Prion protein (PrP) amyloid formation is a central feature of genetic and acquired prion diseases such as Gerstmann-Sträussler-Scheinker disease (GSS) and variant Creutzfeldt-Jakob disease. The major component of GSS amyloid is a PrP fragment spanning residues ϳ82-146, which when synthesized as a peptide, readily forms fibrils featuring GSS amyloid. The present study employed surface plasmon resonance (SPR) to characterize the binding events underlying PrP82-146 oligomerization at the first stages of fibrillization, according to evidence suggesting a pathogenic role of prefibrillar oligomers rather than mature amyloid fibrils. We followed in real time the binding reactions occurring during short term (seconds) addition of PrP82-146 small oligomers (1-5-mers, flowing species) onto soluble prefibrillar PrP82-146 aggregates immobilized on the sensor surface. SPR data confirmed very efficient aggregation/elongation, consistent with the hypothesis of nucleation-dependent polymerization process. Much lower binding was observed when PrP82-146 flowed onto the scrambled sequence of PrP82-146 or onto prefibrillar A42 aggregates. As previously found with A40, SPR data could be adequately fitted by equations modeling the "dock-and-lock" mechanism, in which the "locking" step is due to sequential conformational changes, each increasing the affinity of the monomer for the fibril until a condition of irreversible binding is reached. However, these conformational changes (i.e. the locking steps) appear to be faster and easier with PrP82-146 than with A40. Such differences suggest that PrP82-146 has a greater propensity to polymerize and greater stability of the aggregates.
In developing countries, the adoption of effective climate change adaptation strategies can safeguard rural communities’ livelihoods. Using survey data collected in Guinea in 2012, the paper investigates the factors affecting households’ strategies to face adverse climate change impacts. A three‐step methodology is applied: (1) assessment of the magnitude of real climatic trends in the study area together with farmers’ perception of climate change; (2) identification of physical and socioeconomic variables influencing farmers’ adaptation propensity; and (3) analysis of factors affecting adaptation choices, including climate change perception. The climatic data analysis confirms increase in minimum and maximum temperature trends, increase in annual average millimeters of rain, and decrease in average number of storms per year. Farmers’ perception of climate change turned out to be aligned with historical climatic trends and represents an important determinant for the adoption of adaptation strategies. The regression model results suggest that the propensity to adapt is positively influenced by the level of education and a limited access to water resources and agricultural inputs, forcing households to adopt new cropping calendars. Effective policy action should consider different areas, including climate change awareness, education, access to natural and physical assets, and availability of economic resources to local communities.
This contribution aims to provide an in-depth outlook of the phase-out of coal-fired energy generation in Italy. In particular, this article analyzes the state-of-the-art with regard to both the current role of coal generation and the performance of the main legal and regulatory tools as implemented in Italy thus far to ensure the closure of all coal power plants by 2025 as announced in the Italian National Climate and Energy Plan. Based on existing data and scenarios on both electricity production and demand trends, this article unfolds the marginal role played by coal-fired generation in the Italian energy mix. In addition, this paper aims to highlight the outstanding technical uncertainties and regulatory hurdles in the way towards de-carbonization of energy generation in Italy. This paper argues that several remarkable improvements are needed in order to avoid over-generation (especially through natural gas), to upscale the penetration of renewable energy sources, and develop the necessary infrastructures to adequately deliver on the full phasing-out of coal within the expected timeframes.
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