS-CoV and SARS-CoV-2. Human coronavirus infections were first documented in the 1960s, when members causing seasonal common colds were successfully replicated in human embryonal trachea and kidney cell cultures and classified based on electron microscopy. The history of coronaviruses stretched far back to that point, however, with some representatives causing disease in animals identified several decades prior and evolutionary data pointing towards the origin of this viral group more than 55 million years ago. In the short time period of research since they were discovered, coronaviruses have shown significant diversity, genetic peculiarities and varying tropism, resulting in the three identified causative agents of severe disease in humans—SARS, MERS and the most recent one, COVID-19, which has surpassed the previous two due to causing a pandemic resulting in significant healthcare, social and political consequences. Coronaviruses are likely to have caused pandemics long before, such as the so-called Asian or Russian influenza. Despite being epitheliotropic viruses and predominantly affecting the respiratory system, these entities affect multiple systems and organs, including the kidneys. In the kidneys, they actively replicate in glomerular podocytes and epithelial cells of the tubules, resulting in acute kidney injury, seen in a significant percentage of severe and fatal cases. Furthermore, the endothelial affinity of the viruses, resulting in endotheliitis, increases the likelihood of thrombotic microangiopathy, damaging the kidneys in a two-hit mechanism. As such, recently, COVAN has been a suggested nomenclature change indicating renal involvement in coronavirus infections and its long-lasting consequences.

Consequences of incorrect genetic parameter estimates for single-trait and multi-trait genetic evaluations in honeybees.

Genetic and residual variances of traits are important input parameters for best linear unbiased prediction (BLUP) breeding value estimation. In honeybees, estimates of these variances are often associated with large standard errors, entailing a risk to perform genetic evaluations under wrong premises. The consequences hereof have not been sufficiently studied. In particular, there are no adequate investigations on this topic accounting for multi-trait selection or genetic peculiarities of the honeybee. We performed simulation studies and explored the consequences of selection for honeybee populations with a broad range of true and assumed genetic parameters. We found that in single-trait evaluations, the response to selection was barely compromised by assuming erroneous parameters, so that reductions in genetic progress after 20 years never exceeded 21%. Phenotypic selection appeared inferior to BLUP selection, particularly under low heritabilities. Parameter choices for genetic evaluation had great effects on inbreeding development. By wrongly assuming high heritabilities, inbreeding rates were reduced by up to 74%. When parallel selection was performed for two traits, the right choice of genetic parameters appeared considerably more crucial as several incorrect premises yielded inadvertent negative selection for one of the traits. This phenomenon occurred in multiple constellations in which the selection traits expressed a negative genetic correlation. It was not reflected in the estimated breeding values. Our results indicate that breeding efforts heavily rely on detailed knowledge on genetic parameters, particularly when multi-trait selection is performed. Thus, considerable effort should be invested into precise parameter estimations.

Differential HIF2α Protein Expression in Human Carotid Body and Adrenal Medulla under Physiologic and Tumorigenic Conditions.

Simple SummaryThoraco-abdominal paraganglioma and pheochromocytoma (PPGL) are pathogenically linked to mutations in SDH genes. Loss-of-function of SDH has been associated with stabilization of HIF2α, which otherwise would be degraded via oxygen-sensitive mechanisms. SDH dysfunction also predispose to the development of paragangliomas arising at the carotid body or other head and neck paraganglia (HNPGL). Although PPGL and HNPGL share similar features, they have certain clinical and genetic peculiarities. By comparison of HIF2α expression in HNPGL and PPGL, we found that functional HIF2α is overexpressed in 80% of PPGLs, including those with SDH mutations as compared with non-tumor tissue. However, HIF2α is already highly expressed in the carotid body under physiologic conditions, and it is not overexpressed in HNPGL. These data suggest that selective HIF2α inhibitors already in clinical trials may benefit a wide spectrum of PPGL.Hypoxia-inducible factors (HIF) 2α and 1α are the major oxygen-sensing molecules in eukaryotic cells. HIF2α has been pathogenically linked to paraganglioma and pheochromocytoma (PPGL) arising in sympathetic paraganglia or the adrenal medulla (AM), respectively. However, its involvement in the pathogenesis of paraganglioma arising in the carotid body (CB) or other parasympathetic ganglia in the head and neck (HNPGL) remains to be defined. Here, we retrospectively analyzed HIF2α by immunohistochemistry in 62 PPGL/HNPGL and human CB and AM, and comprehensively evaluated the HIF-related transcriptome of 202 published PPGL/HNPGL. We report that HIF2α is barely detected in the AM, but accumulates at high levels in PPGL, mostly (but not exclusively) in those with loss-of-function mutations in VHL and genes encoding components of the succinate dehydrogenase (SDH) complex. This is associated with upregulation of EPAS1 and the HIF2α-regulated genes COX4I2 and ADORA2A. In contrast, HIF2α and HIF2α-regulated genes are highly expressed in CB and HNPGL, irrespective of VHL and SDH dysfunctions. We also found that HIF2α and HIF1α protein expressions are not correlated in PPGL nor HNPGL. In addition, HIF1α-target genes are almost exclusively overexpressed in VHL-mutated HNPGL/PPGL. Collectively, the data suggest that involvement of HIF2α in the physiology and tumor pathology of human paraganglia is organ-of-origin-dependent and HIF1α-independent.

Gene Action for Kernel Weight Per Plant in Spring Barley

The breeding and genetic peculiarities for kernel weight per plant in spring barley varieties of different origin (Ukraine, Western European countries, and Canada), purposes of usage (forage, malting, food) and botanical varieties (covered and naked, awned and awnless) under conditions of Ukrainian Forest-Steppe were revealed. In the diallel crossing scheme with only elite malting barley varieties accordance with the additive-dominant system and overdominance in loci were found. The manifestation of kernel weight per plant was reliably increased by the dominant effects. Accordingly to the indicator of the degree of phenotypic dominance, parameters of genetic variation, graphical regression analysis, effects of GCA and constants of SCA in the hybrid populations will be effective final selection for high kernel weight per plant in later generations, when dominant alleles become homozygous. When different botanical varieties were involved in crosses much more complex gene action for the trait manifestation with strong epistasis and multidirectional dominance were determined. Thus, it is theoretically possible to select plants with high productivity on recessive or dominant basis. The negative aspect is that it will require further extensive evaluation of the splitting generations. Awned spring barley varieties Datcha and MIP Myroslav, as well as awnless variety Kozyr can be used as an effective genetic source for involvement in crossings aimed to improving the kernel weight per plant. Naked spring barley varieties require more breeding improvement in plant productivity compare to covered ones.

Genetic peculiarities associated with interleukins exchange in patients with hepatocellular carcinoma resulting from viral hepatitis C

Genetic peculiarities associated with interleukins exchange in patients with hepatocellular carcinoma resulting from viral hepatitis C