Conformational aspects in the formation of structures of the backbone of polypeptide chains in proteins. Relationship between conformational stability/lability and β-turns

Torshin Y.Y., Filatov I.V., Batyanovskii A.V., Smirnov K.V., Anashkina A.A., Esipova N.G., Tumanyan V.G.

Abstract

To assess the nature of the relationship between the integral conformational stability of tetrapeptides and the main types of β-turns (which are also tetrapeptides), calculations were performed using spectrum diagrams and asymmetry in the distribution of conformationally stable and unstable tetrapeptides. It was shown that type I', II, and II' β-turns are comprised of predominantly conformationally labile peptides, that is consistent with the predetermined nature of their structure as described earlier. As previously shown in our study, in this case the conformation is imposed by external conditions (namely the cycle closuring) and the prevalence of conformationally labile peptides facilitates the formation of the structure by virtue of external factors. Type I β-turn is an exception: peptides with different conformational lability are fairly evenly distributed. Most likely, this indicates that the formation of the type I β-turn is not predetermined.

Biofizika. 2023;68(1):5-10

Induction of damage to the dna structure of tumor cells by aurum polyacrylate

Chigasova A.K., Ostrovskaya L.A., Korman D.B.

Abstract

The ability of aurum polyacrylate (aurumacryl) to cause changes in the DNA structure of tumor cells (culture of MCF-7 human breast cancer cells) was studied. It was established that the molecular mechanism under- lying the effects of aurumacryl on tumor cells is associated with the induction of single-strand breaks and cross-links in the DNA molecule. At the same time, it was shown that aurumacryl can reduce the number of spontaneous, or irradiated, DNA double-strand breaks in MCF-7 cells.

Biofizika. 2023;68(1):11-19

Meconic acid is a possible neuroprotector: justification on in vitro experiments and its physico-chemical properties

Kozin S.V., Ivashchenko L.I., Kravtsov A.A., Vasilyeva L.V., Vasiliev A.M., Bukov N.N., Dorohova A.A., Lyasota O.M., Bespalov A.V.

Abstract

Main representatives of gamma pyronic acid are meconic, comenic, chelidonic and kojic acid. It was found that comenic acid exerts a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. It was not studied whether meconic acid exhibits neuroprotective effects. The aim of this work was to assess the neuroprotective potential of meconic acid, taking into accout its physicochemical properties, using an in vitro model of ischemic stroke. Primary neuroglial culture was obtained from the cerebellum of 7-8-day-old Wistar rat pups by mechanical tissue dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using the model of glutamate toxicity and oxygen-glucose deprivation. Quantum mechanical calculations were used and experiments in the model system citrate-phosphate-luminol were conducted by the method of chemiluminescent analysis to investigate the antioxidant activity of meconic acid. The chelating properties of meconic acid with respect to Fe3+ in solutions were studied using Job's method. Meconic acid has been found to have a protective effect in in vitro models of ischemia. Its action leads to a decrease in the level of intracellular calcium and the restoration of the membrane potential of mitochondria in a culture of cerebellar neurons under glutamate exposure, resulting in an increase in the percentage of living cells under oxygen-glucose deprivation. Meconic acid has a high calculated antioxidant potential, confirmed experimentally. With an increase in the pH of the medium, stepwise binding of meconic acid with Fe3+ occurs with the formation of complexes with different ligand/metal ratios. At physiological pH, the composition of the resulting complex is 1:3. The obtained antioxidant, chelating, and cytoprotective action of meconic acid provides a basis for further study of the possible neuroprotective properties of this compound in in vivo experiments, and the data obtained in the work on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on meconic acid.

Biofizika. 2023;68(1):20-32

Study of heme and globin conformation in fractionated rat erythrocytes by means of raman spectroscopy

Yushkov B.G., Zuev M.G., Brilliant S.A., Vasin A.A.

Abstract

Conformational changes of heme and globin in fractionated rat erythrocytes have been investigated using Raman spectroscopy. The results obtained show that normal isoforms (common variants) of hemoglobin, which plays a key role in oxygen transport and a protective role against oxidative stress, are dominant (more than 80%) in rat blood. However, heavy chain (3%) and light chain isoforms (11%) formed as a result of protein polymerization or degradation perform important roles in the body because they also function in signal transmission and binding to exogenous ligands.

Biofizika. 2023;68(1):33-40

Model of lipid diffusion in cytoplasmic membranes

Mokrushnikov P.V., Rudyak V.Y.

