Tau polymerization: role of the amino terminus

The abnormal polymerization of the tau molecule into insoluble filaments is a seminal event in the neurodegenerative process underlying Alzheimer's disease. Previous experimentation has shown that the microtubule-binding repeat region of the molecule is vital for its ability to polymerize in vitro into filaments similar to those found in Alzheimer's disease. However, it is becoming clear that regions outside the microtubule-binding repeat, such as exons 2 and 3 and the carboxy-terminal tail, can greatly influence its polymerization. Since it has been previously postulated that the amino terminus of tau could be involved in generating pathological conformations in the disease state, its role in the polymerization process was investigated. This report demonstrates that the removal of the amino terminus greatly inhibits the polymerization of the tau molecule, reducing both the rate and extent of polymerization. These results support the hypothesis that the ability of tau to form specific conformations involving the amino terminus is an early event in the formation of tau polymers in the disease state. Furthermore, the mutation of arginine 5 to leucine ((R)5(L)), mimicking an amino-terminal tau mutation found in a single case of FTDP-17, enhances the polymerization of the tau molecule. Therefore, the amino terminus of the tau molecule, while largely overlooked in studies of its polymerization, is a significant contributor to the polymerization process.     

Formation of a new original material based on genetic heterogeneity of disomal wheat plants from offspring of aneuploids

A series of disomic lines of spring wheat Opal selected on the basis of monosomic lines of this cultivar has been studied. The lines have been tested for combining ability, and the heterosis effect has been studied in disomic lines of F1 hybrids obtained by topcrossing. The line have been demonstrated to differ both from one another and from cultivar Opal in the expression of quantitative traits, combining ability, and the degree of heterosis in F1. These data suggest that recombinations accompanying the formation of the monosomic series have changed their genetic program. To test this suggestion, intramolecular heterogeneity of 42-chromosome plants has been analyzed using polymerase chain reaction (PCR) and isoenzyme analysis. The results confirmed the differences at the DNA and protein levels. According to the results of molecular analyses, A-genome lines are the most polymorphic. Strong heterosis effects have been detected in hybrid combinations contributed by D- and B-genome lines, which are characterized by medium and low degrees of molecular genetic polymorphism. Lines that are promising in terms of breeding programs have been identified.     

Was August Weismann right?

A new hypothesis of the genetic regulation of cell differentiation is put forward. The hypothesis is based on the assumption that the diminution and hyper-replication patterns of repetitive nucleotide sequences depend on the differentiation pathways of cells and tissues.     

Variation of mini- and microsatellite DNA repeats in parthenogenetic lizard Darevskia armeniaca as revealed by DNA fingerprinting analysis

Population and family samples of two morphological forms (mutant and normal with respect to dorsal color) of pathogenetic lizard Darevskia armeniaca were examined by means of DNA fingerprinting using M13 mini- and (GATA)n and (TCC)n microsatellite DNA markers. The morphological forms examined were characterized by clonally inherited, species-specific patterns of the DNA markers, which were different from the species-specific DNA fingerprints of the other parthenogenetic species of the genus Darevskia (D. dahli. D. unisexualis, and D. rostombekovi). The mean index of similarity (S) obtained for a sample of 36 individuals from three isolated populations using three types of DNA markers was 0.966. This was similar to the variability level observed in D. dahli (0.962) (P > 0.05), but higher than that in D. unisexualis (0.950) (P < 0.05) and D. rostombekovi (0.875) (P < 0.01). Inheritance of M13 minisatellite and (TCC)n microsatellite DNA markers in the F1 offspring of parthenogenetic lizards was examined. It was shown that variability and clonal diversity of the fingerprint phenotypes observed in the populations and families of D. armeniaca could be at least partly explained by RFLP mutations in microsatellite repeats.     

Characteristics of radish lines and hybrids from the spectrum of multiple molecular forms of enzymes

We characterized radish lines from a genetic collection on the basis of six enzyme systems, identified genes controlling these enzymes, and examined joint inheritance of some biochemical and morphological traits.     

Role of conserved residues in structure and stability: tryptophans of human serum retinol-binding protein, a model for the lipocalin superfamily

Serum retinol binding protein (RBP) is a member of the lipocalin family, proteins with up-and-down beta-barrel folds, low levels of sequence identity, and diverse functions. Although tryptophan 24 of RBP is highly conserved among lipocalins, it does not play a direct role in activity. To determine if Trp24 and other conserved residues have roles in stability and/or folding, we investigated the effects of conservative substitutions for the four tryptophans and some adjacent residues on the structure, stability, and spectroscopic properties of apo-RBP. Crystal structures of recombinant human apo-RBP and of a mutant with substitutions for tryptophans 67 and 91 at 1.7 A and 2.0 A resolution, respectively, as well as stability measurements, indicate that these relatively exposed tryptophans have little influence on structure or stability. Although Trp105 is largely buried in the wall of the beta-barrel, it can be replaced with minor effects on stability to thermal and chemical unfolding. In contrast, substitutions of three different amino acids for Trp24 or replacement of Arg139, a conserved residue that interacts with Trp24, lead to similar large losses in stability and lower yields of native protein generated by in vitro folding. The results and the coordinated nature of natural substitutions at these sites support the idea that conserved residues in functionally divergent homologs have roles in stabilizing the native relative to misfolded structures. They also establish conditions for studies of the kinetics of folding and unfolding by identifying spectroscopic signals for monitoring the formation of different substructures.     

Adenovirus-mediated expression of pig α(1,3) galactosyltransferase reconstructs Gal α(1,3) Gal epitope on the surface of human tumor cells

INTRODUCTIONGal a(1, 3) Gal (gal epitope) is a carbohydrate epitope, which is produced in large amounton the cells of pigs, mice and New World monkey(monkey of South America) by the glycosylationenzyme G alal 1 ) 4G IcNAc3- a- D- galactosyltransferase[or(1, 3)GT; EC2.4.1.511111. This enzyme is active in the Golgi appaxatus of cells and transfers galactose from the sugandonor uridine diphoSphate galactose (UDP-galactose) to the acceptor Nacetyllactosamine residue (Galaal-4GlcNAc-R…