Development Of Different Forms Research Articles

Proteomic Analysis of Myocardia Containing the Obscurin R4344Q Mutation Linked to Hypertrophic Cardiomyopathy.

Obscurin is a giant cytoskeletal protein with structural and regulatory roles encoded by the OBSCN gene. Recently, mutations in OBSCN were associated with the development of different forms of cardiomyopathies, including hypertrophic cardiomyopathy (HCM). We previously reported that homozygous mice carrying the HCM-linked R4344Q obscurin mutation develop arrhythmia by 1-year of age under sedentary conditions characterized by increased heart rate, frequent incidents of premature ventricular contractions, and episodes of spontaneous ventricular tachycardia. In an effort to delineate the molecular mechanisms that contribute to the observed arrhythmic phenotype, we subjected protein lysates prepared from left ventricles of 1-year old R4344Q and wild-type mice to comparative proteomics analysis using tandem mass spectrometry; raw data are available via ProteomeXchange with identifier PXD017314. We found that the expression levels of proteins involved in cardiac function and disease, cytoskeletal organization, electropotential regulation, molecular transport and metabolism were significantly altered. Moreover, phospho-proteomic evaluation revealed changes in the phosphorylation profile of Ca2+ cycling proteins, including sAnk1.5, a major binding partner of obscurin localized in the sarcoplasmic reticulum; notably, this is the first report indicating that sAnk1 undergoes phosphorylation. Taken together, our findings implicate obscurin in diverse cellular processes within the myocardium, which is consistent with its multiple binding partners, localization in different subcellular compartments, and disease association.

GSK3: A Kinase Balancing Promotion and Resolution of Inflammation.

GSK3 has been implicated for years in the regulation of inflammation and addressed in a plethora of scientific reports using a variety of experimental (disease) models and approaches. However, the specific role of GSK3 in the inflammatory process is still not fully understood and controversially discussed. Following a detailed overview of structure, function, and various regulatory levels, this review focusses on the immunoregulatory functions of GSK3, including the current knowledge obtained from animal models. Its impact on pro-inflammatory cytokine/chemokine profiles, bacterial/viral infections, and the modulation of associated pro-inflammatory transcriptional and signaling pathways is discussed. Moreover, GSK3 contributes to the resolution of inflammation on multiple levels, e.g., via the regulation of pro-resolving mediators, the clearance of apoptotic immune cells, and tissue repair processes. The influence of GSK3 on the development of different forms of stimulation tolerance is also addressed. Collectively, the role of GSK3 as a kinase balancing the initiation/perpetuation and the amelioration/resolution of inflammation is highlighted.

The impact of Russian-speaking community of the state of Israel upon Israel-Russia relations

This article is dedicated to examination of a large and rapidly developing community of the State of Israel – the “Russian Street”, and its influence upon Israel-Russia relations. The author considers such aspects of the topic as: the differences between “Great Aliyah” of the 1990s and the first wave of repatriation of the 1970s; factors that formed the unique “Russian-Jewish” identity among the “Russian street” representatives; political and economic potential of the “Russian Israel”, key areas of cooperation of two countries, and the role of the “Russian” community thereof. In the course of this research, the author applies the means and procedures of formal logic, specific-sociological approach, and interpretation tools of various sources. The main conclusion lies in the following thesis: if in political regard the community does not produce a decisive influence upon the actions of Israeli authorities, then in economic aspect, it unequivocally contributes to strengthening of economic ties between Israel and Russia. Russia’s initiatives on the development of different forms of economic, cultural and media cooperation can stimulate the expansion of influence of the Russian-speaking community.

ФОРМУВАННЯ МОТИВАЦIЇ НАВЧАЛЬНОЇ ДIЯЛЬНОСТІ В ПРОЦЕСI ВИВЧЕННЯ АНГЛIЙСЬКОЇ МОВИ ПРИ НАВЧАННІ АСПIРАНТIВ

The article is devoted to the study of the stages of formation of motivation of educational activity in the process of learning a foreign language in the training of post graduate students. Rapid development of different forms of teaching foreign languages, changes in social and cultural life involves changing demands of our society for the whole education and particularly learning foreign languages. Since some students do not have physical need of using foreign languages as a means of communication, one of the most important factors which stimulate the process of communication in a foreign language is motivation in leaning foreign languages. In our paper motivation is referred to as a system of motives which leads the learning process to thorough knowledge of foreign languages with the positive aim of teachers. We have formulate the specific methodical principle underlying in the organization of teaching foreign languages to post graduates students. It was considered different ways of forming a positive sustainable motivation of graduate students’ educational activity. The formation of such motivation should not use one way, but all the ways in a certain system, in complex, because one of them, without others, cannot play a decisive role in the formation of post graduate students motivation.

