Effect of lethal yellow (AY) mutation and photoperiod alterations on mouse behavior

Decrease in natural illumination in fall/winter months causes depressive-like seasonal affective disorders in vulnerable individuals. Obesity is another risk factor of depression. The lethal yellow (AY) mutation causes ectopic expression of agouti protein in the brain. Mice heterozygous for AY mutation (AY/a) are obese compared to their wild-type littermates (a/a). The main aims of the study were to investigate the effects of AY mutation, photoperiod and the interaction between these factors on daily activity dynamics, feeding, locomotor and exploratory activities, anxiety-related and depressive-like behaviors in mild stress condition. Six weeks old mouse males of AY/a and a/a lines were divided into four groups eight animals each and exposed to long- (14 h light and 10 h darkness) or short- (4 h light and 20 h darkness) day conditions for 28 days. Then the behavior of these mice was successively investigated in the home cage, open field, elevated plus-maze and forced swim tests. We did not observed any effect of AY mutation on the general activity, water and food consumption in the home cage; locomotion and exploration in the open field test; anxiety-related behavior in the open field and elevated plus-maze tests. At the same time, AY mutation increased depressive-like immobility time in the forced swim test (F1.28 = 20.03, p = 0.00012). Shortday conditions decreased nocturnal activity in the home cage, as well as locomotion (F1.28 = 16.33, p = 0.0004) and exploration (F1.28 = 16.24, p < 0.0004) in the open field test. Moreover, short-day exposition decreased time spent in the center of the open field (F1.28 = 6.57, p = 0.016) and in the open arms of the elevated plus-maze (F1.28 = 12.08, p = 0.0017) tests and increased immobility time in the forced swim test (F1.28 = 9.95, p = 0.0038). However, no effect of the interaction between AY mutation and photoperiod on immobility time in the forced swim test was observed. Therefore, short-day photoperiod and AY mutation increased depressive-like behavior in the forced swim test by means of different mechanisms

Optimized properties of live vaccine influenza reassortant strains obtained by reverse genetics

Classical reassortment in developing chicken eggs is a well-established technique for obtaining LAIV strains. Naturally generated reassortant vaccine strains are characterized by high reproductive capacity, genetically stable characteristics of temperature sensitivity and cold resistance, which correspond to the characteristics of the MDV involved in crossing with the epidemic virus. Along with antigenic relevance, natural reassortment ensures attenuation of vaccine strains, good reproduction capacity in upper respiratory tract cells and inability to reproduction in the lower respiratory tract. With classical reassortment, the speed and efficiency of obtaining vaccine reassortants largely depend on the properties of epidemic virus, and therefore cannot be stable. The potential of reverse genetics is attractive because it allows to obtain vaccine reassortants quickly and efficiently, reduce the likelihood of spontaneous mutations; however, the vaccine strain is deprived of the advantages of natural selection, in which the most viable clones are selected. This study presents the results of comparatively assessed A(H3N2) LAIVs obtained in parallel by classical reassortment and reverse genetics according to criteria confirming that vaccine strains inherit the necessary properties that guarantee their harmlessness and high reproduction in chicken embryos. Strains for LAIV obtained by both methods retained all attenuating mutations inherited from the MDV, were highly reproductive at the optimal temperature, with temperature sensitivity corresponded to the MDV. However, strains obtained by reverse genetics, was observed to have partial loss of cold resistance in comparison with that of the MDV and classical reassortants. Reduced cold adaptation may negatively affect vaccine effectiveness. It is important that after several additional passages in chicken embryos at low temperature, the cold resistance of the vaccine strain, assembled by reverse genetics, was increased. Credibly that cold resistance is a phenotypic trait, the degree of manifestation of which depends on the temperature conditions of virus multiplication. The selective factor of reduced incubation temperature is missing in reverse genetics. In order for the cold-adapted phenotype to be fully realized, additional passages at low temperature of RG-reassortants are necessary. Thus, the reverse genetics method using plasmid technology allows to effectively prepare reassortant strains for LAIV. An important stage in obtaining vaccine strains using genetic engineering techniques should be the control of their cold-adapted phenotype and its optimization by additional passages at low temperature

Tax Ad ministration of Large Taxpayers: Global Trends and Features of Russ ian Experience

