Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction1,2,3. The properties of these materials evolve dynamically and heterogeneously4 with applied voltage through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation5. The catalytic state is thus inherently far from

Although RAF monomer inhibitors (type I.5, BRAF(V600)) are clinically approved for the treatment of BRAFV600-mutant melanoma, they are ineffective in non-BRAFV600 mutant cells1,2,3. Belvarafenib is a potent and selective RAF dimer (type II) inhibitor that exhibits clinical activity in patients with BRAFV600E- and NRAS-mutant melanomas. Here we report the first-in-human phase I study investigating the

Exciting phenomena may emerge in non-centrosymmetric two-dimensional electronic systems when spin–orbit coupling (SOC)1 interplays dynamically with Coulomb interactions2,3, band topology4,5 and external modulating forces6,7,8. Here we report synergetic effects between SOC and the Stark effect in centrosymmetric few-layer black arsenic, which manifest as particle–hole asymmetric Rashba valley formation

A balanced intake of macronutrients—protein, carbohydrate and fat—is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor1. Taste receptors (T1R1–T1R3)2 can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor)3 monitor the levels of amino acids in the cell. When deprived

Mitochondrial fission is a highly regulated process that, when disrupted, can alter metabolism, proliferation and apoptosis1,2,3. Dysregulation has been linked to neurodegeneration3,4, cardiovascular disease3 and cancer5. Key components of the fission machinery include the endoplasmic reticulum6 and actin7, which initiate constriction before dynamin-related protein 1 (DRP1)8 binds to the outer mitochondrial

Disulfide bonds between cysteine residues are important post-translational modifications in proteins that have critical roles for protein structure and stability, as redox-active catalytic groups in enzymes or allosteric redox switches that govern protein function1,2,3,4. In addition to forming disulfide bridges, cysteine residues are susceptible to oxidation by reactive oxygen species, and are thus

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR–Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1,2,3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1,2,3,4,5,6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS)

The Paris Agreement aims to limit global mean warming in the twenty-first century to less than 2 degrees Celsius above preindustrial levels, and to promote further efforts to limit warming to 1.5 degrees Celsius1. The amount of greenhouse gas emissions in coming decades will be consequential for global mean sea level (GMSL) on century and longer timescales through a combination of ocean thermal expansion

Odours are transported in turbulent plumes, which result in rapid concentration fluctuations1,2 that contain rich information about the olfactory scenery, such as the composition and location of an odour source2,3,4. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond

In only a few decades, lithium-ion batteries have revolutionized technologies, enabling the proliferation of portable devices and electric vehicles1, with substantial benefits for society. However, the rapid growth in technology has highlighted the ethical and environmental challenges of mining lithium, cobalt and other mineral ore resources, and the issues associated with the safe usage and non-hazardous

Galaxy clusters are known to harbour magnetic fields, the nature of which remains unresolved. Intra-cluster magnetic fields can be observed at the density contact discontinuity formed by cool and dense plasma running into hot ambient plasma1,2, and the discontinuity exists3 near the second-brightest galaxy4, MRC 0600-399, in the merging galaxy cluster Abell 3376 (redshift 0.0461). Elongated X-ray emission

The divergence of chimpanzee and bonobo provides one of the few examples of recent hominid speciation1,2. Here we describe a fully annotated, high-quality bonobo genome assembly, which was constructed without guidance from reference genomes by applying a multiplatform genomics approach. We generate a bonobo genome assembly in which more than 98% of genes are completely annotated and 99% of the gaps

Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1,2,3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases

The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2,3,4,5,6,7,8, but primarily used previous-generation

MicroRNAs (miRNAs) have essential functions during embryonic development, and their dysregulation causes cancer1,2. Altered global miRNA abundance is found in different tissues and tumours, which implies that precise control of miRNA dosage is important1,3,4, but the underlying mechanism(s) of this control remain unknown. The protein complex Microprocessor, which comprises one DROSHA and two DGCR8

