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RNA stability MPRA (3 replicates)

The article considers social hygienic characteristics of participants in warfare underwent treatment and rehabilitation in specialized medical organization. It is established that patients of neurological profile and with diseases of cardiovascular system predominated in the studied contingent. The high need for medical rehabilitation was determined according results of examination of participants in warfare by multidisciplinary rehabilitation team. The necessity of observance staging and continuity in carrying out rehabilitation measures at all levels is emphasized.Представлен анализ социально-гигиенических особенностей участников боевых действий, проходивших лечение и реабилитацию в условиях специализированной медицинской организации. Установлено, что среди исследуемого контингента преобладают пациенты неврологического профиля и пациенты с заболеваниями сердечно-сосудистой системы. По результатам осмотра участников боевых действий выявлена высокая потребность в мероприятиях по медицинской реабилитации мультидисциплинарной реабилитационной командой. Отмечена необходимость соблюдения этапности и непрерывности при проведении реабилитационных мероприятий на всех уровнях.

The article presents the age-sex structure of people who have suffered severe traumatic brain injury on the example of a municipal medical organization providing medical care and medical rehabilitation in outpatient settings. The high prevalence of this type of injury among males of working age has been established. The duration of temporary disability and the timing of referral of this category of people for medical and social examination are reflected. There is a high level of disability among people who have suffered severe traumatic brain injury, and in most cases they are assigned more severe first and second disability groups. The article reflects the personnel problems of a municipal medical organization providing outpatient medical care in the formation of a multidisciplinary rehabilitation team, which require their resolution at the regional level.

This descriptive-normative study assessed the graduate school professors’ level of performance along the various dimensions of instruction. The respondents of this study were the Graduate studies professors and students enrolled in Mindanao State University (Main) Marawi, Lanao del Sur, with a total of 122 respondents using convenient sampling techniques. The study utilized a modified questionnaire. The data were treated using weighted mean ranking, and frequency count. The study revealed that: the graduate studies professors always perform the various dimension of instruction along comprehensive knowledge of the teaching field; deontology and availability for teacher-student communication; presentation skills, passion for teaching; class preparation and management; student examination; quality of teaching materials; moderate in research and scientific productivity; administrative skills; and reputation. The researchers concluded that the graduate studies professors possess the essential knowledge and understanding in performing tasks along the various dimensions of instruction. The proposed Faculty Development Program when implemented can effectively improve the level of performance of the graduate studies professors along areas that is found moderate.

RNA modifications are a common occurrence across all domains of life. Several chemical modifications, including N

The current opioid epidemic has dramatically increased the number of children who are prenatally exposed to opioids, including oxycodone. A number of social and cognitive abnormalities have been documented in these children as they reach young adulthood. However, little is known about the mechanisms underlying developmental effects of prenatal opioid exposure. Microglia, the resident immune cells of the brain, respond to acute opioid exposure in adulthood. Moreover, microglia are known to sculpt neural circuits during healthy development. Indeed, we recently found that microglial phagocytosis of dopamine D1 receptors (D1R) in the nucleus accumbens (NAc) is required for the natural developmental decline in NAc-D1R that occurs between adolescence and adulthood in rats. This microglial pruning occurs only in males, and is required for the normal developmental trajectory of social play behavior. However, virtually nothing is known as to whether this developmental program is altered by prenatal exposure to opioids. Here, we show in rats that maternal oxycodone self-administration during pregnancy leads to reduced adolescent microglial phagocytosis of D1R and subsequently higher D1R density within the NAc in adult male, but not female, offspring. Finally, we show that prenatal opioid exposure abolishes the extinction of oxycodone-conditioned place preference in these male offspring. This work demonstrates for the first time that microglia play a key role in translating prenatal opioid exposure to long-term changes in neural systems and behavior.HighlightsPrenatal opioid exposure decreases offspring viability and body weight in males and femalesPrenatal opioid exposure decreases microglial phagocytosis of D1R in the nucleus accumbens in males onlyPrenatal opioid exposure increases nucleus accumbens dopamine D1 receptor expression in males but not femalesAdult males fail to extinguish oxycodone-conditioned place preference following prenatal oxycodone exposure

