[Molecular Mechanisms to Optimize Gene Translation Elongation Differ Significantly in Bacteria with and without Nonribosomal Peptides].

Nonribosomal peptides play an important role in the vital activity of bacteria and have an extremely broad field of biological activity. In particular, they act as antibiotics, toxins, surfactants, siderophores, and also perform a number of other specific functions. Biosynthesis of these molecules does not occur on ribosomes but by special enzymes that form gene clusters in bacterial genomes. We hypothesized that the presence of nonribosomal peptide synthesis pathways is a specific feature of bacterial metabolism, which may affect other vital processes of the cell, including translational ones. This work was the first to show the relationship between the translation regulation mechanism of protein-coding genes in bacteria, which is largely determined by the efficiency of translation elongation, and the presence of gene clusters in the genomes for the biosynthesis of nonribosomal peptides. Bioinformatic analysis of the translation elongation efficiency of protein-coding genes was performed in 11679 bacterial genomes, some of which contained gene clusters of nonribosomal peptide biosynthesis and some of which did not. The analysis showed that bacteria whose genomes contained clusters of nonribosomal peptide biosynthetic genes and those without such gene clusters differ significantly in the molecular mechanisms that ensure translation efficiency. Thus, among microorganisms whose genomes contain gene clusters of nonribosomal peptide synthetases, a significantly smaller part of them is characterized by optimized regulation of the number of local inverted repeats, while most of them have genomes optimized by the averaged energy of inverted repeats studs in mRNA and additionally by codon composition. Our results suggest that the presence of nonribosomal peptide biosynthetic pathways in bacteria may influence the structure of the overall bacterial metabolism, which is also expressed in the specific mechanisms of ribosomal protein biosynthesis.

[Synthesis and Pharmacological Activity of N-Hetaryl-3(5)-Nitropyridines].

Reacting a number chlorosubstituted 3(5)-nitropyridine with some diazoles or 3-chloropyridazin-6-one synthesized previously undescribed various 2-, 4- or 6-substituted hetaryl-3(5)-nitropyridines. Furthermore, pyrazolyl-3-nitropyridine prepared by cyclizing hydrazinopyridine resulting from the nucleophilic substitution of chlorine in chlorosubstituted 3-nitropyridine by hydrazine. It has been shown that these compounds have moderate antibacterial activity against some pathogenic Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Escherichia coli), as well as a strong effect on protistocidal action form Colpoda steinii, surpassing clinically used reference drugs.

[Metabolism and modification of high mobility proteins (HMG) in the liver of rats of various age]. / Obmen i modifikatsii belkov vysokoi podvizhnosti (HMG) pecheni krys raznogo vozrasta.

It is shown that heterogeneity of the high-mobility -group proteins (HMG-proteins) in the rat liver does not depend on the animal age, while relative content of certain classes of these proteins and the HMG-proteins H1 histones ratio obeys age specificity. Metabolism of HMG 1 and 2 proteins in animals who have not achieved sexual maturity is low; the intensity of inclusion of labelled predecessors to proteins HMG 14', 17 and 17' decreases in the postnatal ontogenesis. The highest of HMG-proteins is observed in the liver of young (3 months) animals. In old (24 months) rats this process is inhibited. At all the stages of postnatal ontogenesis in the ribosylation intensity of HMG-proteins 14', is higher than that of the other classes of these proteins. The intensity of ribosylation of most fractions of HMG-proteins increases after 12 months.

[A method of studying variations in the common center of gravity (stabilometry)]. / Metodika issledovaniia kolebanii obshchego tsentra tiazhesti cheloveka (stabilometriia).

A procedure to study variations of the common human centre of gravity (stabilometry) permits using a principle of a biological feedback. It is achieved by application of a device to study the nervous system. A procedure is recommended to be widely used in applied physiology.

[Age-related differences in the inhibition of DNA synthesis in the liver of albino rats by proliferation inhibitors of chalone type]. / Vozrastnye razlichiia podavleniia sinteza DNK v pecheni belykh krys ingibitorami proliferatsii keilonovoi prorody.

It was demonstrated that during postnatal ontogenesis, the heterogeneity of endogenous inhibitors of DNA synthesis in albino rat liver does not change. Upon ageing, the sensitivity of liver cells to the inhibiting effect of chalone-containing extracts and the functional activity of the inhibitor are diminished.

[Metabolism of histones and non-histone proteins in liver cell nuclei and chromatin from rats of various ages]. / Metabolizm gistonov i negistonovykh belkov iader i khromatina kletok pecheni krys raznogo vozrasta.

The metabolism of various classes of histones and nonhistone proteins in intact nuclei and in liver chromatin of albino Wistar rats aged 1, 3, 12 and 24 months, was studied. It was shown that in the course of postnatal development the metabolism of nonhistone proteins extracted with 0.14 M NaCl in murine liver is increased. Later in ontogenesis, the incorporation of labeled precursors into proteins HMG 14 and HMG 17 decreases; the specific radioactivity of proteins HMG 1 + 2 is higher in 3- and 24-month-old animals. The intensity of metabolism of nonhistone proteins and histones is higher within the composition of the chromatin complex than in the intact nucleus at all stages of postnatal development. Among other histone proteins, histones H1 are characterized by the highest level specific radioactivity in rats of all age groups.

[Effect of thyroxine on the protein makeup of condensed and diffuse chromatin from the liver of rats of different ages]. / Vliianie tiroksina na belkovyi sostav kondensirovannogo i diffuznogo khromatina pecheni krys raznogo vozrasta.

