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

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

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

Acknowledgements We thank Professor William Kim (University of North Carolina, Chapel Hill) for his generous gift of the UPPL1591 cell line. We thank Dr. Mark Hill (Department of Oncology, University of Oxford) for assistance with irradiation procedures, and Dr. Jia-Yu Ke and Dr. Vijay Indukuri (Research Diets, Inc.) for formulation of the mouse diets. We thank Dr. Graham Horgan (James Hutton Research Institute, Aberdeen) for statistical advice. We thank Grampian Biorepository at Aberdeen Royal Infirmary for providing the faecal samples from cancer patients.Peer reviewe

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity

Background: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Result: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. Conclusion: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. C3P3Z-i-BEWcsPG8U_9P4fVideo Abstrac

A novel role for the soluble isoform of CTLA-4 in normal, dysplastic and neoplastic oral and oropharyngeal epithelia

Acknowledgments: The authors would like to acknowledge the NHS Grampian Biorepository for their help in acquiring samples, especially Andrea Chapman for confirming the diagnosis of the samples. Microscopy was performed in the Microscopy and Histology Core Facility at the University of Aberdeen. We thank the following for their work during their summer projects: Rory Maciver (INSPIRE National Scholarship, Academy of Medical Sciences through the University of Aberdeen), Ramisha Basharat (summer scholarship by the Development Trust of the University of Aberdeen through funds from CRANES, Scotland), Sara Lucila Lorenzo Guerra (ERASMUS+), and Khaled Shawki (currently at Horus University, Egypt). Funding: This work was supported by funding from Friends of Anchor (RS 17 007), TENOVUS Scotland (G17.11), and the NHS Endowment Grant (17/042 and 18/24). P.C., F.A.-F. and B.R. were funded by the University of Aberdeen doctoral Elphinstone Scholarship.Peer reviewedPublisher PD