Suchergebnisse

This book provides an extended examination of Nietzsche and Tocqueville's political thought, with an eye to shedding light on history's democratic drift. It looks not only to a future that filled both thinkers with dread, but also to an aristocratic past that has been all but drowned beneath democracy's shallow waters

This paper examines Friedrich Nietzsche's treatment of the Jews in the context of his overall project: the revaluation of values. Contrary to common (mis)perceptions, the Jews do not occupy some marginal place in Nietzsche's philosophy nor are they decried outright by the German philosopher; instead, they constitute a central component of Nietzsche's thought and determine constructively the directionality of his thinking. While the feasibility of Nietzsche's ambitions may be open to question, his reverence of the Jews, I argue, is not.

Abstract
We previously presented a bioinformatic method for identifying diseases that arise from a mutation in a protein's low-complexity domain that drives the protein into pathogenic amyloid fibrils. One protein so identified was the tropomyosin-receptor kinase–fused gene protein (TRK-fused gene protein or TFG). Mutations in TFG are associated with degenerative neurological conditions. Here, we present experimental evidence that confirms our prediction that these conditions are amyloid-related. We find that the low-complexity domain of TFG containing the disease-related mutations G269V or P285L forms amyloid fibrils, and we determine their structures using cryo-electron microscopy (cryo-EM). These structures are unmistakably amyloid in nature and confirm the propensity of the mutant TFG low-complexity domain to form amyloid fibrils. Also, despite resulting from a pathogenic mutation, the fibril structures bear some similarities to other amyloid structures that are thought to be nonpathogenic and even functional, but there are other factors that support these structures' relevance to disease, including an increased propensity to form amyloid compared with the wild-type sequence, structure-stabilizing influence from the mutant residues themselves, and double-protofilament amyloid cores. Our findings elucidate two potentially disease-relevant structures of a previously unknown amyloid and also show how the structural features of pathogenic amyloid fibrils may not conform to the features commonly associated with pathogenicity.