Activation of innate immunity by lysozyme fibrils is critically dependent on cross-β sheet structure

Inflammation occurs in many amyloidoses, but its underlying mechanisms remain enigmatic. Here we show that amyloid fibrils of human lysozyme, which are associated with severe systemic amyloidoses, induce the secretion of pro-inflammatory cytokines through activation of the NLRP3 (NLR, pyrin domain containing 3) inflammasome and the Toll-like receptor 2, two innate immune receptors that may be involved in immune responses associated to amyloidoses. More importantly, our data clearly suggest that the induction of inflammatory responses by amyloid fibrils is linked to their intrinsic structure, because the monomeric form and a non-fibrillar type of lysozyme aggregates are both unable to trigger cytokine secretion. These lysozyme species lack the so-called cross-β structure, a characteristic structural motif common to all amyloid fibrils irrespective of their origin. Since fibrils of other bacterial and endogenous proteins have been shown to trigger immunological responses, our observations suggest that the cross-β structural signature might be recognized as a generic danger signal by the immune system.     

Effect of extrinsic mortality on the evolution of senescence in guppies

Classical theories for the evolution of senescence predict that organisms that experience low mortality rates attributable to external factors, such as disease or predation, will evolve a later onset of senescence. Here we use patterns of senescence in guppies derived from natural populations that differ in mortality risk to evaluate the generality of these predictions. We have previously found that populations experiencing higher mortality rates evolve earlier maturity and invest more in reproduction, as predicted by evolutionary theory. We report here that these same populations do not have an earlier onset of senescence with respect to either mortality or reproduction but do with respect to swimming performance, which assesses neuromuscular function. This mosaic pattern of senescence challenges the generality of the association between decreased extrinsic mortality and delayed senescence and invites consideration of more derived theories for the evolution of senescence.     

Ten years of tension: single-molecule DNA mechanics

The basic features of DNA were elucidated during the half-century following the discovery of the double helix. But it is only during the past decade that researchers have been able to manipulate single molecules of DNA to make direct measurements of its mechanical properties. These studies have illuminated the nature of interactions between DNA and proteins, the constraints within which the cellular machinery operates, and the forces created by DNA-dependent motors.