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The ZFTA–RELA fusion, an oncogene for ependymomas, promotes the production of itaconate, and its dependence on this metabolite represents a new therapeutic target for this cancer.

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.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

Moisan, Cowan and colleagues perform a small-molecule screen to identify compounds that promote white-to-brown adipocyte conversion in vitro. They report that two inhibitors of the JAK–STAT signalling pathway stimulate browning of human adipocytes.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Cowan and colleagues have developed a method to efficiently differentiate human pluripotent stem cells into functional white or brown adipocytes, through the transient expression of PPARG2 alone or in combination with CEBP and PRDM16. The programmed cells are able to give rise to ectopic fat pads with white or brown adipose tissue characteristics.

On the basis of data from >329,000 migratory birds, this study presents multispecies migratory connectivity as a parameter representing exposure to global change and shows that connections between breeding regions in Canada and non-breeding regions in South America are at greatest risk from global change.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

The interface between two oxide materials can play host to numerous exotic phenomenon. Here, the authors observe a four order of magnitude change in the conductance at a lanthanum-aluminate–strontium-titanate interface controlled by surface protonation, which can be reversed by exposure to light.

The number of known high-oxidation-state transuranic compounds remains limited, and these typically feature high coordination numbers and/or multiply-bonded donor atoms. Now, a tetrahedral, pentavalent neptunium complex supported by four monoanionic ligands has been isolated and characterized. This complex is stable in the solid state and undergoes a proton-coupled electron transfer reaction in solution.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

The development of a desktop nanofabrication tool allowing high-resolution patterning and high-throughput synthesis is a long-standing goal in many nanoscience fields. Here, the authors report a system that can write arbitrary patterns composed of diffraction-unlimited features over square centimetre areas.

Using historical aerial photographs and new bed topography data, accelerating changes on Kennicott and Root Glaciers, Alaska since 1938 are documented. These observations inform projections showing 38–63% mass loss by 2100, depending on future climate.

The iron–sulphur enzyme IspH catalyses the final step of the methylerythritol phosphate isoprenoid biosynthesis pathway. Spanet al. report that IspH can hydrate acetylenes to aldehydes and ketones, in addition to its role as a 2H⁺/2e⁻reductase.

Currently, gold recovery from waste materials requires inorganic cyanides and more environmentally benign methods are required. Here, the authors report that host–guest interactions between α-cyclodextrin and gold lead to the precipitation of one-dimensional superstructures, offering a selective and green alternative.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Identification and characterization of a third type of adipocyte known as brite (brown-in-white) adipocytes has drawn considerable attention, as these cells are thought to regulate energy expenditure and may help combat obesity. Remarkably, white adipocytes can adopt the characteristics of brite adipocytes following cold stimulation, and this process is reversible in vivo.

LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

The nuclear farnesoid X receptor (FXR) is activated by bile acids and influences energy metabolism. Here, the authors report a small molecule inhibitor of FXR, glycine-ß-muricholic acid, which inhibits FXR in the intestine and improves metabolic homeostasis by repressing intestinal ceramide synthesis.

PBK is a mitotic kinase implicated in cancer. This study reveals how PBK evicts key C2H2-zinc finger transcription factors such as Ikaros, Aiolos and CTCF from DNA as cells divide, regulating mitotic chromatin accessibility and chromosome compaction.

Djeghloul, Cheriyamkunnel et al. apply chromosome sorting to isolate active and inactive X chromosomes and report a role for Hbo1 and Msl histone acetyltransferase complexes in preserving active X chromosomes in female cells during mitosis.

Naturally occurring peptides with high membrane permeability often have backbone ester bonds. Here, the authors investigated the effect of an amide-to-ester substitution on membrane permeability of peptides and found the substitution is useful for improving membrane permeability of cyclic peptides.

Reforms of energy markets are necessary to face the low carbon transition but are problematic to measure. New data evaluate implicit taxes and subsidies for gasoline in almost all countries at monthly intervals showing mixed results that highlight the difficulty in implementing effective policy tools.

There is growing interest in designing electrolytes to enable Li-metal batteries. Here the authors show that asymmetric solvents improve lithium redox kinetics and achieve long cycle life in anode-free cells under electric vertical take-off and landing conditions, demonstrating potential for future high-power applications.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Haspin phosphorylates histone H3 threonine 3 (H3T3) to ensure proper progression through mitosis. Here the authors describe how Haspin engages a nucleosomal DNA supergroove, using electrostatic interactions, thereby promoting H3T3 phosphorylation.

Meta-analysis of 36,760 cases and 375,188 controls identifies 54 loci associated with susceptibility to cutaneous melanoma. Further analysis combining nevus count and hair color GWAS results provide insights into the genetic architecture of melanoma.

Wang, Tang and colleagues develop the low-signal signed iterative random forest pipeline to investigate epistasis in the genetic control of cardiac hypertrophy, identifying epistatic variants near CCDC141, IGF1R, TTN and TNKS loci, and show that hypertrophy in induced pluripotent stem cell-derived cardiomyocytes is nonadditively influenced by interactions among CCDC141, TTN and IGF1R.

The liver possesses the ability to regenerate following sudden injury. Here, the authors use single-cell RNA-sequencing and in situ transcriptional analyses to identify a new phase of liver regeneration in mice aimed at maintaining essential functions throughout the regenerative process.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Many climate models overestimate the snow amount in the Northern Hemisphere despite strong warming. Here the authors find that light snowfall and snow melting processes drive this mismatch and use these relationships to constrain future projections of snow water resources.

Braxton et al. report structures of human p97/VCP bound to the UBXD1 adaptor involved in autophagy. The structures reveal how UBXD1 utilizes multiple interaction domains to remodel and open the hexamer ring, revealing its role in p97 regulation.

The phenotype and function of immune cells could change during spaceflight. Here the authors use simulated microgravity, coupled to validation with spaceflight data, to assess whether there are distinct gene expression changes in resting and TLR 7/8 stimulated PBMCs and found conserved changes in IFN signalling, the cytoskeleton, IL-6 and sirtuin signalling.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Combining geographic information, climate data and colour mechanism at broad phylogenetic and spatial scales, the authors determine how transitions between pigmentary and structural colours influence bird speciation dynamics.

A large proportion of wetland extent is not mapped in currently available national datasets. Incorporating newly revealed wetlands into soil carbon mapping methods increases estimates of wetland soil carbon stock by 482%.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Cone photoreceptors signal to several bipolar cell types at one of the most structurally complex synapses in the central nervous system. Here, the authors show how the 3D organization of this synapse creates different signals in the postsynaptic OFF bipolar cell types.

Extreme weather events may raise public awareness of climate change. This comparative-case analysis shows that single events had limited impact on climate change discussion, but this was more common in Democratic communities and for weather events with a more certain attribution to climate change.

Efforts to produce aromatic monomers through catalytic lignin depolymerization were focused on aryl–ether bond cleavage, while the carbon–carbon bonds of a large fraction of aromatic monomers in lignin are difficult to cleave. Here, the authors report a catalytic autoxidation method using manganese and zirconium salts as catalysts to cleave the C–C bonds in lignin-derived dimers and oligomers from pine and poplar.