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SPX1 is an inositol (pyro)phosphate-dependent negative regulator of DNA binding by the PHR transcription factor. Here the authors show that SPX1 can also bind the promoter element targeted by PHR suggesting a role for SPX1 during phosphate deficiency.

Sticky-ended cohesion has historically been the driving force for DNA self-assembly and was employed for self-assembled crystals to avoid unpredictable packing; however, this limits the diversity of resulting architectures. Here, the authors employ composable DNA tiles to form complex 3D architectures using blunt-ended motifs with single duplex interfaces, leveraging the geometry of the tile and the terminal nucleobase identity to control self-assembly outcomes.

A M5 earthquake triggered the 2018 Sierra Negra eruption after 10 hours. Subsequent microseismicity revealed a cryptic fluid phase facilitated magma intrusion, highlighting that cascading processes are potentially essential for eruption initiations.

Fibrosis is the final common pathway in chronic kidney disease and a potential target for therapeutic interventions. Here, the authors use intravital imaging to show that pyrimidinergic calcium signaling links tubular injury to fibroblast activation, and that blocking this pathway reduces fibrosis

Using large-scale genetics and Genomic SEM/E-SEM, the study shows broad shared genetic risk between many physical illnesses and internalizing, neurodevelopmental, and substance-use disorders, revealing a transdiagnostic illness factor and cross-cutting disease pathways.

Glacial cycles can modulate volcanism. Using models of magma transport under ice loading, this study shows that ice sheets can stall rising magma at depth, suppressing eruptions and promoting magma evolution until deglaciation resumes activity.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

Many GPCRs signal from endosomes, which requires active G proteins at this location. Here, the authors describe how active Gα_s accumulates on endosomes and reveal location-biased selectivity in GPCR-mediated G protein activation.

This study shows that mithramycin suppresses the EWS::FLI1 transcription factor in Ewing sarcoma using a hybrid CUT, Tag & GRO assay, revealing mechanism, need for continuous dosing, and supporting clinical use of next-gen analog AIT-102.

Sepsis is a heterogeneous inflammatory disease and it is believed treatment requires suitable stratification based on the underlying disease pathology and immunology. Here the authors show genetic variation in the regulatory elements of MTOR can impact neutrophil-T cell cross talk in the context of pneumonia associated sepsis, highlighting a genetic framework for targeted patient stratification.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

By combining optimal transport with machine learning, this study infers trade frictions in global food markets, highlighting how conflict, trade disputes, and shifts in political-economic relations are associated with changes in agricultural supply.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Cholera remains a significant public health burden in sub-Saharan Africa, but the mechanisms of continental and regional spread remain undefined. Here, the authors investigate recent patterns of spread using Vibrio cholerae genomic surveillance data collected by a consortium of seven African Union member states from 2019-2024.

Most GWAS have focused on common variants or rare protein coding variants. Here, the authors interrogate the contribution of rare non-coding variants for anthropometric traits, identifying new genes associated with increased BMI and height.

The physiology and behavioral function of proprioceptors that detect joint limits are not fully understood. In this study, the authors used calcium imaging, optogenetics, behavioral genetics, and the connectome to demonstrate that hair plate proprioceptors on the fly leg detect joint limits and engage circuits to drive the leg away from those limits.

Here, the authors conduct a GWAS for eGFR, then a three-stage regional meta-analysis using GWAS summary data from the Eastern, Western, and Southern African geographical regions. Followed by fine mapping, colocalization, functional annotation, pathway analysis, and phenome-wide association studies showing weaker APOL1 effects in Africa.

Many viral vaccine antigen candidates are transmembrane glycoproteins, and their development requires methods which allow their biophysical characterization. Here authors present an optimized nanodisc assembly platform which provides reproducible, scalable, and accurate replication of the vaccine candidates for detailed analysis.

New strategies to synthesise metal-based anticancer agents are critical for advancing chemotherapy. Here, the authors apply click chemistry to derive copper complexes that induce DNA strand breaks in recalcitrant cancer cells, validating an innovative route for metallodrug design.

Small-cell lung cancer (SCLC) is a highly aggressive cancer type with immunosuppressed phenotype. Here, the authors find that depletion of nonhomologous end joining DNA repair regulator PRKDC is able to induce activation of the cGAS/STING pathway and potentiate the efficacy of immunotherapy in SCLC pre-clinical models.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Given rising diabetes prevalence globally, access to diabetes treatments is gaining urgency. Here, the authors show patterns of glucose-lowering medication use for diabetes across 62 low- and middle-income countries.

Repurposing existing drugs to target new disease-associated genes is a promising strategy, but identifying these targets can be challenging. Here, the authors develop GenT, an approach that uses GWAS data to identify disease-associated druggable genes.

