NLRP3 inflammasome as a key molecular target underlying cognitive resilience in amyotrophic lateral sclerosis

Funding Pathological Society of Great Britain and Ireland. Grant Number: Jean Shanks Foundation Clinical Lecturer Support G OR is funded by a Wellcome Trust PhD fellowship (108890/Z/15/Z). JMG is funded by a starter grant for clinical lecturers from the AMS (210JMG 3102 R45620) and a Clinical Lecturer Support Grant from The Pathological Society/Jean Shanks Foundation, and brain bank funding from the MRC (MR/L016400/1). EE is funded by a PhD fellowship from the CSO and MND Scotland: 217ARF R45951.Peer reviewedPublisher PD

Distinct neuroinflammatory signatures exist across genetic and sporadic ALS cohorts

Acknowledgments This research was funded in part by the Wellcome Trust (108890/Z/15/Z) to OMR, a Pathological Society and Jean Shanks Foundation grant (JSPS CLSG 202002) to JMG and JOS, an NIH grant (5-R01-NS127186-02) to JMG, FMW, and JOS, a Motor Neuron Disease (MND) Scotland grant to JMG and CRS (2021/MNDS/RP/8440GREG), and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to CRS. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work would not be possible without the resources of the Edinburgh Brain Bank. The authors declare no conflicts of interest.Preprin

Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts

Acknowledgements This work would not be possible without the resources of the Edinburgh Brain Bank, and the tissue donors and their families. Funding This research was funded in part by the Wellcome Trust (108890/Z/15/Z) to O.M.R., a Pathological Society of Great Britain & Ireland and Jean Shanks Foundation grant (JSPS CLSG 202002) to J.M.G. and J.O., a National Institutes of Health (NIH) grant (5-R01-NS127186-02) to J.M.G., F.M.W., and J.O., a Motor Neuron Disease (MND) Scotland grant to J.M.G. and C.R.S. (2021/MNDS/RP/8440GREG), and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to C.R.S.Peer reviewedPublisher PD

pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis : a case series linking archival surgical biopsies with clinical phenotypic data

Acknowledgements The authors would like to thank the staff at the NHS Lothian BioResource (Vishad Patel and Craig Marshall) and the NHS Grampian biorepository (Joan Wilson) and the staff and corefunded resources of the imaging and histology core facility at the Institute of Medical Sciences (Gillian Milne, Lucinda Wight, and Debbie Wilkinson). This study was funded by the Pathological Society/Jean Shanks Foundation (JSPS CLSG 202002 to JMG and JO’S), The Royal Society (RGS\R1\221396 to JMG) and the Wellcome Trust (108890/Z/15/Z to OR). Funders had no role in study design, data collection, data analyses, interpretation, or writing the manuscriptPeer reviewedPostprin

Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in C9orf72 ‐ALS

Acknowledgments We gratefully acknowledge Professor Tom Gillingwater for his helpful comments and support. This work would not have been possible without the resources of the Edinburgh Brain Bank, and the people with ALS and their families who have generously donated tissue. This research was funded in part by a studentship from the Wellcome Trust (108890/Z/15/Z) to OMR and MDES, a Pathological Society and Jean Shanks foundation grant (217CHA R46564) to JMG and JO, and a Sir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to CRS.Peer reviewedPublisher PD

RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS

Open Access via the Springer Agreement The research leading to this manuscript has been supported by (i) a Target ALS foundation grant to JMG, MHH, GGT, EZ and NS and employing MG and FMW BB-2022-C4-L2; (ii) an NIH grant to JG and MHH, employing HS and FR R01NS127186; (iii) the European Research Council (RIBOMYLOME_309545 and ASTRA_855923) to GGT; and (iv) an MND Association Lady Edith Wolfson Junior Non-Clinical Fellowship to RS Saleeb/Oct22/980-799 (RSS). The authors would also like to thank the University of Aberdeen Microscopy and Histology Core Facility in the Institute of Medical Sciences.Peer reviewe

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure