Aziridines, three-membered nitrogen-containing cyclic molecules, are important synthetic targets. Their significant ring strain and resultant proclivity towards ring opening reactions makes them versatile precursors to diverse amine products1–3 and, in some cases, the aziridine functional group itself imbues important biological (e.g. anti-tumor) activity4–6. Transformation of ubiquitous alkenes into

Rapidly-emerging variants jeopardize antibody-based countermeasures against SARS-CoV-2. While cell culture experiments have demonstrated loss of potency of several anti-spike neutralizing antibodies against SARS-CoV-2 variant strains1–3, the in vivo significance of these results remains uncertain. Using a panel of monoclonal antibodies (mAbs) corresponding to many in advanced clinical development by

Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms1–3. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza)

The central challenge in building a quantum computer is error correction. Unlike classical bits, which are susceptible to only one type of error, quantum bits (qubits) are susceptible to two types of error, corresponding to flips of the qubit state about the X and Z directions. Although the Heisenberg uncertainty principle precludes simultaneous monitoring of X- and Z-flips on a single qubit, it is

DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1,2,3,4,5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6,7,8,9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are

Macrophages have a key role in shaping the tumour microenvironment (TME), tumour immunity and response to immunotherapy, which makes them an important target for cancer treatment1,2. However, modulating macrophages has proved extremely difficult, as we still lack a complete understanding of the molecular and functional diversity of the tumour macrophage compartment. Macrophages arise from two distinct

Despite recent efforts to advance spintronics devices and quantum information technology using materials with non-trivial topological properties, three key challenges are still unresolved1,2,3,4,5,6,7,8,9. First, the identification of topological band degeneracies that are generically rather than accidentally located at the Fermi level. Second, the ability to easily control such topological degeneracies

Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab

Ionotropic glutamate delta receptors 1 (GluD1) and 2 (GluD2) exhibit the molecular architecture of postsynaptic ionotropic glutamate receptors, but assemble into trans-synaptic adhesion complexes by binding to secreted cerebellins that in turn interact with presynaptic neurexins1,2,3,4. It is unclear whether neurexin–cerebellin–GluD1/2 assemblies serve an adhesive synapse-formation function or mediate

In less than a decade, analyses of ancient genomes have transformed our understanding of the Indigenous peopling and population history of the Americas. These studies have shown that this history, which began in the late Pleistocene epoch and continued episodically into the Holocene epoch, was far more complex than previously thought. It is now evident that the initial dispersal involved the movement

Red supergiants are the most common final evolutionary stage of stars that have initial masses between 8 and 35 times that of the Sun1. During this stage, which lasts roughly 100,000 years1, red supergiants experience substantial mass loss. However, the mechanism for this mass loss is unknown2. Mass loss may affect the evolutionary path, collapse and future supernova light curve3 of a red supergiant

Flowing waters have a unique role in supporting global biodiversity, biogeochemical cycles and human societies1,2,3,4,5. Although the importance of permanent watercourses is well recognized, the prevalence, value and fate of non-perennial rivers and streams that periodically cease to flow tend to be overlooked, if not ignored6,7,8. This oversight contributes to the degradation of the main source of

Hippocampal neurons encode physical variables1,2,3,4,5,6,7 such as space1 or auditory frequency6 in cognitive maps8. In addition, functional magnetic resonance imaging studies in humans have shown that the hippocampus can also encode more abstract, learned variables9,10,11. However, their integration into existing neural representations of physical variables12,13 is unknown. Here, using two-photon

Understanding structural dynamics of biomolecules at the single-molecule level is vital to advancing our knowledge of molecular mechanisms. Currently, there are few techniques that can capture dynamics at the sub-nanometre scale and in physiologically relevant conditions. Atomic force microscopy (AFM)1 has the advantage of analysing unlabelled single molecules in physiological buffer and at ambient

Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve around the world, generating new variants that are of concern based on their potential for altered transmissibility, pathogenicity, and coverage by vaccines and therapeutics1–5. Here we report that 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, neutralize engineered SARS-CoV-2 with a USA-WA1/2020 genetic

