The AAA plus chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system

Amyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer's disease. The existence of cellular machinery for the removal of such aggregates has remained unclear, as specialized disaggregase chaperones are thought to be absent inmammalian cells. Here we show in cell culture and in neurons that the hexameric ATPase valosin-containing protein (VCP) is recruited to ubiquitylated Tau fibrils, resulting in their efficient disaggregation. Aggregate clearance depends on the functional cooperation of VCP with heat shock 70 kDa protein (Hsp70) and the ubiquitin-proteasome machinery. While inhibition of VCP activity stabilizes large Tau aggregates, disaggregation by VCP generates seeding-active Tau species as byproduct. These findings identify VCP as a core component of the machinery for the removal of neurodegenerative disease aggregates and suggest that its activity can be associated with enhanced aggregate spreading in tauopathies

Advanced landing gear noise reduction - Test data analysis and assessment of results

Future landing gear designs must account for aeroacoustics requirements at design stage. The development of such advanced low noise landing gears for future aircraft application was performed in Silencer WP 1.5.4, taking production costs, maintenance aspects and acoustic benefits into account. In SILENCER WP 2.3.3 full scale low noise gear mock ups were built and noise tested in the DNW-LLF. The noise test results were compared against those obtained for the baseline A340 landing gears in the RAIN project. For both the nose and the main landing gears each one reference configuration (as designed in WP 1.5.4) and selected configuration modifications were tested. Farfield noise spectra turned out to scale on a Strouhal number basis, with sound intensities increasing with wind speed to the power of 6. In terms of overall A-weighted noise levels the advanced low noise NLG is up to - 7 dB quieter compared to the A340 baseline gear for forward arc radiation directions. The advanced low noise MLG is up to about -5 dB quieter compared to the A340 baseline gear