Positron emission tomography (PET) radioligands are highly enabling tracers which facilitate in vivo characterization of central nervous system (CNS) drug candidates, neurodegenerative diseases, and numerous oncology targets1. While both tritium and carbon-11 radioisotopologs are generally necessary for in vitro and in vivo characterization of radioligands2, there exist few radiolabeling protocols

The distal lung contains terminal bronchioles and alveoli that facilitate gas exchange. Three-dimensional in vitro human distal lung culture systems would strongly facilitate investigation of pathologies including interstitial lung disease, cancer, and SARS-CoV-2-associated COVID-19 pneumonia. We generated long-term feeder-free, chemically defined culture of distal lung progenitors as organoids derived

For most of their existence, stars are fuelled by the fusion of hydrogen into helium. Fusion proceeds via two processes that are well understood theoretically: the proton–proton (pp) chain and the carbon–nitrogen–oxygen (CNO) cycle1,2. Neutrinos that are emitted along such fusion processes in the solar core are the only direct probe of the deep interior of the Sun. A complete spectroscopic study of

In mammals, telomere protection is mediated by the essential protein TRF2, which binds chromosome ends and ensures genome integrity1,2. TRF2 depletion results in end-to-end chromosome fusions in all cell types that have been tested so far. Here we find that TRF2 is dispensable for the proliferation and survival of mouse embryonic stem (ES) cells. Trf2−/− (also known as Terf2) ES cells do not exhibit

Genetic diversity is key to crop improvement. Owing to pervasive genomic structural variation, a single reference genome assembly cannot capture the full complement of sequence diversity of a crop species (known as the ‘pan-genome’1). Multiple high-quality sequence assemblies are an indispensable component of a pan-genome infrastructure. Barley (Hordeum vulgare L.) is an important cereal crop with

The generation, control and transfer of triplet excitons in molecular and hybrid systems is of great interest owing to their long lifetime and diffusion length in both solid-state and solution phase systems, and to their applications in light emission1, optoelectronics2,3, photon frequency conversion4,5 and photocatalysis6,7. Molecular triplet excitons (bound electron–hole pairs) are ‘dark states’

Mammalian telomeres protect chromosome ends from aberrant DNA repair1. TRF2, a component of the telomere-specific shelterin protein complex, facilitates end protection through sequestration of the terminal telomere repeat sequence within a lariat T-loop structure2,3. Deleting TRF2 (also known as TERF2) in somatic cells abolishes T-loop formation, which coincides with telomere deprotection, chromosome

Fibrosis can affect any organ and is responsible for up to 45% of all deaths in the industrialized world. It has long been thought to be relentlessly progressive and irreversible, but both preclinical models and clinical trials in various organ systems have shown that fibrosis is a highly dynamic process. This has clear implications for therapeutic interventions that are designed to capitalize on this

Sea-level rise due to ice loss in the Northern Hemisphere in response to insolation and greenhouse gas forcing is thought to have caused grounding-line retreat of marine-based sectors of the Antarctic Ice Sheet (AIS)1,2,3. Such interhemispheric sea-level forcing may explain the synchronous evolution of global ice sheets over ice-age cycles. Recent studies that indicate that the AIS experienced substantial

Intensive fisheries have reduced fish biodiversity and abundance in aquatic ecosystems worldwide1,2,3. ‘No-take’ marine reserves have become a cornerstone of marine ecosystem-based fisheries management4,5,6, and their benefits for adjacent fisheries are maximized when reserve design fosters synergies among nearby reserves7,8. The applicability of this marine reserve network paradigm to riverine biodiversity

The gut microbiota influences development1,2,3 and homeostasis4,5,6,7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11,12,13,14. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference

The acquisition of terrestrial, limb-based locomotion during tetrapod evolution has remained a subject of debate for more than a century1,2. Our current understanding of the locomotor transition from water to land is largely based on a few exemplar fossils such as Tiktaalik3, Acanthostega4, Ichthyostega5 and Pederpes6. However, isolated bony elements may reveal hidden functional diversity, providing

The zebrafish (Danio rerio) has been widely used in the study of human disease and development, and about 70% of the protein-coding genes are conserved between the two species1. However, studies in zebrafish remain constrained by the sparse annotation of functional control elements in the zebrafish genome. Here we performed RNA sequencing, assay for transposase-accessible chromatin using sequencing

The ability to sense physical forces is conserved across all organisms. Cells convert mechanical stimuli into electrical or chemical signals via mechanically activated ion channels. In recent years, the identification of new families of mechanosensitive ion channels—such as PIEZO and OSCA/TMEM63 channels—along with surprising insights into well-studied mechanosensitive channels have driven further

