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Here, we review the history, advancements, and broad utility of the NTR/prodrug system, and suggest future strategies for developing versatile ablation models. As a chemogenetic tool, the nitroreductase (NTR)/prodrug system enables precise spatiotemporal control over cell ablation. The technology leverages bacterial NTR enzymes (e.g. nfsB) to convert inert prodrugs into cytotoxic agents, thereby allowing researchers to induce targeted cell death. Although the NTR/prodrug approach was first...

Magnesium is traditionally viewed as a permissive electrolyte required for cellular viability. Emerging evidence, however, reveals a more central role for Mg^(2+) as an active regulator of mitochondrial bioenergetics and metabolic resilience. In this Review, we synthesize recent advances in renal magnesium handling, mitochondrial Mg^(2+) transport, and MgATP chemistry to propose a unifying framework in which magnesium functions as a bioenergetic checkpoint. At the cellular level, Mg^(2+)...

Temporal prediction is the ability to anticipate the likely time of occurrence of events and is important for adaptive behaviour in our everyday lives. Studies indicated that predictive aspects of environmental stimuli can be leveraged to reduce reaction times and enhance stimulus processing. Particularly, a recent study showed that this optimized behaviour is associated with a phase adjustment of ongoing neural oscillations aligning with the expected onset of upcoming stimuli. In ageing, there...

Against the backdrop of an accelerating global aging population, the epidemiological correlation between cognitive impairment and osteoporosis has become increasingly prominent. These two conditions exhibit a profound pathological coupling mediated by the bidirectional regulatory network of the "bone-brain axis." The operation of this axis is rooted in an intricate neuro-skeletal signaling network involving hormonal dysregulation, systemic inflammatory cascades, and the aberrant regulation of...

Radar studies produce contradictory results, complicating efforts to gauge sea level rise in vulnerable areas

Unlike their modern counterparts, Atlas bears were strict vegetarians

Poll of nearly 500 scientists reveals how rapid surveys can take researchers’ pulse on controversial topics

A large study of older adults in Brazil found that adding extra salt at the table is still a common habit, especially among men. While too much salt is linked to serious health problems and faster cognitive decline, researchers discovered that women’s salt-shaking habits were tied more closely to lifestyle and diet.

For decades, pancreatic cancer has been one of the most lethal cancers, with few effective treatment options. A new drug, daraxonrasib, targets the KRAS mutation that fuels most pancreatic tumors—something many scientists once thought couldn't be done. In a major clinical trial, the treatment nearly doubled survival for patients with advanced disease and reduced the risk of death by 60%.

Letter also blames Trump for letting China surpass United States in research spending

Whether new neurons contribute to human cognition in old age remains debated. Recently in Cell Stem Cell, Tosoni et al.¹ show that immature-neuron transcriptional programs persist in the aged dentate gyrus and that their molecular state, not simply their abundance, tracks Alzheimer's pathology and cognitive resilience.

Impairments in axonal transport have been implicated in the pathogenesis of tauopathies, including frontotemporal dementia and Alzheimer's disease, yet the underlying mechanisms and reversibility of these deficits are largely unknown. In particular, the impacts of tau mutations, phosphorylation and aggregation on axonal transport in vivo remain controversial. By using two-photon imaging of axonal transport of BDNF granules in the mouse cortex, we reveal that deficits in axonal transport arise in...

Integrating spatial transcriptomics, which maps gene expression location within tissues, with single-cell multi-omics data, profiling gene expression and chromatin accessibility (or other epigenomic data) for the same cell, offers powerful insights into gene regulation. However, commercially available kits for simultaneous spatial multi-omics profiling are currently unavailable, hindering widespread data generation. Here, we present ISON (Integrated Spatial Omics Network), a unified...

GWAS typically focus on SNPs, often excluding complex genetic variants, such as short tandem repeats. Here, we report the results of GWAS analyses systematically assessing the role of short tandem repeats, both imputed and directly genotyped by whole genome sequencing, on risk for Alzheimer's disease in a large collection of ~330,000 individuals (3287 cases; 47,048 Alzheimer's disease-by-proxy cases, 283,111 controls) from the UK biobank. Using short tandem repeat genotype data, we identify 15...

Alzheimer's disease (AD) is not an inevitable outcome of pathology but a dynamic process shaped by how brain cells respond to amyloid-β (Aβ) and tau. To disentangle these responses, we combined spatial transcriptomics and single-nucleus RNA sequencing of the superior frontal cortex from octogenarians living with or without dementia and from cognitively intact centenarians with comparable Aβ accumulation. We identified six distinct tissue domains representing a spatial pathological continuum of...

Whether new neurons contribute to human cognition in old age remains debated. Recently in Cell Stem Cell, Tosoni et al.¹ show that immature-neuron transcriptional programs persist in the aged dentate gyrus and that their molecular state, not simply their abundance, tracks Alzheimer's pathology and cognitive resilience.

Lysine63 polyubiquitination is a prevalent post-translational modification in the central nervous system. Deficiency of CYLD, a lysine63-specific deubiquitinase, is linked to synaptic dysfunction and neurodegenerative disorders. However, our understanding of how CYLD contributes to the manifestation of neuronal deficits, particularly in the context of ageing, remains limited. Here, we report that CYLD-1 is essential for physiological lifespan in the nematode Caenorhabditis elegans. Neuronal...