SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1–4, followed by fusion of virus and cell membranes to release the virus genome into the cell. Both receptor binding and membrane fusion activities are mediated by the virus Spike glycoprotein, S5–7. As with other class I membrane fusion proteins, S is post-translationally cleaved, in this case by furin, into S1 and S2

Viperin is an interferon-induced cellular protein conserved in animals1. It was shown to inhibit the replication of multiple viruses by producing a ribonucleotide called 3’-deoxy-3’4’-didehydro-CTP (ddhCTP), which acts as a chain terminator for the viral RNA polymerase2. Here we show that the eukaryotic viperin has originated from a clade of bacterial and archaeal proteins that protect against phage

The field of plasmonics, which studies the resonant interactions of electromagnetic waves and free electrons in solid-state materials1, has yet to be put to large-scale commercial application2 owing to the large amount of loss that usually occurs in plasmonic materials3. Organic light-emitting devices (OLEDs)4,5,6,7 have been incorporated into billions of commercial products because of their good colour

Array programming provides a powerful, compact and expressive syntax for accessing, manipulating and operating on data in vectors, matrices and higher-dimensional arrays. NumPy is the primary array programming library for the Python language. It has an essential role in research analysis pipelines in fields as diverse as physics, chemistry, astronomy, geoscience, biology, psychology, materials science

Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology1,2,3,4. However, the approaches that are used at present to derive these organoids in three-dimensional matrices5,6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation

Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1,2,3,4,5,6,7,8,9,10,11,12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including

The maritime expansion of Scandinavian populations during the Viking Age (about ad 750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south

The reprogramming of human somatic cells to primed or naive induced pluripotent stem cells recapitulates the stages of early embryonic development1,2,3,4,5,6. The molecular mechanism that underpins these reprogramming processes remains largely unexplored, which impedes our understanding and limits rational improvements to reprogramming protocols. Here, to address these issues, we reconstruct molecular

Climate and physiology shape biogeography, yet the range limits of species can rarely be ascribed to the quantitative traits of organisms1,2,3. Here we evaluate whether the geographical range boundaries of species coincide with ecophysiological limits to acquisition of aerobic energy4 for a global cross-section of the biodiversity of marine animals. We observe a tight correlation between the metabolic

Ultrasound detectors use high-frequency sound waves to image objects and measure distances, but the resolution of these readings is limited by the physical dimensions of the detecting element. Point-like broadband ultrasound detection can greatly increase the resolution of ultrasonography and optoacoustic (photoacoustic) imaging1,2, but current ultrasound detectors, such as those used for medical imaging

Breaks in DNA strands recruit the protein PARP1 and its paralogue PARP2 to modify histones and other substrates through the addition of mono- and poly(ADP-ribose) (PAR)1,2,3,4,5. In the DNA damage responses, this post-translational modification occurs predominantly on serine residues6,7,8 and requires HPF1, an accessory factor that switches the amino acid specificity of PARP1 and PARP2 from aspartate

Ferroptosis—an iron-dependent, non-apoptotic cell death process—is involved in various degenerative diseases and represents a targetable susceptibility in certain cancers1. The ferroptosis-susceptible cell state can either pre-exist in cells that arise from certain lineages or be acquired during cell-state transitions2,3,4,5. However, precisely how susceptibility to ferroptosis is dynamically regulated

Persistent neural activity in cortical, hippocampal, and motor networks has been described as mediating working memory for transiently encountered stimuli1,2. Internal emotional states, such as fear, also persist following exposure to an inciting stimulus3, but it is unclear whether slow neural dynamics are involved in this process. Neurons in the dorsomedial and central subdivisions of the ventromedial

The non-dissipative nonlinearity of Josephson junctions1 converts macroscopic superconducting circuits into artificial atoms2, enabling some of the best-controlled qubits today3,4. Three fundamental types of superconducting qubit are known5, each reflecting a distinct behaviour of quantum fluctuations in a Cooper pair condensate: single-charge tunnelling (charge qubit6,7), single-flux tunnelling (flux

Insect eyes have an anti-reflective coating, owing to nanostructures on the corneal surface creating a gradient of refractive index between that of air and that of the lens material1,2. These nanocoatings have also been shown to provide anti-adhesive functionality3. The morphology of corneal nanocoatings are very diverse in arthropods, with nipple-like structures that can be organized into arrays or

Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals3,4,5, a similar degree of protection to that afforded by the sickle-cell trait and considerably

