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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 Ocean Equity Index provides a systematic, twelve-criteria framework to assess and improve equity in ocean initiatives, projects and policies, producing structured data that guide evidence-based decisions and support more equitable outcomes for coastal communities and ecosystems.

Coastal and marine projects in the Global South can exacerbate existing contextual inequities, particularly in high-stakes locations found across all ocean basins and identified using current investment levels and a composite index of inequity.

Static protein structures can capture the association of lipids, but it is unclear whether the association is due to lipids acting as long-lived ligands or the solvation of preferred lipids around the protein. A computational-experimental framework has now shown that for the protein CLC-ec1, it is the change in lipid solvation energies that drives dimerization, with preferred lipids around the protein modulating this driving force.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

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.

The frequency of severe droughts is increasing in many regions around the world as a result of climate change. An analysis of tree growth and mortality data from forests worldwide suggests that large trees fare worse under drought than small trees.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Grimes and colleagues integrate multiomic features to create a framework that allows the isolation of discrete cell states across hematopoiesis and exploit the underlying gene regulatory networks to identify lineage restriction within multilineage progenitors.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

A retrobiosynthetic algorithm that relates known antibiotics by the similarities of their biosynthetic pathways to cluster them into distinct classes. Focusing on the telomycins helps to define the mechanism of action of this antibiotic class.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

Microbial natural products represent a large reservoir of potential pharmaceutical agents. Here, Johnston et al. describe a computer-automated programme for connecting genome sequences with identified and isolated natural products.

Selvakumar, Clayton et al. use a porcine model of myocardial infarction and PSC-CM transplantation and identify atrial and pacemaker-like cardiomyocytes as the cause of engraftment arrhythmias and surface marker signatures to distinguish between arrhythmogenic and non-arrhythmogenic cardiomyocytes.

PRDM9 is a PR domain containing histone methyl transferase which expression is normally restricted to the germline that has also been linked to a number of somatic cancers. Here the authors describe the identification of a small molecule that selectivity inhibits the methyltransferase activity of PRDM9 in biochemical and cellular assays

Whether or not marine protected areas (MPAs) deliver positive outcomes for both people and nature remains a challenging question. Using a statistical matching approach, this study provides quantitative evidence of co-benefits for fish and people associated with MPAs in the Mesoamerican region.

An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

We find that justice considerations constrain the integrated Earth system boundaries more than safety considerations for climate and atmospheric aerosol loading, and our assessment provides a foundation for safeguarding the global commons for all people.

The global rush to develop the ‘blue economy’ risks harming both the marine environment and human wellbeing. Bold policies and actions are urgently needed. We identify five priorities to chart a course towards an environmentally sustainable and socially equitable blue economy.

Reanalysis of bipedal trackways from Laetoli site A in Tanzania suggest that the footprints were made by a hominin that coexisted with at least one other hominin species.

A meta-analysis reveals that the presence of exotic species has a modest but significantly negative impact on the ecological properties of native marine communities and identifies the exotic species that exert the most harmful effects.

In this Resource article, the authors integrate genomic, bioinformatic and flow cytometric data from human bone marrow to provide an atlas of hematopoietic progenitor cell states in health and disease.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Co-production includes diverse aims, terminologies and practices. This study explores such diversity by mapping differences in how 32 initiatives from 6 continents co-produce diverse outcomes for the sustainable development of ecosystems at local to global scales.

While marine protected areas are key for supporting biodiversity and coastal communities, the outcomes can be, and can be perceived, as a mixed bag. Synthesizing research from 118 articles, this Analysis draws broad insights about both the effects of marine protected areas as well as which aspects remain understudied.

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

Transcriptomic and epigenomic profiling of human microglia identifies putative gene regulatory mechanisms for 21 Alzheimer’s disease (AD) risk loci. SPI1/PU.1 is nominated as a key regulator of microglia gene expression and AD risk.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Achieving inclusive and sustainable ocean economies, long-term climate resilience and effective biodiversity conservation requires urgent and strategic actions from local to global scales. We discuss fundamental changes that are needed to allow equitable policy across these three domains.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Wildlife are central to nature’s contributions to people (NCP) but are often overlooked in NCP policy and management. This Perspective presents evidence for the integral role of wildlife in supporting human well-being and proposes their recognition and incorporation into conservation decision-making as wildlife’s contributions to people (WCP).

Sub-lethal marine heatwaves is shown experimentally to lead to suppression of reproduction in sea urchins. This effect helps explain historical collapses in larval supply that affect population dynamics and is consistent for populations across the latitudinal range.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.