12 research outputs found

    Amyloid Plaques Beyond Aβ: A Survey of the Diverse Modulators of Amyloid Aggregation

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    Aggregation of the amyloid-β (Aβ) peptide is strongly correlated with Alzheimer’s disease (AD). Recent research has improved our understanding of the kinetics of amyloid fibril assembly and revealed new details regarding different stages in plaque formation. Presently, interest is turning toward studying this process in a holistic context, focusing on cellular components which interact with the Aβ peptide at various junctures during aggregation, from monomer to cross-β amyloid fibrils. However, even in isolation, a multitude of factors including protein purity, pH, salt content, and agitation affect Aβ fibril formation and deposition, often producing complicated and conflicting results. The failure of numerous inhibitors in clinical trials for AD suggests that a detailed examination of the complex interactions that occur during plaque formation, including binding of carbohydrates, lipids, nucleic acids, and metal ions, is important for understanding the diversity of manifestations of the disease. Unraveling how a variety of key macromolecular modulators interact with the Aβ peptide and change its aggregation properties may provide opportunities for developing therapies. Since no protein acts in isolation, the interplay of these diverse molecules may differentiate disease onset, progression, and severity, and thus are worth careful consideration

    Radiation damage in phosphates and silicates for nuclear waste disposal

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    Phosphate-based minerals are considered as potential nuclear waste forms because of their resistance to radiation damage when compared to their silicate counterparts, and their propensity to sequester actinides. Understanding the basis of radiation resistance in phosphate minerals is critical for determining the materials’ suitability for radioactive waste disposal and for underpinning the safety case of a waste form in a geological repository

    Biological Impacts of Thermal Extremes: Mechanisms and Costs of Functional Responses Matter

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    Thermal performance curves enable physiological constraints to be incorporated in predictions of biological responses to shifts in mean temperature. But do thermal performance curves adequately capture the biological impacts of thermal extremes? Organisms incur physiological damage during exposure to extremes, and also mount active compensatory responses leading to acclimatization, both of which alter thermal performance curves and determine the impact that current and future extremes have on organismal performance and fitness. Thus, these sub-lethal responses to extreme temperatures potentially shape evolution of thermal performance curves. We applied a quantitative genetic model and found that beneficial acclimatization and cumulative damage alter the extent to which thermal performance curves evolve in response to thermal extremes. The impacts of extremes on the evolution of thermal performance curves are reduced if extremes cause substantial mortality or otherwise reduce fitness differences among individuals. Further empirical research will be required to understand how responses to extremes aggregate through time and vary across life stages and processes. Such research will enable incorporating passive and active responses to sub-lethal stress when predicting the impacts of thermal extremes
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