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Cell state plasticity of neuroblastoma cells is linked to therapy resistance. Here, the authors develop a transcriptomic and epigenetic map of indisulam (RBM39 degrader) resistant neuroblastoma, demonstrating bidirectional cell state switching accompanied by increased NK cell activity, which they therapeutically enhance by the addition of an anti-GD2 antibody.

The transcription factor ATF6 causes an enrichment in long-chain fatty acids in the colonic epithelium, which leads to changes in the gut microbiota and contributes to the development of colorectal cancer in humans and mice, thereby linking endoplasmic reticulum stress responses to lipid metabolism and tumorigenesis.

In this study, Weber et al., investigate the long-term survival and integration of human stem cell-derived neural progenitors into the stroke-injured mouse brains. They report grafted cells integrate into host circuits and mediate repair through graft-host crosstalk via neurexin, neuregulin, neural cell adhesion molecules, and SLIT signalling pathways.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

Studies in mice show that acute stress activates hyperglycaemia via activation of a medial amygdala–ventral hypothalamic circuit that controls glucose metabolic responses in the liver, independently of adrenal and pancreatic hormones.

The discovery of chemosynthesis-based benthic communities at depths of 5,800 m to 9,533 m in the Kuril–Kamchatka and western Aleutian trenches challenges traditional perspectives on the energy sources sustaining hadal fauna.

Prenatal stress triggers molecular dysregulations in fetal neuroimmune circuits, leading to altered mast cell and sensory neuron function, which predisposes offspring to develop eczema in response to otherwise harmless mechanical friction after birth.

Olfactomedin-2 is a pleiotropic glycoprotein emerging as a regulator of energy homeostasis via the hypothalamus. The present findings functionally connect adipose-specific OLFM2 to obesity, and highlight its significance in maintaining adipocyte commitment to avoid metabolic disease.

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

Asymmetrical distribution of tau pathology in Alzheimer’s disease is linked to asymmetrical amyloid-beta deposition, not reduced brain connectivity, suggesting regional vulnerability plays a key role in determining the distribution of tau pathology.

Using an advanced imaging system called EyeRIS, locomotion in deep-sea octopuses could be studied, revealing simplified crawling patterns that could inspire the design of robots.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a neurodegenerative disorder caused by pathogenic CSF1R mutations. Here the authors find that microglial loss is linked to reduced myelinating oligodendrocytes, an expansion of neuropilin-2⁺ oligodendrocytes and a maladaptive stress response in astrocytes.

Expanding the complexity of genetically encoded peptides is a long-standing challenge at the intersection of chemistry and biology. Now it has been shown that linear peptides with a reactive N-terminal β- or γ-keto amide can be synthesized ribosomally and elaborated to generate atropisomeric and/or macrocyclic peptides with embedded pharmacophores.

CSF total tau (t-tau), often used as a marker of neuronal damage, is more strongly linked to synaptic degeneration. Here, the authors show that t-tau better reflects synaptic dysfunction than axonal or neuronal loss in Alzheimer’s disease.

Beck et al. develop a model where striosomes create a flexible “decision-space” that adapts to environmental context and internal state. It explains how we make choices and why decision-making varies between people, and in neuropsychiatric disorders.

Shabanzadeh et al. identify and validate a pathway whereby RGMa cleavage by SKI-1 modifies gene expression related to blood–brain barrier (BBB) integrity after stroke. SKI-1 inhibition restores BBB integrity and neuronal function in mouse and rabbit stroke models.

The placenta plays vital roles in supporting fetal development. Here, Richards et al. develop a high-throughput bioprinted trophoblast organoid model to recapitulate the microenvironment of the early placenta, enabling investigation of placenta development and evaluation of therapeutics for placenta dysfunction disorders.

The human pelvis exhibits distinct spatiotemporal ossification patterns and an ilium cartilage growth plate that is shifted perpendicularly compared with those of other mammals and non-human primates—two key adaptations that underlie bipedalism.

This study maps the connections of layer 5 pyramidal neurons in the mouse cortex, revealing distinct local and intercortical wiring patterns, and provides an open framework for exploring the connectivity of cell types.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Plasma samples from 324 Black and 1,547 white participants underwent analysis with C2N Diagnostics’ Precivity AD test for Aβ42 and Aβ40. Compared to white individuals, Black individuals had higher average plasma Aβ42/40 levels at baseline, consistent with a lower average level of amyloid pathology.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Aging is a risk factor for Parkinson’s disease; however, how DNA damage accumulation, a hallmark of aging, contributes to its pathophysiology remains incompletely understood. Here, the authors identify a blood-based DNA damage signature that is associated with disease progression in patients with Parkinson’s disease.

Here, the authors find that a benign polygenic predisposition to lower white blood cell counts is associated with multiple clinical endpoints, suggesting that predisposed individuals are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.

A mass spectrometry-based approach globally identifies protein regulators of metabolism and reveals the role of LRRC58 in controlling cysteine catabolism.

Cultivation of tropical soil microorganisms combined with physiological experiments and bioinformatics analyses identify a family of clade III lactonase-type nitrous oxide reductases with low sequence identity but high 3D structural similarity to known nitrous oxide reductases.

Basal cells, rather than neuroendocrine cells, have been identified as the probable origin of small cell lung cancer and other neuroendocrine–tuft cancers, explaining neuroendocrine–tuft heterogeneity and offering new perspectives for targeting lineage plasticity.

Genome-wide and targeted perturbation of DNA methylation at centromeres affects CENP-A positioning and centromere structure, resulting in aneuploidy and reduced cell viability.

Available methods for deeper super-resolution imaging in plants require specialized hardware or fluorescent reagents. Here, the authors report a dynamic, deep-tissue single-molecule bioimaging technology and show its application in tracking two vernalization-specific proteins with which Arabidopsis forms memory of winter cold.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Here the authors provide a deep tissue analysis of patients with autoimmune kidney diseases, identifying a conserved spatiotemporal immune program for the development of glomerular crescents and sclerosis.

Fanjiang Kong, Zhixi Tian, Xingliang Hou, Baohui Liu and colleagues report the cloning and functional characterization of J, the locus underlying the long-juvenile (LJ) trait that has enabled tropical cultivation of soybean. They show that J, an ortholog of Arabidopsis ELF3, downregulates the expression of E1, thereby promoting flowering under short-day conditions.

Black and white fonio are two small indigenous grain cereals grown in West Africa. Here, the authors reveal their independent domestication and cultivation histories through population genetics and demographic history analyses.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Lesion initiation and progression in multiple sclerosis is a dynamic but unclear process. Here, the authors highlight cell type-specific gene sets characterizing the action lesion rims and identify trajectories, predicting how normal-appearing white matter can develop into active and mixed active/inactive lesions.

In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

The major ion chemistry of a North American river shows decreased lateral carbon transport due to exacerbated secondary carbonate formation and CO₂ evasion, according to analyses conducted during a 195-day drought.

The blood-brain barrier (BBB) regulates the extracellular composition of the central nervous system (CNS), but it is not known whether its properties differ across CNS regions. Here, the authors show in mice that the BBB exhibits regional specializations, and that such specializations can be important for the function of specific neural circuits.

The genetic susceptibility to breast cancer remains understudied in non-European populations. Here, the authors analyse pathogenic variants associated with breast cancer susceptibility in Hispanic/Latina women using genomics, and find that loss of function variants in FANCM are strongly associated with ER-negative breast cancer risk.

The study reveals maps of the heliosphere’s termination shock strength. Asymmetries in the shock strength across the sky, from nose to tail and port to starboard flanks, are caused by the solar wind and interstellar medium dynamics.

STING is a promising drug target, but selective activation is necessary for safety and efficacy. Researchers have developed a two-component prodrug system for potent pharmacological activation of STING that offers excellent tumour targeting.

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

Phenotype variation is higher in mutants than wild types. Examining a range of mutant severities, this study unexpectedly found that variation decreases in severe conditions. A quadratic trend best fits the relationship between severity and variation.

The vertebrate brain forms during embryonic development through mechanical processes that are precisely coordinated in space and time. Here, the authors uncover how extrinsic forces regulate tissue flows and cellular rearrangements to shape the early neural plate during zebrafish gastrulation.