Plasma membrane rupture (PMR) is the final cataclysmic event in lytic cell death. PMR releases intracellular molecules termed damage-associated molecular patterns (DAMPs) that propagate the inflammatory response1–3. The underlying mechanism for PMR, however, is unknown. Here we show that the ill-characterized nerve injury-induced protein 1 (NINJ1)4–8 — a cell surface protein with two transmembrane

There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)—as well as the current pandemic of coronavirus disease 2019 (COVID-19). Notably, all of these outbreaks have been linked to suspected zoonotic transmission of bat-borne viruses. Bats—the only

Metamaterials are designed to realize exotic physical properties through the geometric arrangement of their underlying structural layout1,2. Traditional mechanical metamaterials achieve functionalities such as a target Poisson’s ratio3 or shape transformation4,5,6 through unit-cell optimization7,8,9, often with spatial heterogeneity10,11,12. These functionalities are programmed into the layout of the

Lake ecosystems, and the organisms that live within them, are vulnerable to temperature change1,2,3,4,5, including the increased occurrence of thermal extremes6. However, very little is known about lake heatwaves—periods of extreme warm lake surface water temperature—and how they may change under global warming. Here we use satellite observations and a numerical model to investigate changes in lake

The water–gas shift (WGS) reaction is an industrially important source of pure hydrogen (H2) at the expense of carbon monoxide and water1,2. This reaction is of interest for fuel-cell applications, but requires WGS catalysts that are durable and highly active at low temperatures3. Here we demonstrate that the structure (Pt1–Ptn)/α-MoC, where isolated platinum atoms (Pt1) and subnanometre platinum clusters

Active forgetting is an essential component of the memory management system of the brain1. Forgetting can be permanent, in which prior memory is lost completely, or transient, in which memory exists in a temporary state of impaired retrieval. Temporary blocks on memory seem to be universal, and can disrupt an individual’s plans, social interactions and ability to make rapid, flexible and appropriate

The cortex projects to the dorsal striatum topographically1,2 to regulate behaviour3,4,5, but spiking activity in the two structures has previously been reported to have markedly different relations to sensorimotor events6,7,8,9. Here we show that the relationship between activity in the cortex and striatum is spatiotemporally precise, topographic, causal and invariant to behaviour. We simultaneously

Topological crystalline insulators (TCIs) can exhibit unusual, quantized electric phenomena such as fractional electric polarization and boundary-localized fractional charge1,2,3,4,5,6. This quantized fractional charge is the generic observable for identification of TCIs that lack clear spectral features5,6,7, including ones with higher-order topology8,9,10,11. It has been predicted that fractional

Women (compared to men) and individuals from minority ethnic groups (compared to the majority group) face unfavourable labour market outcomes in many economies1,2, but the extent to which discrimination is responsible for these effects, and the channels through which they occur, remain unclear3,4. Although correspondence tests5—in which researchers send fictitious CVs that are identical except for

The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset—part of the Allen Brain Observatory2—that surveys spiking from tens

Blue jets are lightning-like, atmospheric electric discharges of several hundred millisecond duration that fan into cones as they propagate from the top of thunderclouds into the stratosphere1. They are thought to initiate in an electric breakdown between the positively charged upper region of a cloud and a layer of negative charge at the cloud boundary and in the air above. The breakdown forms a leader

Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1,2,3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer’s disease4,5,6. Systemically, circulating pro-inflammatory factors can promote cognitive decline7

In dynamic environments, subjects often integrate multiple samples of a signal and combine them to reach a categorical judgment1. The process of deliberation can be described by a time-varying decision variable (DV), decoded from neural population activity, that predicts a subject’s upcoming decision2. Within single trials, however, there are large moment-to-moment fluctuations in the DV, the behavioural

Most natural and artificial materials have crystalline structures from which abundant topological phases emerge1,2,3,4,5,6. However, the bulk–edge correspondence—which has been widely used in experiments to determine the band topology from edge properties—is inadequate in discerning various topological crystalline phases7,8,9,10,11,12,13,14,15,16, leading to challenges in the experimental classification

Break-induced replication (BIR) repairs one-ended double-strand breaks in DNA similar to those formed by replication collapse or telomere erosion, and it has been implicated in the initiation of genome instability in cancer and other human diseases1,2. Previous studies have defined the enzymes that are required for BIR1,2,3,4,5; however, understanding of initial and extended BIR synthesis, and of how

