bluuebunny/crossref_metadata_2025 huggingface dataset:
Location and orientation of the genetic toxin-antitoxin element hok/sok in the plasmid affects the expression level of pharmaceutically significant proteins
Authors: Khodak Yu. A , Shaifutdinov R. R , Khasanov D. S , Orlova N. A , Vorobiev I. I
Published: April 2024

The genetic toxin-antitoxin element hok/sok from the natural Escherichiacoli R1 plasmid ensures the segregation stability of the plasmids. Bacterial cells that have lost all copies of the plasmid encoding the short-lived antitoxin die under the action of the long-lived toxin. The hok/sok element in vector plasmids for bacterial expression can increase the productive time of biosynthesis of recombinant proteins, slowing down the accumulation of non-producing cells lacking the target plasmid in the population. In this work, we studied various variants of the position and orientation of the hok/sok element in the standard plasmid pET28a with the inducible T7lac promoter and the kanamycin resistance gene. It was found that the hok/sok element retained functional activity regardless of location on the plasmid and orientation, bacterial cells retained hok/sok plasmids after four days of cultivation without antibiotics and lost the control plasmid without this element. Using the example of three target proteins - E. coli type II asparginase, human growth hormone, and the SARS-CoV-2 virus nucleoprotein, it was demonstrated that for cytoplasmic target proteins, the maximum productivity of bacteria is maintained only when the hok/sok element is located on the plasmid upstream of the target gene promoter. In the case of periplasmic localization of the protein, the productivity of bacteria decreases for all variants of the hok/sok location during cultivation with an antibiotic, and in the case of periodic cultivation of bacteria without an antibiotic, productivity is also better preserved when the hok/sok element is located upstream of the target gene promoter. This variant of the pEHU vector plasmid makes it possible to more than double the biosynthesis of human growth hormone, which is insoluble in the cytoplasm of bacteria, when bacteria are cultivated without antibiotics, and also to maintain asparaginase biosynthesis during periodic cultivation without antibiotics for four days at a level of at least 10 mg/liter. The developed segregation-stabilized plasmid vector can be used to obtain various recombinant proteins in E. coli cells without the use of antibiotics.
Effect of biotin starvation on gene expression in Komagataella phaffii cells
Authors: Makeeva A. S , Sidorin A. V , Ishtuganova V. V , Padkina M. V , Rumyantsev A. M
Published: April 2024

Methylotrophic yeast Komagataella phaffii are widely used in biotechnology as a host for recombinant protein production. Due to the practical significance of this yeast, it is extremely important to properly select the cultivation conditions and optimize the media composition. In this study the effect of biotin starvation on K. phaffii gene expression was investigated at transcriptomic level. It was demonstrated, that K. phaffii cell response to biotin deficiency strongly depends on the carbon source in the medium. In media containing glycerol, biotin deficiency led to activation of genes involved in biotin metabolism, glyoxylate cycle and synthesis of acetyl-CoA in cytoplasm, as well as repression of genes, involved in lipo- and gluconeogenesis. In methanol containing media, biotin deficiency primarily led to repression of genes, involved in protein synthesis, and activation of cell response to oxidative stress.
Lel A. Drachev and the direct electrometric method
Authors: Ptushenko V. V , Semenov A. Y
Published: April 2024

In the bioenergetics studies, the direct electrometric method played an important role. This method is based on measuring the electrical potential difference (Δψ) between two compartments of the experimental cell generated by some membrane proteins. These proteins are incorporated into closed lipid-protein membrane vesicles associated with an artificial lipid membrane that separates the compartments. The very existence of such proteins able to generate Δψ was one of the consequences of Peter Mitchell’ s chemiosmotic concept. The discovery and investigation of their functioning contributed to the recognition of this concept and, eventually the well-deserved awarding of the Nobel Prize to P. Mitchell. Lel A. Drachev (1926-2022) was one of the main authors of the direct electrometrical method. With his participation, key studies were carried out on the electrogenesis of photosynthetic and respiratory membrane proteins, including bacteriorhodopsin, visual rhodopsin, photosynthetic bacterial reaction centers, cytochrome oxidase and others.
Electron transport in chloroplasts: regulation and alternative pathways of electron transfer
Authors: Tikhonov A. N
Published: April 2024

This work represents an overview of electron transport regulation in chloroplasts as considered in the context of structure-function organization of photosynthetic apparatus in plants. A basic focus of the article is concentrated on a bifurcated oxidation of plastoquinol by the cytochrome b6f complex, which represents the rate-limiting step of electron transfer between photosystems 2 and 1. Electron transport along the chains of the noncyclic, cyclic and pseudocyclic electron flow, their relationships to generation of the trans-thylakoid difference in electrochemical potentials of protons in chloroplasts, and the pH-dependent mechanisms of regulation of the cytochrome b6f complex, are considered. Redox reactions with the participation of molecular oxygen and ascorbate, the alternative mediators of electron transport in chloroplasts, have also been discussed.
Electrical signals of the plasma membrane and their effect on chlorophyll fluorescence in chara chloroplasts in vivo
Authors: Bulychev A. A , Shapiguzov S. Yu , Alova A. V
Published: April 2024

