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ATTR amyloidosis is a fatal disease associated with the accumulation of transthyretin (ATTR) fibrils that lead to organ failure and death. Mutations in the TTR gene or aging may accelerate the deposition of variant (ATTRv) or wild-type (ATTRwt) transthyretin, respectively. Although ATTR amyloidosis patients accumulate ATTR fibrils in virtually every organ, the clinical presentation is often unpredictable and variable. Recent studies in cryo-electron microscopy (cryo-EM) have revealed that in tauopathies and synucleinopathies, diseases involving amyloidosis of tau and α-synuclein, respectively, all the patients of the same disease display the same fibril fold, or polymorph. In this study, we use cryo-EM to explore whether fibrils from heart tissue of different patients with cardiac ATTR amyloidosis share a common fold. We determined the molecular structures of fibrils extracted from the hearts of seven patients, including both ATTRv and ATTRwt carriers, at resolutions of 3.0 to 3.7 Å. We found that ATTRv mutations perturb the fibril conformation whereas ATTRwt fibrils share a common structure fold. Our findings suggest that unlike in tauopathies and synucleinopathies, ATTRv fibrils display structural polymorphism driven by each individual and their genotypes. ATTR polymorphism challenges the current paradigm of ″one disease equals one fibril polymorph,″ and questions whether similarly novel conformations occur in other amyloidoses.

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In action civics education, an emerging promising practice, students learn civics through taking action on a community issue of interest. We examine the action civics programme Generation Citizen (GC) using quantitative and qualitative student survey data. Our quantitative analyses used a quasi-experimental study design and a multilevel model. Participation in GC was associated with increased action civics knowledge, and there were some variations in impact by programme and classroom characteristics. We also qualitatively analysed students’ short reflections upon programme completion and found that students feel more prepared for civic action. Action civics shows promise for improving student civic outcomes, but more research, including longitudinal follow-up, is needed. Given the variations in impact that we observed, action civics practitioners should carefully choose the implementation setting.