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ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Zika and chikungunya virus are co-circulating in many regions and currently there is no approved vaccine for either virus. Here, the authors engineer one vaccinia virus based vaccine for both, Zika and chikungunya, and show protection from infection and pathogenesis in mice.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

A cortical premotor network in HVC, once initiated, can sustain and regulate the sequential production of zebra finch song syllables without major extrinsic inputs.

Mineral ages and chemical analysis of fragments of the Altar Stone from the Neolithic stone circle at Stonehenge suggest that it was transported from northeast Scotland, more than 750 km away, probably by sea.

Scourzic et al. show that germinal centre B cells display an enhanced ability to reprogram to induced pluripotent stem cells compared to mature B cells. This ability indicates their higher plasticity level and is T follicular helper cell-dependent.

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

Here they combine in vivo imaging with proteomics to characterize a protein complex comprised of Ccdc78 and Ccdc33 that acts at the extreme distal tip of 9 + 2 motile cilia to control tip architecture, cilia length, and cilia beating.

Microglia survey the parenchyma, which leads to morphology changes over time. Here the authors show using 2 photon imaging of microglia in vivo that sleep modulates microglial morphodynamics through Cx3cr1 signaling.

How higher-order thalamic feedback modulates sensory-evoked cortical activity is not fully understood. This study reveals that synaptic feedback from the thalamus selectively increases the excitability of distinct cortical neurons through NMDARs and mGluR-mediated modulation of potassium channels, thereby enhancing sensory processing.

Synthetic data generated by generative artificial intelligence models can serve as a substitute for real patient data. In this Review, Eckardt et al. discuss how synthetic data sets can overcome barriers to data access and sharing, democratize scientific discovery in cancer research, and reduce the costs and failure rates of cancer clinical trials. They also discuss how this will only become possible if we can overcome the challenges of a lack of standardization in training data selection, model evaluation, bias mitigation, privacy preservation and quality assurance.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

How seizures emerge in epileptic brain remains an enigma. The authors show that the transition to seizure follows a ubiquitous dynamical principle inherent to many processes in nature characterized by repeated transitions between contrasting regimes.

The STAR experiment at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory demonstrates evidence of spin correlations in \(\Lambda \bar{\Lambda }\) hyperon pairs inherited from virtual spin-correlated strange quark–antiquark pairs during QCD confinement.

Neutrophils infiltrate the ischemic brain. Here, the authors show a disease-stage dependent neutrophil diversification in neonatal brain injury; neutrophils aggravating tissue damage in the acute phase while promoting regeneration in the later stage.

The selective autophagy receptor p62/SQSTM1 is organized in a structured double helical filament in vitro, the cryo-electron tomographic images in ATG5 knockdown conditions reveal Ca-rich layers of p62 oligomers enwrapping lipid droplets in situ.

CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

Reducing the competitive advantage conferred by driver mutations can abrogate expansions of mutant clones in healthy tissue in mice. This suggests ways to prevent cancer and other diseases that are associated with somatic mutations in humans.

The VGLUT3-p.T8I mutation was identified in patients with SUDs and EDs and introduced in a mouse line. Here, authors show that mutant mice have an imbalanced DA signaling in the dorsal striatum associated with maladaptive cocaine and food consumption.

How myelin plays a role in long-range processing of disparate inputs remains elusive. Here, the authors show that myelin loss within the neocortex reduces the reliability to propagate cortical bursts across axons, causing an impaired temporal sharpening to compute sensory and cortical signals within the thalamus.

Clonal haematopoiesis of indeterminate potential is driven by somatic mutations in hematopoietic stem/progenitor cells and may progress to myelodysplastic syndromes (MDS). Here authors show that the two conditions share a similar pattern of bone marrow remodeling, characterized by the emergence of inflammatory mesenchymal stromal cells and IFN-responsive T cells, reinforcing their shared etio-pathology.

This study established the HIF1a–SOX9 axis as a key regulatory barrier that limits epithelial cell fate plasticity, safeguarding against premature responses to incomplete or inadequate instructive cues during tissue repair.

Primary cilia are cell organelles disrupted in developmental diseases and cancer. Here, the authors identify cilia regulators that generate a specific cilia membrane lipid, which may help to better understand diseases caused by mutations in PI3-kinase subunits.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Researchers discovered five phases of brain rewiring across the lifespan. The eras of childhood, adolescence, adulthood, early aging, and late aging each have characteristic rewiring of structural connections across the whole brain.

Weaver and colleagues report that enrichment of the extracellular matrix with tenascin C promotes aggressiveness of IDH1-mutant glioblastoma by activating a HIF1α-controlled mechanosignalling feedback loop.