Background. Myopia is the most common clinical refractive error of the eye. Only in Russia, there are about 15 million myopic people. Currently, in addition to traditional correction (glasses, soft contact lenses), keratorefractive surgery actively develops; however, due to the initial parameters of the cornea or the magnitude of the refractive error, it may be contraindicated to the patient. Nowadays an alternative to these correction methods for young patients with refractive errors of high and ultra-high degrees is the implantation of a phakic intraocular lens.The aim. To evaluate the efficiency of refractive errors correction using phakic IOL implantation.Materials and methods. We carried out a retrospective analysis of outpatient records of 56 patients who received surgical treatment for myopia and complex myopic astigmatism at the Orenburg branch of the S. Fyodorov Eye Microsurgery Federal State Institution in the period from 2019 to 2020 (110 eyes), all patients underwent implantation of a phakic intraocular lens IPCL V2.0, IPCL V2.0 TORIC. Patients were examined before surgery and on the first day after surgery. In addition to standard, special clinical and functional examination methods were used: optical biometry on the IOL-Master 700, determination of the density of endothelial cells using an endothelial microscope, examination of the fundus under cycloplegia; if necessary, peripheral laser coagulation of the retina was performed before calculating phakic IOLs.Results. All operations and the early postoperative period went without complications. The target BCVA (0.75–1.0) was achieved in 90 (81.8 %) eyes. All patients were satisfied with the treatment results.Conclusion. Implantation of IPCL V2.0 and IPCL V2.0 TORIC phakic IOLs is an effective method for correcting refractive errors, regardless of the degree of myopia and the presence of astigmatism.

The 3’ terminal oligo-uridylation, a post-transcriptional mRNA modification, is conserved among eukaryotes and drives mRNA degradation, thereby affecting several key biological processes such as animal development and viral infection. Our TAIL-seq experiment of mouse liver mRNA collected from six zeitgeber times reveals transcripts with rhythmic poly(A) tail lengths and demonstrates that overall 3’ terminal uridylation frequencies at mRNA poly(A) tail very-ends undergo rhythmic change. Consistently, major terminal uridylyl transferases, TUT4 and TUT7, have cycling protein expression in mouse liver corresponding to 3’ terminal uridylation rhythms, indicating that the cycling expression of TUTases correlates with the rhythmic pattern of uridylation. Furthermore, the double knockdown of TUT4 and TUT7 in U2OS cells lengthens the circadian period and decreases the rhythmic amplitude of clock gene expression. Our work thoroughly profiles the dynamic changes in poly(A) tail lengths and terminal modifications and uncovers uridylation as a post-transcriptional modulator in the mammalian circadian clock.

Now crushers are one of the most common types of crushing equipment using the principle of a mechanical method of material destruction (for example, rollers, jaws, cone crushers, etc.). To provide effective parameters of the crusher, it is necessary to take into account the correlation between the physical and mechanical characteristics of the material (sizes, shapes, strengths, fragility, uniformity, etc.) and the energy parameters of the crusher (operation and power) at the design stage. The existing theories describing the mentioned dependence and relying on different classical hypotheses allow obtaining a very approximate (inaccurate) result. Consequently, it is necessary to develop a detailed theory of crushing capable of an accurate description of the mechanical process of material destructions by working members of the crushers. Thus, the authors have developed the crushing theory as an original solution of a complex constructively nonlinear engineering and technical problem on the static contact of a spherical model of a comminuted brittle substance with absolutely rigid convex-concave surfaces of cylindrical rolls designed for coarse and medium grinding. The theory is based on the classical assumptions of the mechanics of an elastically deformable continuous medium, the fundamental analytical dependences of Hertz-Shtaerman and the Kirpichev-Kick volumetric energy hypothesis. During the quantitative assessment of the bearing capacity of the ball, we used the well-known physical and mathematical problem of Weber on the stress state of a sphere loaded by two equal forces applied at the poles, and the Kulon-Mor’s strength criterion, which describes the process of destruction of a wide class of brittle homogeneous materials. The developed theory of fragmentation has been brought to the design formulas and illustrated with a typical numerical example.

