Status Of The FAIR Synchrotron Projects SIS18 And SIS100

A large fraction of the program to upgrade the existingheavy ion synchrotron SIS18 as injector for the FAIR synchrotron SIS100 has been successfully completed. With the achieved technical status, a major increase of theaccelerated number of heavy ions could be reached. Thenow available performance especially demonstrates thefeasibility of high intensity beams of medium charge stateheavy ions with a sufficient control of the dynamicvacuum and connected charge exchange loss. Two furtherupgrade measures, the installation of additional magneticalloy (MA) acceleration cavities and the exchange of themain dipole power converter, are presently beingimplemented. For the FAIR synchrotron SIS100, theprocurement of all major components with longproduction times has been started. With the delivery andtesting of several pre-series components, the phase ofoutstanding technical reserach and developments could becompleted and the readiness for series productionachieved

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues