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Item Open Access ONE HEALTH PROBIOTICS AS BIOCONTROL AGENTS: ONE HEALTH TOMATO PROBIOTICS(Plants, 2022) Harutyunyan, Natalya; Kushugulova, Almagul; Hovhannisyan, Narine; Pepoyan, AstghikTomato (Lycopersicon esculentum) is one of the most popular and valuable vegetables in the world. The most common products of its industrial processing in the food industry are juice, tomato paste, various sauces, canned or sun-dried fruits and powdered products. Tomato fruits are susceptible to bacterial diseases, and bacterial contamination can be a risk factor for the safety of processed tomato products. Developments in bioinformatics allow researchers to discuss target probiotic strains from an existing large number of probiotic strains for any link in the soil–plant– animal-human chain. Based on the literature and knowledge on the “One Health” concept, this study relates to the suggestion of a new term for probiotics: “One Health probiotics”, beneficial for the unity of people, animals, and the environment. Strains of Lactiplantibacillus plantarum, having an ability to ferment a broad spectrum of plant carbohydrates, probiotic effects in human, and animal health, as well as being found in dairy products, vegetables, sauerkraut, pickles, some cheeses, fermented sausages, fish products, and rhizospheric soil, might be suggested as one of the probable candidates for “One Health” probiotics (also, for “One Health—tomato” probiotics) for the utilization in agriculture, food processing, and healthcare.Item Open Access MESENCHYMAL STEM CELLS COATED WITH SYNTHETIC BONE-TARGETING POLYMERS ENHANCE OSTEOPOROTIC BONE FRACTURE REGENERATION(MDPI AG, 2020-10-12) Safarova, Yuliya; Olzhayev, Farkhad; Umbayev, Bauyrzhan; Tsoy, Andrey; Hortelano, Gonzalo; Tokay, Tursonjan; Murata, Hironobu; Russell, Alan; Askarova, SholpanOsteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration.Item Open Access SCREENING OF ANTIMICROBIAL AND ADHESIVE ACTIVITY OF LACTOBACILLI ISOLATED FROM THE NATIONAL FOOD PRODUCTS FROM DIFFERENT DISTRICTS OF THE KARAGANDA REGION (KAZAKHSTAN)(Scientific Foundation SPIROSKI, 2021-09-14) Amirkhanova, Zhanerke; Akhmetova, Saule; Kozhakhmetov, Samat; Kushugulova, Almagul; Bodeeva, Rahat; Issina, Zauresh; Tusbayev, MaratBACKGROUND: It is a national priority to look for new probiotic bacteria with highly active biological properties to create a new generation of probiotics, ferments, therapeutic, and prophylactic fermented milk products, taking into account ethnocultural and regional characteristics. AIM: The aim of the study is to assess probiotic properties of strains of lactobacilli (antimicrobial and adhesive), which are isolated from national lactic acid products from different districts of the Karaganda region (Kazakhstan). MATERIALS AND METHODS: There were modern microbiological methods applied during the experiment. To determine the morpho-cultural properties, the following methods were used: Gram staining, a catalase test, serial dilutions. The Matrix Supported Laser Desorption/Ionization Flight Time Mass Spectrometry was used for identification, and the deferred-antagonism method was used to determine the antimicrobial activity. The buccal epithelial cells were used for the cell object as a test system to determine the adhesive activity. RESULTS: In this experiment, 26 lactobacillus isolates were isolated from 68 samples of national lactic acid products produced in a traditional homemade way in different districts of the Karaganda region (Kazakhstan). As a result of the studies carried out on the cultural and morphological characteristics and identification by the mass spectrometer, the following lactobacilli were obtained: Lactobacillus acidophilus (two strains), Lactobacillus delbrueckii subsp. bulgaricum (two strains), Lactobacillus rhamnosus (seven strains), Lactobacillus plantarum (two strains), Lactobacillus paracasei (11 strains), and Lactobacillus fermentum (two strains). Twenty-six isolates of lactobacilli were tested for antimicrobial activity, 13 isolates of which showed an inhibitory effect, but the degree of antagonism varied among