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The CD1 system responds to lipids, not proteins, driving reactions to bee stings, bacteria, and possibly poison ivy

Agency director announces literature search tool, other plans to improve reliability of science findings

A major Swedish study of 3.7 million people has found that rare TORCH infections passed from a pregnant woman to the fetus are linked to much higher risks of autism and intellectual disability later in life. Children with a congenital TORCH infection were about three times more likely to be diagnosed with autism, more than seven times more likely to have an intellectual disability, and up to 30 times more likely to have severe to profound intellectual disability.

A topical drug that removes aging, damaged cells helped older mice heal skin wounds significantly faster. The treatment appeared to reactivate repair pathways involved in inflammation, collagen production, and new blood vessel growth.

Study reignites debate over what, if anything, machines can feel

Alzheimer's disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on population-scale single-nucleus RNA-seq data, with cross-cohort validation across multiple cohorts comprising over 1900 individual brains, capturing donor-level cell type interactions and gene regulatory networks. Using a...

Advances in single-cell and -nucleus transcriptomics have enabled generation of increasingly large-scale datasets from hundreds of subjects and millions of cells. These studies promise to give unprecedented insight into the cell type specific biology of human disease. Yet performing differential expression analyses across subjects remains difficult due to challenges in statistical modeling of these complex studies and scaling analyses to large datasets. Our open-source R package dreamlet (...

Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited^(1,2). Here, to gain deeper insights into the aetiology of different brain diseases, we used specimens from 1,494 unique donors to generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, comprising over 6.3 million individual...

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. Here we present a comprehensive, single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384...

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The complexity of Alzheimer's disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-nucleus RNA sequencing dataset comprising over 6 million nuclei from the prefrontal cortex of >1,000 individual brains, covering a variety of disease phenotypes. Here, leveraging this dataset, we developed a computational...

Nearly a century ago, restricting diet during early-life periods was suggested to extend lifespan in rats and in Daphnia^(1,2). The effect of juvenile diet on adult physiology and lifespan has subsequently been described in other model organisms, including fruit flies^(3-5) and mice^(6-8); however, its mechanism remains poorly understood. Here, using Drosophila as a model, we show that restricting protein intake during the larval stage (early-life protein restriction; ePR) promotes adult...

Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes that are crucial for physiological homeostasis and ageing¹. mTORC1 preferentially regulates the translation of 5'-terminal oligopyrimidine (TOP) motif-containing mRNAs (which encode mainly ribosomal proteins) through the 4E-BP translational repressor²; however, this function of mTORC1 is resistant to rapamycin inhibition³. TOP mRNAs are exceptionally abundant, and thus impose a...

Centuries ago, Thomas Sydenham famously wrote, "A man is as old as his arteries", highlighting the importance of the vasculature for health and healthy aging. Here, we review recent developments in vascular aging research, focusing on how microvascular aging drives tissue dysfunction and the emerging therapeutic opportunities for vascular rejuvenation. Although macrovascular aging has long been studied, microvascular aging remains an emerging frontier. Recent single-cell and multiomic...

Changes in cell type composition play an important role in human health and disease. Recent advances in single-cell technology have enabled the measurement of cell type composition at increasing cell lineage resolution across large cohorts of individuals. Yet this raises new challenges for statistical analysis of these compositional data to identify changes in cell type frequency. We introduce crumblr ( DiseaseNeurogenomics.github.io/crumblr ), a scalable statistical method for analyzing count...

Disrupted rest-activity rhythms have been associated with aging and chronic disease, yet longitudinal evidence from free-living populations has been lacking. Here we integrate multi-year Fitbit activity data from the All of Us Research Program with clinical biomarker-derived PhenoAge from 2,222 participants (8,447 person-years). Through high-dimensional digital phenotyping, we show that circadian rest-activity rhythm intensity, timing, and stability are associated with biological aging...

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease^(1,2). Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal ageing and its relationship to psychiatric and neurodegenerative disorders. The dorsolateral prefrontal cortex has a central role in higher cognitive functions and is particularly sensitive to age-related decline³,...

Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited^(1,2). Here, to gain deeper insights into the aetiology of different brain diseases, we used specimens from 1,494 unique donors to generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, comprising over 6.3 million individual...

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