Search

Intracellular binding of small-molecule phospho-Ags to the HMBPP receptor complex in infected cells leads to extracellular detection by T cells expressing the Vγ9Vδ2 TCR, a noncanonical method of Ag detection. The butyrophilin proteins BTN2A1 and BTN3A1 are part of the complex; however, their precise roles are unclear. We suspected that BTN2A1 and BTN3A1 form a tetrameric (dimer of dimers) structure, and we wanted to probe the importance of the BTN2A1 homodimer. We analyzed mutations to human BTN2A1, using internal domain or full-length BTN2A1 constructs, expressed in Escherichia coli or human K562 cells, that might disrupt its structure and/or function. Although BTN2A1 is a disulfide-linked homodimer, mutation of cysteine residues C247 and C265 did not affect the ability to stimulate T cell IFN-γ production by ELISA. Two mutations of the juxtamembrane region (at EKE282) failed to impact BTN2A1 function. In contrast, single point mutations (L318G and L325G) near the BTN2A1 B30.2 domain blocked phospho-Ag response. Size exclusion chromatography and nuclear magnetic resonance (NMR) experiments showed that the isolated BTN2A1 B30.2 domain is a homodimer, even in the absence of its extracellular and transmembrane region. [31P]-NMR experiments confirmed that HMBPP binds to BTN3A1 but not BTN2A1, and binding abrogates signals from both phosphorus atoms. Furthermore, the BTN2A1 L325G mutation but not the L318G mutation prevents both homodimerization of BTN2A1 internal domain constructs in size exclusion chromatography (and NMR) experiments and their binding to HMBPP-bound BTN3A1 in isothermal titration calorimetry experiments. Together, these findings support the importance of homodimerization within the BTN2A1 internal domain for phospho-Ag detection.

The paper proposes a contemporary interdisciplinary method to identify consistent patterns within cyclical dynamics of GDP and its macroeconomics determinants in the Russian Federation. This method may contribute to better recognition of the stages of economic cycle and of potential early predicators to recessions and crises. We first identify the trend component of Russian GDP and then apply the spectral data analysis to its cyclical component which reveals its multi-frequency, and non-linear vibrations. These vibrations are then further investigated by transforming time series data on GDP and its determinants into a frequency spectrum series via Fourier transform techniques. Wavelength scanning of selected macroeconomic indicators shows the basic economic cycle of real GDP with duration time of approx. 3.13 years. Other procyclical indicators nevertheless discover asynchronous behavior towards GDP due to the relative autonomy of the sectors standing behind these indicators. Their autonomy lies behind differences in reaction forces (shifts) and periods (lags) to both internal and external shocks. We estimate differentials between the dynamics of GDP and its determinants by evaluating phase deviations of their pairwise harmonic components, mutual pairwise phase shifts, and by comparison of their pairwise cross-spectrum. The one of output is the quantification of time lags between GDP and key macroeconomic indicators of individual economic sectors. This result reveals the complexity of GDP dynamics that sends an aliased rather than a unit signal to economic agents. Our decomposition of this signal into signals from key economic sectors and quantification of phase discrepancies between sectoral signals may contribute to findings in early crisis predicators. We also estimate the depth and velocity of shocks penetrations into both economy as a whole and its particular sectors.

The lower body negative pressure (LBNP) effect has been studied in terms of phase synchronization between spontaneous oscillations of blood pressure (BP) and heart rate (HR). The effect of LBNP (‒30 mmHg) was generated by the Chibis-M complex, which was used for training the cardiovascular system in cosmonauts on-board the International Space Station (ISS) as a countermeasure to the post-flight orthostatic intolerance. According to the measurement procedure protocol, the subjects (seven young men) were in a supine position. It has been shown that LBNP leads to an increase in the strength of phase synchronization between spontaneous BP and HR oscillations in the frequency range of baroreflex waves (about 0.1 Hz).

Strength training remains the most effective way to maintain or increase muscle mass and strength. Strength training is used during rehabilitation after injuries and prolonged hypokinesia, to prevent the development of age-related sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular diseases. Also, strength training is widely used by athletes of various specializations. The effectiveness of strength training varies depending on the individual characteristics, diet, and training program used. In recent years, significant progress has been achieved in understanding the mechanisms of skeletal muscle adaptation in response to strength training. The review addresses the most important mechanisms for increasing muscle mass and strength, which correspond to the current understanding of the problem in the modern literature. We consider the role of neural adaptation, as well as signaling processes that increase the muscle protein synthesis rate, in the development of adaptive changes in response to strength training. Based on the knowledge of these mechanisms, we analyze the key variables of strength training, such as training loads, work volume and movement velocities. The knowledge of the mechanisms that determine the effectiveness of the training process provides a better insight into the most important aspects of strength training.

Changes in the baroreflex control of heart rate were studied in male subjects during their aerobic veloergometric exercises, using the phase synchronization index (PSI) of the mean arterial pressure (MAP) and heart rate (HR) oscillations in the frequency range of baroreflex waves (from 0.06 to 0.12 Hz). The protocol of tests included continuous recordings of blood pressure (by the photocompensation method) and ECG in volunteers (young men), with the load intensity specified individually for each subject in reference to his anaerobic threshold (AT). It has been shown in the test with a stepwise change in the load power, at a relatively moderate load (60% AT) PSI did not change compared with the value at rest, but significantly decreased when the load was increased up to 80% AT. To assess the time of the PSI, which can characterize the dynamics in the baroreflex resetting, changes caused by variations in the load we used the test with sinusoidally varying power (the mean value was 50% AT, the amplitude was 30% AT, and the power modulation period varied from 1000 to 100 s), MAP, HR and PSI values were calculated for successive 4-min intervals with 3-min overlapping. Whereas under this test, the PSI modulation, due to load power variations, almost disappeared as the period decreased from 1000 to 500 s, but the MAP and HR modulation was preserved until the 250-s period. Thus, the phase synchronization of MAP and HR oscillations at frequencies of baroreflex waves decreases during intensive aerobic exercise, and the pattern of its changes due to load variations are characterized by a relatively slow temporal dynamics.

Computational design of high-functioning electrocatalysts is an integral part of catalyst discovery. However, as we approach the limits of performance imposed by scaling relations, finding active c...

The aim of the study was to evaluate the possibility to predict the muscle fiber-type proportion in men of different sports specialization by testing the maximal torque production by knee extensors at different velocities. For this reason the proportion of fast- and slow-twitch muscle fibers (MFs) in m. vastus lateralis of 23 athletes (11 endurance and 12 power athletes), as well the maximal torque production of knee extensors at various angular velocities in isokinetic mode were determined. The group of strength trained athletes significantly exceeded the group of endurance trained athletes in body mass, body mass index, volume of the m. quadriceps femoris, maximum torque production, and specific force at angular velocities 30, 180 and 300 degrees per second. In contrast to cross-sectional area (CSA) of slow-twitch MFs, the average CSA of fast-twitch MFs and the proportion of fast-twitch MFs in the group of power athletes significantly exceeded those in the group of endurance athletes. In the combined group of volunteers (n = 23), the proportion of fast-twitch MFs significantly correlated with the torque production at high angular velocities (r = 0.51 and p = 0.01 at 180 deg/s; r = 0.47 and p = 0.02 at 300 deg/s). We did not find any correlation between these parameters in the separate groups of power and endurance athletes. The results indicate a low accuracy in predicting the proportion of fast-twitch MF in m. vastus lateralis in athletes using the maximal torque production of knee extensors at different angular velocities. Significant correlation between the proportion of fast-twitch MF and maximal torque at high angular velocities in the general group (n = 23) was due to the presence of two significantly different subgroups.

A plethora of membrane proteins are found along the cell surface and on the convoluted labyrinth of membranes surrounding organelles. Since the advent of various structural biology techniques, a sub-population of these proteins has become accessible to investigation at near-atomic resolutions. The predominant bona fide methods for structure solution, X-ray crystallography and cryo-EM, provide high resolution in three-dimensional space at the cost of neglecting protein motions through time. Though structures provide various rigid snapshots, only an amorphous mechanistic understanding can be inferred from interpolations between these different static states. In this review, we discuss various techniques that have been utilized in observing dynamic conformational intermediaries that remain elusive from rigid structures. More specifically we discuss the application of structural techniques such as NMR, cryo-EM and X-ray crystallography in studying protein dynamics along with complementation by conformational trapping by specific binders such as antibodies. We finally showcase the strength of various biophysical techniques including FRET, EPR and computational approaches using a multitude of succinct examples from GPCRs, transporters and ion channels.

The article discusses the features of labor rehabilitation in the conditions of non-profi t organizations as an eff ective form of rehabilitation of people with mental development disorders. The article analyzes the theoretical aspects of the labor rehabilitation process, including the characteristics, tasks and principles of labor rehabilitation. The analysis of the legislative base and statistical data on employment of people with disabilities is presented. The features of work of socially oriented non-profi t organizations with people with mental disorders are considered. Presents the experience of a care Centre for people with autism "Anton near here" (Saint-Petersburg).

