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Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1<sup>+</sup> microglia

6 months ago
Microglia and border-associated macrophages (BAMs) are critical for brain health, and their dysfunction is associated to disease. Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Here, we demonstrate that monocytes can efficiently replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably...
Jonathan Bastos

CLU alleviates Alzheimer's disease-relevant processes by modulating astrocyte reactivity and microglia-dependent synaptic density

6 months ago
Genetic studies implicate clusterin (CLU) in the pathogenesis of Alzheimer's disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased nuclear factor κB (NF-κB)-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia-dependent modulation of extracellular apolipoprotein E (APOE) and phosphorylated tau, as well as increased microglial...
Alexandra M Lish

Synaptic vesicle-omics in mice captures signatures of aging and synucleinopathy

6 months ago
Neurotransmitter release occurs through exocytosis of synaptic vesicles. α-Synuclein's function and dysfunction in Parkinson's disease and other synucleinopathies is thought to be tightly linked to synaptic vesicle binding. Age is the biggest risk factor for synucleinopathy, and ~15% of synaptic vesicle proteins have been linked to central nervous system diseases. Yet, age- and disease-induced changes in synaptic vesicles remain unexplored. Via systematic analysis of synaptic vesicles at the...
Virginia Gao

Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1<sup>+</sup> microglia

6 months ago
Microglia and border-associated macrophages (BAMs) are critical for brain health, and their dysfunction is associated to disease. Replacing brain macrophages holds substantial therapeutic promise but remains challenging. Here, we demonstrate that monocytes can efficiently replace all brain macrophages. Monocytes readily replaced embryonal BAMs upon their depletion and engrafted as monocyte-derived microglia (Mo-Microglia) upon more sustained niche availability. Mo-Microglia expanded comparably...
Jonathan Bastos

Inducing mechanical self-healing in polymer glasses

6 months ago
Polymer glasses such as the plastics used in pipes, structural materials, and medical devices are ubiquitous in daily life. The nature of their low molecular mobility is still poorly understood and it leads to brittle mechanical behavior, damage, and fracture over time. It also prevents the design of self-healing mechanisms that expand the material's lifespan, as more commonly done in recent years for higher mobility amorphous polymers such as gels and rubbers. We demonstrate through numerical...
José Ruiz-Franco

Aging promotes reactivation of the Barr body at distal chromosome regions

6 months ago
Decades ago, evidence of age-related reactivation of a single gene on the female inactive X chromosome was observed in mice. While stable silencing of the Barr body is crucial for balancing gene dosage between sexes, it remains unclear whether silencing is maintained during aging. Here we used allele-specific multi-omics approaches to capture a comprehensive catalog of genes escaping X chromosome inactivation throughout mouse development and aging. We found substantially elevated escape rates...
Sarah Hoelzl

Global genetic diversity of human gut microbiome species is related to geographic location and host health

6 months ago
The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to...
Sergio Andreu-Sánchez

NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging

6 months ago
Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide...
Sabina Chubanava

All-Cause Acute Illness Hospitalisations in the Preceding Two Years Are Associated With Cognitive Decline in Older Adults: The Sydney Memory and Ageing Study

6 months ago
CONCLUSIONS: This study confirms and adds nuance to international findings that overnight hospitalization is associated with accelerated cognitive decline. This association was dose-dependent, had a recency effect and was independent of illness severity in the case of cLOS. These findings suggest that all-cause acute hospitalization may be a reversible risk factor for cognitive decline. This needs further clarification and the development of interventions to minimise the impact of acute illness...
Lucia Chinnappa-Quinn

Geriatric-led transitional care for older adults discharged from the emergency department: impact on hospital readmissions and disability. Protocol for the controlled prospective quasi-experimental study LASUITE

6 months ago
BACKGROUND: Even when older people are discharged directly home after an emergency department (ED) visit, the risk of deterioration of health status and loss of independence persists. We hypothesize that among older adults discharged from the ED, hospital-community transition care provided by geriatric mobile teams (GMTs) may reduce the early readmission rate and level of disability. Such approaches have rarely been evaluated and cannot be generalized yet. Providing evidence of the positive...
Manuel Sanchez