Rational design of disordered proteins for sequence–function investigation - Nature

GOOSE enables the design and testing of thousands of disordered protein region sequences to reveal distinct sequence-to-function relationships.

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Epigenetic and 3D genome reprogramming during the aging of the human hippocampus

Changes in gene expression have been observed in the aging human brain, but our understanding of the underlying regulatory mechanisms remains limited. To unravel these complexities, we analyzed single...

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Somatic mutations reveal the ontogeny of microglia in human aging - Nature

Nature - Somatic mutations reveal the ontogeny of microglia in human aging

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Efficient and precise programmable DNA knock-in without double-strand breaks - Nature

Kilobase-scale nickase-targeting (KNIT) editing enables single-nick-based DNA insertion across genomic loci and cell types, supporting insertion of DNA fragments exceeding 10 kb, with high effici...

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Mitochondrial metabolism and epigenetic crosstalk drive SASP - Nature

In senescent cells, mitochondria-derived acetyl-CoA promotes histone acetylation and increases chromatin accessibility at inflammatory gene loci. Inhibition of SLC25A1 attenuates these effects, unders...

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Alternate RNA decoding results in stable and abundant proteins in mammals - Nature

Alternate RNA decoding, an understudied process, leads to peptide sequence modifications that can have substantial functional effects on protein stability, tissue-specific proteomes and dise...

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Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch

Mammals display prominent diversity in the ability to regenerate damaged ear pinna, but the genetic changes underlying the failure of regeneration remain elusive. We performed comparative single-cell ...

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Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging

Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescen...

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Epiblast diversification and blood formation in a human pregastrula - Nature

High-resolution spatial transcriptome analysis of a human embryo at Carnegie stage 6 reveals three distinct developmental trajectories from the epiblast towards amnion, primitive streak and axial meso...

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Cerebellar aging is spatially heterogeneous and supports cognitive resilience in later life - Nature Neuroscience

The cerebellum ages unevenly, with some regions showing preservation that may help protect the brain from decline. The authors show that large cerebellar volume is associated with stronger cognitive r...

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Semaglutide attenuates neuroinflammation in male mice - Nature Communications

Semaglutide attenuates brain inflammation in mice, coordinately reversing inflammatory gene programs across diverse brain cell types likely engaging both neuronal circuits and peripheral immune respon...

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Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer’s disease pathogenesis

Microglia-mediated neuroinflammation drives Alzheimer’s disease progression. In this article, Liu et al. show that the histone acetyltransferase KAT7 promotes mitochondrial DNA-dependent inflammation ...

cell.com

Transcriptional profiles of immature neurons in aged human hippocampus track Alzheimer’s pathology and cognitive resilience

Tosoni and colleagues identify immature neurons in the aged human hippocampus with signatures of younger biological age and cellular fitness. Their molecular programs and intercellular interactions ar...

cell.com

Memory reactivation underlies experience-dependent adaptive regulation of sleep

Recent memories are consolidated during sleep by spontaneous reactivation. However, whether and how memory reactivation affects sleep dynamics remain unclear. By tracking and modulating memory activit...

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Human microglial transitions at the Aβ–tau inflection point associate with divergent pathways to dementia and resilience - Nature Medicine

Microglia cellular changes underlie divergent resilience-associated mechanisms in human aging.

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In vitro neurons learn and exhibit sentience when embodied in a simulated game-world

The DishBrain system is the first real-time synthetic biological intelligence platform that demonstrates that biological neurons can adjust firing activity in a way that suggests the ability to learn ...

cell.com

AhR inhibition promotes axon regeneration via a stress–growth switch - Nature

AhR functions as a neuronal brake on axon regeneration, integrating environmental sensing, protein homeostasis and metabolic signalling to control the balance between stress adaptation and axonal repa...

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Universal transcriptomic hallmarks of mammalian ageing and mortality - Nature

Integration of gene expression data from multiple tissues across four mammalian species reveals conserved transcriptomic signatures of mammalian ageing and mortality and uncovers the modular...

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Human haematopoietic stem cells remember inflammatory stress - Nature

Using xenograft inflammation–recovery models and single-cell multiomics, a haematopoietic stem cell population after inflammatory stress is identified.

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TranscriptFormer: A generative cell atlas across 1.5 billion years of evolution

Single-cell transcriptomics is revolutionizing our understanding of cellular diversity, yet comparing transcriptional programs across the tree of life remains challenging. We developed TranscriptForme...

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Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits in tauopathy mice - Nature Neuroscience

In PS19 mice, microglia-derived glycoprotein nonmetastatic melanoma protein B promotes mitochondrial extracellular vesicle secretion, enabling mitochondrial transfer to astrocytes. This improves astro...

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Decoding sequence determinants of gene expression in diverse cellular and disease states - Nature Methods

Decima learns to predict cell-type-specific gene expression based on DNA sequences, contributing to the analysis of gene regulation and design of context-specific regulatory elements.

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In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia | NEJM

Persons carrying loss-of-function variants of proprotein convertase subtilisin–kexin type 9 (PCSK9) have reduced levels of low-density lipoprotein (LDL) cholesterol and fewer atherosclerotic cardio...

nejm.org

An AI system to help scientists write expert-level empirical software - Nature

Nature - An AI system to help scientists write expert-level empirical software

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Lineage and organ signals sequentially build organ intrinsic nervous systems - Nature

Systems-level analyses of organ intrinsic nervous systems reveal that these networks are initially configured by lineage-dependent programmes, and their architecture and molecular identity are refined...

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Spatial proteomic analysis in human Alzheimer’s disease brains enables identification of microenvironment-dependent microglial cell states - Nature Neuroscience

Myeloid cells show marked heterogeneity in Alzheimer’s disease. This study introduces CODEX-CNS, a single-cell spatial proteomics pipeline, and identifies a human microglial subpopulation enriched in ...

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Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson’s disease models

A mitochondrial transplantation approach rescues mitochondrial deficiency and prevents mitochondrial DNA depletion syndrome, Leigh syndrome, and Parkinson’s disease in cellular and mouse models.

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Immune cells in the blood drive cognitive ageing — blocking them improves memory

Old T cells secrete an enzyme that can impair brain function in mice.

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Immune evasive DNA donors and recombinases license kilobase-scale writing - Nature

INSTALL overcomes fundamental challenges for DNA delivery and integration methods by synergizing immune-stealth nucleic acids with recombinases to enable kilobase-scale integration strategies without ...

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