Dissolved Fe(II) could greatly enhance uptake of dissolved phosphorus by common phyllosilicate minerals in the Archean and Proterozoic ferruginous oceans, serving as a key mediator in early phosphorus cycling and habitability

Optical skyrmions can be generated in free space, but topologically protected information transfer requires skyrmions to be stable upon propagation through complex media. Here, authors demonstrate the topological resilience of classical and quantum optical skyrmions transmitted through experimentally simulated atmospheric turbulence.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Bioactivity benchmarks are key to evaluating and improving methods to predict chemicals’ specific biological activity. Here, the authors find existing benchmarks poorly suit this goal; their assays are often well-predicted simply by counting cells. They propose new guidelines and curated benchmarks.

Quantum fluctuations have been detected in a macroscopic, millimole-scale solid-state spin ensemble without the use of external excitations, enabling non-invasive quantum sensing techniques.

Non-equilibrium two-dimensional melting is less understood than its equilibrium counterpart. Now it is shown that topologically driven melting in a two-dimensional crystal of charged colloids is the same irrespective of the mechanisms that generate the defects

The growing demand for rare earth elements (REEs) underscores the need for sustainable recovery methods and a reliable supply. Here the authors establish a platform using a yeast to produce bio-oxalic acid for REE recovery, achieving 99% REE recovery from low-grade ore.

Schizophrenia is a complex brain disorder with its underlying protein changes generally not well understood. Here, authors show widespread alterations in the prefrontal cortex, marked by reduced energy production and disrupted synaptic function.

Weak social connections are thought to influence how people age. This study finds that deficits such as living alone or low social integration relate to faster physiological ageing, while no statistically significant associations are observed with perceived aging.

Although antiretroviral therapies (ART) have expanded the life expectancy of patients with HIV, they are not curative due to the presence of latently infected cells. Here, the authors present IMC-M113V, a bispecific soluble TCR targeting the HIV peptide Gag_77-85 complexed to HLA-A*02:01 as an approach for targeting HIV reservoirs and test safety, tolerability and pharmacodynamics in a first-in-human clinical trial on 12 HLA-A*02:01-positive male individuals on ART.

Nechanitzky et al. examine the cell-intrinsic role of choline acetyltransferase (ChAT)-expressing B cells in germinal center immune responses.

Neural crest cells are migratory cells unique to vertebrates. Here they show that NR6A1 is a key regulator of neural crest cell formation and survival by downregulating pluripotency-associated genes, while upregulating neural crest cell specifier genes and epithelial cell to mesenchyme cell transition.

Wang et al. analyzed data from the Detroit Neighborhood Health Study to explore links between social adversity, post-traumatic stress and epigenetic regulation through blood-derived micro-RNA profiles.

This study analyses whole-genome sequencing data of cancer samples from 10,983 patients and explores relationships among mutational signatures, various biomarkers and clinical outcomes.

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.

All-van der Waals multiferroic tunnel junctions exhibit four non-volatile resistance states with full layer tailorability, enabling up to 10⁶% tunnelling electroresistance, 10⁴ A cm⁻² ON-state current density and room temperature operation.

This multidisciplinary response to investigate the large outbreak of unknown febrile illness in the Panzi Health Zone in the Democratic Republic of the Congo in late 2024 suggests that the outbreak was largely associated with malarial cases and concurrent viral respiratory infections.

Rare coding variants that reduce the activity of a protein can have a beneficial impact on health. Here, researchers identify rare genetic variants in the CHRNB3 gene that associate with reduced cigarette smoking across diverse populations.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD⁺ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and modulated lipid metabolism in vitro and in a mouse hepatic steatosis model.

Anderson et al. demonstrate that the glucokinase activator AZD1656 reduces inflammation and reverses cardiac dysfunction and metabolic remodeling in mice with diabetic cardiomyopathy.

A new platform making use of hexagonal boron nitride interfaced with the molecular superconductor κ-(BEDT-TTF)₂Cu[N(CN)₂]Br is demonstrated for realizing cavity-altered materials, confirmed by magnetic force microscopy and nano-optical measurements.

A comparative analysis of trait data combined with a mathematical model suggests that dietary specialization drives selection towards the smallest and largest body sizes in terrestrial mammals, as generalists outcompete specialists at intermediate sizes.

A platinum(II) azido complex (complex 1) that releases platinonitrene upon X-ray exposure induces DNA damage and enhances immune checkpoint blockade outcomes via the abscopal effect.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Using 63 globally distributed grassland and shrubland sites from the International Drought Experiment, this study identified plant traits linked to drought resistance after 1 year of extreme drought across growth forms, lifespans and climate.