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Today we are witnessing a transition to new forms of work culture, in the context of the transition from an industrial economy to a digital one. Similar processes took place during the formation of the Soviet state. Then, the culture of work was undergoing its transformation from the conditions of the traditional economy to the conditions of the industrial world. Labor institutions created in the 1920s played a special role in these processes. The main purpose of the article is to analyze the process of forming a new work culture through the activities of the Tsitovites, which took place in the conditions of the cultural revolution in the USSR. The relevance of the topic is due to the historical aspect of the consideration of the described problem, not the economic one. The authors turn to the periodical press of the designated period, to archival documents, as well as to modern scientific research. As a result, the authors come to the conclusion that in the 1920s - 30s in the USSR, the processes of formation of labor culture and the cultural revolution went on in parallel and actively influenced each other. In our country, the principles of scientific organization of labor acquire the character of an important tool for speedy progress towards the restoration of the national economy after the devastation of the First World War and the Civil War. The activities of the Central Institute of Labor laid the foundation for a creative approach to labor relations, a special role in this belonged to the director of the CITA – A.K. Gastev.

Introduction. Managing patients with relapsing-remitting multiple sclerosis (RMS) remains a pressing issue. Objective. To detect the reversible metabolic changes of the brain matter in patients with clinically exacerbated RMS and to follow them up after intravenous glucocorticoid (IVGC) treatment. Materials and methods. Neurological examination and neuroimaging in the RMS patients included expanded disability status scale (EDSS) scoring, conventional brain magnetic resonance imaging (MRI), and proton nuclear magnetic resonance spectroscopy (1H-NMR spectroscopy) before and after IVGC treatment. Multivoxel 1H-NMR spectroscopy was used to assess metabolism in the centra semiovale and cingulate gyri. Results. Based on the multivoxel 1H-NMR spectroscopy, relative metabolite concentrations in the grey and white matter statistically differed within the study cohort before and after the IVGC treatment. The N-acetylaspartate/choline ratio significantly recovered and the choline/creatine ratio decreased in the anterior cingulate gyri in 27% of patients. The brainstem function score significantly improved in the metabolic response group as compared to the non-metabolic response group. Conclusion. We should study the potential predictors of RMS activity and the IVGC response to select the RMS relapses when pulse-therapy with IVGCs is definitely indicated. Spectroscopy may reveal RMS pathogenesis variability earlier than conventional MRI.

The voltage-gated potassium channel Kv1.1, which is abundant in the CNS and peripheral nervous system, controls neuronal excitability and neuromuscular transmission and mediates a number of physiological functions in non-excitable cells. The development of some diseases is accompanied by changes in the expression level and/or activity of the channels in particular types of cells. To meet the requirements of studies related to the expression and localization of the Kv1.1 channels, we report on the subnanomolar affinity of hongotoxin 1 N-terminally labeled with Atto 488 fluorophore (A-HgTx) for the Kv1.1 channel and its applicability for fluorescent imaging of the channel in living cells. Taking into consideration the pharmacological potential of the Kv1.1 channel, a fluorescence-based analytical system was developed for the study of peptide ligands that block the ion conductivity of Kv1.1 and are potentially able to correct abnormal activity of the channel. The system is based on analysis of the competitive binding of the studied compounds and A-HgTx to the mKate2-tagged human Kv1.1 (S369T) channel, expressed in the plasma membrane of Neuro2a cells. The system was validated by measuring the affinities of the known Kv1.1-channel peptide blockers, such as agitoxin 2, kaliotoxin 1, hongotoxin 1, and margatoxin. Peptide pore blocker Ce1, from the venom of the scorpion Centruroides elegans, was shown to possess a nanomolar affinity for the Kv1.1 channel. It is reported that interactions of the Kv1.1 channel with the studied peptide blockers are not affected by the transition of the channel from the closed to open state. The conclusion is made that the structural rearrangements accompanying the channel transition into the open state do not change the conformation of the P-loop (including the selectivity filter) involved in the formation of the binding site of the peptide pore blockers.