During the prokaryotic type III CRISPR-Cas immune response, infection triggers the production of cyclic oligoadenylates, which bind and activate CARF domain-containing proteins1,2. Many type III loci are associated with proteins in which the CARF domain is fused to an endonuclease-like domain3,4; however, with the exception of the well-characterized Csm6/Csx1 RNases5,6, whether and how these inducible

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models1,2. Antibody levels decrease with time, but the nature and quality of the memory B cells that would

Lungfishes belong to lobe-fined fish (Sarcopterygii) that in the Devonian ‘conquered’ land and gave rise to all land vertebrates, including humans1–3. We determined the largest chromosome-quality animal genome, the Australian lungfish, Neoceratodus forsteri. Its vast size (~14x of human) is attributable mostly to huge intergenic regions and introns with high repeat content (≈90%) whose components resemble

Magic-angle twisted bilayer graphene (MATBG) exhibits a range of correlated phenomena that originate from strong electron–electron interactions. These interactions make the Fermi surface highly susceptible to reconstruction when ±1, ±2 and ±3 electrons occupy each moiré unit cell, and lead to the formation of various correlated phases1,2,3,4. Although some phases have been shown to have a non-zero

The activation of mostly quiescent haematopoietic stem cells (HSCs) is a prerequisite for life-long production of blood cells1. This process requires major molecular adaptations to allow HSCs to meet the regulatory and metabolic requirements for cell division2,3,4. The mechanisms that govern cellular reprograming upon stem-cell activation, and the subsequent return of stem cells to quiescence, have

Avalanche phenomena use steeply nonlinear dynamics to generate disproportionately large responses from small perturbations, and are found in a multitude of events and materials1. Photon avalanching enables technologies such as optical phase-conjugate imaging2, infrared quantum counting3 and efficient upconverted lasing4,5,6. However, the photon-avalanching mechanism underlying these optical applications

Endogenous retroviruses (ERVs) are abundant and heterogenous groups of integrated retroviral sequences that affect genome regulation and cell physiology throughout their RNA-centred life cycle1. Failure to repress ERVs is associated with cancer, infertility, senescence and neurodegenerative diseases2,3. Here, using an unbiased genome-scale CRISPR knockout screen in mouse embryonic stem cells, we identify

Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak luminosities1 of 1036 to 1043 erg per second. Occasionally, a giant flare with an energy of around 1044 to 1046 erg is emitted2. These phenomena are thought to arise from neutron stars with extremely high

The development of quantum computing architectures from early designs and current noisy devices to fully fledged quantum computers hinges on achieving fault tolerance using quantum error correction1,2,3,4. However, these correction capabilities come with an overhead for performing the necessary fault-tolerant logical operations on logical qubits (qubits that are encoded in ensembles of physical qubits

RAG endonuclease initiates Igh V(D)J recombination in progenitor B cells by binding a JH-recombination signal sequence (RSS) within a recombination centre (RC) and then linearly scanning upstream chromatin, presented by loop extrusion mediated by cohesin, for convergent D-RSSs1,2. The utilization of convergently oriented RSSs and cryptic RSSs is intrinsic to long-range RAG scanning3. Scanning of RAG

A non-enveloped virus requires a membrane lesion to deliver its genome into a target cell1. For rotaviruses, membrane perforation is a principal function of the viral outer-layer protein, VP42,3. Here we describe the use of electron cryomicroscopy to determine how VP4 performs this function and show that when activated by cleavage to VP8* and VP5*, VP4 can rearrange on the virion surface from an ‘upright’

Magnetars are neutron stars with extremely strong magnetic fields (1013 to 1015 gauss)1,2, which episodically emit X-ray bursts approximately 100 milliseconds long and with energies of 1040 to 1041 erg. Occasionally, they also produce extremely bright and energetic giant flares, which begin with a short (roughly 0.2 seconds), intense flash, followed by fainter, longer-lasting emission that is modulated

In 1986, electron microscopy was used to reconstruct by hand the entire nervous system of a roundworm, the nematode Caenorhabditis elegans1. Since this landmark study, high-throughput electron-microscopic techniques have enabled reconstructions of much larger mammalian brain circuits at synaptic resolution2,3. Nevertheless, it remains unknown how the structure of a synapse relates to its physiological

Dire wolves are considered to be one of the most common and widespread large carnivores in Pleistocene America1, yet relatively little is known about their evolution or extinction. Here, to reconstruct the evolutionary history of dire wolves, we sequenced five genomes from sub-fossil remains dating from 13,000 to more than 50,000 years ago. Our results indicate that although they were similar morphologically

The dominant feature of large-scale mass transfer in the modern ocean is the Atlantic meridional overturning circulation (AMOC). The geometry and vigour of this circulation influences global climate on various timescales. Palaeoceanographic evidence suggests that during glacial periods of the past 1.5 million years the AMOC had markedly different features from today1; in the Atlantic basin, deep waters

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal

Autism spectrum disorder (ASD) is an early-onset developmental disorder characterized by deficits in communication and social interaction and restrictive or repetitive behaviours1,2. Family studies demonstrate that ASD has a substantial genetic basis with contributions both from inherited and de novo variants3,4. It has been estimated that de novo mutations may contribute to 30% of all simplex cases

The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells1,2. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists

Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS)1. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia2. We collected bronchoalveolar lavage fluid samples from

Visible-light absorption and transport of the resultant electronic excitations to a reaction centre through Förster resonance energy transfer1,2,3 (FRET) are critical to the operation of biological light-harvesting systems4, and are used in various artificial systems made of synthetic dyes5, polymers6 or nanodots7,8. The fundamental equations describing FRET are similar to those describing vibration-to-vibration

Fermionic atoms in optical lattices have served as a useful model system in which to study and emulate the physics of strongly correlated matter. Driven by the advances of high-resolution microscopy, the current research focus is on two-dimensional systems1,2,3, in which several quantum phases—such as antiferromagnetic Mott insulators for repulsive interactions4,5,6,7 and charge-density waves for attractive

Regeneration is a complex chain of events that restores a tissue to its original size and shape. The tissue-wide coordination of cellular dynamics that is needed for proper morphogenesis is challenged by the large dimensions of regenerating body parts. Feedback mechanisms in biochemical pathways can provide effective communication across great distances1,2,3,4,5, but how they might regulate growth

Ordered two-dimensional arrays such as S-layers1,2 and designed analogues3,4,5 have intrigued bioengineers6,7, but with the exception of a single lattice formed with flexible linkers8, they are constituted from just one protein component. Materials composed of two components have considerable potential advantages for modulating assembly dynamics and incorporating more complex functionality9,10,11,12

Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions1. However, little is known about the homeostatic anti-inflammatory activities of astrocytes and their regulation. Here, using high-throughput flow cytometry screening, single-cell RNA sequencing and CRISPR–Cas9-based cell-specific in vivo genetic perturbations

Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available1,2,3. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97)4,5,6, a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97–Go complexes bound to the anti-inflammatory

The prevailing mid-latitude westerly winds, known as the westerlies, are a fundamental component of the climate system because they have a crucial role in driving surface ocean circulation1 and modulating air–sea heat, momentum and carbon exchange1,2,3. Recent work suggests that westerly wind belts are migrating polewards in response to anthropogenic forcing4,5. Reconstructing the westerlies during

Egg-laying mammals (monotremes) are the only extant mammalian outgroup to therians (marsupial and eutherian animals) and provide key insights into mammalian evolution1,2. Here we generate and analyse reference genomes of the platypus (Ornithorhynchus anatinus) and echidna (Tachyglossus aculeatus), which represent the only two extant monotreme lineages. The nearly complete platypus genome assembly has

Hutchinson–Gilford progeria syndrome (HGPS or progeria) is typically caused by a dominant-negative C•G-to-T•A mutation (c.1824 C>T; p.G608G) in LMNA, the gene that encodes nuclear lamin A. This mutation causes RNA mis-splicing that produces progerin, a toxic protein that induces rapid ageing and shortens the lifespan of children with progeria to approximately 14 years1,2,3,4. Adenine base editors (ABEs)

Quantum key distribution (QKD)1,2 has the potential to enable secure communication and information transfer3. In the laboratory, the feasibility of point-to-point QKD is evident from the early proof-of-concept demonstration in the laboratory over 32 centimetres4; this distance was later extended to the 100-kilometre scale5,6 with decoy-state QKD and more recently to the 500-kilometre scale7,8,9,10

Structurally disordered materials pose fundamental questions1,2,3,4, including how different disordered phases (‘polyamorphs’) can coexist and transform from one phase to another5,6,7,8,9. Amorphous silicon has been extensively studied; it forms a fourfold-coordinated, covalent network at ambient conditions and much-higher-coordinated, metallic phases under pressure10,11,12. However, a detailed mechanistic

Convolutional neural networks, inspired by biological visual cortex systems, are a powerful category of artificial neural networks that can extract the hierarchical features of raw data to provide greatly reduced parametric complexity and to enhance the accuracy of prediction. They are of great interest for machine learning tasks such as computer vision, speech recognition, playing board games and

