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Sökning: WFRF:(Navarrete Sebastian)

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  • Jacobson, Therese, et al. (författare)
  • Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.
  • 2012
  • Ingår i: Journal of cell science. - 1477-9137 .- 0021-9533. ; 125:21, s. 5073-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
  • Stacey, Simon N, et al. (författare)
  • A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
  • 2011
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
  • Elsler, Laura Gabriele, et al. (författare)
  • Fit between formal management and informal rules related to fisher-trader relationships
  • Annan publikation (övrigt vetenskapligt)abstract
    • Fisher-trader relationships (FTR) encompass a wide range of influential and informal relationships that are present in many small-scale fisheries (SSF) worldwide. FTRs' potential to establish and maintain informal rules (FTR rules) that affect the resilience of fishing practices has shifted them into focus for formal fisheries management. Linking formal management rules to the landscape of informal rules requires a better understanding of fishers and traders’ role in rule-making and types of informal rules related to fishing practices. Here, we map out the informal rules related to fishing practices in Indonesia, Spermonde and compare them to formal fisheries management measures. We further assess fishers and traders' role in shaping certain fishing practices from which we draw preliminary conclusions about how and when formal fisheries management should involve fishers and traders. We find that FTR rules in Spermonde relate to a diversity of fishing practices and correspond to formal fisheries management measures such as in- and output control, temporal and spatial management. The emergence of fishing practices are linked to multiple functions within the FTR and to the network of relations of fishers and traders with other groups. These external relations are primarily served by traders. Thus, we argue that a foundation for linking formal fisheries management and informal rules exists on the basis of their similarity. Understanding the multiple functions and networks of relations can help identify intervention points for building or breaking resilience of fishing practices in Spermonde and beyond.
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