Astronomers have discovered thousands of planets outside the Solar System1, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star2, but more distant planets can survive this phase and remain in orbit around the white dwarf3,4. Some white dwarfs show evidence for rocky material

Neural crest cells (NCCs) are migratory, multipotent embryonic cells that are unique to vertebrates and form an array of clade-defining adult features. The evolution of NCCs has been linked to various genomic events, including the evolution of new gene-regulatory networks1,2, the de novo evolution of genes3 and the proliferation of paralogous genes during genome-wide duplication events4. However, conclusive

The MAPK/ERK kinase MEK is a shared effector of the frequent cancer drivers KRAS and BRAF that has long been pursued as a drug target in oncology1, and more recently in immunotherapy2,3 and aging4. However, many MEK inhibitors (MEKi) are limited due to on-target toxicities5–7 and drug resistance8–10. Accordingly, a molecular understanding of the structure and function of MEK within physiological complexes

The DNA sensor cGAS initiates innate immune responses following microbial infection, cellular stress, and cancer1. Upon activation by double-stranded DNA, cytosolic cGAS produces 2’3’ cyclic GMP-AMP and triggers inflammatory cytokine and type I interferon (IFN) induction2–7. cGAS is also present inside the cell nucleus replete with genomic DNA8, where chromatin has been implicated in restricting its

Pathogen-derived nucleic acids induce potent innate immune responses1–6. Cyclic GMP-AMP synthase (cGAS) is a dsDNA sensor that catalyzes the synthesis of a cyclic dinucleotide cGAMP, which mediates the induction of type I interferons through the STING-TBK1-IRF3 signaling axis7–11. It was widely accepted that cGAS is not reactive to self-DNA due to its cytosolic localization2,12,13. However, recent

cGAS (cyclic GMP–AMP synthase) is an innate immune sensor for cytosolic microbial DNA1. Upon binding DNA, it synthesizes the messenger cGAMP (2’3’ cyclic GMP–AMP)2–4, which triggers cell-autonomous defense and the production of type I interferons and pro-inflammatory cytokines via activation of STING5. Besides responding to cytosolic microbial DNA, cGAS also recognizes mis-localized cytosolic self-DNA

Increased efforts are required to prevent further losses to terrestrial biodiversity and the ecosystem services that it provides1,2. Ambitious targets have been proposed, such as reversing the declining trends in biodiversity3; however, just feeding the growing human population will make this a challenge4. Here we use an ensemble of land-use and biodiversity models to assess whether—and how—humanity

Mitochondria require nicotinamide adenine dinucleotide (NAD+) in order to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD+ transporters have been identified in yeast and plants1,2 but their very existence is controversial in mammals3–5. Here we demonstrate that mammalian mitochondria are capable of taking up intact NAD+ and identify

Metal–organic frameworks (MOFs)1–3 are known for their specific interactions with gas molecules4,5; combined with their rich and ordered porosity, this makes them promising candidates for the photocatalytic conversion of gas molecules to useful products6. Attempts to use MOFs or MOF-based composites for CO2 photoreduction6–13, however, usually result in far lower CO2 conversion efficiency compared

Hydrogen, the simplest and most abundant element in the Universe, develops a remarkably complex behaviour upon compression1. Since Wigner predicted the dissociation and metallization of solid hydrogen at megabar pressures almost a century ago2, several efforts have been made to explain the many unusual properties of dense hydrogen, including a rich and poorly understood solid polymorphism1,3,4,5, an

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing Coronavirus disease 19 (COVID-19) pandemic1. In order to understand SARS-CoV-2 pathogenicity and antigenic potential, and to develop therapeutic tools, it is essential to portray the full repertoire of its expressed proteins. The SARS-CoV-2 coding capacity map is currently based on computational predictions and

The successful operation of quantum computers relies on protecting qubits from decoherence and noise, which—if uncorrected—will lead to erroneous results. Because these errors accumulate during an algorithm, correcting them is a key requirement for large-scale and fault-tolerant quantum information processors. Besides computational errors, which can be addressed by quantum error correction1,2,3,4,5

The dominant gaseous structure in the Galactic halo is the Magellanic Stream. This extended network of neutral and ionized filaments surrounds the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), the two most massive satellite galaxies of the Milky Way1,2,3,4. Recent observations indicate that the LMC and SMC are on their first passage around the Galaxy5, that the Magellanic Stream

Thermal management is one of the main challenges for the future of electronics1,2,3,4,5. With the ever-increasing rate of data generation and communication, as well as the constant push to reduce the size and costs of industrial converter systems, the power density of electronics has risen6. Consequently, cooling, with its enormous energy and water consumption, has an increasingly large environmental