Advances in genomics have expedited the improvement of several agriculturally important crops but similar efforts in wheat (Triticum spp.) have been more challenging. This is largely owing to the size and complexity of the wheat genome1, and the lack of genome-assembly data for multiple wheat lines2,3. Here we generated ten chromosome pseudomolecule and five scaffold assemblies of hexaploid wheat to

The liver connects the intestinal portal vasculature with the general circulation, using a diverse array of immune cells to protect from pathogens that translocate from the gut1. In liver lobules, blood flows from portal triads that are situated in periportal lobular regions to the central vein via a polarized sinusoidal network. Despite this asymmetry, resident immune cells in the liver are considered

The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often

Mesozoic birds display considerable diversity in size, flight adaptations and feather organization1,2,3,4, but exhibit relatively conserved patterns of beak shape and development5,6,7. Although Neornithine (that is, crown group) birds also exhibit constraint on facial development8,9, they have comparatively diverse beak morphologies associated with a range of feeding and behavioural ecologies, in contrast

Choosing a mate is one of the most consequential decisions a female will make during her lifetime. A female fly signals her willingness to mate by opening her vaginal plates, allowing a courting male to copulate1,2. Vaginal plate opening (VPO) occurs in response to the male courtship song and is dependent on the mating status of the female. How these exteroceptive (song) and interoceptive (mating status)

Janus kinases (JAKs) mediate responses to cytokines, hormones and growth factors in haematopoietic cells1,2. The JAK gene JAK2 is frequently mutated in the ageing haematopoietic system3,4 and in haematopoietic cancers5. JAK2 mutations constitutively activate downstream signalling and are drivers of myeloproliferative neoplasm (MPN). In clinical use, JAK inhibitors have mixed effects on the overall

Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields—a longstanding technological goal in spintronics and multiferroics1,2—can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials—especially those in which multiple degrees of freedom or energy scales are delicately balanced—is of

The oxygen evolution reaction has an important role in many alternative-energy schemes because it supplies the protons and electrons required for converting renewable electricity into chemical fuels1,2,3. Electrocatalysts accelerate the reaction by facilitating the required electron transfer4, as well as the formation and rupture of chemical bonds5. This involvement in fundamentally different processes

Venezuelan equine encephalitis virus (VEEV) is a neurotropic alphavirus transmitted by mosquitoes that causes encephalitis and death in humans1. VEEV is a biodefence concern because of its potential for aerosol spread and the current lack of sufficient countermeasures. The host factors that are required for VEEV entry and infection remain poorly characterized. Here, using a genome-wide CRISPR–Cas9-based

Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles1,2,3,4,5,6,7,8,9, it has been difficult to systematically identify and localize all molecular cell types in individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments

Aquatic birds represent a vast reservoir from which new pandemic influenza A viruses can emerge1. Influenza viruses contain a negative-sense segmented RNA genome that is transcribed and replicated by the viral heterotrimeric RNA polymerase (FluPol) in the context of viral ribonucleoprotein complexes2,3. RNA polymerases of avian influenza A viruses (FluPolA) replicate viral RNA inefficiently in human

The modern description of elementary particles, as formulated in the standard model of particle physics, is built on gauge theories1. Gauge theories implement fundamental laws of physics by local symmetry constraints. For example, in quantum electrodynamics Gauss’s law introduces an intrinsic local relation between charged matter and electromagnetic fields, which protects many salient physical properties

Effective and sustained inhibition of non-enzymatic oncogenic driver proteins is a major pharmacological challenge. The clinical success of thalidomide analogues demonstrates the therapeutic efficacy of drug-induced degradation of transcription factors and other cancer targets1,2,3, but a substantial subset of proteins are resistant to targeted degradation using existing approaches4,5. Here we report

Stellar mergers are a brief but common phase in the evolution of binary star systems1,2. These events have many astrophysical implications; for example, they may lead to the creation of atypical stars (such as magnetic stars3, blue stragglers4 and rapid rotators5), they play an important part in our interpretation of stellar populations6 and they represent formation channels of compact-object mergers7

There is a contradiction at the heart of our current understanding of individual and collective mobility patterns. On the one hand, a highly influential body of literature on human mobility driven by analyses of massive empirical datasets finds that human movements show no evidence of characteristic spatial scales. There, human mobility is described as scale free1,2,3. On the other hand, geographically

