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The RNA-binding ubiquitin E3 ligase TRIM25 plays a critical role in antiviral immunity. Here the authors identify key RNA-binding residues of TRIM25, link RNA binding to antiviral activity, reveal RNA structural and sequence preferences, and investigate binding to the viral genome.

Forest restoration in LMICs can contribute to global C mitigation targets. Here, the authors assess the economic feasibility of forest restoration methods in Panama, i.e. natural regeneration, native species plantings, and enrichment planting, showing that not all methods are economically viable.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

The structure-function relationships of a β-helix, a folding motif formed by parallel β-strands arranged in a helical repetitive pattern, remain poorly understood and underexploited. Here, the authors reconstitute a protein β-helix by design from an elementary sequence of 18 amino acids, which self-assembles into a self-contained multifunctional motif exhibiting a range of biological functions.

GPCR dynamics are critical for signal transmission into the cell. Here, the authors probe receptor plasticity using molecular dynamics simulations, enabling the detection of allosteric sites and drug entry gateways for a broad range of GPCR types.

Single-cell analysis of patient brains and cortical organoids links disrupted developmental metabolic reprogramming to postnatal synaptic dysfunction in dup15q syndrome, revealing shared neuronal changes with idiopathic autism.

Here, the authors have identified a mutation in the gene GNA13 in patients with hypomelanosis of Ito and developmental anomalies, which triggers excessive RHOA/ROCK signaling and actin polymerization, leading to melanocyte rounding and failure in melanosome transfer to keratinocytes.

Liu et al. developed a platform to identify transcription factors (TFs) that turn stem cells into desired cell types. They discovered six key TFs that produce microglia efficiently, enhancing cell differentiation methods.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

Large language models are increasingly used for diverse tasks, yet we have limited insight into their understanding of chemistry. Now ChemBench—a benchmarking framework containing more than 2,700 question–answer pairs—has been developed to assess their chemical knowledge and reasoning, revealing that the best models surpass human chemists on average but struggle with some basic tasks.

In a cluster-randomized trial conducted across 70 medical centers in six countries, a 16-week structured educational program for healthcare providers improved adherence to guidelines for rhythm control but not for stroke prevention in individuals with atrial fibrillation.

Feynman’s diagrammatic technique is widely used in the description of quantum many-body systems. This work demonstrates an efficient method for summing Feynman diagrams with exponential computational cost in the diagram order, translating into polynomial scaling of the calculation time with the required accuracy.

Analysis of data on 971 bird species in natural habitat and cattle pasture in Colombia finds that near-national-scale losses of bird diversity greatly exceed losses recorded at the local scale, suggesting that extrapolations from local studies will severely underestimate biodiversity losses.

Heo, Xu et al. used comprehensive plasma proteomics to identify 416 plasma proteins (294 new) associated with Alzheimer’s disease and applied machine learning to select 7 proteins that were highly predictive of Alzheimer’s disease across multiple cohorts.

Ataxia-telangiectasia mutated protein (ATM) phosphorylates CD98HC to promote neutral amino acid antiporter trafficking. Here the authors show that ATM loss impairs glutamate, cystine, and arginine transport, driving metabolic stress and ataxia telangiectasia–like phenotypes.

Microbial communities, exposed to early Earth-like conditions in a modern microbialite reef, change cyclically due to seasonal environmental variations, implying evolved metabolic processes in microbialites over time, based on multiple chemical, physical, and biological analyses.

Ozone-depleting substances have been controlled by the 1987 Montreal Protocol, ensuring atmospheric concentrations are now in decline. Here, the authors use a 3D model and suggest that these controls have already had significant benefits, with much larger ozone depletion than previously thought avoided by the protocol.

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

Historical ecology uses a wide and varied range of sources to investigate long-term dynamics of ecosystems, species and their traits, and different dimensions of nature–human interactions. This Perspective discusses the value of this approach for biodiversity and conservation science, and offers a strategy for the continued development of the field.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

DNA methylation is a repressive modification that is essential for development. Here the authors reveal a critical role for DNA methylation in placental development during pregnancy. Failure to properly establish placental DNA methylation patterns compromises not only placental function, but embryo survival.

Using a new computational approach to identify senescent cells from single-cell transcriptomic data, the authors find that most senescent cells in the human brain are excitatory neurons with elevated CDKN2D/p19 expression, which often display Alzheimer’s disease-associated tau pathology.

In proliferative retinopathies, pathological vessels replace healthy ones, impairing vision. Here, the authors show that reprogramming the metabolic environment of retinal blood vessels from fatty acid oxidation to glycolysis promotes healthy revascularization and improves vision in proliferative retinopathy.

Renormalisation group methods serve for finding analytic solutions, critical points and computing phase diagrams of many-body systems. Here the authors demonstrate that renormalisation group schemes can be constructed for undecidable many-body systems, giving rise to the types of renormalisation group flow which are strictly more unpredictable than chaotic flows.

Here the authors show that chromosomal instability signatures can predict resistance to anthracycline-, taxane- and platinum-based chemotherapeutics in breast, ovarian and prostate cancer and sarcoma. Validation is performed through emulation of phase 2 and 3 clinical trials using real-world data.

The likelihood of severe COVID-19 increases with age upon SARS-CoV-2 infection and even milder disease manifestations might differ among age groups. Here authors show, by immune transcriptome analysis of samples from the upper respiratory tract and peripheral blood of participants from different age groups, that interferon responses are more typical for the young, while activation of myeloid, inflammatory, and coagulation pathways is exclusive to adults.

The replicative helicase CMG is targeted for removal or proteolysis by the E3 ubiquitin ligase TRAIP. This study describes how the de-ubiquitylating enzyme USP37 protects genome stability by preventing premature TRAIP-dependent CMG unloading when replication stress impedes timely termination.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Phase diagrams describe how a system changes phenomenologically as an external parameter, such as a magnetic field strength, is varied. Here, the authors prove that in general such a phase diagram is uncomputable, by explicitly constructing a one-parameter Hamiltonian for which this is the case.

Overexpression of c-MYC regulates tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). Here the authors identify ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target of PDAC.

The Human Endometrial Cell Atlas integrates single-cell transcriptomic datasets from women with and without endometriosis. Novel and known cell types are registered using spatial transcriptomics to provide a comprehensive map of the human endometrium in controls and endometriosis cases.