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Cold exposure in mice activates brown fat to deny tumours glucose, and the future of extreme heatwaves.

Property coupling by heteroepitaxy is severely limited in material combinations with highly dissimilar bonding. This report presents a chemical boundary condition methodology to actively engineer two-dimensional film growth in such systems that otherwise collapse into island formation and rough morphologies.

Experts say the country’s strong scientific performance is likely to be sustained in the coming years.

In a randomized trial enrolling Black adults residing in food deserts in Boston, Massachusetts, who were undergoing treatment for hypertension, home-delivery for 3 months of groceries designed to provide a low-sodium diet, together with dietician counseling, reduced blood pressure beyond a monetary stipend, an effect that was maintained for an additional 3 months after the intervention ended.

Laser cooling of molecules with more than six atoms is challenging, mainly due to vibrational loss to dark states. Now, taking a step towards the development of a ‘quantum functional group’, it has been shown that such vibrational loss in molecules like phenol can be greatly restricted by functionalizing with a Ca(I)–O unit, which may serve as a generic qubit moiety.

Multimodal spatial imaging of Leishmania donovani-induced hepatic granulomas reveals LPCAT2-mediated lipid membrane remodeling in myeloid cells as a key immunometabolic feature of granuloma formation and macrophage activation.

Photosystems need auxiliary proteins to assist their assembly. Cryo-electron microscopy of a cyanobacterial photosystem II assembly intermediate at 2.94 Å reveals mechanisms protecting against photodamage during vulnerable stages of biogenesis.

Here the authors identify nicotine-derived inhibitors of the SARS-CoV−2 main protease that outperform Paxlovid in cells and mice, remain effective against resistant variants, and show broad activity against multiple human coronaviruses.

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.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Interesting proximity effects can occur at the interface of superconducting and ferromagnetic oxides, but they are poorly understood. Here, the authors use scanning tunnelling and electron microscopy techniques to investigate such an interface, showing that the charge transfer has an upper limit of 1 nm.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

Authors provide real-world evidence demonstrating that rifaximin use in patients with cirrhosis and hepatic encephalopathy was associated with increased antimicrobial resistance, increasing the risk of infection-related complications and mortality.

The study presents a recyclable polymer system that stores solar energy and releases it as hydrogen on demand, offering an efficient and sustainable route for renewable energy storage and fuel generation.

A circular economy for plastics offers a promising solution to the pollution crisis. Here the authors take advantage of the unique chemistry of polydiketoenamine resins, showing how plastics can be biorenewable and recyclable by incorporating biosourced triacetic acid lactone.

Certain specific antigens have been shown to activate T cells in an MHC independent manner. Here the authors show a phycoerythrin reactive mouse TCR which recognises native protein and characterise the molecular nature of this interaction and that this specific TCR can be selected in the thymus.

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.

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.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The authors present a scalable mass spectral search tool that identifies both known molecules and structural variants by estimating match significance. The method revealed biosynthetic pathways in Streptomyces, expanding the scope of metabolite discovery.

Snowball Earth glaciations were some of the most extreme climate events in Earth history, and are temporally linked to major biogeochemical changes. Here, using geochemical proxies, the authors show that during the Marinoan glaciation, there was likely open water, active oxygen production, and nitrogen cycling.

Here, the authors describe scDEEP-mC, an improved single-cell whole-genome bisulfite sequencing method for complex libraries and deep genomic coverage, and show advanced analyses of allele-specific methylation, replication dynamics, and X-inactivation.

The study shows that exciton diffusivity in semiconducting moiré superlattices can be strongly modulated by correlated electrons, revealing intriguing interactions and ushering in avenues for quantum optoelectronic technologies.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Many major mass extinction events have been associated with large volcanic eruption events, with the argument that large volumes of volcanic degassing could trigger past global climate changes. Here, the authors find that during the end-Triassic extinction event volcanic pulses emitted large amounts of CO₂ comparable to projected anthropogenic emissions for the 21^st century in the future 2 °C warming scenario.

Square and rectangular beams made with new condenser apertures enable more efficient image capture in low-dose transmission electron microscopy with no compromise to image quality in single-particle cryoelectron microscopy.

The amyloid beta peptide can aggregate into insoluble plaques, which may indicate the onset of Alzheimer's disease. In a mouse model of Alzheimer's disease, Cao and colleagues report a phenotype of altered connectivity in the olfactory neuronal circuit that precedes amyloid plaque deposition.

Not all megakaryocytes are created equal, with sub-populations identified that generate platelets and differentially regulate blood stem cells. These sub-populations, conserved in humans, are important in treating blood and clotting disorders.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.