Aggregator

In Alzheimer's disease, tau pathology spreads across brain regions as the disease progresses. Intracellular tau can be released and taken up by nearby neurons. We evaluated single domain anti-tau antibodies, also called VHHs, as inhibitors of tau internalization. We identified three VHH inhibitors of tau uptake: A31, H3-2, and Z70(mut1). These VHHs compete with the membrane protein LRP1, a major receptor mediating neuronal uptake of tau. A31 and Z70(mut1) bind to microtubule binding domain...

GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants. Our GWAS analysis replicates...

No abstract

Phylodynamic inference (PI) quantifies population dynamics and evolutionary trajectories using phylogenetic trees. Single-cell lineage tracing enables phylogenetic tree reconstruction for thousands of cells in multicellular organisms, facilitating PI at the cellular level. However, cell differentiation and somatic evolution challenge the direct application of existing PI frameworks to somatic tissues. We introduce scPhyloX, a computational framework modeling structured cell populations by...

Dysregulated chromatin remodelers have emerged as critical disease targets. However, owing to the pleiotropic functions of chromatin remodelers, the underlying mechanisms of their effects on cancer have been difficult to elucidate. Here, we investigated the helicase lymphoid-specific (HELLS) oncogenic mechanism by identifying a new direct transcriptional target. Using loss or gain experiments, we identified Mitochondrial elongation factor 1 (MIEF1) as a critical target of the HELLS molecular...

Retrotransposable elements (RTEs) are interspersed repetitive sequences that represent a large portion of eukaryotic genomes. Ancestral expansions of RTEs directly contributed to the shaping of these genomes and to the evolution of different species, particularly mammals. RTE activity is tightly regulated by different epigenetic mechanisms but this control becomes compromised as cells age and RTEs are reactivated. This dysregulation of RTEs leads to perturbation of cell function and organ and...

CONCLUSIONS: High-quality trials are needed to clarify the neurobiological impact of music-making, particularly in MCI populations.

This study aimed to investigate the relationship between total antioxidant capacity (TAC) and phenotypic age acceleration (PhenoAgeAccel), a measure of accelerated biological aging, using data from the National Health and Nutrition Examination Survey (NHANES). Data from the 2003-2010 NHANES surveys, encompassing 16,395 participants, were analyzed. Principal component analysis (PCA) was used to reduce data dimensionality. Multivariate logistic regression models were employed to evaluate the...

CONCLUSIONS: Our findings suggest that PA is associated with a better health-related QOL. However, no association was observed between PA and psychological well-being in this population. We found that calisthenics were the most commonly performed and that more physically active older adults performed several types of exercises/sports in addition to calisthenics and walking for longer durations. Since few studies have investigated the types of exercises/sports in this age group, these findings...

The number of patients requiring dialysis therapy continues to increase worldwide because of the lack of effective treatments for chronic kidney disease (CKD). Furthermore, no curative treatments for acute kidney injury (AKI) have been established. The therapeutic effects of human induced pluripotent stem cell-derived nephron progenitor cells (hiPSC-NPCs) on AKI have been reported in mice but not clinically confirmed. There are also no reports examining the therapeutic potential of hiPSC-NPCs on...

CONCLUSIONS: In cohort studies conducted in the United States and Europe, greater wealth was associated with lower mortality, and the association between wealth and mortality appeared to be more pronounced in the United States than in Europe.