Vol 68, No 5 (2023)

Biomolecular solvation plays one of the key roles in nature. The biological activity of molecules and the performance of their target functions depend on the features of this process. However, the study of the biomolecule hydration is a non-trivial task for both experimental methods and computer simulations. The paper demonstrates the possibilities of the non-empirical 3D-SDFT/3D-RISM approach based on the 3D-distribution of the solvent atomic density to study the features of biomolecule hydration using the example of a number of amino acids such as Gly-ZW, L-Ala-ZW, L-Val-ZW, L -Pro-ZW, two model proteins such as BP-TI (bovine pancreatic trypsin inhibitor) and PTP1B (protein tyrosine phosphatase 1B), as well as complexes of the PTP1B protein with inhibitors. The presented results show that the approach allows one to describe in detail and at the same time a holistic description of the hydration shell structure of biomolecules.

Solanum tuberosum polysaccharide (STP) was isolated from the water extract of Solanum tuberosum L. and purified by ion-exchange and gel-filtration chromatography. Its molecular weight was determined by using gel permeation chromatography method and high performance liquid chromatography technique and its monosaccharide composition was analyzed using high performance liquid chromatography and gas chromatography with a flame ionization detector and a capillary column. It was shown that STP was consisted of galactose (Gal) and arabinose (Ara) (37.5 and 23.5%, respectively), along with uronic acids (9.7%), glucose monosaccharide residues (15%) and proteins (no less than 9%). The molecular weight of STP was 70 kDa. The Fourier-transform infrared technique was used for structural analysis of STP. The mitogenic activity of extracted polysaccharide is comparable to that of lipopolysaccharide.

In Alzheimer's disease, beta-amyloid peptide (Ав) plays an important role in the mechanism of neurodegeneration. A small fragment of Лв(25-35) (with the sequence GSNKGAIIGLLM) is regarded to be the functional domain of Лв, responsible for its neurotoxic properties and represents the biological active region of Лв. Conformational analysis of each C-terminal segment of the peptide by the method of molecular mechanics revealed a limited number of most probable conformations and quite clearly helped to clarify what forces stabilize the structures. The obtained results showed that Лв(25-35) energetically has a propensity for adopting alpha-helix conformation of the C-terminal octapeptide segment. A molecular dynamics method was used to build a model of intramolecular mobility in the Лв(25-35) molecule. It was demonstrated that in low-energy conformations, Лв(25-35), the orientation of flexible structures of the N-terminal region with respect to the structures of the C-terminal region is different.

The nonhistone chromosomal protein HMGB1 and histone H1 are chromatin linker proteins. The functions of linker proteins are closely related to their conformational state. Currently, the structure of proteins that play a key role in the formation of higher levels of chromatin structural organization is being actively studied. In this work, a comparative analysis of the secondary structure of the linker histone H1 and the nonhistone protein HMGB1 was carried out. By using UV-circular dichroism and FTIR spectroscopy it was shown that the positively charged histone H1 binds to the C-terminal fragment of HMGB1, stabilizing the resulting complex and inducing the formation of additional a-helical regions in both proteins.

This paper presents the mechanism of signal transformation by which a signal from the magnetic component of the low-frequency electromagnetic field with extremely low energy is changed into chemical and biochemical signals which elicit a biological response in aqueous solutions of biopolymers based on nucleic acids and proteins. A theoretical model developed shows that the basis of oxidative DNA damage and conformational transitions of proteins is a universal mechanism associated with a change in the amount of the most long-lived form - hydrogen peroxide in a chemical oscillator of mutual transformations of reactive oxygen species under the influence of low-intensity electromagnetic field exposure. It has been experimentally established that the quantitative content of hydrogen peroxide in solutions of biopolymers resonantly depends on the frequency of applied field. Conformational changes in proteins are accompanied by an increase in the availability and activity of the nucleophilic centers that are potential targets for reactive oxygen species. Complete unfolding and denaturation of the amino acid chain of the protein under the influence of low-frequency electromagnetic field exposure do not occur. It has been shown that enhanced hydrogen peroxide formation at 3 Hz and 50 Hz leads to oxidative modification of nitrogenous bases in DNA.