The Ad26.COV2.S vaccine1–3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the

Superfluidity in its various forms has been of interest since the observation of frictionless flow in liquid helium II1,2. In three spatial dimensions it is conceptually associated with the emergence of long-range order at a critical temperature. One of the hallmarks of superfluidity, as predicted by the two-fluid model3,4 and observed in both liquid helium5 and in ultracold atomic gases6,7, is the

The performance of light microscopes is limited by the stochastic nature of light, which exists in discrete packets of energy known as photons. Randomness in the times that photons are detected introduces shot noise, which fundamentally constrains sensitivity, resolution and speed1. Although the long-established solution to this problem is to increase the intensity of the illumination light, this is

In the last few decades, topological phase1,2,3,4,5,6,7,8,9,10,11 has emerged as a new classification of matter states beyond the Ginzburg–Landau symmetry-breaking paradigm. The underlying global invariant is usually well characterized by integers, such as Chern numbers or winding numbers—the Abelian charges12,13,14,15. Very recently, researchers proposed the notion of non-Abelian topological charges16

The evolution of satellite galaxies is shaped by their constant interaction with the circumgalactic medium surrounding central galaxies, which in turn may be affected by gas and energy ejected from the central supermassive black hole1,2,3,4,5,6. The nature of such a coupling between black holes and galaxies is, however, much debated7,8,9 and observational evidence remains scarce10,11. Here we report

Perceptual constancy requires the brain to maintain a stable representation of sensory input. In the olfactory system, activity in primary olfactory cortex (piriform cortex) is thought to determine odour identity1,2,3,4,5. Here we present the results of electrophysiological recordings of single units maintained over weeks to examine the stability of odour-evoked responses in mouse piriform cortex.

Liquid–liquid phase separation is a major mechanism of subcellular compartmentalization1,2. Although the segregation of RNA into phase-separated condensates broadly affects RNA metabolism3,4, whether and how specific RNAs use phase separation to regulate interacting factors such as RNA-binding proteins (RBPs), and the phenotypic consequences of such regulatory interactions, are poorly understood. Here

Tissue stem cells are generated from a population of embryonic progenitors through organ-specific morphogenetic events1,2. Although tissue stem cells are central to organ homeostasis and regeneration, it remains unclear how they are induced during development, mainly because of the lack of markers that exclusively label prospective stem cells. Here we combine marker-independent long-term 3D live imaging

T cell immunoglobulin and mucin-containing molecule 3 (TIM-3), first identified as a molecule expressed on interferon-γ producing T cells1, is emerging as an important immune-checkpoint molecule, with therapeutic blockade of TIM-3 being investigated in multiple human malignancies. Expression of TIM-3 on CD8+ T cells in the tumour microenvironment is considered a cardinal sign of T cell dysfunction;

Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates

Genetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut

Since the start of the COVID-19 pandemic, SARS-CoV-2 has caused millions of deaths worldwide. While many vaccines have been deployed to date, the continual evolution of the viral receptor-binding domain (RBD) has challenged their efficacy. In particular, emerging variants B.1.1.7 (U.K.), B.1.351 (South Africa) and P.1 (Brazil) have compromised convalescent sera and immunotherapies that received emergency

Following its emergence in late 2019, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1,2 has been tracked via phylogenetic analysis of viral genome sequences in unprecedented detail3–5. While the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, within Europe travel resumed in the summer of 2020. Here

Resistance represents a major challenge for antibody-based therapy for coronavirus disease 2019 (COVID-19)1–4. Here we engineered an immunoglobulin M (IgM) neutralizing antibody (IgM-14) to overcome the resistance encountered by IgG-based therapeutics. IgM-14 is >230-fold more potent than its parental IgG-14 in neutralizing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IgM-14 potently