lactobacillus isolates. In general, the inhibitory activity of lactobacillus isolates was shown against the Gram-negative indicator microorganisms Salmonella typhimurium NCTC 12023, Escherichia coli NCTC 12923. The antibacterial activity was shown against the Staphylococcus aureus NCTC 12973 indicator microorganism in nine isolates of lactobacilli. Only six isolates of lactobacilli showed antifungal activity against the test strain of Candida albicans NCPF 3179. Out of 13 isolates of lactobacilli, nine isolates of medium and high activity competed for binding to buccal epithelial cells. CONCLUSION: The obtained isolates from traditional dairy products are considered to be promising candidates and competitive isolates with some probiotic potential. This study calls for further researches to be made in this area.Item Open Access EPIDEMIOLOGY SURVEY OF MEASLES IN KAZAKHSTAN(Scientific Foundation SPIROSKI, 2021-07-21) Zhuzzhasarova, Aygerim; Baesheva, Dinagul; Turdalina, Bayan; Seidullaeva, Aliya; Altynbekova, Alena; Nurgaziev, Madiyar; Abdullaev, Bakhytzhan; Kushugulova, AlmagulBACKGROUND: Measles (rubella) is a highly contagious disease that is caused by a virus in the Paramyxoviridae family. The measles virus is directly responsible for more than 100,000 deaths each year. Epidemiological studies have linked measles to increased morbidity and mortality many years after infection, but the reasons underlying this phenomenon are poorly understood. The virus attacks immune cells, causing acute suppression of the immune system. The World Health Organization recommends a two-dose vaccination policy, with the first dose administered during the 1st year of life, and coverage should be maintained in at least 90–95% of the population to halt transmission. In many countries, the measles vaccine is included in the immunization program and is freely available to all. Today, despite active immunization of the population, measles still occurs in the Republic of Kazakhstan. AIM: The objective of our study was to analyze the epidemiological characteristics of measles in the Republic of Kazakhstan during the rise of the disease. METHODS: Statistical data were obtained from the Committee on Public Health Protection on the incidence of measles in The Republic of Kazakhstan for the period from November 1, 2018 to December 30, 2019. STUDY DESIGN: Epidemiology survey. RESULTS: The article contains epidemiological data on the incidence of measles in the regions of the Republic of Kazakhstan among children, age, and gender characteristics. CONCLUSION: In the period from November 2018 to December 2019, there was a tendency to increase the incidence of measles in the republic. In terms of morbidity, Nur-Sultan was the leader, where the number of cases was 22.9% (n = 3181). The largest number of registered cases, 58.2% (n = 5745), occurred in children aged 1–14 years. Measles remains an unresolved global problem and groups of undervaccinated and unvaccinated populations remain vulnerable during epidemics.Item Open Access PLANT EXTRACT OF LIMONIUM GMELINII ATTENUATES OXIDATIVE RESPONSES IN NEURONS, ASTROCYTES, AND CEREBRAL ENDOTHELIAL CELLS IN VITRO AND IMPROVES MOTOR FUNCTIONS OF RATS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION(MDPI, 2021-11-15) Nurkenov, Tulendy; Tsoy, Andrey; Olzhayev, Farkhad; Abzhanova, Elvira; Turgambayeva, Anel; Zhussupova, Aizhan; Avula, Bharathi; Ross, Samir; Aituarova, Aigerim; Kassymova, Dariya; Zhusupova, Galiya; Shalakhmetova, Tamara; Tokay, Tursonjan; Lee, James C.; Askarova, SholpanThere are numerous publications demonstrating that plant polyphenols can reduce oxidative stress and inflammatory processes in the brain. In the present study we have investigated the neuroprotective effect of plant extract isolated from the roots of L. gmelinii since it contains a rich source of polyphenols and other biologically active compounds. We have applied an oxidative and inflammatory model induced by NMDA, H2O2 , and TNF-α in human primary neurons and astrocytes, and mouse cerebral endothelial cell (CECs) line in vitro. The levels of ROS generation, NADPH oxidase activation, P-selectin