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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.

Centennial-scale variations in methane carbon isotope ratios are attributed to changes in pyrogenic and biogenic sources that can be correlated with anthropogenic activities, such as varying levels of biomass burning during the period of the Roman empire and the Han dynasty, and changes in natural climate variability.

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.

Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

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.

Genetic predictors of health outcomes often drop in accuracy when applied to people dissimilar to participants of large genetic studies. Here, the authors investigate the root causes and highlight open questions underlying this problem.

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.

Owing to electron localization, two-dimensional materials are not expected to be metallic at low temperatures, but a field-induced quantum metal phase emerges in NbSe₂, whose behaviour is consistent with the Bose-metal model.

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 authors describe the discovery of a series of potent non-competitive allosteric inhibitors of the ZIKV NS2B-NS3 protease, which exhibit antiviral activity in vitro and robust oral efficacy against ZIKV infections in a mouse model.

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 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 a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship between environmental antigen exposure and subsequent allergy.

Non-invasive strategies to detect and track activated myeloid cells will facilitate disease diagnosis and monitoring in patients affected by neuroinflammatory disorders. Here, the authors present 18F-FMD, a dendrimer-based PET tracer that detects and monitors activated myeloid cells at different stages (presymptomatic and symptomatic) of Experimental Autoimmune Encephalomyelitis (EAE) in mice and in response to disease-modifying therapies.

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.

The study introduces radio interferometric multiplexed spectroscopy (RIMS), a method designed to efficiently monitor the radio emissions of massive samples of stars. Applying it to LOFAR data, the authors identify stellar bursts, offering clues to possible star–planet magnetic interactions.

A modular, point-of-care device combining hemispheric plasmonic nanoarrays and automated microfluidics enables nucleic acid amplification and metabolic cell viability assay for rapid bacterial identification and antibiotic susceptibility testing.

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.

Respiratory virus genomic surveillance output is unevenly distributed globally. Here, the authors show that addressing this imbalance could substantially reduce the time to first detection of novel (variant) viruses, enhancing surveillance effectiveness and efficiency.

Aadvanced computer simulations of three-dimensional turbulence reveal that the ab initio generation of large-scale magnetic fields is driven by shear-flow-induced jets; an analytical model is derived which reproduces the essential features of the flow- and field-generation mechanisms.

Highly pathogenic avian influenza H5N1 viruses are of global concern. This study shows that a low-dose H5N1 clade 2.3.4.4b Alum/CpG-adjuvanted vaccine elicits broad, durable antibody and T cell responses and protects female mice against lethal homologous and heterologous H5N1 challenges.

This study of magic-angle twisted trilayer graphene moiré superconductors using scanning tunnelling microscopy and spectroscopy identifies two energy gaps that develop from many-body resonance in this highly tunable class of materials.

Single iron atoms on nitrogen-doped carbon catalysts are a promising alternative to platinum for the oxygen reduction reaction on fuel cell cathodes, but commonly suffer from low stability. Here an in situ chemical vapour deposition synthetic approach is presented, enabling high iron active site dispersion and reducing surface porosity, which mitigates demetallation and carbon corrosion, ensuring high activity and stability.

People constantly decide whether to stop what they are doing to do something else. Here, the authors show that the quality of available options has a greater influence on people’s decisions to help others than to help themselves.

Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

To humanize models of liver metabolic disease research, authors develop a microfluidic platform leveraging human hepatic spheroids integrated with microvasculature and circulating monocytes to model hepatic insulin resistance.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

In a phase 1 trial testing healthy donor fecal microbial transplantation with immune checkpoint blockade in patients with previously untreated renal cell carcinoma, treatment was safe with an encouraging response signal and microbiome analyses, suggesting specific donor taxa associations with toxicity.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

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.

Conventional methods for human motion analysis using sensors tightly attached to the body are often uncomfortable. Here, the authors demonstrate motion recognition and prediction using sensors embedded in garments. The results provide guidance for the development of wearable technology integrated into everyday clothing.

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.

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.

An allosteric site on the E3 ligase adapter cereblon can be targeted to modulate the efficacy of cereblon in targeted protein degradation applications.

Long-period radio transients emit periodic radio pulses of unknown origin. The longest-lived source, GPM J1839−10, has a 21-min spin and 9-h orbit, resembling the more rapid white dwarf pulsars that are powered by binary interaction, potentially linking the classes.

Chang et al. found that nuclear reactive electrophile stress suppresses translation through HNEylation at C436 of NCBP1, triggering alternative splicing of S6K1, a key regulator of translation.

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.

Hole spin qubits in germanium have seen significant advancements, though improving control and noise resilience remains a key challenge. Here, the authors realize a dressed singlet-triplet qubit in germanium, achieving frequency-modulated high-fidelity control and a tenfold increase in coherence time.

Laser flash melting experiments have rendered cryo-EM fast enough to observe the microsecond motions of proteins. The authors extend the observation window of this emerging technique tenfold, to hundreds of microseconds, by sealing cryo-EM samples in ultrathin liquid cells.

GATA6 maintains epithelial traits and limits EMT in pancreatic cancer. Combined MEK and HDAC inhibition restores GATA6+ tumor cells, boosting MHCI expression and CD8+ T cellmediated anti-tumor immunity.

Energy gaps can be induced by spatial modulation of the electronic potential. Here, the authors demonstrate a large and robust energy gap in a free-standing carbon nanotube utilizing a 15-gate keyboard that spatially modulates the local potential.

Circadian clock in adipocytes maintains metabolic health by regulating mitochondrial complex I respiration.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

Projected impacts of climate change on malaria burden in Africa by 2050 highlight the urgent need for climate-resilient malaria control strategies and robust emergency response systems to safeguard progress towards malaria eradication.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

This study reveals high-spin state formation and quintet-mediated emission in diphenylhexatriene oligomers. Quintet states dominate delayed fluorescence up to room temperature, establishing a spin-selective platform for quantum technologies.

An integrated optical parametric amplifier on thin-film lithium niobate achieves more than 17 dB gain with less than 200 mW input power.