The publication is aimed at studying the attitude of middle-aged and older Russians to physical culture and sports. The scope of the results embraces studying the dynamics of perception of physical culture and sports in the minds of middle-aged and older Russians. The research subject is studying the dynamic changes in the system of value consciousness of Russians. The method of obtaining empirical data includes focused online interviews, traditional analysis of documents, including legislative acts of the Russian Federation. Conducting focused online interviews with respondents from Nizhny Novgorod and Volgograd is due to the conditions of self-isolation of Russians during the study period. The result of the study is presented as a description of the specifics of the perception of physical culture and sports by middle-aged and older Russians. The scientific novelty of the publication lies in the author's understanding of the influence of self-isolation on changes in the values of Russians in the perception of physical culture and sports worthiness by middle-aged and older people in Russian regions. During the interviewing online focus groups, respondents' suggestions on how to encourage middle-aged and older Russians to engage in physical culture and sports were revealed.

Due to the modern economic situation shaped by the COVID-19 pandemic, entrepreneurial activity significantly depleted in all spheres of the economy not only in Russia but across the world. However, there are some industrial spheres the development of which did not stop completely despite being restrained by the COVID-19 pandemic. The industry of children’s tourism having suffered certain understandable changes continues to function since the industry of children’s recreation is directly connected to a child’s development and adaptation in society, their socialization which generates the need for the development of this industry, as well as the need of society and parents for the organization of children’s recreation, leisure, and tourism. The article presents a study of organizational and economic factors of the development of tourism for primary school children in Russia both before the COVID-19 pandemic and in the post-pandemic conditions. The need and demand of society for the development of these services – the children’s recreation industry – is revealed.

The voltage-gated potassium Kv1.3 channel is an essential component of vital cellular processes which is also involved in the pathogenesis of some autoimmune, neuroinflammatory and oncological diseases. Pore blockers of the Kv1.3 channel are considered as potential drugs and are used to study Kv1 channels’ structure and functions. Screening and study of the blockers require the assessment of their ability to bind the channel. Expanding the variety of methods used for this, we report on the development of the fluorescent competitive binding assay for measuring affinities of pore blockers to Kv1.3 at the membrane of mammalian cells. The assay constituents are hongotoxin 1 conjugated with Atto488, fluorescent mKate2-tagged Kv1.3 channel, which was designed to improve membrane expression of the channel in mammalian cells, confocal microscopy, and a special protocol of image processing. The assay is implemented in the “mix and measure”, format and allows the screening of Kv1.3 blockers, such as peptide toxins, that bind to the extracellular vestibule of the K+-conducting pore, and analyzing their affinity.

The analysis of innovation activity and its elements in the quantitative and qualitative characteristics of tourism enterprises belonging to small and medium-sized businesses has been presented. The changes taking place in the world in the tourism market, including under the influence of COVID, as well as the peculiarities of tourism as part of the service sector and industry, determine the search for new non-traditional destinations with innovative elements. The purpose of this article is to present the innovation activity in quantitative and qualitative characteristics, which allows informatively characterizing the Russian practice in general and in small and medium-sized businesses on the example of the tourism sector. The research methods used were content analysis, comparative analysis, the method of expert assessments, and statistical methods. The results of the research of innovation activity based on monitoring, taking into account the industry characteristics, characterize a low share of small enterprises interested in innovation, an insignificant connection with higher educational institutions, a low share of environmental and managerial innovations. The results of the monographic observation of tourism enterprises allow assessing innovation activity positively for most enterprises, however, there is a lack of state support for regional administration, financial capabilities, and strategic planning at enterprises. Conducting research and obtaining new information will be necessary for the development of innovative projects and strategic development of tourism in Russia in the future, in innovative activities, especially in terms of marketing. As a priority area – the interaction of small and medium-sized businesses with scientific departments of universities to integrate their joint activities.

The article analyzes the concept and role of biobanks in carrying out genomic research and concludes that it is necessary, on the basis of an agreed conceptual apparatus, to formulate general provisions on the status of subjects with biobanks, on the regime of bio samples and information obtained on their basis. It is proposed to ensure interaction of organizations engaged in biobanking by improving the legal regime of biobanks, forming registers of genetic data and strengthening state control over their activities. The idea is substantiated that the legal regulation of biobanking in Russia should be based on the principles laid down in international acts, ethical rules and doctrine. In the article, considerations were made regarding the need to separate within the framework of the general rules of procedure for the provision of biomaterials and genetic information for scientific purposes, special attention was paid to the procedure for transboundary exchange of information.

In recent decades, the active interaction of innovative technologies and politics has given a rise to a new specific phenomenon –technopolitics. It is acquiring clearer outlines and seeks to obtain the status of a separate applied discipline. Technopolitics includes the whole range of tools used by politicians, political organizations and political strategists within the Internet space in order to collect information about the potential electorate, form a strategy and influence the mood of voters. The main elements of technopolitics are social networks, mobile applications and specialized sites. They become an ideal platform for understanding the mood in society, forming a roadmap on key issues, which allows solving both internal and foreign policy tasks. The authors of this research set the aim to analyze examples of technopolitics functioning in the countries of the Ibero-American region, which includes countries with an impressive number of Internet users and one of the highest levels of political participation. As a result of the research, the authors come to the conclusion that Spain and the countries of Latin America are actively involved in technopolitics, which is proved by the activities of local political organizations that develop their activity in the framework of Internet communications. The creation of social media accounts and own websites is aimed at an active interaction with citizens without the participation of traditional media as an intermediary. Operative response to changes in shades of public opinion allows political parties to timely change the vector of their movement. Citizens’ general engagement in technopolitics led to truly revolutionary changes in the hierarchy of the “candidatevoter”, endowing the voter with truly democratic instruments of influencing the government, and thereby increasing the percentage of political participation of citizens disenchanted with the former relations between the institution of power and the people. The Internet has allowed an ordinary person to turn into a real political actor organizing transparent discussions, easily involving a large number of people in solving political issues. People are no longer required to vote within the framework of the proposed alternative, but asked for their opinion. Much of this change is due to the creation of Twitter, a platform opened to discussion of various issues and free from censorship, very popular in the countries of the Ibero-American region.

Light-driven proton transport by microbial retinal proteins such as archaeal bacteriorhodopsin involves carboxylic residues as internal proton donors to the catalytic center which is a retinal Schiff base (SB). The proton donor, Asp96 in bacteriorhodopsin, supplies a proton to the transiently deprotonated Schiff base during the photochemical cycle. Subsequent proton uptake resets the protonated state of the donor. This two step process became a distinctive signature of retinal based proton pumps. Similar steps are observed also in many natural variants of bacterial proteorhodopsins and xanthorhodopsins where glutamic acid residues serve as a proton donor. Recently, however, an exception to this rule was found. A retinal protein from Exiguobacterium sibiricum, ESR, contains a Lys residue in place of Asp or Glu, which facilitates proton transfer from the bulk to the SB. Lys96 can be functionally replaced with the more common donor residues, Asp or Glu. Proton transfer to the SB in the mutants containing these replacements (K96E and K96D/A47T) is much faster than in the proteins lacking the proton donor (K96A and similar mutants), and in the case of K96D/A47T, comparable with that in the wild type, indicating that carboxylic residues can replace Lys96 as proton donors in ESR. We show here that there are important differences in the functioning of these residues in ESR from the way Asp96 functions in bacteriorhodopsin. Reprotonation of the SB and proton uptake from the bulk occur almost simultaneously during the M to N transition (as in the wild type ESR at neutral pH), whereas in bacteriorhodopsin these two steps are well separated in time and occur during the M to N and N to O transitions, respectively.

The research presented in the article is the basis for the subsequent development of the concept of religious tourism development in the framework of the expansion of domestic and inbound Russian tourism. Based on various ideas about religious tourism and pilgrimage, the authors assessed the current state of religious tourism, clarified the conceptual framework; conducted a study of the system of marketing and promotion of pilgrimage and religious tourism, evaluated the activities of pilgrimage centers for organizing domestic tours and international trips; identified opportunities and problems that limit the development of religious tourism and provided recommendations for overcoming them. The results of the study of the current state and prospects for the development of religious tourism, in general, are significant and can be used by the pilgrim services of the Russian Orthodox Church, tourist associations, and organizations in the development and implementation of measures for the development of religious tourism based on existing and reviving spiritual centers of the Russian Orthodox Church.

Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the V1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa.