expression, and activity of ERK1/2 were evaluated by quantitative immunofluorescence analysis, confocal microscopy, and MAPK assay. In vivo, sensorimotor functions in rats with middle cerebral artery occlusion (MCAO) were assessed. In neurons NMDA induced overproduction of ROS, in astrocytes TNF-α initiated ROS generation, NADPH oxidase activation, and phosphorylation of ERK1/2. In CECs, the exposure by TNF-α induced oxidative stress and triggered the accumulation of P-selectin on the surface of the cells. In turn, pre-treatment of the cells with the extract of L. gmelinii suppressed oxidative stress in all cell types and pro-inflammatory responses in astrocytes and CECs. In vivo, the treatment with L. gmelinii extract improved motor activity in rats with MCAO. Keywords: antioxidants; neurons; astrocytes; CECs; L. gmelinii; plant polyphenolsItem Open Access WHOLE-GENOME SEQUENCING DATA OF KAZAKH INDIVIDUALS(BMC Res Notes, 2021-02-04) Kairov, Ulykbek; Molkenov, Askhat; Rakhimova, Saule; Kozhamkulov, Ulan; Sharip, Aigul; Karabayev, Daniyar; Daniyarov, Asset; H.Lee, Joseph; D.Terwilliger, Joseph D.; Akilzhanova, Ainur; Zhumadilov, ZhaxybayKazakhstan is a Central Asian crossroad of European and Asian populations situated along the way of the Great Silk Way. The territory of Kazakhstan has historically been inhabited by nomadic tribes and today is the multi-ethnic country with the dominant Kazakh ethnic group. We sequenced and analyzed the whole-genomes of five ethnic healthy Kazakh individuals with high coverage using next-generation sequencing platform. This whole-genome sequence data of healthy Kazakh individuals can be a valuable reference for biomedical studies investigating disease associations and population-wide genomic studies of ethnically diverse Central Asian region....Item Open Access DYNAMIC CHANGES IN MICROBIOME COMPOSITION FOLLOWING MARE’S MILK INTAKE FOR PREVENTION OF COLLATERAL ANTIBIOTIC EFFECT(Frontiers Media S.A., 2021-04-21) Kushugulova, Almagul R.; Löber, Ulrike; Akpanova, Saniya; Rysbekov, Kairat; Kozhakhmetov, Samat S.; Khassenbekova, Zhanagul R.; Essex, Morgan; Nurgozhina, Ayaulym; Nurgaziyev, Madiyar; Babenko, Dmitriy; Marko, Lajos; Forslund, Sofia K.Introduction: Probiotics and prebiotics are widely used for recovery of the human gut microbiome after antibiotic treatment. High antibiotic usage is especially common in children with developing microbiome. We hypothesized that dry Mare’s milk, which is rich in biologically active substances without containing live bacteria, could be used as a prebiotic in promoting microbial diversity following antibiotic treatment in children. The present pilot study aims to determine the impacts of dry Mare’s milk on the diversity of gut bacterial communities when administered during antibiotic treatment and throughout the subsequent recovery phase. Methods: Six children aged 4 to 5 years and diagnosed with bilateral bronchopneumonia were prescribed cephalosporin antibiotics. During the 60 days of the study, three children consumed dry Mare’s milk whereas the other three did not. Fecal samples were collected daily during antibiotic therapy and every 5 days after antibiotic therapy. Total DNA was isolated and taxonomic composition of gut microbiota was analyzed by 16S rRNA amplicon sequencing. To assess the immune status of the gut, stool samples were analyzed by bead-based multiplex assays. Results: Mare’s milk treatment seems to prevent the bloom of Mollicutes, while preventing the loss of Coriobacteriales. Immunological analysis of the stool reveals an effect of Mare’s milk on local immune parameters under the present conditions.Item Open Access RE-SEARCHER: GUI-BASED BIOINFORMATICS TOOL FOR SIMPLIFIED GENOMICS DATA MINING OF VCF FILES(PeerJ Inc., 2021-05-03) Karabayev, Daniyar; Molkenov, Askhat; Yerulanuly, Kaiyrgali; Kabimoldayev, Ilyas; Daniyarov, Asset; Sharip, Aigul; Seisenova, Ainur; Zhumadilov, Zhaxybay; Kairov, UlykbekBackground. High-throughput sequencing platforms generate a massive amount of high-dimensional genomic datasets that are available for analysis. Modern and user-friendly bioinformatics tools for analysis and