Abstract

An analytical model of lateral lipid diffusion in heterogeneous native cytoplasmic membranes is presented. The Fourier transform method was used to solve the diffusion equation for the coordinate distribution function of lipids in a periodically inhomogeneous membrane, in which the diffusion coefficient is described by a harmonic function of the coordinates. It is shown that advection and diffusion are present in membrane. The model explains different types of lipid diffusion in membrane observed previously in experiments as a result of structural transitions of periodically located fixed protein-lipid domains associated with the spectrin-actin-ankyrin network. If these domains are the same, then super- and subdiffusion can be seen in experiments, when the mean square displacement of lipids depends non-linearly on time, and their average displacement is zero. Drift during advection was less than the chaotic Brownian displacement of lipids, advection was not observed in the experiment. When not all membrane proteins associated with the spectrin-actin-ankyrin network undergo conformational change in the same way upon ligand binding, two periodic sublattices of inhomogeneities arise in the membrane from fixed protein-lipid domains around membrane proteins associated with the cytoskeleton and nested in one another. In this case, hop diffusion can be found in experiments, when periods of nonlinear diffusion of molecules are replaced by periods of advection-diffusion, in which the average displacement of molecules is not zero. Advection is local in nature and occurs near individual protein-lipid domains. In the presented work, criteria are analytically obtained under which hop diffusion is experimentally observed in a periodically inhomogeneous membrane.

Biofizika. 2023;68(1):41-56

Local optical tomography of a nerve cell

Levin G.G., Samoilenko A.A., Kazakova T.A., Marakutsa T.A., Maksimov G.V.

Abstract

The presented modification of the method of local optical tomography makes it possible to study the dynamic processes of subcellular structures of native nerve cells. The advantage of this approach is that it is possible to analyze the dynamics of the distribution of neuron structures at a point or area of interest inside the cell without performing a complete reconstruction of the cell image. It has been proved that it becomes possible to determine the dimensions, the cell area of interest, and the coordinates of subcellular structures for further study of their dynamics. In this modification, the method of local tomography could be used to study both cells and cellular structures, because it is not necessary to probe a full field of view. Local probing of the region of interest during the functioning of the nerve cell will, firstly, reduce the time of data recording for obtaining local tomograms, and, secondly, provide the opportunity to explore the dynamics of several regions inside the cell at the same time.

Biofizika. 2023;68(1):57-65

Mechanisms involved in regulation of blood coagulation: history of research and perspectives

Nechipurenko D.Y., Panteleev M.A., Sinauridze E.I., Troyanova K.S., Megalinsky A.D., Podoplelova N.A., Shibeko A.M., Balandina A.N., Koltsova E.V.

Abstract

Blood clotting is the most important physiological response in the body to disruption to vascular structure or vessel wall abnormalities. This process is non-stationary, involving many not fully established mechanisms of spatial regulation, and an understanding of this process is essential for the prevention of a large number of life-threatening conditions. This review is focused on investigations into the research of blood clotting processes by a team of biophysicists, alumni and employees of the Biophysics Department of the Faculty of Physics, Lomonosov Moscow State University, who created one of the leading Russian scientific schools for experimental and theoretical approaches to the study of the hemostasis system. The review describes the main directions of research, which included many diverse aspects of the problem - from the development of theoretical models of blood coagulation to the development and clinical studies of new methods for assessing the state of the hemostasis system.

Biofizika. 2023;68(1):66-78

Comparative analysis of the nitrogen monoxide content and optical-morphometric characteristics of erythrocyte-containing blood components during storage

Akulich N.V., Zinchuk V.V.

Abstract

Flow cytometry was used to analyze the content of intracellular nitrogen monoxide in erythrocyte-containing blood components during blood storage with hemopreservative for 4 weeks. It was found that storing of blood is accompanied by increased levels of intracellular nitrogen monoxide in erythrocytes and thus by a change in optical and morphometric parameters of red blood cells. In the early stages of storage, erythrocytes were represented by discocytes, and during long storage erythrocytes became more spherical (spherocytes) as the percentage of microcytes that accumulated nitrogen monoxide increased and their intracellular hemoglobin levels were decreased.

Biofizika. 2023;68(1):79-86

Paracrine effects of stem cell conditioned medium on production of oxygen reactive species in blood neutrophils in acetaminophen-induced liver failure

Temnov A.A., Sklifas A.N., Zhalimov V.K., Sharapov M.G., Fadeev R.S., Kobyakova M.I., Kukushkin N.I., Rogov K.A.