Many peptide ligands of nicotinic acetylcholine receptors (nAChRs) contain a large number of positively charged amino acid residues, a striking example being conotoxins RgIA and GeXIVA from marine mollusk venom, with an arginine content of >30%. To determine whether peptides built exclusively from arginine residues will interact with different nAChR subtypes or with their structural homologs such as the acetylcholine-binding protein and ligand-binding domain of the nAChR α9 subunit, we synthesized a series of R3, R6, R8, and R16 oligoarginines and investigated their activity by competition with radioiodinated α-bungarotoxin, two-electrode voltage-clamp electrophysiology, and calcium imaging. R6 and longer peptides inhibited muscle-type nAChRs, α7 nAChRs, and α3β2 nAChRs in the micromolar range. The most efficient inhibition of ion currents was detected for muscle nAChR by R16 (IC50 = 157 nM) and for the α9α10 subtype by R8 and R16 (IC50 = 44 and 120 nM, respectively). Since the R8 affinity for other tested nAChRs was 100-fold lower, R8 appears to be a selective antagonist of α9α10 nAChR. For R8, the electrophysiological and competition experiments indicated the existence of two distinct binding sites on α9α10 nAChR. Since modified oligoarginines and other cationic molecules are widely used as cell-penetrating peptides, we studied several cationic polymers and demonstrated their nAChR inhibitory activity. SIGNIFICANT STATEMENT By using radioligand analysis, electrophysiology, and calcium imaging, we found that oligoarginine peptides are a new group of inhibitors for muscle nicotinic acetylcholine receptors (nAChRs) and some neuronal nAChRs, the most active being those with 16 and 8 Arg residues. Such compounds and other cationic polymers are cell-penetrating tools for drug delivery, and we also demonstrated the inhibition of nAChRs for several of the latter. Possible positive and negative consequences of such an action should be taken into account.

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

The purpose of the article is to critically analyze and generalize the historiographical material devoted to the study of the process of gradual introduction of mathematical methods, methods of informatization and digitalization, computer technology into the everyday life of one of the most humanitarian sciences—history. Based on a number of studies, the history of the introduction of mathematical methods for working with mass historical sources is considered. It is impossible not to note the huge contribution of the outstanding Russian source historian, academician I.D. Kovalchenko, his colleagues and followers who paved the way for the introduction of computer technology in historical research. For the first time in the Russian historiography devoted to this problem, the authors raise the question of the entry of modern humanity into a time of actively developing contradictions between new high-tech digital means of production and industrial and social relations lagging behind technological progress, with the resulting socioeconomic, political and cultural consequences. Some elements of this process have been noted by many researchers in different countries, primarily in terms of the risks that the introduction of digitalization, robotics and artificial intelligence in our lives, especially in the economy. The authors believe that in this case we may not be talking about risks, most of which are historically usually overcome, but, and in this they rely on the opinion of modern researchers in this field, about changing the model of socio-economic development of mankind in General. As for the problem of correlation between historical science and digitalization, generalizing the views of most modern specialists in the field of application of Informatization and digitalization in historical research, it is impossible to completely replace a person in historical and other Humanities.

Purpose: to conduct a comprehensive analysis of the prerequisites and factors for the development of ethnographic tourism in the Moscow region and the conditions for the formation of tourist flows of this type of tourism in the region, to assess problems and develop ways to solve them.

The purpose of the article is to reveal the peculiar features of information systems’ application in genomic research, including the circadian genetics topic, and to establish the relationship and consistency of general and special rules in this regard. The main approaches to the study of the above problem are interdisciplinary, systemic and dialectical. These approaches allow estimating the application of information systems in genomic research from the perspective of the general terms “information contained in the database” and “information technology”. Findings: it has been found out that genomic research should be closely related to the application of state information systems. The authors have suggested developing leverages for the communication of various structural and other units of the field (system) within which this application is allowed by law and to advance the legal conceptual framework for differentiation of the legal status of parties depending on the application of databases when dealing with genomic information. Also, the authors have determined the need for bringing the regime of information technologies and databases related to the genomic research into line with the common rules on any information databases, on the one hand, and separation from cases of genomic information exchange out of their scope, on the other hand. The prospects of using blockchain technology research for fixing circadian gene research findings have been positively assessed and the impact of cross-border relations in this field on the exercise of parties’ powers has been discovered. The article is of practical value both for lawyers and other specialists, including geneticists, biologists, physicians, etc. who carry out genomic research or use genomic information. Besides, the conclusions made by the authors can be used in lawmaking.

