[Molecular genetic aspects of glaucoma pathogenesis].

To improve our understanding of glaucoma pathophysiology it is important to investigate endophenotypes which are determined by heritable quantitative traits, such as intraocular pressure, vertical cup-to-disc ratio, optic disc area, and central corneal thickness. Glaucoma is associated with increased intraocular pressure and defects of trabecular meshwork and anterior chamber which lead to derangement of intraocular fluid outflow, progressive optic nerve degeneration, loss of nerve cells, and blindness. Factors that are not affected by intraocular pressure also contribute to glaucoma degeneration. In progressive degenerative diseases, such as glaucoma, chronic astrocyte activation exacerbates the damage to neurons and impairs the regeneration of their axons. This review considers the polymorphism of predisposition factors to glaucoma-associated endophenotypes, optic nerve degeneration, and side effects of antiglaucomatous drugs.

[Molecular genetic basis of age-related macular degeneration].

Visual loss due to age-related macular degeneration (AMD) is caused by one or both forms of advanced disease: "wet" (neovascular) or "dry" (geographic atrophy). Immune system plays a central role in pathogenesis and progression of both AMD forms. Main genetic polymorphisms associated with risk of AMD development and progression were found to be genes that regulate inflammation especially in complement factor H gen (1q31 locus) and 10q26 locus (PLEKHAI/ARMS2/HTRA1). Association of response to treatment and genotype was shown in patients with AMD. Complete characterization of both common and rare alleles that influence AMD risk is necessary for accurate determination of individual genetic risk as well as identification of new targets for therapeutic intervention.

[Genetic recombination and steroid metabolism in Drosophila]. / Geneticheskaia rekombinatsiia i steroidnyi metabolizm u Drozofily.

A double-species ecologo-genetical model, including Drosophila and yeast, has been used as a new methodological instrument for investigation of the physiological mechanism of recombination. Incubation of Drosophila females in the medium containing yeast of the strain mutant for ergosterol synthesis leads to suppression of temperature-induced crossing over. The mass-spectrum analysis of steroid fraction from Drosophila females has shown that incubation of the yeast medium without ergosterol results in arrest of ecdysterone synthesis. These data are explained by the absence of ecdysterone synthesis precursor in the fly organism. The endocrinal control of crossing over is discussed in the light of hormonal regulation of meiosis.

[The effect of sterol metabolism in a model ecological system Drosophila-yeasts on the crossing-over in Drosophila]. / Vliianie sterinovogo metabolizma v model'noi ékologicheskoi sisteme drozofila-drozhzhi na krossingover u drozofily.

The absence of sterols available for metabolism causes the death of Drosophila larva. Addition of suboptimal cholesterol doses to this medium allows the portion of larvae to survive. Sterol-deficient diet at the preimaginal stages leads to suppression of both spontaneous and high-temperature induced crossingover in Drosophila females. Two possible explanations for dependence of recombination process on sterol metabolism are suggested: 1) the shortage of precursor for ecdisons biosynthesis was the cause of discordance of meiotic events; 2) suppression of crossingover occurs, due to alteration of cell membrans' structure.

[Genetic mapping of the NYS1 gene in Saccharomyces cerevisiae]. / Geneticheskoe kartirovanie gena NYS1 drozhzhei Saccharomyces cerevisiae.

The NYS1 gene of Saccharomyces cerevisiae yeasts is linked to the centromere marker of chromosome IV - gene TRP1 and is located at 16.2 cM distance from it.

[Resistance of yeasts to polyene antibiotics]. / Rezistentnost' drozhzhei k polienovym antibiotikam.

The strains of Saccharomyces cerevisiae yeast with mutations in two genes NYS3 NYS4 were obtained by tetrad analysis. Sterol fraction of these mutants contains two sterols: ergosta-7-en-3 beta-ol (fungisterol) and ergosta-7,24-dien-3 beta-ol (episterol). The findings allowed to testify the sequence of the ergosterol biosynthesis reactions. Dehydrogenization of the sterol nucleus in C5(6) which is controlled by gene NYS3 occurs simultaneously with the introduction of double bond in C22(23) site of the side chain regulated by gene NYS4.

[Characteristics of the final stages of ergosterol biosynthesis in Saccharomyces cerevisiae yeasts]. / Nekotorye osobennosti konechnykh stadii biosinteza érgosterina u drozhzhei Saccharomyces cerevisiae.

A scheme of ergosterol cyclic intermediate transformations in S. cerevisiae has been proposed. It is based on the analysis of sterol composition in strains with mutant blocks of one or two reactions of enzymatic synthesis. Biochemical reactions of modification of cyclic part and side branch of sterol molecule are supposed to be carried out independently.

[Genetico-ecological aspects of the use of nystatin-resistant yeast mutants in the yeast-Drosophila system]. / Genetiko-ékologicheskie aspekty ispol'zovaniia nistatinustoichivykh mutantov drozhzhei v sisteme drozhzhi-drozofila.

Nystatin-resistant strains of Saccharomyces cerevisiae with mutations in final steps of ergosterol biosynthesis have been studied in the ecologo-genetic yeast--drosophila system. It has been shown that yeast strains which belong to the Petersghoff genetic yeast stock collection, with mutations in NYSX, NYS2 and NYS3 genes, provide the development of Drosophila melanogaster. In the process of nutrition with yeasts having mutations in the NYS2 gene, the development of drosophila larvae takes place, due to ergosterol accumulated in the yeast cells. Drosophila melanogaster was shown to be unable to utilize the sterols with 8(9) and 24(25) double bonds.

[Yeast resistance to polyene antibiotics. VI. Isolation and biochemical analysis of strains of Saccharomyces cerevisiae yeasts with mutations in the 2 nystatin-resistance genes]. / Rezistentnost' drozhzhei k polienovym antibiotikam. Soobshchenie VI. Poluchenie i biokhimicheskii analiz shtammov drozhzhei Saccharomyces cerevisiae s mutatsiiami v dvukh genakh nistatinustoichivosti.

The comparative analysis of sterol content in the yeast Saccharomyces cerevisiae strains singly or doubly defective in nystatin resistance genes was carried out. The strains with two mutations in NYS genes were shown to accumulate the sterol mixture, similar to that of the parental singly defective mutant. This type of gene interaction allows to define the main biochemical order of reaction in ergosterol synthesis: methylation in C24 (NYS1), delta 8----delta 7 isomerization (NYS2), C5 (6) and C22 (23) desaturation (NYS3 and NYSX).