825 research outputs found

    Positively Correlated miRNA-miRNA Regulatory Networks in Mouse Frontal Cortex During Early Stages of Alcohol Dependence

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    Although the study of gene regulation via the action of specific microRNAs (miRNAs) has experienced a boom in recent years, the analysis of genome-wide interaction networks among miRNAs and respective targeted mRNAs has lagged behind. MicroRNAs simultaneously target many transcripts and fine-tune the expression of genes through cooperative/combinatorial targeting. Therefore, they have a large regulatory potential that could widely impact development and progression of diseases, as well as contribute unpredicted collateral effects due to their natural, pathophysiological, or treatment-induced modulation. We support the viewpoint that whole mirnome-transcriptome interaction analysis is required to better understand the mechanisms and potential consequences of miRNA regulation and/or deregulation in relevant biological models. In this study, we tested the hypotheses that ethanol consumption induces changes in miRNA-mRNA interaction networks in the mouse frontal cortex and that some of the changes observed in the mouse are equivalent to changes in similar brain regions from human alcoholics. Results: miRNA-mRNA interaction networks responding to ethanol insult were identified by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Important pathways (coexpressed modular networks detected by WGCNA) and hub genes central to the neuronal response to ethanol are highlighted, as well as key miRNAs that regulate these processes and therefore represent potential therapeutic targets for treating alcohol addiction. Importantly, we discovered a conserved signature of changing miRNAs between ethanol-treated mice and human alcoholics, which provides a valuable tool for future biomarker/diagnostic studies in humans. We report positively correlated miRNA-mRNA expression networks that suggest an adaptive, targeted miRNA response due to binge ethanol drinking. Conclusions: This study provides new evidence for the role of miRNA regulation in brain homeostasis and sheds new light on current understanding of the development of alcohol dependence. To our knowledge this is the first report that activated expression of miRNAs correlates with activated expression of mRNAs rather than with mRNA downregulation in an in vivo model. We speculate that early activation of miRNAs designed to limit the effects of alcohol-induced genes may be an essential adaptive response during disease progression.NIAAA 5R01AA012404, 5P20AA017838, 5U01AA013520, P01AA020683, 5T32AA007471-24/25Waggoner Center for Alcohol and Addiction Researc

    Spatial transformation as an institutional factor of the public management of macroeconomic systems

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    Purpose: The article analyzes the issue of substantiating the impact of the spatial organization of the territory of the Russian Federation on the public management at the level of macroeconomic systems. Design/Methodology/Approach: The federal districts were chosen as the object of the study as macro-regional socio-economic systems, the Southern Federal District and its constituent regions (subjects of the Russian Federation). The article investigates the main transformational processes taking place in the RF spatial development, concerning the development of the regional systems of the public management and the necessity of their consistency at the supra-regional (macro-regional) level. Findings: The authors propose a set of measures to form supra-regional system to coordinate the regional development priorities considering the peculiarities of the spatial transformation of Russia's territory and the position of the Southern macro-region in the spatial system of the country. This system formation allows involving as many interested parties as possible. Practical Implications: The results may be implemented into macro-region public administration to maximize the advantages of the geo-economic and strategic position, natural and climatic conditions of Russian regions' development. Originality/Value: The main contribution of this study is a tailored approach to the public administration of the social and economic development of the macro-regions in the context of the spatial transformation.peer-reviewe

    Theoretical and methodological grounds for the modernization of the tax administration system

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    The article stands for the theoretical underpinning of economic grounds of tax system and its building on the basis of social- and business-oriented socioeconomic features. Authors proved the need for tax process management that represent the features of government-society-taxpayer relations with taxpayer’s leading role as macroeconomic tool for economic regulation process as well as providing the sustainable and balanced economic growth and innovative modernization of Russian economy.peer-reviewe

    The use of OLAP-technology analysis of the international logistics system

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    В данной статье рассмотрено применение OLAP-технологии международной логистической системе на основе данных компании. Рассчитаны статистические данные услуг грузоперевозчика и определены зависимости показателей деятельности компании.This article discusses the use of OLAP-technology international logistics system based on company data. Calculated statistical data service cargo carrier and determined according to the activities of the company

