Volume 64, Nº 2 (2019)

Based on the theory of the formation of sign-alternating hierarchical structures in macromolecular systems, a quantitative approach was developed to assess the chirality sign of individual levels in hierarchical protein structures. Quantitative estimates are necessary for modeling the folding of proteins and their function as molecular machines. Mutual attraction between the α-carbon atoms of amino acids is a sufficient condition for characterizing the level in the hierarchical structure and determining the chirality sign of protein blocks. A quantitative estimate of the twist in helical (secondary) and superhelical (tertiary) structures is provided by the absolute value of the sum of vector cross products. The sign of the scalar product of the direction vector to the vector of the sum of vector products indicates the direction of the twist. Chiral maps were constructed for the secondary and tertiary structures of several proteins. The reliability of the maps was confirmed by analyzing the respective real structures.

Some difficulties in the application of various methods of computer modeling for the study of regularities of formation of spatial structure of DNA are analyzed. Computations of intermolecular interaction energy for all ten pairwise combinations of methylated bases (1-methylpyrimidines and 9-methylpurines) in various mutual base positions were performed due to the important role of nitrous bases. Local energy minima that correspond to different mutual positions of the molecules have been found using different molecular mechanics force fields, ab initio quantum mechanics, and density functional theory. The energy minima that correspond to three types of mutual molecule positions, namely, (1) base positions with two N–H…O and/or N–H…N hydrogen bonds; (2) nearly parallel arrangements of base ring planes, that is, base stacking; and (3) T-shaped (nearly perpendicular) base ring positions and hydrogen bond formation were extensively studied. The majority of these minima were obtained using methods of different complexities; however, the method of calculation determines which minimum is the deepest (global) for certain base combination and relative depths of various minima. Analysis of these simulations and of the computations on simple DNA fragments, as well as of extensive data from the literature suggests that there has been no method suitable for quantitative description of all the experimental data on non-bonded interactions in DNA. The comparison of energy and structure characteristics of the complexes calculated by various methods demonstrates their abilities and shortcomings. A valid description of non-bonded interactions of nucleic acids requires additional investigations of their simple fragments and the combined use of various methods.

β-Bends are typical local structures of the polypeptide chain, are widespread in proteins, and play an important structural and functional role. It is possible to expect a priori with a good degree of certainty that β-bending structures are quite predictable; i.e., there are only a small number of β-bending conformations. Because a pseudo-cycle is closed through hydrogen bonding at the base of a β-bend, the number of independent parameters can be decreased to the extent such that a geometric analysis can be employed instead of a conformational analysis. As an example, a β-bending conformational set can be determined with high accuracy and reliability without using force fields. A conformational analysis of β-bends of the main types (I, I', II, and II') was performed using two independent methods, the original distance geometry procedure and the conformation enumeration procedure with subsequent optimization. A geometric analysis in the developed form was found to be sufficient for a conformational analysis of β-bends; i.e., the number of geometrically consistent β-bending conformations was reduced to two. The first solution found coincided with experimental data from X-ray structural analyses. The second solution was correct based on the geometric analysis, but was improbable in terms of energy because the corresponding values of the dihedral angles fell into strictly forbidden areas of the Ramachandran map as a result of disallowed convergence of atoms; the solution has not been observed experimentally. The results clarified the formation of the main β-bend conformation types, including those containing the so-called forbidden conformations.

It has been shown that various chemical agents (ethylenediaminetetraacetic acid, zinc sulphate, ethyl alcohol, and rotenone) have different effects on preactivation (priming) of neutrophils that develop under weak combined collinear static and alternating magnetic fields (combined magnetic fields: a static field of 42 μT and an alternating field of 0.86 μT with the sum of frequencies 1.0, 4.4 and 16.5 Hz). Low concentrations (0.05%) of ethylenediaminetetraacetic acid decrease the intensity of luminol dependent chemiluminescence of neutrophils in response to an activator of the respiratory burst the peptide N-formyl-Met–Leu–Phe under the action of combined magnetic fields to a lesser extent than in the control. In contrast, ethyl alcohol (0.45%) and zinc sulphate (0.1 mM) have a greater effect on this process under the action of combined magnetic fields. Rotenone (1 μM) has a weak effect on neutrophil chemiluminescence both under the action of combined magnetic fields and in the control.

The effect of different polyoxyethylene–polyoxypropylene triblock copolymers, their concentration, and mode of action on the loading of poly-(lactic-co-glycolic acid) copolymer-based microparticles containing such medicinal agents as radachlorin (chlorin e₆) or ethidium bromide in mesenchymal stem cells was studied. It has been shown that medicinal agents encapsulated inside microparticles affect the loading of these particles in the cytoplasm of mesenchymal stem cells. The number of cells that absorbed the particles with chlorin e₆ is approximately two times lower than that in the experiments with ethidium bromide. It has been shown that pretreatment of microparticles with triblock copolymers is more efficient for loading them in cells compared with simultaneous introduction of triblock copolymers and particles into the culture medium. Treatment of ethidium bromide-containing microparticles with triblock copolymers is not efficient for their loading in mesenchymal stem cells compared to the control. The exception is Pluronic 123; when particles are treated with it at concentrations of 1 and 2%, the loading of particles in cells increases compared to the control by factors of approximately 11 and 5, respectively. For particles with chlorin e₆, their pretreatment with triblock copolymers at a concentration of 4% is most efficient; the loading of the pretreated particles in cells is increased by factors of approximately 3 to 11.