Action potentials of plant cells are involved in regulation of many cell processes, such as photosynthesis and cytoplasmic streaming. Excitable cells of characean algae submerged in media with elevated K+ content are able to generate hyperpolarizing electrical responses. This active response of plasma membrane arises upon the passage of inward electric current comparable in extent to natural currents circulating in illuminated Chara internodes. It remains currently unknown whether the hyperpolarizing electrical signals in Chara affect the photosynthetic activity. Here we show that the negative shift of cell membrane potential, which causes the K+ influx into the cytoplasm, is accompanied by a delayed decrease in the effective chlorophyll fluorescence yield (F′) and maximal yield (Fm′) under low background light (12.5 µmol m-2 s-1). The transient changes in F′ and Fm′ were evident under illumination only, which indicates their close relation to photosynthetic energy conversion in chloroplasts. The passage of inward current caused an increase in pH at the cell surface (pHo), which reflects a high H+/OH- conductance of the plasmalemma and points to the decrease in cytoplasmic pH due to H+ entry into the cell. The shifts in pHo arising in response to the first hyperpolarizing pulse disappeared upon repeated stimulations, thus indicating the long-term inactivation of plasmalemmal H+/OH- conductance. Despite the suppression of plasmalemmal H+ fluxes, the hyperpolarizing responses and the analyzed chlorophyll fluorescence changes did not disappear. The results indicate the participation of K+ flows between the outer medium, cytoplasm, and stroma in chloroplast functional changes that are reflected by the dynamics of F′ and Fm′.
Investigation of the mechanism of membrane potential generation by heme-copper respiratory oxidases in real time mode
Authors: Siletsky S. A
Published: April 2024

Heme-copper respiratory oxidases are highly efficient molecular machines. These membrane enzymes catalyze the final stage of cellular respiration of eukaryotes and many prokaryotes: the transfer of electrons from cytochromes or quinols to molecular oxygen and the reduction of O2 to water. The free energy released in this redox reaction is converted by heme-copper respiratory oxidases into a transmembrane gradient of the electrochemical potential of hydrogen ions (ΔµH+). Heme-copper respiratory oxidases have a unique mechanism for generation ΔµH+ - a redox-coupled proton pump. The use of a combination of a direct electrometric method for measuring the kinetics of membrane potential generation with approaches and methods of prestationary kinetics and directed mutagenesis in the study of heme-copper oxidases makes it possible to obtain unique information about the movement of protons inside the protein in real time. The review summarizes the results of the use of the permitted time.
Channelrhodopsins: from phototaxis to optogenetics
Authors: Govorunova E. G , Sineshchekov O. A
Published: April 2024

Channelrhodopsins stand out among other retinal proteins because of their capacity to generate passive ionic currents following photoactivation. Owing to that, channelrhodopsins are widely used in neuroscience and cardiology as instruments for optogenetic manipulation of the activity of excitable cells. Photocurrents generated by channelrhodopsins were first discovered in the cells of green algae in the 1970s. In this review we describe this discovery and discuss the current state of research in this field.
Retinal-based anion pump from the cyanobacterium Tolypothrix campylonemoides
Authors: Rokitskaya T. I , Alekseev A. A , Tsybrov F. M , Bukhalovich S. M , Antonenko Y. N , Gordeliy V. I
Published: April 2024

In this work, a functional characterization of TcaR rhodopsin from the cyanobacterium Tolypothrix campylonemoides was obtained. Analysis of the amino acid sequence of TcaR revealed that this protein possesses a TSD motif that differs by only one amino acid from the motif of the known halorodopsin chloride pump TSA. The TcaR protein was expressed in E. coli, purified and incorporated into proteoliposomes and nanodiscs. Functional activity was measured by electric current generation through the planar bilayer lipid membranes (BLMs) with proteoliposomes adsorbed on one membrane surface, as well as by fluorescence using voltage-dependent dye oxonol VI. We have shown that TcaR rhodopsin functions as a powerful anion pump. Our results show that the novel microbial anion transporter TcaR deserves deeper study and may be of interest both for fundamental studies of membrane proteins and as a tool for optogenetics.
The role and molecular mechanisms of alternative splicing of Th2-cytokines IL-4 and IL-5 in atopic bronchial asthma
Authors: Shilovskiy I. P , Kovchina V. I , Timotievich E. D , Nikolskii A. A , Khaitov M. R
Published: April 2024

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. Allergic asthma is the most common (up to 80% of cases) phenotype developing through Th2-dependent mechanisms involving cytokines: IL-4, IL-5, IL-9 and IL-13. The genes encoding Th2-cytokines have a mosaic structure (encode exons and introns). Therefore, several mature mRNA transcripts and protein isoforms can be derived from a single mRNA precursor through alternative splicing, and they may contribute to BA pathogenesis. Analysis of published studies and databases revealed the existence of alternative mRNA transcripts for IL-4, IL-5, and IL-13. Alternative transcripts of IL-4 and IL-5 carry open reading frames and therefore can encode functional proteins. It was shown that not only alternative mRNA transcripts are exist for IL-4, but alternative protein isoforms, as well. Natural protein isoform IL-4δ2 lacking part encoded by exon-2 was identified. Similarly, alternative mRNA transcript omitting exon-2 (IL-5δ2) was also identified for IL-5. In this review, we summarize current knowledge about identified alternative mRNA transcripts and protein isoforms of Th2-cytokinins, first of all IL-4 and IL-5. We have analyzed biological properties of alternative variants of these cytokines, their possible role in the allergic asthma pathogenesis, and considered their diagnostic and therapeutic potential.
“If i were in nature’s place, i would do it like this...”. Life and hypotheses of Alexey Olovnikov
Authors: Olovnikova N. I , Olovnikov I. A , Kalmykova A. I
Published: April 2024

