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Approved antibody–drug conjugates (ADCs) remain constrained by a limited repertoire of payloads with restricted modes of action. Here, the authors present phosphoramidate-based self-immolative linker units that facilitate stable attachment in serum and traceless drug release in the target cell from aliphatic and aromatic alcohols with various modes of action.

Iceberg calving can act as a submarine melt amplifier through excitation of transient internal waves.

Monoclonal antibodies targeting the conserved neuraminidase catalytic site mimic sialic acid and use coordinated water molecules to inhibit diverse influenza A and B viruses, including H5N1, providing broad prophylactic protection in mice.

Natriuretic peptides (NPs) are important hormones that regulate cardiovascular physiology by increasing cGMP levels in cardiomyocytes. Here the authors use scanning ion conductance microscopy and a cGMP FRET sensor to identify a differential localisation pattern for the natriuretic peptide receptors within the heart.

Changes in penguin populations on the Antarctic Peninsula in recent decades have been linked to environmental factors such as sea ice. Here, the authors show that penguin colony change on Ardley Island, NW Antarctic Peninsula during the last 8,500 years was primarily driven by volcanic activity.

In this work, researchers address a key question for maternal group B Streptococcus (GBS) vaccine assessment: What newborn antibody concentrations protect against invasive infant GBS disease? They present serologic thresholds by age at onset and serotype based on a large U.S. case-control study.

This study investigates drivers of redox potential in several salt marsh sites on the basis of time series datasets. Wavelet and mutual information analyses show that the terrestrial groundwater level, rather than the marsh groundwater level, is the dominant control on redox potential.

Jamaican fruit bats support disseminated infection of Ebola but not Marburg virus. The differences in infection dynamics are partially attributable to Marburg’s less efficient entry and impaired antagonism of type I interferon signaling.

cAMP is a second messenger that acts in distinct intracellular locations regulating diverse cellular functions. Here the authors design a FRET-based cAMP biosensor and use it to measure in vivodynamics of cAMP concentration changes in the sarcoplasmatic reticulum of mouse cardiomyocytes in health and disease.

Erosion and velocity data from 15 outlet glaciers covering temperate to polar glacier thermal regimes from Patagonia to the Antarctic Peninsula reveal that over the past century the basin-averaged erosion rates vary by three orders of magnitude as a function of climate across this latitudinal transect.

Differences in a non-coding enhancer region of the HOXDB locus underlie the differences between stickleback species in dorsal spine length and number. These differences include single-nucleotide polymorphisms, deletions and transposable element insertions.

Recent Dense Shelf Water outflow from the Dibble Polynya in East Antarctica followed a reduction of Antarctic Bottom Water upstream, according to hydrographic observations.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.

Jungnickel, Guelle et al. use metabolomics, electrophysiology and cryo-EM approaches to show that MFSD1 is a lysosomal dipeptide uniporter, which provides an additional route to recycle lysosomal proteolysis products to lysosomal amino acid exporters.

Corals may vary in their ability to regulate reactive oxygen species (ROS) that can influence coral health. Diaz and colleagues conductin vivomeasurements of the ROS superoxide at the surface of corals and find substantial species-level variation in superoxide regulation that is independent of bleaching status.

Hagfish slime contains fibres that are produced in gland cells, but how these threads are assembled within the cell is unclear. Here, using electron microscopy and three-dimensional modelling, the authors show that during gland cell maturation the shape of the nucleus changes, permitting the coiling of the threads around it.

Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

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.

A geological climate archive documents the effects of ocean warming on Antarctic marine ice-sheets. Large sediment fluxes from the interior of West Antarctica precede the onset of sustained retreat to a smaller footprint for the ice-sheet.

Offshore wind and wave energy may play a key role in the energy transition. Here, authors identify cost targets for these technologies to become cost effective and show how the grid’s installed capacity decreases, and generation and transmission change as offshore energy deployment increase.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

A projection of ocean surface isotherm deepening under emissions scenarios RCP8.5 and RCP4.5 reveals that the potential habitat of many marine organisms will rapidly become tightly compressed between depth levels imposed by isotherm deepening, the thickness of the photic layer and the seafloor.

In 355 coastal coral reef fish species, body size changed with warming, but the direction of a species’ body size response to warming through time was generally consistent with its response to temperature changes through space, rather than generally negative.

A decade of BGC-Argo and plankton records shows North Pacific heatwaves reshape food webs and trap small particles in midwater, slowing deep-ocean carbon export. Impacts vary by event, underscoring the need for sustained ocean monitoring.

The polygonal patterns in permafrost regions are caused by the formation of ice wedges. Observations of polygon evolution reveal that rapid ice-wedge melting has occurred across the Arctic since 1950, altering tundra hydrology.

This study shows that combining land- and ocean-based Carbon Dioxide Removal methods does not compromise their effectiveness. This offers flexibility in designing diverse, sustainable mitigation strategies, reducing pressure on land systems.

Recent estimates of sugar-sweetened beverages (SSBs) intake are generally unavailable. Here the authors show a global SSBs intake of 2.7 servings/week in 2018 in adults (range: 0.7 South Asia, 7.8 Latin America/Caribbean); intakes were higher among males, younger, more educated, and urban adults.

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.

Glacial melt can modify heat transport, and therefore ocean processes, associated with ice front retreat, as revealed by direct observations from the Pine Island Bay region of Antarctica.

The combined use of genome sequencing, cultivation and phenotypic characterization of 79 globally distributed strains from the bacterial phylum Planctomycetes sheds light on their varied cell shapes, modes of cell division and extensive signalling and metabolic potential.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Endothelial Sirtuin1 downregulation in metabolic disorders causes vascular dysfunction and inflammation. Here, the authors show that deficiency of endothelial Sirtuin1, while having deleterious effects on the vasculature, stimulates skeletal muscle insulin sensitivity and improves glucose disposal.

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.

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.

How the carbon stocks of the Arctic–Boreal Zone change with warming is not well understood. Here the authors show that wildfires and large regional differences in net carbon fluxes offset the overall increasing CO₂ uptake.

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.

Responses of agriculture and fisheries to climate change are interlinked, yet rarely studied together. Here, the authors analyse more than 3000 households from 5 tropical countries and forecast mid-century climate change impacts, finding that communities with higher fishery dependence and lower socioeconomic status communities face greater losses.

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.

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.

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.

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.