Despite its size and rigidity, the cell nucleus can be moved or reorganized by cytoskeletal filaments under various conditions (for example, during viral infection)1,2,3,4,5,6,7,8,9,10,11. Moreover, whereas chromatin organizes into non-random domains12, extensive heterogeneity at the single-cell level13 means that precisely how and why nuclei reorganize remains an area of intense investigation. Here

Isoprene is the dominant non-methane organic compound emitted to the atmosphere1,2,3. It drives ozone and aerosol production, modulates atmospheric oxidation and interacts with the global nitrogen cycle4,5,6,7,8. Isoprene emissions are highly uncertain1,9, as is the nonlinear chemistry coupling isoprene and the hydroxyl radical, OH—its primary sink10,11,12,13. Here we present global isoprene measurements

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional

Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3,4,5 to achieve X-chromosome inactivation

Advances in machine learning and contactless sensors have given rise to ambient intelligence—physical spaces that are sensitive and responsive to the presence of humans. Here we review how this technology could improve our understanding of the metaphorically dark, unobserved spaces of healthcare. In hospital spaces, early applications could soon enable more efficient clinical workflows and improved

The RNA polymerase II (Pol II) core promoter is the strategic site of convergence of the signals that lead to the initiation of DNA transcription1,2,3,4,5, but the downstream core promoter in humans has been difficult to understand1,2,3. Here we analyse the human Pol II core promoter and use machine learning to generate predictive models for the downstream core promoter region (DPR) and the TATA box

Platinum is a much used catalyst that, in petrochemical processes, is often alloyed with other metals to improve catalytic activity, selectivity and longevity1,2,3,4,5. Such catalysts are usually prepared in the form of metallic nanoparticles supported on porous solids, and their production involves reducing metal precursor compounds under a H2 flow at high temperatures6. The method works well when

Genomic instability is a hallmark of cancer, and has a central role in the initiation and development of breast cancer1,2. The success of poly-ADP ribose polymerase inhibitors in the treatment of breast cancers that are deficient in homologous recombination exemplifies the utility of synthetically lethal genetic interactions in the treatment of breast cancers that are driven by genomic instability3

Centrosomes catalyse the formation of microtubules needed to assemble the mitotic spindle apparatus1. Centrosomes themselves duplicate once per cell cycle, in a process that is controlled by the serine/threonine protein kinase PLK4 (refs. 2,3). When PLK4 is chemically inhibited, cell division proceeds without centrosome duplication, generating centrosome-less cells that exhibit delayed, acentrosomal

The transport of carbon into Earth’s mantle is a critical pathway in Earth’s carbon cycle, affecting both the climate and the redox conditions of the surface and mantle. The largest unconstrained variables in this cycle are the depths to which carbon in sediments and altered oceanic crust can be subducted and the relative contributions of these reservoirs to the sequestration of carbon in the deep

Influenza A virus causes millions of severe cases of disease during annual epidemics. The most abundant protein in influenza virions is matrix protein 1 (M1), which mediates virus assembly by forming an endoskeleton beneath the virus membrane1. The structure of full-length M1, and how it oligomerizes to mediate the assembly of virions, is unknown. Here we determine the complete structure of assembled

Caenorhabditis elegans must distinguish pathogens from nutritious food sources among the many bacteria to which it is exposed in its environment1. Here we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance in the treated worms and in four subsequent generations of progeny. The RNA interference (RNAi) and

Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent1,2,3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations

LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis

Adaptive behaviour crucially depends on flexible decision-making, which in mammals relies on the frontal cortex, specifically the orbitofrontal cortex (OFC)1,2,3,4,5,6,7,8,9. How OFC encodes decision variables and instructs sensory areas to guide adaptive behaviour are key open questions. Here we developed a reversal learning task for head-fixed mice, monitored the activity of neurons of the lateral

Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP–AMP signalling during viral infection and antitumour immunity1–5. STING shares no structural homology with other known signalling proteins6–9, limiting functional analysis and preventing explanation of the origin of cyclic dinucleotide

Quinones are produced and sensed in all kingdoms of life1,2,3,4. Plants are primary producers of quinone1,2, but the role of quinone as a signalling agent in plants remains largely unknown. One well-documented role of quinone is in the induction of haustoria (specialized feeding structures) in plants that parasitize roots, which occurs in the presence of the host-derived quinone compound 2,6-dimethoxy-1