Genomic structural variations (SVs) are one of the main sources of genetic diversity. Structural variants as mutagens may have a significant impact on human health and lead to hereditary diseases and cancers. Existing methods of finding structural variants are based on analysis of high-throughput sequencing data and despite significant progress in the development of the detection methods, there is still a need for improving the identification of structural variations with accuracy appropriate for use in a diagnostic procedure. Analysis of the signal of sequencing coverage (i.e., the number of sequencing fragments that aligned to every point of a genome) holds new potential for the design of approaches for structural variations discovery, and can be used as time-series analysis. Here, we present an approach for identification of patterns in the coverage signal. The method has been developed based on algorithms used for analysis of time series data, namely KNN (K-nearest neighbour) search algorithm and the SAX (Symbolic Aggregation Approximation) method. Using the rich dataset encompassing full genomes of 911 individuals with different ethnic backgrounds generated by the Human Genome Diversity Project initiative, we constructed generalized patterns of signal coverage in the vicinity of breakpoints corresponding to various structural variant types. Also, with the benefit of the SAX models of the motifs we developed a software package for fast detection of anomalies in the coverage signal.

This study examined radiosensitivity at low and high dose exposure to X-rays in human lymphocytes and the ability of low and high dose radiation to induce radioadaptive response when the peripheral blood cells from patients with secondary immune deficiency syndrome and healthy donors of different ages were irradiated in vitro. The frequency of micronuclei in cytochalasin-blocked binuclear lymphocytes in culture served as an indication of cytogenetic damage. It was found that the spontaneous level of cytogenetic damage in blood lymphocytes of patients with secondary immune deficiency syndrome was 2.5 times greater than that of healthy young and older volunteers and there was also a substantial interindividual variability in outcome parameters as compared to the data of control groups. There were no differences in mean values for radiosensitivity at low and high dose exposure of X-rays between the groups. In all groups, no correlation was shown between the spontaneous level of micronuclei in lymphocytes and the radiosensitivity of individuals. The adaptive response was induced with the same frequency and to the same extent in lymphocytes in patients with secondary immune deficiency syndrome and in healthy donors of different ages.

The effect of molixan, a disulfide-containing immunomodulator which is an analogue of oxidized glutathione, on Na⁺ transport across frog skin epithelium has been studied. Using the voltage-clamp technique, the capacity of molixan to modulate Na⁺ transport across frog skin epithelium has been revealed for the first time. It was also found that when molixan is applied to the apical surface of frog skin, it suppresses Na⁺ transport, while molixan added on the basolateral surface may mimic the effect of insulin and stimulate Na⁺ transport. The results obtained indicate that oxidized glutathione and its analogs molixan and glutoxim unidirectionally modulate Na⁺ transport across frog skin.

During the hibernation season, the values for the parameters of the cell cycle of red bone marrow cells in the hibernating ground squirrels Urocitellus undulatus, when they return to an active-like state between periods of torpor and interbout arousal, do not differ from those observed in summer-active animals. In animals that enter a state of torpor, the cumulative percentage of cells in the resting phase (G0 phase) and pre-synthesis phase (G1 phase) increased from 71.8 to 76.0%, the percentage of cells in the synthesis phase (S phase) decreased from 19.3 to 15.3% compared to those animals that return to an active-like state between periods of torpor and interbout arousal. The cumulative percentage of cells in the post DNA synthesis phase (G2 phase) and mitosis (M) does not change, but (G2 + M)/S ratio increases. When animals enter a state of torpor, changes in parameter values are observed when the animal’s body temperature drops below 25°C, this effect refers to a system whose thermal relaxation time is a nonmonotonic function of the initial temperature. The activity of the key enzyme of polyamine synthesis ornithine decarboxylase, a marker of cell activation and proliferation during interbout arousal does not significantly differ from that observed in summer-active animals; the enzymatic activity decreases sharply, when animals decrease their body temperature below 25°C and enter a state of torpor, and this activity remains at a low level during hibernation and arousal until body temperature reaches 30°C. The role of changes in the parameter values associated with proliferative activity in adaptation of hematopoietic tissue during hibernation of the Yakutian ground squirrel is discussed.

Interactions of the anticancer drug cisplatin or the antioxidant drug lutein with liposomes as model membranes were characterized. All liposomes had the almost spherical shape, taking into account that lyposomes without the said drugs were more evenly dispersed and tended to aggregate less. The mean size diameter of empty liposomal samples was 617.90 ± 75.64 nm, while liposomes loaded with cisplatin, lutein and a cisplatin+lutein combination were 425.60 ± 64.74 nm, 877.85 ± 93.90 nm and 189.91 ± 136.84 nm, respectively, in diameter. The incorporation of cisplatin or lutein into liposome membranes resulted in an increase in the zeta potential values. The lowest zeta potential value was achieved in lyposomes containing cisplatin in combination with lutein. The addition of cisplatin to liposomes caused a shift in the melting temperature towards higher values than those of the main peak of empty liposomes indicating a conformational disorder within the phospholipids. Encapsulation of lutein into liposomes resulted in the disappearance of the main characteristic endothermic peak of pure liposomes. FTIR spectroscopy confirmed the interaction of lutein or cisplatin with functional groups in liposomes. In the absence of external gamma-irradiation, the IC₅₀ value for free lutein in the cytotoxic assay with MCF-7 treated cells was 10.62 gg/ml, while free cisplatin showed the IC5₀ value of 41.02 gg/ml. IC5₀ was 65.84 gg/ml and 34.29 gg/ml for nanoliposomal lutein and cisplatin, respectively. Using the combined therapy of gamma irradiation at dose rate 5 Gray followed by 10 Gray, the IC₅₀ value for free lutein changed from 17.0 to 9.5 gg/ml. IC₅₀ for free cisplatin changed from 51.00 to 43.09 gg/ml. This study showed that cytotoxic effect of a standard form of lutein is stronger than that of nanoliposomal lutein. The current evidence reveals a new regimen for the treatment during which replacing cisplatin with free lutein increases anticancer activity against the MCF-7 cancer cell line.

The present study examined the effects of the в-adrenergic receptor agonist, isoproterenol, on contractile activity of right ventricle papillary muscles in the rat heart at near-physiological temperature (30°C) and under conditions of deep hypothermia (10°C). Isoproterenol exerts a pronounced positive inotropic effect at 30°C. After agonist addition, the force of contraction increases from 1.2 ± 0.1 mN in control to 2.4 ± 0.4 mN that leads to a reliable acceleration of time parameters of contraction. So, time-to-maximum contraction decreased from 101 ± 6 ms to 85 ± 4 ms; time-to-50% relaxation declined from 55 ± 3 ms to 36 ± 1 ms. Under hypothermic conditions, isoproterenol produced a powerful negative inotropic effect, reducing the force of contraction from 2.2 ± 0.4 mN to 1.2 ± 0.4 mN. Similarly as at 30°C, there was a tendency for increase in contraction speed, so time-to-maximum contraction decreased from 717 ± 52 ms to 624 ± 50 ms, and time-to-50% relaxation was shortened from 667 ± 86 ms to 450 ± 40 ms. Thus, under conditions of deep hypothermia at 10°C, the isoproterenol-induced inotropy changes from positive to negative, while negative lusitropic effect remains clear.

A minimal mathematical model of the wall of a small arterial vessel is described. This model is created based on the published results of experiments performed on rat cerebral vessels. It is assumed that the active stress has only a circumferential component and depends on the circumferential stretch, calcium concentration in the cytoplasm, and the membrane potential of smooth muscle cells. The presented model for a small artery can qualitatively reproduce the results of more sophisticated models for other vessels under normal physiological conditions. Unlike a similar model, that accounts for only one cellular parameter, the addition of membrane potential as one of the main parameters was crucial to reveal a qualitative change in the dependency of circumferential stress on stretch and the radial coordinate with an alteration in vascular tone. At fixed values of membrane potential and calcium concentration in the phase of a development of vascular tone, stress decreases as it approaches the outer wall of the vessel and increases as stretch increases, and after it is formed, the direction of changes in the circumferential stress reverses.