Proteomics must target specific synapse types to reveal how molecules shape their unique functions. Here, authors show that hippocampal synapses differ in proteome and that neuron-specific glutamate receptor regulation shapes synaptic diversity.

Ambroziak, Nencini, Pohle and colleagues identify a slowly emerging plasticity mechanism in a discrete set of hypothalamic preoptic neurons that is triggered by long-term heat exposure and that drives thermal acclimation to promote heat tolerance in mice.

The discovery that DNA methylation of different CpG sites can serve as digital barcodes of clonal identity led to the development of EPI-Clone, an algorithm that enables single-cell lineage tracing through cellular differentiation at scale.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

A diverse range of molecular and genetic manipulations all alter lifespan distributions of Caenorhabditis elegans by an apparent stretching or shrinking of time.

The role of the nuclear lamina (NL) in chromatin architecture is still poorly understood. Here, the authors provide evidence that disruption of the NL in Drosophila cells leads to overall chromatin compaction and repositioning from the nuclear envelope, whereas lamina-associated regions become less compacted and transcription within them is increased.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

The molecular etiology of hypertensive disorders of pregnancy is largely unknown. Here the authors show from a prospective study of diverse pregnancies that the disease can be split into molecular subtypes based on RNA data and validated a classifier for individuals with no preexisting high risk factors.

Combining patch-clamp recordings and subsequent STORM imaging of individual cells, the authors show that the axon terminals of perisomatically- and dendritically-projecting GABAergic interneurons show differences in CB₁ receptor number, active zone complexity, and receptor:effector ratio. Chronic exposure to THC evoked a dose-dependent and long-lasting downregulation of CB₁ at these synapses.

Salisbury Plain detrital zircon ages align with southern British rocks from the London Basin, indicating local sedimentary recycling without glaciogenic evidence, negating glacial transport of the Stonehenge blocks, according to detrital zircon and apatite U-Pb isotopic fingerprinting of stream sediments across the Salisbury Plain.

Recent studies unexpectedly indicate involvement of ventral tegmental area dopamine neurons in Alzheimer’s disease (AD). Here, the authors identified the enzyme casein kinase 2 as a mechanistic link between abnormal firing activity and AD pathology.

Heart failure with preserved ejection fraction (HFpEF) is a global, major health issue for which no effective therapies are available. Here, the authors discover that the interplay between two transcription factors, Xbp1s and FoxO1, is critical for metabolic adaptation and lipid handling in HFpEF-stressed cardiomyocytes.

Intracellular transport along microtubules involves runs, pauses and directional reversals. Here, D’Souza et al. mimic these dynamics in vitro using a minimal system of Dynein-Dynactin-BICD2 and Kinesin-3 on vesicles without the need for regulators.

The authors of this study perform simulations with a high-resolution climate model and show that global warming may trigger an abrupt shift in the tropical climate system towards stronger and more predictable ENSO cycles, intensifying climate impacts across the globe.

This study reveals a broken age–frequency relation of hot Jupiters, which simultaneously constrains the tidal factor of host stars and indicates different timescales in hot Jupiter formation, with ~40% forming late on billion-year timescales through secular chaos.

The functions of small nucleolar RNAs (snoRNAs) in cancer remain to be studied. Here the authors show that the snoRNA Snord67 promotes lymph node metastasis of breast cancer cells through guiding modifications of the spliceosome and regulating the splicing landscape.

The ALICE Collaboration provides details on the microscopic mechanism that ends up creating antideuteron in high-energy proton–proton collisions at the Large Hadron Collider.

Blue Stragglers Stars (BSSs) are anomalously luminous main sequence stars in clusters. Here, the authors show evidence that the fraction of fast rotating BSSs increases for decreasing central density of the host system, suggesting fast spinning BSSs prefer low-density environments.

Here, the authors identify the microbiota-derived corisin as a driver of diabetic kidney fibrosis via cellular aging and show that targeting corisin with a monoclonal antibody alleviates disease in mice, suggesting a potential therapeutic avenue.

The authors induce selective astrocytosis in the mouse hippocampus and examine the consequences on synaptic transmission in CA1 pyramidal neurons. They report a specific reduction in inhibitory synaptic currents mediated by downregulation of glutamine synthetase that results in hyperexcitability.

Cancer genomes are rife with genetic variants, and one key outcome of this variation is widespread gain-of-cysteine mutations. Here, the authors pair cysteine chemoproteomics with genomics to investigate the landscape of cysteine genetic variation.