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Abstract The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein’s crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.

Introduction. Evaluation of the content of impurities is the most important step in confirming the safety and efficacy in the quality control of the medicinal product. Aluminum, being an acceptable impurity in a number of pharmaceutical substances, can adversely affect the human body, as a result of which its content is normalized. The admixture of aluminum in the State Pharmacopoeia of the Russian Federation XV is determined by the spectrofluorimetric method using the ligand – 8-hydroxyquinoline in chloroform. In the present work, it is proposed to replace 8-hydroxyquinoline with the more accessible rutin, which also forms fluorescent complexes with metals. This approach involves the exclusion of the stage of extraction of the aluminum complex into chloroform from sample preparation, which improves the accuracy of the technique, and the replacement of chloroform has a positive effect on safety.Aim. To create an alternative approach for the spectrofluorimetric determination of aluminum impurities using rutin and "potassium chloride" as an active pharmaceutical ingredient.Materials and methods. The following substances and reagents were used as research materials: CRS of aluminum ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS of iron ion (II) 1 mg/ml (LLC "EKROSHIM", Russia), CRS of zinc ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS of lead-ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS nickel-ion 1 mg/ml (LLC "EKROSHIM", Russia), CRS copper-ion 1 mg/ml (LLC "EKROSHIM", Russia), chromium (III) cation standard 1 mg/ml (imp., Sigma-Aldrich, USA) rutin (imp., Sichuan Guangsong Pharmaceutical Co., Ltd., China), ammonium acetic acid (imp., Molekula GmbH, Germany), glacial acetic acid (chemically pure, JSC "Base No. 1 Himreaktivov", Russia), potassium chloride (pharmaceutical substance, LLC "MZHR", Russia). The spectrofluorimetric study was carried out on an FL 6500 instrument (PerkinElmer Inc., USA). The aluminum impurity content was also evaluated using an Optima 8000 inductively coupled plasma atomic emission spectrometer (ICP AES) (PerkinElmer Inc., USA) and a Multi-Element Solution standard sample (PerkinElmer Inc., USA).Results and discussion. The approach given in the article eliminates the use of 8-hydroxyquinoline in chloroform and replaces it with rutin in 70 % ethyl alcohol. The aluminum-rutin complex has an excitation wavelength at 445 nm and an emission wavelength at 565 nm. The proposed method was tested on the substance "Potassium chloride" to assess the indicator "Aluminum", the content of which should not exceed 0.0001 %. Method validation was carried out according to three parameters "Specificity", "Linearity" and "Limit of detection". Comparison of the data obtained was carried out using atomic emission spectroscopy, during which the relevance of the technique was proved.Conclusion. An ergonomic approach has been developed for the spectrofluorimetric determination of aluminum impurities using rutin with approbation on the substance "Potassium chloride". The results obtained during the experiment were confirmed by the ICP AES method.

Serial crystallography (SX) has become an established technique for protein structure determination, especially when dealing with small or radiation-sensitive crystals and investigating fast or irreversible protein dynamics. The advent of newly developed multi-megapixel X-ray area detectors, capable of capturing over 1000 images per second, has brought about substantial benefits. However, this advancement also entails a notable increase in the volume of collected data. Today, up to 2 PB of data per experiment could be easily obtained under efficient operating conditions. The combined costs associated with storing data from multiple experiments provide a compelling incentive to develop strategies that effectively reduce the amount of data stored on disk while maintaining the quality of scientific outcomes. Lossless data-compression methods are designed to preserve the information content of the data but often struggle to achieve a high compression ratio when applied to experimental data that contain noise. Conversely, lossy compression methods offer the potential to greatly reduce the data volume. Nonetheless, it is vital to thoroughly assess the impact of data quality and scientific outcomes when employing lossy compression, as it inherently involves discarding information. The evaluation of lossy compression effects on data requires proper data quality metrics. In our research, we assess various approaches for both lossless and lossy compression techniques applied to SX data, and equally importantly, we describe metrics suitable for evaluating SX data quality.

