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Amyloid precursor protein ortholog Appl acts with Vnd during mushroom body axon growth in Drosophila
The amyloid precursor protein (APP) is associated with Alzheimer's disease. Appl is the single Drosophila APP ortholog and is expressed in all neurons throughout development. Appl was previously shown to cell-autonomously modulate axon outgrowth in the mushroom bodies (MBs), the fly olfactory memory center. However, we found that Appld, the only reported null allele, affects the normal function of vnd, the gene just proximal to Appl. To decipher developmental and memory defects specifically due...
Ligand-Independent Activation of Notch1 by Cathepsin L Induces CUX1/p16(INK4a)-Dependent Endothelial Senescence Associated With Atherosclerosis
Our post-GWAS functional analysis revealed that cathepsin L (CTSL) is an upstream regulator of CUX1, and it induces p16^(INK4a)-dependent and atherosclerosis-associated senescence by indirectly activating CUX1 transcription in a process that requires its proteolytic activity. This suggests an unidentified transcription regulator between CTSL and CUX1, and CTSL-mediated cleavage of this regulator could transcribe CUX1, inducing senescence. Here, in search of this transcriptional regulator, we...
Personalized-Context-Aware Age Gap: A New Multi-Omics Measurement Based on Age-Enhanced Model AOE-Net for Aging Acceleration and Chronic Disease Risk Prediction
Aging is a global issue that affects human health and increases disease risk. The traditional concept of the "age gap (AG)," defined as the difference between estimated biological age and an individual's chronological age, has been used for self-monitoring the risk of age-related diseases. However, the current AG does not account for the stratified aging patterns across different stages of chronological age, which may lead to biased or paradoxical interpretations of aging acceleration. To...
Nuclear accumulation of PANK4 in hippocampal astrocytes aggravates cuproptosis in association with mild cognitive impairment in aged mice
CONCLUSION: This study identifies a novel pathological mechanism in age-related MCI: the nuclear accumulation of PANK4 in hippocampal exacerbates cuproptosis susceptibility by specifically impairing ATP7B-dependent copper efflux, leading to copper overload. Astrocyte-specific PANK4 ablation mitigates these effects, highlighting PANK4 as a potential therapeutic target for preventing or treating age-associated cognitive decline.
Stereoselective effects of nicotine enantiomers on the gut-brain axis and neuroinflammation in a mouse model of Parkinson's disease
INTRODUCTION: Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, neuroinflammation, and emerging evidence of gut microbiota dysbiosis. Although nicotine has been implicated in neuroprotection, whether its enantiomers exert stereoselective effects on the gut-brain axis remains unknown.
Brazil’s ‘rolling stone reefs’ teem with hidden diversity, DNA reveals
Vast offshore habitats face threats including mining, trawling, and drilling for oil
‘That could be a game changer’: antiviral pill gets first test for Ebola prevention
Researchers are preparing to launch an unprecedented trial to protect people exposed to Ebola in the DRC and Uganda