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Reconstructed cell-type-specific rhythms in human brain link Alzheimer's pathology, circadian stress, and ribosomal disruption

3 months 2 weeks ago
Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing (snRNA-seq) from post-mortem cortical samples, we informatically estimated the relative circadian phases of 409 persons with and without AD dementia, reconstructing circadian expression profiles across cell types. Although core clock rhythms were preserved in AD, many cell-type-specific circadian outputs were disrupted....
Henry C Hollis

Strategies to rescue mitochondria in Parkinson's disease: The significance of mitochondrial transfer

3 months 2 weeks ago
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal degeneration and pathological α-synuclein accumulation. Mitochondrial dysfunction is a central feature in PD pathogenesis, contributing to impaired bioenergetics, oxidative stress, neuroinflammation, and defective organelle communication. This review synthesizes the current understanding of mitochondrial quality control mechanisms, including fission, fusion, mitophagy, and biogenesis, and their...
Junhan Liang

Strengthening Africa's brain health and economic resilience

3 months 2 weeks ago
Africa stands at a decisive moment in which urgent action is essential to safeguard its brain health and economic stability. While Africa's population remains predominantly young, it is expanding and aging rapidly. This demographic shift is projected to drive a sharp rise in neurodegenerative diseases, including Alzheimer's, with profound health and economic costs-but brain health research, policy, funding and care across the continent remain critically underdeveloped. In this Perspective, we...
Mie Rizig

Composite transposons with bivalent histone marks function as RNA-dependent enhancers in cell fate regulation

3 months 2 weeks ago
Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in...
Ziqiang Zhou

Mitigating ion flux vortex enables reversible zinc electrodeposition

3 months 2 weeks ago
Metal anodes hold considerable promise for high-energy-density batteries but are fundamentally limited by electrochemical irreversibility caused by uneven metal deposition and dendrite formation, which compromise battery lifespan and safety. The chaotic ion flow (or ion flux vortex) near the electrode surface, driving these instabilities, has remained elusive due to limitations in conventional techniques such as scanning electron and atomic force microscopies, which are invasive and incapable of...
Yuhang Dai

Beyond the 900-day rule: Reclaiming healthspan as geroscience's primary goal

3 months 2 weeks ago
The recently proposed "900-day rule" in mouse aging studies-requiring lifespan extension over ultra-long-lived controls-aims to identify interventions that modulate intrinsic aging. While this standard raises scientific rigor, it may reduce relevance to how most organisms, including humans, actually age. In reality, aging unfolds under metabolically and immunologically stressful conditions-not in sterile, genetically uniform environments. Most people experience chronic inflammation, metabolic...
Stef F Verlinden

Strengthening Africa's brain health and economic resilience

3 months 2 weeks ago
Africa stands at a decisive moment in which urgent action is essential to safeguard its brain health and economic stability. While Africa's population remains predominantly young, it is expanding and aging rapidly. This demographic shift is projected to drive a sharp rise in neurodegenerative diseases, including Alzheimer's, with profound health and economic costs-but brain health research, policy, funding and care across the continent remain critically underdeveloped. In this Perspective, we...
Mie Rizig

Healthcare providers perspectives on HIV-NCD integration to Meet the needs of older adults living with HIV

3 months 2 weeks ago
CONCLUSION: The findings of this study highlight healthcare providers' perceived facilitators and barriers to the integration of NCD care into HIV care platforms. The insights gained from this study hold the potential to inform tailored interventions, policy decisions, and capacity-building initiatives aimed at fostering successful integration and improving overall health care delivery to meet the needs of OALWH in resource-constrained settings.
Jepchirchir Kiplagat

Transferrin receptor-targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA

3 months 2 weeks ago
Amyloid-related imaging abnormalities (ARIA), side effects of anti-amyloid drugs seen in magnetic resonance imaging of the brain, are a major safety concern in patients with Alzheimer's disease. We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-β protein (anti-Aβ) using asymmetrical Fc mutations (ATV^(cisLALA)) that mitigates TfR-related liabilities and retains effector function when bound to Aβ. Administration of...
Michelle E Pizzo

Reduction of TRAF3 by heterozygosity or aging impacts B cell function

3 months 2 weeks ago
TNF receptor-associated factor 3 (TRAF3) is a signaling adaptor protein that is ubiquitously expressed but has highly distinct cell type-specific functions. TRAF3 plays critical roles in restraint of B lymphocyte activation, differentiation, and homeostatic survival. Consistent with such roles, loss-of-function mutations in TRAF3 have long been found in various human B cell malignancies. Mice lacking TRAF3 specifically in B cells have autoimmune manifestations, lymphadenopathy, and increased...
Emma L Hornick

Protracted circum-continent subduction: A mechanism for craton destruction and a rationale for craton longevity

3 months 2 weeks ago
The evolution of continents is shaped by the growth and destruction of long-lived cratons, which serve as their stable cores. Processes for craton destruction are controversial because most invoked mechanisms occur frequently throughout Earth history, making the preservation of cratons for billions of years problematic. Here, we address this issue by presenting a crustal-scale analytical signal-amplitude model obtained from high-resolution airborne and shipborne magnetic data across cratons...
Xi Xu