Abstract Nrf2 is a key transcription factor responsible for antioxidant defense in many tissues and cells, including alveolar epithelium, endothelium, and macrophages. Furthermore, Nrf2 functions as a transcriptional repressor that inhibits expression of the inflammatory cytokines in macrophages. Critically ill patients with COVID-19 infection often present signs of high oxidative stress and systemic

Abstract Transcriptional factor p53 is a master regulator of energy metabolism. Energy metabolism strongly depends on thiamine (vitamin B1) and/or its natural derivatives. Thiamine diphosphate (ThDP), which is a major thiamine derivative, affects p53 binding to DNA. In order to elucidate the mechanism of regulation of thiamine-dependent metabolism by p53, we assessed putative p53-binding sites near

Abstract Increased expression or amplification of HER2 receptor tyrosine kinase gene ERBB2 is well-known and widely used as a prognostic biomarker of breast cancer (BC) response to the targeted treatment with trastuzumab and its analogs. Considering that part of the BC patients overexpressing HER2 does not respond to trastuzumab, clinical trial NCT03521245 was initiated to identify additional gene

Abstract The concept of “electric cables” involved in bioenergetic processes in a living cell was proposed half a century ago [Skulachev, V. P. (1971) Curr. Top. Bioenerg., Elsevier, pp. 127-190]. Membrane structures of a cell were considered as probable pathways for transferring transmembrane electrochemical potential. Further studies have shown that coupling membranes (inner mitochondrial membrane

Abstract The effect of bioresorbable materials on aging in cultured mouse NIH 3T3 fibroblasts treated with elevated glucose concentration was investigated. The cells were grown on films produced from the silkworm fibroin and rS1/9, a recombinant analog of Nephila clavipes spidroin 1. Exposure to 50 mM glucose of the cells grown on uncoated glass support resulted in the cell growth retardation. The

Abstract Phytoene and phytofluene – uncolored C40 carotenoids with short chain of conjugated double bonds (3 and 5, respectively) – are known to be universal precursors in biosynthesis of colored carotenoids in photosynthesizing organisms. It is commonly recognized that C40 carotenoids are photoprotectors of cells and tissues. We have shown that phytofluene is an exception to this rule. By measuring

Abstract Spliceosomal introns, which have been found in most eukaryotic genes, are non-coding sequences excised from pre-mRNAs by a special complex called spliceosome during mRNA splicing. Introns occur in both protein- and RNA-coding genes and can be found in coding and untranslated gene regions. Because intron sequences vary greatly due to a high rate of polymorphism, the functions of intron had

Abstract RNA polymerase (RNAP) recognizes promoter DNA through many interactions that determine specificity of transcription initiation. In addition to the dedicated transcription initiation σ factor in bacteria, the core enzyme of RNAP can also participate in promoter recognition. In particular, guanine residue at the +2 position (+2G) of the nontemplate DNA strand is bound in the CRE pocket formed

Abstract For the first time, the chymosin gene (CYM) of a maral was characterized. Its exon/intron organization was established using comparative analysis of the nucleotide sequence. The CYM mRNA sequence encoding a maral preprochymosin was reconstructed. Nucleotide sequence of the CYM maral mRNA allowed developing an expression vector to ensure production of a recombinant enzyme. Recombinant maral

Abstract Main factors involved in carcinogenesis are associated with somatic mutations in oncogenes and tumor suppressor genes representing changes in the DNA nucleotide sequence. Epigenetic changes, such as aberrant DNA methylation, modifications of histone proteins, and chromatin remodeling, are equally important in the development of human neoplasms. From this perspective, mutations in the genes

Abstract Yanbian yellow cattle are one of the top five largest breeds of cattle in China. We had previously found that bta-miR-1271 is differentially expressed in the longissimus dorsi muscles of Yanbian yellow bulls and steers. However, whether bta-miR-1271 affects bovine fat formation is unclear. In this study, we used target gene prediction, dual-luciferase reporter assay, and transfection-mediated

Abstract The structure and functional organization of the photosystem I (PSI) reaction center (RC) donor side has a significant similarity to the reaction centers of purple bacteria (bRCs), despite the fact that they belong to different types of RCs. Moreover, the redox potential values of their primary electron donors are identical (~0.5 V). In our earlier reports [Khorobrykh et al. (2008) Phylos