The article deals with the history and current trends of tax administration of large taxpayers in the Russian Federation. The world experience of tax administration is analyzed as regards the peculiarities of large taxpayers. The following stages of the evolution of tax administration in developed countries are highlighted: the allocation of special units controlling large taxpayers in tax administrations; structuring control functions by industry; introduction of the principle of co-operative compliance. The characteristics and conditions of implementation in the OECD countries of the concept of co-operative compliance were analyzed. The results of tax administration of large taxpayers in the Russian Federation are considered. Particular attention was paid to the first results of the introduction of tax monitoring. The stages of the development of tax administration in developed countries and the Russian Federation are highlighted. It was concluded that the tendencies in the administration of large taxpayers in the Russian Federation are centralization, the introduction of information systems and a system of agreements, which generally corresponds to global practice. The main difference of the Russian practice of tax administration of large taxpayers, which is granting them preferences in exchange for access to their information and management, is highlighted. The analysis of the indicators confirmed the special tax status of the largest taxpayers as it showed the absence of a direct relationship between the performance indicators of the largest taxpayers and their tax liabilities. It was shown that subjective factors determine about 20% of the variation of the tax liabilities of a large taxpayer. It was concluded that the introduction of new forms of control in the form of tax monitoring is an effective way of state influence on the largest companies and a way to ensure the predictable social policy.В статье рассматривается история и современные тенденции налогового администрирования крупных налогоплательщиков в Российской Федерации. Анализируется мировой опыт налогового администрирования, соответствующий особенностям крупных налогоплательщиков. Выделены следующие этапы развития налогового администрирования в развитых странах: выделение специальных подразделений контролирующих крупных налогоплательщиков в налоговых администрациях; структурирование функций контроля по отраслевому признаку; внедрение принципа совместного соблюдения правил. Проанализированы характеристики и условия внедрения в странах ОЭСР концепции совместного соблюдения правил. Рассматриваются результаты налогового администрирования крупных налогоплательщиков в Российской Федерации. Особое внимание уделяется первым результатам внедрения налогового мониторинга. Выделены этапы развития налогового администрирования в развитых странах и Российской Федерации. Сделан вывод о том, что тенденциями в администрировании крупных налогоплательщиков в Российской Федерации являются централизация, внедрение информационных систем и системы соглашений, что в целом соответствует общемировой практике. Выделено основное отличие российской практики налогового администрирования крупных налогоплательщиков, заключающееся в предоставлении им преференций в обмен на доступ к своей информации и управление. Проведенный анализ показателей подтвердил особый налоговый статус крупнейших налогоплательщиков, так как показал отсутствие прямой зависимости между показателями деятельности крупнейших налогоплательщиков и их налоговыми обязательствами. Показано, что субъективные факторы определяют около 20 % вариации налоговых обязательств крупного налогоплательщика. Сделан вывод о том, что внедрение новых форм контроля в виде налогового мониторинга является эффективным способом государственного воздействия на крупнейшие компании способом обеспечения прогнозируемой социальной политики

Lence in parent-child relationships: a case study of preschool age

This article presents the results of research on the presence and manifestation of the signs of psychological abuse by parents on preschool children. The attitude of parents to their children is investigated using the method of diagnosing parental relationships by A. Varga, V.V. Stolin. As a result of the interpretation of the information obtained, general tendencies in child-parental relations, characteristic of this age, were revealedВ данной статье представлены результаты исследования наличия и проявление признаков психологического насилия со стороны родителей на детей дошкольного возраста. Исследуются отношение родителей к своим детям с помощью методики диагностики родительских отношений А.Я. Варга, В.В. Столин. В результате интерпретации полученных сведений, были выявлены общие тенденции в детско-родительских отношениях характерные данному возраст

