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Beefy tracks point to a Cretaceous critter as big as a large dog or mountain lion

Knee osteoarthritis can seriously affect mobility and quality of life, but its progression isn’t completely out of your control. Exercise, stronger leg muscles, a healthier diet, and even modest weight loss can dramatically reduce stress on the knees and help keep pain in check.

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.

Discovery of lymphatic tubes suggested new possibilities for bone healing, but challenge has prompted dueling papers and publication delay in prominent journal

Novel rescue craft unable to connect with doomed Swift Observatory

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.

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...

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...

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...

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.

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...

Neurodegenerative diseases associated with ageing are characterized by progressive neuronal dysfunction and loss, yet effective disease-modifying therapies remain elusive. Increasing evidence indicates that mitochondrial dysfunction is not merely a downstream consequence of neurodegeneration but represents an early and active driver of disease initiation and progression. This review addresses this critical gap by establishing an integrated framework that systematically connects mechanistic...

Ageing is a fundamental biological process marked by declining physiological function and the accumulation of stress-induced damage. It contributes to chronic disease and drives widespread alterations across organ systems, including the vasculature. Ageing of the macro- and microvasculature impairs nutrient delivery, promotes tissue degeneration, and reduces repair capacity in many tissues, including those of the musculoskeletal system. Tendons and ligaments become increasingly injury-prone with...

Aging is associated with blood-brain barrier (BBB) breakdown and microvascular rarefaction, key contributors to cerebral neuroinflammation, hypoperfusion, and vascular cognitive impairment and dementia (VCID). Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore BBB integrity and enhance cerebrovascular function in aged mice, suggesting that circulating factors can rejuvenate the aging brain. However, the molecular mediators responsible for these effects...

While aging is the greatest risk factor for the development of neurodegenerative disease, the role of aging in these diseases is poorly understood. Our previous work has shown that targeting aging pathways can be neuroprotective in animal models of neurodegenerative disease. Based on these findings, we believe that by gaining insight into the aging process that knowledge can be applied to identify novel therapeutic targets for neurodegenerative disease. To advance our understanding of aging, we...

CONCLUSION: Improvements in neuropsychological status and subjective memory were associated with reduced resting MCAv following exercise training. These exploratory associations suggest that variability in cerebrovascular responses may relate to cognitive responses; however, without consistent group-level effects, findings should be interpreted cautiously and do not imply causality.

INTRODUCTION: Hippocampal atrophy is frequently observed in neurodegenerative diseases such as Alzheimer's disease (AD) or hippocampal sclerosis of aging (HS-aging). Volume loss in the hippocampus is described as prodromal stage of dementia and has been associated with AD polygenic risk score (PRS). CA1 and subiculum atrophy have been suggested to be a promising in vivo biomarker for HS-aging. Recent studies suggest that some loci associated with AD may be more related to other brain diseases...

Cognitive decline and neurodegenerative diseases are progressive, multifactorial conditions that may begin years before overt clinical diagnosis and reflect interactions among biological vulnerability, modifiable exposures, environmental determinants, and reduced brain resilience. This structured narrative review examines how artificial intelligence (AI) and machine learning (ML) can integrate clinical, biological, behavioral, and digital data to support earlier, personalized, and clinically...

Alzheimer's disease is now defined by underlying pathology, with elevated amyloid-beta (Aβ) sufficient for diagnosis in the absence of cognitive symptoms. We combined longitudinal magnetic resonance imaging and Aβ positron emission tomography data from three cognitively healthy cohorts to examine cortical thickness trajectories in individuals who later converted to Aβ-positive status, using magnetic resonance images acquired years before conversion. Individuals who subsequently developed...

Reference bias is an issue that affects most genomic studies analysing short reads mapped to a reference genome^(1,2). It can be mitigated by mapping to multiple haplotypes represented in a pangenome^(3-5). Here we introduce two new methods to address reference bias: Emblask for pangenome construction and Weaver for mapping to pangenomes at scale. Emblask is a hybrid long- and short-read haplotype-resolved dual assembly pipeline for parent-offspring trio data. Using Emblask, we assembled 698...