Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs

When it is difficult to develop selective ligands within a family of related G-protein-coupled receptors (GPCRs), chemically engineered receptors activated solely by synthetic ligands (RASSLs) are useful alternatives for probing receptor function. In the present work, we explored whether a RASSL of the free fatty acid receptor 2 (FFA2) could be developed on the basis of pharmacological variation between species orthologs. For this, bovine FFA2 was characterized, revealing distinct ligand selectivity compared with human FFA2. Homology modeling and mutational analysis demonstrated a single mutation in human FFA2 of C4.57G resulted in a human FFA2 receptor with ligand selectivity similar to the bovine receptor. This was exploited to generate human FFA2-RASSL by the addition of a second mutation at a known orthosteric ligand interaction site, H6.55Q. The resulting FFA2-RASSL displayed a >100-fold loss of activity to endogenous ligands, while responding to the distinct ligand sorbic acid with pEC(50) values for inhibition of cAMP, 5.83 ± 0.11; Ca(2+) mobilization, 4.63 ± 0.05; ERK phosphorylation, 5.61 ± 0.06; and dynamic mass redistribution, 5.35 ± 0.06. This FFA2-RASSL will be useful in future studies on this receptor and demonstrates that exploitation of pharmacological variation between species orthologs is a powerful method to generate novel chemically engineered GPCRs

Development of мusical thinking in youngerstudents in the process of learningin children's art schools

Introduction. The article highlights the problem of development of musical thinking, conditioned by the needs of practice and priority directions of the state education policy.В статье освещается проблема развития музыкального мышления, обусловленная потребностями практики и приоритетными направлениями государственной образовательной по-литики

Віталітетна структура популяцій деяких видів бур’янів у посівах зернових культур

Features of development of populations of weed species (Cirsium arvense (L.) Scop., Sonchus arvensis L., Melandium album (Mill.) Garke, Setaria glauca (L.) Beauv., Fallopia convolvulus (L.) А. Lоve) in most typical crops in the forest-steppe zone of the Sumy region. It was studied the crop sowings (winter wheat, rye, barley, buckwheat, pea) which was not subjected to the herbicide treatment. Исследованы особенности развития популяций сегетальных видов (Cirsium arvense (L.) Scop., Sonchus arvensis L., Melandium album (Mill.) Garke, Setaria glauca (L.) Beauv., Fallopia convolvulus (L.) А. Lоve) в посевах зерновых культур (пшеницы озимой, ржи, ячменя, гречихи, гороха), которые не подвергались обработке гербицидами в хозяйствах лесостепной зоны на территории Сумской области. Досліджено особливості розвитку популяцій сегетальних видів (Cirsium arvense (L.) Scop., Sonchus arvensis L., Melandium album (Mill.) Garke, Setaria glauca (L.) Beauv., Fallopia convolvulus (L.) А. Lоve) у посівах зернових культур (пшениці озимої, жита, ячменю, гречки, гороху), які не оброблялися гербіцидами у господарствах лісостепової зони на території Сумської області.

PROFESSIONAL SELF-DETERMINATION OF MOSCOW YOUTH: SOCIOLOGICAL ANALYSIS

The article considers the problem of primary professional self-determination of youth. Also it presents the results of a sociological survey aimed at investigating factors influencing professional self-determination among Moscow senior and high school students and at specification the role of the existing career guidance system in Moscow schools in this process. The survey has revealed the role of subjective and objective factors influencing Moscow students' future career choice, as well as the range of problems in the organization of career guidance in Moscow school

PROFESSIONAL SELF-DETERMINATION OF MOSCOW YOUTH: SOCIOLOGICAL ANALYSIS

The article considers the problem of primary professional self-determination of youth. Also it presents the results of a sociological survey aimed at investigating factors influencing professional self-determination among Moscow senior and high school students and at specification the role of the existing career guidance system in Moscow schools in this process. The survey has revealed the role of subjective and objective factors influencing Moscow students' future career choice, as well as the range of problems in the organization of career guidance in Moscow school

Tensile behavior of an austenitic stainless steel subjected to multidirectional forging

The mechanical behavior of a chromium -nickel austenitic stainless steel with submicrocrystalline structures produced by multidirectional forging (MDF) to a total strain of ∼ 4 at temperatures of 700 and 600° C was studied. This processing resulted in the formation of uniform ultrafine grained structure with an average crystallite size of 360 and 300 nm, respectively, and high dislocation density. The tensile tests were carried out in a wide temperature range 20 -650° C. At ambient temperature, the yield stress (YS) comprised 900 MPa and 730 MPa in the samples subjected to MDF at 600 and 700° C, respectively. It should be noted that this strength was achieved along with elongations of 16% and 22% in the samples subjected to MDF at 600 and 700° C. The YS decreased and elongati on-to-failure tends to increase with increasing test temperature and approaching 235 MPa and 51%, respectively, at 650° C. Effect of temperature on mechanical behavior of stainless steel with submicrocrystalline structure is discusse

Optical Monitoring in Elaboration of Metal Matrix Composites by Direct Metal Deposition

AbstractDevelopment of composites with multi-functional properties is a challenging problem that could be solved by laser cladding. The objective of the present work is to demonstrate the advantages of optical monitoring in optimizing deposition of carbide-reinforced metal matrix composites. Multi-wavelength pyrometer and infrared camera are applied to analyse high temperature heat – and mass transfer in the cladding zone. The influence of laser power, laser cladding speed and powder feeding rate on the brightness temperature are studied. The thermal images of the molten pool obtained by infrared camera for different TiC contents in the powder blend are analysed as well as the beads geometry, microstructure and microhardness

Techniques of synergistic effect formation in marketing communications on the aesthetic medicine market

The article analyses the experience of the Russian distribution company of the market of aesthetic medicine in implementing the communication strategy of a new educational product in a turbulent marketing environment. The paper formulates the principles of establishing profitable communication with core audiences, substantiates the choice of marketing communications instruments, as well as the techniques for their combination and the development of advertising material used for achieving synergistic effect from marketing and advertising activities. The authors notice a high value of Integrated marketing communications in the projects of launching new products to the market. The results of the study can be used by marketing specialists to form an effective communication system in small and medium-sized businesses that provides a commercial enterprise with a highly profitable result from advertising campaigns with limited deadlines and budgets

An effect of anti-stress feed additives on broiler productivity and meat quality

The paper presents the study on an impact of feed additives Peak anti-stress and SPAO (SPAO-complex) with different lithium content on meat productivity and meat quality of broiler chickens. The feed additives exert a pronounced metabolic effect, have adaptogen properties and allow forming a mechanism that facilitates compensation of the expenditure of the body, which significantly increases upon stress development. It was established that the average daily gain of the broiler chickens increased by 1.8% and 4.3% on the background of using SPAO-complex and Peak anti-stress, respectively, compared to the broiler chickens that did not receive the feed additives in the daily diet. It was shown that addition of feed additives with lithium into a diet led to an improvement of the indices of broiler meat productivity and meat quality: a level of yield of the carcasses of the 1st category increased up to 56.2–79.1%, high organoleptic indices of meat were ensured, the protein content in white and red chicken meat increased and functional-technological properties of minced meat improved. The use of feed additives ensured profitability of industrial poultry production; the highest indices of profitability were established upon introduction of the feed additive Peak anti-stress into a diet — up to 8.67 rubles per each ruble of expenses. The obtained results of the study should be taken into consideration in the technological processes when raising broiler chickens

Cancel Culture in Constructing National Identity of the Caspian Macro-region Countries (on the Example of Textbooks in Kazakhstan and Turkmenistan)

The process of the formation of independent states on the territories of post-Soviet republics raised the problem of the construction of their national identities. This process was propelled by the rejection of Soviet identity and the cultural legacy of the Soviet era. This rejection necessitated a reinterpretation of the historical past of the nations and a revision of the pantheon of national heroes. To achieve this goal, the mechanism of cancel culture was used, which aimed at rejecting the values of a certain culture and constructing a new worldview. In this research, we are interested in the Caspian macro-region, which is an object of interest both geopolitically and economically not only for the five international actors (Russia, Turkmenistan, Kazakhstan, Iran, Azerbaijan) having access to the water area but also for more distant states (China, Turkey, the USA, and leading European countries) fighting for influence in the Caspian basin. In the Caspian region there is heightened tension, manifested in ethnic conflicts (Armenian-Azerbaijani, Kazakhstan, Iran, etc.), therefore the study of the process of national identity construction in each subject individually and in the whole region is not only a matter of scientific interest but also a strategic task to ensure both Caspian and Russian security. The main purpose of the article is to analyze the mechanisms of constructing a new national identity of the Caspian countries through the cancel culture, reconsidering their experience and historical development. This process can be seen most clearly in the example of changes in the educational systems of the Caspian region countries. To conduct a comparative analysis, we took history and local history textbooks from secondary schools and institutions of higher education in the republics of Kazakhstan and Turkmenistan. This research was limited to the study of textbooks published in the Russian language. The selection was made by random sampling. A series of research projects on the construction of national identity in the post-Soviet space through the mechanism of cancel culture starts with this article presenting the results of the study of two countries in the Caspian Sea region — Kazakhstan and Turkmenistan