Cytokine-induced beta-cell apoptosis and its regulation by SOCS-1 and imidazoline compounds

A selective destruction of pancreatic β-cells as a consequence of inflammation in the islets of Langerhans is a feature of type 1 diabetes. Pro-inflammatory cytokines secreted by T lymphocytes and macrophages infiltrating the pancreatic islets participate in the development of this autoimmune disease by acting directly on the β-cell. The aim of this thesis was to investigate mechanisms of β-cell dysfunction and death induced by the mixture of proinflammatory cytokines IL-1β, IFNγ and TNFα, i.e., under conditions modelling those during inflammation in type 1 diabetes. Furthermore, we aimed to study whether imidazoline compounds RX871024 and efaroxan can affect pancreatic β-cell death under these conditions and if so, to explore underlying molecular mechanisms. Some imidazoline compounds can promote insulin secretion and have been discussed as potential therapeutic drugs in type 2 diabetes. Among those compounds are insulinotropic imidazolines RX871024 and efaroxan. It was previously shown that these imidazolines do not induce apoptosis in mouse pancreatic β-cells but even protect against IL-1β-induced primary β-cell apoptosis. The protective effect of RX871024 on IL-1β-induced β-cell apoptosis has been accompanied by inhibition of IL-1β-induced NO production. However, in a first study we have shown that the imidazoline compounds cannot protect pancreatic β-cells against death induced by a combination of pro-inflammatory cytokines IL-1β, IFNγ and TNFα, despite RX871024 decreases the cytokine-induced NO production both in islets and in β-cells. RX871024-induced decrease in p38 MAPK phosphorylation may explain the partial inhibitory effect of RX871024 on cytokine-induced NO production. Thus pancreatic β-cell death triggered by a mixture of pro-inflammatory cytokines IL-1β, IFNγ and TNFα, conditions resembling those that take place in type 1 diabetes, does not directly correlate with NO production and rather relies on other players which cannot be counteracted with agents such as imidazoline compounds. Malignant insulinoma is an uncommon tumour, however, it has a poor prognosis. Chemotherapy to this tumour is not very effective. Therefore, search for effective and specific chemotherapeutical drugs for patients with malignant insulinomas is of utmost importance. Unlike primary β-cells where RX871024 was without any effect, the imidazoline compound selectively destructs insulinoma MIN6 cells and potentiates cytokine-induced insulinoma cell death. The cytotoxic effects of RX871024 does not include changes in NO production but involve increase in basal and cytokine-induced JNK activation associated with stimulation of initiator caspases-1, -8 and -9 and executor caspase-3. In contrast to primary mouse β-cells, there was no effect of cytokines or imidazolines on p38 activation in MIN6 cells. It has been shown that expression of SOCS-1, an endogenous inhibitor of IFNγ-induced signalling, in pancreatic β-cells protects NOD mice against diabetes. In a third study we investigated how signaling via JAK/STAT pathway controls cytokine-induced β-cell death. SOCS-1 overexpression diminishes activation of both caspase-8 and -9 in primary mouse β-cells leading to inhibition of cytokine-induced β-cell death. This finding in association with the observation that SOCS-1 does not affect glucose stimulated insulin release and islet cell death in the absence of cytokines indicates the possibility to use an elevation of SOCS-1 expression in the treatment of type 1 diabetes. In conclusion, results of this thesis implicate that pancreatic β-cell death induced by mixture of pro-inflammatory cytokines IL-1β, IFNγ and TNFα cannot be counteracted with agents such as imidazoline compounds, but can be suppressed by inhibition of IFNγ-induced signalling. We have also found that RX871024 exerts selective cytotoxic effect towards insulinoma cells

INFORMATIONAL TECHNOLOGIES IN MODERN KAZAKHSTAN'S EDUCATION: THE INNOVATIVE POTENTIAL

The article contemplates the issue of modern informational technologies application at Kazakhstan’s high education institutions. The attention is paid on both positive and negative sides of the usage of these means. Update studies show that informational technologies are not only instrumental tools of educating process. They are gradually changing the conceptual and methodological foundations of education and they have substantial potential in innovating and developing educational processes at higher institutions.Education, information technology, Internet, Kazakhstan., Teaching/Communication/Extension/Profession, I23,