Lynx1, membrane-bound protein co-localized with the nicotinic acetylcholine receptors (nAChRs) and regulates their function, is a three-finger protein (TFP) made of three &beta, structural loops, similarly to snake venom &alpha, neurotoxin TFPs. Since the central loop II of &alpha, neurotoxins is involved in binding to nAChRs, we have recently synthesized the fragments of Lynx1 central loop, including those with the disulfide between Cys residues introduced at N- and C-termini, some of them inhibiting muscle-type nAChR similarly to the whole-size water-soluble Lynx1 (ws-Lynx1). Literature shows that the main fragment interacting with TFPs is the C-loop of both nAChRs and acetylcholine binding proteins (AChBPs) while some ligand-binding capacity is preserved by analogs of this loop, for example, by high-affinity peptide HAP. Here we analyzed the structural organization of these peptide models of ligands and receptors and its role in binding. Thus, fragments of Lynx1 loop II, loop C from the Lymnaea stagnalis AChBP and HAP were synthesized in linear and Cys-cyclized forms and structurally (CD and NMR) and functionally (radioligand assay on Torpedo nAChR) characterized. Connecting the C- and N-termini by disulfide in the ws-Lynx1 fragment stabilized its conformation which became similar to the loop II within the 1H-NMR structure of ws-Lynx1, the activity being higher than for starting linear fragment but lower than for peptide with free cysteines. Introduced disulfides did not considerably change the structure of HAP and of loop C fragments, the former preserving high affinity for &alpha, bungarotoxin, while, surprisingly, no binding was detected with loop C and its analogs.

Venoms of viperid snakes affect mostly hemostasis, while C-type lectin-like proteins (CTLPs), one of the main components of viperid venoms, act as anticoagulants, procoagulants, or agonists/antagonists of platelet activation. However, we have shown earlier that CTLPs from the saw-scaled viper Echis multisquamatus, called emunarecins EM1 and EM2, were able to inhibit nicotinic acetylcholine receptors (nAChRs) in neurons of a pond snail (Lymnaea stagnalis). Here we analysed the structure of the emunarecins by mass spectrometry and report that EM1 and EM2 inhibit fluorescent α-bungarotoxin binding to both muscle-type nAChRs from Torpedo californica and human neuronal α7 nAChRs. EM1 at 23µM and EM2 at 9µM almost completely prevented fluorecsent α-bungarotoxin binding to muscle-type nAChRs. Interaction with human neuronal α7 nAChR was weaker; EM1 at the concentration of 23µM blocked the α-bungarotoxin binding only by about 40% and EM2 at 9µM by about 20%. The efficiency of the EM2 interaction with nAChRs was comparable to that of a non-conventional toxin, WTX, from Naja kaouthia cobra venom. Together with the data obtained earlier, these results show that CTLPs may represent new nAChR ligands.

Snake venom α-neurotoxins, invaluable pharmacological tools, bind with high affinity to distinct subtypes of nicotinic acetylcholine receptor. The combinatorial high-affinity peptide (HAP), homologous to the C-loop of α1 and α7 nAChR subunits, binds biotinylated α-bungarotoxin (αBgt) with nanomolar affinity and might be a protection against snake-bites. Since there are no data on HAP interaction with other toxins, we checked its binding of α-cobratoxin (αCtx), similar to αBgt in action on nAChRs. Using radioiodinated αBgt, we confirmed a high affinity of HAP for αBgt, the complex formation is supported by mass spectrometry and gel chromatography, but only weak binding was registered with αCtx. A combination of protein intrinsic fluorescence measurements with the principal component analysis of the spectra allowed us to measure the HAP-αBgt binding constant directly (29 nM). These methods also confirmed weak HAP interaction with αCtx (>10000 nM). We attempted to enhance it by modification of HAP structure relying on the known structures of α-neurotoxins with various targets and applying molecular dynamics. A series of HAP analogues have been synthesized, HAP[L9E] analogue being considerably more potent than HAP in αCtx binding (7000 nM). The proposed combination of experimental and computational approaches appears promising for analysis of various peptide-protein interactions.

α-Cobratoxin is the main neurotoxin in the cobra Naja kaouthia venom; it binds efficiently and selectively with neuronal α7 and muscle type nicotinic acetylcholine receptor and can be used for specific labeling and visualization of these receptors in organs and tissues. For these applications we have prepared conjugates of α-cobratoxin with CdSe quantum dots which have many benefits as compared to organic fluorescent labels. To prepare the conjugate, CdSe quantum dots with ZnS shell were functionalized using a tripeptide glutathione and coupled to toxin using water soluble carbodiimide. The conjugate was purified by gel-filtration chromatography and tested for biological activity. It was found that conjugate preserved the capacity to interact with both neuronal α7 and muscle type nicotinic acetylcholine receptor. Its cytotoxicity to mammalian cells was not higher than that of functionalized quantum dots.

