Avoidance of an immune response is critical to completion of the human papillomavirus (HPV) life cycle, which occurs in the stratified epithelium and is linked to epithelial differentiation. We previously demonstrated that high-risk HPVs use apoptotic caspases to suppress an antiviral innate immune response during the productive phase of the life cycle. We found that caspase-8 and caspase-3 suppress a type I IFN-β and type III IFN-λ response by disabling the MDA5/MAVS double-stranded RNA (dsRNA) sensing pathway, indicating that immunogenic RNAs increase upon differentiation in HPV+ cells.
View Article and Find Full Text PDFCoping with surprise and uncertainty resulting from the emergence of undesired and unexpected novelty or the sudden reorganization of systems at multiple spatiotemporal scales requires both a scientific process that can incorporate diverse expertise and viewpoints, and a scientific framework that can account for the structure and dynamics of interacting social-ecological systems (SES) and the inherent uncertainty of what might emerge in the future. We argue that combining a convergence scientific process with a panarchy framework provides a pathway for improving our understanding of, and response to, emergence. Emergent phenomena are often unexpected (e.
View Article and Find Full Text PDFA ring expansion of tetramic acids (pyrrolidine-2,4-diones) to -oxy-2,5-diketopiperazines (DKPs) is described. This method allows for the facile and late-stage construction of the hydroxamic acid moiety and can thereby serve as a general method for accessing -oxy-2,5-DKP natural products.
View Article and Find Full Text PDFTwo key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction.
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