In this article, we commemorate the life and scientific journey of the brilliant gerontologist-theorist Alexey Olovnikov (1936-2022). In 1971, he published his famous “marginotomy” hypothesis, in which he predicted the replicative shortening of telomeres and its role as a counter of cell divisions and biological age of an organism. This work put forth several remarkable assumptions, including the existence of telomerase, which were confirmed two decades later. Despite this, Alexey Olovnikov moved further in his theoretical studies of aging and proposed a series of new hypotheses that seem no less exotic than the marginotomy hypothesis once appeared. Alexey Olovnikov had an extraordinary way of looking at biological problems and, in addition to aging, authored striking concepts about development, biorhythms, and evolution.
Olovnikov, telomeres and telomerase. is it possible to prolong a healthy life?
Authors: Yegorov Y. E
Published: April 2024

The science of telomeres and telomerase has made tremendous progress in recent decades. In this review, we consider it first in a historical context (the Carrel-Hayflick-Olovnikov-Blackburn chain of discoveries) and then review current knowledge of telomere structure and dynamics in norm and pathology. Central to the review are the consequences of telomere shortening, including telomere position effects, DNA damage signaling, and increased genetic instability. Cell senescence and the role of telomere length in its development are discussed separately. Therapeutic aspects and risks of telomerase and other telomere lengthening methods are also discussed.
Unstable DNA in neurons: counter of the life span and a driver of evolution
Authors: Dyakonova V. E
Published: April 2024

The data on postmitotic instability of neuronal DNA, which have been reported in the last decade, are changing the theoretical landscape not only of neuroscience, but more broadly, of biology. A. M. Olovnikov suggested in 2003 that it is the DNA of neurons that can be the “initial substrate of aging”. The current data significantly increases the likelihood of this hypothesis. How does neuronal DNA accumulate damage, in what regions of the genome, what factors contribute to its accumulation, and how can they be associated with aging and the life span? These questions will be considered in the review. In addition, instability of the neuronal DNA had apparently been accompanied by a search for various ways to reduce the biological costs of brain function in Metazoan evolution. Phenomena such as sleep, an increase in the number of neurons in the vertebrate brain evolution, adult neurogenesis, distributed neuronal activity, somatic polyploidy, RNA editing in cephalopods can be reconsidered in the light of “DNA plasticity-instability trade-off” in neurons. The topic is of obvious importance not only for fundamental neuroscience, but also for translational medicine.
Potential geroprotectors - from the banch to the clinic
Authors: Moskalev A. A
Published: April 2024

Geroprotectors are substances that slow down the aging process and can be used in the prevention of age-related diseases. Geroprotectors can improve the functioning of various organ systems and enhance their homeostatic capabilities. We have developed a system of criteria for geroprotectors and proposed their classification based on the mechanisms of action on the aging processes. It is necessary for geroprotectors to reduce mortality, improve human aging biomarkers, have minimal side effects, and enhance quality of life. Additionally, there are approaches based on combining geroprotectors targeted at different targets and mechanisms of aging to achieve maximum effectiveness. Currently, numerous preclinical studies are being conducted to identify new molecular targets and develop new approaches to extend healthy aging, although the number of clinical trials is limited. Geroprotectors have the potential to become a new class of preventive medicines as they prevent the onset of certain diseases or slow down their progression.
To be mobile or not: the variety of reverse transcriptases and their recruitment by host genomes
Authors: Arkhipova I. R , Yushenova I. A
Published: April 2024

Reverse transcriptases (RT), or RNA-dependent DNA polymerases, are unorthodox enzymes that originally added a new angle to the conventional view of the unidirectional flow of genetic information in the cell from DNA to RNA to protein. First discovered in vertebrate retroviruses, RTs were since re-discovered in most eukaryotes, bacteria, and archaea, spanning essentially all domains of life. For retroviruses, RTs provide the ability to copy the RNA genome into DNA for subsequent incorporation into the host genome, which is essential for their replication and survival. In cellular organisms, most RT sequences originate from retrotransposons, the type of self-replicating genetic elements that rely on reverse transcription to copy and paste their sequences into new genomic locations. Some retroelements, however, can undergo domestication, eventually becoming a valuable addition to the overall repertoire of cellular enzymes. They can be beneficial yet accessory, like the diversity-generating elements, or even essential, like the telomerase reverse transcriptases. Nowadays, ever-increasing numbers of domesticated RT-carrying genetic elements are being discovered. It may be argued that domesticated RTs and reverse transcription in general is more widespread in cellular organisms than previously thought, and that many important cellular functions, such as chromosome end maintenance, may evolve from an originally selfish process of converting RNA into DNA.
Peptide carriers as delivery vehicles for therapeutic nucleic acids. Мechanisms and potential applications in medicine
Authors: Timotievich E. D , Shilovskiy I. P , Khaitov M. R
Published: April 2024

