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The type VI secretion system (T6SS) and Eag chaperones deliver toxic membrane protein effectors into rival cells. However, it is unknown how Eags and their effectors dissociate. Here, the authors show Eag chaperones bind effectors tightly and may release them via a subtle conformational change.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Functional studies of O-GlcNAcylation have often focused on individual modifications. Now, a systems-level approach has identified simultaneous O-GlcNAcylation events that coordinate cellular activities and tissue-specific functions.

The phase 2/3 DEVOTE trial demonstrated that high-dose nusinersen significantly improved motor function and was safe in patients with spinal muscular atrophy, compared with a matched sham control.

In this work, an exotic nuclear decay in one dimension is simulated using IonQ trapped-ion quantum computers. The coherent evolution of many decay channels is classically hard and quantum simulation of these processes may impact future searches for new physics.

In the phase 1/2 TRIDENT-1 trial, treatment of patients with NTRK fusion–positive advanced solid tumors with the tyrosine kinase inhibitor repotrectinib—selective for ROS1, TRKA−C and ALK—was safe and resulted in durable systemic and intracranial clinical response.

Sabatino and colleagues examine expanded CD8⁺ T cell clonotypes from a small cohort of multiple sclerosis patients. They identified several cognate peptide epitopes that derive from Epstein–Barr virus, suggesting EBV reactivation may drive pathogenesis in these patients.

Genome-wide association analyses using data from 19 biobanks identify variants influencing risk of thyroid diseases and yield polygenic risk scores associated with features of aggressive thyroid cancer.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

A wearable that continuously measures the concentration of a drug is demonstrated in humans.

Sheep producers face growing expectations to produce more food, conserve biodiversity, stay profitable and cut emissions. The authors find that interventions work best when addressing underperforming environmental, economic, or psychological areas.

Scanning nitrogen-vacancy microscopy unveils super-moiré spin textures emerging in twisted double-bilayer CrI₃ and provides real-space evidence of antiferromagnetic Néel-type skyrmions spanning multiple moiré cells.

Concerns over health misinformation online are becoming increasingly important. Here the authors show that older adults are more likely than younger people to encounter low-credibility health information online. Although exposure is limited overall, it is highest among those who already believe inaccurate health claims.

Phosphatidylinositol phosphates together with cholesterol bind at the interface between STING dimers, directly promoting high-order oligomerization.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

This study reports that de novo germline missense variants in SF3B1, distinct from the somatic variants frequently observed in cancer, cause a neurodevelopmental disorder and disrupt global RNA splicing.

A hidden quality-control system to filter out defective sperm during development is exploited by selfish genes to eliminate competing chromosomes.

The use of antimicrobial agents can exacerbate the proliferation of antimicrobial resistance genes, which can put public health at risk; evaluating this risk requires proper monitoring. An extensive investigation of Australian wastewater reveals a distinct correlation between the type of antimicrobial used and the socioeconomic status of the population.

Aqueous two-phase systems have potential as biomimetic materials, but often lack stability and are prone to collapse. Here, the authors use interfacial assembly of chitin nanofibres and cellulose nanocrystals to prepare a biobased system with permeability and switchable motility.

Nanomechanical measurements of molecular thin films are non-trivial due to ease of perturbation of the molecular surface. The authors present a direct, experimental demonstration of the tunability in the nanomechanical properties for a family of molecular semiconductors with systematic alkyl sidechain substitution.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

It remains unknown why only some sickle cell disease (SCD) patients develop lung thrombosis. Here, the authors show that an extracellular vesicle-dependent mechanism prevents lung thrombosis in SCD and how a CD39 polymorphism impairs this protection to promote lung thrombosis in subset of patients.

The study used snMultiome-seq to map gene expression and chromatin accessibility in human central amygdala cells from people with and without AUD. Here, the authors show that inhibitory neurons are most affected, with KLF16-driven regulatory changes and AUD-risk variants disrupting gene activity.

Virtual nature exposure reduces self-reported pain and is associated with decreased brain responses linked to somatosensory and nociceptive processing, providing new insights into the underlying mechanisms of nature-induced analgesia.

Native top-down proteomics reveals epidermal growth factor receptor–estrogen receptor-alpha (EGFR–ER) signaling crosstalk in breast cancer cells and dissociation of nuclear transport factor 2 (NUTF2) dimers to modulate ER signaling and cell growth.

Using artificial neural networks applied to human data, Eckstein et al. show that good models of reinforcement learning require memory components that track representations of the past.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

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.

The relative contribution of lipid catabolism on fasting-induced longevity was unknown. Authors showed lifespan extension from fasting depend on silencing lipid catabolism upon nutrient replenishment through phosphorylation of NHR-49 by KIN-19.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

An anti-HIV-1 antibody that targets an N332_gp120 glycan-independent V3 epitope, a site of Env vulnerability, can decline viremia in HIV-1-infected humanized mice while overcoming classical V3 escape mutations.

Li et al. reveal projection neuron-type-specific dynamics that coordinate corticothalamic communication during reach-to-consume behavior in mice.

A covariate-aware analysis reveals that microbiome changes in the gut of patients with chronic kidney disease are better explained by intestinal transit time than by kidney function.

The Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

Juno radio occultations precisely redefine Jupiter’s shape, measuring a polar diameter of 66,842 km and an equatorial diameter of 71,488 km, both smaller than long-used values, bringing models of the planet’s interior into better agreement with observations.

Proxy records from Lake Baikal show that rapid cooling coincided with Northern Hemisphere ice sheet expansion 2.7 million years ago, a change accompanied by a transition to open steppe ecosystems.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

A new platform comprising large-scale 2D arrays of quantum dots patterned with sub-nanometre precision, with each quantum dot defined by tens of phosphorus atoms doped into silicon, allows for analogue simulation of quantum materials on arbitrary lattices.

Earth’s core dynamo, which produces the magnetic field, may have been influenced by spatial variations in heat flux across the core–mantle boundary, according to combined palaeomagnetic datasets and geodynamo simulations.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

Rearrangement of the B cell receptor is sequential, and pairing of the successfully assembled heavy chain with the surrogate light chain proteins VpreB and λ5 to form the pre-B cell receptor is an important checkpoint signal for continued B cell development. Here, the authors show that λ5 plays a key role in the multi-step assembly process involving association-induced folding reactions.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

Neural mechanism underlying behavioural flexibility is not fully understood. Here authors study decision-making of macaques in a reversal task. They identify two complementary cognitive processes. Distinct neural patterns link these processes to the dorsomedial prefrontal cortex, thalamus, and hippocampus.

High-resolution satellite data enables a unique verification of national methane emissions worldwide. Global estimates are 63 Tg a⁻¹ for oil-gas, 30% higher than the UNFCCC reports due to under-reporting by four largest emitters, and 33 Tg a⁻¹ for coal, consistent with previous estimates.