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Phage predation, disease severity, and pathogen genetic diversity in cholera patients
Science, Volume 384, Issue 6693, April 2024.
Africa intensifies battle against mpox as ‘alarming’ outbreaks continue
New variant identified in Congolese mining town renews worries about global spread
Where did Earth’s oddball ‘quasi-moon’ come from? Scientists pinpoint famed lunar crater
Impact that created the asteroid also blasted out the famous Giordano Bruno crater
Daring ‘James Bond’ mission to drill Antarctic ice cores could reveal future of sea level rise
To understand vulnerable glaciers, climate scientists extract ice from continent’s remote and stormy coast
Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated...
Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain
Alzheimer's disease (AD) and dementia in general are age-related diseases with multiple contributing factors, including brain inflammation. Microglia, and specifically those expressing the AD risk gene TREM2, are considered important players in AD, but their exact contribution to pathology remains unclear. In this study, using high-throughput mass cytometry in the 5×FAD mouse model of amyloidosis, we identified senescent microglia that express high levels of TREM2 but also exhibit a distinct...
LKRSDH-dependent histone modifications of insulin-like peptide sites contribute to age-related circadian rhythm changes
To understand aging impact on the circadian rhythm, we screened for factors influencing circadian changes during aging. Our findings reveal that LKRSDH mutation significantly reduces rhythmicity in aged flies. RNA-seq identifies a significant increase in insulin-like peptides (dilps) in LKRSDH mutants due to the combined effects of H3R17me2 and H3K27me3 on transcription. Genetic evidence suggests that LKRSDH regulates age-related circadian rhythm changes through art4 and dilps. ChIP-seq analyzes...
Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila
Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated...
Identification of senescent, TREM2-expressing microglia in aging and Alzheimer's disease model mouse brain
Alzheimer's disease (AD) and dementia in general are age-related diseases with multiple contributing factors, including brain inflammation. Microglia, and specifically those expressing the AD risk gene TREM2, are considered important players in AD, but their exact contribution to pathology remains unclear. In this study, using high-throughput mass cytometry in the 5×FAD mouse model of amyloidosis, we identified senescent microglia that express high levels of TREM2 but also exhibit a distinct...
LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD(+) depletion
Although dysregulated cholesterol metabolism predisposes aging tissues to inflammation and a plethora of diseases, the underlying molecular mechanism remains poorly defined. Here, we show that metabolic and genotoxic stresses, convergently acting through liver X nuclear receptor, upregulate CD38 to promote lysosomal cholesterol efflux, leading to nicotinamide adenine dinucleotide (NAD^(+)) depletion in macrophages. Cholesterol-mediated NAD^(+) depletion induces macrophage senescence, promoting...
Towards prolonging ovarian reproductive life: Insights into trace elements homeostasis
Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal...
Aging as a loss of morphostatic information: A developmental bioelectricity perspective
Maintaining order at the tissue level is crucial throughout the lifespan, as failure can lead to cancer and an accumulation of molecular and cellular disorders. Perhaps, the most consistent and pervasive result of these failures is aging, which is characterized by the progressive loss of function and decline in the ability to maintain anatomical homeostasis and reproduce. This leads to organ malfunction, diseases, and ultimately death. The traditional understanding of aging is that it is caused...
Parkinsonism Sac domain mutation in Synaptojanin-1 affects ciliary properties in iPSC-derived dopaminergic neurons
Synaptojanin-1 (SJ1) is a major neuronal-enriched PI(4, 5)P(2) 4- and 5-phosphatase implicated in the shedding of endocytic factors during endocytosis. A mutation (R258Q) that impairs selectively its 4-phosphatase activity causes Parkinsonism in humans and neurological defects in mice (SJ1^(RQ)KI mice). Studies of these mice showed, besides an abnormal assembly state of endocytic factors at synapses, the presence of dystrophic nerve terminals selectively in a subset of nigro-striatal dopamine...
Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence
Telomeres, TTAGGGn DNA repeat sequences located at the ends of eukaryotic chromosomes, play a pivotal role in aging and are targets of DNA damage response. Although we and others have demonstrated presence of short telomeres in genetic cardiomyopathic and heart failure cardiomyocytes, little is known about the role of telomere lengths in cardiomyocyte. Here, we demonstrate that in heart failure patient cardiomyocytes, telomeres are shortened compared to healthy controls. We generated isogenic...
Daily briefing: ‘Goldene’ is a gilded cousin of graphene that is one atom thick
Nearly half of China’s major cities are sinking — some ‘rapidly’
Why queasiness kills hunger: brain circuit identified
Technological risks are not the end of the world
Science, Volume 384, Issue 6693, April 2024.