NendoU from SARS-CoV-2 is responsible for the virus's ability to evade the innate immune system by cleaving the polyuridine leader sequence of antisense viral RNA. Here we report the room-temperature structure of NendoU, solved by serial femtosecond crystallography at an X-ray free-electron laser to 2.6 Å resolution. The room-temperature structure provides insight into the flexibility, dynamics, and other intrinsic properties of NendoU, with indications that the enzyme functions as an allosteric switch. Functional studies examining cleavage specificity in solution and in crystals support the uridine-purine cleavage preference, and we demonstrate that enzyme activity is fully maintained in crystal form. Optimizing the purification of NendoU and identifying suitable crystallization conditions set the benchmark for future time-resolved serial femtosecond crystallography studies. This could advance the design of antivirals with higher efficacy in treating coronaviral infections, since drugs that block allosteric conformational changes are less prone to drug resistance.

The study is aimed to identify urgent problems in the field of communication between young men and women and other significant participants in unregulated interaction. Using standardised test methods, questionnaires were adapted for this study and were collected the primary material that reflects the essential characteristics of unregulated communication between high school students in Russia. The sample of the study was 378 people. The main results were the data indicating a serious gap between high school students' need to communicate and the actual satisfaction of this need in the interaction with other significant participants. The main meaning of young people's need for trustful reference unregulated communication is not so much the communicative component as the emotional-affective content, which consists of acceptance, support, emotional exchange and understanding on the part of other people. Currently, there is a gap between the need for unregulated confidential communication of young men and women with significant adults and the real system of such communication. The results were put into the development of recommendations that allow psychologists to build an optimal interaction with family systems and the pedagogical community to optimise communication between high school students. As a prospect for further research, the tasks of developing parent-child relationships are identified.

Background Management of bone defects with autologous bone grafting has always been the "gold standard" but it is not always possible to use it for a number of reasons. Preprocessed materials of biological and non-biological origin were developed as an alternative. A new branch of these materials is tissue-engineered constructs that fully imitate autologous bone in required volume. Aim is to study in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs. Methods The study was carried out on 24 NZW line rabbits, since this line has a fully characterized stromal-vascular fraction formula (SVF). The study design included 3 groups. Fiкst group (control) had surgical modeling of bone defects in the diaphysis of the contralateral femur without reconstruction; Group 2 had bone defect reconstruction using fragments of a deproteinized cancellous bone graft; group 3 underwent bone defect reconstruction using fragments of deproteinized cancellous bone matrix along with the autologous adipose tissue SVF (obtained according to ACP SVF technology). Animals were sacrificed with ether anesthesia at 2, 4 and 6 weeks after the operation and subsequent histological study followed. Result During all periods of the study, the newly formed bone tissue volume density in the 3rd group (reconstruction with deproteinized human cancellous bone + stromal-vascular fraction) was 1.78 times higher (p < 0.001) than in the first group (bone defect without reconstruction), 1.21 times higher (p < 0.001) than in the 2nd group (reconstruction with deproteinized cancellous bone alone). The dynamics of changes in the mature bone tissue volume density was similar to those of the newly formed bone tissue. Discussion The comparative analysis of reparative processes using a tissue engeneered construst based on deproteinized cancellous human bone with adipose tissue stromal vascular fraction revealed that the use of these bone substitute materials contributes not only to the early activation of reparative regeneration of the main structural elements of bone tissue at the site of bone defect, but also their timely differentiation. Conclusion The use of deproteinized cancellous bone matrix combined with stromal-vascular fraction to create a tissue-engineered construct could unleash several regeneration mechanisms and accelerate the process of bone defect site repair, compared with 1st and 2nd group of study.

