One week after fertilization, human embryos implant into the uterus. This event requires that the embryo forms a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model, which we termed blastoid1. Here we show that naive human pluripotent stem cells (PXGL hPSCs)2 triply inhibited for the Hippo, TGF-β, and ERK pathways efficiently (>70%)

Understanding the structure and dynamic process of water at the solid–liquid interface is an extremely important topic in surface science, energy science and catalysis1,2,3. As model catalysts, atomically flat single-crystal electrodes exhibit well-defined surface and electric field properties, and therefore may be used to elucidate the relationship between structure and electrocatalytic activity at

Nonlinear wave–matter interactions may give rise to solitons, phenomena that feature inherent stability in wave propagation and unusual spectral characteristics. Solitons have been created in a variety of physical systems and have had important roles in a broad range of applications, including communications, spectroscopy and metrology1,2,3,4. In recent years, the realization of dissipative Kerr optical

Armoured dinosaurs are well known for their evolution of specialized tail weapons—paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs1. Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria2,3,4. Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1,2,3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the

The practice of mathematics involves discovering patterns and using these to formulate and prove conjectures, resulting in theorems. Since the 1960s, mathematicians have used computers to assist in the discovery of patterns and formulation of conjectures1, most famously in the Birch and Swinnerton-Dyer conjecture2, a Millennium Prize Problem3. Here we provide examples of new fundamental results in

The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems1,2. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule that is a variant of cyclic ADP-ribose3,4. This molecule is hypothesized to mediate plant cell death through a pathway that has yet to be resolved5. TIR domains have also been shown

Pro-inflammatory T cells in the central nervous system (CNS) are causally associated with multiple demyelinating and neurodegenerative diseases1,2,3,4,5,6, but the pathways that control these responses remain unclear. Here we define a population of inflammatory group 3 innate lymphoid cells (ILC3s) that infiltrate the CNS in a mouse model of multiple sclerosis. These ILC3s are derived from the circulation

Local circuit architecture facilitates the emergence of feature selectivity in the cerebral cortex1. In the hippocampus, it remains unknown whether local computations supported by specific connectivity motifs2 regulate the spatial receptive fields of pyramidal cells3. Here we developed an in vivo electroporation method for monosynaptic retrograde tracing4 and optogenetics manipulation at single-cell

Although the role of Earth’s orbital variations in driving global climate cycles has long been recognized, their effect on evolution is hitherto unknown. The fossil remains of coccolithophores, a key calcifying phytoplankton group, enable a detailed assessment of the effect of cyclic orbital-scale climate changes on evolution because of their abundance in marine sediments and the preservation of their

Translation of the genetic code into proteins is realized through repetitions of synchronous translocation of messenger RNA (mRNA) and transfer RNAs (tRNA) through the ribosome. In eukaryotes translocation is ensured by elongation factor 2 (eEF2), which catalyses the process and actively contributes to its accuracy1. Although numerous studies point to critical roles for both the conserved eukaryotic

Mass selection into groups of like-minded individuals may be fragmenting and polarizing online society, particularly with respect to partisan differences1,2,3,4. However, our ability to measure the social makeup of online communities and in turn, to understand the social organization of online platforms, is limited by the pseudonymous, unstructured and large-scale nature of digital discussion. Here

In quantum fluids, the quantization of circulation forbids the diffusion of a vortex swirling flow seen in classical viscous fluids. Yet, accelerating quantum vortices may lose their energy into acoustic radiations1,2, similar to the way electric charges decelerate on emitting photons. The dissipation of vortex energy underlies central problems in quantum hydrodynamics3, such as the decay of quantum

Centromeric integrity is key for proper chromosome segregation during cell division1. Centromeres have unique chromatin features that are essential for centromere maintenance2. Although they are intrinsically fragile and represent hotspots for chromosomal rearrangements3, little is known about how centromere integrity in response to DNA damage is preserved. DNA repair by homologous recombination requires

Confocal microscopy1 remains a major workhorse in biomedical optical microscopy owing to its reliability and flexibility in imaging various samples, but suffers from substantial point spread function anisotropy, diffraction-limited resolution, depth-dependent degradation in scattering samples and volumetric bleaching2. Here we address these problems, enhancing confocal microscopy performance from the

During the current SARS-CoV-2 pandemic, a variety of mutations have accumulated in the viral genome, and currently, four variants of concern (VOCs) are considered potentially hazardous to human society1. The recently emerged B.1.617.2/Delta VOC is closely associated with the COVID-19 surge that occurred in India in the spring of 20212. However, its virological properties remain unclear. Here, we show

Heavy-fermion systems represent one of the paradigmatic strongly correlated states of matter1,2,3,4,5. They have been used as a platform for investigating exotic behaviour ranging from quantum criticality and non-Fermi liquid behaviour to unconventional topological superconductivity4,5,6,7,8,9,10,11,12. The heavy-fermion phenomenon arises from the exchange interaction between localized magnetic moments