interpretation of genomics data becomes essential during the analysis of sequencing data. Different standard data types and file formats have been developed to store and analyze sequence and genomics data. Variant Call Format (VCF) is the most widespread genomics file type and standard format containing genomic information and variants of sequenced samples. Results. Existing tools for processing VCF files don’t usually have an intuitive graphical interface, but instead have just a command-line interface that may be challenging to use for the broader biomedical community interested in genomics data analysis. re-Searcher solves this problem by pre-processing VCF files by chunks to not load RAM of computer. The tool can be used as standalone user-friendly multiplatform GUI application as well as web application (https://nla-lbsb.nu.edu.kz). The software including source code as well as tested VCF files and additional information are publicly available on the GitHub repository (https://github.com/LabBandSB/re-Searcher).Item Open Access ANALYSIS OF BACTEROIDES FRAGILIS CLINICAL STRAINS ISOLATED IN KAZAKHSTAN(Microbiology Resource Announcements, 2021-02-04) Zholdybayeva, Elena V.; Kozhahmetova, Saniya; Tarlykov, Pavel; Atavliyeva, Sabina; Mukhtarova, Kymbat; Syzdykov, Tleuli; Khasenov, Ruslan; Shevtsov, Alexsandr; Amirgazin, Asylulan; Daniyarov, Asset; Ramankulov, YerlanOur aim was to study the nucleotide sequences of 9 previously undescribed strains of B. fragilis collected from patients with intra-abdominal diseases at city hospitals in Nur-Sultan, Kazakhstan.Item Open Access TRENDS OF COLORECTAL CANCER PREVALENCE IN KAZAKHSTAN RELATED TO SCREENING(Clinical Endoscopy, 2020-05) Zhylkaidarova, Alma; Kaidarova, Dilyara; Batyrbekov, Kanat; Shatkovskaya, Oxana; Begimbetova, DinaraColorectal cancer (CRC) is one of the global health problems and is the third leading cause of morbidity and second leading cause of mortality from cancer worldwide [1,2]. In the United States and European countries, the incidence is in the range of 20–40 per 100,000 population. In Asian countries, it varies widely (4.4 in India; 44.5 in Korea per 100,000) [1]. In one study that conducted CRC screening in one of the regions of Kazakhstan [3], the high number of CRC cases detected indicated the need for more screening programs. An increase in the incidence rate of this pathology was observed since 2011, with the introduction of CRC screening; stage-related data indicate the predominance of stages I and II....Item Open Access PALINDROMIC SEQUENCE-TARGETED (PST) PCR, VERSION 2: AN ADVANCED METHOD FOR HIGH-THROUGHPUT TARGETED GENE CHARACTERIZATION AND TRANSPOSON DISPLAY(Frontiers Media S.A., 2021-06-22) Kalendar, Ruslan; Shustov, Alexandr V.; Schulman, Alan H.Genome walking (GW), a strategy for capturing previously unsequenced DNA fragments that are in proximity to a known sequence tag, is currently predominantly based on PCR. Recently developed PCR-based methods allow for combining of sequence-specific primers with designed capturing primers capable of annealing to unknown DNA targets, thereby offering the rapidity and effectiveness of PCR. This study presents a methodological improvement to the previously described GW technique known as palindromic sequence-targeted PCR (PST-PCR). Like PST-PCR, this new method (called PST-PCR v.2) relies on targeting of capturing primers to palindromic sequences arbitrarily present in natural DNA templates. PST-PCR v.2 consists of two rounds of PCR. The first round uses a combination of one sequence-specific primer with one capturing (PST) primer. The second round uses a combination of a single (preferred) or two universal primers; one anneals to a 5′ tail attached to the sequence-specific primer and the other anneals to a different 5′ tail attached to the PST primer. The key advantage of PST-PCR v.2 is the convenience of using a single universal primer with invariable sequences in GW processes involving various templates. The entire procedure takes approximately 2–3 h to produce the amplified PCR fragment, which contains a portion of a template flanked by the sequence-specific and capturing