In situ high resolution studies of the FG-nucleoporins in the central channel of the nuclear pore complex

The nuclear pore complex (NPC) is the largest protein complex in the nuclear envelope of eukaryotic cells. It provides a permeability barrier for rapid and selective transport of biomolecules in and out of the nucleus. While the scaffold structure and composition of the NPC are well understood, little is known about the permeability barrier, which is formed of multiple copies of about ten different intrinsically disordered nucleoporins. These proteins characteristically contain multiple phenylglycine repeats in their sequence and are referred to as FG-Nups. Due to technical limitations in the study of these highly flexible and dynamic proteins, the conformational dynamics and spatial arrangement of FG-Nups in the permeability barrier of the NPC remain elusive. In this thesis I developed and established two complementary imaging techniques to visualise FG-Nups in the NPC in mammalian cells. To achieve this, I further developed a combination of genetic code expansion using unnatural amino acids and click-chemistry technologies suitable for high resolution fluorescence imaging. This method allows for efficient site-specific labelling of two sites in FG-Nups with small, photostable organic fluorophores with residue precision in situ. The first imaging approach used super-resolution localisation microscopy to precisely map the labelled site of the FG-Nups to a reference in the NPC. This resulted in images showing two-dimensional projection of FG-Nups distribution in NPCs, resolving distances down to 10nm. The second approach involved a complimentary technique based on confocal scanning microscopy: using fluorescence lifetime imaging microscopy (FLIM) to directly measure end-to-end distances between two sites in an FG-Nup less than 10nm apart using Förster resonance energy transfer (FRET). The ultimate goal of my work was to use the approaches to determine the structural arrangement of FG-Nups in the permeability barrier of the NPC. I further applied polymer physics concepts of scaling laws to my results from FLIM-FRET studies. I was able to show that the two major players in the permeability barrier FG-Nups, Nup62 and Nup98, tend to resemble a state between a collapsed coil and an ideal chain. This finding demonstrates the first experimental evidence of the actual scaling of FG-Nups in vivo, which has implications for existing transport models. Aside from its contribution to understanding the NPC permeability barrier function, the developed approach lays the groundwork for a more detailed understanding of disordered protein dynamics, dimensions and functions inside the cell

Cyclic AMP system in muscle tissue during prolonged hypokinesia

Components of the cyclic Adenosine-cyclic-35-monophosphate (AMP) system in the muscle tissue of white rats were studied during 70-75 days of hypokinesia, created by placing the animals in small booths which restricted their movements, and during the readaptation period. In the initial period, cyclic AMP levels and the activities of phosphodiesterase and adenylate cyclase in muscle tissue were increased. The values for these indices were roughly equal for controls and experimental animals during the adaptation period, but on the 70th day of the experiment cAMP levels dropped, phosphodiesterase activity increased, and the stimulative effect of epinephrine on the activity of adenylate cyclase decreased. The indices under study normalized during the readaptation period

Применение смешанных технологий обучения физике для организации самостоятельной работы студентов

The article generalizes the experience of application of mixed technology of physics teaching for organization of self-instruction of students.Статья обобщает опыт использования смешанных технологий обучения физике для организации самостоятельной работы студентов

Labour migration: the benefits and negative consequences

В статье представлены различные точки зрения на трудовую миграцию, проведен обзор научных теорий с точки зрения причин и социально-экономических последствий трудовой миграции, представлены позитивные и негативные результаты влияния трудовой миграции и необходимости развития миграционной политики в России.The article presents different perspectives on labor migration, review of scientific theories from the point of view of the causes and socio-economic impacts socio-economic impacts of labour migration, presents a positive and negative impact of labour migration and the need for the development of migration policy in Russia

The necessity to organize learner autonomy in the process of acquiring foreign language

The article considers the organization of learner autonomy in learning foreign language. The authors examine the term "autonomy" in modern methodological literature. The learner autonomy is interpreted differently by scientists and by now there is no a common explanation of this term. Despite different nuances we can certainly say that the learner autonomy is connected with a greater independence, the learners' responsibility in educational process, the ability to organize their own education and assess the results. Moreover it is paid attention to examination of the Language learning portfolio as an effective method of learner autonomy and the instrument of self-learning. It helps student to implement self-assessment and self-control of acquired linguistic skills that promotes the creating of conditions for development of educational competence and autonomy. The authors show the results of their research carried out with the students of the faculty of foreign languages of TSU to illustrate the effectiveness of the ELP

A miniaturized nigrostriatal-like circuit regulating locomotor performance in a protochordate

To gain insight into the evolution of motor control systems at the origin of vertebrates, we have investigated higher-order motor circuitry in the protochordate Oikopleura dioica. We have identified a highly miniaturized circuit in Oikopleura with a projection from a single pair of dopaminergic neurons to a small set of synaptically coupled GABAergic neurons, which in turn exert a disinhibitory descending projection onto the locomotor central pattern generator. The circuit is reminiscent of the nigrostriatopallidal system in the vertebrate basal ganglia, in which disinhibitory circuits release specific movements under the modulatory control of dopamine. We demonstrate further that dopamine is required to optimize locomotor performance in Oikopleura, mirroring its role in vertebrates. A dopamine-regulated disinhibitory locomotor control circuit reminiscent of the vertebrate nigrostriatopallidal system was thus already present at the origin of ancestral chordates and has been maintained in the face of extreme nervous system miniaturization in the urochordate lineage.publishedVersio

Evaluation of the sociocultural competence on the basis of the platform Moodle according to the competency-based approach

International audienceThe choice of criteria and methods of evaluation of the sociocultural competence is determined by the principles of thecompetency-based approach and the structure of this competence. In our opinion, it is not enough to use only socioculturalquestionnaire. In addition to the cognitive criterion it is necessary to take into consideration motivational, behavioral, functionaland technological criteria. We believe that the major tools of evaluation are the psychological tests and the method of the casestudy.To evaluate the general level of the sociocultural competence it is indispensable to apply all the aforementioned criteria. Itcan be done via the platform Moodle

The Combined Method of Forecasting the Investments within the Framework of Panel Data Models

The article is devoted to the panel data modeling of the firm's investments depending on its market value and the size of fixed assets. The Grunfeld's investment data as provided in R package were used as the initial data. The data frame contains annual observations for 11 firms over 20 years. The main econometric models for panel data (pooled model, fixed effects model, random effects model) were estimated. To make choice the most effective specification of the model the character of effects was tested. The heterogeneity of firms was explained by individual random factors. The comparative analysis of parameters' estimates was performed using the basic panel data models and their optimal combination in the framework of combined assessment (forecasting). Weight coefficients of hybrid forecasts are assigned as directed by the combined model list in accordance with standard optimality requirements. It was shown that the results of the combined assessment coincided with the estimates of the random effects model

PROTECTION OF RIGHTS OF CHILDREN UNDER INTERNATIONAL AND RUSSIAN LEGISLATION

Abstract.This study was aimed at discussing the main aspects regarding the protection of rights of childrenunder international and Russian law. An analysis of the norms regarding the protection of the rights, freedoms and legitimate interests of children from the point of view of international and Russian legislation was presented. The main directions of the state policy on the protection of the rights and legitimate interests of children were also covered.Keywords: Children's Rights, Protection of Children's Rights, Constitutional Law of Protection, Minor, International Regulations, International Law, Adolescent, Legitimate Interests of Children, International Documents, Constitution of Russian Federation