Arginine-containing peptides R3, R8, and R16 were obtained by solid-phase peptide synthesis, and their binding to nicotinic acetylcholine receptors (nAChRs) of muscle and neuronal (α7) types was studied by competitive radioligand assay with the use of 125I-α-bungarotoxin. The resulting peptides exhibited a significantly greater binding activity with respect to the muscle-type nAChRs than to the α7 receptor. Thus, we have discovered a new class of nAChR ligands. The affinity of the synthesized oligoarginines for nAChR depended on the number of amino acid residues in the chain. The highest affinity was exhibited by the R16 peptide, which contained 16 arginine residues.

Excitatory α7 neuronal nicotinic receptors (nAChR) are widely expressed in the central and peripheral nervous and immune systems and are important for learning, memory, and immune response regulation. Specific α7 nAChR ligands, including positive allosteric modulators are promising to treat cognitive disorders, inflammatory processes, and pain. One of them, PNU-120596, highly increased the neuron response to α7 agonists and retarded desensitization, showing selectivity for α7 as compared to heteromeric nAChRs, but was not examined at the inhibitory ligand-gated channels. We studied PNU-120596 action on anion-conducting channels using voltage-clamp techniques: it slightly potentiated the response of human glycine receptors expressed in PC12 cells, of rat GABAA receptors in cerebellar Purkinje cells and mouse GABAA Rs heterologously expressed in Xenopus oocytes. On the contrary, PNU-120596 exerted an inhibitory effect on the receptors mediating anion currents in Lymnaea stagnalis neurons: two nAChR subtypes, GABA and glutamate receptors. Acceleration of the current decay, contrary to slowing down desensitization in mammalian α7 nAChR, was observed in L. stagnalis neurons predominantly expressing one of the two nAChR subtypes. Thus, PNU-120596 effect on these anion-selective nAChRs was just opposite to the action on the mammalian cation-selective α7 nAChRs. A comparison of PNU-120596 molecule docked to the models of transmembrane domains of the human α7 AChR and two subunits of L. stagnalis nAChR demonstrated some differences in contacts with the amino acid residues important for PNU-120596 action on the α7 nAChR. Thus, our results show that PNU-120596 action depends on a particular subtype of these Cys-loop receptors.

The article discusses the legal regulation of interrelated information on circadian genes and intellectual property items within the transition of the Russian Federation to the digital economy. We find out that the legal regime of copyright items will be the most appropriate for the introduction of circadian gene research findings into the economy of the Russian Federation. The relevance of the issue under research is connected to the essential improvement of the legislation on the regulation of genomic research set out in the national program “Digital Economy of the Russian Federation.” The purpose of the research is to outline the main directions of legislation improvement that determine forms and methods of connecting the information on circadian genes and intellectual property items. The main approaches of the research are interdisciplinary, systemic dialectical. These approaches make it possible to investigate the relation between the legal regulation of information circulation and intellectual property in its entirety to solve the problems of the introduction of genomic research findings within the implementation of the national program “Digital Economy.” Findings: the paper analyzed the legal regulation of genomic research and discovers the peculiarities of the relationship between circadian gene research findings and intellectual property. We assessed the applicability of some intellectual property items in the research information circulation and introduction of the genomic research findings into the economy. We find out that the legal regime of copyright items will be the most appropriate for the introduction of the genomic research findings into the economy. On the one hand, such a legal regime assists the introduction of information, and on the other hand, it allows classifying the information obtained as databases. This article is of practical value for multidisciplinary specialists, including geneticists, biologists, lawyers and economists who deal with the genomic research findings in their professional activity. Besides, the article is of interest to lawmakers.