When placed over a less dense medium, a liquid layer will typically collapse downwards if it exceeds a certain size, as gravity acting on the lower liquid interface triggers a destabilizing effect called a Rayleigh–Taylor instability1,2. Of the many methods that have been developed to prevent the liquid from falling3,4,5,6, vertical shaking has proved to be efficient and has therefore been studied

Organic–inorganic lead halide quasi-two-dimensional (2D) perovskites are promising gain media for lasing applications because of their low cost, tunable colour, excellent stability and solution processability1,2,3. Optically pumped continuous-wave (CW) lasing is highly desired for practical applications in high-density integrated optoelectronics devices and constitutes a key step towards electrically

Introductions of species by humans are causing the homogenization of species composition across biogeographic barriers1,2,3. The ecological and evolutionary consequences of introduced species derive from their effects on networks of species interactions4,5, but we lack a quantitative understanding of the impacts of introduced species on ecological networks and their biogeographic patterns globally

Rechargeable lithium-ion batteries with high energy density that can be safely charged and discharged at high rates are desirable for electrified transportation and other applications1,2,3. However, the sub-optimal intercalation potentials of current anodes result in a trade-off between energy density, power and safety. Here we report that disordered rock salt4,5 Li3+xV2O5 can be used as a fast-charging

Abnormal epigenetic patterns correlate with effector T cell malfunction in tumours1,2,3,4, but the cause of this link is unknown. Here we show that tumour cells disrupt methionine metabolism in CD8+ T cells, thereby lowering intracellular levels of methionine and the methyl donor S-adenosylmethionine (SAM) and resulting in loss of dimethylation at lysine 79 of histone H3 (H3K79me2). Loss of H3K79me2

Nuclear pore complexes (NPCs) fuse the inner and outer membranes of the nuclear envelope. They comprise hundreds of nucleoporins (Nups) that assemble into multiple subcomplexes and form large central channels for nucleocytoplasmic exchange1,2. How this architecture facilitates messenger RNA export, NPC biogenesis and turnover remains poorly understood. Here we combine in situ structural biology and

The masses of the lightest atomic nuclei and the electron mass1 are interlinked, and their values affect observables in atomic2, molecular3,4,5 and neutrino physics6, as well as metrology. The most precise values for these fundamental parameters come from Penning trap mass spectrometry, which achieves relative mass uncertainties of the order of 10−11. However, redundancy checks using data from different

Loss of normal tissue architecture is a hallmark of oncogenic transformation1. In developing organisms, tissues architectures are sculpted by mechanical forces during morphogenesis2. However, the origins and consequences of tissue architecture during tumorigenesis remain elusive. In skin, premalignant basal cell carcinomas form ‘buds’, while invasive squamous cell carcinomas initiate as ‘folds’. Here

Most general anaesthetics and classical benzodiazepine drugs act through positive modulation of γ-aminobutyric acid type A (GABAA) receptors to dampen neuronal activity in the brain1,2,3,4,5. However, direct structural information on the mechanisms of general anaesthetics at their physiological receptor sites is lacking. Here we present cryo-electron microscopy structures of GABAA receptors bound to

Cosmological models in which dark matter consists of cold elementary particles predict that the dark halo population should extend to masses many orders of magnitude below those at which galaxies can form1,2,3. Here we report a cosmological simulation of the formation of present-day haloes over the full range of observed halo masses (20 orders of magnitude) when dark matter is assumed to be in the

El Niño and La Niña, collectively referred to as the El Niño–Southern Oscillation (ENSO), are not only highly consequential1,2,3,4,5,6 but also strongly nonlinear7,8,9,10,11,12,13,14. For example, the maximum warm anomalies of El Niño, which occur in the equatorial eastern Pacific Ocean, are larger than the maximum cold anomalies of La Niña, which are centred in the equatorial central Pacific Ocean7

Chromosomal instability in cancer consists of dynamic changes to the number and structure of chromosomes1,2. The resulting diversity in somatic copy number alterations (SCNAs) may provide the variation necessary for tumour evolution1,3,4. Here we use multi-sample phasing and SCNA analysis of 1,421 samples from 394 tumours across 22 tumour types to show that continuous chromosomal instability results

Scanning probe techniques can leverage atomically precise forces to sculpt matter at surfaces, atom by atom. These forces have been applied quasi-statically to create surface structures1,2,3,4,5,6,7 and influence chemical processes8,9, but exploiting local dynamics10,11,12,13,14 to realize coherent control on the atomic scale remains an intriguing prospect. Chemical reactions15,16,17, conformational