Glycine receptors (GlyRs) are pentameric, ‘Cys-loop’ receptors that form chloride-permeable channels and mediate fast inhibitory signaling throughout the central nervous system1,2. In the spinal cord and brainstem, GlyRs regulate locomotion and cause movement disorders when mutated2,3. However, the stoichiometry of native GlyRs and the mechanism by which they are assembled remain unclear, despite extensive

Throughout the COVID-19 pandemic, countries relied on a variety of ad-hoc border control protocols to allow for non-essential travel while safeguarding public health: from quarantining all travellers to restricting entry from select nations based on population-level epidemiological metrics such as cases, deaths or testing positivity rates1,2. Here we report the design and performance of a reinforcement

The recent progress in nanotechnology1,2 and single-molecule spectroscopy3,4,5 paves the way for emergent cost-effective organic quantum optical technologies with potential applications in useful devices operating at ambient conditions. We harness a π-conjugated ladder-type polymer strongly coupled to a microcavity forming hybrid light–matter states, so-called exciton-polaritons, to create exciton-polariton

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and—inspired by wind-dispersed seeds6—we examined passive

The leaf economics spectrum1,2 and the global spectrum of plant forms and functions3 revealed fundamental axes of variation in plant traits, which represent different ecological strategies that are shaped by the evolutionary development of plant species2. Ecosystem functions depend on environmental conditions and the traits of species that comprise the ecological communities4. However, the axes of

Particle accelerators are essential tools in science, hospitals and industry1,2,3,4,5,6. Yet their costs and large footprint, ranging in length from metres to several kilometres, limit their use. The recently demonstrated nanophotonics-based acceleration of charged particles can reduce the cost and size of these accelerators by orders of magnitude7,8,9. In this approach, a carefully designed nanostructure

Earth’s magnetic field is recorded as oceanic crust cools, generating lineated magnetic anomalies that provide the pattern of polarity reversals for the past 160 million years1. In the lower (gabbroic) crust, polarity interval boundaries are proxies for isotherms that constrain cooling and hence crustal accretion. Seismic observations2,3,4, geospeedometry5,6,7 and thermal modelling8,9,10 of fast-spread

Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart1,2. Native Kv4 tetrameric channels form macromolecular ternary complexes with two auxiliary β-subunits—intracellular Kv channel-interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase-related proteins (DPPs)—to evoke rapidly activating and

One of the hallmarks of the cerebral cortex is the extreme diversity of interneurons1,2,3. The two largest subtypes of cortical interneurons, parvalbumin- and somatostatin-positive cells, are morphologically and functionally distinct in adulthood but arise from common lineages within the medial ganglionic eminence4,5,6,7,8,9,10,11. This makes them an attractive model for studying the generation of

Polynesia was settled in a series of extraordinary voyages across an ocean spanning one third of the Earth1, but the sequences of islands settled remain unknown and their timings disputed. Currently, several centuries separate the dates suggested by different archaeological surveys2,3,4. Here, using genome-wide data from merely 430 modern individuals from 21 key Pacific island populations and novel

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1,2,3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4,5,6,7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare

All structures within living cells must form at the right time and place. This includes condensates such as the nucleolus, Cajal bodies and stress granules, which form via liquid–liquid phase separation of biomolecules, particularly proteins enriched in intrinsically disordered regions (IDRs)1,2. In non-living systems, the initial stages of nucleated phase separation arise when thermal fluctuations

Star formation in half of massive galaxies was quenched by the time the Universe was 3 billion years old1. Very low amounts of molecular gas seem to be responsible for this, at least in some cases2,3,4,5,6,7, although morphological gas stabilization, shock heating or activity associated with accretion onto a central supermassive black hole are invoked in other cases8,9,10,11. Recent studies of quenching

Luteinizing hormone and chorionic gonadotropin are glycoprotein hormones that are related to follicle-stimulating hormone and thyroid-stimulating hormone1,2. Luteinizing hormone and chorionic gonadotropin are essential to human reproduction and are important therapeutic drugs3,4,5,6. They activate the same G-protein-coupled receptor, luteinizing hormone–choriogonadotropin receptor (LHCGR), by binding