primers. PST-PCR v.2 is highly suitable for simultaneous work with multiple samples. For this reason, PST-PCR v.2 can be applied beyond the classical task of GW for studies in population genetics, in which PST-PCR v.2 is a preferred alternative to amplified fragment length polymorphism (AFLP) or next-generation sequencing. Furthermore, the conditions for PST-PCR v.2 are easier to optimize, as only one sequence-specific primer is used. This reduces non-specific random amplified polymorphic DNA (RAPD)-like amplification and formation of non-templated amplification. Importantly, akin to the previous version, PST-PCR v.2 is not sensitive to template DNA sequence complexity or quality. This study illustrates the utility of PST-PCR v.2 for transposon display (TD), which is a method to characterize inter- or intra-specific variability related to transposon integration sites. The Ac transposon sequence in the maize (Zea mays) genome was used as a sequence tag during the TD procedure to characterize the Ac integration sites.Item Open Access GUT MODULATION OF DYSBIOSIS INDUCED BY DEXTRAN SULFATE SODIUM(Elsevier Ltd, 2021-06-08) Kozhakhmetov, Samat S.; Babenko, Dmitriy; Kozhakhmetova, Saniya; Tuyakova, Altynay; Nurgaziyev, Madiyar; Nurgozhina, Ayaulym; Muhanbetganov, Nurislam; Chulenbayeva, Laura; Sergazy, Shynggys; Gulyayev, Alexander; Tanabayev, Baimakhan; Saliev, Timur; Kushugulova, Almagul R.Inflammatory bowel disease is one of the serious burdens of clinical medicine and healthcare. This study investigated the potential of a biological product based on mare's milk and metabolites of symbiotic microflora for modulation of intestinal microflora affected by dextran sulfate sodium (DSS)-induced dysbiosis. Symbiotic microflora was isolated from the stool of healthy volunteers. Lysates for the production of short-chain fatty acids of screened microorganisms were mixed with mare's milk. The activity of the biological product was evaluated on the DSS model of induced colitis. Histological changes in the intestinal epithelium were determined. The structure of the microbiome was evaluated based on the analysis of 16S rRNA microbial sequences. Histological examination of rat intestinal tissues after application of the biological product showed reduced infiltration of granulocytes, macrophages, and lymphocytes. The results of sequencing demonstrated a decrease in the biological diversity of microbiota affected by colitis. The full recovery was observed after 21 days of the application of the biological product. The product induced the structural changes of the microbiome damaged by DSS. Likewise, the number of the pathogenic intestinal microflora was decreased Representatives of SCFA producing bacteria increased concentrations of genus Lactobacillus.Item Open Access WHOLE-GENOME SEQUENCING DATA OF KAZAKH INDIVIDUALS(BioMed Central Ltd, 2021-02-04) Kairov, Ulykbek; Molkenov, Askhat; Rakhimova, Saule; Kozhamkulov, Ulan; Sharip, Aigul; Karabayev, Daniyar; Daniyarov, Asset; Lee, Joseph H.; Terwilliger, Joseph D.; Akilzhanova, Ainur; Zhumadilov, ZhaxybayObjectives: Kazakhstan is a Central Asian crossroad of European and Asian populations situated along the way of the Great Silk Way. The territory of Kazakhstan has historically been inhabited by nomadic tribes and today is the multi-ethnic country with the dominant Kazakh ethnic group. We sequenced and analyzed the whole-genomes of five ethnic healthy Kazakh individuals with high coverage using next-generation sequencing platform. This whole-genome sequence data of healthy Kazakh individuals can be a valuable reference for biomedical studies investigating disease associations and population-wide genomic studies of ethnically diverse Central Asian region. Data description: Blood samples have been collected from five ethnic healthy Kazakh individuals living in Kazakhstan. The genomic DNA was extracted from blood and sequenced. Sequencing was performed on Illumina HiSeq2000 next-generation sequencing platform. We sequenced and analyzed the whole-genomes of ethnic Kazakh individuals with the coverage ranging from 26 to 32X. Ranging from 98.85 to 99.58% base pairs were