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Fracto-mechanoluminescence is the emission of light from fracturing solids. Here, the authors show that this emission in Mn halides arises from elastic stiffness, electromechanical coupling, and trap states that activate Mn²⁺ d−d transitions.

Dysregulated protein levels can cause disease. The authors present a scalable platform capable of identifying small molecules that alter disease-linked target protein levels, and report >40 that increase SynGAP protein abundance, with SR1815 restoring neuronal function in Syngap1 deficient neurons.

Genes encoding key epigenetic regulators, including Lysine Demethylase 6A (KDM6A), are frequently mutated in bladder cancer. Here, the authors show that loss of KDM6A promotes formation of extrachromosomal circular DNA (eccDNA), genomic instability, and metabolic reprogramming, driving resistance to cisplatin chemotherapy while simultaneously enhancing sensitivity to immune checkpoint inhibitors.

Optical access to the brain is limited by light scattering in the skull. Here, the authors present SeeThrough, a rationally designed skull clearing technique that enables simple, minimally-invasive, high-resolution, mesoscale, and longitudinal imaging of the brain parenchyma and brain-skull interface without skull removal.

Using infant fMRI, the authors show that, by 2 months of age, representations in high-level visual cortex encode visual categories that align with deep neural networks, and lateral object-selective regions are later to develop.

Whether mRNA SARS-CoV-2 vaccines promote T cells within the nasal mucosa of vaccine recipients is not known. Here the authors show that after mRNA SARS-CoV-2 vaccination, antigen specific T cells can be measured in the nasal mucosa and that these T cells may be localised to respond to a subsequent virus infection.

Clinical trial registration NCT04713163

Netrin-4 is a tumor suppressor that interferes with laminin lattice formation. Here, Kulczyk et al. present a cryo-EM structure of the netrin-4-laminin γ1 complex. The structure reveals how netrin-4 inhibits laminin polymerization and disassembles the laminin matrix.

Mutant forms of the transmembrane receptor activin receptor-like kinase 2 are associated with different genetic diseases. Here, the authors report that disease-associated forms of this receptor cause intracellular domains to dimerize in response to ligand binding of extracellular domains.

The authors use a combination of viral tracing and genetics to characterize the diversity of neurons projecting from mouse brainstem to motor neurons that control limb movements; in particular they discover that the medullary reticular formation ventral part (MdV) is functionally specialized for skilled forelimb motor control.

Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

A pyramidal cell type and the 5-HT_2A receptor in the medial frontal cortex have essential roles in psilocybin’s long-term drug action.

Taveneau et al. leverage artificial-intelligence-driven protein design to create inhibitors that control RNA-targeting enzymes in cells, revealing a strategy to rapidly design off-switches for RNA-editing systems.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development remains unknown. Here, the authors show that JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

Hexokinase detachment from the outer mitochondrial membrane is shown to support aerobic glycolysis in cancer cells. Differential localization of the HK1 isoform to the outer mitochondrial membrane, compared to the HK2 isoform, explains the conditional essentiality of HK2 in cancer cells cultured in physiologic media.

Scott, Tan et al. characterize the neural circuits that link mechanic stimuli in the heart and gut with whole-body energy homeostasis and vigilance.

Host antibodies can alter the glycan binding of adhesin proteins from infectious bacteria, but the antibodies’ mechanisms of action remain unclear. Here, the authors define four mechanisms of modulation, including ligand mimicry and multiple modes of allosteric interference.

A combination of optogenetic, electrophysiological and neuroanatomical tracing methods defines midbrain periaqueductal grey circuits for specific defensive behaviours.

Engineering gene expression systems that can be programmed to respond to specific environmental conditions is challenging. Here, the authors develop a synthetic bow-tie circuit that is able to sense signals from microRNA molecules and affect a change in protein dynamics in mammalian cells.

Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.

A workflow combining optogenetic perturbations with spatial transcriptomics to program spatiotemporal gene expression patterns in organoids.

