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The viscosity of tumour cells is shown to govern their ability to disseminate through the bloodstream and extravasate, establishing a key biomechanical factor of metastasis.

CD44 expressed by fibroblastic reticular cells in secondary lymphoid organs regulates trafficking of dendritic cells, and thus has an essential role in the priming of T cells and the adaptive immune response.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

Tissue stiffness mediated by Piezo1 is shown to regulate the expression of diffusive guidance cues in the developing Xenopus laevis brain, revealing a crosstalk between mechanical signals and long-range chemical signalling.

Changes in ocean fronts could impact biological productivity and carbon exchange. By analysing satellite and reanalysis data, the authors identify areas with active frontal activity and rapid change in properties, as well as highlighting the correspondence with surface productivity and CO₂ uptake.

Albumin selectively inhibits Mucorales growth through the release of bound free fatty acids.

Mejía-Ramírez, Iáñez Picazo, Walter et al. explore how nuclear biomechanical changes limit the regenerative capacity of aged hematopoietic stem cells and show that targeting RhoA rejuvenates aged hematopoietic stem cells by reducing nuclear envelope tension and remodeling nuclear architecture.

Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

Symmetry breaking is key to tissue formation. Now it is shown that symmetry breaking of epithelial spheroids is controlled by an interplay of collective migration with curvature and matrix remodelling.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

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

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Here the authors functionally test and resolve the spatial genome organization of cis-regulatory elements and genetic variants in atrial, ventricular, and failing human cardiomyocytes and linked them to heart disease traits, including QT syndrome.

Two groups of ammonia-oxidizing archaea drive marine nitrification. Stuehrenberg et al. reveal that their distribution reflects substrate use, with one relying on urea and the other on ammonia to maintain nitrification in open-ocean waters.

This study provides new insights into the role of endoglin (ENG) as a co-receptor in endothelial cells and addresses a gap-in-knowledge on how ENG could be involved in both TGF-β and BMP9 signalling. Such knowledge greatly facilitates therapeutic targeting of ENG-related pathways.

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.

Extracellular vesicles are central to immune regulation and stress responses. Here, the authors show how pathogen-derived compounds regulate host EV production showcasing new insight into how animals anticipate and prepare themselves for infection.

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

Current human tandem repeat catalogs are derived from short-read sequencing data, thus limiting the size range and sequence complexity of captured genotypes. Here the authors generate a comprehensive catalog de novo using long-read sequencing data.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

There are limited data on mpox immunity in West Africa. In this study, authors present serological and genomic evidence of residual smallpox vaccination immunity and possibly unrecognized mpox exposure among ostensibly healthy Nigerian adults.

Disease course and pathology an infection may cause can change owing to the structural and functional physiological changes that accumulate with age, but therapy can be tailored accordingly; disease tolerance genes show antagonistic pleiotropy.

The choroid plexus is a vital brain ventricular organ that produces cerebrospinal fluid. This study shows how developmental origins and local niches shape the specialization of choroid plexus macrophages, a key first line of immune defense for the brain.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

Genetic and isotopic analyses of samples from the northeast Atlantic reveal that suspended prokaryotic dark carbon fixation substantially fuels carbon inputs below the sunlit ocean, while particle-attached communities make an overlooked contribution to carbon demand.

Authors introduce ELLA, a computational framework that maps gene expression within cells at subcellular resolution, uncovering localization patterns and revealing how mRNA features and the cell cycle shape spatial gene regulation.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Discovery proteomics offers deep insights but is currently not applied clinically in diagnostics. Here, the authors present ADAPT-MS, a flexible machine learning framework that enables fast, personalized diagnostic and prognostic decisions directly from proteome-wide data.

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.

Arsenic-rich globules are thought to be evidence of early microbial life. Here, the authors show how microbialite arsenic enrichment patterns vary with microbial activity and environmental conditions, reinforcing arsenic’s value as a biosignature.

This study assessed the durability of immunity in humans after vaccination with an MVA-based MERS vaccine. The data show that antibodies and T cells persist for at least two years, with the antibodies capable of cross-neutralizing MERS-CoV variants.

TCR-engineered T cells have shown limited efficacy in part due to the absence of co-stimulation leading to limited accumulation in solid tumors. The authors here show engineering the CD8β coreceptor with an intracellular CD28 domain enhances cytokine production, persistence, and tumor control in vivo independent of tumor-associated co-stimulatory ligand encounter.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

Demand-side food policies show small average effects, with effectiveness varying across intervention types. Targeted strategies and a better understanding of how context and population influence outcomes can advance food system sustainability.

Neonatal brain injury from intermittent hypoxemia increases fatty acid oxidation and causes long-term changes in hippocampal lipid profile. Here authors demonstrate oral treatment with glycerol-triacetate restores lipid fatty acid profile and promotes functional recovery.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

Myeloid derived suppressor cells (MDSC) use different metabolic mechanisms to adapt to the tumour microenvironment. Here the authors show that 6-phosphogluconate dehydrogenase (6PGD) is important for MSDC function and that blockade of 6PGD impaired MDSC function and suppresses tumour growth leading to metabolic and functional changes in the MDSC and a more pro-inflammatory phenotype.

Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

This study provides insights into the chromatin-looping-dependent and chromatin-looping-independent roles of cohesin and CTCF in controlling gene regulation.

The impact of negative energy balance on dopamine transmission is unclear. Here, authors show that the ABA model disrupts dopamine transmission via loss of GABAergic control over VTA dopamine neurons contributing to the development of hyperactivity.

Huang et al. analyzed serial samples from participants with metastatic non-small cell lung cancer treated with radiotherapy followed by immunotherapy and report improved clinical outcomes and enhanced antitumor responses in immunologically cold tumors.