The problems of using two-beam Laser Locators (LL) on Unmanned Vehicles (UV) are analyzed. The article discusses the solution to the problem of automatic assessment of the possibility of collision of a UV with other traffic participants based on information generated by the LL. LL performs controlled scanning of the road surface at a given distance from the vehicle. To generate the error signal in the tilt angle control loop, a special filtering of the correction sequence is applied. Such filtering eliminates numerous outliers and forms a sample of correction values that do not lead to abrupt changes in the road sensing range. The modeling of the system is performed, the adequacy of which is due to the results of the conducted field experiments with a real LL. It is shown that the threat of collision arises if the vehicle speed is in a certain (dangerous) interval, the boundaries of which are functions of the following arguments: – the angle between the tangents to the trajectories of the UV and the vehicle during the LL measurements “angle-angle-range”; – distances between the UV and the vehicle at the same time interval. Tasks solved: – estimates of the angle and distances between the UV and the vehicle based on the current LL measurements “angle-angle-range”; – determination of the boundaries of the dangerous range of vehicle speeds at known UV speeds and dimensions of the UV and vehicle; – estimation of the vehicle speed according to LL measurements “angle-angle-range”. Simulation methods were used to determine the accuracy of estimates of the boundaries of the vehicle speeds dangerous range, which made it possible to create an algorithm for warning about a possible collision.

Objective: study of psychoemotional-volitional sphere and endothelium-dependent factors of cardiovascular risk, the level of performance and recovery time in athletes before and after a 2-month intake of a specialized athlete’s nutrition product (SANP) honey bar-candy “Gold F25 ApiSpeis Light”.Materials and methods: the main group of 58 athletes (under the age of 18) used SANP for 2 months. Control group-1 included 32 schoolchildren and students, not athletes, to assess the age limits of endothelium-dependent vasodilation, blood composition and the presence of risk factors for atherosclerosis in young athletes. The control group-2 included 30 young athletes under 18 years old without the use of SANP to compare the indicators in the main group before and after taking the honey bar. The psycho-emotional sphere was studied using the Spielberger-Hanin scale of anxiety and WAM testing: Well-being, Activity and Mood. In addition, the maximum achieved load, maximum oxygen consumption, time to reach the threshold of anaerobic metabolism, systolic blood pressure, heart rate, neurovegetative stress index and recovery time after exercise were determined. Also, tests with reactive hyperemia (TRH) and hyperventilation (TGV) on the brachial artery were performed to assess endothelium-dependent vasodilation and vasoconstriction, conjunctival biomicroscopy on a slit lamp with calibrometry of arterioles and venules, general and biochemical blood tests.Results: the normalization of situational anxiety, psychoemotional stress and hyperfunction of the sympathoadrenal system was established. There was a decrease in the levels of cortisol, neurovegetative stress index, improvement of well-being, activity and mood against the background of elimination of endothelial dysfunction, improved performance and reduced recovery time after work. The analysis of multiple canonical correlations revealed a close relationship between the psychoemotional state, endothelial dysfunction and microcirculation spasm (R = 0.86; p < 0.0001).Conclusion: it has been proven that a combination of increased situational anxiety, neurovegetative overexertion, hyperfunction of the sympathoadrenal system and endothelial dysfunction can form a spastic type of peripheral circulation and provoke the onset of arterial hypertension. It was found that the course intake of honey ingot has anti-stress, antioxidant, erythropoietic, vasodilating and antispastic effects, improves performance and recovery after stress. Ingot “Gold F25 ApiSpeis Light” is included in the FMBA Formulary as a specialized product for the nutrition of young athletes of the Russian national teams.