Multistage Voting Model with Alternative Elimination

The voting process is formalized as a multistage voting model with successive alternative elimination. A finite number of agents vote for one of the alternatives each round subject to their preferences. If the number of votes given to the alternative is less than a threshold, it gets eliminated from the game. A special subclass of repeated games that always stop after a finite number of stages is considered. Threshold updating rule is proposed. A computer simulation is used to illustrate two properties of these voting games

Figurative-aesthetic Understanding of the Phenomenon of the Native Language: Poem by M. Rylsky “Mova” and its Translations into Russian

The problem of comprehending the essence of the concept of “native language”, despite the rather long interest in it of both linguists and representatives of a number of other sciences (first of all — “joint” with linguistics), remains very urgent at the present time. This is due, on the one part, to the complexity and multidimensionality of the phenomenon being interpreted; on the other part, the originality of accents placed on various aspects of this definition when interpreting it within the framework of various scientific fields (psycholinguistics, sociolinguistics, language teaching methodology, etc.). In this situation, it seems appropriate to pay attention to the figurative and aesthetic understanding of the concept of “native language” when it is included in the verbal and artistic structures, where, in addition to constructive, key for the semantic structure, components, by definition, the components that are potentially present in the semantic scope of the concept are also actualized. In this article, the material for consideration in the stated manner was a poem by the classic of Ukrainian literature M.F. Rylsky’s “Mova” (“Language”), which comprehends the phenomenon of the native language, and two of its translations into Russian. The analysis shows that the figurative-aesthetic interpretation of the category of scientific property allows a more detailed and deep description of not only its semantic, but also its conceptual properties. When translating this poem into another, in this case, a closely related language, the translator’s priority task is to preserve the conceptual and aesthetic significance inherent in the image of the language in the original work

Kvantitativne karakteristike mikrostrukture građevinskih kompozita

The article deals with the algorithm of the building material structure based on its photomicrographs by means of point images statistical analysis. The obtained values allow the defining of the basic characteristics of the material structure.U radu se razmatra algoritam strukture građevinskog materijala na temelju njegove fotomikrografije pomoću statističke analize točkastih slika. Dobivene vrijednosti omogućavaju definiranje osnovnih karakteristika strukture materijala