    Instruments of investment attraction in order to fulfill the structural priorities of sustainable regional development (study based on the Rostov Region)

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    The aim of the study is devoted to defining most effective tools of investment funds attraction. These funds can be used in implementation of strategic priorities for socio-economic regional development requiring, in areas that are in need of economic restructuring. The authors have selected the Rostov region as the research target, the economy of which is in need of structural change in the direction of increasing innovational, high-tech and scientific production, in order to reduce import dependency and move closer towards the post-industrial model of economic development. The study considers currently available instruments of attraction of private sector closer to solving the stated problems of Rostov region, analyzing their regulatory, financial and organizational consulting security on both state and federal level. Main directions of economic restructuring of Rostov region are also defined. Authors also outline the main problems that private enterprises come across while doing business in the investigated area. On the basis of the research, investigating federal and regional instruments of private sector involvement authors form a number of proposals and recommendations focusing on regional improvement. As a result of the conducted study, the authors reached the conclusion, that there is a number of strategic measures that should be performed in the Rostov region. These don't only include the improvement of financial instruments, but also best available technologies, national technology initiative, and clustering.peer-reviewe

    Налогообложение доходов физических лиц в контексте проблем социальной справедливости

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    The subject. The leading position of the personal income tax in most countries is due to a number of circumstances. First, it is a personal tax, the object of which is the income actually received by the payer, and not the estimated average income that could be received in specific economic conditions. Second, income tax allows to maximize the implementation of the basic principles of taxation - universality and uniformity. In recent decades, national regimes of personal income taxation regimes have been actively developed both in foreign countries and in Russia.Purpose of the study. The article shows the results of analysis of the framework of personal income taxation in the Russian Federation in the context of the principle of the social fairness. Dealing with selected provisions of the national legislation of European countries and Russia the article shows that elements of progressive taxation can be applied only in particular aspects. The proposals of taxation of rich taxpayers are also brought into light. Methodology. The research was carried out with the application of the formally legal interpretation of legal acts as well as the comparative analysis of Russian and European legal literature. Structural and systemic methods are also the basis of the research,The main results. After studying the European experience of personal income taxation the authors come to the conclusion that some of the ideas described can be transferred to the Russian tax legislation, but this should be done with caution. It is not necessary to introduce a progressive tax system in its pure form in the Russian Federation, but it is worth considering options for switching to a dualistic system. The authors believe that the elements of borrowing foreign experience should be aimed rather at a fair distribution of benefits, for example, through rules that fix tax benefits.Conclusions. The following proposals can be formulated to improve the legal regulation of personal income taxation in the Russian Federation: the distinction between taxation of taxpayers with ultra-high incomes and those with minimal incomes should be based not on the income criterion, but on the expenditure criterion; to establish a non-taxable minimum in the amount of the minimum wage, which will ensure tax fairness for taxpayers with lower-average incomes; to review the criteria of taxation of luxury vehicles, raising the border separating the mass and premium segments of the Russian car market by at least two times - up to 6 million rubles. The best solution would be to abolish the vehicle tax and impose an increased excise tax on fuel and lubricants for personal transport.Рассматривается правовое регулирование налогообложения доходов физических лиц в Российской Федерации в контексте проблем социальной справедливости. На основании сравнительного анализа опыта стран ЕС и ОЭСР делается вывод о том, что элементы заимствования зарубежного опыта должны быть нацелены скорее на справедливое распределение благ, например с помощью норм, закрепляющих налоговые льготы. Ставки налога должны быть максимально эффективными, обеспечивать принципы определенности и справедливости налогообложения. Кроме того, результаты сравнительного анализа опыта государств - членов ЕС показывают неэффективность прогрессивной шкалы подоходного налогообложения как инструмента борьбы с социальным неравенством. По итогам исследования сделан вывод о том, что за основу разграничения налогообложения налогоплательщиков со сверхвысокими доходами и с минимальными доходами необходимо взять не критерий дохода, а критерий расходов