Small, compact genomes confer a selective advantage to viruses, yet human cytomegalovirus (HCMV) expresses the long non-coding RNAs (lncRNAs); RNA1.2, RNA2.7, RNA4.9, and RNA5.0. Little is known about the function of these lncRNAs in the virus life cycle. Here, we dissected the functional and molecular landscape of HCMV lncRNAs. We found that HCMV lncRNAs occupy ~ 30% and 50–60% of total and poly(A)+viral transcriptome, respectively, throughout virus life cycle. RNA1.2, RNA2.7, and RNA4.9, the three abundantly expressed lncRNAs, appear to be essential in all infection states. Among these three lncRNAs, depletion of RNA2.7 and RNA4.9 results in the greatest defect in maintaining latent reservoir and promoting lytic replication, respectively. Moreover, we delineated the global post-transcriptional nature of HCMV lncRNAs by nanopore direct RNA sequencing and interactome analysis. We revealed that the lncRNAs are modified with N6-methyladenosine (m6A) and interact with m6A readers in all infection states. In-depth analysis demonstrated that m6A machineries stabilize HCMV lncRNAs, which could account for the overwhelming abundance of viral lncRNAs. Our study lays the groundwork for understanding the viral lncRNA–mediated regulation of host-virus interaction throughout the HCMV life cycle.

The work is devoted to assessing the effect of thioctic acid on the main laboratory parameters of carbohydrate metabolism (blood glucose, C-peptide and insulin levels, glycated hemoglobin) in diabetes mellitus against the background of glucose-lowering therapy with metformin hydrochloride. The studies were conducted with the participation of 32 volunteers aged 52 to 63 years, 26 of whom type II diabetes mellitus proceeded with III-degree obesity. At the time of the study, all patients were taking metformin hydrochloride (MH) as a hypoglycemic agent. The experiment was carried out for 3 months. All study participants were divided into groups: the first group - the control group, who took only MG 850 mg once a day for; the second group, patients with normal body weight, who took metformin hydrochloride 850 mg and thioctic acid (TA) 600 mg per day; the third group - obese patients receiving the test compound at the same dosage. After 3 months of treatment, all patients underwent biochemical blood tests for the following parameters: blood glucose, glycated hemoglobin, C-peptide and insulin levels. The results obtained indicate that thioctic acid contributed to a more pronounced decrease in carbohydrate metabolism in comparison with the group of patients receiving only MH as a hypoglycemic agent. It was noted that the normalization of the studied parameters was expressed in the group of patients with normal body weight. Thus, the additional introduction of thioctic acid into the treatment regimen for patients with type II diabetes mellitus contributes to a more effective decrease in carbohydrate metabolism and compensation of the disease in comparison with standard therapy.

L1 retrotransposons can pose a threat to genome integrity. The host has evolved to restrict L1 replication. However, mechanisms underlying L1 propagation out of the host surveillance remains unclear. Here, we propose an evolutionary survival strategy of L1, which exploits RNA m6A modification. We discover that m6A ‘writer’ METTL3 facilitates L1 retrotransposition, whereas m6A ‘eraser’ ALKBH5 suppresses it. The essential m6A cluster that is located on L1 5′ UTR serves as a docking site for eukaryotic initiation factor 3 (eIF3), enhances translational efficiency and promotes the formation of L1 ribonucleoprotein. Furthermore, through the comparative analysis of human- and primate-specific L1 lineages, we find that the most functional m6A motif-containing L1s have been positively selected and became a distinctive feature of evolutionarily young L1s. Thus, our findings demonstrate that L1 retrotransposons hijack the RNA m6A modification system for their successful replication. L1 is a group of active retrotransposons in humans. Here the authors show that m6A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M6A motifs are more enriched in evolutionary young L1s.

