Acta Naturae

Acta Naturae is a new international journal on life sciences based in Moscow, Russia. Our goal is to present scientific work and discovery in molecular biology, biochemistry, biomedical disciplines and biotechnology. These fields represent the most important priorities for the research and engineering development both in Russia and worldwide. Acta Naturae is also a periodical for those who are curious in various aspects of biotechnological business, innovations in pharmaceutical areas, intellectual property protection and social consequences of scientific progress. The journal will publish analytical industrial surveys focused on the development of different spheres of modern life science and technology.

Being a radically new and totally unique publication in Russia, Acta Naturae will be useful to both representatives of fundamental research and experts in applied sciences.

The editorial council and editorial board include prominent scientists from Russia and abroad: Anatoly Grigoriev, Take Rolex vice-president of Russian Academy of sciences, Alexander Gabibov, Sergey Kochetkov, Patrick Masson, Alan Friboulet, Alfonso Tramontano, Knud Nierhaus.

The journal is published since April 2009, 4 times a year.

Announcements More Announcements...

 

Academician Anatoly I. Grigoriev passed away on February 11, 2023

Posted: 17.02.2023

The editorial board of the journal Acta Naturae informs with deep regret that on February 11, 2023, the founder of the journal, the permanent chairman of the editorial board, academician Anatoly I. Grigoriev, passed away.


 

Free Full Open Access to the jornal

Posted: 30.10.2019

Journal “Acta Naturae” is now available in open access in PubMed Central and eLIBRARY.RU.


 

Current Issue

Vol 15, No 4 (2023)

Reviews

Animal Models of Mitochondrial Diseases Associated with Nuclear Gene Mutations
Averina O.A., Kuznetsova S.A., Permyakov O.A., Sergiev P.V.
Abstract

Mitochondrial diseases (MDs) associated with nuclear gene mutations are part of a large group of inherited diseases caused by the suppression of energy metabolism. These diseases are of particular interest, because nuclear genes encode not only most of the structural proteins of the oxidative phosphorylation system (OXPHOS), but also all the proteins involved in the OXPHOS protein import from the cytoplasm and their assembly in mitochondria. Defects in any of these proteins can lead to functional impairment of the respiratory chain, including dysfunction of complex I that plays a central role in cellular respiration and oxidative phosphorylation, which is the most common cause of mitopathologies. Mitochondrial diseases are characterized by an early age of onset and a progressive course and affect primarily energy-consuming tissues and organs. The treatment of MDs should be initiated as soon as possible, but the diagnosis of mitopathologies is extremely difficult because of their heterogeneity and overlapping clinical features. The molecular pathogenesis of mitochondrial diseases is investigated using animal models: i.e. animals carrying mutations causing MD symptoms in humans. The use of mutant animal models opens new opportunities in the study of genes encoding mitochondrial proteins, as well as the molecular mechanisms of mitopathology development, which is necessary for improving diagnosis and developing approaches to drug therapy. In this review, we present the most recent information on mitochondrial diseases associated with nuclear gene mutations and animal models developed to investigate them.

Acta Naturae. 2023;15(4):4-22
pages 4-22 views
Cooperation and Competition of RNA Secondary Structure and RNA–Protein Interactions in the Regulation of Alternative Splicing
Vorobeva M.A., Skvortsov D.A., Pervouchine D.D.
Abstract

The regulation of alternative splicing in eukaryotic cells is carried out through the coordinated action of a large number of factors, including RNA-binding proteins and RNA structure. The RNA structure influences alternative splicing by blocking cis-regulatory elements, or bringing them closer or farther apart. In combination with RNA-binding proteins, it generates transcript conformations that help to achieve the necessary splicing outcome. However, the binding of regulatory proteins depends on RNA structure and, vice versa, the formation of RNA structure depends on the interaction with regulators. Therefore, RNA structure and RNA-binding proteins are inseparable components of common regulatory mechanisms. This review highlights examples of alternative splicing regulation by RNA-binding proteins, the regulation through local and long-range RNA structures, as well as how these elements work together, cooperate, and compete.