The science of cities seeks to understand and explain regularities observed in the world’s major urban systems. Modelling the population evolution of cities is at the core of this science and of all urban studies. Quantitatively, the most fundamental problem is to understand the hierarchical organization of city population and the statistical occurrence of megacities. This was first thought to be described

Dozens of genes contribute to the wide variation in human pigmentation. Many of these genes encode proteins that localize to the melanosome—the organelle, related to the lysosome, that synthesizes pigment—but have unclear functions1,2. Here we describe MelanoIP, a method for rapidly isolating melanosomes and profiling their labile metabolite contents. We use this method to study MFSD12, a transmembrane

Recent analyses have reported catastrophic global declines in vertebrate populations1,2. However, the distillation of many trends into a global mean index obscures the variation that can inform conservation measures and can be sensitive to analytical decisions. For example, previous analyses have estimated a mean vertebrate decline of more than 50% since 1970 (Living Planet Index2). Here we show, however

The formation of synapses during neuronal development is essential for establishing neural circuits and a nervous system1. Every presynapse builds a core ‘active zone’ structure, where ion channels cluster and synaptic vesicles release their neurotransmitters2. Although the composition of active zones is well characterized2,3, it is unclear how active-zone proteins assemble together and recruit the

Adaptive radiation is the likely source of much of the ecological and morphological diversity of life1,2,3,4. How adaptive radiations proceed and what determines their extent remains unclear in most cases1,4. Here we report the in-depth examination of the spectacular adaptive radiation of cichlid fishes in Lake Tanganyika. On the basis of whole-genome phylogenetic analyses, multivariate morphological

Confinement of the X chromosome to a territory for dosage compensation is a prime example of how subnuclear compartmentalization is used to regulate transcription at the megabase scale. In Drosophila melanogaster, two sex-specific non-coding RNAs (roX1 and roX2) are transcribed from the X chromosome. They associate with the male-specific lethal (MSL) complex1, which acetylates histone H4 lysine 16

The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates

Particulate matter is a component of ambient air pollution that has been linked to millions of annual premature deaths globally1,2,3. Assessments of the chronic and acute effects of particulate matter on human health tend to be based on mass concentration, with particle size and composition also thought to play a part4. Oxidative potential has been suggested to be one of the many possible drivers of

CrAss-like phages are a recently described expansive group of viruses that includes the most abundant virus in the human gut1,2,3. The genomes of all crAss-like phages encode a large virion-packaged protein2,4 that contains a DFDxD sequence motif, which forms the catalytic site in cellular multisubunit RNA polymerases (RNAPs)5. Here, using Cellulophaga baltica crAss-like phage phi14:2 as a model system

The regulation of signalling capacity, combined with the spatiotemporal distribution of developmental signals themselves, is pivotal in setting developmental responses in both plants and animals1. The hormone auxin is a key signal for plant growth and development that acts through the AUXIN RESPONSE FACTOR (ARF) transcription factors2,3,4. A subset of these, the conserved class A ARFs5, are transcriptional

How diverse cell fates and complex forms emerge and feed back to each other to sculpt functional organs remains unclear. In the developing heart, the myocardium transitions from a simple epithelium to an intricate tissue that consists of distinct layers: the outer compact and inner trabecular layers. Defects in this process, which is known as cardiac trabeculation, cause cardiomyopathies and embryonic

Endogenous viral elements (EVEs)—viruses that have integrated their genomes into those of their hosts—are prevalent in eukaryotes and have an important role in genome evolution1,2. The vast majority of EVEs that have been identified to date are small genomic regions comprising a few genes2, but recent evidence suggests that some large double-stranded DNA viruses may also endogenize into the genome

Eukaryotic ribosomes consist of a small 40S and a large 60S subunit that are assembled in a highly coordinated manner. More than 200 factors ensure correct modification, processing and folding of ribosomal RNA and the timely incorporation of ribosomal proteins1,2. Small subunit maturation ends in the cytosol, when the final rRNA precursor, 18S-E, is cleaved at site 3 by the endonuclease NOB13. Previous

Tumours often contain B cells and plasma cells but the antigen specificity of these intratumoral B cells is not well understood1,2,3,4,5,6,7,8. Here we show that human papillomavirus (HPV)-specific B cell responses are detectable in samples from patients with HPV-positive head and neck cancers, with active production of HPV-specific IgG antibodies in situ. HPV-specific antibody secreting cells (ASCs)

Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties1,2. Most existing neural taxonomies are based on either transcriptomic3,4 or morpho-electric5,6 criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells7. Here we used Patch-seq8 to combine patch-clamp recording, biocytin