totally mapped and aligned on the human reference genome GRCh37 hg19. Het/Hom and Ts/Tv ratios for each whole genome ranged from 1.35 to 1.49 and from 2.07 to 2.08, respectively. Sequencing data are available in the National Center for Biotechnology Information SRA database under the accession number PRJNA374772.Item Open Access GALACTOSE-INDUCED SKIN AGING: THE ROLE OF OXIDATIVE STRESS(Hindawi, 2020-06-17) Umbayev, Bauyrzhan; Askarova, Sholpan; Almabayeva, Aigul; Saliev, Timur; Masoud, Abdul-Razak; Bulanin, DenisSkin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable of damaging the skin’s vital components through nonenzymatic glycation, the covalent attachment of sugar to a protein, and subsequent production of advanced glycation end products (AGEs). This review is focused on the role of D-galactose in the development of skin aging and its relation to oxidative stress. The interest in this problem was dictated by recent findings that used in vitro and in vivo models. The review highlights the recent advances in the underlying molecular mechanisms of D-galactose-mediated cell senescence and cytotoxicity. We have also proposed the possible impact of galactosemia on skin aging and its clinical relevance. The understanding of molecular mechanisms of skin aging mediated by D-galactose can help dermatologists optimize methods for prevention and treatment of skin senescence and aging-related skin diseases.Item Open Access IMPROVEMENT OF NEUROLOGICAL FUNCTION IN RATS WITH ISCHEMIC STROKE BY ADIPOSEDERIVED PERICYTES(SAGE Publications, 2020-09-04) Ogay, Vyacheslav; Kumasheva, Venera; Li, Yelena; Mukhlis, Sholpan; Sekenova, Aliya; Olzhayev, Farkhad; Tsoy, Andrey; Umbayev, Baurzhan; Askarova, Sholpan; Shpekov, Azat; Kaliyev, Assylbek; Zhetpisbayev, Berik; Makhambetov, Yerbol; Akshulakov, Serik; Saparov, Arman; Ramankulov, YerlanPericytes possess high multipotent features and cell plasticity, and produce angiogenic and neurotrophic factors that indicate their high regenerative potential. The aim of this study was to investigate whether transplantation of adipose-derived pericytes can improve functional recovery and neurovascular plasticity after ischemic stroke in rats. Rat adipose-derived pericytes were isolated from subcutaneous adipose tissue by fluorescence-activated cell sorting. Adult male Wistar rats were subjected to 90 min of middle cerebral artery occlusion followed by intravenous injection of rat adipose-derived pericytes 24 h later. Functional recovery evaluations were performed at 1, 7, 14, and 28 days after injection of rat adipose-derived pericytes. Angiogenesis and neurogenesis were examined in rat brains using immunohistochemistry. It was observed that intravenous injection of adipose-derived pericytes significantly improved recovery of neurological function in rats with stroke compared to phosphate-buffered saline– treated controls. Immunohistochemical analysis revealed that the number of blood capillaries was significantly increased along the ischemic boundary zone of the cortex and striatum in stroke rats treated with adipose-derived pericytes. In addition, treatment with adipose-derived pericytes increased the number of doublecortin positive neuroblasts. Our data suggest that transplantation of adipose-derived pericytes can significantly improve the neurologic status and contribute to neurovascular remodeling in rats after ischemic stroke. These data provide a new insight for future cell therapies that aim to treat ischemic stroke patients.Item Open Access THE MAJOR SATELLITE DNA FAMILIES OF THE DIPLOID CHENOPODIUM ALBUM AGGREGATE SPECIES: ARGUMENTS FOR AND AGAINST THE “LIBRARY HYPOTHESIS”(Public Library of Science, 2020-10-27) Belyayev, Alexander; Jandova, Michaela; Josefiova, Jiřina; Kalendar, Ruslan; Mahelka, Va´clav; Manda´k, Bohumil; Krak, KarolSatellite DNA (satDNA) is one of the major fractions of the eukaryotic nuclear genome. Highly variable satDNA is involved in various genome functions, and a clear link between satellites and phenotypes exists in a wide range of organisms. However, little is known about the origin and temporal dynamics of satDNA. The “library