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Acta Naturae

R U Ostrovskaya, S S Yagubova, T A Gudasheva, S B Seredenin
Based on the comorbidity of diabetes, depression, and dementia and recognizing that a deficiency of the nerve growth factor (NGF) is involved in all of these kinds of pathologies, we studied the effect of the mimetic of dimeric dipeptide NGF loop 4, GK-2, on a model of streptozotocin-induced type 2 diabetes in C57Bl/6 mice. GK-2 [hexamethylenediamide bis-(N-monosuccinyl-glutamyl-lysine)] was synthesized at the V.V. Zakusov Scientific Research Institute of Pharmacology. The study revealed the ability of GK-2 to ameliorate hyperglycemia induced by streptozotocine (STZ 100 mg/kg i...
April 2017: Acta Naturae
R A Maksyutov, S N Yakubitskyi, I V Kolosova, S N Shchelkunov
The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VACΔ6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VACΔ6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice...
April 2017: Acta Naturae
P A Levashov, D A Matolygina, E D Ovchinnikova, D L Atroshenko, S S Savin, N G Belogurova, S A Smirnov, V I Tishkov, A V Levashov
The bacteriolytic activity of interleukin-2 and chicken egg lysozyme in the presence of various substances has been studied. Glycine and lysine do not affect the activity of interleukin-2 but increase that of lysozyme, showing a bell-shape concentration dependence peaking at 1.5 mM glycine and 18 mM lysine. Arginine and glutamate activate both interleukin-2 and lysozyme with a concentration dependence of the saturation type. Aromatic amino acids have almost no effect on the activity of both interleukin-2 and lysozyme...
April 2017: Acta Naturae
A M Kudzhaev, A G Andrianova, E S Dubovtseva, O V Serova, T V Rotanova
Multidomain ATP-dependent Lon protease of E. coli (Ec-Lon) is one of the key enzymes of the quality control system of the cellular proteome. A recombinant form of Ec-Lon with deletion of the inserted characteristic α-helical HI(CC) domain (Lon-dHI(CC)) has been prepared and investigated to understand the role of this domain. A comparative study of the ATPase, proteolytic, and peptidase activities of the intact Lon protease and Lon-dHI(CC) has been carried out. The ability of the enzymes to undergo autolysis and their ability to bind DNA have been studied as well...
April 2017: Acta Naturae
S S Efimova, O S Ostroumova
In this study we report on experimental observations of giant unilamellar liposomes composed of ternary mixtures of cholesterol (Chol), phospholipids with relatively low Tmelt (DOPC, POPC, or DPoPC) and high Tmelt (sphingomyelin (SM), or tetramyristoyl cardiolipin (TMCL)) and their phase behaviors in the presence and absence of dipole modifiers. It was shown that the ratios of liposomes exhibiting noticeable phase separation decrease in the series POPC, DOPC, DPoPC regardless of any high-Tmelt lipid. Substitution of SM for TMCL led to increased lipid phase segregation...
April 2017: Acta Naturae
I V Gushchina, D K Nilov, A L Zakharenko, O I Lavrik, V K Švedas
The DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) represents a potential molecular target for anticancer therapy. A human Tdp1 model has been constructed using the methods of quantum and molecular mechanics, taking into account the ionization states of the amino acid residues in the active site and their interactions with the substrate and competitive inhibitors. The oligonucleotide- and phosphotyrosine-binding cavities important for the inhibitor design have been identified in the enzyme's active site...
April 2017: Acta Naturae
A A Fedotova, A N Bonchuk, V A Mogila, P G Georgiev
The emergence of whole-genome assays has initiated numerous genome-wide studies of transcription factor localizations at genomic regulatory elements (enhancers, promoters, silencers, and insulators), as well as facilitated the uncovering of some of the key principles of chromosomal organization. However, the proteins involved in the formation and maintenance of the chromosomal architecture and the organization of regulatory domains remain insufficiently studied. This review attempts to collate the available data on the abundant but still poorly understood family of proteins with clusters of the C2H2 zinc finger domains...