Contant composition of histones and marked alterations in the non-histone proteins were found in condensed and diffuse chtomatins of rat liver tissue during postnatal ontogenesis both in normal state and in treatment with thyroxine. Thyroxine affected the ratio histones (non-histone proteins in condensed chromatin of animals of the all age groups studied, except the old rats, in which the ration did not differ from the control values. After thyroxine administration the ratio histones) non-histone proteins was increased in diffuse chromatin of predolescent rats; the ratio was slightly decreased in diffuse chromatin of puberal rats and it was remarkably unaltered in the chromatin of adult and t was remarkably unaltered in the chromatin of adult an old animals. Considering the fact that thyroxine increased in the condensed chromatin the content of non-histone proteins and decreased the content of histones, the data obtained suggest that the hormone caused a shift in the ratio condensed/diffuse chromatin towards the increase in content of the diffuse chromatin.

[Protein composition of fragmented rat liver chromatin during postnatal ontogenesis]. / Belkovyi sostav fragmentirovannogo khromatina pecheni krys v postnatal'nom ontogeneze.

It was shown that after treatment by Ca2+- and Mg2+-dependent DNAses and subsequent dosed ultrasonication the fractions of active and relatively inactive chromatins isolated from liver cell nuclei of rats differing in age contain all main types of histones, but differ considerably in the relative amounts of individual fractions of these proteins. In all age groups studied the proteins of relatively inactive chromatin are largely histones, while the amount of non-histone proteins is higher in active chromatin. In the course of postnatal development the amount of histones in both chromatin fractions is increased and that of non-histone proteins is decreased. This is probably due to heterochromatization of the chromatin complex in liver cells with ageing. In the course of postnatal ontogenesis the spectrum of non-histone proteins in both chromatin fractions is changed.

[Acetylation of histone and acid proteins of rat liver cells chromatin complex in postnatal ontogenesis]. / Atsetilirovanie gistonov i kislykh belkov khromatinovogo kompleksa kletok pecheni krys v postnatal'nom ontogeneze.

No significant differences in acetylation of acid proteins was found in 1, 3- and 12-month animals in the process of postnatal development, but in old rats this process is noticeably intensified. The acetate label incorporation into histones H2 and H3 does not vary essentially in impuberal and young animals but intensifies in adult and old animals. A gradual intensification of acetylation during the whole postnatal development is registered for lysin-rich histones Hla and Hlb. The old animals differ by the highest level of acetate label incorporation into all studied fractions of chromatin proteins.

[Methylation of liver cell chromatin proteins at different stages of post-natal development of albino rats]. / Metilirovanie belkov khromatin kletok pecheni na raznykh etapakh Postnatal'nogo Razvitiia belykh krys

Methylation of acid proteins and various histone fractions of liver cell chromatin was studied. The intensity of methylation of acid proteins of animals, differing in age, was shown to be 8--16 times higher than that for histone methylation, despite the fact that the rates of 2-14C-methionine incorporation into these two groups of proteins were practically the same. The intensity of methylation of acid proteins and total histones significantly increased during the post-natal development of the animals. Histone methylation largely occurred at the expense of the arginine-rich H3 fraction and the H2 fraction with a moderate level of arginine and lysine. Lysine-rich histone fractions were not subjected to methylation. It is assumed that chromatin proteins methylation regulates conformational properties of the complex and matrix properties of the genome.

[Effect of insulin of acetylation of histones and non-histone proteins in the cell nuclei of the liver of albine rats of different age]. / Vliianie insulina na atsetilirovanie gistonov i negistonovykh belkov iader kletok pecheni belykh krys raznogo vozrasta

After administration of insulin acetylation of histones and acid proteins in liver cell nuclei was decreased within 30 min; it increased gradually within 120 min and there was no difference as compared with control within 360 min in young animals. Incorporation of acetate label into proteins was inhibited within 90 min after the hormone loading in old animals and it did not differ from control within 120 min. Under these conditions acetylation of globulin proteins was decreased within 30 min; it approached the control level within 60 min after which it did not distinctly alter ad compared with the control.

[Electrophoretic study of liver histones in the postnatal ontogeny of white rats: the effect of testosterone propionate and gonadectomy]. / Elektroforeticheskoe izuchenie gistonov pecheni v postnatal'nom ontogeneze belykh krys: vliianie testosterona propionata i gonadéktomii

By means of polyacrylamide gel disc electrophoresis heterogeneity, electrophoretic mobility and relative content of different fractions of histones in nuclei of liver cells were studied in gonadectomized Wistar rats and in castrated in intact animals, administered with testosteone propionate. In all the experiments a significant conservatism of histone proteins was found in postnatal development. In animals, treated with the endocrine preparations, the age peculiarities were shown to reflect the quanitative proportion of different histone fractions.

[Effect of calorie deficient nutrition on thiol group content of liver cell nuclei from white rats of different ages]. / Vliianie nedostatochnogo po kaloriinosti pitaniia na soderzhanie tiolovykh grupp v gistonakh iader kletok pecheni belykh krys raznogo vozrasta

The sulfydryl and disulfide groups content in summary histones of the hepatic cell nuclei in the Wistar albino rats aged 1, 3, 12 and 24 months was studied by employing amperometric titration under normal conditions and under the action on the organism of calorifically substandard nutrition tending to significantly prolong the life-span in these animals. In intact animals the content of thiol groups in histones was found to reach the maximum on the 3d month of their life, to continue at this level during the first year and to decline in old (34 month old) animals. In the post-natal ontogenesis of the rats the ratio of sulfhydryl to disulfide groups in the histone proteins does not show any noticeable changes. With calorific deficiency this ratio increases in histones of old animals. The possible significance of the thiol groups balance in the histone proteins in regulating the genome activity during age-dependent development of the animals is discussed.