3 resultados para PRAIRIE VOLES

em AMS Tesi di Dottorato - Alm@DL - Università di Bologna


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A complete stratigraphic assessment and revision of the middle Campanian to upper Maastrichtian Wapiti Formation in north-western Alberta and north-eastern British Columbia is the main aim of this research project. The study area encompasses an area of approximately 200X180 km in the Grande Prairie County (west-central Alberta) and easternmost British Columbia, Canada. Results presented here indicate that the 1300m thick succession currently reported in the literature as “undifferentiated lithostratigraphic unit”, consists of five lithostratigraphic units and four unconformity-bounded depositional sequences; their study and description have been documented integrating several geological disciplines, including sequence stratigraphic methods, well-log signatures, facies analysis, and fossil associations. On the whole, particular attention has been given to 1) age and nature of both basal and upper contacts of the Wapiti Formation, 2) effective mappability of lithostratigraphic units and depositional sequences in western Alberta, and 3) the identification of previously undetermined maximum flooding surface of the Bearpaw seaway and Drumheller Marine Tongue, which are reference marine unit in central and southern Alberta. A second, but not less important, guideline for the project has been the rich paleontological record of the Wapiti deposits. Detailed paleoenvironmental and taxonomical information on old and new finds have been the base for correlation with well known associations of Alaska, southern Alberta, and Montana. Newly discovered rich fossil localities documented an extraordinarily diverse fauna during the latest Cretaceous, including dinosaurs, squamates, and fresh-water fishes and reptiles. Lastly, in order to better characterize the Wapiti Formation, major marker beds were described: these include several bentonites (altered volcanic ash deposits) which have been documented over an area of almost 30.000 km2, as well as four major coal zones, characterized by tabular coal seams with an overall thickness of 2 meters. Such marker beds represent a formidable tool for high-resolution chronology and regional correlations within the Late Cretaceous Alberta foreland basin.

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Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative disorders that affect humans and mammals. Creutzfeldt-Jakob disease (CJD), the most common TSE in humans, can be sporadic (sCJD), genetic (gCJD), or acquired by infection. All TSEs are characterised by the accumulation of PrPSc, a misfolded form of the cellular protein PrPC. PrPSc is insoluble in detergents, partially resistant to proteolysis and shows a highly enriched β-sheet secondary structure. Six clinico-pathological phenotypes of sCJD have been characterized which correlate at the molecular level with two types (1 or 2) of PrPSc with distinctive physicochemical properties and the genotype at the polymorphic (methionine or valine) codon 129 of the prion protein gene. According to the protein-only hypothesis, which postulates that prions are composed exclusively of PrPSc, the strains of prions that are largely responsible for the wide spectrum of TSE phenotypes are enciphered in PrPSc conformation. In support to this view, studies mainly conducted in experimental scrapie, have shown that several prion strains can be identified based on distinguishing PrPSc biochemical properties. To further contribute to the understanding of the molecular basis of strains and to develop more sensitive strain typing assays in humans we have analyzed PrPSc biochemical properties in two experimental setting. In the first we compared the size of the core after protease digestion and the glycoform pattern of PrPSc before and after transmission of human prions to non human primates or bank voles, whereas in the second we analyzed the conformational stability of PrPSc associated with sCJD, vCJD or fCJD using guanidine hydrochloride (GdnHCl) as denaturant. Combining the results of the two studies, we were able to distinguish five human strains for at least one biochemical property. The present data extend our knowledge about the extent of strain variation and its relationship with PrPSc properties in human TSEs.

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Transmissible spongiform encephalopathies (TSE) are neurodegenerative diseases caused by the conversion of the host-encoded cellular protein (PrPC) to a disease-associated isoform (PrPSc). The agent responsible for prion diseases may exist as different strains with specific biological and biochemical properties. According to the protein-only hypothesis, prion strain diversity is enciphered in PrPSc conformation. Molecular strain typing methods are based on the electrophoretic mobility of protease resistant core of PrPSc, on the susceptibility to protease digestion, on the glycosylation profile of PrPres and on the conformational stability of PrPSc. In this study a new conformational stability assay was developed based on the differential solubility of PrPC and PrPSc: CSSA (conformational stability and solubility assay). The conformational stability assay was performed by measuring PrPSc solubility in homogenates treated with increasing concentrations of GdnHCl, in the absence of proteinase K. Indeed, dose-response curves allowed estimation of the concentration of GdnHCl able to solubilise 50% of PrPSc. The results showed that this method is valuable for the biochemical typing of strains in bank voles and it is also a promising tool for molecular analysis of natural prion isolates. CSSA also revealed strain-specific PrPSc conformational stabilities of ovine natural isolates so that this feature, combined with the N-terminal PrPSc cleavage, allowed differentiation of classical scrapie, including CH1641-like, from natural goat BSE and experimental sheep BSE. In view of the implications concerning strain similarity between animal and human TSEs, the physico-chemical properties of the Nor98 with two human prion diseases (VPSPr and GSS) were compared in order to investigate the extent of the similarity between animal and human prion strains. The results showed an unexpected heterogeneity of the molecular features among human and sheep TSEs associated with internal PrPres fragments with the possible exception of Nor98 and a case of GSS P102L. These similarities and differences need further investigation by N- and C-terminal sequencing and biological characterization.