Over the past decades, the approaches to writing and formatting scientific articles, as well as to the choice of editions for publication by scientists of the results of their research (both experimental and theoretical) have changed dramatically. Much attention is now paid by most specialists to formal ratings of scientific journals, since it is they which determine mainly how great the chances of the scientists published in them are to get grants for their research. And without serious funding at the present stage, it is practically impossible to engage in not only applied, but also fundamental science. In particular, this has become especially important for biologists and biomedical specialists working in a wide variety of fields, because they tend to use expensive equipment, reagents and experimental animals in their work. In this regard, any scientists working in the field of Life Sciences must be able to choose the right journals for their publications, based on the scientometric indicators of the editions. No less important is the problem of formatting/designing scientific articles, since high ranked journals reject a significant percentage of manuscripts that do not meet the requirements, not only after peer-reviewing, but also before it (in the “rapid rejection” mode). The authors of this article consider it necessary to introduce appropriate courses of lectures into the curricula of students of biological and biomedical specialties. A list of issues that are proposed to be touched in such lectures is considered, including the basics of scientometrics, work on lists of references, search for possible borrowings in a manuscript, requirements for illustrations, compliance with ethical standards, determining whether a scientific publication is a “predatory” one, peer-reviewing scientific articles, their correct structuring, etc.

The effect of the cytostatic antitumor drug ONC201 on the number of mitochondrial nucleoids and the average size of mitochondria in the BT474 human breast cancer cells was studied. It was shown that incubation of BT474 cells with ONC201 (10 μM) for 24 h reduces the number of nucleoids from 262 ± 46 to 140 ± 27 per cell, and in cells incubated with drug for 48 h the number of mitochondrial nucleoids was further reduced to 67 ± 22 per cell. It was found that the ONC201-induced change in the number of nucleoids per cell depends on the duration of treatment. Short-term (24 h) and long-term (48 h) exposure of cells to a single dose of ONC201 led to a reversible and irreversible change in the number of nucleoids per cell, respectively. Thus, after 24 h of exposure and subsequent 120 h washout with ONC201-free medium, the number of nucleoids was restored to 211 ± 47 per cell, while 120-hour washout of drug after 48 hours of treatment did not lead to the restoration of the number of nucleoids, and their number remained at the level of 70 ± 59 per cell. Changes in the number of mitochondrial nucleoids, regardless of the duration of cell treatment with ONC201, positively correlated with changes in the average size of mitochondria as an indicator of their morphology. It is concluded that ONC201 has a cytostatic effect on BT474 cells in culture, suppresses cell proliferation and induces a reversible or irreversible decrease in the number of mitochondrial nucleoids and fragmentation of mitochondria, depending on the duration of treatment.

The problem of correct interpretation of data on the mean age of death of people in different historical periods based on information presented in Wikipedia and included in the “Personalities of the Encyclopedia” database is considered. The specificity of these data, associated with censoring and the nature of their collection, leading to selectivity, is noted. An approach is proposed that takes into account these circumstances, which makes it possible to clarify the obtained patterns of life expectancy and expand the historical range of research. 

The antioxidant system activity during normal pregnancy and pregnancy following by hypoxic stress

Pregnancy in mammals is characterized by an increase in basal oxygen consumption, as it develops there is an increase in oxidative stress while in pregnancy complicated by hypoxic stress the oxidative damage enhances. The oxidative stress during prenatal development seems to be one of the key factors in the pathogenesis of most pregnancy disorders, including preterm birth and preeclampsia. The growing demand for oxygen increases either the production of reactive oxygen species or the synthesis of antioxidant defense components. To assess the antioxidant defense activity in rats, the content of non-protein thiols in the blood and liver homogenate, catalase activity in liver homogenate, superoxide dismutase activity in blood plasma and liver homogenate, total antioxidant activity in blood plasma, and the intensity of lipid peroxidation in blood plasma and liver homogenate were determined. According to data obtained a decrease in antioxidant defense activity in blood plasma and liver of females is shown in the prenatal period of normal pregnancy and, particularly, in the same period of pregnancy complicated by hypoxic stress. It can be assumed that changes in blood antioxidant defense parameters reflect changes not only in mother’s body, but also in placenta, providing potential danger to the developing fetus.

The skeletal muscles contractile activity is associated with increased reactive oxygen species (ROS) production. Respiratory and locomotor muscles differ in the patterns of contractile activity, which can create different conditions for ROS production and their effect on feed arteries. The aim of this work was to study the role of ROS, including produced by NADPH oxidases (NOX), in diaphragm artery (a. phrenica) and deep shoulder artery (a. profunda brachii) tone regulation of the rat. Vasomotor responses of arterial preparations were studied in isometric regimen. The NOX inhibitor, VAS2870, caused relaxation, which was more pronounced in the diaphragm arteries compared to the shoulder arteries: at the concentration of 1 μM, the diaphragm arteries relaxed to 33%, and the shoulder arteries – to 91% of the precontraction level. Tiron (O2. - scavenger) showed similar results: at the 10 mM concentration, it caused relaxation of the diaphragm arteries to 38%, and the shoulder arteries – to 66%. At the same time, catalase (3000 U/ml) increased the deep shoulder arteries contraction but did not affect it in the diaphragm arteries. Using quantitative PCR, it was shown that the contents of mRNA isoforms NOX, p22phox, p47phox, p67phox, Poldip2, Gpx-1, SOD-1 and catalase do not differ between arteries, while the content of SOD-3 mRNA in the diaphragm arteries is less than in the shoulder arteries. Thus, the contribution of ROS, produced by NOX, to the feed arteries tone regulation of the respiratory muscles is higher than in the locomotor muscles. Experiments using tiron and catalase have shown that O2. - increases the arteries contractile responses, while H2O2, on the contrary, causes the shoulder arteries relaxation. One of the reasons for the more pronounced effect of O2 - in the diaphragm arteries may be the relatively low SOD-3 expression.