Abstract The gene coding for PMGL2 esterase, which belongs to the family of mammalian hormone-sensitive lipases (HSLs), was discovered by screening a metagenomic DNA library from a permafrost soil. The active site of PMGL2 contains conserved GXSXG motif which includes Cys173 residue next to the catalytic Ser174. In order to clarify the functional role of the cysteine residue in the GCSAG motif, we

Abstract A recombinant strain producing a complex of extracellular enzymes including chitinase from Myceliophtora thermophila was created based on the fungus Penicillium verruculosum. The activity of the enzyme preparations obtained from the cultural fluid of the producer strain was 0.55, 0.53, and 0.66 U/mg protein with chitin and chitosans with the molecular weight of 200 and 1000 kDa, respectively

Abstract Functional compartmentalization of the cell nucleus plays an important role in the regulation of genome activity by providing accumulation of enzymes and auxiliary factors in the reaction centers, such as transcription factories, Cajal bodies, speckles, etc. The mechanisms behind the nucleus functional compartmentalization are still poorly understood. There are reasons to believe that the

Abstract SASH1 is an adapter and signaling protein that contains SH3 and SAM domains responsible for protein–protein interactions. SASH1 downregulation has been observed in many tumors. We examined localization of SASH1 in cultures of normal IAR-20 epithelial cells and HT-29 colorectal cancer cells using immunofluorescence staining and confocal microscopy. IAR-20 normal epithelial cells and HT-29 cells

Abstract Cryptophyte algae belong to a special group of oxygenic photosynthetic organisms containing pigment combination unique for plastids – phycobiliproteins and chlorophyll a/c-containing antenna. Despite the progress in investigation of morphological and ecological features, as well as genome-based systematics of cryptophytes, their photosynthetic apparatus remains poorly understood. The ratio

Abstract The objective of this study was screening of ommochromes from the compound eyes of insects and comparison of their antioxidant properties. Ommochromes were isolated in preparative quantities from insects of five different families: Stratiomyidae, Sphingidae, Blaberidae, Acrididae, and Tenebrionidae. The yield of ommochromes (dry pigment weight) was 0.9-5.4% of tissue wet weight depending on

Abstract NAD+-dependent formate dehydrogenase from Staphylococcus aureus (SauFDH) is one of the key enzymes responsible for the survival of this pathogen in the form of biofilms. 3D structure of the enzyme might be helpful in the search for highly specific SauFDH inhibitors that can be used as antibacterial agents exactly against S. aureus biofilms. Here, we prepared a recombinant SauFDH in Escherichia

Abstract Up to now numerous studies in the field of gerontology have been published. Nevertheless, a well-known food restriction remains the most reliable and efficient way of lifespan extension. Physical activity is also a well-documented anti-aging intervention being especially efficient in slowing down the age-associated decline of skeletal muscle mass. In this review we focus on the molecular mechanisms

Abstract Plasmodesmata (PD) are intercellular channels in plant tissues providing continuity of the cytoplasm, the plasma membrane (PM) and the endoplasmic reticulum (ER) of neighboring cells. These channels allow the active transport of macromolecules such as proteins or RNAs. Thus, PD are believed to play a critical role in the functional unity of plant tissues and the transport of signals required

Abstract Determination of biological sex to human remains is a fundamental requirement in anthropological, archeological, and forensic anthropological studies. Sex determination based on morphological criteria is significantly limited in the cases of juvenile remains and adult skeletons in a poor state of preservation. Regular attempts have been made to use alternative techniques to resolve this issue

Abstract Association between lymphocyte activation and formation of immune tolerance, as well as pregnancy outcome, in the case of immunocytotherapy (ICT) was studied in women with idiopathic recurrent pregnancy loss (IRPL). The content and phenotypic characteristics of activated T lymphocytes and NK cells were investigated in the peripheral blood of IRPL patients with different pregnancy outcomes

Abstract Lichens are symbiotic photosynthesizing organisms with thalli formed by fungi and algae/cyanobacteria that possess high stress tolerance. One of the factors that contributes to the ability of a lichen to tolerate harsh environmental conditions is the presence of unique metabolites, including high-molecular-weight dark pigments termed melanins. The chemical composition and structure of lichen