Extrachromosomal DNA (ecDNA) is prevalent in human cancers and mediates high expression of oncogenes through gene amplification and altered gene regulation1. Gene induction typically involves cis-regulatory elements that contact and activate genes on the same chromosome2,3. Here we show that ecDNA hubs—clusters of around 10–100 ecDNAs within the nucleus—enable intermolecular enhancer–gene interactions

Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC)1. However, such oncogenic drivers are not found in 25–40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC2. Here we identify a novel fusion transcript of CLIP1 and

Amorphous materials inherit short- and medium-range order from the corresponding crystal and thus preserve some of its properties while still exhibiting novel properties1,2. Due to its important applications in technology, amorphous carbon with sp2 or mixed sp2–sp3 hybridization has been explored and prepared3,4, but synthesis of bulk amorphous carbon with sp3 concentration close to 100% remains a

Beginning in the summer of 2020, a variant of SARS-CoV-2, the cause of the COVID-19 pandemic, emerged in the United Kingdom. This B.1.1.7 variant, also known as Alpha, increased rapidly in prevalence, attributed to an increase in infection and/or transmission efficiency1. The Alpha variant has 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. We conducted a phase I open-label trial, recruiting

All life forms defend their genome against DNA invasion. Eukaryotic cells recognize incoming DNA and limit transcription through repressive chromatin modifications. The human silencing hub (HUSH) complex transcriptionally represses long interspersed element-1 retrotransposons (L1s) and retroviruses through histone H3 Lys9 trimethylation (H3K9me3)1–3. How HUSH recognizes and initiates silencing of these

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus

Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2,3,4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein–protein interaction networks to

The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1,2,3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole

Coronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported

Stress responses allow cells to adapt to changes in external conditions by activating specific pathways1. Here we investigate the dynamics of single cells that were subjected to acute stress that is too strong for a regulated response but not lethal. We show that when the growth of bacteria is arrested by acute transient exposure to strong inhibitors, the statistics of their regrowth dynamics can be

Propulsion is a critical subsystem of many spacecraft1,2,3,4. For efficient propellant usage, electric propulsion systems based on the electrostatic acceleration of ions formed during electron impact ionization of a gas are particularly attractive5,6. At present, xenon is used almost exclusively as an ionizable propellant for space propulsion2,3,4,5. However, xenon is rare, it must be stored under

The MRGPRX family of receptors (MRGPRX1–4) is a family of mas-related G-protein-coupled receptors that have evolved relatively recently1. Of these, MRGPRX2 and MRGPRX4 are key physiological and pathological mediators of itch and related mast cell-mediated hypersensitivity reactions2,3,4,5. MRGPRX2 couples to both Gi and Gq in mast cells6. Here we describe agonist-stabilized structures of MRGPRX2 coupled

A central question in chordate evolution is the origin of sessility in adult ascidians, and whether the appendicularian complete free-living style represents a primitive or derived condition among tunicates1. According to the ‘a new heart for a new head’ hypothesis, the evolution of the cardiopharyngeal gene regulatory network appears as a pivotal aspect to understand the evolution of the lifestyles

Californium (Cf) is currently the heaviest element accessible above microgram quantities. Cf isotopes impose severe experimental challenges due to their scarcity and radiological hazards. Consequently, chemical secrets ranging from the accessibility of 5f/6d valence orbitals to engage in bonding, the role of spin–orbit coupling in electronic structure, and reactivity patterns compared to other f elements

Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from their reduced dimensionality1,2,3,4,5. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are

In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals1,2. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions3,4,5,6. MRGPRX2 has been targeted by drug development

The systematic tuning of crystal lattice parameters to achieve improved kinematic compatibility between different phases is a broadly effective strategy for improving the reversibility, and lowering the hysteresis, of solid–solid phase transformations1,2,3,4,5,6,7,8,9,10,11. (Kinematic compatibility refers to the fitting together of the phases.) Here we present an apparently paradoxical example in

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1,2,3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased

Current models to explain how signals emanating from cutaneous mechanoreceptors generate representations of touch are based on comparisons of the tactile responses of mechanoreceptor subtypes and neurons in somatosensory cortex1,2,3,4,5,6,7,8. Here we used mouse genetic manipulations to investigate the contributions of peripheral mechanoreceptor subtypes to cortical responses to touch. Cortical neurons

Mental health is an important component of public health, especially in times of crisis. However, monitoring public mental health is difficult because data are often patchy and low-frequency1,2,3. Here we complement established approaches by using data from helplines, which offer a real-time measure of ‘revealed’ distress and mental health concerns across a range of topics4,5,6,7,8,9. We collected

Neurotropic alphaherpesviruses initiate infection in exposed mucosal tissues and, unlike most viruses, spread rapidly to sensory and autonomic nerves where life-long latency is established1. Recurrent infections arise sporadically from the peripheral nervous system throughout the life of the host, and invasion of the central nervous system may occur, with severe outcomes2. These viruses directly recruit

