151 results on '"Makarov VV"'
Search Results
2. Tryptophan catabolites and predicted gut flora enzyme-encoding genes
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Shatova, OP, primary, Gaponov, AM, additional, Grigoryeva, TV, additional, Vasilyev, IYu, additional, Stoletova, LS, additional, Makarov, VV, additional, Yudin, SM, additional, Roumiantsev, SA, additional, and Shestopalov, AV, additional
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- 2023
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3. N protein based vaccine against SARS-CoV-2 produces a strong T cell immune response to N Protein of novel strains
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Rabdano, SO, primary, Mukhin, VE, additional, Makarov, VV, additional, Rudakov, GO, additional, Ruzanova, EA, additional, Arakelov, SA, additional, Khaitov, MR, additional, Yudin, SM, additional, Kryuchko, DS, additional, Berzin, IA, additional, Evtushenko, AE, additional, Trukhin, VP, additional, and Skvortsova, VI, additional
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- 2022
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4. The proper structure of a biosafety system as a way of reducing the vulnerability of a society, economy or state in the face of a biogenic threat
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Tkachuk Ap, Manuilov Va, Makarov Vv, and Gushchin Va
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Structure (mathematical logic) ,Biological safety ,Biosafety ,State (polity) ,Natural resource economics ,media_common.quotation_subject ,Vulnerability ,Face (sociological concept) ,General Medicine ,Business ,media_common - Abstract
To understand how vulnerable are a society, an economy and a state in the face of a biohazard, one should attempt to identify any potential holes in the national biosafety system, such as the lack of important components or technologies for biological monitoring and the inadequacy of existing analytical methods used to prevent or counteract biogenic threats. In Russia, biological monitoring is quite advanced. However, the agencies that ensure proper functioning of its components lack collaboration and do not form a well-coordinated network. Each of such agencies alone cannot provide comprehensive information on the subject. In the Russian Federation, there are at least 4 state-funded programs that collect epidemiological data and are quite efficient in performing the narrow task of monitoring infections. But because there is no central database where epidemiological data can be channeled and subsequently shared, these agencies do not complete each other. This leaves the Russian society, economy and state vulnerable to biogenic threats. We need an adequately organized, modern, fully functional and effective system for monitoring biohazards that will serve as a basis for the national biosafety system and also a tool for the identification and elimination of its weaknesses.
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- 2018
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5. Genetic determinants of the response to coronavirus infection COVID-19
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Poyarkov, SV, primary, Makarov, VV, additional, Kraevoy, SA, additional, and Yudin, SM, additional
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- 2020
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6. African Swine Fever in Russian Federation Current Epizootic Situation and Control
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Makarov Vv
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Natural history ,Geography ,African swine fever ,Transmission (medicine) ,Mortality rate ,medicine ,Russian federation ,Disease ,Socioeconomics ,Colonialism ,medicine.disease ,Epizootic - Abstract
A brief interpretation of the natural history and value of the African swine fever ASF at the actual stage is given Epidemic dynamics of the emergence and spread of the disease in in the Russian Federation its emergence out of the country to the territory of neighboring countries including the EU countries are described The references to the normative documents regulating the control of the ASF in the Russian Federation are given African swine fever ASF concerns of the most important trans boundary infections with catastrophic potential This is one of the most serious epidemic problems due to the ability to emergence and spread widely in the most unexpected regions of the world as well as extremely large direct damage high lethality of susceptible animals costs of various restrictive measures and eradication and the impossibility of specific prevention The disease has been known since the beginning of the th century from the first attempts to introduce pigs of cultivated species into the colonial countries of subequatorial and southern Africa At the first stage of natural history prior to export to Portugal and Spain ASF had a stereotype of a typical transmissive natural focal exotic disease with natural circulation of the virus in populations of wild African swine intra family transmission and the course of a persistent tolerant infection When the first cases occurred among domestic non native born pigs the disease acquired an acute course with a mortality rate of up to Later ASF evolved towards an independent anthropurgic cycle with rooting in the southern European countries and a two fold emergent traffic to the countries of Central and South America and a sharp decrease in mortality and a predominance of unclinical forms of course of the disease
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- 2017
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7. Red Cell Enzyme Types in Rheumatic Diseases
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Krylov MYu, Benevolenskaya Li, Makarov Vv, and Gurbanov Vp
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Genetic Markers ,Erythrocytes ,animal structures ,Heart disease ,Acid Phosphatase ,Population ,Scleroderma ,Carboxylesterase ,Gene Frequency ,immune system diseases ,Polymorphism (computer science) ,Rheumatic Diseases ,PGM1 ,Genetics ,medicine ,Humans ,skin and connective tissue diseases ,education ,Allele frequency ,Genetics (clinical) ,education.field_of_study ,business.industry ,medicine.disease ,Phenotype ,Phosphoglucomutase ,Rheumatoid arthritis ,Immunology ,business ,Carboxylic Ester Hydrolases - Abstract
We studied the frequencies of red cell enzyme types, AcP, PGM1 and EsD in 213 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), rheumatic heart disease (RHD), scleroderma (Scl) and psoriatic arthropathy (PsA). The differences in frequency of AcP phenotypes between RA, Scl, and PsA and the Moscow population were significant. In PsA the PGM1 phenotype 1-1 frequency was significantly decreased, while the phenotype 2-1 frequency was significantly increased.
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- 1985
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8. Humidity regulator for air conditioners
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Makarov Vv
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Medical Laboratory Technology ,Air conditioning ,business.industry ,Biomedical Engineering ,Regulator ,Environmental engineering ,Medicine (miscellaneous) ,Environmental science ,Humidity ,Air Conditioning ,business - Published
- 1973
9. Features of Metabolism and Its Regulation in the Dynamics of Experimental Models of Metabolic Disorders.
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Shestopalov AV, Krolenko EV, Nedorubov AA, Borisenko OV, Popruga KE, Makarov VV, Yudin SM, Gaponov AM, and Rumyantsev SA
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Changes in the lipid and carbohydrate metabolism, adipokines, and growth factors during the development of metabolic disorders were studied in three mouse models: C57BL/6 (alimentary obesity), db/db (leptin-resistant obesity), and NOD (diabetes mellitus) lines. In the group of alimentary obesity, moderate fatty infiltration of the liver and hypertrophy of the adipose tissue, hyperglycemia, and increased concentrations of adiponectin, transforming growth factor β1 (TGF-β1), leptin, and cholesterol were detected. In the group of leptin-resistant obesity, multiple pathological changes in tissues, severe hyperglycemia and hyperleptinemia, hyperinsulinemia, and reduced concentrations of triglycerides, adiponectin, myostatin, and TGF-β1 were detected. In NOD mice, reduced number of insulin-positive β cells, hyperinsulinemia, and a decrease in adiponectin, TGF-β1, leptin, and myostatin concentrations were detected., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2025
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10. Multireflecting gas chromatography-multireflecting time-of-flight mass spectrometer with high dynamic range.
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Vorobyev AV, Khasin YI, Makarov VV, Kirillov SN, and Verenchikov AN
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Gas chromatography-mass spectrometry (GC-MS) is a cornerstone technique for analyses of volatile and semivolatile compounds, constantly evolving to meet new challenges. The adoption of time-of-flight mass spectrometers (TOFMS) has enhanced GC-MS with faster spectral acquisition and broader mass coverage, enabling rapid GC separations. Multireflecting TOFMS (MRT) further improves resolution compared to traditional single-reflecting TOFMS, facilitating the detection of minor analytes within complex matrices. This paper presents a significant improvement in MRT sensitivity and dynamic range achieved through an ion beam compression within the ion guide and the use of a conventionally oriented orthogonal accelerator. Sensitivity is improved to 100 000 ion/pg at a resolution of R = 25,000, enabling the detection of low fg analyte quantities within 3 μg of matrix material into MS. The demonstrated linear dynamic range exceeding 6 orders of magnitude potentially enables even deeper exploration of complex mixtures with a bench top instrument., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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11. A Perspective of Multi-Reflecting TOF MS.
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Verenchikov AN, Makarov VV, Vorobyev AV, and Kirillov SN
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Time-of-flight mass spectrometry (TOF MS) excels in rapid and high-sensitivity analysis, making it a cornerstone of analytical chemistry. But as sample complexity explodes in omics studies, so does the need for higher resolving power to ensure accurate results. Traditional TOF instruments face a challenge: achieving high resolution often requires a very large instrument. To overcome this limitation, scientists developed alternative designs for TOF analyzers called multi-pass TOF analyzers (MPT). These MPT analyzers come in two main configurations: multi-turn (MTT) and multi-reflecting (MRT). Drawing on the authors' extensive experience, this review describes two decades of MPT advancements. It highlights the critical development of optimized analyzer designs, tracing the evolution towards mirror-based MRT instruments, generally providing superior resolution and spatial acceptance compared to MTT. While the manuscript attempts to overview MTT advances, it primarily focuses on MRT technology. Additionally, the review explores the role of orthogonal accelerators and trap pulse converters, comparing their efficiency and the dynamic range limits imposed by space charge effects. By comparing various MRT configurations and commercially available instruments, the review sets out to inform and empower researchers so they can make informed decisions about MRT mass spectrometers., (© 2024 The Author(s). Mass Spectrometry Reviews published by Wiley Periodicals LLC.)
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- 2024
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12. Pharmacokinetic and preclinical safety studies of endolysin-based therapeutic for intravenous administration.