April 2017: Acta Naturae
Y A Kolobkova, V A Vigont, A V Shalygin, E V Kaznacheyeva
Huntington's disease (HD) is a severe inherited neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and mental impairment. At the molecular level, HD is caused by a mutation in the first exon of the gene encoding the huntingtin protein. The mutation results in an expanded polyglutamine tract at the N-terminus of the huntingtin protein, causing the neurodegenerative pathology. Calcium dyshomeostasis is believed to be one of the main causes of the disease, which underlies the great interest in the problem among experts in molecular physiology...
April 2017: Acta Naturae
I V Demidyuk, K N Chukhontseva, S V Kostrov
Glutamyl endopeptidases (GEPases) are chymotrypsin-like enzymes that preferentially cleave the peptide bonds of the α-carboxyl groups of glutamic acid. Despite the many years of research, the structural determinants underlying the strong substrate specificity of GEPases still remain unclear. In this review, data concerning the molecular mechanisms that determine the substrate preference of GEPases is generalized. In addition, the biological functions of and modern trends in the research into these enzymes are outlined...
April 2017: Acta Naturae
E E Alemasova, O I Lavrik
RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer - poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage...
April 2017: Acta Naturae
E A Novoselova, O B Riabova, I A Leneva, V G Nesterenko, R N Bolgarin, V A Makarov
A novel compound, 3,3'-(5-nitropyrimidine-4,6-diyl)bis-3,12-diaza-6,9-diazoniadispiro[]hexadecane tetrachloride dihydrochloride, was synthesized. The compound was found to inhibit the replication of various viral families by blocking specific heparan sulfate receptors on the host cell's surface. In experiments, the compound was found to be highly effective against several strains of HIV retroviruses.
January 2017: Acta Naturae
L S Melnikova, E A Pomerantseva, V V Molodina, P G Georgiev
The structure of the new enhancer En1A of the 1A region of the X chromosome of D. melanogaster was investigated. Two distinct regulatory elements were found. The first element is responsible for transcription activation, and the second element provides specific interaction with the promoter of the yellow gene. The findings support the hypothesis of a modular structure for enhancers, including certain sequences that bind transcription activators and special communication elements providing long-distance enhancer-promoter interaction...
January 2017: Acta Naturae
D A Yakovlev, A A Kuznetsova, O S Fedorova, N A Kuznetsov
The MBD4 enzyme initiates the process of DNA demethylation by the excision of modified DNA bases, resulting in the formation of apurinic/apyrimidinic sites. MBD4 contains a methyl-CpG-binding domain which provides the localization of the enzyme at the CpG sites, and a DNA glycosylase domain that is responsible for the catalytic activity. The aim of this work was to clarify the mechanisms of specific site recognition and formation of catalytically active complexes between model DNA substrates and the catalytic N-glycosylase domain MBD4cat...
January 2017: Acta Naturae
O V Chertkov, G A Armeev, I V Uporov, S A Legotsky, N N Sykilinda, A K Shaytan, N L Klyachko, K A Miroshnikov
Lytic transglycosylases are abundant peptidoglycan lysing enzymes that degrade the heteropolymers of bacterial cell walls in metabolic processes or in the course of a bacteriophage infection. The conventional catalytic mechanism of transglycosylases involves only the Glu or Asp residue. Endolysin gp144 of Pseudomonas aeruginosa bacteriophage phiKZ belongs to the family of Gram-negative transglycosylases with a modular composition and C-terminal location of the catalytic domain. Glu115 of gp144 performs the predicted role of a catalytic residue...