АМЕРИКАНСЬКИЙ МЮЗИКЛ: ПИТАННЯ СТАНОВЛЕННЯ ТА ЖАНРОУТВОРЕННЯ

Purpose of Article. The aim of the study is to give reasons for the American musical's process of formation as a special variety of show forms, the historical aspect of this form, the definition of genre signs of musical and their features. Methodology. Research methodology consists in applying analytical, functional, comparative and art studying, systematic research methods of the American musical's role in stage art, the study of these show forms origins and their importance in modern theatre. Scentific novelty. The scientific novelty of the research lies in the assertion that the general trend of theatrical forms since the late 80s of the last century gave reasons for increasing of the theatricality role in the socio-cultural reality. Conclusion. As a result of the research it can be concluded the following: firstly, the Broadway musical with its brilliance, imagination, rhythmic tact became a special commodity, recognized and admired throughout the world, although its forms were borrowed from many sources; secondly, since the late 80s of the last century an idea of a fancy, carnival nature of social life and the means of its reproduction became popular among Western theorists; thirdly, "Black crook" paved the way for musical to the American scene, launching tradition of luxury entertainment spectacles with various stage effects and dance numbers; fourthly – the most attention was paid to the creation of bright numbers in the structure of the musical comedy score, they were inserted on the advice of artists and kept a strong impression on the audience. According to this the role of the composer-songwriter was growing; fifthly, at the beginning of the XIX century the USA became a centre of musical comedies instead of the Old World. Broadway turned to the capital of the world show business, and gradually musical was turning into a leading genre; and finally – the question of the current state of the classic American genre of the musical theatre periodically rises for producers and critics. It causes debates, generates various predictions about the continued existence of traditional Broadway show, including pessimistic ones.Целью работы является обоснование процесса становления американского мюзикла как особой разновидности зрелищных форм, исторического аспекта данной формы, определения особенностей жанровых признаков мюзикла. Методология исследования заключается в применении аналитического, функционального, сравнительного, искусство- ведческого, системного методов исследования роли американского мюзикла в сценическом искусстве, истоков зрелищно-развлекательных форм и их значения в современном театральном искусстве. Научная новизна исследования за- ключается в утверждении, что общая тенденция театрализации с конца 80-х годов прошлого века дала основания для роста роли театральности в социокультурной реальности. Выводы. Во-первых, бродвейский мюзикл, с его блеском, фантазией, ритмическим тактом, стал особым товаром, который признали и которым восхищались во всем мире, хотя форма его заимствована из многих источников; во-вторых, с конца 80-х годов прошлого века среди западных теоретиков приобрела популярность идея о маскарадном, карнавальном характере общественной жизни и средств его воспроизве- дения; в-третьих, "Черный плут" проложил путь мюзиклу на американской сцене, положив начало традиции роскошных развлекательных зрелищ с применением различных сценических эффектов и использованием танцевальных номеров; четвертый, именно созданию ярких номеров уделяли главное внимание в структуре партитуры музыкальной комедии, вставляли их по совету исполнителей, поскольку они производили впечатление на зрителей. Соответственно, возраста- ла роль композитора-песенника; в-пятых, в начале XIX века центром создания музыкальных комедий вместо Старого Света становится Америка. Бродвей превращается в столицу мирового шоу-бизнеса, а мюзикл – на ведущий жанр; и последнее, вопрос о современном состоянии классического американского жанра мюзикла периодически возникает перед театральными продюсерами и критиками. Он вызывает дискуссии, порождает различные прогнозы относительно дальнейшего существования традиционного бродвейского шоу, в том числе пессимистичные.Метою роботи є обґрунтування процесу становлення американського мюзиклу як особливого різновиду видовищних форм, історичного аспекту даної форми, визначення особливостей жанрових ознак мюзиклу. Методологія полягає у застосуванні аналітичного, функціонального, порівняльного, мистецтвознавчого, системного методів дослідження ролі американського мюзиклу, витоків видовищно-розважальних форм та їх значення у сучасному театральному мистецтві. Наукова новизна дослідження полягає у ствердженні, що загальна тенденція театралізації з кінця 80-х років минулого століття дала підстави для зростання ролі театральності у соціокультурній реальності. Висновки: По-перше, бродвейський мюзикл, з його блиском, фантазією, ритмічним тактом, став особливим товаром, який визнали і яким захоплювалися у всьому світі, хоча його форма запозичена з багатьох джерел; по-друге, з кінця 80-х років минулого століття серед західних теоретиків набули популярності ідея про маскарадний, карнавальний характер суспільного життя і засоби його відтворення; по-третє, "Чорний шахрай" проклав шлях мюзиклу на американській сцені, започаткувавши традицію розкішних розважальних видовищ із за- стосуванням різних сценічних ефектів та використанням танцювальних номерів; вчетверте, саме створенню яскравих номе- рів приділяли головну увагу в структурі партитури музичної комедії, вставляли їх за порадою виконавців, оскільки вони спра- вляли найбільше враження на глядачів. Відповідно, зростала роль композитора-пісняра; по-п`яте, на початку XIX ст. центром створення музичних комедій замість Старого Світу стає Америка. Бродвей перетворюються на столицю світового шоу- бизнесу, а мюзикл – на провідний жанр; і останнє, питання про сучасний стан класичного американського жанру мюзиклу періодично постає перед театральними продюсерами і критиками. Воно викликає дискусії, породжує різні прогнози щодо подальшого існування традиційного бродвейського шоу, зокрема песимістичні

Un estudio de aprendizaje sobre el voluntariado en el sistema de recuperación de emergencia en Rusia: sobre la interacción entre el estado y las organizaciones civiles

The purpose of the article is to identify the motives, types, and areas of volunteering in the system of emergency response in the Lipetsk region, Russia. To obtain quantitative characteristics of the problem studied, we have used the method of mass polling at the place of residence, work, and study of respondents. The main motive for participants in volunteer activities is the altruistic reason. 8.1% of volunteers have defined their sphere of activity as volunteerism in emergencies. 31.9% are potentially ready to help people in emergency situations. This variance in figures we could explain by the fact that many volunteers do not have enough necessary skills. Besides, the participation in emergency situations liquidation, traffic accidents, fire extinguishing, etc., is associated with possible risk.El propósito del artículo es identificar los motivos, tipos y áreas de voluntariado en el sistema de respuesta de emergencia en la región de Lipetsk, Rusia. Para obtener las características cuantitativas del problema estudiado, se ha utilizado el método de sondeo masivo en el lugar de residencia, trabajo y estudio de los encuestados. El motivo principal de los participantes en las actividades de voluntariado es la razón altruista. El 8,1% de los voluntarios ha definido su ámbito de actividad como voluntariado en situaciones de emergencia. El 31,9% está potencialmente preparado para ayudar a las personas en situaciones de emergencia. Esta variación en las cifras podría explicarse por el hecho de que muchos voluntarios no tienen las habilidades necesarias suficientes. Además, la participación en situaciones de emergencia, liquidación, accidentes de tráfico, extinción de incendios, etc., está asociada a un posible riesgo