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Antonova NP, Vasina DV, Grigoriev IV, Laishevtsev AI, Kapustin AV, Savinov VA, Vorobev AM, Aleshkin AV, Zackharova AA, Remizov TA, Makarov VV, Yudin SM, and Gushchin VA
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- Animals, Mice, Female, Male, Rats, Drug Evaluation, Preclinical, Endopeptidases pharmacokinetics, Endopeptidases administration & dosage, Administration, Intravenous, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents adverse effects
- Abstract
Pharmacokinetics and safety studies of innovative drugs is an essential part of drug development process. Previously we have developed a novel drug for intravenous administration (lyophilizate) containing modified endolysin LysECD7-SMAP that showed notable antibacterial effect in different animal models of systemic infections. Here we present data on pharmacokinetics of endolysin in mice after single and multiple injections. Time-concentration curves were obtained, and pharmacokinetic parameters for preparation (C
0 , kel t1/2 , AUC0-∞ , MRT, ClT , Vss ) were calculated. It was shown that although endolysin is rather short-lived in blood serum (t1/2 = 12.5 min), the therapeutic concentrations of LysECD7-SMAP (in degraded and non-degraded form) were detected for 60 minutes after injection that is sufficient for antibacterial effect. Based on the obtained data, it was proposed that endolysin distributes presumably in murine blood, degrades in blood and liver, and is eliminated via glomerular filtration. Safety profile of the preparation relating to general toxicity, immunotoxicity and allergenicity was assessed in rodents. It was demonstrated that LysECD7-SMAP in potential therapeutic (12.5 mg/kg), 10-fold (125 mg/kg) and 40-fold (500 mg/kg) doses showed no signs of intoxication and significant abnormalities after single and repeated i.v. administrations, preparation was non-immunogenic and induced minor and reversible allergic reaction in animals., Competing Interests: Declaration Funding: This work was supported by the Centre for Strategic Planning of FMBA of Russia (State Contract n. 0373100122120000008). Competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VDV, NPA, VVM, SMY and VAG are listed as the inventors in patent (RU2792679C1) on LysECD7-SMAP dosage form for parenteral use. VVM and SMY are the current employees of Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency. All other authors declare no competing interests. Authorship contributions: Nataliia P. Antonova: Methodology, Investigation, Formal analysis, Visualization, Writing–original draft. Daria V. Vasina: Conceptualization, Methodology, Data curation, Visualization, Writing–review & editing. Igor V. Grigoriev: Methodology, Investigation, Formal analysis. Aleksei I. Laishevtsev: Methodology, Investigation. Andrey V. Kapustin: Investigation. Vasiliy A. Savinov: Investigation. Andrey V. Aleshkin: Formal analysis, Data curation. Aleksei M. Vorobev: Investigation. Anastasia A. Zackharova: Project administration, Resources. Timofey A. Remizov: Project administration, Resources. Valentine V. Makarov: Funding acquisition. Sergey M. Yudin: Funding acquisition. Vladimir A. Gushchin: Conceptualization, Supervision, Writing–review & editing., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)- Published
- 2024
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13. Characteristics of the Gut Microbiota Composition of the Arctic Zone Residents in the Far Eastern Region.
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Nekrasova AI, Kalashnikova IG, Korobeynikova AV, Ashniev GA, Bobrova MM, Bakoev SY, Petryaikina ES, Nekrasov AS, Zagainova AV, Lukashina MV, Tolkacheva LR, Bobrovnitskii IP, Yudin VS, Keskinov AA, Makarov VV, and Yudin SM
- Abstract
Background . In many studies over the past decade, scientists have made a connection between the composition of gut microbiota and human health. A number of publications have shown that gut bacteria are involved in many metabolic and physiological processes of the organism. The composition of the gut microbiome is unique for each person and is formed under the influence of various factors associated with both the individual characteristics of the body and the characteristics of the environment. Different regional characteristics make it necessary for the body to adapt to certain conditions, including temperature fluctuations. Living in areas with low temperatures, such as the Arctic zone, dictates the need for increased energy consumption, which affects the composition of the gut microbiome. Methods. In our study, an extensive questionnaire was conducted among the participants, where many questions were included about the dietary preferences of the study participants, which allowed them us to further divide them into groups according to their diets. Stool samples were collected from participants from 3 groups: Arctic native, Arctic newcomer and the control group. The next step was the isolation of bacterial DNA and sequencing the 16S rRNA gene. The analysis of the results of the diversity of the intestinal microbiota was carried out both with and without taking into account the dietary preferences of the participants. Results . As a result of comparing the intestinal microbiota obtained from residents of the Arctic zone with the gut microbiota of residents of other regions with a milder climate, significant differences are found. These differences may be related to limited food resources and a reduction in the variety of food products characteristic of this Arctic region. t was also found that representatives of the bacterial families Christensenellaceae and Muribaculaceae dominated the control group, both with traditional nutrition and with a dairy-free diet in comparison with the Arctic groups. The control group was dominated by representatives of the Prevotellaceae, Enterobacteriaceae and Comamonadaceae families compared to the Arctic group (with a traditional diet). The results also show that the number of representatives of the families Desulfovibrionaceae (with traditional diet) and Enterobacteriaceae (with milk-free diet) is growing in the Arctic group. Conclusions. In the course of this work, bacterial families characteristic of people living in the Arc-tic zone of the Far Eastern region of the Russian Federation were identified. Poor diet, difficult climatic conditions, and problems with logistics and medical care can have a strong impact on the health of this population. The main type of diet for the inhabitants of the Arctic is the traditional type of diet. They consume a large number of low-cost products, obtainget animal protein from poultry and canned food, and also eat a small number of fresh vegetables and fruits. Such a diet is due to the social status of the study participants and the climatic and geographical features of the region (difficulties in agriculture). With such a diet, we observe a decrease in representatives of the Christensenellaceae, Muribaculaceae, Eubacteriaceae , and Prevotellaceae families and an increase in representatives of the Enterobacteriaceae and Desulfovibrionaceae families among Arctic residents. This imbalance in the futuremay cause, this population may to develop various diseases in the future, including chronic diseases such as obesity, intestinal dysbiosis, inflammatory bowel diseases, and type 2 diabetes.
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- 2024
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14. Gut Microbiota and Metabolic Alterations Associated with Heart Failure and Coronary Artery Disease.
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Yafarova AA, Dementeva EV, Zlobovskaya OA, Sheptulina AF, Lopatukhina EV, Timofeev YS, Glazunova EV, Lyundup AV, Doludin YV, Kiselev AR, Shipulin GA, Makarov VV, Drapkina OM, and Yudin SM
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- Humans, Male, Female, Middle Aged, Aged, Cross-Sectional Studies, Methylamines metabolism, Methylamines blood, Machine Learning, Feces microbiology, High-Throughput Nucleotide Sequencing, Gastrointestinal Microbiome, Coronary Artery Disease microbiology, Coronary Artery Disease metabolism, Heart Failure microbiology, Heart Failure metabolism
- Abstract
This study investigates the role of gut microbiota in cardiovascular diseases, with an additional focus on pro-atherogenic metabolites. We use advanced network analysis and machine learning techniques to identify key microbial features linked to coronary artery disease (CAD) and heart failure with reduced ejection fraction (HFrEF). This cross-sectional study included 189 participants divided into three groups: coronary artery disease ( n = 93), heart failure with reduced ejection fraction ( n = 43), and controls ( n = 53). Assessments included physical exams, echocardiography, dietary surveys, blood analysis, and fecal analysis. Gut microbiota composition was analyzed using next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Statistical analysis methods for testing hypotheses and correlations, alpha and beta-diversity analyses, co-occurrence networks, and machine learning were conducted using Python libraries or R packages with multiple comparisons corrected using the Benjamini-Hochberg procedure. Significant gut microbiota alterations were observed, with higher Bacillota/Bacteroidota ratios in CAD and HFrEF groups compared to controls ( p < 0.001). Significant differences were observed in α-diversity indices (Pielou, Chao1, Faith) between disease groups and controls ( p < 0.001). β-diversity analyses also revealed distinct microbial profiles ( p = 0.0015). Interestingly, trimethylamine N-oxide (TMAO) levels were lower in CAD and HFrEF groups compared to controls ( p < 0.05), while indoxyl sulfate (IS) levels were comparable between the study groups. Co-occurrence network analysis and machine learning identified key microbial features linked to these conditions, highlighting complex interactions within the gut microbiota associated with cardiovascular disease.
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- 2024
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15. The Association between Gut Microbiota and Serum Biomarkers in Children with Atopic Dermatitis.
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Kalashnikova IG, Nekrasova AI, Korobeynikova AV, Bobrova MM, Ashniev GA, Bakoev SY, Zagainova AV, Lukashina MV, Tolkacheva LR, Petryaikina ES, Nekrasov AS, Mitrofanov SI, Shpakova TA, Frolova LV, Bulanova NV, Snigir EA, Mukhin VE, Yudin VS, Makarov VV, Keskinov AA, and Yudin SM
- Abstract
Background. Currently, it is known that the gut microbiota plays an important role in the functioning of the immune system, and a rebalancing of the bacterial community can arouse complex immune reactions and lead to immune-mediated responses in an organism, in particular, the development of atopic dermatitis (AD). Cytokines and chemokines are regulators of the innate and adaptive immune response and represent the most important biomarkers of the immune system. It is known that changes in cytokine profiles are a hallmark of many diseases, including atopy. However, it remains unclear how the bacterial imbalance disrupts the function of the immune response in AD. Objectives . We attempted to determine the role of gut bacteria in modulating cytokine pathways and their role in atopic inflammation. Methods. We sequenced the 16S rRNA gene from 50 stool samples of children aged 3-12 years who had confirmed atopic dermatitis, and 50 samples from healthy children to serve as a control group. To evaluate the immune status, we conducted a multiplex immunofluorescence assay and measured the levels of 41 cytokines and chemokines in the serum of all participants. Results. To find out whether changes in the composition of the gut microbiota were significantly associated with changes in the level of inflammatory cytokines, a correlation was calculated between each pair of bacterial family and cytokine. In the AD group, 191 correlations were significant (Spearman's correlation coefficient, p ≤ 0.05), 85 of which were positive and 106 which were negative. Conclusions . It has been demonstrated that intestinal dysbiosis is associated with alterations in cytokine profiles, specifically an increase in proinflammatory cytokine concentrations. This may indicate a systemic impact of these conditions, leading to an imbalance in the immune system's response to the Th2 type. As a result, atopic conditions may develop. Additionally, a correlation between known AD biomarkers (IL-5, IL-8, IL-13, CCL22, IFN-γ, TNF-α) and alterations in the abundance of bacterial families ( Pasteurellaceae, Barnesiellaceae, Eubacteriaceae ) was observed.