January 2017: Acta Naturae
E A Tsvetkov, N N Potatieva, K V Bolshakov
The interaction of TRPV1-receptors agonists (capsaicin and protons) has been studied on cultured CHO cells transfected by TRPV1-receptors. Using the whole-cell patch-clamp approach, it was shown that summation of the currents induced by agonist application was dependent on the membrane potential. The TRPV1-mediated currents induced by the pH and Capsaicin demonstrated arithmetical summation at potentials between 40--40 mV, while they were potentiated at potentials below -40 mV. Currents induced by the pH and Capsaicin combined were higher in comparison with the arithmetic sum of the currents induced by the pH and Capsaicin applied separately at such potentials...
January 2017: Acta Naturae
E S Philonenko, M V Shutova, E A Khomyakova, E M Vassina, O S Lebedeva, S L Kiselev, M A Lagarkova
Induced pluripotent stem cells (iPSCs) have the capacity to unlimitedly proliferate and differentiate into all types of somatic cells. This capacity makes them a valuable source of cells for research and clinical use. However, the type of cells to be reprogrammed, the selection of clones, and the various genetic manipulations during reprogramming may have an impact both on the properties of iPSCs and their differentiated derivatives. To assess this influence, we used isogenic lines of iPSCs obtained by reprogramming of three types of somatic cells differentiated from human embryonic stem cells...
January 2017: Acta Naturae
T S Gerashchenko, M V Zavyalova, E V Denisov, N V Krakhmal, D N Pautova, N V Litviakov, S V Vtorushin, N V Cherdyntseva, V M Perelmuter
Breast cancer (BC) demonstrates considerable intratumoral morphological heterogeneity. The aim of this work was to evaluate the relationship among different morphological structures, the rate of metastasis, and efficacy of neoadjuvant chemotherapy (NAC) in NAC-treated (n = 427) and NAC-naïve (n = 249) BC patients. We also studied the involvement of an epithelial-mesenchymal transition (EMT) in the development of the intratumoral morphological heterogeneity of BC. We found a significant association between the intratumoral morphological heterogeneity and the rate of BC metastasis and response to NAC, which, in most cases, correlated with the presence of alveolar and trabecular structures...
January 2017: Acta Naturae
N S Bondarenko, A N Shneiderman, A A Guseva, B A Umarova
This study was aimed at investigating the effect of prolyl-glycyl-proline (PGP) tripeptide on vascular permeability in rats with an inflammation. It was found that the peptide reduces the rat paw edema induced by a subcutaneous administration of histamine to the same extent as the conventional anti-inflammatory agent diclofenac. However, an assessment of the relative expression level of the cox-2 gene at the inflammation focus using real-time PCR showed that, in contrast to diclofenac, PGP does not affect the cox-2 gene expression...
January 2017: Acta Naturae
S M Baldin, N M Misiura, V K Švedas
L,D-transpeptidase 2 from Mycobacterium tuberculosis plays a key role in the formation of the cell wall of a pathogen and catalyzes the cross-linking of growing peptidoglycan chains by non-classical 3-3 bonds, which causes resistance to a broad spectrum of penicillins. Molecular modeling of enzyme interactions with the N- and C-terminal tetrapeptide fragments of growing peptidoglycan chains has been performed for the first time and has allowed us to highlight the peculiarities of their binding at the formation of 3-3 cross-linkages, as well as to build a full-atom model of L,D-transpeptidase 2 for the screening and optimizing of inhibitors' structures...
January 2017: Acta Naturae
I V Balalaeva, E A Sokolova, A D Puzhikhina, A A Brilkina, S M Deyev
Tumor response to therapeutic treatment is largely determined by its heterogeneity and the presence of intercellular junctions, hindering the penetration of large molecules deep into the three-dimensional structure of the tumor. In that context, 3D in vitro tumor models such as cancer cell spheroids are becoming increasingly popular. We obtained spheroids of human breast adenocarcinoma SKBR-3 overexpressing the HER2 cancer marker. The toxicity of HER2-targeted immunotoxin 4D5scFv-PE40 against spheroids was shown to be several orders of magnitude lower compared to a monolayer cell culture...
January 2017: Acta Naturae
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