Abstract

The current study examined the effects of mesenchymal stem cells-derived conditioned medium on the severity of systemic inflammatory response induced by the administration of acetaminophen, as well as its long-term effects on hepatic tissues. A conditioned medium fraction <30 кDа showed maximum protective effect. Proteins of this fraction reduce the degree of systemic inflammatory response and liver tissue fibrosis long after the toxin administration. Liver tissues from experimental animals were examined, and a correlation between the reduction of granulocytic infiltration scoring and the degree hepatic parenchymal necrosis was demonstrated (confirmed by the cytolytic enzyme level). The <30 кDа fraction increased the spontaneous but decreased phobrol-12-myristate-13-acetate-induced intracellular production of reactive oxygen species. Results from this study show that the level of macrophage migration inhibitory factor and expression of thioredoxin significantly increase as compared to controls during increased spontaneous production of reactive oxygen species in neutrophils.

Biofizika. 2023;68(1):87-97

Frequency and time domain characteristics of the insect visual system in optic flow

Zienko S.I., Zhbanova V.L.

Abstract

Frequency and time domain properties of the monochromatic, dichromatic, and trichromatic visual system in an insect have been studied. The research method is based on the representation of the optical flow field of the insect visual system in the form of a dynamic link with an input and output. The Gaussian function was used to approximate the spectral curves. The study of the inertial properties of such a link in the time domain was performed by applying signals to its input in the form of a δ-function or a unit function. The steady-state forced oscillations at the output of the investigated dynamic link are determined when a harmonic effect is applied to the input. A technique for constructing spectral sensitivity curves for monochrome, dichromatic, and trichromatic vision of insects in the frequency domain is proposed; it has been established that the spectra exhibit the properties of ultra wideband signals. It has been found that the dynamic link of the insect visual system is capable of amplifying the optical signal over ultraviolet and blue parts of the spectrum in the time and frequency domain. It has been revealed that at a frequency equal to or higher than the frequency of dielectric relaxation, the optical flow field of the insect's visual system does not sense electromagnetic radiation. This phenomenon is most pronounced in ultraviolet and blue parts of the spectrum. It has been established that the optical signal wideband index μ varies from 0.41 to 1.21; thus, the visual system of an insect has ultra wideband properties. It has been shown that the number of periods of light oscillations in the visual system of insects, which has a spectrum in the form of a Gaussian curve, is related to the exponent μ by a simple relationship. New knowledge gained can be used for creation of matrix solid-state photodetectors in ultraviolet and blue parts of the spectrum.

Biofizika. 2023;68(1):98-107

Epr study of the generation of short-lived reactive oxygen species in rat heart homogenate

Timoshin A.A., Lakomkin V.L., Abramov A.A., Ruuge E.K.

Abstract

The aim of the present study was to investigate the protective effects of a mitochondrial-targeted antioxidant such as plastomitin through ROS hypergeneration in animals. The average rate of the generation of highly reactive oxygen radicals during oxidative stress, induced by doxorubicin injection in rats and a protective impact of plastomitin use were investigated. The experiments were carried out with rat heart tissue homogenates using EPR spectroscopy. It was found that in case of doxorubicin injection in rats, there is a significant 26% increase in the rate of short-lived reactive oxygen species generation in the homogenate but when doxorubicin and plastomitin were used in combination, this effect was greatly suppressed.

Biofizika. 2023;68(1):108-111

Comparison of the dynamics of DNA damage in blood leukocytes and survival of mice after total body irradiation with Bragg peak carbon ions or x-rays

Kuznetsova E.A., Rozanova O.M., Smirnova E.N., Glukhov S.I., Sirota T.V., Belyakova T.A., Sirota N.P.

Abstract

This study has determined a survival rate of mice irradiated with accelerated carbon ions (450 MeV/nucleon) in the Bragg peak or X-ray at a dose of 6.5 Gy, using the comet assay. Levels of DNA damage (%TDNA) in blood leukocytes from mice were measured 1 day before, 1-23 days after exposure to carbon ions and 1-28 days after exposure to X-ray radiation at the same dose. According to survival and % TDNA parameters, it was found that a damaging effect of carbon ions is greater than that of X-rays and substantial variations in % TDNA, which occur in individual animals, could appear to cause individual differences in the development of genome instability in the long term. It is assumed that a higher % TDNA in leukocytes after carbon ion exposure compared to that of X-rays, a wide range of variations and asynchronous changes in individuals in the post-irradiation period are associated with the induction of clustered DNA damages and mitochondrial dysfunction, and are also due to genetic and epigenetic factors. The results obtained point to the need to assess the state of blood leukocytes in animals with a heterogeneous genetic background using the comet assay before irradiation in order to form a group with similar %TDNA values. The revealed differences in individual laboratory animals require further study in order to improve animal models in the light of the development of personalized biomedicine.