The diaphragm is a unique skeletal muscle; it is active throughout the lifetime and, therefore, differs from locomotor muscles in the properties of muscle fibers and the mechanisms of blood supply control. The aim of this review was to survey the structural characteristics of diaphragm muscle tissue, which provide its integral contractile properties; to compare the activity of vascular tone control mechanisms in the diaphragm and locomotor muscles; and to explore their relationship with the regulation of contractile function. The diaphragm differs from the majority of skeletal muscles by a high content of both slow fatigue-resistant muscle fibers of type I and fast fibers of type IIb, which provides endurance and high force-velocity characteristics of the diaphragm. The muscle fibers in the diaphragm are smaller, and the density of capillarization is much higher than in locomotor muscles. Arteries and arterioles that regulate blood supply to the diaphragm capillary bed combine the properties of arteries from muscles composed mainly of oxidative or mainly of glycolytic fibers. Such variety provides blood flow in the diaphragm adequate to its functional load with various patterns of activity. The mechanisms of vasoregulation in the diaphragm can qualitatively differ in the proximal and distal parts of the vascular bed. The functional properties of the proximal arteries can in part be explained by their proximity to the aorta and their small length. The contractile characteristics and blood supply of the diaphragm in various conditions should be considered when conducting respiratory muscle training in sports and rehabilitation medicine.

Lysenko, EA, Popov, DV, Vepkhvadze, TF, Sharova, AP, and Vinogradova, OL. Moderate-intensity strength exercise to exhaustion results in more pronounced signaling changes in skeletal muscles of strength-trained compared with untrained individuals. J Strength Cond Res 34(4): 1103-1112, 2020-The aim of our investigation was to compare the response pattern of signaling proteins and genes regulating protein synthesis and degradation in skeletal muscle after strength exercise sessions performed to volitional fatigue in strength-trained and untrained males. Eight healthy recreationally active males and 8 power-lifting athletes performed 4 sets of unilateral leg presses to exhaustion (65% 1 repetition maximum). Biopsy samples of m. vastus lateralis were obtained before, 1 and 5 hours after cessation of exercise. Phosphorylation of p70S6k, 4EBP1, and ACC increased, whereas phosphorylation of eEF2 and FOXO1 decreased only in the trained group after exercise. Expression of DDIT4, MURF1, and FOXO1 mRNAs increased and expression of MSTN mRNA decreased also only in the trained group after exercise. In conclusion, moderate-intensity strength exercise performed to volitional fatigue changed the phosphorylation status of mTORC1 downstream signaling molecules and markers of ubiquitin-proteasome system activation in trained individuals, suggesting activation of protein synthesis and degradation. In contrast to the trained group, signaling responses in the untrained group were considerably less pronounced. It can be assumed that the slowdown in muscle mass gain as the athletes increase in qualification cannot be associated with a decrease in the sensitivity of systems regulating protein metabolism, but possibly with inadequate intake or assimilation of nutrients necessary for anabolism. Perhaps, the intake of highly digestible protein or protein-carbohydrate dietary supplements could contribute to the increase in muscle mass in strength athletes.

A review of the currently available ideas about the role of gravitational factor in the activity of the sensorimotor and cardiovascular systems, as well as new fundamental problems and questions for space medicine and physiology, is presented. The review presents data on the embryogenesis of animals under conditions of weightlessness, the evolution of the motor and cardiovascular systems and the peculiarities of their functioning under conditions of gravity, as well as in the change of gravitational load. Much attention is paid to the results of unique studies in modeling gravitational unloading on Earth: antiorthostatic hypokinesia, dry immersion and suspension, which made it possible to study the mechanisms of regulation of various body systems under conditions of altered gravity. Terrestrial organisms have learned to function in the gravitational field. Almost all systems of their body are gravitationally dependent. However, the extent and mechanisms of this dependence have long remained unclear. Space flights have opened up the possibility of studying the activity of living systems in the absence of gravity. Among the factors mediating the effect of weightlessness on the motor system, changes in the activity of sensory systems occupy an important place. Under the Earth conditions, the afferent support of motion control systems is polyreceptive: this is vision, and the vestibular apparatus, supporting and muscular afferentations. In zero gravity, the activity of some channels is completely eliminated (support afferentation), others are distorted (vestibular apparatus), and still others are weakened (proprioception). Similar processes occur in the cardiovascular system: with the loss of the pressure gradient caused by gravity, profound changes occur in the structure and functioning of the heart and vessels, both resistive and capacitive. The question of how much the various changes occurring in the cardiovascular system are associated with the disappearance of the gravitationally dependent pressure gradient is still open. It is not possible to solve all the problems of gravitational physiology In space flights. Therefore, various methods have been developed for simulating gravitational unloading on Earth. New data on the mechanisms of changes occurring in the sensorimotor system were obtained by comparing flight data and data obtained in model experiments. The fundamental problem for the gravitational physiology of cardiovascular system is the degree of correspondence of the changes observed in laboratory animals and under model conditions (antiorthostatic hypokinesia, immersion, suspension) with the changes that are recorded in real space flight in humans. This problem is specially discussed in the review. At the same time, in the light of the upcoming interplanetary expeditions, many questions remain unresolved, in particular, the problems of post-flight readaptation of the motor and cardiovascular systems to gravity conditions. This is a fight against loss of strength, endurance, orthostatic instability. The development and improvement of a system for preventing the negative effects of space flight factors is impossible without understanding the mechanisms of development of the observed changes.

