OST Catalytic Subunit Redundancy Enables Therapeutic Targeting of N-Glycosylation.

Protein asparagine (N)-glycosylation, which promotes folding and trafficking of cell surface receptors such as the EGFR, has not been considered a viable target in oncology due to the essential and non-redundant enzymatic activities required for glycan synthesis and transfer. In mammals an exception to this rule is the presence of the oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A and STT3B. Here we delineate the chemical biology of OST inhibitors and develop an approach for limited inhibition of N-glycosylation optimized for downstream effects on EGFR.

Comparative lifespan and healthspan of nonhuman primate species common to biomedical research.

There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Sex-specific Kaplan-Meier survival curves were computed in 12 translational aging models: baboon, bonnet macaque, chimpanzee, common marmoset, coppery titi monkey, cotton-top tamarin, cynomolgus macaque, Japanese macaque, pigtail macaque, rhesus macaque, squirrel monkey, and vervet/African green. After employing strict inclusion criteria, primary results are based on 12,269 NHPs that survived to adulthood and died of natural/health-related causes.

Chemical entity normalization for successful translational development of Alzheimer's disease and dementia therapeutics.

Background: Identifying chemical mentions within the Alzheimer's and dementia literature can provide a powerful tool to further therapeutic research. Leveraging the Chemical Entities of Biological Interest (ChEBI) ontology, which is rich in hierarchical and other relationship types, for entity normalization can provide an advantage for future downstream applications. We provide a reproducible hybrid approach that combines an ontology-enhanced PubMedBERT model for disambiguation with a dictionary-based method for candidate selection.

Medial Amygdalar Tau Is Associated With Mood Symptoms in Preclinical Alzheimer's Disease.

Background: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms.

Methods: We examined 598 individuals (347 amyloid positive [58% female], 251 amyloid negative [62% female] subset in tau positron emission tomography and functional magnetic resonance imaging cohorts) from the A4 (Anti-Amyloid Treatment in Asymptomatic AD) Study.