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The environmental effects of deep-seabed mining can only be managed within acceptable limits if they are effectively monitored. To achieve this for deep-seabed mining in international waters, four critical components first need to be addressed by the International Seabed Authority: baseline knowledge, indicators and thresholds, area-based management tools, and technical capabilities.

The TREK K_2P channel activity is dynamically regulated by protein kinase-dependent signaling pathways involved in the development of various human diseases. Here, the authors report how phosphorylation at the proximal C-terminus induces allosteric deactivation of the selectivity filter gate.

High-quality listening behaviors (e.g., follow-up questions) are linked to behavioral and self-reported markers of social connection in conversations between strangers and may account for the effectiveness of a social connectedness intervention.

The Global Flourishing Study provides a comprehensive view of the distribution and determinants of well-being by assessing domains such as health, happiness, meaning, character, relationships and financial security. Initial findings reveal significant variations in flourishing across countries and demographic groups, with factors such as age, marital status and religious service attendance showing strong associations with well-being.

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.

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.

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.

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.

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.

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.

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.

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

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 characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

Activation of thermogenic adipocytes is a strategy to combat metabolic diseases. Here the authors report that GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1, and contributes to the regulation of glucose and energy metabolism.

Leigh syndrome (LS) is a severe neurometabolic disorder which lacks effective models. Here, the authors developed human neuronal models of LS carrying mutations in SURF1 which show impaired neuronal morphogenesis due to metabolic deficiencies.

Receiving a favour may induce a feeling of indebtedness in a beneficiary. Here, the authors develop and validate a model that captures the psychological, computational, and neural bases of how indebtedness arises and influences reciprocity behaviour.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models. Here the authors report CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time at increased throughput.

A rash of road construction is causing widespread change in the world's largest tropical forest — with potentially global consequences.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Individuality in social behaviour is of interest across several academic fields, yet there are many barriers to interdisciplinary efforts. In this Perspective, Kuper et al propose an integrative, interdisciplinary approach, and detail their recommendations for researchers interested in this topic.

Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.

Large language models (LLMs) can enhance experimental research via the design and implementation of studies, and data analysis. When available, we suggest using LLM-based tools that require no coding skills and only a simple human–AI interaction. We discuss the social risks associated with this integration.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Insects use the sun for navigation, compensating for its movement throughout the day; a process that remains poorly understood. This study proposes a model of how oscillatory signals of clock neurons could allow insects to transform the sun position into a stable geocentric heading reference.

The characterisation of the molecular features of multiple myeloma (MM) remains challenging. Here, the authors identify a subset of MM patients with a dismal clinical outcome, harbouring both chromosomes 1q CN gain and 13 CN loss and overexpressing CCND2.

The iRGD tumor-penetrating peptide can achieve tumor specific drug delivery but whether and how it can penetrate into desmoplastic tumors is unknown. Here, the authors show that β5 integrin expression on tumor cells, mediated by CAFs-derived TGF-β, is required for iRGD penetration into the desmoplastic PDAC microenvironment and that iRGD-based combination therapy is effective in PDAC mouse models.

A study introduces curcumin biosynthesis in Arabidopsis by expressing the turmeric genes DIKETIDE-CoA SYNTHASE and CURCUMIN SYNTHASE 2, and the monomers curcumin and phenylpentanoids were successfully incorporated into the lignin cell wall to enhance biomass processing.

Thyroid dysfunction is involved in many diseases. Here, the authors provide insights into the genetics and biological pathways influencing important thyroid function parameters, showing potential causal effects on many clinical outcomes.

In this Consensus Statement, a consortium of microbiome scientists discuss current sequencing data sharing policies and propose the use of a Data Reuse Information (DRI) tag to promote equitable and collaborative data sharing.

Spondyloarthropathies are characterized by a distinct pattern of inflammation at distinct anatomical sites and are associated with elevated expression of interleukin 23 (IL-23). Daniel Cua and his colleagues identify an IL-23–responsive CD4⁻CD8⁻ T cell population located within entheses. Systemic overexpression of IL-23 activates these cells and recapitulates aspects of the human disease in mice, and neutralization of IL-17 and IL-22 decreases pathology, suggesting new therapeutic targets for these disorders.

A vacuum-packaged resonator has been designed that contains the solution with particles of interest inside microfluidic channels. It is demonstrated that this device can weigh single nanoparticles, single bacterial cells and sub-monolayers of proteins adsorbed on the channel walls with sub-femtogram resolution.