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Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes

1 month 2 weeks ago
While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In...
Jing L Guo

Diagnosis of Alzheimer's disease using plasma biomarkers adjusted to clinical probability

1 month 2 weeks ago
Recently approved anti-amyloid immunotherapies for Alzheimer's disease (AD) require evidence of amyloid-β pathology from positron emission tomography (PET) or cerebrospinal fluid (CSF) before initiating treatment. Blood-based biomarkers promise to reduce the need for PET or CSF testing; however, their interpretation at the individual level and the circumstances requiring confirmatory testing are poorly understood. Individual-level interpretation of diagnostic test results requires knowledge of...
Joseph Therriault

Root cap cell corpse clearance limits microbial colonization in <em>Arabidopsis thaliana</em>

1 month 2 weeks ago
Programmed cell death occurring during plant development (dPCD) is a fundamental process integral for plant growth and reproduction. Here, we investigate the connection between developmentally controlled PCD and fungal accommodation in Arabidopsis thaliana roots, focusing on the root cap-specific transcription factor ANAC033/SOMBRERO (SMB) and the senescence-associated nuclease BFN1. Mutations of both dPCD regulators increase colonization by the beneficial fungus Serendipita indica, primarily in...
Nyasha Charura

Recommendations and quality of multimorbidity guidelines: A systematic review

1 month 2 weeks ago
CONCLUSION: The methodological and reporting quality of multimorbidity guidelines were suboptimal. The recommendations of these guidelines covered primarily the management process of multimorbid patients. Future guidelines should pay more attention to the scientific quality of the development methodology and the feasibility of implementing the guidelines in practice.
Zijun Wang

Plasma proteomics-based brain aging signature and incident dementia risk

1 month 2 weeks ago
Investigating brain-enriched proteins with machine learning methods may enable a brain-specific understanding of brain aging and provide insights into the molecular mechanisms and pathological pathways of dementia. The study aims to analyze associations of brain-specific plasma proteomic aging signature with risks of incident dementia. In 45,429 dementia-free UK Biobank participants at baseline, we generated a brain-specific biological age using 63 brain-enriched plasma proteins with machine...
Minghao Kou

HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling

1 month 2 weeks ago
Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1. We find that hsf-1 overexpression leads to transcriptional downregulation of all components of the CDC-48-UFD-1-NPL-4 complex, which is central to both endoplasmic reticulum and...
Annmary Paul Erinjeri

Factors associated with a high level of suicide risk among patients with late-life depression: a cross-sectional study from a tertiary psychiatric hospital in Guangzhou China

1 month 2 weeks ago
CONCLUSION: This study found that LLD patients with severe depression-anxiety, low activation, normal cognitive function, involuntary admission, and strong objective support exhibited a high level of suicide risk. These patients should receive intensified monitoring and comprehensive measures should be implemented to prevent the occurrence of suicidal behaviors during hospitalization.
Fei Liu