Acta Naturae. 2023;15(4):23-31
pages 23-31 views
Soft X-ray Microscopy in Cell Biology: Current Status, Contributions and Prospects
Golyshev S.A., Kazakov E.P., Kireev I.I., Reunov D.G., Malyshev I.V.
Abstract

The recent advances achieved in microscopy technology have led to a significant breakthrough in biological research. Super-resolution fluorescent microscopy now allows us to visualize subcellular structures down to the pin-pointing of the single molecules in them, while modern electron microscopy has opened new possibilities in the study of protein complexes in their native, intracellular environment at near-atomic resolution. Nonetheless, both fluorescent and electron microscopy have remained beset by their principal shortcomings: the reliance on labeling procedures and severe sample volume limitations, respectively. Soft X-ray microscopy is a candidate method that can compensate for the shortcomings of both technologies by making possible observation of the entirety of the cellular interior without chemical fixation and labeling with an isotropic resolution of 40–70 nm. This will thus bridge the resolution gap between light and electron microscopy (although this gap is being narrowed, it still exists) and resolve the issue of compatibility with the former, and possibly in the near future, the latter methods. This review aims to assess the current state of soft X-ray microscopy and its impact on our understanding of the subcellular organization. It also attempts to look into the future of X-ray microscopy, particularly as relates to its seamless integration into the cell biology toolkit.

Acta Naturae. 2023;15(4):32-43
pages 32-43 views
Muscarinic Cholinoreceptors in Skeletal Muscle: Localization and Functional Role
Kovyazina I.V., Khamidullina A.A.
Abstract

The review focuses on the modern concepts of the functions of muscarinic cholinoreceptors in skeletal muscles, particularly, in neuromuscular contacts, and that of the signaling pathways associated with the activation of various subtypes of muscarinic receptors in the skeletal muscles of cold-blooded and warm-blooded animals. Despite the long history of research into the involvement of muscarinic receptors in the modulation of neuromuscular transmission, many aspects of such regulation and the associated intracellular mechanisms remain unclear. Now it is obvious that the functions of muscarinic receptors in skeletal muscle are not limited to the autoregulation of neurosecretion from motor nerve endings but also extend to the development and morphological rearrangements of the synaptic apparatus, coordinating them with the degree of activity. The review discusses various approaches to the study of the functions of muscarinic receptors in motor synapses, as well as the problems arising when interpreting experimental data. The final part of the review is devoted to an analysis of some of the intracellular mechanisms and signaling pathways that mediate the effects of muscarinic agents on neuromuscular transmission.

Acta Naturae. 2023;15(4):44-55
pages 44-55 views
The Potential and Application of iPSCs in Gene and Cell Therapy for Retinopathies and Optic Neuropathies
Lapshin E.V., Gershovich J.G., Karabelsky A.V.
Abstract

This review focuses on in vitro modeling of diseases and the development of therapeutic strategies using iPSCs for the two most common types of optical pathologies: hereditary neuropathies and retinopathies. Degeneration of retinal ganglion cells and the subsequent optic nerve atrophy leads to various types of neuropathies. Damage to photoreceptor cells or retinal pigment epithelium cells causes various retinopathies. Human iPSCs can be used as a model for studying the pathological foundations of diseases and for developing therapies to restore visual function. In recent years, significant progress has also been made in creating ganglionic and retinal organoids from iPSCs. Different research groups have published data pertaining to the potential of using iPSCs for the modeling of optic neuropathies such as glaucoma, Leber hereditary optic neuropathy, etc., including in the development of therapeutic approaches using gene editing tools.

Acta Naturae. 2023;15(4):56-64
pages 56-64 views

Research Articles

RIPK3 Expression in Fibroblasts in an in vivo and in vitro Skin Wound Model: A Controversial Result
Izumov I.S., Shitova M.S., Sabirov M.S., Sheleg S.A., Cherkashina O.L., Kalabusheva E.P., Vorotelyak E.A., Morgun E.I.
Abstract

One of the major problems of regenerative medicine is the development of hypertrophic scars and keloids. The protein kinase RIPK3 is involved in necroptosis; however, recent evidence indicates that it also has non-canonical functions, including its involvement in the development of renal fibrosis. The aim of our work was to study the expression of RIPK3 in mouse and human skin models of fibrotic processes. A subpopulation of RIPK3+Vim+ cells was found in both human keloid and a mouse wound, with the cell number being significantly greater in the mouse wound bed compared to healthy skin. Real-time polymerase chain reaction (RT-PCR) detected expression of the Ripk3 and fibroblast biomarkers Acta2, Fap, Col1a1, and Fn1 in the cells isolated from the wound bed, indicating that RIPK3 can be expressed by wound bed fibroblasts. An analysis of the human fibroblasts stained with anti-RIPK3 antibodies demonstrated an increase in the fluorescence intensity in the presence of lipopolysaccharide (LPS) at concentrations of 5, 10, 25, 50, and 100 ng/ml and TGF-β at concentrations of 0.1, 1, 2, and 5 ng/ml compared to the control. At the same time, the expression levels of RIPK3 and fibroblast activation markers in the presence of TGF-β and LPS did not differ significantly from the control. It is possible that RIPK3 expression in wound fibroblasts is not directly associated with fibrotic processes, and that kinase plays a different, yet unknown role in wound healing.

Acta Naturae. 2023;15(4):65-74
pages 65-74 views
Testing a Hypothesis of 12S rRNA Methylation by Putative METTL17 Methyltransferase
Mashkovskaia A.V., Mariasina S.S., Serebryakova M.V., Rubtsova M.P., Dontsova O.A., Sergiev P.V.
Abstract

Mitochondrial ribosome assembly is a complex multi-step process involving many additional factors. Ribosome formation differs in various groups of organisms. However, there are universal steps of assembly and conservative factors that have been retained in evolutionarily distant taxa. METTL17, the object of the current study, is one of these conservative factors involved in mitochondrial ribosome assembly. It is present in both bacteria and the mitochondria of eukaryotes, in particular mice and humans. In this study, we tested a hypothesis of putative METTL17 methyltransferase activity. MALDI-TOF mass spectrometry was used to evaluate the methylation of a putative METTL17 target – a 12S rRNA region interacting with METTL17 during mitochondrial ribosome assembly. The investigation of METTL17 and other mitochondrial ribosome assembly factors is of both fundamental and practical significance, because defects in mitochondrial ribosome assembly are often associated with human mitochondrial diseases.

Acta Naturae. 2023;15(4):75-82
pages 75-82 views
In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2
Narovlyansky A.N., Filimonova M.V., Tsyshkova N.G., Pronin A.V., Grebennikova T.V., Karamov E.V., Larichev V.F., Kornilayeva G.V., Fedyakina I.T., Dolzhikova I.V., Mezentseva M.V., Isaeva E.I., Poloskov V.V., Koval L.S., Marinchenko V.P., Surinova V.I., Filimonov A.S., Shitova A.A., Soldatova O.V., Sanin A.V., Zubashev I.K., Ponomarev A.V., Veselovsky V.V., Kozlov V.V., Stepanov A.V., Khomich A.V., Kozlov V.S., Ivanov S.A., Shegai P.V., Kaprin A.D., Ershov F.I., Gintsburg A.L.
Abstract

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012–2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility − high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) − this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.

Acta Naturae. 2023;15(4):83-91
pages 83-91 views
BODIPY Dye Derivative for Irreversible Fluorescent Labeling of Eukaryotic Cells and Their Simultaneous Cytometric Analysis
Frolova A.Y., Kutyakov S.V., Martynov V.I., Deyev S.M., Pakhomov A.A.
Abstract

In this work, we synthesized a green fluorescent dye derivative, 1,3,5,7-tetramethyl-BODIPY, with a heptyl substituent at the 8-position. The obtained highly hydrophobic compound was able to rapidly and irreversibly bind to eukaryotic cells. Incubation of cells with the dye over different periods of time or at different concentrations allowed us to control the degree of cell labeling and the level of fluorescence. This made it possible to modulate the fluorescence level of different eukaryotic cell cultures and then distinguish them by their level of fluorescence signal in the green channel in cytometric experiments. The labeled cells can be combined and further analyzed in the same test tube under identical conditions using the channels in which the dye does not fluoresce. This approach has been tested on a number of tumor cell cultures containing the HER2 receptor on their surface. The representation of the receptor in these cells was analyzed in one test tube in one run using a HER2-specific ligand based on the hybrid protein DARPin9_29-mCherry, which fluoresces in the red region of the spectrum.

Acta Naturae. 2023;15(4):92-99
pages 92-99 views
System for Self-excited Targeted Photodynamic Therapy Based on the Multimodal Protein DARP-NanoLuc-SOPP3
Shramova E.I., Frolova A.Y., Filimonova V.P., Deyev S.M., Proshkina G.M.
Abstract

Despite the significant potential of photodynamic therapy (PDT) as a minimally invasive treatment modality, the use of this method in oncology has remained limited due to two serious problems: 1) limited penetration of the excitation light in tissues, which makes it impossible to affect deep-seated tumors and 2) use of chemical photosensitizers that slowly degrade in the body and cause photodermatoses and hyperthermia in patients. To solve these problems, we propose a fully biocompatible targeted system for PDT that does not require an external light source. The proposed system is based on bioluminescent resonance energy transfer (BRET) from the oxidized form of the luciferase substrate to the photosensitizing protein SOPP3. The BRET-activated system is composed of the multimodal protein DARP-NanoLuc-SOPP3, which contains a BRET pair NanoLuc-SOPP3 and a targeting module DARPin. The latter provides the interaction of the multimodal protein with tumors overexpressing tumor-associated antigen HER2 (human epidermal growth factor receptor type II). In vitro experiments in a 2D monolayer cell culture and a 3D spheroid model have confirmed HER2-specific photo-induced cytotoxicity of the system without the use of an external light source; in addition, experiments in animals with subcutaneous HER2-positive tumors have shown selective accumulation of DARP-NanoLuc-SOPP3 on the tumor site. The fully biocompatible system for targeted BRET-induced therapy proposed in this work makes it possible to overcome the following limitations: 1) the need to use an external light source and 2) the side phototoxic effect from aberrant accumulation of chemical photosensitizers. The obtained results demonstrate that the fully protein-based self-excited BRET system has a high potential for targeted PDT.

Acta Naturae. 2023;15(4):100-110
pages 100-110 views
Membrane Partitioning of TEMPO Discriminates Human Lung Cancer from Neighboring Normal Cells
Gasymov O.K., Bakhishova M.J., Aslanov R.B., Melikova L.A., Aliyev J.A.
Abstract

The plasma membranes of normal and cancer cells of the lung, breast, and colon tissues show considerably different lipid compositions that greatly influence their physicochemical properties. Partitioning of the spin probe 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) into the membranes of human lung normal and carcinoma cells was assessed by EPR spectroscopy to estimate the impact of the lipid compositions. The goal was to reveal potential strategies for cancer therapy attributable to the membrane properties. The study was conducted at pH values of 7.3 and 6.2, relevant to the microenvironments of normal and cancer cells, respectively. The TEMPO partitioning was examined in the temperature interval of 283–317K to reveal the efficacy of local hyperthermia used in chemotherapy. Results indicate that the TEMPO partitioning coefficient for the membranes of human lung carcinoma cells is significantly higher compared with that of neighboring normal cells. Increased partition coefficients were observed at relatively higher temperatures in both normal and cancer cells. However, compared to the normal cells, the cancer cells demonstrated higher partition coefficients in the studied temperature range. The data obtained with C12SL (spin-labeled analog of lauric acid) indicate that increased membrane dynamics of the cancer cells is a possible mechanism for enhanced partitioning of TEMPO. Free energy values for partitioning estimated for pH values of 6.2 and 7.3 show that TEMPO partitioning requires 30% less energy in the cancer cells at pH 7.3. TEMPO and its derivatives have previously been considered as theranostic agents in cancer research. Data suggest that TEMPO derivatives could be used to test if complementary alkalization therapy is effective for cancer patients receiving standard chemotherapy with local hyperthermia.

Acta Naturae. 2023;15(4):111-120
pages 111-120 views

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