    Optimization of grain quality parameters for winter rye breeding

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    The purpose of this work was to evaluate the phenotypic variability of grain quality indicators and to identify the set of the most informative indicators for the selection of different use varieties of winter rye. The research was carried out in Tatar Scientific Research Institute of Agriculture – Subdivision of the “Kazan Scientific Center of Russian Academy of Sciences” in 2001–2015 on 15 varieties of winter rye. Twenty parameters defining quality of grain and raw value were estimated: technological indicators (thousand grain mass, full-scale weight and grain uniformity), parameters preharvest sprouting (falling number, rate of amylogram, temperature of peak of starch gelatinization), kinematic water extract viscosity (WEV) of grain meal, baking properties (organoleptic assessment of trial baking bread). The greatest influence of genotype was found on WEV (34.8 %) and protein content (27.8 %). These features should be primarily the subject of phenotypic evaluation in the breeding process. Phenotypic variability of criteria of carbohydrate-amylase complex, α-amylases activity and technological parameters was determined predominantly (68.6…82.5 %) by environmental factors. There was no significant relationship between falling number and protein content. The falling number correlated with the rate of amylogram and the temperature of gelatinization. Positive conjugation of the average power of WEV with the rate of amylogram and falling number was found. On the basis of a prolonged phenotypic evaluation using principal component analysis we have optimized the analyzed indicators of quality properties of winter rye grain. For breeding evaluation of winter rye it is proposed to use four integral indi cators having the greatest weight load: protein content, falling number, water extract viscosity and thousand grain mass. This complex of features will provide objectivity and completeness of the evaluation of the breeding material. It was shown that the kinematic viscosity of the water extract should become an important selection index, both for determining the baking qualities of rye, and for revealing the fodder grain advantages

    Функціональний стан нирок у дітей, що перенесли гостре пошкодження нирок, в катамнезі спостереження.

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    Гостре пошкодження нирок (ГПН) у дітей має поліетіологічну структуру, особливості перебігу залежні від віку захворювання і високий ризик розвитку хронічної хвороби нирок (ХХН) в катамнезі. Метою дослідження стало вивчення функціонального стану нирок у дітей, що перенесли ГПН, у віддалених термінах. Матеріали та методи. Було ретроспективно  проаналізовано функціональний стан нирок (швидкість клубкової фільтрації (ШКФ)за Шварцом, рівень паратіреоідного гормону (ПТГ), альбумінурії (АУ),  динамічної і статичної реносцинтиграфіі(РСГ)) за даними 60 історій хвороб дітей від 1 до 18 років, що перенесли ГПН протягом 2000-2016 р.р. Результати. Протягом першого року спостереження у 61,5% хворих зберігалась азотемія,, уповільнення ШКФ та високий рівень АУ. Подальше спостереження за цією групою хворих виявило тенденцію нормалізації рівнів креатиніну, сечовини, ШКФ, але зростання рівнів АУ. В динаміці спостереження від 5 до 15 років, визначено, що у 13,3% пацієнтів ШКФ становила від 90 до 85 мл/мін, а у 36,7% - від 85 до 30 мл/мін. У 46,7% дітей при не змінених показниках креатиніну і ШКФ, відмічено зростання рівню альбумінурії від 45 до 601 мг/добу. За період спостереження, від 15 років і більше, повністю одужало 53,3% дитини, у 31,6% хворих констатована хронічна ниркова недостатність (ХНН), а у 30,0% спостерігалось одужання з дефектом - стійке зниження функції з наявними маркерами пошкодження нирок. Висновки. Гостре пошкодження нирок частіше зустрічалось серед дітей перших 3 років життя, переважно у хлопчиків. Етіологічним чинником виникнення захворювання був гемолітико-уремічний синдром на фоні гострої кишкової інфекції. Повне одужання документоване у 20,0% реконвалесцентів ГПН, у 30,0%  констатовано персистенцію маркерів пошкодження нирки з відновленням функції, а у 18,3% значне, стійке зниження функції нирок. Багатоцільове сцинтиграфічне дослідження з радіофірмпрепаратами різного типу виведення виявило ознаки порушення канальцевих та гломерулярних функцій за 7-8 років до появи лабораторних змін
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