If a bulk material can withstand a high load without any irreversible damage (such as plastic deformation), it is usually brittle and can fail catastrophically1,2. This trade-off between strength and fracture toughness also extends into two-dimensional materials space3,4,5. For example, graphene has ultrahigh intrinsic strength (about 130 gigapascals) and elastic modulus (approximately 1.0 terapascal)

The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity1,2, nutrient biogeochemistry3, greenhouse gas emissions4, and the quality of drinking water5. The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity6,7, but little is known about the changes in dissolved oxygen concentrations in

The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment1,2,3. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a unique therapeutic window for preventing metastatic disease, a comprehensive

Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1,2,3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model—the Red2Onco system—that

A delicate equilibrium of WNT agonists and antagonists in the intestinal stem cell (ISC) niche is critical to maintaining the ISC compartment, as it accommodates the rapid renewal of the gut lining. Disruption of this balance by mutations in the tumour suppressor gene APC, which are found in approximately 80% of all human colon cancers, leads to unrestrained activation of the WNT pathway1,2. It has

Moiré superlattices formed by van der Waals materials can support a wide range of electronic phases, including Mott insulators1,2,3,4, superconductors5,6,7,8,9,10 and generalized Wigner crystals2. When excitons are confined by a moiré superlattice, a new class of exciton emerges, which holds promise for realizing artificial excitonic crystals and quantum optical effects11,12,13,14,15,16. When such

In perovskite solar cells, doped organic semiconductors are often used as charge-extraction interlayers situated between the photoactive layer and the electrodes. The π-conjugated small molecule 2,2′,7,7′-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9-spirobifluorene (spiro-OMeTAD) is the most frequently used semiconductor in the hole-conducting layer1,2,3,4,5,6, and its electrical properties considerably

The tumour suppressor APC is the most commonly mutated gene in colorectal cancer. Loss of Apc in intestinal stem cells drives the formation of adenomas in mice via increased WNT signalling1, but reduced secretion of WNT ligands increases the ability of Apc-mutant intestinal stem cells to colonize a crypt (known as fixation)2. Here we investigated how Apc-mutant cells gain a clonal advantage over wild-type

Our understanding of the dielectric response of interfacial water, which underlies the solvation properties and reaction rates at aqueous interfaces, relies on the linear response approximation: an external electric field induces a linearly proportional polarization. This implies antisymmetry with respect to the sign of the field. Atomistic simulations have suggested, however, that the polarization

AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning1. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength2. However, their mechanisms of action are poorly understood

Compartmentalization is a defining characteristic of eukaryotic cells, and partitions distinct biochemical processes into discrete subcellular locations. Microscopy1 and biochemical fractionation coupled with mass spectrometry2,3,4 have defined the proteomes of a variety of different organelles, but many intracellular compartments have remained refractory to such approaches. Proximity-dependent biotinylation

Future quantum networks will enable the distribution of entanglement between distant locations and allow applications in quantum communication, quantum sensing and distributed quantum computation1. At the core of this network lies the ability to generate and store entanglement at remote, interconnected quantum nodes2. Although various remote physical systems have been successfully entangled3,4,5,6

Owing to the inevitable loss in communication channels, the distance of entanglement distribution is limited to approximately 100 kilometres on the ground1. Quantum repeaters can circumvent this problem by using quantum memory and entanglement swapping2. As the elementary link of a quantum repeater, the heralded distribution of two-party entanglement between two remote nodes has only been realized

Sickle cell disease (SCD) is caused by a mutation in the β-globin gene HBB1. We used a custom adenine base editor (ABE8e-NRCH)2,3 to convert the SCD allele (HBBS) into Makassar β-globin (HBBG), a non-pathogenic variant4,5. Ex vivo delivery of mRNA encoding the base editor with a targeting guide RNA into haematopoietic stem and progenitor cells (HSPCs) from patients with SCD resulted in 80% conversion

BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) that encodes the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike glycoprotein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy in preventing coronavirus disease-19 (COVID-19)1. Here we extend our previous phase 1/2 trial report2 and present BNT162b2 prime/boost induced

Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine1,2. Patients with leukaemia can be identified using machine learning on the basis of their blood transcriptomes3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation4,5. Here, to facilitate the integration of

Accurate quantification of global land evapotranspiration is necessary for understanding variability in the global water cycle, which is expected to intensify under climate change1,2,3. Current global evapotranspiration products are derived from a variety of sources, including models4,5, remote sensing6,7 and in situ observations8,9,10. However, existing approaches contain extensive uncertainties;

Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and ‘trauma- and stressor-related’ disorders1. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the

Folates (also known as vitamin B9) have a critical role in cellular metabolism as the starting point in the synthesis of nucleic acids, amino acids and the universal methylating agent S-adenylsmethionine1,2. Folate deficiency is associated with a number of developmental, immune and neurological disorders3,4,5. Mammals cannot synthesize folates de novo; several systems have therefore evolved to take

The second integument of the angiosperm ovule is unique among seed plants, with developmental genetics that are distinct from those of the inner integument1. Understanding how the second integument should be compared to structures in other seed plants is therefore crucial to resolving the long-standing question of the origin of angiosperms2,3,4,5,6. Attention has focused on several extinct plants with

The functional engagement between an enhancer and its target promoter ensures precise gene transcription1. Understanding the basis of promoter choice by enhancers has important implications for health and disease. Here we report that functional loss of a preferred promoter can release its partner enhancer to loop to and activate an alternative promoter (or alternative promoters) in the neighbourhood

Van der Waals heterostructures display numerous unique electronic properties. Nonlocal measurements, wherein a voltage is measured at contacts placed far away from the expected classical flow of charge carriers, have been widely used in the search for novel transport mechanisms, including dissipationless spin and valley transport1,2,3,4,5,6,7,8,9, topological charge-neutral currents10,11,12, hydrodynamic

Liquid–liquid phase separation (LLPS) has emerged as a central paradigm for understanding how membraneless organelles compartmentalize diverse cellular activities in eukaryotes1,2,3. Here we identify a superfamily of plant guanylate-binding protein (GBP)-like GTPases (GBPLs) that assemble LLPS-driven condensates within the nucleus to protect against infection and autoimmunity. In Arabidopsis thaliana

Atomically defined assemblies of dye molecules (such as H and J aggregates) have been of interest for more than 80 years because of the emergence of collective phenomena in their optical spectra1,2,3, their coherent long-range energy transport, their conceptual similarity to natural light-harvesting complexes4,5, and their potential use as light sources and in photovoltaics. Another way of creating

The phase behaviour of warm dense hydrogen−helium (H−He) mixtures affects our understanding of the evolution of Jupiter and Saturn and their interior structures1,2. For example, precipitation of He from a H−He atmosphere at about 1−10 megabar and a few thousand kelvin has been invoked to explain both the excess luminosity of Saturn1,3, and the depletion of He and neon (Ne) in Jupiter’s atmosphere as

Human mobility impacts many aspects of a city, from its spatial structure1,2,3 to its response to an epidemic4,5,6,7. It is also ultimately key to social interactions8, innovation9,10 and productivity11. However, our quantitative understanding of the aggregate movements of individuals remains incomplete. Existing models—such as the gravity law12,13 or the radiation model14—concentrate on the purely

Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate1. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. More specifically, there is a major unmet need for a new class of

Trypanosomes are protozoan parasites that cause infectious diseases, including African trypanosomiasis (sleeping sickness) in humans and nagana in economically important livestock1,2. An effective vaccine against trypanosomes would be an important control tool, but the parasite has evolved sophisticated immunoprotective mechanisms—including antigenic variation3—that present an apparently insurmountable

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear—particularly in the setting of cancer predisposition

Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies1–7. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent individuals have a significantly lower risk of reinfection8–10. Nonetheless, it has been reported that anti-SARS-CoV-2 serum antibodies experience rapid decay in the first few months after infection, raising concerns