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Stress-induced nucleolar rejuvenation via chaperone-mediated segregation in a filamentous fungus

2 weeks 4 days ago
How the nucleolus recovers from acute proteostatic stress, particularly in multinucleate syncytia, remains poorly understood. In the highly polarized hyphae of the model filamentous fungus Magnaporthe oryzae, we uncover a novel stress-induced spatial quality control pathway that promotes the inheritance of rejuvenated nucleolar material during nuclear division. This pathway discriminates between newly formed and damaged nucleolar compartments, selectively partitioning and sequestering the...
Audra M Rogers

scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies

2 weeks 4 days ago
Transcriptome-wide association studies (TWAS) have successfully identified genes associated with complex traits and diseases, but most have been performed using bulk gene expression data, which aggregate signals across heterogeneous cell types. Population-scale single-cell RNA sequencing data now make it possible to perform TWAS at the cell-type resolution, but present unique challenges due to strong noises, technical variations, and high sparsity. Here, we propose scTWAS, a statistical method...
Zhaotong Lin

Testing the redox theory of aging under parasitism

2 weeks 4 days ago
The redox theory of aging proposes that an oxidative imbalance, possibly amplified by infection, drives senescence. We experimentally evolved mosquitoes under early or late reproduction with or without parasite exposure, and quantified longevity, fecundity, and redox markers. Although selection generated the expected life-history divergence, there was only a poor, non-linear association between a redox gradient and longevity. Thus, oxidative stress contributed to, but did not determine, the...
Luís M Silva

The REDD1-NF-kappaB-miRNAs-eNOS/SIRT1 axis mediates obesity-induced endothelial cell senescence and hypertension

2 weeks 4 days ago
Vascular dysfunction, including endothelial cell (EC) senescence and hypertension, is a hallmark of metabolic syndrome, yet its underlying mechanisms remain unclear. Here, we show that metabolic stress upregulates regulated in development and DNA damage response 1 (REDD1), driving vascular dysfunction. Overexpression of REDD1, but not the REDD1^(KK219/220AA) mutant, which cannot activate atypical NF-κB, promotes EC senescence and hypertension through NF-κB-dependent induction of miR-155-5p and...
Yoon Kyung Choi

Recycling senescent cell lipids for targeted senotherapy

2 weeks 4 days ago
Senescent cells (SnCs) are increasingly recognized as key contributors to osteoarthritis, with conventional strategies centered on their elimination. However, senolytic approaches face mounting limitations, driving the need for refined interventions. Here, we exploit SnCs' lipid metabolic signature to develop a senotherapeutic strategy. Given the universal lipid accumulation in SnCs and the dual role of lipids as both metabolic liabilities and essential lubricants, we engineer an injectable...
Xiaoxiao Ji

Age-related variations of the hemodynamic response function spatially resolved across human cerebral cortex

2 weeks 4 days ago
Normal aging leads to regional vascular and neural alterations. Age-related impairments in neurovascular coupling (NVC) affect the blood-oxygen-level-dependent (BOLD) hemodynamic response function (HRF) measured with functional magnetic resonance imaging, causing changes in both amplitude and temporal dynamics. Previously, global, systematic age-related changes in HRF characteristics were demonstrated, consistent with known microvascular aging effects. In this follow-up study, a standard space...
Nooshin J Fesharaki