Abstract Human uracil-DNA glycosylase SMUG1 removes uracil residues and some other noncanonical or damaged bases from DNA. Despite the functional importance of this enzyme, its X-ray structure is still unavailable. Previously, we performed homology modeling of human SMUG1 structure and suggested the roles of some amino acid residues in the recognition of damaged nucleotides and their removal from DNA

Abstract Two glycosyl 1-phosphate polymers containing monoglycosyl 1-phosphate, -6)-α-D-Glcp-(1-P., and diglycosyl 1-phosphate, -6)-α-D-GalpNAc-(1→6)-α-D-GlcpNAc-(1-P., in the repeating unit were identified in the cell wall of Glutamicibacter protophormiae VKM Ac-2104T (formerly, Arthrobacter protophormiae). The structures of these polymers were described for the first time in prokaryotes. Teichulosonic

Abstract Deterioration of energy metabolism in affected cells is an important feature of synucleinopathies, including Parkinson's disease. Here, we studied the association between α-synuclein accumulation and glycolysis using SH-SY5Y neuroblastoma cell lines stably expressing wild-type α-synuclein or its A53T mutant linked to the autosomal dominant form of the disease. Overexpression of both proteins

Abstract Aerobic gram-negative bacterium Acinetobacter baumannii has recently become one of the most relevant pathogens associated with hospital-acquired infections worldwide. A. baumannii produces a capsule around the cell, which represents a thick viscous layer of structurally variable capsular polysaccharide (CPS). The capsule protects the bacteria against unfavorable environmental factors and biological

Abstract In the pathogenesis of the infectious process in the respiratory tract by SARS, MERS, and COVID-19 coronaviruses, two stages can be distinguished: early (etiotropic) and late (pathogenetic) ones. In the first stage, when the virus multiplication and accumulation are prevalent under insufficient host immune response, the use of chemotherapeutic agents blocking the reproduction of the virus

Abstract “Mitochondrial transplantation” refers to a procedure for introducing isolated mitochondria into a damaged area of a heart or other organ. A considerable amount of data has been accumulated on the therapeutic effects of “mitochondrial transplantation” in animals with ischemic heart damage. In 2017, the first attempts were made to apply this procedure in a clinic. The authors of the method

Abstract Phenylacetone monooxygenase (EC 1.14.13.92, PAMO) catalyzes oxidation of ketones with molecular oxygen and NADPH with the formation of esters. PAMO is a promising enzyme for biotechnological processes. In this work, we generated genetic constructs coding for PAMO from Thermobifida fusca, containing N- or C-terminal His6-tags (PAMO N and PAMO C, respectively), as well as PAMO L with the His6-tag

Abstract Inactivated (whole-virion, split, subunit, and adjuvanted) vaccines and live attenuated vaccine were tested in parallel to compare their immunogenicity and protective efficacy. Homologous and heterosubtypic protection against the challenge with influenza H5N1 and H1N1 viruses in a mouse model were studied. Single immunization with live or inactivated whole-virion H5N1 vaccine elicited a high

Abstract Ribosome-binding factor A (RbfA) from Staphylococcus aureus is a cold adaptation protein that is required for the growth of pathogenic cells at low temperatures (10-15°C). RbfA is involved in the processing of 16S rRNA, as well as in the assembly and stabilization of the small 30S ribosomal subunit. Structural studies of the 30S–RbfA complex will help to better understand their interaction

Abstract Despite physiological importance of aldonic sugar acids for living organisms, little is known about metabolic pathways of these compounds. Here, we investigated the functional diversity of homologs of L-threonic acid dehydrogenase (ThrDH; UniProt ID: Q0KBC7), an enzyme composed of two NAD-binding domains (PF14833 and PF03446). Ten ThrDH homologs with different genomic context were studied;

Abstract The catalytic subunit of protein kinase A (PKAc) is conserved in all eukaryotic protein kinases. PKAc consists of two lobes that form the catalytic cleft containing the ATP-binding, peptide-binding site, and catalytic sites. During folding, PKAc secondary structures organize so that the non-polar regions form a globular core, while mobile loops and tails are exposed and can act as regulatory