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- 2024
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16. Search for signals of positive selection of circadian rhythm genes PER1, PER2, PER3 in different human populations.
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Mishina AI, Bakoev SY, Oorzhak AY, Keskinov AA, Kabieva SS, Korobeinikova AV, Yudin VS, Bobrova MM, Shestakov DA, Makarov VV, and Getmantseva LV
- Abstract
The diversity of geographically distributed human populations shows considerable variation in external and internal traits of individuals. Such differences are largely attributed to genetic adaptation to various environmental influences, which include changes in climatic conditions, variations in sleep and wakefulness, dietary variations, and others. Whole-genome data from individuals of different populations make it possible to determine the specific genetic sites responsible for adaptations and to further understand the genetic structure underlying human adaptive characteristics. In this article, we searched for signals of single nucleotide polymorphisms (SNPs) under selection pressure in people of different populations. To identify selection signals in different population groups, the PER1, PER2 and PER3 genes that are involved in the coordination of thermogenic functions and regulation of circadian rhythms, which is directly reflected in the adaptive abilities of the organism, were investigated. Data were analyzed using publicly available data from the 1000 Genomes Project for 23 populations. The Extended Haplotype Homozygosity Score statistical method was chosen to search for traces of selection. The comparative analysis performed identified points subject to selection pressure. The SNPs were annotated through the GWAS catalog and manually by analyzing Internet resources. This study suggests that living conditions, climate, and other external factors directly influence the genetic structure of populations and vary across races and geographic locations. In addition, many of the selection variants in the PER1, PER2, PER3 genes appear to regulate biological processes that are associated with major modern diseases, including obesity, cancer, metabolic syndrome, bipolar personality disorder, depression, rheumatoid arthritis, diabetes mellitus, lupus erythematosus, stroke and Alzheimer's disease, making them extremely interesting targets for further research aimed at identifying the genetic causes of human disease., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)
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- 2024
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17. Benchmarking of Approaches for Gene Copy-Number Variation Analysis and Its Utility for Genetic Aberration Detection in High-Grade Serous Ovarian Carcinomas.
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Grebnev PA, Meshkov IO, Ershov PV, Makhotenko AV, Azarian VB, Erokhina MV, Galeta AA, Zakubanskiy AV, Shingalieva OS, Tregubova AV, Asaturova AV, Yudin VS, Yudin SM, Makarov VV, Keskinov AA, Makarova AS, Snigir EA, and Skvortsova VI
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Objective : The goal of this study was to compare the results of CNV detection by three different methods using 13 paired carcinoma samples, as well as to perform a statistical analysis of the agreement. Methods : CNV was studied using NanoString nCounter v2 Cancer CN Assay (Nanostring), Illumina Infinium CoreExome microarrays (CoreExome microarrays) and digital droplet PCR (ddPCR). Results : There was a good level of agreement (PABAK score > 0.6) between the CoreExome microarrays and the ddPCR results for finding CNVs. There was a moderate level of agreement (PABAK values ≈ 0.3-0.6) between the NanoString Assay results and microarrays or ddPCR. For 83 out of 87 target genes studied (95%), the agreement between the CoreExome microarrays and NanoString nCounter was characterized by PABAK values < 0.75, except for MAGI3, PDGFRA, NKX2-1 and KDR genes (>0.75). The MET, HMGA2, KDR, C8orf4, PAX9, CDK6, and CCND2 genes had the highest agreement among all three approaches. Conclusions : Therefore, to get a better idea of how to genotype an unknown CNV spectrum in tumor or normal tissue samples that are very different molecularly, it makes sense to use at least two CNV detection methods. One of them, like ddPCR, should be able to quantitatively confirm the results of the other.
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- 2024
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18. Pharmacokinetics and Preclinical Safety Studies of Modified Endolysin-based Gel for Topical Application.
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Antonova NP, Vasina DV, Grigoriev IV, Usachev EV, Aleshkin AV, Vorobev AM, Laishevtsev AI, Kapustin AV, Savinov VA, Anurova MN, Zackharova AA, Remizov TA, Makarov VV, Yudin SM, and Gushchin VA
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- Animals, Female, Male, Mice, Administration, Topical, Skin metabolism, Skin drug effects, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents pharmacology, Endopeptidases administration & dosage, Endopeptidases pharmacokinetics, Endopeptidases pharmacology, Gels
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Antibacterial therapy with phage-encoded endolysins or their modified derivatives with improved antibacterial, biochemical and pharmacokinetic properties is one of the most promising strategies that can supply existing antibacterial drugs array. Gram-negative bacteria-induced infections treatment is especially challenging because of rapidly spreading bacterial resistance. We have developed modified endolysin LysECD7-SMAP with a significant antibacterial activity and broad spectra of action against gram-negative bacteria. Endolysin was formulated in a bactericidal gel for topical application with pronounced effectivity in local animal infectious models. Here we present preclinical safety studies and pharmacokinetics of LysECD7-SMAP-based gel. We have detected LysECD7-SMAP in the skin and underlying muscle at therapeutic concentrations when the gel is applied topically to intact or injured skin. Moreover, the protein does not enter the bloodstream, and has no systemic bioavailability, assuming no systemic adverse effects. In studies of general toxicology, local tolerance, and immunotoxicology it was approved that LysECD7-SMAP gel local application results in the absence of toxic effects after single and multiple administration. Thus, LysECD7-SMAP-containing gel has appropriate pharmacokinetics and can be considered as safe that supports the initiation of the phase I clinical trials of novel antibacterial drug intending to treat acute wound infections caused by resistant gram-negative bacteria., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nataliia P. Antonova, Daria V. Vasina, Igor V. Grigoriev, Evgeny V. Usachev, Anastasia A. Zackharova, Timofey A. Remizov, Vladimir A. Gushchin reports financial support was provided by center for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency. Valentine V. Makarov, Sergey M. Yudin reports a relationship with center for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency that includes: employment. Nataliia P. Antonova, Daria V. Vasina, Evgeny V. Usachev, Andrey V. Aleshkin, Aleksei M. Vorobev, Maria N. Anurova, Valentine V. Makarov, Sergey M. Yudin, Vladimir A. Gushchin has patent #RU2781050C1 "Bactericidal pharmaceutical composition for topical application in the form of an endolysin-containing bactericidal gel" licensed to center for Strategic Planning of FMBA of Russia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
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- 2024
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19. Development of novel antimicrobials with engineered endolysin LysECD7-SMAP to combat Gram-negative bacterial infections.
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Vasina DV, Antonova NP, Gushchin VA, Aleshkin AV, Fursov MV, Fursova AD, Gancheva PG, Grigoriev IV, Grinkevich P, Kondratev AV, Kostarnoy AV, Lendel AM, Makarov VV, Nikiforova MA, Pochtovyi AA, Prudnikova T, Remizov TA, Shevlyagina NV, Siniavin AE, Smirnova NS, Terechov AA, Tkachuk AP, Usachev EV, Vorobev AM, Yakimakha VS, Yudin SM, Zackharova AA, Zhukhovitsky VG, Logunov DY, and Gintsburg AL
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- Animals, Mice, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents administration & dosage, Rats, Male, Protein Engineering methods, Gram-Negative Bacterial Infections drug therapy, Endopeptidases pharmacology, Endopeptidases administration & dosage, Mice, Inbred BALB C, Gram-Negative Bacteria drug effects
- Abstract
Background: Among the non-traditional antibacterial agents in development, only a few targets critical Gram-negative bacteria such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii or cephalosporin-resistant Enterobacteriaceae. Endolysins and their genetically modified versions meet the World Health Organization criteria for innovation, have a novel mode of antibacterial action, no known bacterial cross-resistance, and are being intensively studied for application against Gram-negative pathogens., Methods: The study presents a multidisciplinary approach, including genetic engineering of LysECD7-SMAP and production of recombinant endolysin, its analysis by crystal structure solution following molecular dynamics simulations and evaluation of antibacterial properties. Two types of antimicrobial dosage forms were formulated, resulting in lyophilized powder for injection and hydroxyethylcellulose gel for topical administration. Their efficacy was estimated in the treatment of sepsis, and pneumonia models in BALB/c mice, diabetes-associated wound infection in the leptin receptor-deficient db/db mice and infected burn wounds in rats., Results: In this work, we investigate the application strategies of the engineered endolysin LysECD7-SMAP and its dosage forms evaluated in preclinical studies. The catalytic domain of the enzyme shares the conserved structure of endopeptidases containing a putative antimicrobial peptide at the C-terminus of polypeptide chain. The activity of endolysins has been demonstrated against a range of pathogens, such as Klebsiella pneumoniae, A. baumannii, P. aeruginosa, Staphylococcus haemolyticus, Achromobacter spp, Burkholderia cepacia complex and Haemophylus influenzae, including those with multidrug resistance. The efficacy of candidate dosage forms has been confirmed in in vivo studies. Some aspects of the interaction of LysECD7-SMAP with cell wall molecular targets are also discussed., Conclusions: Our studies demonstrate the potential of LysECD7-SMAP therapeutics for the systemic or topical treatment of infectious diseases caused by susceptible Gram-negative bacterial species and are critical to proceed LysECD7-SMAP-based antimicrobials trials to advanced stages., (© 2024. The Author(s).)