Mononucleosomes assembled using DNA templates of various lengths that contain a nucleosome-positioning sequence are widely used in molecular biological studies, but their structural features require detailed investigation. The single-particle fluorescence microscopy based on the Förster resonance energy transfer was used to compare the structure of nucleosomes with two 20 bp length DNA linkers and core-nucleosomes without linkers (CN) in solutions containing 150 mM KCl, 5 mM MgCl2 (or without MgCl2), as well as in solutions with increased ionic strength (0.5 and 0.7 M KCl). It was found that these nucleosomes are present in solutions as two dominant subpopulations, which differ in the DNA folding on the histone octamer. It was revealed that CN and 2LN differ in the ratio of these subpopulations, and the differences increase in the presence of Mg2+ ions. With an increase in the ionic strength, conformational reorganizations occur in the core region of the nucleosomes. The character of the reorganizations differs in 2LN and CN at 0.5 M KCl, but becomes similar at 0.7 M KCl. The obtained data indicate that, despite the similar conformations of 2LN and CN, the same factors can induce different effect on the structure of these nucleosomes, and it should be taken into account when, for example, studying the interactions of mononucleosomes with various nuclear proteins in vitro.

The effect of non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase (COX)-2 inhibitor etoricoxib and non-selective COX inhibitor diclofenac sodium, on the behavior of rats was evaluated with a single oral administration at doses of 1 and 10 mg/kg individually and in combination with 2-ethyl-6-methyl-3-hydroxypyridine succinate (mexidol). Both COX inhibitors at a dose of 10 mg/kg decrease locomotor activity in the open field test, and the selective COX-2 inhibitor at a dose of 10 mg/kg also increases the duration of immobility of animals in the tail suspension test. The use of etoricoxib and diclofenac sodium at a low dose (1 mg/kg) with mexidol at a dose of 25 mg/kg, in which the latter enhances the antiinflammatory effect of the COX inhibitors, does not lead to behavioral deviations similar to those associated with the NSAIDs at a dose of 10 mg/kg. Moreover, combinations of COX inhibitors (1 mg/kg) and mexidol (25 mg/kg) increase the locomotor activity of rats. This justifies further research of the effect of antioxidants on the severity of the main and side effects of NSAIDs, especially when administered as a course.

The SARS-CoV-2 virus causes the coronavirus infection COVID-19 and remains in the focus of the researchers around the world. The penetration of the SARS-CoV-2 virus into the cell begins with the binding of its S-protein to the angiotensin-converting enzyme-2 (ACE2) expressed on the cell surface. The study of the spatial structure of the S-protein is necessary for the understanding of the molecular aspects of its functioning. At present, the structure of almost the entire S-protein molecule has been well studied by experimental methods, with the exception of its endodomain, transmembrane domain, and adjacent ectodomain residues. We performed molecular modeling of the structure of the S-protein fragment corresponding to its supercoiled HR2 domain and fully palmitoylated transmembrane domain. The stability of the model in the lipid bilayer is confirmed by means of molecular dynamics simulations in full-atomic and coarse-grained representation. It was shown that palmitoylation leads to a significant decrease in the mobility of the transmembrane domain and local thickening of the bilayer, which may be important for the process of protein trimerization.

Women around the world live longer than men. The question of why this is happening is very interesting, but still unresolved in gerontology. There are a number of proposals to explain the mechanisms underlying this phenomenon, but there are no clearly confirmed or refuted ones among them. This is probably due to the fact that it is extremely difficult to organize testing of such hypotheses for Homo sapiens, and the available data on animals are often contradictory and their results cannot be fully transferred to humans. In the article, we tried to identify one of the possible mechanisms leading to sex differences in life expectancy in the human population. The depressing effect of testosterone on the immune system of women is much weaker than on the immune system of men. The concentration of testosterone in the blood of men is 10–18 times higher than that of women, and after the onset of menopause, the already low concentration of testosterone in women drops by another 25–50%. The inhibitory effect of testosterone on the immune system of women is much weaker than on the immune system of men with respect to both concentration and duration of the effect. The immune system of men weakens with age to a greater extent, which leads to an increased incidence of infectious, oncological, and other immune-dependent pathologies, which just reduces the minimal, middle, and maximum life span of men compared with women.

A patient with asymptomatic QT interval prolongation was found to have missense mutation c.277G>A (p.Val93Ile) in the KCNJ2 gene, previously described in the literature as the cause of a familial form of atrial fibrillation only. The corresponding amino acid substitution was introduced into the plasmid encoding the Kir2.1 channel and the mutant gene was expressed in Chinese hamster ovary cells (CHO-K1) to evaluate the effect of the mutation on IK1 current parameters. Using the whole-cell patch-clamp technique in the potential fixation mode, the integral current of IK1 was studied. As a result of the study, it was shown that the c.277G>A (p. Val93Ile) mutation is implemented according to the “gain of function” type and significantly changes the functioning of Kir 2.1 channel. The presence of a stable activating effect on protein function argues in favor of the clinical significance of the identified variant.

Correction to: "Effect of cyclooxygenase inhibitors etoricoxib and diclofenac sodium as well as their combinations with mexidol on behavior in rats"

https://vestnik-bio-msu.elpub.ru/jour/article/view/992