Biofizika. 2023;68(1):112-119

Dynamics of temperature and body weight in irradiated mice: the dose-effect and time-effect relationships

Zrilova Y.A., Nikitenko O.V., Bychkova T.M., Parfenova I.M., Karaulova T.A., Ivanov A.A.

Abstract

In an experiment on outbred male ICR CD-1 mice irradiated at a wide range of doses of gamma irradiation 60Co from 7.4 to 9.4 Gy with a 30-day survival rate from 100 to 5%, the dose-effect and time-effect relationships in relation to animals’ temperature and body mass index during acute radiation sickness were studied. The latent phase of acute radiation sickness is already related to a decrease in body temperature, which is determined using a remote infrared thermometer, in presence of body weight loss. A maximum dose-dependent fall in body temperature was observed in the critical phase of acute radiation sickness, when animals die in large numbers. In the recovery phase, body temperature returned to normal with subsequent body weight gain. Body temperature of irradiated mice is considered as an important criterion for their asthenia and can be used both in theoretical and applied studies.

Biofizika. 2023;68(1):120-124

Investigation of changes in lung volume caused by high-intensity acoustic oscillations at the resonant frequency of the respiratory system

Dragan S.P., Kezik V.I., Bogomolov A.V., Drozdov S.V.

Abstract

This paper presents an experimentally determined dependency of an increase in the volume of the lungs of laboratory animals on the level of high-intensity low-frequency sound at the resonant frequency of their respiratory system. Experiments were conducted on 16 rabbits. A modified two-microphone technique was used for the measurement of the resonant frequency of the respiratory system in the frequency range from 5 Hz to 100 Hz for a step in frequency of 3 Hz. Having determined the resonant frequency, a tone signal was delivered to the lungs at this frequency with an adjustable sound amplitude from 120 to 138 dB. The measurement results indicate that the resonant frequencies of the respiratory system in rabbits decreased by an average of 13%, that corresponds to an increase in lung volume by 33% due to the opening of the alveolar oxygen reserve. The observed phenomenon relating to lung volume increase under the influence of a stimulating high-intensity sound signal at a resonant frequency can be used to enhance the effectiveness of bioacoustic stimulation of human lungs in order to increase the volume of the respiratory system.

Biofizika. 2023;68(1):125-133

Numerical modeling of pre-spawning and spawning migrations of the representative of the family hexagrammidae: the case of the arabesque greenling

Chetirbotsky A.N., Vdovin A.N., Chetirbotsky V.A.

Abstract

This paper presents a spatio-temporal model of greenling dynamics during pre-spawning and spawning mass migrations. The developed model is based on original verified long-term observations and data on industrial fishing in the Peter the Great Bay (Sea of Japan), and the equations of the dynamics of the density of males/females and the mass daily movements of fish are written in terms of the transfer equations. These equations are written in the form of the modified Patlak-Keller-Segel equations, according to which the flow of objects/substances is directed along the gradients of stimulus introduced. It is believed that in the pre-spawning season, adaptation in morpho-physiological (biochemical thermoregulation and a number of other endogenous processes) and behavioral responses of fish to sufficiently long and energy-consuming spawning can occur, where the stimulus for mass movements of fish is optimal environmental conditions for spawning events. During the spawning period, selected sites will be found in convenient and well-aerated embayments located at the bottom of reservoir in the coastal area. Modeling of stimuli-related movements is performed based on information about the preferred water depths of the fish's pre-spawning area and relevant features relating to a selection of suitable bedding sites. It is assumed that the intensity of daily motion is proportional to their linear size (the larger the fish becomes, the faster it is). The equations for the spawning stage take into account the spatial competition of males, but in natural conditions it is observed only in the vicinity of spawning areas. Being away from these areas, males continued to look for new sites good for the spawn. For females, their movement is provoked by males that assembled in schools, the signal of which can be certain chemical elements released by males (for example, mucus secretion from males) or visual contact. The diffusion of fish distribution and the viscosity of the habitat (velocity diffusion) are taken into account. The initial distribution of fish is given according to the average distribution of fish in July over a long-term observation period in the Peter the Great Bay.

Biofizika. 2023;68(1):134-141

Therapeutic effects of high-dose inhaled nitric oxide gas against post-covid syndrome, diabetes or AIDS

Vanin A.F., Pekshev A.V., Pechyonkin E.V., Vagapov A.B., Sharapov N.A.

