Institute of Biomedical Problems

A 2D model of an InGaAs/InAlAs single-photon avalanche photodiode has been developed. The influence of the active area structure in the multiplication region on the diode's operating parameters has been studied. It was found that changing the diameter of the structure's active region leads to a change in the dark current in the linear part of the current-voltage curve and a change in the breakdown voltage. Reducing the diameter of the active region from 25 μm to 10 μm allowed decreasing the dark current in the linear mode by about 10 dB. It has been shown that the quality of the SPAD device can be assessed by knowing the avalanche breakdown voltage and the overall current-voltage curve plot if we consider structures with the same multiplication region thickness and different remaining layers. The higher the breakdown voltage, the better the structure's quality due to smaller local increases in the field strength. Following this statement, we conclude that for further use in single-photon detectors, it is reasonable to pick specific SPADs from a batch on the sole basis of their current-voltage curves.

The article describes the formulation of the most challenging and relevant theoretical problems of expert forecasting that are currently unsolved not only in Russia but also globally, and provides descriptions of possible approaches to their resolving. The study briefly describes materials from Russian and foreign articles, which, in the author’s opinion, may contain useful information about possible approaches to resolving the problems under consideration. The main purpose of the article is to improve the effectiveness of resolving process of forecast expert tasks. In conclusion, the author examines the future research prospects in the field of expert forecasting.

The aim of the review is to analyze the system of complex anthropometric research in clinical practice. Fundamental non-periodical literature on anthropometry and dietetics was studied, a search for scientific publications was carried out using the library platforms eLIBRARY, PubMed, Elsevier using the keywords anthropometry, body composition, obesity, sarcopenia, bioimpedancemetry. The article presents from a modern standpoint the current methods for assessing the physical development of a person, used in clinical practice to study the nutritional status of a person, assess the risks of development and prevention of alimentary-dependent diseases, as well as used in the process of diet therapy of patients who need medical care in the profile of “Dietetics”. The system of complex anthropometric research in clinical practice is presented. This system in clinical practice is applicable in many areas of medicine and allows systematizing the diversity of anthropometric studies to assess the nutritional status of a person.

In some branches of physiology (for example, space physiology), researchers have to deal with small samples, which makes it impossible to use classical data analysis methods and requires different approaches. Small samples are characterized by an increased influence of individual characteristics of a particular organism on the nature of the adaptation process, and therefore, an urgent task is to separate the effect of the influencing factor and individual reactions. The authors propose a new approach to the analysis of these small samples on the example of adaptive changes in the cardiovascular system (CVS) in women when reproducing the effects of microgravity in the conditions of 5-day “dry” immersion (DI). Changes in the CVS were assessed by indicators reflecting hemodynamics and autonomic modulating effects on heart rhythm. The aim of the work was to identify indicators reflecting the effect of the influencing factor, as well as indicators reflecting the individual characteristics of the subjects of the experimental sample. Methodological approach to data analysis based on analysis of variance (ANOVA) was used for this purpose. Full analysis of the small sample data with a statistically justified separation of the influence of both the studied factor and individual reactions was carried out, and specific subjects that affect the uniformity of the entire sample were identified. The presented approach allows selecting those indicators that reflect the impact of the studied factor at the initial stage of analysis, and, accordingly, meet the set goals, while excluding indicators in which the contribution of individual characteristics is so large that it makes them inappropriate for consideration in the current scientific search.

The study is aimed at analyzing the differences in central hemodynamics and blood flow in the microcirculatory bed in men and women to identify specific gender characteristics of microcirculation. The study involved 84 women and 406 men. Three-fold measurement of arterial pressure on the brachial artery was performed using the MediTechMT-25 Palm device (United States). Blood flow parameters were measured at rest using high-frequency ultrasound dopplerography on the skin of the nail fold of the index finger of the right hand. The subjects were in a sitting position, the hand on which the measurement was performed was on a solid support at the level of the heart. The Minimax-Doppler-K dopplerograph (Russia) with a 20-MHz sensor was used for the study. Analysis of the results revealed statistically significant differences in microcirculation parameters between men and women. Women had higher values of blood flow velocity in the arteriolar (Vm: 0.98 versus 0.91 cm/s, p = 0.040; Vs: 1.55 versus 1.38 cm/s, p < 0.001; Vas: 0.81 versus 0.55 cm/s, p = 0.003) and venular links (Vad: 0.34 versus 0.25 cm/s, p = 0.002). In men, this is compensated by higher values of capillary blood flow, such as Vam: 0.16 versus 0.19 cm/s, p = 0.030, as well as volumetric blood flow in the capillaries (Qam: 0.08 versus 0.11 mL/min, p < 0.001). In addition, women have higher pulsatility indices (PI: 1.35 vs. 1.16, p = 0.014) and circulatory tension indices (RI: 0.80 vs. 0.73, p = 0.026).

Objective: The cytoskeleton is a complex dynamic cellular structure that not only serves as a scaffold but also participates in cell motility, metabolism, and regulation of biochemical processes. Studying the reaction of the cytoskeleton to various stimuli is an important task of cell biology. Automated microscopy and image processing methods are currently being developed to obtain and analyze extensive volumes of objective data. The aim of this study was to develop an approach for the objective quantitative analysis of cytoskeletal components using CellProfiler and ImageJ software. Methods: CellProfiler, ImageJ, and the Cellpose algorithm were used to segment and analyze fluorescence microphotographs of actin filaments, microtubules, and intermediate filaments. Results: An approach for high-throughput image processing with the ability to analyze the shape, intensity, and fractal dimensions of the cytoskeleton was developed. Conclusion: The proposed approach to cytoskeleton analysis enables high-throughput analysis of a large number of cell images, thereby obtaining a vast amount of diverse data on fluorescence internsity and cytoskeletal structure.