Gastronomski proizvodi u funkciji razvoja različitih oblika turizma u Sremskom okrugu

Food and drinks represent a very important segment in tourist offers that mutually participate in development of a certain touristic region or a specifically defined form of tourism. In certain countries, there are good examples of how gastronomic offer influenced the positive development of different forms of tourism. Gastronomic tourism represents a subset of cultural tourism where history, tourism and food habits of a certain environment are revealed. Other than this form of tourism, there are other ones that are directly or indirectly tied to gastronomic tourism. Other than cultural, wine, religious and other forms of tourism cam be directly tied to gastronomic. The goal of this paper is to show the gastronomic potentials of the Srem district in Republic of Serbia and how they can influence the development of different, certain forms of tourism. The aim of this paper is to show the significance of certain gastronomic products that are prepared and their direct influence on certain forms of tourism of Srem district.

КЛАСИФІКАЦІЙНА ТА ВИДОВА СТРУКТУРА ОСНОВНИХ ФОРМ УЧАСТІ МОЛОДІ В ПУБЛІЧНОМУ УПРАВЛІННІ

Youth participation in democratic countries is an integral part of socio-political life. Active participation of young people involves influence on decisions and actions, participation in actions and events, in order to promote building a better society. The idea of youth participation is based on the assertion that the greatest number of ideas for solving youth issues and problems arises outside the government or at lower levels. After all, it is the young people who know the sources of the problems best and see how national and local programs are working to solve these problems in practice.Among the main forms of youth participation are traditionally distinguished: voting and nomination in elections, participation in referendums, participation in protest actions. However, one should not focus only on voting or nominating for elections, as traditional forms of youth participation, the most decisive for modern democracy is the form of youth participation in the inter-electoral cycle in everyday social and political life.There are many other forms and types of youth participation at different levels of government, at different stages of public policy making, which one should pay attention to. Given the context of the decline of youth participation in traditional political processes, which has been observed in recent years, it is necessary to promote, support and encourage the development of different forms and types of youth participation as a basis for developing public administration.The article deals with the study of the classification of types and forms of youth participation, provides a comprehensive system of their systematization and extended classification. In particular,it was proposed to add characteristics of the specific structure of youth participation and the generalization and supplementation of classification structure of youth participation form.The conducted study of the classification of types and forms of youth participation allowed to systematize and develop on this basis an extended classification.Additional features of the specific structure of youth participation are offered: 1) based on scale – local, national and international (global); 2) based on purpose the activity – mobilization, philanthropy, mediation, social solidarity, change, creation; 3) based on sphere of activity – participation in culture, recreation, sports; in education and research; in health care and social services; in environment protection; in international relations; religious participation; business andprofessional participation; legal, propaganda and politics; participation in addressing basic needs (promoting youth employment, housing and transport services, etc.).The classification structure of the forms of youth participation is generalized and supplemented: 1) traditional political participation (voting and nomination of candidates for election, youth deputies, youth leaders, participation in political campaigns, policy discussions, etc.); 2) non-traditional political participation (legal public actions, signature of petitions, sending of proposals, appeals, requirements to the authorities, support of personal contacts with state administrators, etc.); 3) formal public participation (activities of youth public organizations, associations, trade unions, associations of interests, youth councils and similar structures, pupil and student self-government, etc.); 4) informal public participation (digital participation, social media, sociological surveys and public opinion monitoring, seminars, round tables, consultations, youth exchanges, youth initiatives, volunteering, etc.).

Le travail dans l’économie digitale : le dilemme entre réalité et norme, et les aspects sociaux du travail sur plateforme

L’essor de l’économie collaborative a encouragé le développement de différentes formes d’organisation du travail tout à fait nouvelles, qui sortent des régimes connus. Dans la réflexion sur les prérogatives sociales des travailleurs des plateformes, il faut préalablement définir les protagonistes de la relation d’emploi (et le rôle d’intermédiation des plateformes), parce qu’il faut assurer aux travailleurs qui « habitent » les plateformes des protections minimales sans « soumettre » les rapports à des modèles qui seraient incompatibles avec les nouvelles organisations du travail. En même temps, il faut chercher des solutions pour satisfaire les exigences sociales des travailleurs des plateformes.