The amygdala central nucleus (CeA) has been implicated in feeding regulation, but the underlying circuit mechanisms are incompletely understood. The authors show, in mice, that GABAergic serotonin receptor 2a–expressing CeA neurons are active during eating and promote positive reinforcement and food consumption, partly through long-range inhibition of the parabrachial nucleus.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Sex pheromones that increase mating have been reported across a number of different species, yet there is little known about pheromones that suppress female mating drive. This study reports that juvenile female mice release a pheromone, ESP22, which suppresses sexual receptivity of adult female mice by evoking a robust rejection behavior upon male mounting.

Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through immunoediting.

Single-cell profiling of vagal sensory neurons from seven organs in mice and calcium-imaging-guided spatial transcriptomics reveal that interoceptive signals are coded through three distinct dimensions, allowing efficient processing of multiple signals in parallel using a combinatorial strategy.

The bidirectional loop circuit between layers 5/6 of the lateral entorhinal cortex and the medial prefrontal cortex encodes item–outcome associative memory in mice.

The authors establish the claustrum-Cre transgenic mouse line and demonstrate that the claustrum orchestrates cortical slow-wave activity by synchronously driving the inhibitory interneurons in widespread cortical areas.

In this study, the authors uncover how diverse inhibitory interneurons in the amygdala flexibly contribute to fear and safety learning, revealing a key role for inhibition in emotional memory and adaptive circuit plasticity.

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.

Transcriptomic analysis following epidural electrical stimulation of the lumbar spinal cord during neurorehabilitation in mice identifies a population of neurons that orchestrates the restoration of walking following paralysis.

A bispecific nanobody (BsNb-ncAA) with sites found by computation to improve binding, inhibit immune evasion, boost CD8⁺ T cells, and suppress colon tumor growth, offering promising colorectal cancer immunotherapy strategies.

Krabbe, Paradiso et al. show that amygdala VIP interneurons are activated by instructive cues for associative learning. These interneurons provide a mandatory disinhibitory signal permitting plasticity in response to unexpected salient events.

Whether and how highly penetrant NDD (neurodevelopmental disorder) genes such as Syngap1 regulate sensorimotor integration are not fully understood. This study shows that Syngap1 expression in cortical projection neurons promotes cognitive abilities in mice through forming distributed networks that integrate sensory information with motor signals, a dynamic process required for perception and attention.

The authors developed a computational approach to probe the stability of amyloid fibrils and discover networks of hotspot interactions. Understanding the mechanisms of amyloid folding will help identify novel methods to treat protein (mis)folding diseases.

Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

In the mouse caudal brainstem, functionally distinct neuronal subpopulations, which are distinguishable by neurotransmitter identity, connectivity and location, regulate locomotion parameters.

The ASAP4 family of genetically encoded voltage indicators allows recording of action potentials and subthreshold activity with either one- or two-photon microscopy over extended periods of time.

Optogenetics is applied to the entire mouse spinal cord.

iGluSnFR variants with improved signal-to-noise ratios and targeting to postsynaptic sites have been developed, enabling the analysis of glutamatergic neurotransmission in vivo as illustrated in the mouse visual and somatosensory cortex.

Using large-scale screening and structure-guided mutagenesis, fast and sensitive GCaMP sensors are developed and optimized with improved kinetics without compromising sensitivity or brightness.

The role of oxytocin in modulating astrocytes during stress behaviour is not fully understood. Here the authors show that in the amygdala, oxytocin modulates stress related behaviour by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium.

IκBζ is a rather unknown transcriptional co-factor of NF-κB. Here, the authors show that constitutive IκBζ expression in a subgroup of patients with melanoma drives immunotherapy resistance and enhanced tumor growth.

A small population of prostaglandin E2-responsive glossopharyngeal sensory neurons provides a sensory pathway between airway and brainstem that mediates sickness responses to early-phase influenza virus infection.

Benoit, Ganea et al. show that changes in axon initial segment (AIS) length in the prefrontal cortex of mice accompany fear learning and extinction, revealing AIS plasticity as a key feature of neuronal adaptation and memory formation.

Tan et al. identify PRDM16 as a key repressor of fibrotic switching in smooth muscle cells and show that its downregulation in atherosclerosis drives smooth muscle cells toward a synthetic fate, promoting fibrous plaques.

Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.