Doklady Rossijskoj akademii nauk. Nauki o žizni

Один из крупнейших в мире научных журналов, орган Президиума Российской академии наук. Журнал «Доклады Российской академии наук» публикует сообщения о крупных научных исследованиях, имеющих приоритетный характер, и оригинальных, нигде ранее не опубликованных исследованиях в области математики, естественных и технических наук.

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Vol 510, No 1 (2023)

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Articles

GENE KNOCKOUT SUPPRESSES EXPRESSION OF DNA BASE EXCISION REPAIR GENES
Zakharenko A.L., Malakhova A.A., Dyrkheeva N.S., Okorokova L.S., Medvedev S.P., Zakian S.M., Kabilov M.R., Tupikin A.A., Lavrik O.I.
Abstract

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common “hubs” for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):219-224
pages 219-224 views
INCUBATION OF LYMPHOCYTES WITH IL-2 CAUSES THE APPEARANCE OF ANTITUMOR T CELLS CARRYING FC, CD25 AND LFA-1 ON THE SURFACE
Ivanova O.K., Sharapova T.N., Romanova E.A., Yashin D.V., Sashchenko L.P.
Abstract

To carry out antitumor activity against cells that have lost surface antigens, human lymphocytes must have a certain repertoire of surface proteins capable of contacting a tumor cell and inducing programmed cell death in it. In this work, we showed that activation of healthy donor cells by IL-2 cytokine within 6 days causes the appearance of FasL, CD25 and LFA-1 proteins on CD8+CD25+ T lymphocytes, and also converts the LFA-1 protein into an active form having a high affinity for its target, ICAM-1 integrin. The appearance of these proteins on the surface of this subpopulation of lymphocytes allows them to induce programmed cell death in HLA-negative tumor cells.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):225-230
pages 225-230 views
BARNASE-BARSTAR SPECIFIC INTERACTION REGULATES CAR-T CELLS CYTOTOXIC ACTIVITY TOWARD MALIGNANCY
Kalinin R.S., Shipunova V.O., Rubtsov Y.P., Ukrainskay V.M., Schulga ., Konovalova E.V., Volkov D.V., Yaroshevich I.A., Moysenovich .M., Belogurov A.A., Telegin G.B., Chernov A.S., Maschan M.A., Terekhov S.S., Knorre V.D., Khurs E., Gnuchev N.V., Gabibov A.G., Deyev S.M.
Abstract

The development of CAR-T specific therapy made a revolution in modern oncology. Despite the pronounced therapeutic effects, this novel approach displayed several crucial limitations caused by the complications in pharmacokinetics and pharmacodynamics controls. The presence of the several severe medical complications of CAR-T therapy initiated a set of attempts aimed to regulate their activity in vivo. We propose to apply the barnase-barstar system to control the cytotoxic antitumor activity of CAR-T cells. To menage the regulation targeting effect of the system we propose to use barstar-modified CAR -T cells together with barnase-based molecules. Barnase was fused with designed ankyrin repeat proteins (DARPins) specific to tumor antigens HER2 (human epidermal growth factor receptor 2) The application of the system demonstrates the pronounced regulatory effects of CAR-T targeting.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):231-235
pages 231-235 views
INTERACTOME OF PARAOXONASE PON2 REVEALS NEW PATHWAYS FOR TUMOR GROWTH REGULATION
Karlov V.D., Pestov N.B., Shakhparonov M.I., Korneenko T.V.
Abstract

The interactome of paraoxonase-2 encoded by the PON2 gene was investigated. A cDNA library was screened using a yeast two-hybrid system to search for new proteins interacting with human PON2. Analysis of the identified candidates, along with previously published data on interactors obtained by other methods, indicates the presence of a significant number of indirect interactions between PON2 and EGFR and, consequently, possible regulation of tumor growth with mutant EGFR involving PON2.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):236-242
pages 236-242 views
INFLUENCE OF THE CULTIVATION CONDITIONS OF THE GLIOBLASTOMA NEUROSPHERE ON THE EXPRESSION OF MALAT1 AND LINCROR LONG NON-CODING RNA GENES
Mazur D.V., Mishanova A.V., Kovalenko T.F., Shakhparonov M.I., Antipova N.V.
Abstract