Glutamate-gated kainate receptors are ubiquitous in the central nervous system of vertebrates, mediate synaptic transmission at the postsynapse and modulate transmitter release at the presynapse1,2,3,4,5,6,7. In the brain, the trafficking, gating kinetics and pharmacology of kainate receptors are tightly regulated by neuropilin and tolloid-like (NETO) proteins8,9,10,11. Here we report cryo-electron

Mounting evidence shows that dopamine in the striatum is critically involved in reward-based reinforcement learning1,2. However, it remains unclear how dopamine reward signals influence the entorhinal–hippocampal circuit, another brain network that is crucial for learning and memory3,4,5. Here, using cell-type-specific electrophysiological recording6, we show that dopamine signals from the ventral

The determination of molecular features that mediate clinically aggressive phenotypes in prostate cancer remains a major biological and clinical challenge1,2. Recent advances in interpretability of machine learning models as applied to biomedical problems may enable discovery and prediction in clinical cancer genomics3,4,5. Here we developed P-NET—a biologically informed deep learning model—to stratify

Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1–4. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized

Plant immune responses are mainly activated by two types of receptor. Plasma membrane-localized pattern recognition receptors (PRRs) perceive extracellular microbial features, and nucleotide-binding leucine-rich repeat receptors (NLRs) recognize intracellular effector proteins from pathogens1. NLRs possessing N-terminal Toll/interleukin-1 receptor (TIR) domains activate defence responses via the NADase

The number and variability of the neutralizing epitopes targeted by polyclonal antibodies in SARS-CoV-2 convalescent and vaccinated individuals are key determinants of neutralization breadth and the genetic barrier to viral escape1–4. Using HIV-1 pseudotypes and plasma-selection experiments with vesicular stomatitis virus/SARS-CoV-2 chimeras5, we show that multiple neutralizing epitopes, within and

Southeast Australia experienced intensive and geographically extensive wildfires during the 2019–2020 summer season1,2. The fires released substantial amounts of carbon dioxide into the atmosphere3. However, existing emission estimates based on fire inventories are uncertain4, and vary by up to a factor of four for this event. Here we constrain emission estimates with the help of satellite observations

Adoptive transfer of antigen-specific T cells represents a major advance in cancer immunotherapy, with robust clinical outcomes in some patients1. Both the number of transferred T cells and their differentiation state are critical determinants of effective responses2,3. T cells can be expanded with T cell receptor (TCR)-mediated stimulation and interleukin-2, but this can lead to differentiation into

The Fermi Gamma-ray Space Telescope has revealed a diffuse γ-ray background at energies from 0.1 gigaelectronvolt to 1 teraelectronvolt, which can be separated into emission from our Galaxy and an isotropic, extragalactic component1. Previous efforts to understand the latter have been hampered by the lack of physical models capable of predicting the γ-ray emission produced by the many candidate sources

Transcription-coupled DNA repair removes bulky DNA lesions from the genome1,2 and protects cells against ultraviolet (UV) irradiation3. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4CSA and UV-stimulated scaffold protein A (UVSSA)3. Here we provide five high-resolution structures

Hepatitis C virus (HCV) infection is a causal agent of chronic liver disease, cirrhosis and hepatocellular carcinoma in humans, and afflicts more than 70 million people worldwide. The HCV envelope glycoproteins E1 and E2 are responsible for the binding of the virus to the host cell, but the exact entry process remains undetermined1. The majority of broadly neutralizing antibodies block interaction

During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic–Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak—between 14 February and 19 June 2021—near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths worldwide1. Studies in human tissues and in mouse models have suggested that for many cancers, stem cells sustain early mutations driving tumour development2,3. For the pancreas, however, mechanisms underlying cellular renewal and initiation of PDAC remain unresolved. Here, using lineage tracing from the endogenous

Numerous post-transcriptional modifications of transfer RNAs have vital roles in translation. The 2-methylthio-N6-isopentenyladenosine (ms2i6A) modification occurs at position 37 (A37) in transfer RNAs that contain adenine in position 36 of the anticodon, and serves to promote efficient A:U codon–anticodon base-pairing and to prevent unintended base pairing by near cognates, thus enhancing translational