In this work, we describe the transcriptional profiles of preadapted and non-adapted one-month-old juvenile Baikal whitefish after heat shock exposure. Preadapted fish were exposed to a repeated thermal rise of 6 °C above the control temperature every three days throughout their embryonic development. One month after hatching, preadapted and non-adapted larvae were either kept at control temperatures (12 °C) or exposed to an acute thermal stress (TS) of 12 °C above the control temperature. In response to this acute stress, an increase in HSP gene expression (HSP-30, HSP-40, HSP-47, HSP-70, and HSP-90) and TRIM16 was detected, independent of preadaptation. The expression levels of genes responsible for the response to oxygen levels, growth factors and the immune response, HBA, HBB, Myosin VI, Myosin VII, MHC, Plumieribetin, TnI, CYP450, and LDB3 were higher in individuals that had previously undergone adaptation. Genes responsible for the regulation of metabolism, MtCK, aFGF, ARF, CRYGB, and D-DT, however, increased their activity in non-adapted individuals. This information on transcriptional profiles will contribute to further understanding of the mechanisms of adaptation of whitefish to their environment.

Acclimation through the hormesis effect increases the plasticity of organisms, which has been shown for many ectothermic animals, including fish. We investigated the effect of temperature acclimation in Baikal whitefish Coregonus baicalensis (Dybowski, 1874). Telomere length, telomerase activity, and the expression of genes, whose products are involved in the regulation of telomere length and defense against reactive oxygen species, were selected to assess the state of the larvae. Acclimation and acute temperature stress (+12 °C) had no effect on telomere length, but altered telomerase activity (acclimation decreased it; stress increased it) and the levels of genes expression. Under stress, the expression of superoxide dismutase genes was increased in acclimated larvae and that of glutathione peroxidases in non-acclimated larvae, which may indicate lower reactive oxygen species formation and slower antioxidant responses in acclimated fish. The expression of some telomere-related genes was reduced under temperature stress, but the expression of the tzap and smg genes, whose products improve the control of telomere length by preventing them from lengthening or shortening, was increased in acclimated individuals. The data obtained indicate a positive effect of acclimation on the state of the Baikal whitefish larvae by remodulation of their telomerase activity and the transcriptional profile.

The novel antiparkinsonian agent PA-96 is the focus of our research. PA-96 supported the survival of cultured naïve dopamine neurons, alleviated motor deficits in MPTP and haloperidol-based mice models of Parkinson’s disease, and increased the density of tyrosine hydroxylase positive neurons and dopamine concentration in the midbrain of an MPTP-damaged brain. In this work, an HPLC–MS/MS method was developed and validated, and the pharmacokinetics of the agent was investigated in mice after a single or multiple oral administration (p.o.) and intravenous injection (i.v.) at various doses. The dose proportionality was also evaluated after a single p.o. administration of three ascending doses (1, 5, and 10 mg/kg) and a single i.v. injection of two doses (1 and 10 mg/kg); also, the bioavailability was estimated. The disproportionality of pharmacokinetic parameters could be explained by the saturation of active centres of enzymes or receptors binding the substance: at low doses, part of the compound is bound, leaving a small amount circulating in blood, and rapidly metabolised and/or bound too. The bioavailability of PA-96 was c.a. 7 and 35% for the doses of 5 and 10 mg/kg, correspondingly.

The paper presents results of the desktop analysis on the current status of the problem of the personal potential in terms of psychology. It provides the author's understanding of the term as the formation consistent and structured in its psychological aspect. This is the analysis of the characteristics that the career choice has and the difficulties that the graduates face in this process. We believe that substantial resources for the independent and responsible career choice are inherent in the personal potential. According to the research methods, the structure of the personal potential includes intra and interpsychological characteristics. Internal factors relate to the non-acceptance of the choice situation, the lack of skills that are necessary for subjective construction of its process. They also come from hesitation, lack of confidence, poor self-concept, internal conflicts, low community commitment, etc. In most cases, the powerful influence of relevant adults is an external obstacle. The data obtained justify a need in psychological and education counseling to develop the personal potential of graduates. In this regard, one of the main tasks is to provide graduates with competent and comprehensive support to overcome difficulties in the process of making the career choice and personal potential development.