ABSTRACT Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. One of the reasons for the resistance of MGB to treatment is the extreme heterogeneity of the tumor and, in particular, the presence of cancer stem cells (CSCs) in the population of glioblastoma cells. In this work, we investigated the effect of conditions that reduce the proportion of CSCs in the GBM cell population on the levels of long noncoding RNAs (lincROR and MALAT1) involved in the formation of the phenotype of glioblastoma cancer stem cells. We have shown that culturing under conditions that cause a decrease in cell stemness (when fetal calf serum is added to the culture medium) affected the content of these transcripts: in the cells of most of the analyzed lines, a decrease in the level of the positive stemness regulator lincROR and an increase in the content of MALAT1 were noted.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):243-246
pages 243-246 views
STRUCTURAL MECHANISM OF IONIC CONDUCTIVITY OF THE TRPV1 CHANNEL
Trofimov Y.A., Minakov A.S., Krylov N.A., Efremov R.G.
Abstract

The so-called “hydrophobic gating” is widely discussed as a putative mechanism to control water and ion conduction via ion channels. This effect can occur in narrow areas of the channels pore lined by non-polar residues. In the closed state of the channel, such regions may spontaneously transit to a dehydrated state to block water and ions transport without full pore occlusion. In the open state, the hydrophobic gate is wide enough to provide sustainable hydration and conduction. Apparently, the transport through the open hydrophobic gate may by facilitated by some polar residues that assist polar/charged substances to overcome the energy barrier created by nonpolar environment. In this work, we investigated the behavior of Na+ ions and their hydration shells in the open pore of the rat TRPV1 ion channel by molecular dynamics simulations. We show that polar protein groups coordinate water molecules in such a way as to restore the hydration shell of ions in the hydrophobic gate that ensures ion transport through the gate in a fully hydrated state.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):247-251
pages 247-251 views
INFLUENCE OF TYROSYL-DNA PHOSPHODIESTERASE 1 INHIBITOR ON THE PROAPOPTOTIC AND GENOTOXIC EFFECTS OF ANTICANCER AGENT TOPOTECAN
Chepanova A.A., Zakharenko A.L., Dyrkheeva N.S., Chernyshova I.A., Zakharova O.D., Ilina E.S., Luzina O.A., Salakhutdinov N.F., Lavrik O.I.
Abstract

To date, various strategies have been proposed to increase the effIciency of cancer therapy. It is known that the action of DNA repair system can determine the resistance of cancer cells to DNA-damaging chemotherapy and radiotherapy, and one of these ways to increase therapeutic efficiency is the search for inhibitors of enzymes of the DNA repair system. Inhibition of the DNA repair enzyme tyrosyl-DNA phosphodiesterase1 (Tdp1) leads to an increase in the effectiveness of the topoisomerase 1 (Top1) inhibitor, the anticancer drug topotecan. Covalent complexes Top1-DNA, which are normally short-lived and are not a threat to the cell, are stabilized under the influence of topotecan and lead to cell death. Tdp1 eliminates such stabilized complexes and thus weaken the effect of topotecan therapy. We have previously shown that the use of the usnic acid hydrazonothiazole derivative OL9-119 in combination with topotecan increased the antitumor and antimetastatic efficacy of the latter in a mouse model of Lewis lung carcinoma. In this work, it was shown that the combined use of topotecan and Tdp1 inhibitor, the hydrazonothiazole derivative of usnic acid OL9-119, leads to an increase in the DNA-damaging effect of topotecan which is used in the clinic for the treatment of cancer. The study of the proapoptotic effect of the compound OL9-119 showed that the compound itself does not induce apoptosis, but increases the proapoptotic effect of topotecan. The results of the study could be used to improve the effectiveness of anticancer therapy and/or to reduce the therapeutic dose of topotecan and, therefore, the severity of side effects.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):252-258
pages 252-258 views
MODULAR NANOTRANSPORTERS CAPABLE OF BINDING WITH SARS-COV-2 VIRUS NUCLEOCAPSID PROTEIN INTO TARGET CELLS
Khramtsov Y.V., Ulasov A.V., Lupanova T.N., Georgiev G.P., Sobolev A.S.
Abstract