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- 2024
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20. Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer.
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Shestovskaya MV, Luss AL, Bezborodova OA, Kulikov PP, Antufrieva DA, Plotnikova EA, Makarov VV, Yudin VS, Pankratov AA, and Keskinov AA
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- Animals, Humans, Mice, Cell Line, Tumor, Magnetite Nanoparticles chemistry, Xenograft Model Antitumor Assays, Cell Survival drug effects, Colonic Neoplasms drug therapy, Colonic Neoplasms pathology, Colonic Neoplasms radiotherapy, Mice, Inbred BALB C, Magnetic Iron Oxide Nanoparticles chemistry, Radiation-Sensitizing Agents pharmacology, Radiation-Sensitizing Agents chemistry, Radiation-Sensitizing Agents administration & dosage, Heparin chemistry, Heparin pharmacology
- Abstract
The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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21. Characteristics of the Gut Microbiota in Regard to Atopic Dermatitis and Food Allergies of Children.
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Nekrasova AI, Kalashnikova IG, Bobrova MM, Korobeinikova AV, Bakoev SY, Ashniev GA, Petryaikina ES, Nekrasov AS, Zagainova AV, Lukashina MV, Tolkacheva LR, Zhdanova AS, Mukhin VE, Yudin VS, Keskinov AA, Makarov VV, Kraevoy SA, and Yudin SM
- Abstract
The gut microbiota plays an important role in maintaining human health, as well as in the development of various pathologies, as indicated by a large amount of research. One of the manifestations of an imbalance in the gut microbiome composition is the appearance of various diseases or immune reactions, in particular, atopic dermatitis (AD) and/or food allergies (FA). In this research, using 16S NGS sequencing, it was found that the gut microbiome of children with food allergies and children with atopic dermatitis can be characterized as having higher inflammatory potential. Both groups exhibited an abundance of representatives from the Pasteurellaceae and Erysipelotrichaceae families, as well as a decrease in the relative number of representatives from the Barnesiellaceae family compared to healthy participants. In the group of participants with food allergies, there was a decrease in the relative number of Desulfovibrionaceae representatives and Bifidobacteriaceae family enrichment in relatively healthy participants. In addition, when comparing this group with patients with atopic dermatitis, it was revealed that a number of representatives of such families as Erysipelotrichaceae , Ruminococcaceae and Sutterellaceae prevailed. This information confirms that AD and FA correlate with changes in the composition of the gut microbiota. Further research is needed to determine the cause-effect connections and the effect of compounds derived from the microbiota on the AD and FA development and progression, as well as to create new probiotic drugs to prevent and modulate immune responses, including at an early age.
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- 2024
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22. Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis.
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Yakovchik AY, Tolynyova DV, Kashtanova DA, Sutulova ER, Ivanov MV, Mamchur AA, Erema VV, Matkava LR, Terekhov MV, Rumyantseva AM, Blinova OI, Akinshina AI, Mitrofanov SI, Yudin VS, Makarov VV, Keskinov AА, Kraevoy SA, and Yudin SM
- Abstract
Background: Psycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied., Methods: In 2020-2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set)., Results: There was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647) , DLGAP4 (rs8114927) , and STK24 (rs9517326) ., Conclusion: Our results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yakovchik, Tolynyova, Kashtanova, Sutulova, Ivanov, Mamchur, Erema, Matkava, Terekhov, Rumyantseva, Blinova, Akinshina, Mitrofanov, Yudin, Makarov, Keskinov, Kraevoy and Yudin.)
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- 2024
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23. Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.
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Kashtanova DA, Mamchur AA, Dzhumaniyazova IH, Ivanov MV, Erema VV, Zelenova EA, Yakovchik AY, Gusakova MS, Rumyantseva AM, Terekhov MV, Matkava LR, Akopyan AA, Strazhesko ID, Yudin VS, Makarov VV, Kraevoy SA, Tkacheva ON, and Yudin SM
- Abstract
Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options., Methods: We assessed cognitive status in long-living adults aged 90+ ( n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression)., Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein., Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kashtanova, Mamchur, Dzhumaniyazova, Ivanov, Erema, Zelenova, Yakovchik, Gusakova, Rumyantseva, Terekhov, Matkava, Akopyan, Strazhesko, Yudin, Makarov, Kraevoy, Tkacheva and Yudin.)
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- 2023
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24. Gut Microbiota Patterns in Patients with Non-Alcoholic Fatty Liver Disease: A Comprehensive Assessment Using Three Analysis Methods.
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Korobeinikova AV, Zlobovskaya OA, Sheptulina AF, Ashniev GA, Bobrova MM, Yafarova AA, Akasheva DU, Kabieva SS, Bakoev SY, Zagaynova AV, Lukashina MV, Abramov IA, Pokrovskaya MS, Doludin YV, Tolkacheva LR, Kurnosov AS, Zyatenkova EV, Lavrenova EA, Efimova IA, Glazunova EV, Kiselev AR, Shipulin GA, Kontsevaya AV, Keskinov AA, Yudin VS, Makarov VV, Drapkina OM, and Yudin SM
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- Adult, Humans, RNA, Ribosomal, 16S genetics, Fibrosis, Bacteroidetes, Liver pathology, Non-alcoholic Fatty Liver Disease pathology, Gastrointestinal Microbiome genetics, Microbiota
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in Collinsella sp. and Oscillospiraceae for the control samples and enrichment in Lachnospiraceae (and in particular Dorea sp.) and Veillonellaceae in NAFLD. The families, Bifidobacteriaceae , Lactobacillaceae , and Enterococcaceae (particularly Enterococcus faecium and Enterococcus faecalis ), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in Candida krusei and a decrease in Bacteroides uniformis for NAFLD patients were detected using MALDI-TOF-MS. An increase in Gracilibacteraceae , Chitinophagaceae , Pirellulaceae , Erysipelatoclostridiaceae , Muribaculaceae , and Comamonadaceae , and a decrease in Acidaminococcaceae in NAFLD were observed with 16S NGS, and enrichment in Fusobacterium nucleatum was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
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- 2023
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25. Features of the use of ladder myoplasty of a gunshot wound to the laryngopharynx: Case report.
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Lurin IA, Makarov VV, Khoroshun EM, Nehoduiko VV, Shypilov SA, and Smolianyk KM
- Abstract
Introduction and Importance: The laryngopharynx wound is considered to be one of the most severe wounds of neck both in war and in peace, as it may cause life threatening changes in the whole body (asphyxia, bleeding, shock). Important aspects of surgical treatment are to ensure full breathing, acceptable ways of feeding, and the use of reliable wound closure techniques aimed to prevent digestive tract failure and to maintain the framework and aerostasis of the laryngotracheal region., Case Presentation: A case of unilateral multiple wounds of the laryngopharynx was described in the article. The features of diagnostics, surgical treatment and conservative therapy in the postoperative period with this injury were presented. The wounded man was urgently operated. During surgery the pharynx was mobilized. The metal fragment was removed. The wound of the pharynx was sutured with a two-row suture. The next stage of the surgical treatment was myoplasty. In the case of the patient, the purpose of myoplasty was additional sealing of the pharyngeal suture and myoplasty of the thyroid cartilage injury zone for the purpose of aerostasis. Because of the size of the wounds and their anatomical localization, we used the mobilized lower edge of the Musculus sternocleidomastoideus for myoplasty and proposed the method of ladder myoplasty developed by us., Clinical Discussion: In myoplasty method the following criteria must be followed: the muscle flap must be of sufficient length and width, so as not to cause excessive tension in the myoplasty area; the flap must be thick enough to avoid necrosis that may cause subsequent infectious complications; when taking the flap, the most sparing operative access should be used to avoid functional and anatomical disorders; the volume of the taken muscle flap must not lead to functional and anatomical disorders., Conclusion: The proposed method of ladder myoplasty using Musculus sternocleidomastoideus is unique, and proves its high efficiency in unilateral multiple laryngopharyngeal injuries, and can be recommended for wide clinical implementation in such clinical situations., Competing Interests: Declaration of competing interest There are no conflicts of interest in the creation of this case report as declared by the authors., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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26. Iron Oxide Nanoparticles in Cancer Treatment: Cell Responses and the Potency to Improve Radiosensitivity.
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Shestovskaya MV, Luss AL, Bezborodova OA, Makarov VV, and Keskinov AA
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The main concept of radiosensitization is making the tumor tissue more responsive to ionizing radiation, which leads to an increase in the potency of radiation therapy and allows for decreasing radiation dose and the concomitant side effects. Radiosensitization by metal oxide nanoparticles is widely discussed, but the range of mechanisms studied is not sufficiently codified and often does not reflect the ability of nanocarriers to have a specific impact on cells. This review is focused on the magnetic iron oxide nanoparticles while they occupied a special niche among the prospective radiosensitizers due to unique physicochemical characteristics and reactivity. We collected data about the possible molecular mechanisms underlying the radiosensitizing effects of iron oxide nanoparticles (IONPs) and the main approaches to increase their therapeutic efficacy by variable modifications.
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- 2023
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27. Current Approaches to Epigenetic Therapy.
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Griazeva ED, Fedoseeva DM, Radion EI, Ershov PV, Meshkov IO, Semyanihina AV, Makarova AS, Makarov VV, Yudin VS, Keskinov AA, and Kraevoy SA
- Abstract
Epigenetic therapy is a promising tool for the treatment of a wide range of diseases. Several fundamental epigenetic approaches have been proposed. Firstly, the use of small molecules as epigenetic effectors, as the most developed pharmacological method, has contributed to the introduction of a number of drugs into clinical practice. Secondly, various innovative epigenetic approaches based on dCas9 and the use of small non-coding RNAs as therapeutic agents are also under extensive research. In this review, we present the current state of research in the field of epigenetic therapy, considering the prospects for its application and possible limitations.
