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- Chronosequence (1)
- Diazotrophs (1)
- Fluorinated nucleoside analogues (1)
- Gene therapy (1)
- Glacier forefield (1)
- NifH diversity (1)
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Suicide gene therapy with the herpes simplex virus type-1 thymidine kinase gene (HSV-1 tk) is considered to be a promising approach to the treatment of cancer. Making use of the lower specificity of the viral enzyme compared to human thymidine kinase, the therapy involves the administration of antiviral agents (e.g., ganciclovir) as prodrugs to induce enzymatic cell death in those cells that express the transferred gene. 18F-labelled derivatives have been described for monitoring location, duration, and magnitude of the viral kinase enzyme activity by positron emission tomography (PET). Since an optimal radiotracer has not been developed, novel substances were synthesized for monitoring gene expression. A group of 13 nucleoside analogues were synthesized, among them N1-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (5) and N1-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]guanine (7) as methyl analogues of ganciclovir and penciclovir and their related fluoro compounds (6, 8). Further novel derivatives include N6-methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]-, N6-methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]adenine (9, 10), as well as the uracil derivatives 5-hydroxy-1-[(1,3-dihydroxy-2-propoxy)methyl]uracil (11), 6-methyl-1-[(1,3-dihydroxy-2-propoxy)-methyl]uracil (12), and its 3-fluoro-derivative (13).
Forefields of receding glaciers are unique and sensitive environments representing natural chronosequences. In such habitats, microbial nitrogen fixation is of particular interest since the low concentration of bioavailable nitrogen is one of the key limitations for growth of plants and soil microorganisms. Asymbiotic nitrogen fixation in the Damma glacier (Swiss Central Alps) forefield soils was assessed using the acetylene reduction assay. Free-living diazotrophic diversity and population structure were resolved by assembling four NifH sequence libraries for bulk and rhizosphere soils at two soil age classes (8- and 70-year ice-free forefield). A total of 318 NifH sequences were analyzed and grouped into 45 unique phylotypes. Phylogenetic analyses revealed a higher diversity as well as a broader distribution of NifH sequences among phylogenetic clusters than formerly observed in other environments. This illustrates the importance of free-living diazotrophs and their potential contribution to the global nitrogen input in this nutrient-poor environment. NifH diversity in bulk soils was higher than in rhizosphere soils. Moreover, the four libraries displayed low similarity values. This indicated that both soil age and the presence of pioneer plants influence diversification and population structure of free-living diazotrophs.