Abstract

A therapeutic effect of high-dose nitric oxide gas inhalation (more than 1000 ppm) on patients with post-COVID syndrome, diabetes or AIDS is shown. It has been proposed that nitrosonium cations (NO+), derivatives of nitric oxide gas, the emergence of which in the blood or organ tissues of patients is related to disproportion reaction of NO molecules, forming a co-ordinate bond with the Fe2+ion, carried by transferrin or entered into the labile (free) iron pool may act as a therapeutic agent. It is quite probable that treatment of HIV infection (as well as the earlier revealed effect of NO gas on the patients with COVID-19) could be provided by the effects of S-nitrosylation of NO+ cations on thiol groups of viral proteases and host proteins. A beneficial effect of NO+ cations which emerged in the reaction of NO gas molecules in patients with post-COVID syndrome or diabetes can be also associated with an inhibitory effect of these cations on the thiol-containig proteins that are involved in apoptosis.

Biofizika. 2023;68(1):142-149

On the possibility of non-invasive study of the peripheral mechanisms of autonomous regulation of the human cardiovascular system

Nesterov V.P., Burdygin A.I., Ivanov K.B., Korotkov S.M., Sobol K.V., Soroko S.I., Shemarova I.V.

Abstract

The aim of this study was to evaluate the possibility of using the developed method of arterial piezopulsometry for non-invasive study of peculiarities of the functioning of peripheral mechanisms of autonomic regulation of the cardiovascular system in patients of different age and health state. Study emphasizes the importance of determining the variability of the parameters of blood pressure pulse waves as a measure of assessing the participation and role of the components of the neuroendocrine (sympatho-adrenal) efferent link in the formation of a fast and well-regulated response of systemic hemodynamics, using myocytes of the left ventricle of the heart as effectors. This paper discusses the possibility and expediency of personalized use of the arterial piezopulsometry method for pulsometric diagnostics of the functional state and nature of autonomic regulation of the functions of cardiovascular system in patients in order to be able to detect earlier pathological conditions and disorders of peripheral mechanisms that ensure adequate blood supply in humans.

Biofizika. 2023;68(1):150-159

Pathogenetic mechanisms of burn disease associated with oxidative membrane damage and ways of their correction

Vilyanen D.V., Pashkevich N.I., Borisova-mubarakshina M.M., Osochuk S.S.

Abstract

Despite significant progress in the treatment of burn disease, mortality in this pathology can exceed 50% owing to the development of multiple organ dysfunction syndrome when more than 30% of the body surface area is affected. The review describes the most important molecular and biological mechanisms that underlie the development of multiple organ dysfunction syndrome in which free-radicals cause damage to plasma membranes, mitochondria, damaged mitochondria generate other free radicals, mitochondrial DNA is modified and used as a trigger of inflammatory processes in peripheral organs and systems. Secondary changes in the system of lipid transport in the blood and their role in generalization of multiple organ failure and hormonal imbalance are considered. In view of pathogenic metabolic shifts, use of antioxidants (such as quinones) in combination with lipid metabolism modulators is a reasonable strategy to reduce the activity of the inflammatory process and hormonal imbalance in the treatment of burn disease.

Biofizika. 2023;68(1):160-168

Synaptic aspects of the pathogenesis of autism, amyotrophic lateral sclerosis, and Alzheimer’s disease

Khairullin A.E., Mukhamedyarov M.A., Grishin S.N., Teplov A.Y., Nagiev K.K., Ziganshin A.U.

Abstract

Recently, there has been evidence that alterations in functionality of synapses both at the pre- and postsynaptic level play an important role in the pathogenesis of many neurodegenerative diseases and autism spectrum disorders. Of particular interest may be the data on synaptic defects appearing in the early, asymptomatic stages of the disease, when it might still be possible to prevent mass degeneration of neurons. Probably, modulation of synaptic signal transduction at this stage is very effective through therapy of a number of similar diseases. This review aims to explore the role of synaptic structures in the pathogenesis of Alzheimer's disease, amyotrophic lateral sclerosis and autism spectrum disorders.

Biofizika. 2023;68(1):169-178

Analysis of multifractality of various components of electroencephalograms in mental disorders

Dick O.E.

Abstract

The method of finding maxima of the moduli of the wavelet coefficients was used to perform a comparative analysis of the multifractality of various components of electroencephalograms in normal conditions and in mental disorders such as schizophrenia and depression. It is shown that for each type of mental disorders, the position of the singularity spectrum is stable in most areas of the brain, and the main differences between multifractal properties are associated with the alpha components of electroencephalograms. The group of individuals affected with depression is characterized by anticorrelated dynamics of successive values of the alpha components, and the group of individuals with schizophrenia is characterized by a combination of anticorrelated and correlated dynamics, thus, it can be useful for the clinical diagnosis of neuronal disorders.

Biofizika. 2023;68(1):179-186