The isentropic expansion of shock-compressed porous metals (Cu, W, Nb) are experimentally studied, and the experimental results are used to determine their thermodynamic parameters and electrical conductivity. These results allow us to conclude that some porous metals after shock compression and expansion have a two-phase structure. The presence of an additional phase at the isentropic expansion of these metals significantly changes the character of evaporation and the critical point parameters of the liquid–vapor phase transition that are estimated using experiments on the isentropic expansion of shock-compressed porous metals. In addition, the formation of the two-phase structure explains the large difference between the critical point parameters estimated by different methods for a large group of metals (U, W, V, Co, Mo, Ta, etc.).

In this paper, we analyze the problems of using two-beam laser-ranging systems (often called lidars) on unmanned vehicles to ensure traffic safety and ways to solve them. A cost-effective way to implement a lidar system with controlled (adaptive) scanning of the road surface is proposed. Algorithms for processing information and controlling the inclination angle of laser beams for sounding at a specified distance of the road surface with a complex longitudinal profile are developed. A method for estimating the probability of measuring the speed at which other vehicles are approached in the process of the controlled scanning of the road is proposed and substantiated. The system, the adequacy of which is based on the results of the conducted field experiments with a real lidar, is simulated. Using the modeling methods and statistical data processing, the dependence of the probability of measuring the speed at which objects are approached on the value of this speed and the time spent on measurements is obtained. This dependence indicates the effectiveness of the use of dual-beam guided scanning in unmanned vehicles.

The article analyzes the current regulatory and legal framework for the organization of social services for the elderly and disabled in social service institutions on the territory of the Russian Federation. The article reflects the shortcomings of legal documents regarding the organization of work of such institutions to improve the quality and accessibility of social care for patients receiving social services in social service organizations. The assessment of staffing standards is given.

Objective . To evaluate the hydration in young athletes after a 1-month intake of a specialized isotonic drink for children based on apian and herbal components F25 IsoDrink Light (IsoDrink-L). Materials and methods. From 76 young athletes under 18 years old, of which 70 from the Ugra boarding school of the Olympic reserve of Khanty-Mansiysk (ice hockey, swimming, skiing, biathlon) and 6 highly qualified swimmers from the St. Petersburg Swimming Center Petersburg, the main group included 42 athletes with a monthly course of IsoDrink-L. The control group included 34 people who used college rehydration methods (water and regularly purchased isotonic “X”). Hydration was studied using an impedance assessment of body composition, including the calculation of the total amount of fluid (TAF), as well as intracellular and extracellular fluid (Intracell. fluid and Extracell. fluid), the Extracell. fluid/TAF ratio and a survey of participants about the method of rehydration (water or isotonic). The biochemical composition of blood, specific gravity and color of morning urine before and after a monthly course of isotonics were also evaluated. Results . Bioimpedance measurement of the amount and ratio of body water in combination with an assessment of hematocrit, sodium, potassium, urea and lactate in the blood, as well as the specific gravity and color of morning urine made it possible to detect dehydration in all athletes before taking isotonic. The picture of dehydration in the form of cellular hyperhydration, extracellular hypohydration, hyponatremia, hypovolemia, blood “thickening and acidification” was detailed. A monthly course of isotonic demonstrated its efficiency, dehydration in athletes was eliminated. In the control group, no positive dynamics were noted, which raised the question of the inefficiency of the isotonic “X” and the harmfulness of water, which in 95 % of cases was used as a means of rehydration. The high efficiency of IsoDrink-L and the bioimpedance method was confirmed by the inverse correlation of Extracell. fluid/TAF with the level of hematocrit ( r = –0.71; p < 0.0001) and lactate ( r = –0.56; p < 0.0001), Extracell. fluid with the level of hematocrit ( r = –0.65; p < 0.0001) and lactate ( r = –0.56; p < 0.0001 ). The ratios of Extracell. fluid/TAF with the specific gravity of urine ( r = –0.74; p < 0.0001) and its color ( r = –0.65; p < 0.0001), as well as direct correlations of the Intracellular fluid with the specific gravity of urine ( r = 0.79; p < 0.0001) and its color ( r = 0.87; p < 0.0001). Conclusion . Uncontrolled hydration, especially with water, does not allow maintaining a balance of sodium and fluid in young athletes, as a result of which there is intracellular hyperhydration, extracellular hypohydration, hyponatremia, polycythemic hypovolemia, worsening of blood rheology, its thickening and acidification. Up to 95 % of young athletes perform rehydration with water, not suspecting that this only enhances dehydration. Up to 5 % of highly qualified young athletes use isotonics, not knowing if they are effective. Isotonic F25 IsoDrink Light entered the FMBA Formula as a specialized isotonic drink for young athletes of the Russian national teams.

Aim of the research. To prove the effectiveness of using isotonic honey drink “Gold F25 IsoDrink Light” (IsoDrink-L) based on the study of the hydration process and endothelial function in young athletes. Materials and methods. A randomized controlled study was performed in young athletes under the age of 18 years. Athletes of the main group (n = 40) consumed IsoDrink-L for a month; athletes of the control group (n = 34) consumed water and isotonic drink “X”. A bioimpedance-based device was used to determine the total amount of water, the absolute and relative proportions of intra- and extracellular water, as well as the ratio of extracellular water to the total amount of water. Hematocrit, specific gravity and color of morning urine, samples with reactive hyperemia and hyperventilation in the brachial artery, including the determination of the endothelial sensitivity index were assessed. Results. All athletes had dehydration in the form of extracellular dehydration, cellular hyperhydration, “blood thickening”, hyponatremia, increased specific gravity and urine color, as well as endothelial dysfunction. All symptoms disappeared after using IsoDrink-L for 1 month. No dynamics was observed in the control group, where 95 % of the athletes took water and 5 % – isotonic drink “X”. ROC analysis showed that the endothelial sensitivity index with a sensitivity of 95.8 % and a specificity of 99.4 % detects endothelial dysfunction. The canonical correlation coefficient between the set of hydration-dependent and endothelium-dependent signs was R = 0.71 (p < 0.0001). We established the danger of uncontrolled water consumption for rehydration in young athletes, as well as the high efficiency of isotonic honey drink and the evidence for its use for the correction of dehydration and endothelial dysfunction. A low awareness of athletes, doctors and coaches about the importance of using effective methods of rehydration in children’s sports was revealed. Conclusion. It was found that water imbalance in young athletes directly or indirectly contributes to the development of endothelial dysfunction, thereby increasing cardiovascular risk. Original approaches to the development of honey isotonic drink for young athletes with proven hydrating and endothelium-protective properties are proposed.

We propose an algorithm of a dynamical model for the search-detection-recognition of objects by the onboard thermal-imaging systems operating in the wavelength ranges from 3 to 5 µm and 8 to 12 µm. We provide the main simulation results under the action with respect to ground objects, analyzing the influence of the main agents on the probabilistic-range characteristics of the scene–optical route–thermal-imaging channel–person system under the assumption that the image quality varies within the search because the carrier approaches the object.

Background Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. Objectives To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. Search strategy MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. Selection criteria We included systematic reviews of association of individual variables with stillbirth without language restriction. Data collection and analysis Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. Results The search identified 1198 citations. Sixty-nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and pre-existing hypertension. Conclusion We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP-A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias. Tweetable abstract Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP-A, PLGF and Uterine artery Doppler.

The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate ‘cluster assistance’ in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.

Results of comparative investigations of the pulse-switching characteristics of devices (kivotrons) based on the open discharge in molecular gases (oxygen and nitrogen) and their mixtures with helium are presented. The choice of oxygen and nitrogen is determined by the fact that the coefficients of electron emission under impact of their heavy particles are much higher as compared to that for helium. It is established that this factor, as well as the case of predominantly photoelectron emission mechanism operative in helium, makes the creation of fast switches possible. These switches are advantageous in posing lower requirements on the purity of a working gas medium.

