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Spinocerebellar ataxia type 5 (SCA5) is a neurodegenerative disease caused by mutations in the cytoskeletal protein β-III-spectrin. Previously, a SCA5 mutation resulting in a leucine-to-proline substitution (L253P) in the actin-binding domain (ABD) was shown to cause a 1000-fold increase in actin-binding affinity. However, the structural basis for this increase is unknown. Here, we report a 6.9 Å cryo-EM structure of F-actin complexed with the L253P ABD. This structure, along with co-sedimentation and pulsed-EPR measurements, demonstrates that high-affinity binding caused by the CH2-localized mutation is due to opening of the two CH domains. This enables CH1 to bind actin aided by an unstructured N-terminal region that becomes α-helical upon binding. This helix is required for association with actin as truncation eliminates binding. Collectively, these results shed light on the mechanism by which β-III-spectrin, and likely similar actin-binding proteins, interact with actin, and how this mechanism can be perturbed to cause disease. [ABSTRACT FROM AUTHOR]

The International Committee on Taxonomy of Viruses (ICTV) has recently adopted a comprehensive, hierarchical system of virus taxa. The highest ranks in this hierarchy are realms, each of which is considered monophyletic but apparently originated independently of other realms. Here, we announce the creation of a new realm, Adnaviria, which unifies archaeal filamentous viruses with linear A-form double-stranded DNA genomes and characteristic major capsid proteins unrelated to those encoded by other known viruses. [ABSTRACT FROM AUTHOR]

Background Gastrointestinal symptoms as a common clinical evaluation index require a universal evaluation tool, and the Gastrointestinal Symptom Rating Scale (GSRS) has been widely applicated in domestic studies. However, the versions used are not standardized Chinese versions and their measurement performance has not been reported yet. Objective To explore the measurement performance of the Chinese version of the GSRS, in order to provide an objective basis for expanding the application of the scale. Methods From October 2021 to March 2022, patients with irritable bowel syndrome (IBS), chronic enteritis and chronic gastritis who attended outpatient clinics of splenogastroenterology or gastroenterology in 45 hospitals (community health service centers), including Jilin Provincial People's Hospital and Beijing Changping District Urban Community Health Service Center, etc. The Chinese version of GSRS was used to evaluate the gastrointestinal symptoms of the included patients on treatment days 0, 3, 7 and 14. Reliability and validity analyses were conducted on the Chinese version of GSRS, and the paired Wilcoxon signed rank sum test was applied to compare the changes in the scores of patients before and after treatment. Additionally, effect size (ES), standardized response mean (SRM), and score change rate (CR) were used to assess the responsiveness of the scales. Results A total of 554 patients were included and followed up, including 127 patients (22.93%) with IBS, 244 (44.04%) patientswith chronic enteritis and 183 (33.03%) patients with chronic gastritis. The Cronbach's alpha coefficient for the Chinese version of GSRS was 0.896, the Guttman Split-half coefficient was 0.920, the Spearman-Brown coefficient was 0.926, the intraclass correlation coefficient (ICC) for the two retest results was 0.589, and the Spearman correlation coefficient was 0.662. The content validity index for each item ranged from 0.78 to 1.00. The content validity index (CVI) for the scale-level universal agreement was 0.73, and the average CVI was 0.96. Exploratory factor analysis extracted a total of three common factors with eigenvalues>1, and the rate of cumulative variance contribution is 60.721%.The validation factor analysis demonstrated that the data samples did not fit the initial model M0 well, and each fit index of model M1 is within the acceptable range after correction according to the modification indicator hints in the acceptable range: χ2/df0.900. The total Chinese version of GSRS scores of patients after 14 d of treatment are lower than the total Chinese version of GSRS scores before treatment (P