Currently, a significant number of drugs based on therapeutic nucleic acids are being under development for the treatment of oncological, inflammatory, infectious diseases, and metabolic disorders. A growing number of approved nucleic acid therapeutics demonstrate the potential of gene therapy approaches. Therapeutic nucleic acids realize their biological effect in the cytoplasm, while plasma membrane is the main barrier to their intracellular delivery. Therefore, specially designed carriers are often used during the development of such drugs. The optimal carrier should not only facilitate the internalization of nucleic acids, but also exhibit no toxic effects, provide stabilization, and must be suitable for large scale production at low cost. Cell penetrating peptides (CPPs) match all these requirements. CPPs are effective and low-toxic carriers of nucleic acids. They usually represent basic peptides with a positive charge at physiological pH that capable to form nanostructures with negatively charged nucleic acids. Numerous preclinical studies in which CPP has been used as a carrier have shown promising results. In some cases, CPP-containing drugs successfully passed through clinical trials and the implemented into clinical practice. In this review, we consider the variety of therapeutic nucleic acids and summarize the experience of using CPP for their intracellular delivery. In addition, the classification and mechanisms of CPP cellular uptake are discussed, the understanding of which will accelerate the development of new gene therapy drugs.
Apelin C-terminal fragments: biological properties and therapeutic potential
Authors: Pisarenko O. I , Studneva I. M
Published: April 2024

The creation of bioactive molecules for the treatment of cardiovascular diseases based on natural peptides stimulates intensive experimental research. In recent years, it has been established that the C-terminal fragments of apelin, an endogenous ligand of the APJ receptor, reduce metabolic and functional disorders in experimental heart damage. The review presents literature data and generalized results of our own experiments on the effect of apelin-13, [Pyr]apelin-13, apelin-12, and their chemically modified analogues on the heart in normal conditions and when modeling pathophysiological conditions in vitro and in vivo. It has been shown that the spectrum of action of apelin peptides on the damaged myocardium covers a decrease in the death of cardiomyocytes from necrosis, a decrease in cardiomyocyte membrane damage, an improvement in the metabolic state of the myocardium, and a decrease in the formation of reactive oxygen species and lipid peroxidation products. The mechanisms of the protective action of these peptides associated with the activation of the APJ receptor and the manifestation of antioxidant properties are discussed. The data presented in the review indicate the promise of molecular design of pharmacological APJ receptor agonists, which can serve as the basis for the development of cardioprotectors that affect the processes of free radical oxidation and metabolic adaptation.
Pathological correlates of cognitive decline in Parkinson’s disease: from molecules to neural networks
Authors: Novikov N. I , Brazhnik E. S , Kichigina V. F
Published: April 2024

Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopaminergic neurons in the substantia nigra and the appearance of protein aggregates in neuronal cell bodies composed predominantly of alpha-synuclein, known as Lewy bodies. PD is now recognized as a multisystem disorder characterized by severe motor impairment and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairment (CI), diagnosed already in the early stages of PD, usually leads to deep dementia. The main types of CI observed in PD include executive dysfunction, attention, and memory disfunction, visuospatial decline, and verbal deficits. According to the literature, the following mechanisms play a significant role in the development of cognitive dysfunctions in PD: (1) changes in the conformational structure of synaptic proteins; (2) disruption of synaptic transmission; (3) neuroinflammation (pathological activation of neuroglia); (4) mitochondrial dysfunction and oxidative stress; (5) metabolic conditions; (6) functional remodeling of the neural networks. The listed molecular and synaptic changes in the brain can lead to the death of dopamine-synthesizing cells of the substantia nigra and dysfunction of other mediator systems, as well as partial cellular atrophy in the neocortex and subcortical nuclei. As a result, the functioning of neural networks involved in the transmission of information related to the regulation of motor activity and cognitive functions is disrupted. Elucidation of the causes of changes occurring in PD and the search for methods to eliminate them will help create new approaches in the treatment of this disease. The aim of the review is to analyze the pathological processes in the brain that underlie the onset of cognitive impairment in PD. The review analyzes the data obtained both from studies on patients with PD and animal (rodents and primates) models of this disease used for the evaluation of the mechanisms underlying etiology and the development of PD in humans.
Differences in structural changes and pathophysiologic effects of low-density lipoproteins upon accumulation of acylhydroperoxy derivatives in their outer phospholipid monolayer or upon chemical modification of apoprotein b-100 by natural dicarbonyl
Authors: Lankin V. Z , Tikhaze A. K , Konovalova G. G
Published: April 2024

Nanoparticles of the lipid-transporting system of the organism - low-density lipoproteins (LDL) of blood plasma are easily subjected to free radical peroxidation with formation of their main modified forms - oxidized LDL itself (containing hydroperoxy-acyls in phospholipids of the outer layer of particles) and dicarbonyl-modified LDL (apoprotein B-100 of which was chemically modified by the Maillard reaction). Based on the study of free radical oxidation kinetics of LDL, it was found that the existing in the literature designation “oxidized lipoproteins” is incorrect because it does not reveal the nature of oxidative modification of LDL. It is shown that “atherogenic” LDL (particles of which are actively captured by cultured macrophages) are not the oxidized LDL (in which LOOH-derivatives of phospholipids are formed by enzymatic oxidation of of C-15 lipoxygenase of rabbit reticulocytes), but dicarbonyl-modified LDL. The important role of dicarbonyl-modified LDL in the molecular mechanisms of atherogenesis and endothelial dysfunction is discussed.
Changes in the glutamate/gaba system in the hippocampus of rats with age and during the Alzheimer’s disease signs development
Authors: Burnyasheva A. O , Stefanova N. A , Kolosova N. G , Telegina D. V
Published: April 2024

GABA and glutamate are the most abundant neurotransmitters in the CNS and play a pivotal part in synaptic stability/plasticity. Glutamate and GABA homeostasis is important for healthy aging and reducing the risk of various neurological diseases, while long-term imbalance can contribute to the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Its normalization discussed as a promising strategy for the prevention and/or treatment of AD, however, data on changes in the GABAergic and glutamatergic systems in with age, as well as in the dynamics of AD development, are limited. It is not clear whether the imbalance of the excitatory/inhibitory systems is a cause or a consequence of the development of the disease. Here we analyzed age-related alterations of the expression of glutamate, GABA, and enzymes that synthesize them (glutaminase, glutamine synthetase, GABA-T, and GAD67), transporters (GLAST, GLT-1, and GAT1), and relevant receptors (GluA1, NMDAR1, NMDA2B, and GABAAr1) in the whole hippocampus of Wistar rats and of senescence-accelerated OXYS rats, a model of the most common (> 95%) sporadic AD. Our results suggest that there is a decline of glutamate and GABA signaling with aging in the hippocampus of the both rat strains. However, we have not identified significant changes or compensatory enhancements in this system in the hippocampus of OXYS rats during development of neurodegenerative processes that are characteristic of AD.
Role of mitochondrial DNA in yeast replicative aging
Authors: Azbarova A. V , Knorre D. A
Published: April 2024

Despite the variety of manifestations of aging, there are some common features and underlying mechanisms. In particular, mitochondria appears to be one of the most vulnerable systems in both metazoa and fungi. In this review, we discuss how mitochondrial dysfunction is related to replicative aging in the simplest eukaryotic model, the baker’s yeast Saccharomyces cerevisiae. We discuss a chain of events that starts from asymmetric inheritance of mitochondria by mother and daughter cells. With age, yeast mother cells start to experience a decrease in mitochondrial transmembrane potential and, consequently, a decrease in mitochondrial protein import efficiency. This induces mitochondrial protein precursors accumulation in the cytoplasm, the loss of mitochondrial DNA, and at the later stages - cell death. Interestingly, yeast strains without mitochondrial DNA can have both increased and increased lifespan compared to their counterparts with mtDNA. The direction of the effect depends on their ability to activate compensatory mechanisms preventing or mitigating negative consequences of mitochondrial dysfunction. The central role of mitochondria in yeast aging and death indicates that it is one of the most complex and, therefore, deregulation-prone systems in eukaryotic cells.
Role of ubiquitin-proteasome system in stem cell biology
Authors: Burov A. V , Rodin A. A , Karpov V. L , Morozov A. V
Published: April 2024

Selective degradation of cellular proteins by the ubiquitin -proteasome system is one of the key regulatory mechanisms in eukaryotic cells. Accumulating data indicate that the ubiquitin - proteasome system is involved in the regulation of fundamental processes in mammalian stem cells, including proliferation, differentiation, cell migration, aging and programmed cell death. Regulation can be carried out either by proteolytic degradation of key transcription factors and signaling pathway proteins, or by posttranslational modifications of target proteins with ubiquitin or other ubiquitin-like modifiers. Studies of the molecular mechanisms of proteostasis maintenance in stem cells are of great importance for the development of new therapeutic approaches aimed at the treatment of autoimmune and neurodegenerative diseases, cancer and other socially significant pathologies. This review covers current data on the function of the ubiquitin-proteasome system in stem cells.
Opposing effects of CRABP1 and CRABP2 homologs on the proliferation of breast cancer cells and their sensitivity to retinoic acid
Authors: Enikeev A. D , Abramov P. M , Elkin D. S , Komelkov A. V , Belyaeva A. A , Sylantieva D. M , Tchevkina E. M
Published: April 2024

Resistance of tumor cells to retinoic acid (RA), a promising therapeutic agent, is the major factor limiting the use of RA in clinical practice. The mechanisms of RA resistance are still poorly understood. Cellular Retinoic Acid Binding Proteins, CRABP1 and CRABP2, are essential mediators of RA signaling, but the role of the two CRABP homologs in regulating cellular sensitivity to RA has not been well studied. In addition, the effects of CRABP1 and CRABP2 on cell proliferation have not been compared. Here, using a broad panel of breast cancer cell lines with different levels of RA sensitivity/resistance, we show for the first time that in RA-sensitive cells, CRABP1 expression is restricted by methylation and protein levels are highly variable. In moderately RA-resistant lines, a high level of CRABP1 is observed both at the mRNA and protein levels, unchanged by inhibition of DNA methylation. The maximally resistant cell lines are characterized by complete repression of CRABP1 implemented at transcriptional and posttranscriptional levels, and exogenous expression of each of CRABP homologs has no effect on the studied characteristics. CRABP1 and CRABP2 proteins have opposing effects on proliferation and sensitivity to RA. Specifically, in initially RA-sensitive cells CRABP1 stimulates and CRABP2 reduces proliferation and resistance to RA, while in more resistant cells the role of each homolog in both of these indications is reversed. Overall, we have shown for the first time that CRABP proteins exert different effects on the growth and sensitivity to RA of breast cancer cells (stimulation, suppression, or no effect) depending on the baseline level of RA-sensitivity, with the effects of CRABP1 and CRABP2 homologs on the studied properties always being opposite.
Nocistatin and products of its proteolysis as dual modulators of type 3 acid-sensing ion channels (ASIC3) with an algesic and analgesic effect
Authors: Osmakov D. I , Tarasova N. V , Nedorubov A. A , Palikov V. A , Palikova Y. A , Dyachenko I. A , Andreev Y. A , Kozlov S. A
Published: April 2024

The neuropeptide nocistatin (NS) is expressed by cells of the nervous system and neutrophils as part of a precursor protein and can undergo limited proteolysis through stepwise degradation. Previously, it was shown that rat NS (rNS) is able to activate acid-sensing ion channels (ASIC), but this effect correlated with the acidic nature of NS. In this work, we investigated the change in the properties of rNS during its degradation by a comparison of rNS and its two synthesized fragments. We estimated their activity on rat ASIC3 channels expressed in X. laevis oocytes, and the effects in pain tests on mice. We have shown that rNS combines the properties of both positive and negative modulators of ASIC3, which is expressed in the ability to lower the channel’s steady-state desensitization in the pH range 6.8-7.0 and the reduction of the channel’s response to stimuli in the 6.0-6.9 pH range. A shortened analogue (rNSΔ21) (21 amino acid residues (aa) from the N-terminus) retained the effect of the ASIC3 positive modulator only, while the C-terminal pentapeptide (rNSΔ30) retained the ability of the ASIC3 negative modulator only. This tendency was confirmed in animal tests, where rNS and rNSΔ21 induced pain related behavior, but rNSΔ30 showed an analgesic effect. Thus, we have shown the change of the rNS action mode during stepwise degradation, from an algesic molecule through a pain-enhancer to a pain-relief wherefore the final pentapeptide can even be considered as a promising starting point for further drug development.
The Present-Day Structure of the Temperature and Current Fields in Lake Sevan
Authors: Poddubnyi S. A. , Gabrielyan B. K. , Tsvetkov A. I.
Published: April 2024

Long-term features of the vertical and horizontal structure of water temperature field in Lake Sevan are discussed. It is shown that the climate warming has led to an increase in epilimnion temperature in Bol’shoi Sevan in July by 2.0‒3.0°C. The increase in water temperature in hypolimnion was not greater than 1.1°C. In autumn (October), the epilimnion became 1.2°C warmer, while hypolimnion temperature practically has not changed on the average over years. Temperature fields were used to calculate the density currents in summer and autumn periods. A dominating cyclonic water circulation was revealed all over the lake, confirmed by chlorophyll distribution by satellite image data. In the case of large horizontal gradients of water density, the flow velocity can reach 50 cm/s. Autonomous buoy stations revealed a wide range of water temperature variations due to internal waves of different nature. The reversible vertical mixing of water mass by internal waves plays an important role in the distribution of nutrients and plankton within the water mass. The water level rise by ~3 m, unlike it drop by 1981 by 18.48, has not caused any significant changes in lake hydrological regime.
Specific Features of the Formation and Regulation of Diffuse Pollution in Urban Areas: Case Study of the Yauza R.
Authors: Polyanin V. O. , Fashchevskaya T. B. , Slovyagina A. N.
Published: April 2024

Specific features of water quality formation are considered for the Yauza R. flowing in an urbanized drainage basin containing Moscow City and nearest Moscow region. It has been found that the deep transformation of the natural hydrographic network along with diffused pollution from sources scattered over its basin have an adverse effect on water quality formation in the urban watercourse and its self-purification potential. The current ecological state of the river can be evaluated as unsatisfactory, notwithstanding the water protection measures taken in its basin. The existing system for managing the urban surface runoff has been analyzed. It is shown that monitoring the volumes and formation conditions of pollution runoff from the urban territory is not effective enough for an objective estimate of the environmental conditions of water bodies and reduces the efficiency of water protection measures.
The Effect of Natural and Anthropogenic Factors on the Seasonal Ecohydrological Dynamics of the Eastern Basin of the Hypersaline Sakskoe Lake, the Republic of Crimea
Authors: Rudneva I. I. , Chaban V. V. , Shaida V. G. , Korepanov A. L.
Published: April 2024