Indices of the patterns of energy metabolism in the rabbit myocardium were studied after vertical whole body vibration with an amplitude of 0.5 mm at frequencies of 8 and 44 Hz generated by an industrial unit. The energy dependent reactions of native mitochondria were investigated by a polarographic technique using a Clark-type closed membrane electrode. The metabolic states of mitochondria were modeled in vitro by varying exogenous energy substrates (succinic acid, a mixture of glutamic and malic acids) before and after the effect of the 2,4-dinitrophenol uncoupler of oxidative phosphorylation. Amital or malonate-inhibitory analysis was used to estimate the contributions of nicotinamide dinucleotide and flavinadenin dinucleotide-dependent substrates to the endogenous respiratory activity of mitochondria. The results show that changes in the functional activity of myocardial mitochondria in response to vibration depend on the frequency and duration of exposure and are seen as inhibition of the NAD-dependent link of the respiratory chain and activation of the oxidation system of succinic acid, the ligand of metabotropic purinergic G-protein-conjugated receptor GPR91 from the P2Y-family. Due to a systematic deregulated effect vibration can be used as a factor to model bio-energetic cellular hypoxia, to study vibration phenomena at the level of energy producing systems of tissues and organs and for assessment of the vibroprotective properties of drugs.

The formation of steady-state visual evoked potentials on the basis of visual evoked potentials was analyzed. Using the regression model, it was shown that the accumulation of steady-state visual evoked potentials depends in part on the time position of visual evoked potentials, as suggested by different regression coefficients set for visual evoked potentials with different relative phase shifts. The description of steady-state visual evoked potentials using a linear regression model with iteration of visual evoked potentials was better at the photostimulation frequency of 14 Hz than at the frequency of 8 Hz. In the vast majority of cases, the number of groups of frequency peaks (chains of local maxima) detected on the spectra in the frequency–time domain was greater for signals induced at 8 Hz than for those induced at 14 Hz. This relationship was maintained both for steady-state visual evoked potentials recorded directly in test subjects and for signals artificially reconstituted from visual evoked potentials. For photostimulation at 14 Hz, the frequency components of the signal that increased and decreased their period were equally common, while at 8 Hz the number of chains of local maxima increased and their frequency decreased. It was shown that a group of subjects exists whose response to high-frequency photostimulation involves a decrease in the number of pronounced frequency components that contribute to the formation of the steady state evoked potential. At the same time, the modulation of frequency components in the native steady-state visual evoked potentials was predominantly characterized by a decrease in the signal frequency, which was not observed in the model signal reconstituted from a series of visual evoked potentials of the same subject.

The effect of deuterium-depleted water on oxidative processes in the rat brain under physiological or hypoxic conditions was studied. The results obtained by a tissue culture method that characterize the functional parameters of neurons under stress are also presented. Results on free radical processes in the rat brain tissues demonstrated that consumption of deuterium-depleted water over 2 weeks has a stress effect. The long-term consumption of deuterium-depleted water caused activation of non-specific protective systems. The effect of a saline solution prepared with deuterium-depleted water on a cerebellar tissue culture was also studied. When incubation occurred in a saline solution based on deuterium-depleted water, glucose deprivation and temperature stress (39°C) were found to result in increased cell death in the neuronal culture. The neuron death rates under physiological conditions were similar in the case of both 150 and 50 ppm deuterium. At the same time, the mitochondrial membrane potential of cerebellar neurons decreased in the deuterium-depleted medium. Thus, incubation of cerebellar neurons in the deuterium-depleted saline solution had no cytoprotective effect.

This paper presents two new fundamental principles of the functioning of real neural networks of the brain. These principles have inspired the design of artificial neural networks (a neuro-computer). In addition to well-known properties of artificial neurons (threshold properties, neural network formation, and backward propagation of errors), we describe two new major properties of real neural networks of the brain by which a neuroemulator may work. We discuss the practical usefulness of these properties for the neuro-computer. The first property is permanent statistical chaos in the structure and functions of the brain neural networks. The second property is reverberations, or multiple iterations, in the work of neural networks. The introduction of these two properties to the work of the common artificial neural network provides a new quality, that is, solving the problem of systemic synthesis and finding rank parameters. Modern science has not investigated and solved this problem, which is a general fundamental problem in medicine. It has been shown that this task is identical to the heuristic activity of the brain.

The dynamics and specific features of the restoration of forbs–grass–wormwood and wormwood–grass phytocoenoses on fallow lands in the Altai region, the Republic of Khakassia, were determined on the basis of terrain and satellite data. The species composition, structure, and phytomass of the phytocoenoses were revealed. A gradual formation of structural elements of steppe communities in the studied areas was determined. This work showed the usefulness of time series of satellite data on the NDVI (Normalized Difference Vegetation Index) obtained with the use of MODIS (Moderate Resolution Imaging Spectroradiometer) for the study of specific features of restored fallows. In general the biological parameters, projective cover, and phytomass determine the value of the NDVI. Interannual NDVI variability reflects the rate and time period of fallow restoration. From a certain point, the parameters increased and became close to the steppe (control variant). It has been revealed that not only abiotic factors (climate and soils), but also biotic parameters (grazing and recreational load) affect the NDVI. In this connection, the duration of restoration stages does not always correspond to the published data. They vary under different conditions. Climatic data of the Abakan meteorological station (index 29862 in the network of the World Meteorological Organization) for the period from 2000 to 2017 were statistically treated. The long-term annual average norms of temperatures and precipitation amounts (year and month) for the World Meteorological Organization base period of 1961–1990 were calculated. The dynamics of the temperature and precipitation, using long-term series of data, has been analyzed.