The proteins of the Ly6 family have a three-finger folding as snake venom α-neurotoxins, targeting nicotinic acetylcholine receptors (nAChRs), and some of them, like mammalian secreted Ly6/uPAR protein (SLURP1) and membrane-attached Ly-6/neurotoxin (Lynx1), also interact with distinct nAChR subtypes. We believed that synthetic fragments of these endogenous proteins might open new ways for drug design because nAChRs are well-known targets for developing analgesics and drugs against neurodegenerative diseases. Since interaction with nAChRs was earlier shown for synthetic fragments of the α-neurotoxin central loop II, we synthesized a 15-membered fragment of human Lynx1, its form with two Cys residues added at the N- and C-termini and forming a disulfide, as well as similar forms of human SLURP1, SLURP2, and of Drosophila sleepless protein (SSS). The IC50 values measured in competition with radioiodinated α-bungarotoxin for binding to the membrane-bound Torpedo californica nAChR were 4.9 and 7.4 µM for Lynx1 and SSS fragments, but over 300 µM for SLURP1 or SLURP2 fragments. The affinity of these compounds for the α7 nAChR in the rat pituitary tumor-derived cell line GH4C1 was different: 13.1 and 147 µM for SSS and Lynx1 fragments, respectively. In competition for the ligand-binding domain of the α9 nAChR subunit, SSS and Lynx1 fragments had IC50 values of about 40 µM, which correlates with the value found for the latter with the rat α9α10 nAChR expressed in the Xenopus oocytes. Thus, the activity of these synthetic peptides against muscle-type and α9α10 nAChRs indicates that they may be useful in design of novel myorelaxants and analgesics.

Four dimeric disintegrins were isolated from the venom of the steppe viper V. ursinii using liquid chromatography. Disintegrins prevented adhesion of MCF7 cells to fibronectin, which indicates their interaction with integrin receptors of the αVβ1 type. According to mass spectrometry data, the molar masses of disintegrins are about 14 kDa. The method of peptide mapping established the structure of a new heterodimeric disintegrin weighing 13 995.5 Da and shows that it belongs to the class of RGD/KGD-containing disintegrins.

The chapter is aimed at comprehensive discovery of the basic legal tools to improve the quality of corporate governance from the standpoint of efficient revealing, preventing and shooting negative implications of internal corporate disputes. The subject of the study, in particular, is regulatory and non-regulatory enactments in this area. Within the study we employ basic approaches that allow to reveal the conditions ensuring efficient corporate governance, i.e., dialectical, historical, systemic, formal-logic, and comparative-law ones. Therewith, the main focus is on the application of system theory developments in terms of the methodological techniques to describe any system object. Regarding the disputes between participants of the corporation, we substantiate the need of creating conditions for the highest account of opinions of all the participants in the development of collective will, as well as for restraint of major participants from potential abuses (through accumulative voting mechanism, implementing “two keys” principle, etc.). Special attention is paid to the issues of procedure and content of interest-collision transactions made by economic societies. The authors point out definite guidelines to improve legislation in anti-conflict aspect (forms of holding general meetings of participants, exclusive and non-exclusive competence of governing bodies, the content of acts coordinating interested-party transactions, etc.).

The article is devoted to the formation and development of the main lexical and grammatical and communicative competences in foreign (Spanish) language and presents a tutorial created at the Department of Spanish Language of MGIMO of the University of the Ministry of Foreign Affairs of Russia "Collection of vocabulary and grammatical exercises. Levels of А1-А2 "Authors Associate Professor E. V. Kryukova and Associate Professor Savchuk E. A. The article analyses the methods of working out and fixing certain grammatical and lexical phenomena, which form the basis of deeper mastery of the language at the professional level in students of 1-2 courses of higher education institutions and everyone wishing to learn the language from scratch.

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.

It is not the first year that the information space has been marked by trends in the revision of evaluations of the events of the Great Patriotic War. Student youth are actively and rapidly developing, adapting to the new social realities. That is why the issues of preserving historical memory and developing the historical consciousness of contemporary young people have become so relevant. The present work is based on the analysis of the survey results of the 1st and 2nd-year students conducted at the State University of Management (SUM, Moscow, Russia), and is a continuation of the research devoted to the evaluation of the end results of the Great Patriotic War in the perception of University students. An attempt was made to determine the level of students’ knowledge about the main facts of the Great Patriotic War. Within the framework of this study, the results of similar works by domestic and foreign authors were considered. As a rule, in Russia, the problem of awareness of the importance of the Great Patriotic War is emphasized in terms of its results, including the perception of these issues by student youth. At the same time, several foreign authors put forward the issue of reevaluating the results of the Second World War and make it with clear politicization of the proposed conclusions, primarily, in determining the historical responsibility for war unleashing. The authors of the present study propose to strengthen the role of archival documents, memoirs, chronicles, and testimonies of direct participants and victims of the wartime events in military-historical education, which should not allow distorting the historical feat of the USSR and its decisive contribution to the defeat of Nazi Germany.