Глобальные риски, как факторы, влияющие на современную систему международных отношений

The problem of the globalization of risks is examined in this article. Based on the World Economic Forum (WEF) report on global risks 2015-2017, the impact of global risks on the social and economic development of countries is examined. Economic, social, environmental, geopolitical, technological risks are analyzed in a coordinated fashion. The article notes that the main risks are in the field of environment and ecology. Anthropogenic pressure amplification, scientific and technological advance have an influence on the natural environment. The risks of infrastructure and environmental damage in danger zone are increased because of the growth of the frequency of extreme weather events. The measures for the protection of the environment are examined. The unilateral approach to solving international issues, instead of the collective efforts of the international community; the deployment of weapons of mass destruction (nuclear, chemical, biological) and technologies for the production of radioactive materials; escalation of economic and resource nationalization (the desire of States to expropriate or restrict the export of important for the world economy of resources), etc. promote the increasing geopolitical risks.Economic risks include the risk in terms of their likelihood their impact on the macroeconomic, as from the financial systems and infrastructure to price volatility and regulatory issues. Social risks are the risks relating to instability of population dynamics, social crises and human survival.Technological risks include such problems as software defects, failure of important information systems, upon which today industrial production is depended, the services and communications sector; the escalation of large-scale cyber-attacks; theft of electronic information and the illegal usage of personal data. The trends that can intensify the global risks or to change the correlation between them are analyzed in this article.В статье рассматривается проблема глобализации рисков. Используя данные экспертов Всемирного экономического форума (ВЭФ) за 2015-2017 гг. автором рассмотрено влияние глобальных рисков на социально-экономическое развитие стран. Экономические, социальные, экологические, геополитические, технологические риски анализируются во взаимосвязи. Отмечается, что главные риски находятся в области окружающей среды и экологии. Усиление антропогенного давления, научно-технический прогресс влияют на природную среду. Рост частоты экстремальных погодных явлений увеличивает риски инфраструктурного и экологического ущерба в районах повышенной опасности. Анализируются меры по охране окружающей среды. Возрастанию геополитических рисков способствуют такие факторы, как односторонний подход к решению международных вопросов, вместо коллективных усилий мирового сообщества; развертывание оружия массового поражения (ядерного, химического, биологического) и технологий по производству радиоактивных материалов; эскалация экономической и ресурсной национализации (стремление государств экспроприировать или ограничить экспорт важных для мировой экономики ресурсов) и др. К экономическим рискам относятся риски, вызывающие обеспокоенность с точки зрения вероятности их возникновения и воздействия на макроэкономику, начиная с финансовых систем и инфраструктуры и заканчивая нестабильностью цен и регулятивными вопросами. Социальные риски - это риски, связанные с нестабильностью динамики населения, социальными кризисами и выживанием человека. К технологическим рискам относятся такие проблемы как дефекты программного обеспечения, выход из строя ключевых информационных систем, от которых сегодня зависят промышленное производство, сфера услуг и коммуникации; эскалация крупномасштабных кибер-атак; кражи электронных данных и противоправное использование персональных данных. Также в статье анализируются тенденции, способные усилить глобальные риски или изменить соотношение между ними

Socio-psychological factors affecting professional burnout among social workers (based on the experiences of students and professionals)

The aim of the article is to establish the level of professional burnout and assess it in the context of social-professional characteristics of social workers in Russia. The quantitative characteristics of the studied problem are examined using the survey method in the form of formalized questionnaires and testing. The authors proceed from the notion that the profession of a social worker, which presupposes direct contact with people in difficult life situations, is clearly one of the jobs that are the most conducive to the development of professional burnout syndrome and is viewed by society as such. Low pay grade combined with severe emotional load serve as factors contributing to the professional disorganization of a worker. It is found that in the specific conditions of Russia, the general characteristics of social workers assume not only a desire to continue professional activity within the chosen specialty but also a relatively low percentage of people, in whom a high degree of professional burnout can be found