The paper analyses data of automated evaluation of syntactical complexity of scholarly texts from four comparable corpora – two of expert texts and two of learner texts – in two subject areas. The research applied two different computer tools – UDPipe parser and AntConc set of programs. The following conclusions were made: – Expert scholarly texts demonstrated high clausal and phrasal complexity, and its level was higher in Business Studies than in Economics. – Clausal complexity in expert texts was much higher than in student texts, while phrasal complexity was at about the same level as, or even slightly lower than that of students. The largest difference was attested for genitive construction with preposition of, which was 1.7 times as frequent in student texts in both subject areas as in expert texts. The results contradict the conclusion of the prior research that with the growth in proficiency clausal complexity decreases, while phrasal complexity grows.

The theory of electrokinetic ion transport in cylindrical channels of a fixed surface charge density is revisited. Attention is focused on impact of the hydrophobic slippage and mobility of adsorbed surface charges. We formulate generalised Onsager relations for a cylinder of an arbitrary radius and then derive exact expressions for the mean electro-osmotic mobility and conductivity. To employ these expressions we perform additional electrostatic calculations, with the special focus on the non-linear electrostatic effects. Our theory provides a simple explanation of a giant enhancement of the electrokinetic mobility and conductivity of hydrophobic nanotubes by highlighting the role of appropriate electrostatic and hydrodynamic length scales and their ratios. We also propose a novel interpretation of zeta potentials of cylindrical channels., Comment: 12 pages, 10 figures

The goal of the present study was to identify the possible disturbances in the synchronization of spontaneous fluctuations in arterial pressure (AP) and heart rate (HR) at the frequency of baroreflex waves (~0.1 Hz) in patients prone to vasovagal fainting. In healthy volunteers and patients diagnosed with vasovagal syncope, AP (photo-compensation method) and ECG were continuously recorded, first in a horizontal position, and then during a passive orthostatic test (60°) lasting for 40 min. According to the results of the test, all patients were divided into two groups: subjects with a positive (development of the presyncopal or syncopal states) and a negative result of the orthostatic test. These groups of patients did not differ from each other and from the control group in terms of baseline AP and HR. The values of the phase synchronization index (PSI) of AP and HR were calculated in the frequency range from 0.02 to 0.8 Hz within 10-min recording intervals in the horizontal position and at the initial stage of orthostasis (starting from the second minute after the transition to the vertical position). Initially, all three groups had a distinct peak at the frequency of ~0.1 Hz in the PSI spectra. In the control group and in patients with a negative orthostatic result, a transition to the state of orthostasis was accompanied by an increase in the PSI in this frequency domain, in contrast to the patients with a positive orthostatic test, in which the PSI did not increase. Thus, the lack of amplification of phase synchronization of AP and HR at the early stage of orthostatic test is associated with the subsequent decompensation of hemodynamics and the development of syncope.