Kidney fibrosis is the hallmark of chronic kidney disease progression, however, currently no antifibrotic therapies exist.1–3 This is largely because the origin, functional heterogeneity and regulation of scar-forming cells during human kidney fibrosis remains poorly understood.1,2,4 Here, using single cell RNA-seq, we profiled the transcriptomes of proximal tubule and non-proximal tubule cells in

Expansion of anthropogenic noise and night lighting across our planet1,2 is of increasing conservation concern3,4,5,6. Despite growing knowledge of physiological and behavioural responses to these stimuli from single-species and local-scale studies, whether these pollutants affect fitness is less clear, as is how and why species vary in their sensitivity to these anthropic stressors. Here we leverage

When a hurricane strikes land, the destruction of property and the environment and the loss of life are largely confined to a narrow coastal area. This is because hurricanes are fuelled by moisture from the ocean1,2,3, and so hurricane intensity decays rapidly after striking land4,5. In contrast to the effect of a warming climate on hurricane intensification, many aspects of which are fairly well understood6

The ubiquitous heat shock protein 70 (HSP70) family consists of ATP-dependent molecular chaperones, which perform numerous cellular functions that affect almost all aspects of the protein life cycle from synthesis to degradation1,2,3. Achieving this broad spectrum of functions requires precise regulation of HSP70 activity. Proteins of the HSP40 family, also known as J-domain proteins (JDPs), have a

The threat of criminal activity in the fisheries sector has concerned the international community for a number of years. In more recent times, the presence of organized crime in fisheries has come to the fore. In 2008, the United Nations General Assembly asked all states to contribute to increasing our understanding the connection between illegal fishing and transnational organized crime at sea. Policy-makers

Genome introgressions drive evolution across the animal1, plant2 and fungal3 kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast4, has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces

The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However

The deposition of highly ordered fibrillar-type aggregates into inclusion bodies is a hallmark of neurodegenerative diseases such as Parkinson’s disease. The high stability of such amyloid fibril aggregates makes them challenging substrates for the cellular protein quality-control machinery1,2. However, the human HSP70 chaperone and its co-chaperones DNAJB1 and HSP110 can dissolve preformed fibrils

New genome assemblies have been arriving at a rapidly increasing pace, thanks to decreases in sequencing costs and improvements in third-generation sequencing technologies1,2,3. For example, the number of vertebrate genome assemblies currently in the NCBI (National Center for Biotechnology Information) database4 increased by more than 50% to 1,485 assemblies in the year from July 2018 to July 2019

Wavelength is a physical measure of light, and the intricate understanding of its link to perceived colour enables the creation of perceptual entities such as metamers—non-overlapping spectral compositions that generate identical colour percepts1. By contrast, scientists have been unable to develop a physical measure linked to perceived smell, even one that merely reflects the extent of perceptual

Cholesterol is an essential lipid and its synthesis is nutritionally and energetically costly1,2. In mammals, cholesterol biosynthesis increases after feeding and is inhibited under fasting conditions3. However, the regulatory mechanisms of cholesterol biosynthesis at the fasting–feeding transition remain poorly understood. Here we show that the deubiquitylase ubiquitin-specific peptidase 20 (USP20)

Despite its success in achieving the long-term survival of 10–30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune ‘checkpoint’ therapy3,4,5 (so called because its aim is to block proteins that inhibit checkpoint signalling pathways in T cells, thereby freeing those immune

Quantum particles on a lattice with competing long-range interactions are ubiquitous in physics; transition metal oxides1,2, layered molecular crystals3 and trapped-ion arrays4 are a few examples. In the strongly interacting regime, these systems often show a rich variety of quantum many-body ground states that challenge theory2. The emergence of transition metal dichalcogenide moiré superlattices

Perisynaptic astrocytic processes are an integral part of central nervous system synapses1,2; however, the molecular mechanisms that govern astrocyte–synapse adhesions and how astrocyte contacts control synapse formation and function are largely unknown. Here we use an in vivo chemico-genetic approach that applies a cell-surface fragment complementation strategy, Split-TurboID, and identify a proteome

The selectivity of neuronal responses arises from the architecture of excitatory and inhibitory connections. In the primary visual cortex, the selectivity of a neuron in layer 2/3 for stimulus orientation and direction is thought to arise from intracortical inputs that are similarly selective1,2,3,4,5,6,7,8. However, the excitatory inputs of a neuron can have diverse stimulus preferences1,2,3,4,6,7