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Science, Volume 387, Issue 6741, Page 1418-1424, March 2025.

Science, Volume 387, Issue 6741, Page 1397-1401, March 2025.

Science, Volume 387, Issue 6741, Page 1391-1397, March 2025.

Science, Volume 387, Issue 6741, Page 1360-1360, March 2025.

Science, Volume 387, Issue 6741, Page 1359-1359, March 2025.

A mutation that should have cut a protein short instead makes it more sensitive to the stress of exercise

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Synaptic Rho guanosine triphosphatase (GTPase) guanine nucleotide exchange factors (RhoGEFs) play vital roles in regulating the activity-dependent neuronal plasticity that is critical for learning. Ephexin5, a RhoGEF implicated in the etiology of Alzheimer's disease and Angelman syndrome, was originally reported in neurons as a RhoA-specific GEF that negatively regulates spine synapse density. Here, we show that Ephexin5 activates both RhoA and Cdc42 in the brain. Furthermore, using live imaging...

CONCLUSION: The prevalence of VI is high older (> 55 years) adults in Cameroon, with clear differences between men and women. The oldest individuals, and women appear to be most vulnerable. The identification of at-risk groups/persons through this cross-sectional study should make it possible to adapt public health strategies to contribute to the WHO objective of healthy ageing.

Ankle proprioception and attentional resources are crucial for maintaining balance and safely driving. However, research exploring the age-related integrity of ankle proprioception has yielded conflicting results, while the attentional demand of proprioceptive processing in seniors remains underexplored. We investigated how aging affects the interaction between proprioception and attention in healthy sedentary adults using a novel dual-task paradigm. Sedentary old and young adults performed an...

N⁴-acetylcytidine (ac⁴C) is deposited on diverse RNAs by N-acetyltransferase 10 (NAT10), a protein with high biological relevance for aging and cancer. We performed a comprehensive survey of ac⁴C using metabolic labeling, sodium cyanoborohydride chemical treatment coupled to next-generation sequencing (NGS), and ac⁴C antibody-based cell and molecular biology techniques. Our analysis shows that NAT10-dependent ac⁴C-acetylation is robust in rRNA and specific tRNAs but low/spurious in mRNA. It also...

Osteoarthritis (OA) is a prevalent joint disease characterized by pain, disability, and loss of physical function, posing a challenge to public health. However, molecular mechanisms of OA pathogenesis have not been fully described. We report that tripartite motif containing 15 (TRIM15) is a regulator in chondrocyte senescence and OA. Our study revealed heightened expression of TRIM15 in chondrocytes of senescent cartilage from patients with OA and in aged wild-type mice. Using gain- and...

Despite remarkable progress in the biomarker field in recent years, local validation of plasma biomarkers of Alzheimer's disease (AD) and dementia is still lacking in Latin America. In this longitudinal cohort study of 145 elderly Brazilians, we assess the diagnostic performance of plasma biomarkers, based on clinical diagnosis and CSF biomarker positivity. Follow-up data of up to 4.7 years were used to determine performance in predicting diagnostic conversions. Participants were clinically...

The amyloid hypothesis has been a leading narrative concerning the pathophysiological foundation of Alzheimer's and Parkinson's disease. At the two ends of the hypothesis lie the functional protein monomers and the pathology-defining amyloid fibrils, while the early stages of protein aggregation are populated by polymorphic, transient and neurotoxic oligomers. As the structure and activity of oligomers are intertwined, here we show oligomers arising from liquid-liquid phase separation and...