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AL amyloidosis is a life-threatening disease caused by deposition of immunoglobulin light chains. While the mechanisms underlying light chains amyloidogenesis in vivo remain unclear, several studies have highlighted the role that tissue environment and structural amyloidogenicity of individual light chains have in the disease pathogenesis. AL natural deposits contain both full-length light chains and fragments encompassing the variable domain (VL) as well as different length segments of the constant region (CL), thus highlighting the relevance that proteolysis may have in the fibrillogenesis pathway. Here, we investigate the role of major truncated species of the diseaseassociated AL55 light chain that were previously identified in natural deposits. Specifically, we study structure, molecular dynamics, thermal stability, and capacity to form fibrils of a fragment containing both the VL and part of the CL (133-AL55), in comparison with the full-length protein and its variable domain alone, under shear stress and physiological conditions. Whereas the full-length light chain forms exclusively amorphous aggregates, both fragments generate fibrils, although, with different kinetics, aggregate structure, and interplay with the unfragmented protein. More specifically, the VL-CL 133- AL55 fragment entirely converts into amyloid fibrils microscopically and spectroscopically similar to their ex vivo counterpart and increases the amorphous aggregation of full-length AL55. Overall, our data support the idea that light chain structure and proteolysis are both relevant for amyloidogenesis in vivo and provide a novel biocompatible model of light chain fibrillogenesis suitable for future mechanistic studies. [ABSTRACT FROM AUTHOR]

• No causal impact of schools reopening on the spread of Omicron was found. • Schools did not increase SARS-CoV-2 transmission in Italy, Germany, and Portugal. • Geography, seasons, and population behavior exerted a more substantial influence. • No differences were observed by age group in SARS-CoV-2 transmission rates. • We are reassured of the involvement of schools, which is crucial during a pandemic. We investigated the impact of school reopening on SARS-CoV-2 transmission in Italy, Germany, and Portugal in autumn 2022 when the Omicron variant was prevalent. A prospective international study was conducted using the case reproduction number (R c) calculated with the time parametrization of Omicron. For Germany and Italy, staggered difference-in-differences analysis was employed to explore the causal relationship between school reopening and R c changes, accounting for varying reopening dates. In Portugal, interrupted time series analysis was used due to simultaneous school reopenings. Multivariable models were adopted to adjust for confounders. In Italy and Germany, post-reopening R c estimates were significantly lower compared to those from regions/states that had not yet reopened at the same time points, both in the student population (overall average treatment effect for the treated subpopulation [O-ATT]: -0.80 [95% CI: -0.94;-0.66] for Italy; O-ATT-0.30 [95% CI: -0.36;-0.23] for Germany) and the adult population (O-ATT: -0.04 [95% CI: -0.07;-0.01] for Italy; O-ATT: -0.07 [95% CI: -0.11;-0.03] for Germany). In Portugal, there was a significant decreasing trend in R c following school reopenings compared to the pre-reopening period (sustained effect: -0.03 [95% CI: -0.04; -0.03] in students; -0.02 [95% CI: -0.03; -0.02] in adults). We found no evidence of a causal relationship between school reopenings in autumn 2022 and Omicron SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]