Objective: to assess with exercise tests the endothelial dysfunction (ED) and performance before and after the treatment with specialized athlete’s nutrition product (SANP) with apian and herbal components. Materials and methods: 88 athletes aged 16-18 we tested. The main group included 58 athletes, who took SANP (candy bar «Gold F25 ApiSpeis Light») for 2 months. The control group-1 included 32 schoolchildren and students, non-athletes, with normal endothelium-dependent vasodilatation function of the brachial artery (EDVD BA) at the peak of the reactive hyperemia test (RHT). Control group-2, 30 athletes who did not take SANP, was formed for the comparison with the main group after taking SANP. For all individuals, we evaluated the level of EDVD, endothelium-dependent vasoconstriction (EDVC BA) at the peak of the hyperventilation test (HVT), the coefficients (C) of the endothelial sensitivity to shear stress and the blood flow velocity (Vps) of the BA at the peak of the RHT and HVT, the endothelial sensitivity index (ESI), and the maximum load (Wmax), the anaerobic threshold time (ATT). We also did general and biochemical blood tests. Results: the earliest manifestation of endothelial dysfunction is a decrease in sensitivity to shear stress during RHT and HVT resulting from endotheliocyte overstrain which can be assessed with ESI (sensitivity 80.9%, specificity 99.4 The EDVD diagnostic significance was 5.6 times lower than that of EIS, while 10.5% of athletes with over 10% EDVD actually had ED, with a predominant vasospasm and high cardiovascular risk. After the course of SANP in the main group, EDVD increased by 70%, EDVC decreased by 2.2 times, and the ESI increased by 2.3 times, against the background of improved performance. Total cholesterol decreased by 13%, triglycerides by 17%, cortisol by 14%, lactate by 25%. Red blood cell and mineral levels increased. A correlation was found between an increase in ATT a decrease in cortisol (r=-0.53; p

After describing characteristics of auxiliary government agencies, the author compares auxiliary government agencies with the institution of plenipotentiary representatives of the President of Russia in federal districts and defines the concept of “auxiliary government agencies “ (auxiliary bodies of state power). The paper demonstrates that the concept of auxiliary bodies in the Russian legal doctrine originated more than 100 years ago. It has continued in the works of prominent scholars of modern times. The author relies on the regulatory framework in his assumption claiming the primacy of the Presidential Administration of Russia over the institution of plenipotentiaries in federal districts. It is concluded that the institution of plenipotentiary representatives in federal districts, or more precisely — administrative officers of plenipotentiary representatives of the President of Russia in federal districts, not only substantially fit into the concept under consideration, but also have a genuine constitutional and legal character, since the establishment of this institution is permitted by the Constitution of the Russian Federation (reference in Chapter 4).

RNA tailing, or the addition of non-templated nucleotides to the 3' end of RNA, is the most frequent and conserved type of RNA modification. The addition of tails and their composition reflect RNA maturation stages and have important roles in determining the fate of the modified RNAs. Apart from canonical poly(A) polymerases, which add poly(A) tails to mRNAs in a transcription-coupled manner, a family of terminal nucleotidyltransferases (TENTs), including terminal uridylyltransferases (TUTs), modify RNAs post-transcriptionally to control RNA stability and activity. The human genome encodes 11 different TENTs with distinct substrate specificity, intracellular localization and tissue distribution. In this Review, we discuss recent advances in our understanding of non-canonical RNA tails, with a focus on the functions of human TENTs, which include uridylation, mixed tailing and post-transcriptional polyadenylation of mRNAs, microRNAs and other types of non-coding RNA.

TENT4 enzymes generate 'mixed tails' of diverse nucleotides at 3' ends of RNAs via nontemplated nucleotide addition to protect messenger RNAs from deadenylation. Here we discover extensive mixed tailing in transcripts of hepatitis B virus (HBV) and human cytomegalovirus (HCMV), generated via a similar mechanism exploiting the TENT4-ZCCHC14 complex. TAIL-seq on HBV and HCMV RNAs revealed that TENT4A and TENT4B are responsible for mixed tailing and protection of viral poly(A) tails. We find that the HBV post-transcriptional regulatory element (PRE), specifically the CNGGN-type pentaloop, is critical for TENT4-dependent regulation. HCMV uses a similar pentaloop, an interesting example of convergent evolution. This pentaloop is recognized by the sterile alpha motif domain-containing ZCCHC14 protein, which in turn recruits TENT4. Overall, our study reveals the mechanism of action of PRE, which has been widely used to enhance gene expression, and identifies the TENT4-ZCCHC14 complex as a potential target for antiviral therapeutics.

In this article, the author concludes that the institution of plenipotentiaries of the President in the federal districts is a legal tool of the President of Russia, which was created to facilitate the exercise of his powers in the federal districts, which can and should be applied in the process of monitoring the implementation of the Development Strategy Implementation Plan mineral resource base of Russia until 2035, even despite the fact that authorized representatives in federal districts are not indicated in the text of the Strategy as part of controlling persons. The territorial bodies of the Federal Subsoil Use Agency (Rosnedra), established at the level of federal districts, should be the conductors of this control: the provisions on the establishment of territorial bodies of the Rosnedra at the level of federal districts contain regulatory provisions that allow direct interaction with the Presidential plenipotentiary representatives in federal districts. In addition, Presidential Decree No. 849 of May 13, 2000, which established federal districts and plenipotentiaries, directly indicates the possibility of plenipotentiaries to monitor the implementation of orders of the Government of Russia — the Strategy was approved in the form of a government order.

The severe acute respiratory coronavirus 2 (SARS-CoV-2), which emerged in December 2019 in Wuhan, China, has spread rapidly to over a dozen countries. Especially, the spike of case numbers in South Korea sparks pandemic worries. This virus is reported to spread mainly through person-to-person contact via respiratory droplets generated by coughing and sneezing, or possibly through surface contaminated by people coughing or sneezing on them. More critically, there have been reports about the possibility of this virus to transmit even before a virus-carrying person to show symptoms. Therefore, a low-cost, easy-access protocol for early detection of this virus is desperately needed. Here, we have established a real-time reverse-transcription PCR (rtPCR)-based assay protocol composed of easy specimen self-collection from a subject via pharyngeal swab, Trizol-based RNA purification, and SYBR Green-based rtPCR. This protocol shows an accuracy and sensitivity limit of 1-10 virus particles as we tested with a known lentivirus. The cost for each sample is estimated to be less than 15 US dollars. Overall time it takes for an entire protocol is estimated to be less than 4 hours. We propose a cost-effective, quick-and-easy method for early detection of SARS-CoV-2 at any conventional Biosafety Level II laboratories that are equipped with a rtPCR machine. Our newly developed protocol should be helpful for a first-hand screening of the asymptomatic virus-carriers for further prevention of transmission and early intervention and treatment for the rapidly propagating virus.

Protein expression levels are regulated through both translation and degradation mechanisms. Levels of degradation intermediates, that is, partially degraded proteins, cannot be distinguished from those of intact proteins by global proteomics analysis, which quantify total protein abundance levels. This study aimed to develop a tool for assessing the aspects of degradation regulation via proteolytic processing through a new multiplexed N-terminomics method involving selective isobaric labeling of protein N-termini and immunoaffinity capture of the labeled N-terminal peptides. Our method allows for not only identification of proteolytic cleavage sites, but also highly multiplexed quantification of proteolytic processing. We profiled a number of potential cleavage sites by signal peptidase and provided experimental confirmation of predicted cleavage sites of signal peptide. Furthermore, the present method uniquely represents the landscape of proteomic proteolytic processing rate during early embryogenesis in Drosophila melanogaster, revealing the underlying mechanism of stringent decay regulation of zygotically expressed proteins during early stages of embryogenesis.

Quantitative proteomic platforms based on precursor intensity in mass spectrometry (MS1-level) uniquely support in vivo metabolic labeling with superior quantification accuracy but suffer from limi...