The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates