Vol 484, No 1 (2019)

The synthesized new binary conjugates of tetrahydro-γ-carbolines, which contained ditriazole spacers of different length, exhibited considerable anticholinesterase and antioxidant activity as well as the potential ability to block the acetylcholinesterase-induced aggregation of β-amyloid in contrast to the original prototype Dimebon. This makes the compounds promising candidates for further investigation as drugs for the treatment of Alzheimer’s disease. Special attention should be given to the conjugate containing the hexamethylene intertriazole spacer, which can be considered as a leader in this series of compounds.

An effective bacterial system for the production of β-toxin Ts1, the main component of the Brazilian scorpion Tityus serrulatus venom, was developed. Recombinant toxin and its ¹⁵N-labeled analogue were obtained via direct expression of synthetic gene in Escherichia coli with subsequent folding from the inclusion bodies. According to NMR spectroscopy data, the recombinant toxin is structured in an aqueous solution and contains a significant fraction of β-structure. The formation of a stable disulfide-bond isomer of Ts1, having a disordered structure, has also been observed during folding. Recombinant Ts1 blocks Na⁺ current through Na_V1.5 channels without affecting the processes of activation and inactivation. At the same time, the effect upon Na_V1.4 channels is associated with a shift of the activation curve towards more negative membrane potentials.

On the basis of the first dipeptide ligand of TSPO, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), which was obtained by us earlier, we synthesized a new dipeptide, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102). GD-102 exhibited anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD-102 was one order of magnitude lower than that of GD-23. Compound PK11195, a selective antagonist of TSPO, completely blocked the anxiolytic activity of GD-102, which testified to the involvement of TSPO in the realization of the anxiolytic effect of GD-102. The results were confirmed by molecular docking data.

For the first time the intracellular concentrations of N-acetylaspartate (NAA), aspartate (Asp), and glutamate (Glu) were measured in human brain in vivo, and the effect of severe traumatic brain injury on NAA synthesis in acute and remote posttraumatic phases was revealed. In non-damaged (MRI-negative) lobes the next day after injury, Asp and Glu decreased by 45% and 35%, respectively, while NAA decreased only by 16%. A negative correlation between NAA and Asp/Glu ratio was found. The Glu level returned to the norm long after injury, Asp remained below the norm by 60%, NAA decreased by 65% relative to the norm, and Asp/Glu decreased significantly. The results obtained educe the leading role of neuronal aspartate–malate shuttle in NAA synthesis alterations.

We tested the activity of the PRE element from the Drosophila virilis genome, which is the homologue of the known Drosophila melanogasterbxdPRE element from the regulatory region of the Ubx gene. It is easy to select unique primers to this element that do not occur in the Drosophila melanogaster genome. We showed that the studied PRE element causes a strong repression of the white marker gene upon insertion into the Drosophila melanogaster genome and interacts with the PcG proteins of the PRC1 and PhoRC complexes.

Avicin A is a bacteriocin from the gram-positive bacterium Enterococcus avium. It exhibits a high microbicidal activity against bacteria of the genus Listeria, a causative agent of the severe human infection listeriosis. We developed a biotechnological method for obtaining avicin A and characterized its structure and biological activity. We also proposed a possible mechanism of the antimicrobial action of avicin A.

To select the optimum method for disinfecting scaffolds before recellularization, the effects of octenisept and chlorhexidine at different concentrations on lung biological matrices before and after decellularization were studied by using morphological methods (studies of biomechanical strength of extracellular matrix fibers) and by analyzing chemiluminescence in rats. Chlorhexidine diluted 1 : 10 had the least damage on the matrix properties and to the greatest extent contributed to disinfection of scaffolds for their further storage and experimental studies.

The molecular and chromosomal localization of the dunce gene was studied. This gene (167.3 kb) consists almost entirely of introns, in which a cluster of seven short tissue-specific genes is located. On the basis of the results of FISH analysis of the gene fragments, we established that the dunce gene is located within nine chromosomal structures (four bands and five interbands), which contradicts the common idea that genes are located in only one structure (band or interband) or at the boundary of these structures. Our results are quite unexpected and original and greatly expand the current understanding of the genetic organization of interphase chromosomes.

Using voltage-clamp technique, the involvement of sigma-1 receptors in the regulation of Na⁺ transport in frog skin by the immunomodulatory drug glutoxim was investigated. We have shown for the first time that preincubation of the frog skin with the sigma-1 receptor antagonists haloperidol and chlorpromazine attenuates the stimulatory effect of glutoxim on the Na⁺ transport. The results suggest the possible involvement of the sigma-1 receptors in the regulation of Na⁺ transport in frog skin epithelium by glutoxim.

The conditions for constructing an immunosorbent reagent for solid-phase NMR analysis were optimized. For this purpose, we increased the area of ​​the sensitized portion of the membrane to fit the relaxometer coil size and added the agent sorption buffer. This provided the penetration of the anti-ligand molecules into the membrane thickness and their uniform distribution.

The biofilm formation by bacteria E. coli is a magnetosensitive process. The combined effects of a magnetic magnesium isotope ²⁵Mg and a static magnetic field in the range of 20–35 mT stimulate biofilm formation by E. coli compared to nonmagnetic magnesium isotopes ^24.26Mg. Magnetic field effects in the range of 2–10 mT, recorded for all bacteria regardless of the magnesium-isotope enrichment of the nutrient medium, indicate the sensitivity of intracellular processes to weak magnetic fields.

Tag7 (PGRP-S) is an innate immune protein that is involved in the antibacterial and antitumor defense and stimulates the maturation of cytotoxic lymphocyte subpopulations. It was found that the incubation of lymphocytes with Tag7 for 3 days promotes the appearance of cytotoxic NK cells that are active against a number of tumor cell lines.