The intensive application of inorganic nitrogen underlies marked increases in crop production, but imposes detrimental effects on ecosystems1,2: it is therefore crucial for future sustainable agriculture to improve the nitrogen-use efficiency of crop plants. Here we report the genetic basis of nitrogen-use efficiency associated with adaptation to local soils in rice (Oryza sativa L.). Using a panel

Crystal defects affect the thermal and heat-transport properties of materials by scattering phonons and modifying phonon spectra1,2,3,4,5,6,7,8. To appreciate how imperfections in solids influence thermal conductivity and diffusivity, it is thus essential to understand phonon–defect interactions. Sophisticated theories are available to explore such interactions, but experimental validation is limited

With the proliferation of ultrahigh-speed mobile networks and internet-connected devices, along with the rise of artificial intelligence (AI)1, the world is generating exponentially increasing amounts of data that need to be processed in a fast and efficient way. Highly parallelized, fast and scalable hardware is therefore becoming progressively more important2. Here we demonstrate a computationally

Neural mechanisms that mediate the ability to make value-guided decisions have received substantial attention in humans and animals1,2,3,4,5,6. Experiments in animals typically involve long training periods. By contrast, choices in the real world often need to be made between new options spontaneously. It is therefore possible that the neural mechanisms targeted in animal studies differ from those

Most supernova explosions accompany the death of a massive star. These explosions give birth to neutron stars and black holes, and eject solar masses of heavy elements. However, determining the mechanism of explosion has been a half-century journey of great numerical and physical complexity. Here we present the status of this theoretical quest and the physics and astrophysics upon which its resolution

The mitochondrial outer membrane contains so-called β-barrel proteins, which allow communication between the cytosol and the mitochondrial interior1,2,3. Insertion of β-barrel proteins into the outer membrane is mediated by the multisubunit mitochondrial sorting and assembly machinery (SAM, also known as TOB)4,5,6. Here we use cryo-electron microscopy to determine the structures of two different forms

The brainstem is a key centre in the control of body movements. Although the precise nature of brainstem cell types and circuits that are central to full-body locomotion are becoming known1,2,3,4,5, efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord6,7,8,9,10,11,12. Here we define the logic of a functional

In strongly correlated materials, quasiparticle excitations can carry fractional quantum numbers. An intriguing possibility is the formation of fractionalized, charge-neutral fermions—for example, spinons1 and fermionic excitons2,3—that result in neutral Fermi surfaces and Landau quantization4,5 in an insulator. Although previous experiments in quantum spin liquids1, topological Kondo insulators6,7

Haematopoietic stem cells (HSCs) reside in specialized microenvironments in the bone marrow—often referred to as ‘niches’—that represent complex regulatory milieux influenced by multiple cellular constituents, including nerves1,2. Although sympathetic nerves are known to regulate the HSC niche3,4,5,6, the contribution of nociceptive neurons in the bone marrow remains unclear. Here we show that nociceptive

Focal chromosomal amplification contributes to the initiation of cancer by mediating overexpression of oncogenes1,2,3, and to the development of cancer therapy resistance by increasing the expression of genes whose action diminishes the efficacy of anti-cancer drugs. Here we used whole-genome sequencing of clonal cell isolates that developed chemotherapeutic resistance to show that chromothripsis is

Gene expression is an inherently stochastic process1,2; however, organismal development and homeostasis require cells to coordinate the spatiotemporal expression of large sets of genes. In metazoans, pairs of co-expressed genes often reside in the same chromosomal neighbourhood, with gene pairs representing 10 to 50% of all genes, depending on the species3,4,5,6. Because shared upstream regulators

Histone methyltransferases of the nuclear receptor-binding SET domain protein (NSD) family, including NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis1,2. NSD enzymes exhibit an autoinhibitory state that is relieved by binding to nucleosomes, enabling dimethylation of histone H3 at Lys36 (H3K36)3,4,5,6,7. However, the molecular basis that underlies this

Reinforcement learning models postulate that neurons that release dopamine encode information about action and action outcome, and provide a teaching signal to striatal spiny projection neurons in the form of dopamine release1. Dopamine is thought to guide learning via dynamic and differential modulation of protein kinase A (PKA) in each class of spiny projection neuron2. However, the real-time relationship

Isoprenoids are vital for all organisms, in which they maintain membrane stability and support core functions such as respiration1. IspH, an enzyme in the methyl erythritol phosphate pathway of isoprenoid synthesis, is essential for Gram-negative bacteria, mycobacteria and apicomplexans2,3. Its substrate, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), is not produced in metazoans, and in