Implicating Calpain in Tau-Mediated Toxicity In Vivo

Alzheimer's disease and other related neurodegenerative disorders known as tauopathies are characterized by the accumulation of abnormally phosphorylated and aggregated forms of the microtubule-associated protein tau. Several laboratories have identified a 17 kD proteolytic fragment of tau in degenerating neurons and in numerous cell culture models that is generated by calpain cleavage and speculated to contribute to tau toxicity. In the current study, we employed a Drosophila tauopathy model to investigate the importance of calpain-mediated tau proteolysis in contributing to tau neurotoxicity in an animal model of human neurodegenerative disease. We found that mutations that disrupted endogenous calpainA or calpainB activity in transgenic flies suppressed tau toxicity. Expression of a calpain-resistant form of tau in Drosophila revealed that mutating the putative calpain cleavage sites that produce the 17 kD fragment was sufficient to abrogate tau toxicity in vivo. Furthermore, we found significant toxicity in the fly retina associated with expression of only the 17 kD tau fragment. Collectively, our data implicate calpain-mediated proteolysis of tau as an important pathway mediating tau neurotoxicity in vivo

Low-temperature mechanical dissipation of thermally evaporated indium film for use in interferometric gravitational wave detectors

Indium bonding is under consideration for use in the construction of cryogenic mirror suspensions in future gravitational wave detectors. This paper presents measurements of the mechanical loss of a thermally evaporated indium film over a broad range of frequencies and temperatures. It provides an estimate of the resulting thermal noise at 20 K for a typical test mass geometry for a cryogenic interferometric gravitational wave detector from an indium layer between suspension elements