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Here, the authors have mapped the antibody response of the adeno-associated virus 9 (AAV9) gene therapy vector Zolgensma. AAV9 capsid variants were designed to escape this response while preserving manufacturing and biodistribution properties.

During the last glacial termination, climate changes associated with the Bølling–Allerød warming were seen throughout much of the Northern Hemisphere. A combination of ice-core records and box modelling shows that this climate change was nearly synchronous across high and temperate latitudes.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

CRISPR-TO, a system for programmable control of spatial localization of cellular RNAs, is presented and enables functional investigation of endogenous RNA localization in diverse living cells.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Synthetic apparel is a major contributor to global plastic leakage driven by mismanaged apparel waste.

Drivers of crop yield variability require quantification, and historical records can help in improving understanding. Here, Webber et al. report that drought stress will remain a key driver of yield losses in wheat and maize across Europe, and benefits from CO₂ will be limited in low-yielding years.

The Verwey transition in magnetite was reported 80 years ago but identifying the underlying mechanism has been difficult. Here the authors show that structural distortions associated with the Verwey transition emerge as local fluctuations at the Curie temperature, confirming their link with magnetic order.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

Joana Carlevaro-Fita, Andrés Lanzós et al. present the Cancer LncRNA Census (CLC), a manually curated dataset of 122 long noncoding RNAs (lncRNAs) with experimentally-validated functions in cancer based on data from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. CLC lncRNAs have unique gene features, and a number display evidence for cancer-driving functions that are conserved from humans to mice.

Peter Campbell and colleagues identify PLCG1 and PTPRB as new driver genes for angiosarcoma through whole-exome sequencing of tumor samples. They find somatic PTPRB mutations in 10 of 39 cases and PLCG1 mutations in 3 of 34 cases, along with mutations in known cancer-related genes.

Here, the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person are sequenced, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The data provide insight into the causes of tumour formation and the development of the cancer genome, with the dominant mutational signature reflecting DNA damage due to ultraviolet light exposure.

Using single-cell and multi-omics data of fetal blood, a high-resolution molecular map of dysregulated haematopoiesis in Down syndrome is provided.

Pathogenic germline variants associated with childhood cancer risk could be subject to evolutionary constraints. Here, the authors analyse publicly available germline data in large cohorts and observe that paediatric cancer predisposition syndrome genes are highly constrained in the general population.

Pancreatic cancer is highly aggressive, usually because of widespread metastasis. Here, next-generation DNA sequencing has been used to detect genomic rearrangements in 13 patients with pancreatic cancer and to explore clonal relationships among metastases. The results reveal not only considerable inter-patient heterogeneity, but also ongoing genomic instability and evolution during the development of metastases.

Circular extrachromosomal DNA in high-risk medulloblastoma contributes to tumor heterogeneity and associates with relapse and survival. Enhancer rewiring events involving known oncogenes are frequent events, affecting transcription and proliferation.

Tree mortality has been shown to be the dominant control on carbon storage in Amazon forests, but little is known of how and why Amazon forest trees die. Here the authors analyse a large Amazon-wide dataset, finding that fast-growing species face greater mortality risk, but that slower-growing individuals within a species are more likely to die, regardless of size.

Unusual atmospheric conditions, combined with a strong positive NAO, induced a record-intense marine heatwave in northern Norway in 2024, triggering a surge in salmon lice infestations at aquaculture sites, according to an analysis of observational data and ocean model hindcasts.

High-dimensional datasets derived from time-resolved live imaging of leukocytes in mice were used to identify leukocyte identities and dynamic neutrophil states with high cellular resolution.

Simanek et al. discovered variants that arise in the protein responsible for synthesizing a molecule required for bacterial communication, which mediates the progression of virulence in the pathogen Pseudomonas aeruginosa.

Disturbance regimes from fire, drought, harvest and insects will probably intensify in the future and under climate change. Despite partial offsets from regrowth, disturbance from fire and harvest reduces carbon uptake and storage in boreal forests, impacting the strength of this carbon sink.

Cassini’s Cosmic Dust Analyzer mass spectra of ice grains emitted by Enceladus show the presence of sodium phosphates, suggesting that phosphorus is readily available in Enceladus’s ocean in the form of orthophosphates.

Cities may host surprisingly diverse and functionally distinct biological communities. This global analysis on 5302 vertebrate and invertebrate species finds evidence of 4 trait syndromes in urban animal assemblages, modulated by spatial and geographic factors.

Across large spatial scales, climate is more important than soil conditions for plant adaptation and variation in root-associated filamentous eukaryotic communities.

In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.

Mutant RAS family members occur in a wide range of tumour types, and there is a great interest in identifying isoform-specific inhibitors. Here, the authors characterise two designed ankyrin repeat proteins (DARPins) that specifically inhibit the KRAS isoform by binding to the region around the KRAS-specific residue histidine 95 and show that they affect KRAS/effector interactions in different ways.

Aberrant thymocyte developmental programming results when interactions between thymic stroma and pre-T cell receptors occur in the absence of major histocompatibility complex bound to antigen peptide.

Reconstructing biodiversity trends in deep time is confounded by uneven sampling of the available fossil record. Here the authors apply a subsampling approach to a tetrapod fossil occurrence dataset and show extinction of important clades was driven by variation in sea level.

Diabetes is associated with aberrations in glucose metabolism. Here the authors perform a genomic screen in fruit flies to identify new regulators of fly glucose metabolism, and show that mice lacking the murine homologue of one of their hits, the protein kinase CK1alpha, in the adipose lineage develop diabetes.

The dorsal pons in the brainstem is packed with clusters of neurons, including the parabrachial nucleus, that are involved in many vital functions. Here, authors use single nucleus RNA sequencing and MERFISH to create a spatially defined transcriptional atlas of this region.

Coventry et al. show that spatial demonstratives—such as ‘this’ and ‘that’ in English—are selected on the basis of whether the speaker is able to reach the object or not, across 29 diverse languages.

Global spatiotemporal patterns of plant diversification are unclear. Here, the authors use a genus-level phylogeny and global distribution data for 14,244 flowering plant genera, finding a negative correlation between spatial patterns of diversification and genus diversity.

Understanding the dynamics of species interactions can help predict community responses to climate change. A spatially explicit model finds that species interactions and competition mitigate the harmful impacts of climate change, and that temperature-dependent competition makes communities more variable and responsive to changing climates.

Neutrophils are versatile immune cells that may also serve as antigen-presenting cells (APC). Here the authors show that engaging FcγRs on neutrophils with immune complexes or an anti-FcγR-antigen conjugate induces neutrophil APC with comparable functions as classical dendritic cells, and with therapeutic potentials for cancer and infectious diseases.

Immune-checkpoint inhibitors (ICI) constitute a paradigm shift in the treatment of non-small-cell lung cancer (NSCLC); however, identifying the minority of patients who derive long-term benefit remains problematic, particularly among those with targetable oncogenic drivers who have typically been under-represented in or excluded from clinical trials of ICIs. This Review summarizes the associations of common oncogenic drivers of NSCLC with sensitivity or resistance to ICIs as well as the underlying effects on the immune tumour microenvironment. Potential vulnerabilities that could potentially be exploited to overcome primary resistance to ICIs conferred by certain oncogenic drivers are also highlighted.

Fasting-activated hypothalamic AgRP-expressing neurons trigger fasting-induced hypothalamic–pituitary–adrenal axis activation through projections to the paraventricular hypothalamus, where they activate CRH neurons by presynaptically inhibiting the terminals of tonically active GABAergic afferents from the bed nucleus of the stria terminalis.

Liquid biopsies could be valuable tools to monitor breast cancer progression and evolution. Here, the authors investigate genomic profiling of tissue and liquid biopsies in a large cohort of patients with breast cancer during the course of therapy to characterise tumour evolution and acquired mutations.

Both host diet and phylogeny have been argued to shape mammalian microbiome communities. Here, the authors show that diet predicts the presence of ancient bacterial lineages in the microbiome, but that co-speciation between more recent bacterial lineages and their hosts may drive associations between microbiome composition and phylogeny.

Adipocyte progenitor cells (APCs) are found tethered to adipose tissue blood vessel walls and can differentiate into adipocytes. Here the authors show that PPARγ controls angiogenesis by stimulating APC–blood vessel interaction and retention via a transcriptional network that includes PDGFRβand VEGF.

Contrary to expectations from pollen and dust records, Southern Hemisphere subtropical regions experienced the greatest climatic moisture during glacial periods of the Late Pleistocene, which may not have been an obstacle to movement and expansion of animals and plants.

The 79 North Glacier features Greenland’s largest floating ice tongue, which has been thinning from below in the last few decades. Here, the drivers of the upward trend and interannual variability of basal melt are disentangled.

Researchers at Newcastle University have discovered a mechanism by which earthquakes create bursts of hydrogen peroxide and oxygen in hot underground fractures. These may have played a vital role in the early evolution and origin of life on Earth.