Crimean salt lakes have a high resource potential used in various types of human activity, i.e., balneology, chemical industry, and therapy; now, they are attractive tourist sites. A combination of biotic and abiotic factors creates specific conditions for the development and functioning of biota and the formation of unique ionic composition of brine and bottom sediments, which are used in balneology and the production of spa-products. Sakskoe Lake is among the largest coastal salt lakes of Crimea, located on the southwestern coast of the Black Sea. The effect of climate conditions and biota caused the formation of a specific ecosystem in the lake, which has a peculiar ionic composition of brine, changing within the year, and a brine shrimp population. The concentrations of cations and anions in the brine increased in summer because of active evaporation and decreased in winter and spring because of dilution of atmospheric precipitation and snowmelt water. The dynamics of the brine population also showed characteristic seasonal features: the life cycle begins in April, the maximal number of various life stages is recorded in May–June, and the end, in November–December. The artificial regulation of the water–salt regime of the water body through addition of seawater in summer contributed to maintaining optimal conditions, thus ensuring a high vital activity of the biota. The obtained data can reflect the seasonal dynamics of processes in the salt lake, governed by climatic, seasonal, and anthropogenic factors.
Modeling Channel Deformation and Pollutant Transport in Rivers in Permafrost Zone with Local Channel Curvature
Authors: Debolskaya E. I. , Debolskii V. K. , Gritsuk I. I.
Published: April 2024

The results of laboratory and mathematical modeling of pollutant propagation from thawed sources on bank slopes in curvilinear reaches of rivers in permafrost zone are presented. Particular attention is paid to studying the effect of channel deformations caused by thermal erosion on the speed and character of pollutant spot propagation. The laboratory experiments in the hydraulic flume were primarily focused on determining the difference in the deformation dynamics and solute propagation from thawing sources at different shapes of channel curvature for the farther use of these data as input parameters of mathematical model for its verification. The analysis of a series of numerical calculations at a scale of laboratory experiment and an actual natural object suggested the conclusion regarding the effect of channel morphometric characteristics, the hydrological and thermal parameters of water flow, the characteristics of permafrost channel-forming ground on the dynamics of pollutant propagation in curvilinear reaches of the permafrost zone.
Studying the Composition and Genesis of Organic Matter in Bottom Sediments of Polluted Small Watercourses in Khabarovsk City Territory
Authors: Garetova L. A. , Fisher N. K. , Kirienko O. A.
Published: April 2024

The distribution of organic matter, hydrocarbons, phytopigments, and ecological-trophic groups of microorganisms was studied in the bottom sediments of ten small tributaries of the Amur R. near Khabarovsk. The water showed high concentrations of organic matter, varying from 44.47 to 279.3 mg/L. The concentration of Corg in bottom sediments varied from 1.9 to 23.1% in different types of sediments; the amount of hydrocarbons reached 5081 mg/kg, exceeding the background level by a factor of up to 50. Studies of the molecular composition of hydrocarbons in sediments revealed in some streams the predominance (up to 100% of the total) of light (C8–C13) n-alkanes, typical of oil products and the products of vegetation combustion. High-molecular compounds dominated in HC composition in most watercourses, including n-alkanes, genetically associated with terrestrial vegetation, and heavy fractions of oil products with various levels of microbial degradation. Volatile organic compounds were quantitatively dominated by the products of microbiological transformation (acetaldehyde and methanol). In terms of the concentration of sedimentary pigments (up to 400 µg/g), the sediments of the majority of watercourses belong to the hypereutrophic type. The total abundance of microorganisms in water varied from 2.7 to 488.0 thousand CFU/mL; in sediments, it was distributed symbatically, but ranged from 0.1 to 19.3 million CFU/g. The number of heterotrophic bacteria in bottom sediments correlated with the parameter of overload of the self-purification capacity (r = 0.718), and the number of oil-oxidizing bacteria correlated with hydrocarbon concentration (r = 0.967), thus confirming the indication properties of this bacterial group.
Methane Distribution in Lake Baikal Water
Authors: Gar’kusha D. N. , Fedorov Yu. A. , Tambieva N. S. , Andreev Yu. A. , Adzhiev R. A.
Published: April 2024

Data on the distribution of methane concentration in water in the open water area and the northern end of Lake Baikal and in the source of the Angara R. collected in September 2016 and 2019 are analyzed. To apply correlation analysis, in addition to methane, various hydrochemical characteristics were also determined, including the temperature, pH, the concentrations of О2, suspended matter, Corg, Norg, Porg, mineral compounds of nitrogen and phosphorus. Methane concentration in Baikal water in 2016 varied within 0.44–3.41 µL/dm3 (on the average, 0.80 µL/dm3); in 2019, within 0.20–5.19 µL/dm3 (on the average, 1.22 µL/dm3). The maximal methane concentration was recorded in the water mass of the deepest central depression of the lake, and the minimal, in its southern depression. Among shallow areas, minimal methane concentrations were recorded in the coastal zone of Listvenichnyi Bay, and its maximal concentrations, in the northern part of the lake, into which many rivers empty, as well as in Selenginskoe shallows. Most stations, either deep-water or shallow, showed a peak of subsurface maximum of methane concentration at depths of 25–50 m (thermocline zone), after which its concentrations commonly dropped, reaching their minimal values either in the intermediate water mass or in bottom layers. Shallow areas, in addition to higher methane concentrations compared to deep-water areas, also featured a higher contrast in its vertical distribution in the water mass. The analysis of correlation relationships between the examined hydrochemical characteristics revealed significant direct correlations of methane concentration with the concentrations of Corg and Norg and an inverse correlation with O2 concentrations.
Space–Time Variations of Fish Communities from the Belbek River
Authors: Karpova E. P. , Statkevich  S. V. , Ablyazov E. R.
Published: April 2024

This paper presents the results of studying the species composition, diversity, and dynamics of fish communities from the middle reaches of the Belbek River, one of the small rivers of the Crimean Peninsula, which is actively used to eliminate the shortage of water supply in recent years. The river is currently exposed to significant anthropogenic impact. Trends of change in the structure of the fish community with the economic development of the river have been observed and the main forms of negative environmental impact have been identified. A deterioration in the structure of aquatic communities and a sharp decrease in their diversity have been recorded over a short time period. A decrease in the abundance and a deformation of the population structure of native fish species (Crimea shemaya Alburnus mentoides, Crimean barbel Barbus tauricus, and Salgir gudgeon Gobio krymensis) are also observed. The determining influence of hydraulic engineering and hydrotechnical measures on destructive processes in aquatic ecosystems is shown.
Statistical Modeling of Extreme Precipitation in Summer in the Baikal Region with the Use of the Correlation Theory of Random Fields
Authors: Bolgov M. V. , Trubetskova M. D.
Published: April 2024

A probabilistic model of the sums of extreme precipitation was developed for heavy showers covering large areas in the Baikal region. The spatial correlation functions of precipitation fields over one day and the entire rain period were studied. Data on the Iya River basin were used to evaluate the errors in estimating the mean values over a specified contour of extreme precipitation. Errors in the interpolation of precipitation estimates for the Baikal region were evaluated in the absence of observation data with estimation of the errors of the obtained values by Drozdov–Shepelevskii formulas. These errors amounted to about 10–15% and more. The specific features of precipitation field structures were studied with the use of their expansion in series in natural orthogonal functions for one day and over a rain period for different samples: for the entire combination of cases and for samples containing 10 and 30 maximal precipitation totals for each weather station, i.e., for extreme events. It was found that, if the observation data are limited to a range of maximal values, the structure of precipitation fields is simplified and the first 4–5 decomposition components are enough for its description. The obtained results are of importance for forecast problems and for the construction of simulation models of precipitation fields for further use in deterministic runoff simulation.
Correction of Algacenoses by Chlorella Introduction: Analysis of Application Cases
Authors: Pavlyuk T. E. , Popov A. N. , Ushakova O. S. , Mukhutdinov V. F. , Padalka A. A.
Published: April 2024

Public data of applied studies in the recent decade and the theoretical base and functioning principles of aquatic ecosystems, including phytoplankton, were analyzed to study the effect of the active introduction of the method for correction of water bodies algacenoses (the so-called “algalization”) with the use of introduction of a wide range of strains of chlorella algae. A review of the most widely known cases to rehabilitate problematic water bodies is given; errors, delusions, and deliberate distortions of facts by representatives of agricultural industry, promoting the idea of rehabilitation of water bodies by correction of natural algacenoses, are considered.
Numerical 2D-Modeling of Rain Runoff Transformation in the Drainage Basin of Gelendzhik City Taking into Account the Mountain Collector and Accumulating Reservoirs
Authors: Belikov V. V. , Borisova N. M.
Published: April 2024

A digital relief model of a mountain cluster and location schemes of mountain collectors and reservoir dams were used to develop a numerical hydrodynamic 2D-model of the mountain part of the drainage basin of Gelendzhik City area and to perform variant calculations of rain flood waves, taking into account their transformations in mountain collectors and accumulation in reservoirs. The rains considered in the model were assumed to have the exceedance probability of 1% and the duration of 20 and 720 min (12 h) with a total rainfall depths of 51 and 206 mm, respectively. Conclusions were made that the carrying capacity of the collector should be calculated for the parameters of a short-time intense rain and that the accumulating hydraulic structures, for their efficient operation, should be designed to allow continuous regulation of discharge rates.
Modeling the Genetic Components of the Water and Chemical Runoff of Heavy Metals in the Basin of the Nizhnekamskoe Reservoir
Authors: Fashchevskaya T. B. , Motovilov  Yu. G. , Kortunova K. V.
Published: April 2024

A semi-distributed physical-mathematical model ECOMAG-HM is used to simulate the genetic structure of water and chemical runoff of copper, zinc, and manganese in a large river basin of the Nizhnekamsk Reservoir. The model was tested against long-term data of hydrological and hydrochemical monitoring of water bodies. The contributions of the surface, soil, and subsoil components of the water and chemical runoff of metals are estimated for different segments of river network. It was found that, in the major portion of the catchment, river pollution by metals is mostly due to their diffuse washout from the soil layer. The effect of the genetic structure of water and chemical runoff on the year-to-year and seasonal variations of metal concentrations in the river network is demonstrated.