Adamantyl-ureas with pyrazoles substituted by fluoroalkanes as soluble epoxide hydrolase inhibitors.

A series of soluble epoxide hydrolase (sEH) inhibitors containing halogenated pyrazoles was developed. Inhibition potency of the obtained compounds ranges from 0.8 to 27.

Novel method for screening Saccharomyces cerevisiae mutants with increased sulfur-containing compounds: color-based selection of colonies using the met30 strain.

Glutathione overproducers were detected by examining the pigmentation intensity of Saccharomyces cerevisiae met30 yeast carrying wild-type alleles for ADE1 and ADE2. Highly pigmented colonies, phenocopies of the ade2 or ade1 mutants, were observed among yeast grown in minimal biotin-free medium with a high methionine content.

Novel method for screening Saccharomyces cerevisiae mutants with increased sulfur-containing compounds: color-based selection of ade1 or ade2 mutants.

We identified Saccharomyces cerevisiae mutants with 100% higher intracellular glutathione using 1-methyl-3-nitro-1-nitrosoguanidine mutagenesis. This method employs visual selection of the most pigmented colonies among met30 strains carrying ade1 and ade2 mutations. Since the method does not involve genetic engineering, the mutants are suitable for use in the food industry.

[Using adaptive mutagenesis system for identification of early genes encoding de novo purine biosynthesis in methylotrophic yeast Pichia methanolica MH4].

A collection of spontaneous "Roman's mutants" (1654 mutants) for early genes of purine biosynthesis PUR1-PUR5 was obtained from 16 parental ade1(pur6) and ade2(pur7) strains of the methylotrophic yeast Pichia methanolica. Two genes, bifunctiional ADE7,4(PUR2,5) and ADES(PUR4), were identified earlier. For identification of the two remaining early genes (ADE3 and ADE8), a novel approach was used: a comparison of spectra of spontaneous Roman's mutants and relative sizes of genes (with regard to the length of polypeptides in amino acid residues).

[The regulation of peroxisomal matrix enzymes (alcohol oxidase and catalase) formation by the product of the gene Mth1 in methylotrophic yeast Pichia methanolica].

Two independent mutant strains of methylotrophic yeast Pichia methanolica (mth1 arg1 and mth2 arg4) from the initial line 616 (ade1 ade5) were investigated. The mutant strains possessed defects in genes MTH1 and MTH2 which resulted in the inability to assimilate methanol as a sole carbon source and the increased activity of alcohol oxidase (AO). The function of the AUG2 gene encoding one of the subunits of AO and CTA1, a probable homolog of peroxisomal catalase of Saccharomyces cereviseae, was investigated by analyses of the molecular forms of isoenzymes.

[Specific topographic-anatomical and technical features of resection of the stomach by the Roux method].

The topographic-anatomical investigations of the extraorganic part of the arterial and nervous systems of the duodenum and the initial part of the jejunum in combination with the results of the clinical use of gastric resection by the Roux method allowed to draw a conclusion that the development of Roux syndrome can be prevented by a transection of the jejunum with the saved arcades between the first jejunal artery, the duodenal branch and the second jejunal arteries. The rules of gastric resection by the Roux method and indications to this procedures in patients with ulcer disease of the stomach and duodenum are described. Good and excellent long-term results were obtained in 75.

[Structural, functional and genetic aspects of peroxisome biogenesis].

Intracellular organelles, peroxisomes, occur in cells of most eukaryotic species. Human severe congenital disorders are associated with defective assembly and functioning of peroxisomes, which partly explains the attention of researchers paid to peroxisome biogenesis. It has been shown that peroxisomes are involved in the realization of eukaryotic developmental programs (in particular, neuroblast differentiation and postembryonic development).

[Isolation and primary identification of methylotrophic yeast Hansenula polymorpha mutants for peroxisome biogenesis].

After exposure of cells of the methylotrophic yeast Hansenula polymorpha HF246 leu1-1 to N-nitro-N-nitrosoguanidine, a collection of 227 mutants unable to grow on methanol at elevated temperature (45 degrees C) was obtained. Ninety four ts mutants (35% of the total number of mutants), which were unable to grow on methanol only at 45 degrees C but could grow at optimal temperature (37 degrees C), were isolated. Complementation analysis of mutants using 12 deletion mutants for genes of peroxisome biogenesis (PEX) (available in this yeast species by the beginning of our work) allowed to assign 51 mutants (including 16 ts) to the separate group of mutants unable to complement deletion mutants with defects in eight PEX genes.

[Genetic control of purine biosynthesis in Pichia methanolica yeast. The ADE5 (PUR4) gene, controlling 5'-phosphoribosylformyl glycineamide synthetase].

By comparing published and experimental data on spontaneous mutability of early genes controlling biosynthesis of purine nucleotides (BPN) in different yeast species in the system "from red to white," it was shown that the PUR4 gene encoding 5'-phosphoribosylformyl glycinamidine synthetase (FGAM-synthetase) (EC 6.3.5.

[Genetic control of purine biosynthesis in the yeast Pichia methanolica. "Roman's effect" in red adenine-dependent pur6 and pur7 mutants].

Most ade1 and ade2 mutants of the yeast Pichia methanolica generate white and pink secondary colonies (SCs) on the surface of red colonies in complete medium. The formation of SCs was shown to be caused by "Roman's effect" described in Saccharomyces cerevisiae. This effect is known to result from the preferential growth in a colony of spontaneous mutations for genes controlling the first five steps of purine biosynthesis.

["Illegal" transformation of red adenine-dependent mutants of the yeast Pichia pinus by the pYE(ADE2)2 plasmid].

The red adenine-dependent mutants ade1 of the yeast Pichia pinus blocked in the VI step of adenine biosynthesis (lack of AIR-carboxylase) and ade2 mutants blocked in the VII step of adenine biosynthesis (lack of SAIKAR-synthase) were transformed with the plasmid pYE(ADE2)2 containing ADE2 gene of Saccharomyces cerevisiae encoding AIR-carboxylase. The appearance of white Ade+ clones with the frequency 2-7.10(-8) (which is ten-fold higher than reversion frequency) was only observed in the case of ade2 transformation.

[Ploidy and liquid-holding recovery in yeasts sensitive to radiation and nitrous acid].

The effects of genome ploidy and posttreatment incubation on inactivation by nitrous acid (NA) were studied in normal, radio- and nitrous acid-sensitive strains of yeast. In normal yeast cells the increase of ploidy (haploid to triploid) resulted in "the protective effect", i.e.