Психология дидактической коммуникации: инновации конструктивистского подхода

The article deals with the problems of constructivist reflection and the construction of didactic communication, the innovations, opportunities and limitations that the constructivist model of pedagogical interaction offers. The aim of the work was an analysis of innovations and perspectives of understanding the modern educational process in the context of the constructivist approach. Postmodern, the era of the late twentieth and early twenty-first centuries, leaving, leaves many interesting and productive developments, which undoubtedly include constructivism. Contesting the existence of reality as such, constructivism offered several solutions to the problem of man's comprehension of himself and the world. These solutions united by a common idea of producing internal and external reality in social dialogue, in the interaction of people and groups (actors and co-actors) interested in solving problems, united in situational, subject, active collaborations (associations, groups) to develop the best and satisfying all participants as stakeholders of a consensus solution of the problem. Constructivism has changed the view of what is happening in the relations of people in a number of areas, including management and education. Findings. Due to its debatable nature, the development of constructivism ideas in the context of the development of educational ideologies and technologies activates the processes of reconceptualization of the traditional model of didactic communication, and the constructionist model of education itself can and should become an object of systematic methodological, theoretical, empirical and applied research. Any of these approaches can be disclosed as an example of a constructivist educational model. The leading signs of this model are the dialogue nature of education, the focus on understanding the internal and external world in a dialogue with significant other people. This model assumes the consideration of such a dialogue as a process by which a person builds his own life world and himself, as a creative «rediscovery» of the basic truths of human existence, as making socially and personally meaningful decisions in a situation of educational, professional and life choices.В статье рассматриваются проблемы конструктивистского осмысления и конструирования дидактической коммуникации, т. е. инновации, возможности и ограничения, которые предлагает конструктивистская модель педагогического взаимодействия. Целью работы выступил анализ инноваций и перспектив осмысления современного образовательного процесса в контексте конструктивистского подхода. Постмодерн, эпоха конца ХХ и начала XXI в., уходя, оставляет множество интересных и продуктивных разработок, к числу которых относится, несомненно, и конструктивизм (constructivism). Оспаривая существование реальности как таковой, конструктивизм предложил несколько вариантов решения проблемы постижения человеком себя и мира, объединенных общей идеей производства внутренней и внешней реальности в социальном диалоге, во взаимодействии заинтересованных в решении проблем людей и групп (акторов и ко-акторов), объединенных в ситуативные, предметные, деятельные коллаборации (ассоциации, группы) для выработки оптимального и удовлетворяющего всех участников как стейкхолдеров консенсусного решения проблемы. Конструктивизм изменил взгляд на происходящее в отношениях людей в целом ряде сфер, включая менеджмент и образование. Выводы. Благодаря своей дискуссионности, развитие идей конструктивизма в контексте разработки образовательных идеологий и технологий активизирует процессы реконцептуализации традиционной модели дидактической коммуникации, а сама конструкционистская модель образования может и должна стать объектом систематических методологических, теоретических, эмпирических и прикладных исследований. Любой из перечисленных подходов может быть раскрыт как пример конструктивисткой модели образования, ведущими признаками которой являются диалогичность образования, нацеленность на осмысление внутреннего и внешнего мира в диалоге со значимыми другими людьми, рассмотрение такого диалога как процесса построения человеком собственного жизненного мира и самого себя, как творческого «переоткрытия» базовых истин человеческого существования, как принятие социально и личностно значимых решений в ситуации учебного, профессионального, жизненного выбора

Stress-induced aggression in heterozygous TPH2 mutant mice is associated with alterations in serotonin turnover and expression of 5-HT6 and AMPA subunit 2A receptors

Background: The contribution of gene-environment interactions that lead to excessive aggression is poorly understood. Environmental stressors and mutations of the gene encoding tryptophan hydroxylase-2 (TPH2) are known to influence aggression. For example, TPH2 null mutant mice (Tph2−/−) are naturally highly aggressive, while heterozygous mice (Tph2+/−) lack a behavioral phenotype and are considered endophenotypically normal. Here we sought to discover whether an environmental stressor would affect the phenotype of the genetically ‘susceptible’ heterozygous mice (Tph2+/−). Methods: Tph2+/− male mice or Tph2+/+ controls were subjected to a five-day long rat exposure stress paradigm. Brain serotonin metabolism and the expression of selected genes encoding serotonin receptors, AMPA receptors, and stress markers were studied. Results: Stressed Tph2+/− mice displayed increased levels of aggression and social dominance, whereas Tph2+/+ animals became less aggressive and less dominant. Brain tissue concentrations of serotonin, its precursor hydroxytryptophan and its metabolite 5-hydroxyindoleacetic acid were significantly altered in all groups in the prefrontal cortex, striatum, amygdala, hippocampus and dorsal raphe after stress. Compared to non-stressed animals, the concentration of 5-hydroxytryptophan was elevated in the amygdala though decreased in the other brain structures. The overexpression of the AMPA receptor subunit, GluA2, and downregulation of 5-HT6 receptor, as well as overexpression of c-fos and glycogen-synthase-kinase-3β (GSK3-β), were found in most structures of the stressed Tph2+/− mice. Limitations: Rescue experiments would help to verify causal relationships of reported changes. Conclusions: The interaction of a partial TPH2 gene deficit with stress results in pathological aggression and molecular changes, and suggests that the presence of genetic susceptibility can augment aggression in seemingly resistant phenotypes. © 2020 The Authors602805Seventh Framework Programme, FP7Deutsche Forschungsgemeinschaft, DFG: CRC TRR 58 A1/A5Horizon 2020 Framework Programme, H2020: 728018Russian Foundation for Basic Research, RFBR: 15-04-03602Deutsche Forschungsgemeinschaft, DFGRussian Foundation for Basic Research, RFBRThe authors’ work reported here was supported Deutsche Forschungsgemeinschaft (DFG: CRC TRR 58 A1/A5), the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant No. 602805 (Aggressotype) and the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE) (to KPL and TS), the “5-100” Russian Academic Excellence Project (to KPL and TS) and the Russian Foundation of Basic Research (RFBR Grant No. 15-04-03602 to TS). We appreciate the valuable technical help of Dr. Joao Costa-Nunes and Dolores Bonopartos with this project