Droughts and climate-change-driven warming are leading to more frequent and intense wildfires1,2,3, arguably contributing to the severe 2019–2020 Australian wildfires4. The environmental and ecological impacts of the fires include loss of habitats and the emission of substantial amounts of atmospheric aerosols5,6,7. Aerosol emissions from wildfires can lead to the atmospheric transport of macronutrients

The precise stacking of different two-dimensional (2D) structures such as graphene and MoS2 has reinvigorated the field of 2D materials, revealing exotic phenomena at their interfaces1,2. These unique interfaces are typically constructed using mechanical or deposition-based methods to build a heterostructure one monolayer at a time2,3. By contrast, self-assembly is a scalable technique, where complex

Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18–21 and are established driver mutations in non-small cell lung cancer (NSCLC)1,2,3. Targeted therapies are approved for patients with ‘classical’ mutations and a small number of other mutations4,5,6. However, effective therapies have not been identified for additional EGFR mutations. Furthermore, the frequency and effects

Near the boundary between ordered and disordered quantum phases, several experiments have demonstrated metallic behaviour that defies the Landau Fermi paradigm1,2,3,4,5. In moiré heterostructures, gate-tuneable insulating phases driven by electronic correlations have been recently discovered6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23. Here, we use transport measurements to characterize metal–insulator

β-Arylethylamine-containing molecules display important indications in the modulation of pain, treatment of neurological disorders and management of opioid addiction, amongst others, making it a privileged scaffold in drug discovery1,2. De novo methods for their assembly are reliant on transformations that convert a small class of feedstocks into the target compounds via time consuming multi-step syntheses3–5

Derailed cytokine and immune cell networks account for organ damage and clinical severity of COVID-191–4. Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and accompanied by a senescence-associated secretory phenotype (SASP), composed

Plants deploy cell-surface and intracellular leucine rich-repeat domain (LRR) immune receptors to detect pathogens1. LRR receptor kinases and LRR receptor proteins at the plasma membrane recognize microorganism-derived molecules to elicit pattern-triggered immunity (PTI), whereas nucleotide-binding LRR proteins detect microbial effectors inside cells to confer effector-triggered immunity (ETI). Although

The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC

Spontaneous formation of ordered structures—self-assembly—is ubiquitous in nature and observed on different length scales, ranging from atomic and molecular systems to micrometre-scale objects and living matter1. Self-ordering in molecular and biological systems typically involves short-range hydrophobic and van der Waals interactions2,3. Here we introduce an approach to micrometre-scale self-assembly

A key aspect of living cells is their ability to harvest energy from the environment and use it to pump specific atomic and molecular species in and out of their system—typically against an unfavourable concentration gradient1. Active transport allows cells to store metabolic energy, extract waste and supply organelles with basic building blocks at the submicrometre scale. Unlike living cells, abiotic

The adenosine A1 receptor (A1R) is a promising therapeutic target for non-opioid analgesic agents to treat neuropathic pain1,2. However, development of analgesic orthosteric A1R agonists has failed because of a lack of sufficient on-target selectivity as well as off-tissue adverse effects3. Here we show that [2-amino-4-(3,5-bis(trifluoromethyl)phenyl)thiophen-3-yl)(4-chlorophenyl)methanone] (MIPS521)

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical

Parties to the 2015 Paris Agreement pledged to limit global warming to well below 2 °C and to pursue efforts to limit the temperature increase to 1.5 °C relative to pre-industrial times1. However, fossil fuels continue to dominate the global energy system and a sharp decline in their use must be realized to keep the temperature increase below 1.5 °C (refs. 2,3,4,5,6,7). Here we use a global energy

Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans1,2,3. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state4,5,6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing

Polaritons are hybrid excitations of matter and photons. In recent years, polaritons in van der Waals nanomaterials—known as van der Waals polaritons—have shown great promise to guide the flow of light at the nanoscale over spectral regions ranging from the visible to the terahertz. A vibrant research field based on manipulating strong light–matter interactions in the form of polaritons, supported