Background. Pigment concentration is a species trait, and is an integral indicator of adaptive response to changes in environmental factors and the growing conditions. The intensive development of modern cities imposes certain requirements on the selection of plants for landscaping, one of which is a high level of adaptive responses. Purpose. The purpose of this study was to determine the content of photosynthetic pigments in the leaves of the genus Acer species in urban conditions of the city of Maуkop, the Adygea Republic. Materials and methods. We used the spectrophotometric method to determine the content of photosynthetic pigments in the leaves of the genus Acer L. species: A. platanoides, A. pseudoplatanus, A. saccharinum, A. negundo, A. campestre in an urban environment of the city of Maуkop and the zone of conditional control (Botanical garden). We carried out statistical processing of experimental data by using the MS Excel 2010 package. Results. We have revealed that in the conditions of an urbanized environment the total content of chlorophylls is 1.1-2.2 times higher in comparison with that of the zone of control. Taking into account the level of variability of the total content of green pigments in the city, we arranged the studied species in the following order: A. saccharinum A. campestre ˂ A. pseudoplatanus ˂ A. platanoides ˂ A. negundo. The ratio of the amount of chlorophylls to carotenoids reacted very sensitively to the impact of urban environmental factors. A. campestre and A. saccharinum differed from A. negundo, A. pseudoplatanus, and A. platanoides for this indicator. Conclusion. The study made allow us to state that in the conditions of an urbanized environment, the studied species of the genus Acer undergo restructuring in the structure of pigment complexes. An increase in the synthesis of chlorophylls and carotenoids raises their adaptive capabilities to the negative impact of urban environmental factors.

Abstract For decades, researchers have elucidated essential enzymatic functions on the atomic length scale by tracing atomic positions in real-time. Our work builds on possibilities unleashed by mix-and-inject serial crystallography (MISC) at X-ray free electron laser facilities. In this approach, enzymatic reactions are triggered by mixing substrate or ligand solutions with enzyme microcrystals. Here, we report in atomic detail (between 2.2 and 2.7 Å resolution) by room-temperature, time-resolved crystallography with millisecond time-resolution (with timepoints between 3 ms and 700 ms) how the Mycobacterium tuberculosis enzyme BlaC is inhibited by sulbactam (SUB). Our results reveal ligand binding heterogeneity, ligand gating, cooperativity, induced fit, and conformational selection all from the same set of MISC data, detailing how SUB approaches the catalytic clefts and binds to the enzyme noncovalently before reacting to a trans-enamine. This was made possible in part by the application of singular value decomposition to the MISC data using a program that remains functional even if unit cell parameters change up to 3 Å during the reaction.

Here, we illustrate what happens inside the catalytic cleft of an enzyme when substrate or ligand binds on single-millisecond timescales. The initial phase of the enzymatic cycle is observed with near-atomic resolution using the most advanced X-ray source currently available: the European XFEL (EuXFEL). The high repetition rate of the EuXFEL combined with our mix-and-inject technology enables the initial phase of ceftriaxone binding to the Mycobacterium tuberculosis β-lactamase to be followed using time-resolved crystallography in real time. It is shown how a diffusion coefficient in enzyme crystals can be derived directly from the X-ray data, enabling the determination of ligand and enzyme-ligand concentrations at any position in the crystal volume as a function of time. In addition, the structure of the irreversible inhibitor sulbactam bound to the enzyme at a 66 ms time delay after mixing is described. This demonstrates that the EuXFEL can be used as an important tool for biomedically relevant research.

