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Scientists discover how gut bacteria “train” the intestine to fight inflammation

2 weeks ago
A compound made when gut bacteria break down dietary fiber may do more than briefly calm inflammation—it could leave a lasting protective “memory” in the gut. Northwestern Medicine researchers found that butyrate can reprogram intestinal lining cells so they continue encouraging anti-inflammatory immune responses even after the compound is gone. In mice, this effect boosted production of the immune-calming molecule IL-10 and reduced the severity of colitis-like disease.

Schizophrenia’s lost brain connections follow a surprising pattern

2 weeks ago
Specialized brain scans reveal that schizophrenia is linked to widespread loss of the synapses that connect brain cells, with the left side of the brain hit especially hard. The damage follows a surprisingly organized pattern tied to the brain’s chemistry and wiring. Researchers also identified a left frontal region that may serve as a starting point for the loss.

The hallmarks of skeletal muscle health

2 weeks ago
Skeletal muscle is a central determinant of organismal health. Preserving muscle quality is therefore critical for preventing disease and sustaining quality of life across the lifespan. Despite its central role, the field lacks a unifying framework that defines the core properties of skeletal muscle health. Here, we propose a conceptual framework for muscle homeostasis built around seven interconnected hallmarks-metabolism and bioenergetics, proteostasis, genomics, excitability, structure,...
Anna Vainshtein

Inhibiting cyclin D1-CDK6 suppresses senescence-associated inflammatory gene expression and age-related functional decline

2 weeks ago
Cellular senescence contributes to aging and age-related diseases by driving chronic inflammation through the senescence-associated secretory phenotype (SASP), including interferon-stimulated genes (ISGs). Here we confirm and extend previous observations that cyclin D1 (CCND1), a key cell cycle regulator, is paradoxically upregulated across models of nonproliferating senescent cells. We show that CCND1 and its kinase partner CDK6 drive SASP and ISG expression in senescent cells by promoting DNA...
Adarsh Rajesh

STINGing the brain: S-nitrosylation drives neuroinflammation in Alzheimer's disease

2 weeks ago
Neuroinflammation is a major secondary driver of Alzheimer's disease (AD). In this issue of Cell Chemical Biology, Carnevale et al.¹ demonstrate that S-nitrosylation of the cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway sustains pathological neuroinflammation in AD, identifying a promising therapeutic target for this devastating disease.
Andrew A Pieper

Risk of transmission of amyloid β pathology via transfused blood products

2 weeks ago
Seeded protein misfolding and aggregation are relevant to many neurodegenerative diseases. The archetype are prions: protein-only infectious agents that cause fatal neurodegenerative diseases including Creutzfeldt-Jakob disease (CJD). The recent recognition of iatrogenic amyloid β cerebral amyloid angiopathy (CAA) and Alzheimer's disease, caused by inadvertent seeding of amyloid β pathology following historical medical procedures, raises concerns that these conditions might also be transmitted...
Gargi Banerjee

Neurodegeneration as a dysregulation of neuroimmune crosstalk

2 weeks ago
Neurodegeneration is increasingly recognized not only as a disorder of neurons but also as a breakdown of dialogue between the nervous and immune systems. Recent discoveries reveal that immune cells and inflammatory signals are deeply interwoven with brain function across the lifespan. Far from passive responders, immune cells act as sentinels and shapers of neuronal resilience, vulnerability, and repair. Together, robust data support a model in which neurodegeneration emerges from complex...
F Chris Bennett

Multimodal evidence for bone lymphatics in skeletal health and repair

2 weeks ago
Previous studies predominantly associated lymphatics with skeletal disease and bone loss. However, building on our work, bone lymphatics are emerging as a paradigm-shifting component of the skeletal microenvironment, illustrating their role as positive regulators of bone mass and repair. Here, we present a comprehensive analysis integrating spatial transcriptomics, single-cell RNA sequencing, and imaging across murine and human bones. Spatial transcriptomics identifies Prox1^(+) endothelial...
Yang Yang

Making zombies to kill cancer

2 weeks ago
Genotoxic drugs induce apoptosis-resistant senescent "zombie" cells. In this issue of Cell Chemical Biology, Gallagher Aldave et al.¹ show that these cells acquire dependence on BCL-xL and MCL-1, creating a therapeutic vulnerability to their inhibitors and degraders.
Tudor Moldoveanu

Cell-type-specific damage scores reveal kidney and liver disease trajectories in single-cell and spatial transcriptomics

2 weeks ago
Degenerative diseases progress through gradual cell-intrinsic damage that is difficult to resolve with bulk transcriptomics or discrete cell-state analysis. We introduce a generalizable single-cell and spatial transcriptomics framework that quantifies continuous damage trajectories in vivo using cell-type-specific scores. Applied to chronic kidney disease and metabolic dysfunction-associated steatotic liver disease, the podocyte damage score (PDS) and hepatocyte damage score (HDS) place...
Tsimafei Padvitski