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- 2023
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28. GWAS reveals genetic basis of a predisposition to severe COVID-19 through in silico modeling of the FYCO1 protein.
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Gusakova MS, Ivanov MV, Kashtanova DA, Taraskina AN, Erema VV, Mikova VM, Loshkarev RI, Ignatyeva OA, Akinshina AI, Mitrofanov SI, Snigir EA, Yudin VS, Makarov VV, Keskinov AA, and Yudin SM
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is heavily reliant on its natural ability to "hack" the host's genetic and biological pathways. The genetic susceptibility of the host is a key factor underlying the severity of the disease. Polygenic risk scores are essential for risk assessment, risk stratification, and the prevention of adverse outcomes. In this study, we aimed to assess and analyze the genetic predisposition to severe COVID-19 in a large representative sample of the Russian population as well as to build a reliable but simple polygenic risk score model with a lower margin of error. Another important goal was to learn more about the pathogenesis of severe COVID-19. We examined the tertiary structure of the FYCO1 protein, the only gene with mutations in its coding region and discovered changes in the coiled-coil domain. Our findings suggest that FYCO1 may accelerate viral intracellular replication and excessive exocytosis and may contribute to an increased risk of severe COVID-19. We found significant associations between COVID-19 and LZTFL1 , FYCO1 , XCR1 , CCR9 , TMLHE-AS1 , and SCYL2 at 3p21.31. Our findings further demonstrate the polymorphic nature of the severe COVID-19 phenotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gusakova, Ivanov, Kashtanova, Taraskina, Erema, Mikova, Loshkarev, Ignatyeva, Akinshina, Mitrofanov, Snigir, Yudin, Makarov, Keskinov and Yudin.)
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- 2023
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29. Telemedicine support aids lower limb reconstruction after combat injury in Ukraine.
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Khomenko IP, Lurin IA, Gumeniuk KV, McKnight G, Makarov VV, Nehoduyko VV, Khoroshun E, and Tertyshnyi SV
- Abstract
Since the destructive and illegal full-scale invasion of Ukraine in February 2022, caring for the victims of war trauma has been an essential function of Ukrainian clinicians [ 1, 2]. The authors present a case where using novel dynamic digital thermography (DDT), combined with international telemedicine support, contributed to saving the lower limb of an injured Ukrainian soldier. A male soldier in his 30s presented with a 'through and through' fragmentation wound to the right thigh from an artillery shell exploding nearby. After initial haemorrhage control and resuscitation, the patient was transferred to a tertiary hospital. Using telemedicine support, reconstructive surgery was planned and performed successfully using a perforating flap technique. DDT was used pre-operatively to identify a perforating vessel and post-operatively to ensure perfusion of the flap. The patient made a good recovery and was discharged 14 d post-operatively., Competing Interests: The authors declare no conflict of interest., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.)
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- 2023
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30. Functional Characteristics of Serum Anti-SARS-CoV-2 Antibodies against Delta and Omicron Variants after Vaccination with Sputnik V.
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Radion EI, Mukhin VE, Kholodova AV, Vladimirov IS, Alsaeva DY, Zhdanova AS, Ulasova NY, Bulanova NV, Makarov VV, Keskinov AA, and Yudin SM
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- Humans, SARS-CoV-2, Antibodies, Viral, Vaccination, Antibodies, Neutralizing, COVID-19 prevention & control
- Abstract
Anti-SARS-CoV-2 vaccination leads to the production of neutralizing as well as non-neutralizing antibodies. In the current study, we investigated the temporal dynamics of both sides of immunity after vaccination with two doses of Sputnik V against SARS-CoV-2 variants Wuhan-Hu-1 SARS-CoV-2 G614-variant (D614G), B.1.617.2 (Delta), and BA.1 (Omicron). First, we constructed a SARS-CoV-2 pseudovirus assay to assess the neutralization activity of vaccine sera. We show that serum neutralization activity against BA.1 compared to D614G is decreased by 8.16-, 11.05-, and 11.16- fold in 1, 4, and 6 months after vaccination, respectively. Moreover, previous vaccination did not increase serum neutralization activity against BA.1 in recovered patients. Next, we used the ADMP assay to evaluate the Fc-mediated function of vaccine-induced serum antibodies. Our results show that the antibody-dependent phagocytosis triggered by S-proteins of the D614G, B.1.617.2 and BA.1 variants did not differ significantly in vaccinated individuals. Moreover, the ADMP efficacy was retained over up to 6 months in vaccine sera. Our results demonstrate differences in the temporal dynamics of neutralizing and non-neutralizing antibody functions after vaccination with Sputnik V.
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- 2023
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31. Mortality and survival in nonagenarians during the COVID-19 pandemic: Unstable equilibrium of aging.
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Kashtanova DA, Erema VV, Gusakova MS, Sutulova ER, Yakovchik AY, Ivanov MV, Taraskina AN, Terekhov MV, Matkava LR, Rumyantseva AM, Yudin VS, Akopyan AA, Strazhesko ID, Kordiukova IS, Akinshina AI, Makarov VV, Tkacheva ON, Kraevoy SA, and Yudin SM
- Abstract
Introduction: Aging puts the human body under an immense stress and makes it extremely susceptible to many diseases, often leading to poor outcomes and even death. Long-living individuals represent a unique group of people who withstood the stress of time and offer an abundance of information on the body's ability to endure the pressure of aging. In this study, we sought to identify predictors of overall one-year mortality in 1641 long-living individuals. Additionally, we analyzed risk factors for COVID-19-related morality, since statistics demonstrated an extreme vulnerability of older adults., Methods: We conducted a two-stage evaluation, including a comprehensive geriatric assessment for major aging-associated: frailty, cognitive impairment, frontal lobe dysfunction, chronic pain, anxiety, risk of falls, sensory deficit, depression, sarcopenia, risk of malnutrition, fecal and urinary incontinence, dependence in Activities of Daily Living, dependence in Instrumental Activities of Daily Living, polypragmasia, and orthostatic hypotension; extensive blood testing, a survey, and a one-year follow-up interview., Results: The most reliable predictors of overall mortality were cognitive impairment, malnutrition, frailty, aging-associated diseases and blood markers indicating malnutrition-induced metabolic dysfunctions (decreased levels of protein fractions, iron, 25-hydroxyvitamin D, and HDL), and aging biomarkers, such as IGF-1 and N-terminal pro b-type natriuretic peptide. In post-COVID 19 participants, the most significant mortality predictors among geriatric syndromes were depression, frontal lobe dysfunction and frailty, and similar to overall mortality blood biomarkers - 25-hydroxyvitamin D, IGF-1, HDL as well as high white blood cell, neutrophils counts and proinflammatory markers. Based on the results, we built a predictive model of overall mortality in the long-living individuals with f-score=0.76., Conclusion: The most sensitive and reliable predictors of mortality were modifiable. This is another evidence of the critical importance of proper geriatric care and support for individuals in their "golden years". These results could facilitate geriatric institutions in their pursuit for providing improved care and could aid physicians in detecting early signs of potentially deadly outcomes. Additionally, our findings could be used in developing day-to-day care guidelines, which would greatly improve prevention statistics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kashtanova, Erema, Gusakova, Sutulova, Yakovchik, Ivanov, Taraskina, Terekhov, Matkava, Rumyantseva, Yudin, Akopyan, Strazhesko, Kordiukova, Akinshina, Makarov, Tkacheva, Kraevoy and Yudin.)
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- 2023
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32. GUNSHOT SHRAPNEL WOUND OF THE THIGH WITH DAMAGE TO THE SUPERFICIAL FEMORAL ARTERY (FEATURES OF CLINICAL MANIFESTATIONS, DEVELOPMENT OF COMPLICATIONS WITH LATE MEDICAL CARE AND PRESERVATION OF THE LIMB).
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Lurin IA, Makarov VV, Nehoduiko VV, Smolianyk KM, Chobey SM, and Ott OY
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- Male, Humans, Middle Aged, Thigh surgery, Femoral Artery surgery, Treatment Outcome, Lower Extremity surgery, Wounds, Gunshot complications, Wounds, Gunshot surgery, Plastic Surgery Procedures, Soft Tissue Injuries complications, Soft Tissue Injuries surgery
- Abstract
Objective: The aim: To demonstrate the features of clinical manifestations and complications that occur with delayed medical treatment in cases of gunshot shrapnel through a wound of the thigh with damage to the superficial femoral artery., Patients and Methods: Materials and methods: The wounded individual, S., was 52 years old and had sustained a gunshot wound through a shrapnel wound of the left thigh with damage to the superficial femoral artery and soft tissue defect. Medical assistance was provided during the stages of medical evacuation., Results: Results: The soldier sustained a gunshot wound through the upper third of the left thigh, resulting in damage to the vascular-nerve bundle and a soft tissue defect. First aid was provided at the scene, and surgical procedures were performed during the stages of medical evacuation, including primary surgical treatment of wounds in the upper third of the left thigh. On the second day following the injury, the wounded man was transferred to the Vinnytsia Military Medical Clinical Center and admitted to the vascular surgery department. After an ultrasound examination and repeated surgical treatment of the wound on the left thigh, damage to the superficial femoral artery was identified., Conclusion: Conclusions: The presence of features of blood circulation in gunshot wounds of the main vessels of the lower limbs can favorably affect the possibility of saving the limb, as evidenced by the case presented.
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- 2023
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33. PROSPECTS OF THE HIGH-SPEED MULTIMEDIA DATA TRANSMISSION TECHNOLOGIES USE IN THE STRUCTURE OF THE SYSTEM FOR PROVIDING AID TO INJURED PERSONS HAVING A GUNSHOT DEFECT OF SOFT TISSUES.