Background. At present, for a number of reasons the complete bone defect replacement with autogenous bone is not always possible. Bone substitute materials are used as an alternative to autogenous bone tissue and can be of either biological or non-biological origin. One of the ways of development of reconstructive technologies is the use of tissue-engineered constructs that fully imitate autogenous bone tissue in the required volume. Aim of study to define in vivo the possibility of using deproteinized human cancellous bone tissue as a matrix for creating tissue-engineered constructs. Methods. An in vivo study was carried out on NZW rabbits. To create a construct, we used the fragments of deproteinized cancellous bone tissue of the human femoral head and stromal vascular fraction of rabbit adipose tissue as a matrix. Bone defect modeling with its subsequent replacement was performed to evaluate the efficacy of reparative osteogenesis during bone defects reconstruction. Study groups were defined: group 1 (control) surgical modeling of a bone defect of the femur without its reconstruction; group 2 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix; group 3 surgical modeling of a bone defect of the femur with its reconstruction using fragments of deproteinized cancellous bone matrix in combination with stromal vascular fraction of adipose tissue (according to ACP SVF technology). Results. Comparative analysis of reparative processes in case of applying tissue-engineered constructs based on deproteinized human cancellous bone matrix in combination with adipose tissue-derived stromal vascular fraction on in vivo experimental model revealed that the use of these bone substitute materials contributes not only to an early activation of reparative regeneration of main structural elements of the bone tissue in the area of the bone defect replacement, but also to its well-timed differentiation. This determines the restoration of structural and functional viability of the bone tissue at the damage site without developing discernible reactive inflammation. Moreover, the effect of the selected tissue-engineered construct with the combined influence of several factors (ACP SVF) in its composition turned out to be more effective in stimulating bone tissue repair and differentiation. Conclusion. Combination of SVF and deproteinized bone matrix for creating tissue-engineered constructs enables to engage several regeneration mechanisms and accelerate the process of bone defect replacement in comparison with isolated deproteinized bone matrix without bone defect reconstruction.

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6Ay) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.

In paediatrics, it is a common practice to use pharmaceuticals outside the approved Summary of Product Characteristics (i.e. off-label). According to the literature, up to 45% of inpatient paediatric prescriptions and 10–20% of outpatient ones are for off-label uses. It is essential to analyse such uses, as it helps medical practitioners act reasonably and professionally.The aim of the study was to explore the possibility of using spontaneous reports to assess the risks of the off-label use of cardiac medicinal products in children in the Irkutsk region.Materials and methods. The authors analysed 25 reporting forms on adverse drug reactions (ADRs) in paediatric cardiac patients from the database of the Regional Centre for Drug Safety Monitoring of the Irkutsk Region and regional data from the Automated Information System (AIS) of the Federal Service for Surveillance in Healthcare of the Russian Federation (Roszdravnadzor) submitted in 2009–2020. The inclusion criterion for reporting forms was a causal relationship between the off-label use of a medicinal product and the ADR that was scored as “possible” or higher on the Naranjo probability scale.Results. According to the reporting forms, the off-label use of cardiac medicinal products in children was associated with ADRs, such as angiooedema, cutaneous symptoms, and bronchospasm. The majority of ADRs (84%) were considered severe. The medicinal products were prescribed for heart failure, arterial hypertension, and cardiac arrhythmias. The majority of ADR reports (75%) were submitted by inpatient medical organisations.Conclusions. The analysis of spontaneous ADR reporting databases is a simple and informative method for studying the safety of medicinal products. It is necessary to raise awareness of ADRs associated with off-label prescribing amongst paediatric cardiologists in order to reduce the incidence of ADRs. The following contributions will improve the quality of medical care: all parties involved with pharmaceuticals should adhere to good pharmacovigilance practices, medical practitioners should be actively involved in treatment safety monitoring, and the professional training curricula of paediatric cardiologists and paediatricians should include specific units on the practical functioning of pharmacovigilance.

The European XFEL (EuXFEL) is a 3.4-km long X-ray source, which produces femtosecond, ultrabrilliant and spatially coherent X-ray pulses at megahertz (MHz) repetition rates. This X-ray source has been designed to enable the observation of ultrafast processes with near-atomic spatial resolution. Time-resolved crystallographic investigations on biological macromolecules belong to an important class of experiments that explore fundamental and functional structural displacements in these molecules. Due to the unusual MHz X-ray pulse structure at the EuXFEL, these experiments are challenging. Here, we demonstrate how a biological reaction can be followed on ultrafast timescales at the EuXFEL. We investigate the picosecond time range in the photocycle of photoactive yellow protein (PYP) with MHz X-ray pulse rates. We show that difference electron density maps of excellent quality can be obtained. The results connect the previously explored femtosecond PYP dynamics to timescales accessible at synchrotrons. This opens the door to a wide range of time-resolved studies at the EuXFEL.

