Information about the paper titled "TWO-DIMENSIONAL SIGNAL IMITATION AS AN ELEMENT OF THEORETICAL AND PRACTICAL TRAINING FOR ENGINEERS IN INFORMATION TECHNOLOGY" at IATED Digital Library

Мутации гена Dmd , кодирующего мембранный белок дистрофин, ассоциированы с развитием тяжелых X-сцепленных мышечными заболеваниями - миодистрофии Дюшенна и Беккера. При этом наряду с классическими симптомами со стороны поперечнополосатой мускулатуры мутации дистрофина могут приводить к снижению когнитивных функций и поведенческим аномалиям. Цель: проведение пилотного анализа поведенческих и когнитивных особенностей у мышей с генетическим дефектом, воспроизводящим фенотип миодистрофии Дюшенна. Материалы и методы. Для оценки особенностей моторных функций и поведения мыши Dmd^Del8-34 (n=13) и контрольные животные дикого типа (n=12) были подвергнуты исследованию в тестах «Удержание груза», «Ротарод», «Приподнятый крестообразный лабиринт» и «Распознавание объектов». Результаты. Было обнаружено, что мыши, несущие мутацию Dmd^Del8-34 характеризуются снижением моторных функций, демонстрируют признаки тревожности, а также проявляют низкую исследовательскую активность. Обнаруженные особенности когнитивного и эмоционального статуса совпадают с клиническими наблюдениями, свидетельствующими о повышенном риске развития у пациентов с мутациями гена Dmd расстройств аутистического спектра и обсессивно-компульсивного расстройства. Таким образом было доказано, что с 8 недели жизни мыши линии Dmd^Del8-34 демонстрируют снижение показателей в тестах «Ротарод» и «Удержание груза». Поведенческое тестирование в тесте «Приподнятый крестообразный лабиринт» выявило снижение времени, достигающее статистически достоверной разницы в сравнении с контролем дикого типа на 12й неделе и при оценке когнитивных функций в тесте «Распознавание объектов» было показано, что мыши Dmd^Del8-34 демонстрируют увеличение значения индекса дискриминации, что является признаком увеличения эффективности гиппокампальной памяти. Заключение. Проведенное исследование позволило выявить некоторые поведенческие аномалии у генетически-модифицированных мышей, несущих крупную делецию экзонов 8-34 гена Dmd , кодирующего дистрофин.

Information about the paper titled "MATLAB AS A LEARNING ENVIRONMENT FOR THE SPECTRAL APPROACH TO SIGNAL SIMULATION" at IATED Digital Library

The aim of the work was to analyze the available therapeutic options for the conventional therapy of hereditary myopathies.Materials and methods. When searching for the material for writing a review article, such abstract databases as PubMed and Google Scholar were used. The search was carried out on the publications during the period from 1980 to September 2022. The following words and their combinations were selected as parameters for the literature selection: “myopathy”, “Duchenne”, “myodystrophy”, “metabolic”, “mitochondrial”, “congenital”, “symptoms”, “replacement”, “recombinant”, “corticosteroids”, “vitamins”, “tirasemtiv”, “therapy”, “treatment”, “evidence”, “clinical trials”, “patients”, “dichloracetate”.Results. Congenital myopathies are a heterogeneous group of pathologies that are caused by atrophy and degeneration of muscle fibers due to mutations in genes. Based on a number of clinical and pathogenetic features, hereditary myopathies are divided into: 1) congenital myopathies; 2) muscular dystrophy; 3) mitochondrial and 4) metabolic myopathies. At the same time, treatment approaches vary significantly depending on the type of myopathy and can be based on 1) substitution of the mutant protein; 2) an increase in its expression; 3) stimulation of the internal compensatory pathways expression; 4) restoration of the compounds balance associated with the mutant protein function (for enzymes); 5) impact on the mitochondrial function (with metabolic and mitochondrial myopathies); 6) reduction of inflammation and fibrosis (with muscular dystrophies); as well as 7) an increase in muscle mass and strength. The current review presents current data on each of the listed approaches, as well as specific pharmacological agents with a description of their action mechanisms.Conclusion. Currently, the following pharmacological groups are used or undergoing clinical trials for the treatment of various myopathies types: inotropic, anti-inflammatory and antifibrotic drugs, antimyostatin therapy and the drugs that promote translation through stop codons (applicable for nonsense mutations). In addition, metabolic drugs, metabolic enzyme cofactors, mitochondrial biogenesis stimulators, and antioxidants can be used to treat myopathies. Finally, the recombinant drugs alglucosidase and avalglucosidase have been clinically approved for the replacement therapy of metabolic myopathies (Pompe’s disease).

α-synuclein is one of the key molecular links in the pathogenesis of Parkinson’s disease. The accumulated data indicate that pathogenic mutations in theSncagene are associated with the development of neurodegenerative brain damage, indicating the relevance of studying the synuclein neurobiological role.The aimof the study was to create a genetically modified clone of mouse stem cells with a conditional knockout of humanized α-synuclein, which can be used for the reinjection into mouse blastocysts, as well as for basic and appliedin vitroresearch in the field of pathophysiology and neuropharmacology.Materials and methods.To create mouse stem cells with a conditional knockout of the humanizedSncagene, a previously obtained clone with the firstSncaexon flanked by LoxP sites, was used. The CRISPR/Cas9-mediated homologous recombination system with donor DNA oligonucleotides of the human sites of the corresponding gene sites was used to humanize the fourth and fifth exons. Cas9 nuclease, single guide RNA, and donor DNA were transfected into mouse cells.Results.An approach to obtaining clones of mouse genetically modified stem cells expressing pathological humanized α-synuclein, has been proposed and implemented. The resulting clones were plated on Petri dishes for propagation and a further genetic analysis. Clone 126-2F4 was found out carrying the necessary genetic modifications. The results obtained are fundamentally important not only for understanding the development of the pathological process in α-synucleinopathies, but which is more important, for the development of new therapeutic approaches that will stop the extension of the human α-synuclein aggregation pathology throughout the nervous system, and the validation of these approaches in preclinical trials.Conclusion.As a result of the study, a strategy for CRISPR/Cas9-assisted homologous recombination in the genome of mouse embryonic stem cells has been developed to create a fully humanizedSncagene encoding α-synuclein, and the clone genome of mouse embryonic stem cells has been edited using a CRISPR technology. The RNA and DNA oligonucleotides necessary for the creation of RNP complexes that carry out a directed homologous recombination in theSncalocus of the mouse genome have been synthesized. The developed cell clone can serve to create a line of genetically modified mice that serve as a test system for pathophysiological and neuropharmacological studies associated with synucleinopathies. Herewith, before the induction of the Cre-dependent recombination, this line is a representative model for studying a biological role of mutantSnca. At the same time, after a Cre-dependent knockout activation, it is possible to imitate the pharmacological inhibition of α-synuclein, which is of particular interest for applied research in neuropharmacology.