BACKGROUND:. During muscle contraction, blood flow in the working muscles increases tens of times due to the mechanisms of sympatholysis. However, there are no studies that would quantitatively describe the effect of epinephrine on arterial alpha-adrenergic receptors during sympatholysis against the background of 5-day cold adaptation. AIM: Objective. To study the effect of five-day cold adaptation on the adrenoreactivity of muscle arterial vessels during sympatholysis to different doses of epinephrine. MATERIAL AND METHODS: Material and methods. The experiments were carried out in 4 groups of rabbits. Control group (N1, n = 20) of rabbits. Sympatholysis group (N2, n = 15): electrical stimulation of muscles (frequency 5 Hz, voltage 10 V, L = 5 ms) to induce sympatholysis. Cold adaptation group (N3, n = 15) after 5-day exposure in a climatic chamber (−10 ° C, 6 h / day). Group (N4, n=15): combination of 5 days of cold adaptation with sympatholysis. In all rabbits, the limb muscles were perfused with blood through the femoral artery after ligation of all anastomoses using a constant-flow pump. After the introduction of 8 doses of epinephrine (0.5–30 μg/kg), the adrenoreactivity of the limb arteries was analyzed using the dose-effect reaction in double inverse Lineweaver–Burk coordinates. This allowed us to determine the number of active adrenoreceptors (Pm) and the sensitivity (1/Km) of adrenoreceptors to epinephrine. RESULTS: Sympatholysis after 5 days of cold adaptation (N4) was much less for all doses of epinephrine than without cold (N2), which proved a decrease in blood flow in the working muscles during sympatholysis against the background of cold. Analysis of this mechanism in double inverse Lineuwer-Burk coordinates revealed an increase in the number of active a-ARs (by 1.407 times or 40.7%) to Pm=312.5 mmHg during sympatholysis after cold with Pm=222 mmHg during sympatholysis without cold. At the same time, after cold (N4) during sympatholysis, the sensitivity (1/Km) of alpha-adrenoreceptors to epinephrine increased by 1.632 times (by 63.2%) to 1/Km=0.08 from the value of 1/Km=0.049 during sympatholysis without cold (N2). Complete leveling of sympatholysis after cold with 30 μg/kg epinephrine confirms the critical role of dose-dependent pharmacokinetics of arterial tone regulation under cold stress conditions. CONCLUSION: Conclusion. The obtained data allow us to draw the following conclusion: sympatholysis against the background of 5 days of cold persists, but was less than sympatholysis without cold. Increased adrenergic vasoconstriction after 5 days of cold optimizes heat conservation, but reduces blood flow in the working muscles, which limits physical performance. The discovered mechanisms explain the phenomenon of "early cold asthenia" in individuals with short-term arctic exposure, characterized by a decrease in tolerance to physical activity while maintaining basic hemodynamic homeostasis.

The imbalance in the ratio of protein synthesis versus protein degradation results in skeletal muscle atrophy following unloading. The onset of these processes is regulated by the sarcoplasmic concentrations of ATP and calcium (Ca2+). We tested the hypothesis that unloading-induced inactivation of sarcoendoplasmic reticulum calcium ATPase (SERCA) results in raised Ca2+ concentrations, triggering catabolic processes. CDN1163, an activator of SERCA, was used to test this hypothesis. Three groups of male rats were used: control rats with intraperitoneal injection of placebo (C), 3 days of unloading with placebo injection (3HS), and 3 days of unloading injected with CDN1163 (3HSC). Treatment with CDN1163 during 3 days of soleus muscle unloading prevented the upregulation of Ca2+ and ATP and the slow-to-fast shift in muscle fiber composition. This treatment blocked the decrease in the phosphorylation of the anabolic markers [glycogen synthase kinase-3β (GSK3β), eukaryotic translation elongation factor 2 (eEF2), and ribosomal protein S6 (S6, Ser240/244/Ser235/236)], and therefore it is likely that it improved the efficiency of translation in the unloaded muscle, but it did not affect mTORC1-dependent signaling. Treatment with CDN1163 also modulated the regulation of the Ca2+-dependent signaling in muscle during unloading via SERCA1 and calsequestrin 2 (CSQ2) and changes in the calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylation and the content of inositol 1,4,5-trisphosphate receptor (IP3R). In addition, CDN1163 prevented the upregulation of the mRNA expression of muscle-specific RING finger protein 1 (MuRF1) [but not ubiquitin ligase muscle atrophy F-box (MAFbx)] and attenuated the increase of casitas B lymphoma-b (Cbl-b) and ubiquitin mRNA expression during unloading. Activation of SERCA with CDN1163 prevents the upregulation of Ca2+ and ATP, as well as calcium-dependent and ubiquitin-proteasome pathways markers, and improves protein translation efficiency in 3-day unloaded soleus muscle.NEW & NOTEWORTHY A hypothesis was tested that unloading-induced inactivation of SERCA results in the accumulation of increased Ca2+ concentrations and activation of catabolic processes. CDN1163, an activator of SERCA, was used to test this hypothesis. CDN1163 prevented the decrease in phosphorylation of anabolic markers, which likely improved translation efficiency in unloaded muscle. CDN1163 prevented unloading-induced upregulation of mRNA expression of MuRF1 (but not MAFbx) and attenuated the increase of Cbl-b and ubiquitin mRNA expression.

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed.