Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer's disease in a mouse model of Aβ amyloidosis

Recently, large-scale human genetics studies identified a rare coding variant in the ABI3 gene that is associated with an increased risk of Alzheimer’s disease (AD). However, pathways by which ABI3 contributes to the pathogenesis of AD are unknown. To address this question, we determined whether loss of ABI3 function affects pathological features of AD in the 5XFAD mouse model. We demonstrate that the deletion of Abi3 locus significantly increases amyloid β (Aβ) accumulation and decreases microglia clustering around the plaques. Furthermore, long-term potentiation is impaired in 5XFAD;Abi3 knockout (“Abi3−/−”) mice. Moreover, we identified marked changes in the proportion of microglia subpopulations in Abi3−/− mice using a single-cell RNA sequencing approach. Mechanistic studies demonstrate that Abi3 knockdown in microglia impairs migration and phagocytosis. Together, our study provides the first in vivo functional evidence that loss of ABI3 function may increase the risk of developing AD by affecting Aβ accumulation and neuroinflammation

Robust single nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity

Single nucleus RNA sequencing (snRNA-seq), an alternative to single cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying adipose tissue remodeling during obesity. By integrating bulk nuclear RNA-seq from adipocyte nuclei of different sizes, we identify distinct adipocyte subpopulations categorized by size and functionality. These subpopulations follow two divergent trajectories, adaptive and pathological, with their prevalence varying by depot. Specifically, we identify a key molecular feature of dysfunctional hypertrophic adipocytes, a global shutdown in gene expression, along with elevated stress and inflammatory responses. Furthermore, our differential gene expression analysis reveals distinct contributions of adipocyte subpopulations to the overall pathophysiology of adipose tissue. Our study establishes a robust snRNA-seq method, providing novel insights into the mechanisms orchestrating adipose tissue remodeling during obesity, with broader applicability across diverse biological systems

Vaccine targets against Moraxella catarrhalis

INTRODUCTION: Moraxella catarrhalis is a prominent pathogen that causes acute otitis media in children and lower respiratory tract infections in adults, resulting in a significant socioeconomic burden on healthcare systems globally. No vaccine is currently available for M. catarrhalis. Promising M. catarrhalis target antigens have been characterized in animal models and should soon enter human clinical trials. AREAS COVERED: This review discusses the detailed features and research status of current candidate target antigens for an M. catarrhalis vaccine. The approaches for assessing M. catarrhalis vaccine efficacy are also discussed. EXPERT OPINION: Targeting the key molecules contributing to serum resistance may be a viable strategy to identify effective vaccine targets among M. catarrhalis antigens. Elucidating the role and mechanisms of the serum and mucosal immune responses to M. catarrhalis is significant for vaccine target selection, testing and evaluation. Developing animal models closely simulating M. catarrhalis-caused human respiratory diseases is of great benefit in better understanding pathogenesis and evaluating vaccine efficacy. Carrying out clinical trials will be a landmark in the progress of M. catarrhalis vaccine research. Combined multicomponent vaccines will be a focus of future M. catarrhalis vaccine studies