Immunological aspects of tuberculosis pathogenesis

The morphological aspects of TB pathogenesis are well described in the publications. Much is also known about the main stages of development and formation of specific adaptive immunity. However, from our point of view, not enough attention is being paid to the involvement of the immune system in the pathogenesis of clinically relevant TB abnormalities, as well as various forms of the disease. Nevertheless, there is no doubt that the variety of clinical manifestations of any disease associated with the penetration of a foreign agent into the body, and Mycobacterium tuberculosis (MTB) in particular, is due to the collective interaction of the infectious agent and the individual response of the macroorganism to this infectious agent. The mosaic of such interactions usually imposes its own adjustments on the development of different forms of the process, its speed and direction, as well as the outcomes. Certainly, the response of a macroorganism to MTB is an integral part of pathogenesis and consists of many general components including the responses associated with the mechanisms of natural and acquired immunity. Intensity of these reactions depends on the characteristics of an agent (MTB) and a macroorganism. For the development of TB disease, massiveness of TB infection, dose and duration of MTB exposure to the human body, as well as virulence of MTB and the level of body's protection during the exposure play a very important role. TB pathogenesis is somewhat different in primary MTB infection and re - infection. With primary infection, 88-90% of individuals do not have clinical manifestations, and only the tuberculin skin test conversion signals the onset of infection. In some cases, without any use of anti-TB drugs limited abnormalities may result in spontaneous cure with the minimal residual changes in the lungs, intrathoracic lymph nodes and tissues of other organs, often in the form of calcifications and limited areas of fibrosis in more advanced cases. Only 10-12% of newly infected individuals develop TB with severe clinical manifestations requiring TB therapy. The absence of clinical manifestations of primary TB infection can be explained by a high level of natural resistance of the human body to tuberculosis, and sometimes can be an effect of acquired protection due to BCG vaccination. This review attempts to discuss the role of immune mechanisms in the pathogenesis both at the beginning of disease development, and in the process of its various manifestations. Issues of genetically determined resistance or susceptibility to TB are not being covered in detail in this manuscript.

131 I-Labeled Multifunctional Polyphosphazene Nanospheres for SPECT Imaging-Guided Radiotherapy of Tumors.

Design of theranostic nanoplatforms represents a major topic for current nanomedicine. Here, the preparation of multifunctional poly(cyclotriphosphazene-co-polyethylenimine) nanospheres (PNSs) labeled with radionuclide 131 I for single photon emission computed tomography (SPECT) imaging-guided radiotherapy of tumors is reported. In this work, PNSs are prepared using hexachlorocyclotriphosphazene as a crosslinker to crosslink branched polyethylenimine (PEI) via a nucleophilic substitution reaction, modified with 3-(4'-hydroxyphenyl) propionic acid-OSu (HPAO) for 131 I labeling, and reacted with 1,3-propane sulfonate (1,3-PS) to render the particles with antifouling property, followed by acetylation of the remaining surface amines and labeling with 131 I. The acquired PNS.NHAc-HPAO(131 I)-PS particles are well characterized. It is shown that the multifunctional PNSs with an average size of 184 ± 29.3 nm exhibit favorable antifouling properties, high 131 I labeling efficiency (76.05 ± 3.75%), and excellent radiostability and colloidal stability. With these properties owned, the developed PNS.NHAc-HPAO(131 I)-PS spheres enable much more efficient SPECT imaging and radiotherapy of a xenografted tumor model in vivo than the PEI counterpart material (PEI.NHAc-HPAO(131 I)-PS). The developed PNSs may be used as a versatile platform for further development of different forms of nanomedicine for various biomedical applications.

Directions of diversification of rural development in the conditions of decentralization

Purpose. The aim of the article is determining the areas of diversification of rural development in decentralization in order to improve the quality of life of rural population and ensure the competitiveness of rural areas and achieve environmental security. Methodology of research. Common methods of study are applied in economic science in the course of the study, in particular: monographic, system and structural - in determining the directions of diversification of rural development in the conditions of decentralization. Findings. The following areas of diversification of rural development under decentralization conditions have been identified in order to ensure the social and ecological and economic development of rural territories: diversification of agricultural production; diversification of non-agricultural activities; diversification of funding sources; diversification of forms of ownership and management. It is suggested to diversify the development of rural territories in the field of agricultural production by expanding the range of products, increasing the volume of organic and niche production. It is determined that the choice of non-agricultural activities for each rural area is different and depends on natural resources and its location. The directions of diversification of non-agricultural activity in rural areas are proposed, such as: industry, rural green tourism, services and folk arts, production of specific regional products, legal entities and individuals, grants. We believe that the diversification of ownership and management in rural areas involves stimulating the development of different forms of ownership, promotion of various forms, creation of cooperatives and clusters. Originality. The scientific and practical recommendations on the formation of directions of diversification of rural development under decentralization conditions, which are determined depending on the object of diversification (agricultural production, non-agricultural activity, sources of financing, forms of ownership and management), have been improved. Practical value. The obtained results of the study are the basis for solving practical problems of rural development in the context of decentralization in Ukraine. Key words: diversification of rural development; agricultural production; non-agricultural activities; sources of financing; ownership and economic management; organic production; cluster.

FARMERS’ SOCIAL INSURANCE SYSTEM IN POLAND AS SEEN BY THE FARMERS

The main purpose of this paper is to examine the farmers’ opinion on the functioning of their dedicated social insurance system. Particular attention was also paid to the development of different forms of social insurance and to the functioning of the Farmers’ Social Insurance Fund (Polish acronym: KRUS). The analysis was based on a literature review and a survey conducted with 114 farmers registered in KRUS offices located in Działdowo, Iława and Ostróda, with assistance from the Olsztyn Regional Branch. The data collected enables an objective assessment of the entire social insurance system and reflects the farmers’ views on the system and its reforms. The research shows that the accident insurance, health insurance and maternity insurance schemes work very well (41%) or well (34%) according to the farmers concerned. The respondents also expressed their satisfaction with activities undertaken by KRUS, especially in the social field (61%).

Riječki primer razvoja propisa o trgovini i formi trgovačkog organiziranja do kraja 18. veka

The author researches the legal history aspect of the evolution of business activities and the influence of the state on the development of different forms of business activities. Besides referring to some examples from the Antiquity, the author analyzes medieval forms of business, particularly in maritime affairs at the Adriatic area. They were developed without special influence of public authorities, through business practices and trade usages. At the Croatian hinterland, the influence of the sovereign as the bearer of public authority upon the development of economy is reflected in the Golden Bull of 1242, an edict issued to Gradec (part of today's Zagreb). The Statute of Rijeka from the year 1530 contains additional commercial norms that bear witness about a tendency of local authorities to ensure safety of business transactions and quick judicial resolution of disputes between merchants and shippers. In 1717, Emperor Charles VI proclaimed the freedom of navigation at the Adriatic Sea. Thus, Rijeka and Trieste became porto franco, which was a new incentive for commercial growth, particularly in maritime affairs. During the 18th century, the sovereigns embarked on a series of administrative and economic reforms which were accompanied by establishing merchandise companies, rudimental joint stock companies involved in different activities, and a growing number of individual merchants.

ANALYSIS OF CANDIDATE POLYMORPHISMS AT EPILEPSY PATIENTS WITHOUT MECHANICAL DISTURBANCES

Thе article presents the results of a molecular-genetics research on patients with diagnosed epilepsy without mechanical disturbance. The aim of this research was the analysis of candidate gene polymorphisms in development of different forms of epilepsy excepting mechanical reasons. 78 patients of V.M. Savinov SVS clinic with different forms of epilepsy were selected for the molecular-genetic analysis. Genotyping on candidate polimorphisms of gene coding the methyl-СрG-binding protein 2 (МЕСР2, 3 polymorphisms), the genes of sodium (SCN1A, 4 polymorphisms) and potassium (KCNT1, 2 polymorphisms) channels was performed by a site-specific PCR-RFLP method. Molecular genetic analysis revealed the presence of normal functioning alleles for 3 investigated candidate polymorphisms (p.Thr158Met, p.Thr197Met, p.Arg306Ter) of 3d exon of МЕСР2 gene at all epilepsy patients. However, 1 case (patient suffering from Dravet syndrome) of de novo mutation was defined for sodium channel gene (SCN1A p.Ala1783Thr) and 3 cases (2 patients suffering from temporal epilepsy and 1 patient with residual encephalopathy) of new mutations in gene responsible for potassium channel (KCNT1 p.Ala934Thr). To determine the inherited SCN1A and KCNT1 mutations, the molecular-genetics analysis was conducted for close relatives of patients. As a result, we conclude that, candidate polymorphisms of SCN1A p.Ala1783Thr and KCNT1 p.Ala934Thr, disrupting the ion channels normal functioning, can be involved in development of non-mechanical forms of epilepsy.

Pulmonary arterial hypertension in systemic sclerosis: Diagnosis and treatment according to the European Society of Cardiology and European Respiratory Society 2015 guidelines.

Scleroderma (systemic sclerosis) is an autoimmune connective tissue disease which presents endothelial dysfunction and fibroblast dysregulation, resulting in vascular and fibrotic disorders. Pulmonary hypertension is frequent in patients with systemic sclerosis: the natural evolution of the disease can induce the development of different forms of pulmonary hypertension, representing one of the main causes of death. Among the different forms of pulmonary hypertension in systemic sclerosis, pulmonary arterial hypertension is the most frequent one (rate of occurrence is estimated between 7% and 12%). This pulmonary vascular complication should be treated with a combination of drugs that is able to counteract endothelial dysfunction, antagonizing the endothelin-1 system and replacing prostaglandin I2 and nitric oxide activity. A correct diagnosis is mandatory, because it is possible only for pulmonary arterial hypertension to use specific drugs that are able to control the symptomatic condition and the evolution of the disease. According to the most recent guidelines, for the patients with systemic sclerosis, also without pulmonary hypertension symptoms, echocardiography screening for the detection of pulmonary hypertension is recommended. Pulmonary arterial hypertension screening programs in systemic sclerosis patients is able to identify milder forms of the disease, allowing earlier management and better long-term outcome.

Surveying digital religion in China: Characteristics of religion on the Internet in Mainland China

ABSTRACTChina’s distinct development of the Internet has provided religious populations within its mainland access, allowing them to create practices and resources related to the development of religion online. Yet this phenomenon has been understudied both within the current Chinese research on the Internet and international studies of digital religion online. This article provides an overview of digital religion in the Chinese context by identifying and exploring the main characteristics of Buddhism, Islam, and Protestantism manifest online. This is done by providing an overview of current research and profiling the development of different forms of digital religious expression found in China. Through this we show how the concept of digital religion is manifest in China and how this compares to Western understandings of such practices, and we highlight the unique characteristics defining the Chinese religious digital landscape.

Russian-Egyptian economic relations: history and mоdernity

The author for the first time generalized information on the Russian-Egyptian economic relations since the beginning of the 60th years of the 19th century so far and allocated a number of stages of their development. However, he pays the main attention to the analysis of the current state of bilateral cooperation and long-term projects, which will define the level of development of trade and economic relations in the near future. The largest of them is the project of the NPP “Dabaa”. Four commercial contracts on this project make nearly $60 bln. According to the signed contracts, Rosatom will build till 2029 four VVER-1200 units generation 3+ of the NPP “Dabaa” in the Matrouh region on the Mediterranean coast, as well as supplying nuclear fuel throughout the plant’s entire operational lifetime. In addition, Rosatom will be conduct personnel training and will assist its Egyptian partners in the operation and maintenance of the NPP for the first ten years of its operation. Besides, the Russian side will construct a purpose-built storage and supply containers for storing spent fuel. Life cycle of this project can make 100 years. Presidents of Russia and Egypt Vladimir Putin and Abdel Fattah el-Sisi accepted the decision in principle on implementation of other large project – the Russian industrial zone (RIZ) in Egypt – at a meeting in 2014. During this time, the parties chose the location of a zone, developed the business plan and the master plan of the RIZ taking into account stage-by-stage development of the territory and coordinated conditions of the special intergovernmental agreement on creation of the RIZ. Implementation of this project has to begin in the nearest future. The research showed the high level of complementarity of economies of two countries, which creates strong base of further development of different forms of mutually beneficial economic relations.