Clinical characteristics of bronchopulmonary dysplasia, evaluation of the effectiveness of therapy in combination with palivizumab vaccination

The article deals the clinical manifestations of bronchopulmonary dysplasia, its diagnosis and treatment with an assessment of effectiveness, specific prevention of respiratory syncytial infection.В статье рассмотрены клинические проявления бронхолегочной дисплазии, ее диагностика и лечение с оценкой эффективности, специфическая профилактика респираторно- синцитиальной инфекции

Идентификация штамма дрожжей cystobasidium slooffiae, выделенных из тестового образца торта

Nowadays, the problem of food safety and quality assurance throughout the product life cycle is topical in the whole world. According to the WHO data, foodborne diseases linked with consumption of unsafe food, including diseases caused by microbial pathogens, are common in many world countries and are still the main cause of morbidity and mortality. Therefore, prevention of the microbiological spoilage of food products is an important task in all food industry sectors. One of the ways for its solution is to carry out investigations to reveal potential sources of microbial contamination of food products including flour confectionery. Cakes are multi-component confectionery products. As a rule, they have the high moisture mass fraction, which conditions the presence of a favorable environment for the development of all types of microorganisms and contributes to the instability of this product type to the effects of environmental conditions during storage. In this study, yeast and mold counts were determined by growing cultures on the solid culture medium (Sabouraud). Pure cultures were isolated by the streak plate method. Stained and unstained microorganisms were examined by the microscopic method. Saccharolytic enzymes of the isolated bacterial cultures were identified using the Hiss’s culture media. Based on the analysis of the ribosomal gene sequence obtained by sequencing the DNA region encoding the ITS-D1/D2 rDNA region, an accurate identification of the strain was performed. The phylogenetic relationship analysis carried out using strains of closely related microorganisms showed that species Cystobasidium slooffiae was the closest relative of the studied strain. The source of Cystobasidium slooffiae was the environment. The detection of this strain indicates violations of the sanitary and hygienic condition of inventory, equipment, industrial premises, including hard-to-reach places, as well as violations of the hygiene rules by personnel; in addition, this indicates the high contamination of raw materials.В настоящее время во всем мире актуальной является проблема обеспечения и сохранения качества и безопасности пищевых продуктов на протяжении всего их жизненного цикла. По данным Всемирной организации здравоохранения, болезни пищевого происхождения, связанные с употреблением некачественных продуктов питания и включающие в себя группу болезней, вызываемых в том числе микробными патогенами, имеют широкое распространение во многих странах мира и по-прежнему являются основной причиной заболеваемости и смертности. В связи с этим предотвращение микробиологической порчи пищевых продуктов является важной задачей, стоящей перед всеми отраслями пищевой промышленности. Одним из путей ее решения становится проведение исследований по выявлению потенциальных источников микробиологической обсемененности продуктов, в том числе мучных кондитерских изделий. Торты — это многокомпонентные кондитерские изделия. Как правило, они являются продуктами с высокой массовой долей влаги, что предопределяет наличие в них благоприятной среды для развития всех видов микроорганизмов и способствует нестабильности данного вида продукции к воздействию условий окружающей среды в процессе хранения. В работе определяли количество плесеней и дрожжей посевом на плотную питательную среду (Сабуро). Чистые культуры выделяли методом истощающего штриха. Исследовали микроорганизмы микроскопическим методом в окрашенном и неокрашенном виде. Идентификацию сахаролитических ферментов выделенных культур бактерий проводили с использованием питательных сред Гисса. На основе анализа последовательности рибосомальных генов, полученных при секвенировании участка ДНК, кодирующего область ITS-D1/ D2 рДНК, провели точную идентификация штамма. Анализ филогенетического родства, построенный с использованием штаммов близкородственных микроорганизмов, показал, что наиболее близким к исследуемому штамму является Cystobasidium, вид Cystobasidium slooffiae. Источником Cystobasidium slooffiae является окружающая среда. Обнаружение этого штамма свидетельствует о  нарушениях санитарно-гигиенического состояния инвентаря, оборудования, производственных помещений, включая труднодоступные места, а также о нарушении правил гигиены персоналом; кроме того, это говорит о высокой обсемененности сырья