Haplotype Diversity and Reconstruction of Ancestral Haplotype Associated with the c.35delG Mutation in the GJB2 (Cx26) Gene among the Volgo-Ural Populations of Russia.

The mutations in theGJB2(Сх26) gene make the biggest contribution to hereditary hearing loss. The spectrum and prevalence of theGJB2gene mutations are specific to populations of different ethnic origins. For severalGJB2 mutations, their origin from appropriate ancestral founder chromosome was shown, approximate estimations of "age" obtained, and presumable regions of their origin outlined. This work presents the results of the carrier frequencies' analysis of the major (for European countries) mutation c.35delG (GJB2gene) among 2,308 healthy individuals from 18 Eurasian populations of different ethnic origins: Bashkirs, Tatars, Chuvashs, Udmurts, Komi-Permyaks, Mordvins, and Russians (the Volga-Ural region of Russia); Byelorussians, Ukrainians (Eastern Europe); Abkhazians, Avars, Cherkessians, and Ingushes (Caucasus); Kazakhs, Uzbeks, Uighurs (Central Asia); and Yakuts, and Altaians (Siberia). The prevalence of the c.35delG mutation in the studied ethnic groups may act as additional evidence for a prospective role of the founder effect in the origin and distribution of this mutation in various populations worldwide. The haplotype analysis of chromosomes with the c.35delG mutation in patients with nonsyndromic sensorineural hearing loss (N=112) and in population samples (N =358) permitted the reconstruction of an ancestral haplotype with this mutation, established the common origin of the majority of the studied mutant chromosomes, and provided the estimated time of the c.35delG mutation carriers expansion (11,800 years) on the territory of the Volga-Ural region.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses.

Translationally controlled tumour protein (TCTP) is a highly conserved protein present in all eukaryotic organisms. Various cellular functions and molecular interactions have been ascribed to this protein, many related to its growth-promoting and antiapoptotic properties. TCTP levels are highly regulated in response to various cellular stimuli and stresses. We have shown recently that the double-stranded RNA-dependent protein kinase, PKR, is involved in translational regulation of TCTP. Here we extend these studies by demonstrating that TCTP is downregulated in response to various proapoptotic treatments, in particular agents that induce Ca(++) stress, in a PKR-dependent manner. This regulation requires phosphorylation of protein synthesis factor eIF2alpha. Since TCTP has been characterized as an antiapoptotic and Ca(++)-binding protein, we asked whether it is involved in protecting cells from Ca(++)-stress-induced apoptosis. Overexpression of TCTP partially protects cells against thapsigargin-induced apoptosis, as measured using caspase-3 activation assays, a nuclear fragmentation assay, using fluorescence-activated cell sorting analysis, and time-lapse video microscopy. TCTP also protects cells against the proapoptotic effects of tunicamycin and etoposide, but not against those of arsenite. Our results imply that cellular TCTP levels influence sensitivity to apoptosis and that PKR may exert its proapoptotic effects at least in part through downregulation of TCTP via eIF2alpha phosphorylation.

Enzymic production of sweet stevioside derivatives: transglucosylation by glucosidases.

For the purpose of improving sweetness and a further study on the structure-sweetness relationship of steviol glycosides, transglycosylation of stevioside by a variety of commercial glucosidases was investigated. It was revealed that two alpha-glucosidases gave glucosylated products. Transglucosylation of stevioside by Pullulanase and pullulan exclusively afforded three products, 13-O-[beta-maltotriosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D-g luc osyl- steviol (1), 13-O-[beta-maltosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D-glucosyl- steviol (2) and 13-O-beta-sophorosyl-19-O-beta-maltotriosyl-steviol (3). All of these products have already been obtained by trans-alpha-1,4-glucosylation of stevioside by the cyclodextrin glucanotransferase starch system, and 1 and 2 have been proven to be tasty and potent sweeteners. Transglucosylation of stevioside by Biozyme L and maltose afforded three new products, 4, 5 and 6, the structures of these compounds being elucidated as 13-O-beta-sophorosyl-19-O-beta-isomaltosyl-steviol (4), 13-O-[beta-isomaltosyl(1----2)-beta-D-glucosyl]-19-O-beta-D-glucosyl- steviol (5) and 13-O-[beta-nigerosyl-(1----2)-beta-D-glucosyl]-19-O-beta-D- glucosyl-steviol (6). A significantly high quality of taste was evaluated for 4.