Based on the literature data, an antibody-like molecule, a monobody, was selected that is capable of interacting with the nucleocapsid protein (N-protein) of the SARS-CoV-2 virus with high affinity (dissociation constant 6.7 nM). We have previously developed modular nanotransporters (MNTs) to deliver various molecules to a selected compartment of target cells. In this work, a monobody to the N-protein of the SARS-CoV-2 virus was included in the MNT using genetic engineering methods. In this MNT, a site for the cleavage of the monobody from the MNT in endosomes was also introduced. It was shown by thermophoresis that the cleavage of this monobody from MNT by the endosomal protease cathepsin B leads to a 12-fold increase in the affinity of the monobody for the N-protein. Cellular thermal shift assay showed the ability of the obtained MNT to interact with the N-protein in A431 cells transfected with the SARS-CoV-2 N-protein fused to the mRuby3 fluorescent protein.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):259-262
pages 259-262 views
THE EFFECT OF THE AGONIST CHOLECYSTOKININ-4 D-GB-115 ON THE CHARACTER OF MOTOR ACTIVITY OF
Gruzdev G.A., Soboleva L.V., Kamensky A.A.
Abstract

The study investigated the effect of GABA in various concentrations and D-GB-115 at a concentration of 10–10 mol/ml on the behavior of Paramecium caudatum. It has been shown that GABA increases motor activity and changes the movement strategy of these protozoa, and the dose-effect relationship is domed, which can be explained by the presence of two types of GABA receptors in the outer membrane of paramecia: GABA-A and GABA-B. The range of active concentrations of GABA ranges from 10–6 to 10–16 mol/ml. The effect of pharmacological agents interacting with the GABA system on the behavior of infusoria: nembutal and D-GB-115.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):263-267
pages 263-267 views
SIMULATED MICROGRAVITY AND COCULTURING WITH HEMATOPOIETIIC CELLS OPPOSITELY MODULATE WNT SIGNALING IN MESENCHYMAL STROMAL CELLS
Ratushnyy A.Y., Tyrina E.A., Buravkova L.B.
Abstract

The osteogenic potential of mesenchymal stromal cells (MSCs) can determine the bone homeostasis and the physical characteristics of bones. Microgravity reduces the ability of these cells to differentiate in osteogenic direction. It has been shown that the addition of hematopoietic stem and progenitor cells (HSPCs) to MSC culture in vitro can have the opposite effect. The aim of this study was to identify transcriptional changes in 84 genes associated with Wnt signaling in MSCs during microgravity simulation and interaction with HSPCs. The results indicate an increase in the non-canonical Wnt signaling activity during MSCs and HSPCs cocultivation, while simulated microgravity enhances the canonical component of this signaling pathway. These changes may underlie the modulation of osteogenic potential of MSCs in hematopoietic niche under microgravity.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):268-272
pages 268-272 views
WATERFOWL WINTERING IN CITIES OF TEMPERATE CLIMATE ZONE AND FACTORS THAT DETERMINE THEM
Avilova K.V., Polezhankina P.L.
Abstract

For the first time, the regularities of the number and species diversity dynamics of wintering waterfowl in 30 cities of Russia over eight years have been analyzed. The total number increased by 35%. The species diversity in total reaches 32 species. Mallards (Anas platyrhynchos) dominate in all 30 cities. According of total characteristics, all cities were divided into seven clusters, significantly differing from each other. The geographical location and climatic characteristics of cities are the main conditions for the existence of both people and birds. The number variability of wintering birds by 93% is determined by the area of the city and the number of its population, and the number of species by 62% is determined by the longitude, the average January temperature of the city and the number of its population (p < 0.001). The number of birds and species correlate with the “age” of wintering place (p < 0.05). If the rate of the urbanization continues, the number and species diversity will continue to grow.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):273-277
pages 273-277 views
SEASONAL VARIABILITY OF IMMUNOHEMATOLOGICAL PARAMETERS OF PERPHERAL BLOOD OF THE BAT (BOIE, 1825) LIVING IN THE URALS
Kovalchuk L.A., Mishchenko V.A., Chernaya L.V., Snit’ko V.P., Bolshakov V.N.
Abstract

A comparative analysis of the immunohematological parameters of bats from fauna of the Urals Myotis dasycneme (Boie, 1825) in seasonal periods of their annual life cycle is presented for the first time. Multivariate nonparametric analysis of variance showed the absence of significant gender differences in bats according to the studied parameters of red blood (p = 0.35). The sexual determination of bats was established by the content of leukocytes, band neutrophils and segments neutrophils, lymphocytes in the blood (p < 0.05). Males are characterized by a higher development of innate immunity in the summer compared to females (p < 0.05). In the autumn-winter hibernation period, males and females have a significant lymphocytic profile (50.6–53.5%), providing immune “supervision” and specifically reactive activation of the acquired adaptive immune response.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):278-282
pages 278-282 views
THE LIFETIME OF COLOUR MORPHS IN THE POLYMORPHIC POPULATIONS OF THE MOLE VOLE AND THE HYPOTHESIS OF ADAPTIVE POLYMORPHISM
Vasil’ev A.G., Bol’shakov V.N., Vasil’eva I.A., Sineva N.V.
Abstract

For the first time, different lifetime was established in representatives of three colour morphs (brown, bicolor, black) in 10 populations of the Mole Vole of the Volga region, the Urals and the Trans-Urals. With the longest life span of the species – 5 years, numerically dominant morphs in the population are able to live 1–4 years longer than the accompanying ones. Spearman’s correlation coefficient between the longest life span of morphs and their proportion in the population was Rsp = 0.81. A number of morphofunctional features of colour morphs have been identified. The results obtained have general biological significance, confirming the hypothesis of adaptive polymorphism, and allowing us to evaluate the evolutionary and ecological mechanisms of the formation of selective advantages of morphs (as probable ecomorphs), using them as a natural model of the initial stage of sympatric formation in different parts of the range.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):283-287
pages 283-287 views
THE FIRST DATA ON THE NUTRITION OF THE URAL CAVE BEAR (MAMMALIA, CARNIVORA, URSIDAE, () KANIVETZ VERESTCHAGIN, 1973) BASED ON THE RESULTS OF THE ANALYSIS OF ISOTOPES C and N
Kosintsev P.A., Simonova G.V., Konovalova K.Y.
Abstract

The first data on the content of isotopes 13C and 15N in the collagen of 16 bones of the Ural cave bear (Ursus (Spelaearctos) kanivetz Verestchagin, 1973) were obtained from the Tayn (Secrets) cave (55°25' N, 57°46' E). The bones date from the middle of MIS 3. The bones of males and females aged about 2 years, about 3 years and older than 4 years were studied. There are no noticeable differences in isotope signatures between individuals of different ages and different sexes. Since the second year of life, cave bears have been eating plant food on their own. The values of δ13C and δ15N of the Ural cave bear are close to the values for U. (S.) spelaeus ingressus.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):288-291
pages 288-291 views
CAN SHREWS AVOID COMPETITION WHEN VIOLATING THE HUTCHINSON’S ECOLOGICAL RULE?
Vasil’ev A.G., Bol’shakov V.N., Vasil’eva I.A., Kourova T.P.
Abstract

It is established that the rule of G. Hutchinson’s idea of the ratio of body weight and size and foraging organs of similar species is not fully respected when comparing the species of shrews of the genus Sorex. The similarity of the centroid sizes of the mandible of large species S. isodon and S. araneus was revealed. By methods of geometric morphometrics, differences in the shape of the mandible, which is actively used in foraging, have been established between the species. Interspecific differences in mandibular indices reflecting trophic specialization and functional features of mandibles were found. Therefore, shrews can avoid competition even if Hutchinson’s rule is violated, and not so much due to the size, but due to the transformation of the lower jaw, its specialization, methods of capturing prey and changing the diet. Consequently, Hutchinson’s ecological rule is not mandatory, but only one of the conditions for reducing competition between closely related species.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):292-296
pages 292-296 views
NON-SELECTIVE EXPRESSION OF SHORT-WAVELENGTH CONE OPSIN IMPROVES LEARNING IN MICE WITH RETINAL DEGENERATION IN A VISUALLY GUIDED TASK
Idzhilova O.S., Kolotova D.E., Smirnova G.R., Abonakour A., Dolgikh D.A., Petrovskaya L.E., Kirpichnikov A.o., Ostrovsky A.o., Malyshev A.Y.
Abstract

Here, we explore the potential of an animal opsin non-selectively expressed in various neuronal elements of the degenerative retina to restore impaired visual function. In this study, a knockout murine model of inherited retinal distrophy was used. Animals were injected intravitreally with either a virus carrying gene of the short-wavelength cone opsin associated with a reporter fluorescent protein, or a control virus carrying the sequence of a modified fluorescent protein that had an enhanced membrane tropism. The viral transduction induced pronounced opsin expression in ganglion, bipolar, and horizontal retinal neurons. Behavioral testing of the treated mice in the visually guided task in the trapezoid Morris water maze showed a partial recovery of learning ability in animals whose retinas had been transduced with the cone opsin.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):297-302
pages 297-302 views
ALLELOTOXICITY OF GREENHOUSE SUBSTRATES AFTER VEGETABLE CULTIVATION
Shoba S.A., Gracheva T.A., Fedotov G.N., Ter-Petrosyants G.E., Jancharov T.M., Gorepekin I.V., Ushkova D.A.
Abstract

It is known that stresses during the cultivation of agricultural plants reduce yields, and the occurrence of stressful effects leads to the release of allelotoxins by plants into the soil. It has been suggested that this factor can have a noticeable effect on the vegetation of vegetables in greenhouses, and a decrease in the concentration of allelotoxins in greenhouse substrates can improve the vegetation of plants. To verify these assumptions, the allelotoxicity of greenhouse substrates and the content of microorganisms in them under well and poorly vegetating plants of cucumbers, tomatoes and peppers were determined. It was found that there are significantly more allelotoxins and fewer prokaryotes in the substrates under poorly vegetating plants, which confirmed the assumption about the significance of the allelotoxins influence on the cultivation of vegetables in greenhouses. The introduction of humate solutions with a high sorption capacity in relation to allelotoxins into the root zone of plants makes it possible to significantly improve the vegetation of cucumbers and may be a promising direction for increasing vegetable yields in greenhouses.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):303-307
pages 303-307 views
SUBSP. NOV. (VESPERTILIONIDAE, CHIROPTERA) FROM THE LOWER PLEISTOCENE OF THE TAURIDA CAVE IN CRIMEA
Lopatin A.V.
Abstract

A new northern serotine bat Eptesicus nilssonii varangus subsp. nov. is described on the base of an incomplete skull and a mandibular fragment from the Lower Pleistocene deposits of the Taurida cave in the central Crimea. This is the earliest record of the species. The presence of E. nilssonii (Keyserling et Blasius, 1839) in the Early Pleistocene bat assemblage of the Taurida cave indicates that this species lived in the south of Eastern Europe before its spreading into Central and Southeastern Europe.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):308-315
pages 308-315 views
IDENTIFICATION OF SIGNIFICANT RNA-BINDING PROTEINS IN THE PROCESS OF CD44 SPLICING USING THE BOOSTED BETA REGRESSION ALGORITHM
Novosad V.O.
Abstract

The expression of RNA-binding proteins and their interaction with the spliced pre-mRNA are the key factors in determining the final isoform profile. Transmembrane protein CD44 is involved in differentiation, invasion, motility, growth and survival of tumor cells, and is also a commonly accepted marker of cancer stem cells and epithelial-mesenchymal transition. However, the functions of the isoforms of this protein differ significantly. In this paper, we developed a method based on the boosted beta regression algorithm for identification of the significant RNA-binding proteins in the splicing process by modeling the isoform ratio. The application of this method to the analysis of CD44 splicing in colorectal cancer cells revealed 20 significant RNA-binding proteins. Many of them were previously shown as EMT regulators, but for the first time presented as potential CD44 splicing factors.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):316-321
pages 316-321 views
184–188 NUCLEOTIDES DELETION OF HUMAN TELOMERASE RNA DOES NOT AFFECT ON THE TELOMERASE FUNCTIONING
Shliapina V.L., Dontsova O.A., Rubtsova M.P.
Abstract

Telomerase is a ribonucleoprotein complex, the main components of which are telomerase RNA and reverse transcriptase. Previously, it was shown in our laboratory that human telomerase RNA contains an open reading frame, starting at adenine in position 176. The open reading frame encodes the hTERP protein, and the deletion of nucleotides 184–188 of human telomerase RNA disrupts the open reading frame and leads to the absence of hTERP. Human telomerase RNA has a conserved structure, changes in which affect telomerase activity. In this work, we have shown that the deletion of nucleotides 184–188 of telomerase RNA does not affect the functioning of telomerase.

Doklady Rossijskoj akademii nauk. Nauki o žizni. 2023;510(1):322-328
pages 322-328 views

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