hypothesis” indicates that the rapid evolutionary changes experienced by satDNAs are mostly quantitative. Although this hypothesis has received some confirmation, a number of its aspects are still controversial. A recently developed next-generation sequencing (NGS) method allows the determination of the satDNA landscape and could shed light on unresolved issues. Here, we explore low-coverage NGS data to infer satDNA evolution in the phylogenetic context of the diploid species of the Chenopodium album aggregate. The application of the Illumina read assembly algorithm in combination with Oxford Nanopore sequencing and fluorescent in situ hybridization allowed the estimation of eight satDNA families within the studied group, six of which were newly described. The obtained set of satDNA families of different origins can be divided into several categories, namely group-specific, lineage-specific and species-specific. In the process of evolution, satDNA families can be transmitted vertically and can be eliminated over time. Moreover, transposable element-derived satDNA families may appear repeatedly in the satellitome, creating an illusion of family conservation. Thus, the obtained data refute the “library hypothesis”, rather than confirming it, and in our opinion, it is more appropriate to speak about “the library of the mechanisms of origin”.Item Open Access THE ARABIDOPSIS THALIANA POLY(ADP-RIBOSE) POLYMERASES 1 AND 2 MODIFY DNA BY ADP-RIBOSYLATING TERMINAL PHOSPHATE RESIDUES(Frontiers Media, 2020-11-26) Taipakova, Sabira; Kuanbay, Aigerim; Saint-Pierre, Christine; Gasparutto, Didier; Baiken, Yeldar; Groisman, Regina; Ishchenko, Alexander A.; Saparbaev, Murat; Bissenbaev, Amangeldy K.Proteins from the poly(ADP-ribose) polymerase (PARP) family, such as PARP1 and PARP2, use NAD+ as a substrate to catalyze the synthesis of polymeric chains consisting of ADP-ribose units covalently attached to an acceptor molecule. PARP1 and PARP2 are viewed as DNA damage sensors that, upon binding to strand breaks, poly(ADP-ribosyl)ate themselves and nuclear acceptor proteins. The flowering plant Arabidopsis thaliana contains three genes encoding homologs of mammalian PARPs: atPARP1, atPARP2, and atPARP3. Both atPARP1 and atPARP2 contain poly(ADP-ribosyl)ating activity; however, it is unknown whether they could covalently modify DNA by ADP-ribosylating the strand break termini. Here, we report that similar to their mammalian counterparts, the plant atPARP1 and atPARP2 proteins ADP-ribosylate 5′-terminal phosphate residues in duplex DNA oligonucleotides and plasmid containing at least two closely spaced DNA strand breaks. AtPARP1 preferentially catalyzes covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 5′-phosphate, whereas atPARP2 preferentially ADP-ribosylates the nicked and gapped DNA duplexes containing the terminal 5′-phosphate. Similar to their mammalian counterparts, the plant PARP-catalyzed DNA ADP-ribosylation is particularly sensitive to the distance that separates two strand breaks in the same DNA molecule, 1.5 and 1 or 2 turns of helix for atPARP1 and atPARP2, respectively. PAR glycohydrolase (PARG) restored native DNA structure by hydrolyzing the PAR–DNA adducts generated by atPARPs. Biochemical and mass spectrometry analyses of the PAR–DNA adducts showed that atPARPs utilize phosphorylated DNA termini as an alternative to protein acceptor residues to catalyze PAR chain synthesis via phosphodiester bond formation between C1′ of ADP-ribose and a phosphate residue of the terminal nucleotide in DNA fragment. Taken together, these data establish the presence of a new type of DNA-modifying activity in Arabidopsis PARPs, suggesting a possible role of DNA ADP-ribosylation in DNA damage signaling and repair of terrestrial plants.Item Open Access IN SILICO ESTIMATION OF THE ABUNDANCE AND PHYLOGENETIC SIGNIFICANCE OF THE COMPOSITE OCT4-SOX2 BINDING MOTIFS WITHIN A WIDE RANGE OF SPECIES(MDPI, 2020-11-29) Kulyyassov, Arman; Kalendar, RuslanHigh-throughput sequencing technologies have greatly accelerated the progress of genomics, transcriptomics, and metagenomics. Currently, a large amount of genomic data from