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Funding multiyear grants up front will sharply cut number of investigators receiving awards

Analysis of DNA from 23andMe users points to variants in genes linked to brain function and sense of rhythm

Imminent termination of the RV Nathaniel B. Palmer shocks polar scientists

Tail feathers can emit narrow beams of light, a first in the animal kingdom

Age-related structural and functional deterioration of the kidneys is common among elderly individuals and contributes to increased mortality and morbidity. Mitochondrial dysfunction and cellular senescence are two hallmarks of aging that drive a progressional renal decline; however, the underlying molecular mechanisms and endogenous regulators behind these processes remain incompletely understood. The metabolism of polyunsaturated fatty acids by CYP450 enzymes produces numerous bioactive lipid...

Benign prostatic hyperplasia (BPH) is an age-related condition characterized by progressive prostate enlargement driven in part by the accumulation of senescent epithelial cells and their pro-inflammatory secretome. Using human single-cell RNA sequencing and laser capture microdissection, we identified C-X-C Motif Chemokine Ligand 13 (CXCL13) as a key chemokine secreted by senescent prostate epithelial cells. CXCL13 recruits CD4^(+) T cells via the C-X-C Chemokine Receptor Type 5 (CXCR5)...

Background Minor and major neurocognitive disorders, depression, and anxiety are common in older adults. The brain and specifically the aging brain, relies heavily on oxygen and is highly sensitive to reductions in oxygen availability. Hypoxia occurs during both acute and prolonged exposure to altitude. While the negative effects of very low oxygen levels at high altitudes (above 3500 m) on cognition and symptoms of depression as well as anxiety are well-documented, we propose that moderate...

Germline genetic architecture of Alzheimer's disease (AD) indicates microglial mechanisms of disease susceptibility and outcomes. However, the mechanisms enabling protective microglial responses remain elusive. Here, we investigate the role of microglial ADGRG1, an adhesion G-protein-coupled receptor (aGPCR) specifically expressed in yolk-sac-derived microglia, in AD pathology using the 5xFAD mouse model. Transcriptomic analyses reveal that ADGRG1 activates the transcription factor MYC, leading...

This study explores the potential of adeno-associated virus serotype 9 (AAV9) to deliver therapeutic genes directly into the memory circuit throughout the olfactory bulb (OB), a critical memory and sensory processing region. Using convection-enhanced delivery (CED) of AAV9 encoding green fluorescent protein (GFP), we mapped the extensive neural connectivity from the OB to key memory-related brain regions, including the entorhinal cortex (EC) and hippocampus. Our findings reveal significant...

Deficits in the autophagy-lysosomal pathway facilitate intracellular microtubule associated protein tau (MAPT) accumulation in Alzheimer disease (AD). Aerobic exercise (AE) has been recommended as a way to delay and treat AD, but the exact effects and mechanisms have not been fully elucidated. Here, we found that AE (8-week treadmill running, 40 min/day, 5 days/week) alleviated autophagy-lysosomal defects and MAPT pathology through the activation of β2-adrenergic receptors (β2-AR) in MAPT P301L...

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Polygenic risk scores (PRSs) predict an individual's genetic risk for complex diseases, yet their utility in elucidating disease biology remains limited. We introduce scPRS, a graph neural network-based framework that computes single-cell-resolved PRSs by integrating reference single-cell chromatin accessibility profiles. scPRS outperforms traditional PRS approaches in genetic risk prediction, as demonstrated across multiple diseases including type 2 diabetes, hypertrophic cardiomyopathy,...

Proteins are the cornerstone of life. However, the proteomic blueprint of aging across human tissues remains uncharted. Here, we present a comprehensive proteomic and histological analysis of 516 samples from 13 human tissues spanning five decades. This dynamic atlas reveals widespread transcriptome-proteome decoupling and proteostasis decline, characterized by amyloid accumulation. Based on aging-associated protein changes, we developed tissue-specific proteomic age clocks and characterized...