Reduction in daily activity leads to dramatic metabolic disorders, while regular aerobic exercise training is effective for preventing this problem. The purpose of this study was to identify genes that are directly related to contractile activity in human skeletal muscle, regardless of the level of fitness. Transcriptome changes after the one-legged knee extension exercise in exercised and contralateral nonexercised vastus lateralis muscle of seven men were evaluated by RNA-seq. Transcriptome change at baseline after 2 mo of aerobic training (5/wk, 1 h/day) was evaluated as well. Postexercise changes in the transcriptome of exercised muscle were associated with different factors, including circadian oscillations. To reveal transcriptome response specific for endurance-like contractile activity, differentially expressed genes between exercised and nonexercised muscle were evaluated at 1 and 4 h after the one-legged exercise. The contractile activity-specific transcriptome responses were associated only with an increase in gene expression and were regulated mainly by CREB/ATF/AP1-, MYC/MAX-, and E2F-related transcription factors. Endurance training-induced changes (an increase or decrease) in the transcriptome at baseline were more pronounced than transcriptome responses specific for acute contractile activity. Changes after training were associated with widely different biological processes than those after acute exercise and were regulated by different transcription factors (IRF- and STAT-related factors). In conclusion, adaptation to regular exercise is associated not only with a transient (over several hours) increase in expression of many contractile activity-specific genes, but also with a pronounced change (an increase or decrease) in expression of a large number of genes under baseline conditions.

The goal of this study was to describe and validate a muscle specific method to evaluate the anaerobic threshold in a working muscle based on the simultaneous measurement of EMG activity and the deoxyhemoglobin content (ATHHb-EMG). The study involved males with different fitness levels. During the cycling (n = 40) and ski double poling (n = 9) incremental ramp tests, blood lactate concentration, and muscle deoxyhemoglobin content and EMG activity were measured. Some participants were involved in the cycling test-retest study (n = 11). In cycling and double poling tests, close and significant correlations (r = 0.89 – 0.92, P < 0.002) were found between lactate threshold (a marker of the anaerobic threshold at the organism level) and the ATHHb-EMG (a marker of the AT at the working muscle level). The coefficient of variation of the ATHHb-EMG in the cycling test-retest was low (~3%). The muscle specific ATHHb-EMG demonstrates low variability and is appropriate to detect the fitness level and training-induced increase in aerobic performance in a working muscle. The emergence on the market of miniature EMG amplifiers and near-infrared spectrometers opens wide possibilities for using our method in laboratory studies and in field tests.

Взгляд на советскую детскую иллюстрацию 20–30-х годов прошлого века, как на явление, вызывавшее интерес и отклик за границей, давно уже стал привычным. В статье рассматривается возможностьобратного влияния: как и где московские художники могли встретиться с зарубежной детской книгой? В 1928 г. в Москве прошли сразу две выставки иностранной детской книги — книги Германии и Японии. В статье рассказывается об истории организации этих выставок, реконструируется их содержание и основные задумки организаторов, анализируются выпущенные к выставкам брошюры и отзывы о них в прессе. Теоретической рамкой для работы стала теория культурно-го трансфера Мишеля Эспаня, а отправной точкой исследования — фигура посредника, то есть агента трансфера. В 1920-е годы одним из самых энергичных популяризаторов искусства детской книги без сомнения был Яков Петрович Мексин. Именно благодаря ему и его сотрудничеству с Всесоюзным обществом культурной связи с заграницей (ВОКС) выставки 1928 г. смогли состояться. Как видно из сопроводительных текстов к выставкам, для Мексина эти экспозиции стали не только способом продемонстрировать новую зарубежную детскую книгу, но и поводом поговорить о традиции в детской иллюстрации — как Германии и Японии, так и дореволюционной России. Ключевые слова: Яков Мексин, ВОКС, Музей детской книги, детская книга 1920-х годов, советская детская книга, детская книга Японии, детская книга Германии, культурный трансфер, Кодомо-но куни, манга, выставки детской книги

In the past decade, mass spectrometry studies of skeletal muscles have become common. In this tissue, the abundance of several contractile proteins significantly limits the depth of the panoramic proteome analysis. The use of isobaric labels allows improving assessment of the changes in the protein content, while analyzing up to 10 samples in a single run. Here we present the results of a comparative study of various methods for the fractionation of skeletal muscle peptides labeled with an isobaric label iTRAQ. Samples from m. vastus lateralis of eight young males were collected with a needle biopsy. After digestion into peptides and labeling, the preparations were carried out according to three different protocols: (1) peptide purification, HPLC-MS/MS; (2) peptide purification, isoelectric focusing, HPLC-MS/MS; (3) high pH reverse-phase LC fractionation, HPLC-MS/MS. Fractionation of labeled peptides by high pH reverse-phase LC was the optimal strategy for increasing the depth of the proteome analysis. This approach, in addition to contractile and mitochondrial proteins, allowed us to detect a variety of regulatory molecules, including the nucleic acids binding the proteins, chaperones, receptors, and transcription factors.