various organisms is being generated, the volume of which is increasing every year. Therefore, the development of methods that allow the rapid search and analysis of DNA sequences is urgent. Here, we present a novel motif-based high-throughput sequence scoring method that generates genome information. We found and identified Utf1-like, Fgf4-like, and Hoxb1-like motifs, which are cis-regulatory elements for the pluripotency transcription factors Sox2 and Oct4 within the genomes of different eukaryotic organisms. The genome-wide analysis of these motifs was performed to understand the impact of their diversification on mammalian genome evolution. Utf1-like, Fgf4-like, and Hoxb1-like motif diversity was evaluated across genomes from multiple species.Item Open Access A NEW INSIGHT ON THE RADIOPROTECTIVE POTENTIAL OF EPSILON-AMINOCAPROIC ACID(MDPI, 2020-11-25) Takagi, Satoshi; Oyama, Takuto; Jimi, Shiro; Saparov, Arman; Ohjimi, HiroyukiNegative pressure wound therapy (NPWT) has been commonly used over the years for a wide range of chronic/refractory lesions. Alternatively, autologous micrografting technology is recently becoming a powerful modality for initiating wound healing. The case presented is of a patient with a lower leg ulcer that had responded poorly to NPWT alone for three weeks. Consequently, the patient was put on a combination therapy of NPWT and micrografting. After injection of a dermal tissue micrografts suspension into the entire wound bed, NPWT was performed successively for two weeks, resulting in fresh granulation tissue formation. Thereafter, the autologous skin graft was taken well. This case study indicates that for a chronic/refractory ulcer patient with poor NPWT outcome, combination therapy using micrografting treatment and NPWT could rapidly initiate and enhance granulation tissue formation, creating a favorable bedding for subsequent skin grafting.Item Open Access WHOLE GENOME SEQUENCE DATA OF MYCOBACTERIUM TUBERCULOSIS XDR STRAIN, ISOLATED FROM PATIENT IN KAZAKHSTAN(Elsevier, 2020-12) Daniyarov, Asset; Molkenov, Askhat; Rakhimova, Saule; Akhmetova, Ainur; Nurkina, Zhannur; Yerezhepov, Dauren; Chingissova, Lyailya; Bismilda, Venera; Toxanbaeva, Bekzat; Akilzhanova, Ainur; Kozhamkulov, Ulan; Kairov, UlykbekDrug-resistant tuberculosis (TB) is a major public health problem. Clinical Mycobacterium tuberculosis (MTB) isolate with Extensively drug-resistant tuberculosis (MTB-XDR) profile was subjected to whole-genome sequencing using a next-generation sequencing platform (NGS) Roche 454 GS FLX+ followed by bioinformatics sequence analysis. Quality of read was checked by FastQC, paired-end reads were trimmed using Trimmomatic. De novo genome assembly was conducted using Velvet v.1.2.10. The assembled genome of XDR-TB-1599 strain was functionally annotated using the PATRIC platform. Analysis of de novo assembled genome was performed using ResFinder, CARD, CASTB and TB-Profiler tools. MIRU_VNTR genotyping on 12 loci and spoligotyping have been performed for XDR-TB-1599 isolate. M. tuberculosis XDR-TB-1599 strain yielded an average read depth of 21-fold with overall 4 199 325 bp. The assembled genome contains 5528 protein-coding genes, including key drug resistance and virulence-associated genes and GC content of 65.4%. We identified that all proteins encoded by this strain contain conserved domains associated with the first-line anti-tuberculosis drugs such as rifampicin, isoniazid, streptomycin and ethionamide. TB-Profiler had higher average concordance results with phenotypic DST (drug susceptibility testing) in comparison with ResFinder, CARD, CASTB profiling to first-line (75% vs 50%) and second-line (25% vs 0%) of anti-TB drugs, correspondingly. To our knowledge, this is the first report of a highly annotated and characterized whole-genome sequence and de novo assembled XDR-TB M.tuberculosis strain isolated from a sputum of new TB case-patient from Kazakhstan performed on Roche 454 GS FLX+ platform. This report highlights an important role of whole-genome sequencing technology and analysis as an advanced approach for drug-resistance investigations of circulated TB isolates.