The temporal resolving power of the visual system is essential for the perception of the objective world. The lowest sampling rate of a sequence of images at which perception becomes fused is called the critical flicker fusion frequency. The variety of experimental data on critical frequency thresholds can be explained from a point of view of a model of the contrast sensitivity of the visual system that based on the tremor modulation signal. The model describes the dependence of critical frequency on stimulus brightness, adaptation brightness, duration, and the angular size of the stimulus. This model demonstrates that for bright stimuli with short duration and a large angular size, critical frequency values lie in the range up to 1000 Hz; the frame rate of 300-500 Hz should be considered optimal for the visual system; for small-sized angular stimuli, the critical frequency lies in the low-frequency region. Differences in the rate of flicker fusion can be explained by temporal sensitivity of magno- and parvocellular neurons.

This research has been carried out by analyzing the specific processes of the local epidemic dynamics of COVID by comparing the qualitative differences in fluctuations in 2020 and 2023. Methods of nonlinear dynamics of the development of epidemic processes in a rapidly changing situation were used to identify and qualify trends and unique situations that sometimes changed extremely fast. A distinctive feature of the modern pandemic is a rather sharp change in local trends: the effect of the fading of the primary outbreak of the disease and the sudden sharp onset of a new epidemic wave after a long trend of decreasing daily infections. Minimization of the exposure to viral infections did not prevent spreading the virus but created the illusion of success. The existing experience in generating forecasts of epidemic outbreaks based on models of past epidemic processes could not help when faced with a new evolving virus. The previously obtained understanding of the development and completion of epidemic processes of influenza virus strains more likely hindered the prediction of the scenario for the completion of the spread of a new infection, which is also associated with the eventual nature of the process and a variety of dynamic situations. A victory over COVID in the phase of the minimum after the wave, which was announced by many countries, turned out to be premature. New Zealand and Japan, which opted for a strict lockdown strategy in 2020, had a surge of COVID cases in early 2023 because new strains came into circulation. Outbreaks of respiratory diseases known as the Spanish flu and swine flu pandemics, data from which were used by many countries to make predictions, had run their course naturally in two or three waves of illness. At the beginning of 2023, against the backdrop of a global positive trend, some countries have reported a record rise in both mortality and daily morbidity due to the emergence of locally circulating “alarm” strains. A current stage on isolation of stable regional strains substantiates the classification of a series of differentiated properties of the dynamics of regional epidemic situations. Among the observed epidemic effects, extreme phenomena in the form of instantaneous bifurcation destruction of established regimes such as a sharp transition from long-term damped oscillations to a new exponential outbreak in some infections are separately highlighted. The selected options for the development of epidemic transient oscillatory processes are separately introduced in equation forms with delay for local epidemic trends. Equations are proposed to describe three variants of development of the observed stages of local epidemics. The task of constructing a generalized predictive model of a pandemic to describe interrelated regional processes at this stage seems insoluble.

The aim of the work was to develop and test a combined method for assessing the structural and functional features of the burn wound and periwound area with the use of microwave dielectrometry and Dopplerometry. The study was performed on twenty Wistar rats, thermal injuries from contact were created on each rat, and ten healthy animals. The assessment of the wound condition was performed 24 and 72 hours after burn injury. The study of the dielectric properties of tissues was carried out using a hardware and software complex for near-field resonant microwave sensing. From the results of our studies, it can be concluded that in the early post-injury period (within the first days), a sharp coordinated decrease in the intensity of microcirculation and dielectric permittivity is observed in the wound tissues, gradually and partially restored by the end of the third day after burning. The increased microcirculatory blood flow to the periwound area, leading to an increase in the degree of tissue hydration was observed, and as a consequence, the values of these two indices became higher. In addition, it has been shown that during thermal trauma, a regulatory imbalance of factors providing capillary blood flow around a burn wound area and surrounding tissues is formed, which is compensatory in nature and, in the absence of adequate correction, contributes to the inhibition of regeneration processes. Thus, the combination of the methods used in this study may potentially provide more specific information for a description of the structural and functional features of the analyzed tissue and their dynamics. This is clearly shown by the example of an experimental burn wound.