Nimesulide (NIM) is a nonsteroid anti-inflammatory drug which acts as a selective cyclooxygenase 2 inhibitor and is widely used for acute pain treatment. In medical practice, a large amount of data has been collected describing the effect of NIM on the body, while a hepatotoxic side effect of the drug has been found. The exact mechanisms of such NIM-induced hepatotoxicity largely remain unknown but likely involve the intermediate reaction of its metabolism. Reduction of the hepatotoxic side effect of NIM is an actual problem for pharmacology. The aim of the present research was to evaluate the hepatotoxicity of the mechanochemically obtained composition of NIM with glycyrrhizic acid disodium salt (Na2GA) compared to pure NIM and a physical mixture of NIM with Na2GA. Material and methods. CD-1 mice were orally administered for 14 days: 1 group – mechanochemical composition NIM/Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 2 group – physical mixture of NIM with Na2GA (1:10, m/m) at a dose of 1650 mg/kg; 3 group – pure NIM at a dose of 600 mg/kg (which pharmacokinetically corresponds to 1650 mg/kg of NIM/Na2GA); 4 group – vehicle (distilled water). The liver damage was assessed using histological studies and enzymatic activity of the alanine aminotransferase and aspartate aminotransferase in blood serum. Results. Histological analysis did not detect any changes in the liver of NIM/Na2GA-treated animals in comparison with a water-treated group. On the opposite, NIM given alone or as a physical mixture with Na2GA induced severe hepatotoxicity in experimental mice. Biochemical analysis of the blood serum revealed that mechanochemical NIM/Na2GA composition significantly reduced activity of the alanine aminotransferase (about 1.5 times) and aspartate aminotransferase (1.3 times) as compared with the pure NIM. Conclusions. The results obtained indicate a high potential for the practical application of the NIM/Na2GA mechanochemical composition.

A novel free fatty acid receptor 1 (FFAR1) agonist has been synthesized and evaluated in vitro. The synthesis of the title compound was performed from commercially available 4-hydroxybenzaldehyde, 2-thiophenecarboxaldehyde, and (+)-camphor. The compound was shown to have an affinity to FFAR1.

Simple Summary: Temperature acclimation enables animals, especially aquatic ones, to safely survive climate fluctuations in the natural environment. The aim of our work was to study how temperature acclimation in aquaculture affects cold-water Baikal whitefish at the embryonic stage and their well-being during a heat shock (24 °C). Selected molecular markers (telomere length, telomerase activity, and expression of target genes) showed that acclimation at the early developmental stages has a positive effect on the Baikal whitefish larvae and allows them to tolerate acute temperature stress without the harmful consequences. The data obtained will improve the survival of fish and increase their plasticity under aquaculture conditions. Acclimation through the hormesis effect increases the plasticity of organisms, which has been shown for many ectothermic animals, including fish. We investigated the effect of temperature acclimation in Baikal whitefish Coregonus baicalensis (Dybowski, 1874). Telomere length, telomerase activity, and the expression of genes, whose products are involved in the regulation of telomere length and defense against reactive oxygen species, were selected to assess the state of the larvae. Acclimation and acute temperature stress (+12 °C) had no effect on telomere length, but altered telomerase activity (acclimation decreased it; stress increased it) and the levels of genes expression. Under stress, the expression of superoxide dismutase genes was increased in acclimated larvae and that of glutathione peroxidases in non-acclimated larvae, which may indicate lower reactive oxygen species formation and slower antioxidant responses in acclimated fish. The expression of some telomere-related genes was reduced under temperature stress, but the expression of the tzap and smg genes, whose products improve the control of telomere length by preventing them from lengthening or shortening, was increased in acclimated individuals. The data obtained indicate a positive effect of acclimation on the state of the Baikal whitefish larvae by remodulation of their telomerase activity and the transcriptional profile. [ABSTRACT FROM AUTHOR]