Abstract Computer models of hemagglutinins from the H3N2 and H7N9 influenza viruses were developed to study structural organization and dynamic characteristics of the binding site for the conformational rearrangement inhibitors. The metadynamics was used to map the binding site free energy and to define the volume of its most energetically favorable states. It was demonstrated by simulation of the

Abstract In some cases, gene transfer from euchromatin to constitutive heterochromatin as a result of chromosomal rearrangement is accompanied by epigenetic inactivation of this gene (cis-inactivation). In the case of trans-inactivation, transgenes in the normal chromosome are repressed by the cis-inactivation-causing rearranged homologous chromosome. Trans-inactivation is a result of the somatic pairing

Abstract Tens of thousands of DNA lesions are formed in mammalian cells each day. DNA translesion synthesis is the main mechanism of cell defense against unrepaired DNA lesions. DNA polymerases iota (Pol ι), eta (Pol η), kappa (Pol κ), and zeta (Pol ζ) have active sites that are less stringent toward the DNA template structure and efficiently incorporate nucleotides opposite DNA lesions. However, these

Abstract In this review, we discuss the principles of regulation and synchronization of metabolic processes in mammalian cells using a two-component model of cell metabolism consisting of a controlling signaling system that regulates major enzymatic cascades and executive metabolic system that directly performs biosynthetic reactions. This approach has allowed us to distinguish two transitional metabolic

Abstract Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the

Abstract Damaged DNA bases are removed by the base excision repair (BER) mechanism. This enzymatic process begins with the action of one of DNA glycosylases, which recognize damaged DNA bases and remove them by hydrolyzing N-glycosidic bonds with the formation of apurinic/apyrimidinic (AP) sites. Apurinic/apyrimidinic endonuclease 1 (APE1) hydrolyzes the phosphodiester bond on the 5′-side of the AP

Abstract Hyaline cartilage is a nonvascular connective tissue covering the joint surface. It consists mostly of the extracellular matrix proteins and a small number of highly differentiated chondrocytes. At present, various techniques for repairing joint surfaces damage, for example, the use of modified cell cultures and biodegradable scaffolds, are under investigation. Molecular mechanisms of cartilage

Abstract The effect of the yeast endopolyphosphatase Ppn2 overproduction on the metabolism of inorganic polyphosphates in Saccharomyces cerevisiae yeast was studied. Expression of the PPN2 gene under control of the strong constitutive promoter of glyceraldehyde 3-phosphate dehydrogenase gene (PKG1) led to a significant increase in the endopolyphosphatase activity stimulated by cobalt/zinc ions. This

Abstract Using classical molecular dynamics, constant-pH molecular dynamics simulation, metadynamics, and combined quantum mechanical and molecular mechanical approach, we identified an alternative pathway of glycosyl-enzyme intermediate formation during oligosaccharide substrate conversion by the influenza H5N1 neuraminidase. The Asp151 residue located in the enzyme mobile loop plays a key role in

Abstract Mitotic division maintains genetic identity of any multicellular organism throughout an entire lifetime. Each time a parent cell divides, chromosomes are equally distributed between the daughter cells due to the action of mitotic spindle. Mitotic spindle is formed by the microtubules that represent dynamic polymers of tubulin protein. Spindle microtubules are attached end-on to kinetochores

The structures of three cell wall glycopolymers of the phytopathogen Rathayibacter tritici VKM Ac-1603T (family Microbacteriaceae, order Micrococcales, class Actinobacteria) were established by chemical methods and NMR spectroscopy. Polymer 1 is a branched rhamnomannan with the repeating unit →3)-α-[β-D-Xylp-(1→2)]-D-Manp-(1→2)-α-D-Rhap-(1→3)-α-D-Manp-(1→2)-α-D-Rhap-(1→; polymer 2 is a linear rhamnomannan

Obesity and latent inflammation can give rise to insulin resistance and type 2 diabetes. Here we established an insulin resistance model of osteoblasts to explore the restoration effect of anti-inflammatory interleukin-4 (IL-4) on insulin sensitivity and its mechanism. We found that IL-4 inhibited cell proliferation in a concentration- and time-dependent manner. Insulation resistance significantly

Lam1–4 proteins perform non-vesicular transport of sterols from the plasma membrane to the endoplasmic reticulum. Disruption of their function leads to an increase in the content of sterols in the plasma membrane. In mammals, homologs of Lam proteins are responsible for the internalization of plasma cholesterol. The biological role of Lam proteins in yeast remains unclear, since the strains lacking

Mitochondria are obligate organelles of most eukaryotic cells that perform many different functions important for cellular homeostasis. The main role of mitochondria is supplying cells with energy in a form of ATP, which is synthesized in a chain of oxidative phosphorylation reactions on the organelle inner membrane. It is commonly believed now that mitochondria have the endosymbiotic origin. In the

The structure of tobacco mosaic virus (TMV) virions and stacked disk aggregates of TMV coat protein (CP) in solution was analyzed by synchrotron-based small-angle X-ray scattering (SAXS) and negative contrast transmission electron microscopy (TEM). TMV CP aggregates had a unique stability but did not have helical symmetry. According to the TEM data, they were stacked disks associated into transversely

Formation of normal tissue structure, homeostasis maintenance, and tissue damage repair require proliferation and differentiation of stem cells. A distinctive feature of these cells is a unique organization of metabolic pathways, in which contribution of energy production mechanisms to the general cellular metabolism is principally different from that in differentiated cells. Moreover, metabolic changes

The genome of influenza A virus consists of eight single-stranded negative-polarity RNA segments. The eighth segment (NS) encodes the anti-interferon protein NS1 (27 kDa) and the nuclear export protein NEP (14 kDa) via the classic negative-sense strategy. It also contains an additional positive-sense open reading frame that can be directly translated into the negative strand protein 8 (NSP8; 18–25

Functionally important multidomain bacterial protein bS1 is the largest ribosomal protein of subunit 30S. It interacts with both mRNA and proteins and is prone to aggregation, although this process has not been studied in detail. Here, we obtained bacterial strains overproducing ribosomal bS1 protein from Thermus thermophilus and its stable fragment bS1(49) and purified these proteins. Using fluorescence

The antirestriction ArdB protein inhibits the endonuclease activity of type I restriction/modification (RM) systems in vivo; however, the mechanism of inhibition remains unknown. In this study, we showed that recombinant ArdB from Escherichia coli cells co-purified with DNA. When overexpressed in E. coli cells, a portion of ArdB protein formed insoluble DNA-free aggregates. Only native ArdB, but not

The importance of studying the action mechanisms of drugs based on natural regulatory peptides is commonly recognized. Particular attention is paid to the peptide drugs that contribute to the restoration of brain functions after acute cerebrovascular accidents (stroke), which for many years continues to be one of the main problems and threats to human health. However, molecular genetic changes in the

Naphthalene, as a component of crude oil, is a common environmental pollutant. Biochemical and genetic aspects of naphthalene catabolism have been examined in most detail in the bacteria of Pseudomonas genus. In pseudomonads, the key intermediate in naphthalene degradation is salicylate. In this study, we investigated the ability of Rhodococcus opacus strain 3D to utilize naphthalene as a sole carbon

Neurodegenerative diseases are accompanied by changes in the activity of thiamine mono- and diphosphate phosphatases, but molecular identification of these mammalian enzymes is incomplete. In this work, the protein fraction of bovine brain synaptosomes displaying phosphatase activity toward thiamine derivatives was subjected to affinity chromatography on thiamine-Sepharose. Protein fractions eluted

Hexameric inorganic pyrophosphatase from Mycobacterium tuberculosis (Mt-PPase) has a number of structural and functional features that distinguish it from homologous enzymes widely occurring in living organisms. In particular, it has unusual zones of inter-subunit contacts and lacks the N-terminal region common for other PPases. In this work, we constructed two mutant forms of the enzyme, Ec-Mt-PPase

Base excision repair (BER) ensures correction of most abundant DNA lesions in mammals. The efficiency of this multistep DNA repair process that can occur via different pathways depends on the coordinated action of enzymes catalyzing its individual steps. The scaffold XRCC1 (X-ray repair cross-complementing protein 1) protein plays an important coordinating role in the repair of damaged bases and a

Recently, there has been a rapid progress in the development of techniques for isothermal amplification of nucleic acids as an alternative to polymerase chain reaction (PCR). The advantage of these methods is that the nucleic acids amplification can be carried out at constant temperature, unlike PCR, which requires cyclic temperature changes. Moreover, isothermal amplification can be conducted directly