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection1,2, yet the host response at the lung tissue-level is poorly understood. Here, we performed single-nucleus RNA-sequencing of ~116,000 nuclei of lungs from 19 COVID-19 decedents who underwent rapid autopsy and 7 control lungs. Integrated analyses revealed significant alterations in cellular composition, transcriptional

COVID-19, caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple-organ failure1–4, but little is known about its pathophysiology. Here, we generated single-cell atlases of 23 lung, 16 kidney, 16 liver and 19 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors. Integrated computational analysis uncovered substantial remodeling in the lung

Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence virtually all metrics associated with their pharmacokinetic and pharmacodynamic profiles.1–4 Drug candidates increasingly contain CF3 and CF2H groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect, and plant life.5,6 New fluoroalkylation

Vascular malformations are considered monogenic disorders that result in dysregulated vessel growth. Cerebral cavernous malformations (CCMs) arise owing to inactivation of the endothelial CCM protein complex required to dampen MEKK3 activity1–4. Environmental factors explain differences in CCM natural history between individuals5, but why single CCMs often exhibit sudden, rapid growth culminating in

The accurate and complete assembly of both haplotype sequences of a diploid organism is essential to understanding the role of variation in genome functions, phenotypes, and diseases1. Here, using a trio-binning approach, we present a high-quality, diploid reference genome, with both haplotypes assembled independently at the chromosome level, for the common marmoset (Callithrix jacchus), an important

The state of deprotonation/protonation of surfaces has far-ranging implications in chemistry, from acid–base catalysis1 and the electrocatalytic and photocatalytic splitting of water2, to the behaviour of minerals3 and biochemistry4. An entity’s acidity is described by its proton affinity and its acid dissociation constant pKa (the negative logarithm of the equilibrium constant of the proton transfer

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1,2,3,4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling

Oxytocin (OXT; hereafter OT) and arginine vasopressin or vasotocin (AVP or VT; hereafter VT) are neurotransmitter ligands that function through specific receptors to control diverse functions1,2. Here we performed genomic analyses on 35 species that span all major vertebrate lineages, including newly generated high-contiguity assemblies from the Vertebrate Genomes Project3,4. Our findings support the

Complex concentrated solutions of multiple principal elements are being widely investigated as high- or medium-entropy alloys (HEAs or MEAs)1,2,3,4,5,6,7,8,9,10,11, often assuming that these materials have the high configurational entropy of an ideal solution. However, enthalpic interactions among constituent elements are also expected at normal temperatures, resulting in various degrees of local chemical

Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes1,2,3,4,5. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life)6,7,8. Here we present a comparative analysis

Cratons are Earth’s ancient continental land masses that remain stable for billions of years. The mantle roots of cratons are renowned as being long-lived, stable features of Earth’s continents, but there is also evidence of their disruption in the recent1,2,3,4,5,6 and more distant7,8,9 past. Despite periods of lithospheric thinning during the Proterozoic and Phanerozoic eons, the lithosphere beneath

Coordinated activity across networks of neurons is a hallmark of both resting and active behavioural states in many species1,2,3,4,5. These global patterns alter energy metabolism over seconds to hours, which underpins the widespread use of oxygen consumption and glucose uptake as proxies of neural activity6,7. However, whether changes in neural activity are causally related to metabolic flux in intact

Molecular quantum gases (that is, ultracold and dense molecular gases) have many potential applications, including quantum control of chemical reactions, precision measurements, quantum simulation and quantum information processing1,2,3. For molecules, to reach the quantum regime usually requires efficient cooling at high densities, which is frequently hindered by fast inelastic collisions that heat

G-protein-coupled receptors (GPCRs) have central roles in intercellular communication1,2. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABAB receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed

Glaciers distinct from the Greenland and Antarctic ice sheets are shrinking rapidly, altering regional hydrology1, raising global sea level2 and elevating natural hazards3. Yet, owing to the scarcity of constrained mass loss observations, glacier evolution during the satellite era is known only partially, as a geographic and temporal patchwork4,5. Here we reveal the accelerated, albeit contrasting

Several enteric pathogens can gain specific metabolic advantages over other members of the microbiota by inducing host pathology and inflammation. The pathogen Clostridium difficile is responsible for a toxin-mediated colitis that causes 450,000 infections and 15,000 deaths in the United States each year1; however, the molecular mechanisms by which C. difficile benefits from this pathology remain unclear

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either

Mediator is a conserved coactivator that enables regulated transcription initiation at eukaryotic genes1–3. Mediator is recruited by transcriptional activators and binds the pre-initiation complex (PIC) to stimulate RNA polymerase II (Pol II) phosphorylation and promoter escape1–6. Here we prepare a recombinant human Mediator, reconstitute a 50-subunit Mediator-PIC complex, and determine the structure

The initiation of transcription is a focal point for the regulation of gene activity during mammalian cell differentiation and development. For transcription initiation, RNA polymerase II (Pol II) assembles with general transcription factors into a pre-initiation complex (PIC) that opens promoter DNA. Previous work provided the molecular architecture of the yeast1–9 and human10,11 PIC and a topological

The N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 catalysed predominantly by the METTL3–METTL14 methyltransferase complex3,4. The m6A writer METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but its true therapeutic importance is still unknown5–7. Here we present the identification and characterization of a highly potent and selective

The acute clinical manifestations of COVID-19 are well characterized1,2; however, its post-acute sequalae have not been comprehensively described. Here, we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequalae including diagnoses, medication use, and laboratory abnormalities in 30-day survivors of COVID-19

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3% of all anthropogenic greenhouse gases emitted from drained peatland3–5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and rewetting

Gravitational interactions between the Large Magellanic Cloud (LMC) and the stellar and dark matter halo of the Milky Way are expected to give rise to disequilibrium phenomena in the outer Milky Way1,2,3,4,5,6,7. A local wake is predicted to trail the orbit of the LMC, and a large-scale overdensity is predicted to exist across a large area of the northern Galactic hemisphere. Here we report the detection

Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis

It has recently been shown that in anaerobic microorganisms the tricarboxylic acid (TCA) cycle, including the seemingly irreversible citrate synthase reaction, can be reversed and used for autotrophic fixation of carbon1,2. This reversed oxidative TCA cycle requires ferredoxin-dependent 2-oxoglutarate synthase instead of the NAD-dependent dehydrogenase as well as extremely high levels of citrate synthase

Palaeorecords suggest that the climate system has tipping points, where small changes in forcing cause substantial and irreversible alteration to Earth system components called tipping elements. As atmospheric greenhouse gas concentrations continue to rise as a result of fossil fuel burning, human activity could also trigger tipping, and the impacts would be difficult to adapt to. Previous studies

From stadium covers to solar sails, we rely on deployability for the design of large-scale structures that can quickly compress to a fraction of their size1,2,3,4. Historically, two main strategies have been used to design deployable systems. The first and most frequently used approach involves mechanisms comprising interconnected bar elements, which can synchronously expand and retract5,6,7, occasionally

As organelles of the innate immune system, inflammasomes activate caspase-1 and other inflammatory caspases that cleave gasdermin D (GSDMD). Caspase-1 also cleaves inactive precursors of the interleukin (IL)-1 family to generate mature cytokines such as IL-1β and IL-18. Cleaved GSDMD forms transmembrane pores to enable the release of IL-1 and to drive cell lysis through pyroptosis1,2,3,4,5,6,7,8,9

The social cost of methane (SC-CH4) measures the economic loss of welfare caused by emitting one tonne of methane into the atmosphere. This valuation may in turn be used in cost–benefit analyses or to inform climate policies1,2,3. However, current SC-CH4 estimates have not included key scientific findings and observational constraints. Here we estimate the SC-CH4 by incorporating the recent upward

The ability to categorize sensory stimuli is crucial for an animal’s survival in a complex environment. Memorizing categories instead of individual exemplars enables greater behavioural flexibility and is computationally advantageous. Neurons that show category selectivity have been found in several areas of the mammalian neocortex1,2,3,4, but the prefrontal cortex seems to have a prominent role4,5

Single-molecule imaging is challenging but highly beneficial for investigating intermolecular interactions at the molecular level1,2,3,4,5,6. Van der Waals interactions at the sub-nanometre scale strongly influence various molecular behaviours under confinement conditions7,8,9,10,11. Inspired by the traditional compass12, here we use a para-xylene molecule as a rotating pointer to detect the host–guest

Africa is forecasted to experience large and rapid climate change1 and population growth2 during the twenty-first century, which threatens the world’s second largest rainforest. Protecting and sustainably managing these African forests requires an increased understanding of their compositional heterogeneity, the environmental drivers of forest composition and their vulnerability to ongoing changes

Successfully interfacing enzymes and biomachinery with polymers affords on-demand modification and/or programmable degradation during the manufacture, utilization and disposal of plastics, but requires controlled biocatalysis in solid matrices with macromolecular substrates1,2,3,4,5,6,7. Embedding enzyme microparticles speeds up polyester degradation, but compromises host properties and unintentionally

Recent multi-dimensional simulations suggest that high-entropy buoyant plumes help massive stars to explode1,2. Outwardly protruding iron (Fe)-rich fingers of gas in the galactic supernova remnant3,4 Cassiopeia A seem to match this picture. Detecting the signatures of specific elements synthesized in the high-entropy nuclear burning regime (that is, α-rich freeze out) would constitute strong substantiating

Telomerase adds telomeric repeats at chromosome ends to compensate for the telomere loss that is caused by incomplete genome end replication1. In humans, telomerase is upregulated during embryogenesis and in cancers, and mutations that compromise the function of telomerase result in disease2. A previous structure of human telomerase at a resolution of 8 Å revealed a vertebrate-specific composition

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike receptor binding domain displayed on a protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human

Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin

The fundamental topology of cellular structures—the location, number and connectivity of nodes and compartments—can profoundly affect their acoustic1,2,3,4, electrical5, chemical6,7, mechanical8,9,10 and optical11 properties, as well as heat1,12, fluid13,14 and particle transport15. Approaches that harness swelling16,17,18, electromagnetic actuation19,20 and mechanical instabilities21,22,23 in cellular

At the liquid–gas phase transition in water, the density has a discontinuity at atmospheric pressure; however, the line of these first-order transitions defined by increasing the applied pressure terminates at the critical point1, a concept ubiquitous in statistical thermodynamics2. In correlated quantum materials, it was predicted3 and then confirmed experimentally4,5 that a critical point terminates

The largest effusive basaltic eruptions are associated with caldera collapse and are manifest through quasi-periodic ground displacements and moderate-size earthquakes1,2,3, but the mechanism that governs their dynamics remains unclear. Here we provide a physical model that explains these processes, which accounts for both the quasi-periodic stick–slip collapse of the caldera roof and the long-term

D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer1, but the mechanisms that regulate their turnover are still being debated2,3. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4AMBRA1 (also known as CRL4DCAF3) as the ubiquitin ligase that targets all three D-type cyclins

Antibiotics that target Gram-negative bacteria in new ways are needed to resolve the antimicrobial resistance crisis1,2,3. Gram-negative bacteria are protected by an additional outer membrane, rendering proteins on the cell surface attractive drug targets4,5. The natural compound darobactin targets the bacterial insertase BamA6—the central unit of the essential BAM complex, which facilitates the folding

The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related

The eye lens of vertebrates is composed of fibre cells in which all membrane-bound organelles undergo degradation during terminal differentiation to form an organelle-free zone1. The mechanism that underlies this large-scale organelle degradation remains largely unknown, although it has previously been shown to be independent of macroautophagy2,3. Here we report that phospholipases in the PLAAT (phospholipase