Genetics Factors in Major Depression Disease.

Depressive disorders (DDs) are one of the most widespread forms of psychiatric pathology. According to the World Health Organization, about 350 million people in the world are affected by this condition. Family and twin studies have demonstrated that the contribution of genetic factors to the risk of the onset of DDs is quite large. Various methodological approaches (analysis of candidate genes, genome-wide association analysis, genome-wide sequencing) have been used, and a large number of the associations between genes and different clinical DD variants and DD subphenotypes have been published. However, in most cases, these associations have not been confirmed in replication studies, and only a small number of genes have been proven to be associated with DD development risk. To ascertain the role of genetic factors in DD pathogenesis, further investigations of the relevant conditions are required. Special consideration should be given to the polygenic characteristics noted in whole-genome studies of the heritability of the disorder without a pronounced effect of the major gene. These observations accentuate the relevance of the analysis of gene-interaction roles in DD development and progression. It is important that association studies of the inherited variants of the genome should be supported by analysis of dynamic changes during DD progression. Epigenetic changes that cause modifications of a gene's functional state without changing its coding sequence are of primary interest. However, the opportunities for studying changes in the epigenome, transcriptome, and proteome during DD are limited by the nature of the disease and the need for brain tissue analysis, which is possible only postmortem. Therefore, any association studies between DD pathogenesis and epigenetic factors must be supplemented through the use of different animal models of depression. A threefold approach comprising the combination of gene association studies, assessment of the epigenetic state in DD patients, and analysis of different “omic” changes in animal depression models will make it possible to evaluate the contribution of genetic, epigenetic, and environmental factors to the development of different forms of depression and to help develop ways to decrease the risk of depression and improve the treatment of DD.

Diseases in men caused by the human papillomavirus: Let's hear it for the boys

Human papillomavirus (HPV) infection can lead to the development of different forms of cancer. In this article Ian Peate looks at HPV-related disease in men and explains why it is important that the HPV immunisation campaign should be extended to include all young people.

Conferences as a Tool for Interdisciplinary (Postgraduate) Learning in Bioethics

In recent years, alongside the general advancement of bioethics in a range of professions, bioethics conferences, both at a national and international level, have developed and become increasingly popular. One challenge for those learning bioethics is often to engage with disciplines outside their own, for instance by exploring new methodological approaches or theoretical frameworks. The interdisciplinary nature of bioethics motivates the development of different forms of interdisciplinary learning. In this paper, the authors discuss the role of bioethics conferences that, it is argued, serve as an important tool for interdisciplinary learning and interaction in bioethics. Special reference is given to the Postgraduate Bioethics Conference, which the authors convened in 2014 and have since overseen, to demonstrate how such a conference can assist learning in bioethics.

Thermal experience during embryogenesis contributes to the induction of dwarfism in whitefish Coregonus lavaretus

Ecotype pairs provide well-suited model systems for study of intraspecific phenotypical diversification of animals. However, little is still known about the processes that account for the development of different forms and sizes within a species, particularly in teleosts. Here, embryos of a normal-growing ‘large’ form and a dwarf form of whitefish Coregonus lavaretus were incubated at two temperatures that are usually experienced at their own spawning sites (2°C for the normal and 6°C for the dwarf form). All fish were subjected to similar thermal treatment after hatching. The present data demonstrate for the first time that different thermal experience in embryonic life has lasting effects on body and muscle growth of this ecotype pair and contributes to the development of the dwarf form. Thus, juvenile fish of the regular form are much smaller and have less muscle mass when pre-hatching thermal conditions were similar to those typical for the spawning sites of the dwarf form (6°C) than when subjected to conditions of their own spawning sites (2°C). Surprisingly, fish of the dwarf form exhibit a similar pattern of response to thermal history (2°-fish much larger than 6°-fish), indicating that in their case, normal spawning site temperature (6°C) is indeed likely to act as a growth limiting factor. Results also demonstrate that the hypertrophic and hyperplastic muscle growth modes are similarly affected by thermal history. Immunolabelling experiments for Pax7, H3P and Mef2 provide evidence that the cellular mechanisms behind the increased growth rates after cold incubation in both ecotypes are increased proliferation and reduced differentiation rates of muscle precursor cells. This is of major significance to aspects of ecological and developmental biology and from the evolutionary perspective.