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Lurin IA, Khomenko IP, Nehoduiko VV, Tertyshnyi SV, Makarov VV, Kvasnevskyi IY, and Kvasnevskyi OA
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- Humans, Russia, Medical Assistance, Ukraine, Multimedia, Wounds, Gunshot surgery
- Abstract
Objective: The aim: To improve the results of providing medical care in the conditions of a full-scale war in Ukraine due to the use of medical technologies., Patients and Methods: Materials and methods: From the first days, the Military Medical Clinical Center of the Southern Region provided medical assistance to the persons wounded as a result of the Russian Federation's armed aggression. The presented multidisciplinary observation includes data received from 24.02.22 to 26.05.22. During this term, the multidisciplinary team assisted by the Teladoc Health system (the connection between the Charite Clinic, Berlin, and the MMCC of the Southern Region, Ukraine) performed 39 reconstructive and remedial operations in the MMCC of the Southern Region (Department of Surgical Infection)., Results: Results: It has been found that the implementation of differentiated surgical tactics (developed in cooperation between Charite clinics, Berlin, and MMCC of the Southern Region, Ukraine, using the Teladoc health system) in wounded patients with gunshot defects of soft tissues at the III and IV levels of medical care improves functional results, increases indicators of satisfactory from 46.9 % to 53.7 %, reducing the relative number of unsatisfactory from 18.8 % to 11.6 %., Conclusion: Conclusions: The information exchange in the Teladoc Health system is performed in telephone mode through protected communication channels. It enabled real-time treatment strategy recommendations and improved functional outcomes, increasing the satisfactory rate from 46.9 % to 53.7 %, and reducing the relative unsatisfactory rate from 18.8 % to 11.6 %.
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- 2023
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34. Biological Age Predictors: The Status Quo and Future Trends.
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Erema VV, Yakovchik AY, Kashtanova DA, Bochkaeva ZV, Ivanov MV, Sosin DV, Matkava LR, Yudin VS, Makarov VV, Keskinov AA, Kraevoy SA, and Yudin SM
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- Humans, Pandemics, Reproducibility of Results, Aging, Biomarkers, Quality of Life, COVID-19 epidemiology
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There is no single universal biomarker yet to estimate overall health status and longevity prospects. Moreover, a consensual approach to the very concept of aging and the means of its assessment are yet to be developed. Markers of aging could facilitate effective health control, more accurate life expectancy estimates, and improved health and quality of life. Clinicians routinely use several indicators that could be biomarkers of aging. Duly validated in a large cohort, models based on a combination of these markers could provide a highly accurate assessment of biological age and the pace of aging. Biological aging is a complex characteristic of chronological age (usually), health-to-age concordance, and medically estimated life expectancy. This study is a review of the most promising techniques that could soon be used in routine clinical practice. Two main selection criteria were applied: a sufficient sample size and reliability based on validation. The selected biological age calculators were grouped according to the type of biomarker used: (1) standard clinical and laboratory markers; (2) molecular markers; and (3) epigenetic markers. The most accurate were the calculators, which factored in a variety of biomarkers. Despite their demonstrated effectiveness, most of them require further improvement and cannot yet be considered for use in standard clinical practice. To illustrate their clinical application, we reviewed their use during the COVID-19 pandemic.
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- 2022
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35. Diversities in the Gut Microbial Patterns in Patients with Atherosclerotic Cardiovascular Diseases and Certain Heart Failure Phenotypes.
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Drapkina OM, Ashniev GA, Zlobovskaya OA, Yafarova AA, Dementeva EV, Kaburova AN, Meshkov IO, Sheptulina AF, Kiselev AR, Kontsevaya AV, Zhamalov LM, Koretskiy SN, Pokrovskaya MS, Akinshina AI, Zagaynova AV, Lukashina MV, Kirillov AV, Abramov IA, Tolkacheva LR, Bikaeva IO, Glazunova EV, Shipulin GA, Bobrova MM, Makarov VV, Keskinov AA, Yudin VS, and Yudin SM
- Abstract
To continue progress in the treatment of cardiovascular disease, there is a need to improve the overall understanding of the processes that contribute to the pathogenesis of cardiovascular disease (CVD). Exploring the role of gut microbiota in various heart diseases is a topic of great interest since it is not so easy to find such reliable connections despite the fact that microbiota undoubtedly affect all body systems. The present study was conducted to investigate the composition of gut microbiota in patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure syndromes with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF), and to compare these results with the microbiota of individuals without those diseases (control group). Fecal microbiota were evaluated by three methods: living organisms were determined using bacterial cultures, total DNA taxonomic composition was estimated by next generation sequencing (NGS) of 16S rRNA gene (V3-V4) and quantitative assessment of several taxa was performed using qPCR (quantitative polymerase chain reaction). Regarding the bacterial culture method, all disease groups demonstrated a decrease in abundance of Enterococcus faecium and Enterococcus faecalis in comparison to the control group. The HFrEF group was characterized by an increased abundance of Streptococcus sanguinus and Streptococcus parasanguinis . NGS analysis was conducted at the family level. No significant differences between patient's groups were observed in alpha-diversity indices (Shannon, Faith, Pielou, Chao1, Simpson, and Strong) with the exception of the Faith index for the HFrEF and control groups. Erysipelotrichaceae were significantly increased in all three groups; Streptococcaceae and Lactobacillaceae were significantly increased in ASCVD and HFrEF groups. These observations were indirectly confirmed with the culture method: two species of Streptococcus were significantly increased in the HFrEF group and Lactobacillus plantarum was significantly increased in the ASCVD group. The latter observation was also confirmed with qPCR of Lactobacillus sp. Acidaminococcaceae and Odoribacteraceae were significantly decreased in the ASCVD and HFrEF groups. Participants from the HFpEF group showed the least difference compared to the control group in all three study methods. The patterns found expand the knowledge base on possible correlations of gut microbiota with cardiovascular diseases. The similarities and differences in conclusions obtained by the three methods of this study demonstrate the need for a comprehensive approach to the analysis of microbiota.
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- 2022
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36. Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults.
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Kashtanova DA, Taraskina AN, Erema VV, Akopyan AA, Ivanov MV, Strazhesko ID, Akinshina AI, Yudin VS, Makarov VV, Kraevoy SA, Korolev DE, Tarasova IV, Beloshevskaya OA, Mkhitaryan EA, Tkacheva ON, and Yudin SM
- Subjects
- Aged, Aged, 80 and over, Aging psychology, Educational Status, Exercise, Health Status, Holistic Health, Humans, Income, Leisure Activities, Life Style, Occupations, Risk Factors, Socioeconomic Factors, Syndrome, Aging physiology, Geriatric Assessment, Health Promotion methods, Longevity
- Abstract
Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals-people over the age of 90 who managed to retain much of their health and functionality-could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).
- Published
- 2022
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37. A Strategy for the Rapid Development of a Safe Vibrio cholerae Candidate Vaccine Strain.
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Karpov DS, Goncharenko AV, Usachev EV, Vasina DV, Divisenko EV, Chalenko YM, Pochtovyi AA, Ovchinnikov RS, Makarov VV, Yudin SM, Tkachuk AP, and Gushchin VA
- Subjects
- Gene Transfer Techniques, Genes, Reporter, Genetic Engineering, Genome, Bacterial, Cholera Vaccines, Operon, Vibrio cholerae genetics
- Abstract
Approximately 1/6 of humanity is at high risk of experiencing cholera epidemics. The development of effective and safe vaccines against Vibrio cholerae, the primary cause of cholera, is part of the public health measures to prevent cholera epidemics. Natural nontoxigenic V. cholerae isolates represent a source of new genetically improved and relatively safe vaccine strains. However, the genomic engineering of wild-type V. cholerae strains is difficult, and these strains are genetically unstable due to their high homologous recombination activity. We comprehensively characterized two V. cholerae isolates using genome sequencing, bioinformatic analysis, and microscopic, physiological, and biochemical tests. Genetic constructs were Gibson assembled and electrotransformed into V. cholerae . Bacterial colonies were assessed using standard microbiological and immunological techniques. As a result, we created a synthetic chromoprotein-expressing reporter operon. This operon was used to improve the V. cholerae genome engineering approach and monitor the stability of the genetic constructs. Finally, we created a stable candidate V. cholerae vaccine strain bearing a recA deletion and expressing the β-subunit of cholera toxin. Thus, we developed a strategy for the rapid creation of genetically stable and relatively safe candidate vaccine strains. This strategy can be applied not only to V. cholerae but also to other important human bacterial pathogens.
- Published
- 2021
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38. Discovering the Potentials of Four Phage Endolysins to Combat Gram-Negative Infections.
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Vasina DV, Antonova NP, Grigoriev IV, Yakimakha VS, Lendel AM, Nikiforova MA, Pochtovyi AA, Remizov TA, Usachev EV, Shevlyagina NV, Zhukhovitsky VG, Fursov MV, Potapov VD, Vorobev AM, Aleshkin AV, Laishevtsev AI, Makarov VV, Yudin SM, Tkachuk AP, and Gushchin VA
- Abstract
Endolysin-based therapeutics are promising antibacterial agents and can successfully supplement the existing antibacterial drugs array. It is specifically important in the case of Gram-negative pathogens, e.g., ESKAPE group bacteria, which includes Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacter species, and are highly inclined to gain multiple antibiotic resistance. Despite numerous works devoted to the screening of new lytic enzymes and investigations of their biochemical properties, there are significant breaches in some aspects of their operating characteristics, including safety issues of endolysin use. Here, we provide a comprehensive study of the antimicrobial efficacy aspects of four Gram-negative bacteria-targeting endolysins LysAm24, LysAp22, LysECD7, and LysSi3, their in vitro and in vivo activity, and their biological safety. These endolysins possess a wide spectrum of action, are active against planktonic bacteria and bacterial biofilms, and are effective in wound and burn skin infection animal models. In terms of safety, these enzymes do not contribute to the development of short-term resistance, are not cytotoxic, and do not significantly affect the normal intestinal microflora in vivo . Our results provide a confident base for the development of effective and safe candidate dosage forms for the treatment of local and systemic infections caused by Gram-negative bacterial species., Competing Interests: NA, DV, AT, and VG are the authors but not the patent holders of the following patents issued according to the results of this work (RU): RU 2730613 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Salmonella typhi, and Staphylococcus haemolyticus (embodiments)”; RU 2730614 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against bacteria P. aeruginosa, K. pneumoniae, Escherichia coli, Salmonella typhi, and Staphylococcus haemolyticus (embodiments)”; RU 2730615 C1 “Antibacterial composition (embodiments) and use of protein as antimicrobial agent directed against Gram-negative bacteria: P. aeruginosa, Acinetobacter baumannii, K. pneumoniae, and Salmonella typhi (embodiments)”; and RU 2730616 C1 “Antibacterial composition (embodiments) and use of protein as an antimicrobial agent directed against A. baumannii bacteria (embodiments).” The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vasina, Antonova, Grigoriev, Yakimakha, Lendel, Nikiforova, Pochtovyi, Remizov, Usachev, Shevlyagina, Zhukhovitsky, Fursov, Potapov, Vorobev, Aleshkin, Laishevtsev, Makarov, Yudin, Tkachuk and Gushchin.)