Monoclonal antibody therapies targeting tumour antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1,2,3,4,5,6,7. However, cancer cells evade phagocytosis using mechanisms that are incompletely understood. Here we develop a platform for unbiased identification of factors that impede antibody-dependent cellular phagocytosis (ADCP) using complementary

Mechanisms that favour rare species are key to the maintenance of diverse communities1,2,3. One of the most critical tasks for conservation of flowering plant biodiversity is to understand how plant–pollinator interactions contribute to the maintenance of rare species4,5,6,7. Here we show that niche partitioning in pollinator use and asymmetric facilitation confer fitness advantage of rarer species

In the past several decades, field studies have shown that woody plants can access substantial volumes of water from the pores and fractures of bedrock1,2,3. If, like soil moisture, bedrock water storage serves as an important source of plant-available water, then conceptual paradigms regarding water and carbon cycling may need to be revised to incorporate bedrock properties and processes4,5,6. Here

The interstellar medium (ISM) comprises gases at different temperatures and densities, including ionized, atomic and molecular species, and dust particles1. The neutral ISM is dominated by neutral hydrogen2 and has ionization fractions of up to eight per cent3. The concentration of chemical elements heavier than helium (metallicity) spans orders of magnitudes in Galactic stars4, because they formed

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative

Universal control of multiple qubits—the ability to entangle qubits and to perform arbitrary individual qubit operations1—is a fundamental resource for quantum computing2, simulation3 and networking4. Qubits realized in trapped atomic ions have shown the highest-fidelity two-qubit entangling operations5,6,7 and single-qubit rotations8 so far. Universal control of trapped ion qubits has been separately

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative

Single-cell sequencing methods have enabled in-depth analysis of the diversity of cell types and cell states in a wide range of organisms. These tools focus predominantly on sequencing the genomes1, epigenomes2 and transcriptomes3 of single cells. However, despite recent progress in detecting proteins by mass spectrometry with single-cell resolution4, it remains a major challenge to measure translation

The SARS-CoV-2 B.1.617.2 (Delta) variant was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type

CRISPR–Cas interference is mediated by Cas effector nucleases that are either components of multisubunit complexes—in class 1 CRISPR–Cas systems—or domains of a single protein—in class 2 systems1,2,3. Here we show that the subtype III-E effector Cas7-11 is a single-protein effector in the class 1 CRISPR–Cas systems originating from the fusion of a putative Cas11 domain and multiple Cas7 subunits that

Biodiversity contributes to the ecological and climatic stability of the Amazon Basin1,2, but is increasingly threatened by deforestation and fire3,4. Here we quantify these impacts over the past two decades using remote-sensing estimates of fire and deforestation and comprehensive range estimates of 11,514 plant species and 3,079 vertebrate species in the Amazon. Deforestation has led to large amounts

Oxygen is critical for a multitude of metabolic processes that are essential for human life. Biological processes can be identified by treating cells with 18O2 or other isotopically labelled gases and systematically identifying biomolecules incorporating labeled atoms. Here we labelled cell lines of distinct tissue origins with 18O2 to identify the polar oxy-metabolome, defined as polar metabolites labelled

Accessing superconductivity via the electric field-effect in a clean, two-dimensional device is a central goal of nanoelectronics. Recently, superconductivity has been realized in graphene moiré heterostructures1–4, however, many of these structures are not mechanically stable, and experiments show signatures of strong disorder. Here we report the observation of superconductivity—manifesting as low-

Ferromagnetism is most common in transition metal compounds where electrons occupy highly localized d-orbitals. However, ferromagnetic order may also arise in low-density two-dimensional electron systems1–5. Here we show that gate-tuned van Hove singularities in rhombohedral trilayer graphene6 drive spontaneous ferromagnetic polarization of the electron system into one or more spin- and valley flavors

Profuse dendritic-synaptic interconnections among neurons in the neocortex embed intricate logic structures enabling sophisticated decision-making that vastly outperforms any artificial electronic analogues1,2,3. The physical complexity is far beyond existing circuit fabrication technologies: moreover, the network in a brain is dynamically reconfigurable, which provides flexibility and adaptability

Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage