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Science, Volume 387, Issue 6740, March 2025.

Science, Volume 387, Issue 6740, March 2025.

New film explores how scientists see nature differently from each other—and from everyone else

Water-resistant armor gives delicate water droplets the nimbleness of white blood cells

Programs at NIH and Defense Department are pared back by bill that keeps funding at 2024 levels

Physicists cast doubt on measurements validating Microsoft’s first quantum chip, Majorana 1

Why there is sex-biased susceptibility to cerebrovascular dysfunction remains enigmatic. Vandal et al.¹ reveal a sex-specific vulnerability to endothelial deficiency in CD2AP, an Alzheimer's disease risk gene, with impaired cerebrovascular reactivity, compromised cerebrovascular function, and cognitive decline, highlighting sex as an important biological variable in Alzheimer's disease.

The apolipoprotein E (APOE) gene is the strongest genetic risk modifier for Alzheimer's disease (AD), with the APOE4 allele increasing risk and APOE2 decreasing it compared with the common APOE3 allele. Using single-nucleus RNA sequencing of the temporal cortex from APOE2 carriers, APOE3 homozygotes, and APOE4 carriers, we found that AD-associated transcriptomic changes were highly APOE genotype dependent. Comparing AD with controls, APOE2 carriers showed upregulated synaptic and...

The pathology of cardiovascular aging is complex, involving mitochondrial dysfunction, oxidative and nitrative stress, oxidative DNA injury, impaired lipid metabolism, cell death, senescence, and chronic inflammation. These processes lead to remodeling and structural changes in the cardiovascular system, resulting in a progressive decline in cardiovascular reserve capacity and health, and an increased risk of diseases and mortality. Excessive alcohol consumption exacerbates these risks by...

Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced...

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Individual heterogeneity shapes ecoevolutionary processes at multiple scales. Yet, the scarcity of long-term life-history data and limitations in classic statistical tools hinder our capacity to uncover and understand individual heterogeneity in wildlife populations. Here, we apply an underused multivariate statistical method to uncover four heterogenous life-history trajectories in wild female bighorn sheep (Ovis canadensis). Remarkably, these trajectories had remained unobserved in the...

Several studies have shown that Parkinson's disease causative gene products, including α-synuclein (α-syn), display tight links with the tumor suppressor p53. The purpose of this study is to determine the implication of α-syn in glioblastoma development and elucidate how it elicits a tumor suppressor function. We show that the expression of α-syn, a TP53 transcriptional target and a key molecular player in Parkinson's disease, is detected in 1p/19q-codeleted and isocitrate dehydrogenase...

Transcranial ultrasound stimulation (TUS) offers precise, non-invasive neuromodulation, though its impact on human deep brain structures remains underexplored. Here we examined TUS-induced changes in the basal ganglia of 10 individuals with movement disorders (Parkinson's disease and dystonia) and 15 healthy participants. Local field potentials were recorded using deep brain stimulation (DBS) leads in the globus pallidus internus (GPi). Compared to sham, theta burst TUS (tbTUS) increased theta...

The surgical treatment of geriatric patients represents a major challenge in traumatology. It is well known that aging affects fracture healing. However, the exact pathophysiology of age-related changes in angiogenesis, inflammation and bone remodeling remains still elusive. Therefore, we herein studied the differences of femoral fracture healing in young adult (3-4 months) and aged (16-18 months) CD-1 mice by using a stable closed femoral fracture model with intramedullary screw fixation. The...

N-acetyltransferase 10 (NAT10) is involved in regulating senescence. However, its role in glomerular diseases remains unclear. Therefore, this study aims to investigate the mechanisms by which NAT10 influences senescence and damage in an adriamycin (ADR)-induced nephropathy model. Senescence (p16 and p21) and DNA damage markers (γ-H2AX (ser139)) were assessed in ADR-induced nephropathy. NAT10 function was demonstrated using Remodelin or small interfering RNA (siRNA) interventions. Transcriptome...

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Ferroptosis is closely linked with various pathophysiological processes, including aging, neurodegeneration, ischemia-reperfusion injury, viral infection and, notably, cancer progression; however, its post-translational regulatory mechanisms remain incompletely understood. Here we revealed a crucial role of S-palmitoylation in regulating ferroptosis through glutathione peroxidase 4 (GPX4), a pivotal enzyme that mitigates lipid peroxidation. We identified that zinc finger DHHC-domain containing...

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The landscapes of somatic mutation in normal cells inform us about the processes of mutation and selection operative throughout life, providing insight into normal ageing and the earliest stages of cancer development¹. Here, by whole-genome sequencing of 238 microdissections² from 30 individuals, including 18 with gastric cancer, we elucidate the developmental trajectories of normal and malignant gastric epithelium. We find that gastric glands are units of monoclonal cell populations that accrue...