- Published
- 2021
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39. Structural and Phase Transformations and Physical and Mechanical Properties of Cu-Al-Ni Shape Memory Alloys Subjected to Severe Plastic Deformation and Annealing.
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Svirid AE, Pushin VG, Kuranova NN, Makarov VV, and Ustyugov YM
- Abstract
Using the methods of electron microscopy and X-ray analysis in combination with measurements of the electrical resistance and magnetic susceptibility, the authors have obtained data on the peculiar features of pre-martensitic states and martensitic transformations, as well as subsequent decomposition, in the alloys with shape memory effect of Cu-14wt%Al-3wt%Ni and Cu-13.5wt%Al-3.5wt%Ni. For the first time, we established the microstructure, phase composition, mechanical properties, and microhardness of the alloys obtained in the nanocrystalline state as a result of severe plastic deformation under high pressure torsion and subsequent annealing. A crystallographic model of the martensite nucleation and the rearrangements β
1 →β1 ' and β1 →γ1 ' are proposed based on the analysis of the observed tweed contrast and diffuse scattering in the austenite and the internal defects in the substructure of the martensite.- Published
- 2021
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40. [The study of tryptophan metabolite concentrations in blood serum and fecal extracts from obese children].
- Author
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Shestopalov AV, Shatova OP, Gaponov AM, Moskaleva NE, Appolonova SA, Tutelyan AV, Makarov VV, Yudin SM, and Rumyantsev SA
- Subjects
- Child, Humans, Kynurenine, Plant Extracts, Tryptophan, Pediatric Obesity
- Abstract
We found that changes in the concentrations of tryptophan metabolites in the blood serum and in the intestinal contents are one of the mechanisms for the formation of metabolic coupling in the system "macroorganism-intestinal microbiota", which undergoes significant changes in the development of obesity. Although blood kynurenine remained basically unchanged in obese children we found an increase in some of its serum metabolites: anthranilic, kynurenic and xanthurenic acids. It is noteworthy that in the analysis of fecal matter in obese children, revealed a 2-fold increase in the level of kynurenine while the concentration of kynurenine pathway metabolites corresponded to the level of the group of healthy children. This may indicate the metabolic activation of the microbiota associated with the intestinal mucosa. This is also supported by the absence of statistically significant differences in the concentration of indole in healthy children and in obese children in fecal analyses, and a significant increase in the concentration of indole-3-lactate and indole-3-acetate in the blood serum of obese children.
- Published
- 2020
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41. Antibiofilm Activity of a Broad-Range Recombinant Endolysin LysECD7: In Vitro and In Vivo Study.
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Fursov MV, Abdrakhmanova RO, Antonova NP, Vasina DV, Kolchanova AD, Bashkina OA, Rubalsky OV, Samotrueva MA, Potapov VD, Makarov VV, Yudin SM, Gintsburg AL, Tkachuk AP, Gushchin VA, and Rubalskii EO
- Subjects
- Animals, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents isolation & purification, Biofilms growth & development, Coliphages enzymology, Coliphages genetics, Disease Models, Animal, Drug Resistance, Multiple, Bacterial, Endopeptidases administration & dosage, Endopeptidases genetics, Endopeptidases isolation & purification, Female, Klebsiella Infections microbiology, Klebsiella Infections prevention & control, Klebsiella pneumoniae physiology, Microbial Sensitivity Tests, Prosthesis-Related Infections microbiology, Prosthesis-Related Infections prevention & control, Rats, Recombinant Proteins administration & dosage, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins pharmacology, Anti-Bacterial Agents pharmacology, Biofilms drug effects, Endopeptidases pharmacology, Klebsiella pneumoniae drug effects
- Abstract
Surfaces of implanted medical devices are highly susceptible to biofilm formation. Bacteria in biofilms are embedded in a self-produced extracellular matrix that inhibits the penetration of antibiotics and significantly contributes to the mechanical stability of the colonizing community which leads to an increase in morbidity and mortality rate in clinical settings. Therefore, new antibiofilm approaches and substances are urgently needed. In this paper, we test the efficacy of a broad-range recombinant endolysin of the coliphage LysECD7 against forming and mature biofilms. We used a strong biofilm producer- Klebsiella pneumoniae Ts 141-14 clinical isolate. In vitro investigation of the antibacterial activity was performed using the standard biofilm assay in microtiter plates. We optimized the implantable diffusion chamber approach in order to reach strong biofilm formation in vivo avoiding severe consequences of the pathogen for the animals and to obtain a well-reproducible model of implant-associated infection. Endolysin LysECD7 significantly reduced the biofilm formation and was capable of degrading the preformed biofilm in vitro. The animal trials on the preformed biofilms confirmed these results. Overall, our results show that LysECD7 is a promising substance against clinically relevant biofilms.
- Published
- 2020
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42. Modulation of Endolysin LysECD7 Bactericidal Activity by Different Peptide Tag Fusion.
- Author
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Antonova NP, Vasina DV, Rubalsky EO, Fursov MV, Savinova AS, Grigoriev IV, Usachev EV, Shevlyagina NV, Zhukhovitsky VG, Balabanyan VU, Potapov VD, Aleshkin AV, Makarov VV, Yudin SM, Gintsburg AL, Tkachuk AP, and Gushchin VA
- Subjects
- Animals, Sheep, Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Endopeptidases chemistry, Gram-Negative Bacteria growth & development, Gram-Positive Bacteria growth & development, Pore Forming Cytotoxic Proteins chemistry, Pore Forming Cytotoxic Proteins pharmacology
- Abstract
The use of recombinant endolysins is a promising approach for antimicrobial therapy capable of counteracting the spread of antibiotic-resistant strains. To obtain the necessary biotechnological product, diverse peptide tags are often fused to the endolysin sequence to simplify enzyme purification, improve its ability to permeabilize the bacterial outer membrane, etc. We compared the effects of two different types of protein modifications on endolysin LysECD7 bactericidal activity in vitro and demonstrated that it is significantly modulated by specific permeabilizing antimicrobial peptides, as well as by widely used histidine tags. Thus, the tags selected for the study of endolysins and during the development of biotechnological preparations should be used with the appropriate precautions to minimize false conclusions about endolysin properties. Further, modifications of LysECD7 allowed us to obtain a lytic enzyme that was largely devoid of the disadvantages of the native protein and was active over the spectra of conditions, with high in vitro bactericidal activity not only against Gram-negative, but also against Gram-positive, bacteria. This opens up the possibility of developing effective antimicrobials based on N-terminus sheep myeloid peptide of 29 amino acids (SMAP)-modified LysECD7 that can be highly active not only during topical treatment but also for systemic applications in the bloodstream and tissues., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of this study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
- Published
- 2020
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43. Coherent resonance in the distributed cortical network during sensory information processing.
- Author
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Pisarchik AN, Maksimenko VA, Andreev AV, Frolov NS, Makarov VV, Zhuravlev MO, Runnova AE, and Hramov AE
- Abstract
Neuronal brain network is a distributed computing system, whose architecture is dynamically adjusted to provide optimal performance of sensory processing. A small amount of visual information needed effortlessly be processed, activates neural activity in occipital and parietal areas. Conversely, a visual task which requires sustained attention to process a large amount of sensory information, involves a set of long-distance connections between parietal and frontal areas coordinating the activity of these distant brain regions. We demonstrate that while neural interactions result in coherence, the strongest connection is achieved through coherence resonance induced by adjusting intrinsic brain noise.
- Published
- 2019
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44. Cryopreservation of the human gut microbiota: Current state and perspectives.
- Author
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Smirnova DV, Zalomova LV, Zagainova AV, Makarov VV, Mezhevikina LM, Fesenko EE Jr, and Yudin SM
- Subjects
- Biological Specimen Banks, Cryopreservation standards, Fecal Microbiota Transplantation, Humans, Probiotics, Specimen Handling, Cryopreservation methods, Gastrointestinal Microbiome
- Abstract
The human intestinal microbiota is a complex ecosystem that consists of thousands of bacterial species that are responsible for human health and disease. The intestinal microbiota is a natural resource for production of therapeutic and preventive medicals, such as probiotics and fecal transplants. Modern lifestyles have resulted in the extinction of evolutionally selected microbial populations upon exposure to environmental factors. Therefore, it is very important to preserve the human gut microbiota to have the opportunity for timely restoration with minimal safety risks. Cryopreservation techniques that are suitable for the preservation of viable, mixed microbial communities and a biobanking approach are currently under development in different countries. However, the number of studies in this area is very limited. The variety of morphological and physiological characteristics of microbes in the microbiota, the different cryopreservation goals, and the criteria for the evaluation of cryopreservation effectiveness are the main challenges in the creation of a universal and standardized cryopreservation protocol. In this review, we summarized the current progress of the main cryopreservation techniques for gut microbiota communities and the methods for the assessment of the effectiveness of these techniques in the context of practical application., (Copyright © 2019 Elsevier GmbH. All rights reserved.)
- Published
- 2019
- Full Text
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45. Statistical Properties and Predictability of Extreme Epileptic Events.
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Frolov NS, Grubov VV, Maksimenko VA, Lüttjohann A, Makarov VV, Pavlov AN, Sitnikova E, Pisarchik AN, Kurths J, and Hramov AE
- Subjects
- Animals, Brain pathology, Disease Models, Animal, Electroencephalography methods, Male, Rats, Epilepsy, Absence pathology, Seizures pathology
- Abstract
The use of extreme events theory for the analysis of spontaneous epileptic brain activity is a relevant multidisciplinary problem. It allows deeper understanding of pathological brain functioning and unraveling mechanisms underlying the epileptic seizure emergence along with its predictability. The latter is a desired goal in epileptology which might open the way for new therapies to control and prevent epileptic attacks. With this goal in mind, we applied the extreme event theory for studying statistical properties of electroencephalographic (EEG) recordings of WAG/Rij rats with genetic predisposition to absence epilepsy. Our approach allowed us to reveal extreme events inherent in this pathological spiking activity, highly pronounced in a particular frequency range. The return interval analysis showed that the epileptic seizures exhibit a highly-structural behavior during the active phase of the spiking activity. Obtained results evidenced a possibility for early (up to 7 s) prediction of epileptic seizures based on consideration of EEG statistical properties.
- Published
- 2019
- Full Text
- View/download PDF
46. Functional Analysis of Coilin in Virus Resistance and Stress Tolerance of Potato Solanum tuberosum using CRISPR-Cas9 Editing.
- Author
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Makhotenko AV, Khromov AV, Snigir EA, Makarova SS, Makarov VV, Suprunova TP, Kalinina NO, and Taliansky ME
- Subjects
- CRISPR-Cas Systems, Disease Resistance, Meristem genetics, Meristem metabolism, Meristem virology, Nuclear Proteins genetics, Nuclear Proteins metabolism, Osmotic Pressure, Plant Diseases virology, Plant Proteins genetics, Plant Proteins metabolism, Rhabdoviridae metabolism, Solanum tuberosum genetics, Solanum tuberosum metabolism, Solanum tuberosum virology
- Abstract
The role of the nuclear protein coilin in the mechanisms of resistance of potato Solanum tuberosum cultivar Chicago to biotic and abiotic stresses was studied using the CRISPR-Cas9 technology. For the coilin gene editing, a complex consisting of the Cas9 endonuclease and a short guide RNA was immobilized on gold or chitosan microparticles and delivered into apical meristem cells by bioballistics or vacuum infiltration methods, respectively. Editing at least one allele of the coilin gene considerably increased the resistance of the edited lines to infection with the potato virus Y and their tolerance to salt and osmotic stress.
- Published
- 2019
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47. Virus-Like Particle Facilitated Deposition of Hydroxyapatite Bone Mineral on Nanocellulose after Exposure to Phosphate and Calcium Precursors.
- Author
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Sinitsyna OV, Makarov VV, McGeachy K, Bukharova T, Whale E, Hepworth D, Yaminsky IV, Kalinina NO, Taliansky ME, and Love AJ
- Subjects
- Biotechnology, Tobacco Mosaic Virus, Calcification, Physiologic, Calcium chemistry, Cellulose chemistry, Durapatite chemistry, Nanocomposites chemistry, Nanocomposites ultrastructure, Phosphates chemistry
- Abstract
We produced and isolated tobacco mosaic virus-like particles (TMV VLPs) from bacteria, which are devoid of infectious genomes, and found that they have a net negative charge and can bind calcium ions. Moreover, we showed that the TMV VLPs could associate strongly with nanocellulose slurry after a simple mixing step. We sequentially exposed nanocellulose alone or slurries mixed with the TMV VLPs to calcium and phosphate salts and utilized physicochemical approaches to demonstrate that bone mineral (hydroxyapatite) was deposited only in nanocellulose mixed with the TMV VLPs. The TMV VLPs confer mineralization properties to the nanocellulose for the generation of new composite materials.
- Published
- 2019
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48. Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative ESKAPE Pathogens.
- Author
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Antonova NP, Vasina DV, Lendel AM, Usachev EV, Makarov VV, Gintsburg AL, Tkachuk AP, and Gushchin VA
- Subjects
- Acinetobacter baumannii drug effects, Endopeptidases chemistry, Escherichia coli drug effects, Klebsiella pneumoniae drug effects, Pseudomonas aeruginosa drug effects, Anti-Bacterial Agents pharmacology, Endopeptidases pharmacology, Gram-Negative Bacteria drug effects, Myoviridae chemistry
- Abstract
The extremely rapid spread of multiple-antibiotic resistance among Gram-negative pathogens threatens to move humankind into the so-called "post-antibiotic era" in which the most efficient and safe antibiotics will not work. Bacteriophage lysins represent promising alternatives to antibiotics, as they are capable of digesting bacterial cell wall peptidoglycans to promote their osmotic lysis. However, relatively little is known regarding the spectrum of lysin bactericidal activity against Gram-negative bacteria. In this study, we present the results of in vitro activity assays of three putative and newly cloned Myoviridae bacteriophage endolysins (LysAm24, LysECD7, and LysSi3). The chosen proteins represent lysins with diverse domain organization (single-domain vs. two-domain) and different predicted mechanisms of action (lysozyme vs. peptidase). The enzymes were purified, and their properties were characterized. The enzymes were tested against a panel of Gram-negative clinical bacterial isolates comprising all Gram-negative representatives of the ESKAPE group. Despite exhibiting different structural organizations, all of the assayed lysins were shown to be capable of lysing Pseudomonas aeruginosa , Acinetobacter baumannii , Klebsiella pneumoniae , Escherichia coli , and Salmonella typhi strains. Less than 50 μg/mL was enough to eradicate growing cells over more than five orders of magnitude. Thus, LysAm24, LysECD7, and LysSi3 represent promising therapeutic agents for drug development.
- Published
- 2019
- Full Text
- View/download PDF
49. Increasing Human Performance by Sharing Cognitive Load Using Brain-to-Brain Interface.
- Author
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Maksimenko VA, Hramov AE, Frolov NS, Lüttjohann A, Nedaivozov VO, Grubov VV, Runnova AE, Makarov VV, Kurths J, and Pisarchik AN
- Abstract
Brain-computer interfaces (BCIs) attract a lot of attention because of their ability to improve the brain's efficiency in performing complex tasks using a computer. Furthermore, BCIs can increase human's performance not only due to human-machine interactions, but also thanks to an optimal distribution of cognitive load among all members of a group working on a common task, i.e., due to human-human interaction. The latter is of particular importance when sustained attention and alertness are required. In every day practice, this is a common occurrence, for example, among office workers, pilots of a military or a civil aircraft, power plant operators, etc. Their routinely work includes continuous monitoring of instrument readings and implies a heavy cognitive load due to processing large amounts of visual information. In this paper, we propose a brain-to-brain interface (BBI) which estimates brain states of every participant and distributes a cognitive load among all members of the group accomplishing together a common task. The BBI allows sharing the whole workload between all participants depending on their current cognitive performance estimated from their electrical brain activity. We show that the team efficiency can be increased due to redistribution of the work between participants so that the most difficult workload falls on the operator who exhibits maximum performance. Finally, we demonstrate that the human-to-human interaction is more efficient in the presence of a certain delay determined by brain rhythms. The obtained results are promising for the development of a new generation of communication systems based on neurophysiological brain activity of interacting people. Such BBIs will distribute a common task between all group members according to their individual physical conditions.
- Published
- 2018
- Full Text
- View/download PDF
50. Non-structural Functions of Hordeivirus Capsid Protein Identified in Plants Infected by a Chimeric Tobamovirus.
- Author
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Makarova SS, Makhotenko AV, Khromov AV, Skurat EV, Solovyev AG, Makarov VV, and Kalinina NO
- Subjects
- Tobamovirus metabolism, Capsid Proteins metabolism, Hybridization, Genetic, Nicotiana virology, Tobamovirus genetics, Tobamovirus physiology
- Abstract
Capsid proteins (CPs) of (+)RNA-containing plant viruses are multifunctional proteins involved in many stages of viral infection cycle, in addition to their main function of virus capsid formation. For example, the tobamoviral CP ensures virus systemic transport in plants and defines the virus-host interactions, thereby influencing the virus host range, virus infectivity, pathogenicity, and manifestation of infection symptoms. Hordeiviruses and tobamoviruses belong to the Virgaviridae family and have rod-shaped virions with a helical symmetry; their CPs are similar in structure. However, no non-structural functions of hordeiviral CPs have been described so far. In this study, we assayed possible non-structural functions of CP from the barley stripe mosaic virus (BSMV) (hordeivirus). To do this, the genome of turnip vein clearing virus (TVCV) (tobamovirus) was modified by substituting the TVCV CP gene with the BSMV CP gene or its mutants. We found that BSMV CP efficiently replaced TVCV CP at all stages of viral infection. In particular, BSMV CP performed the role of tobamoviral CP in the long-distance transport of the chimeric virus, acted as a hypersensitive response elicitor, and served as a pathogenicity determinant that influenced the symptoms of the viral infection. The chimeric tobamovirus coding for the C-terminally truncated BSMV CP displayed an increased infectivity and was transported in plants in a form of atypical virions (ribonucleoprotein complexes).
- Published
- 2018
- Full Text
- View/download PDF
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