Thermalization is a ubiquitous process of statistical physics, in which a physical system reaches an equilibrium state that is defined by a few global properties such as temperature. Even in isolated quantum many-body systems, limited to reversible dynamics, thermalization typically prevails1. However, in these systems, there is another possibility: many-body localization (MBL) can result in preservation

Gastrulation is the fundamental process in all multicellular animals through which the basic body plan is first laid down1,2,3,4. It is pivotal in generating cellular diversity coordinated with spatial patterning. In humans, gastrulation occurs in the third week after fertilization. Our understanding of this process in humans is relatively limited and based primarily on historical specimens5,6,7,8

The breakdown of translational symmetry at heterointerfaces leads to the emergence of new phonon modes localized at the interface1. These modes have an essential role in thermal and electrical transport properties in devices, especially in miniature ones wherein the interface may dominate the entire response of the device2. Although related theoretical work began decades ago1,3,4,5, experimental research

Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-24–11, would expand

Inspired by living organisms, soft robots are developed from intrinsically compliant materials, enabling continuous motions that mimic animal and vegetal movement1. In soft robots, the canonical hinges and bolts are replaced by elastomers assembled into actuators programmed to change shape following the application of stimuli, for example pneumatic inflation2,3,4,5. The morphing information is typically

Climate changes across the past 24,000 years provide key insights into Earth system responses to external forcing. Climate model simulations1,2 and proxy data3,4,5,6,7,8 have independently allowed for study of this crucial interval; however, they have at times yielded disparate conclusions. Here, we leverage both types of information using paleoclimate data assimilation9,10 to produce the first proxy-constrained

Subduction is the major plate driving force, and the strength of the subducting plate controls many aspects of the thermochemical evolution of Earth. Each subducting plate experiences intense normal faulting1,2,3,4,5,6,7,8,9 during bending that accommodates the transition from horizontal to downwards motion at the outer rise at trenches. Here we investigate the consequences of this bending-induced

Inactive state-selective KRAS(G12C) inhibitors1,2,3,4,5,6,7,8 demonstrate a 30–40% response rate and result in approximately 6-month median progression-free survival in patients with lung cancer9. The genetic basis for resistance to these first-in-class mutant GTPase inhibitors remains under investigation. Here we evaluated matched pre-treatment and post-treatment specimens from 43 patients treated

The biophysical properties of neurons are the foundation for computation in the brain. Neuronal size is a key determinant of single neuron input–output features and varies substantially across species1,2,3. However, it is unknown whether different species adapt neuronal properties to conserve how single neurons process information4,5,6,7. Here we characterize layer 5 cortical pyramidal neurons across

Propane dehydrogenation (PDH) to propene is an important alternative to oil-based cracking processes, to produce this industrially important platform chemical1,2. The commercial PDH technologies utilizing Cr-containing (refs. 3,4) or Pt-containing (refs. 5,6,7,8) catalysts suffer from the toxicity of Cr(vi) compounds or the need to use ecologically harmful chlorine for catalyst regeneration9. Here

Human epidermal growth factor receptor 2 (HER2) and HER3 form a potent pro-oncogenic heterocomplex1,2,3 upon binding of growth factor neuregulin-1β (NRG1β). The mechanism by which HER2 and HER3 interact remains unknown in the absence of any structures of the complex. Here we isolated the NRG1β-bound near full-length HER2–HER3 dimer and, using cryo-electron microscopy, reconstructed the extracellulardomain

Fatty acid uptake and altered metabolism constitute hallmarks of metastasis1,2, yet evidence of the underlying biology, as well as whether all dietary fatty acids are prometastatic, is lacking. Here we show that dietary palmitic acid (PA), but not oleic acid or linoleic acid, promotes metastasis in oral carcinomas and melanoma in mice. Tumours from mice that were fed a short-term palm-oil-rich diet

Could learning that uses cognitive control to judiciously use relevant information while ignoring distractions generally improve brain function, beyond forming explicit memories? According to a neuroplasticity hypothesis for how some cognitive behavioural therapies are effective, cognitive control training (CCT) changes neural circuit information processing1,2,3. Here we investigated whether CCT persistently

The origin and early dispersal of speakers of Transeurasian languages—that is, Japanese, Korean, Tungusic, Mongolic and Turkic—is among the most disputed issues of Eurasian population history1,2,3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by ‘triangulating’ genetics, archaeology and linguistics

Zero hunger and good health could be realized by 2030 through effective conservation, characterization and utilization of germplasm resources1. So far, few chickpea (Cicer arietinum) germplasm accessions have been characterized at the genome sequence level2. Here we present a detailed map of variation in 3,171 cultivated and 195 wild accessions to provide publicly available resources for chickpea genomics

Quantized sound waves—phonons—govern the elastic response of crystalline materials, and also play an integral part in determining their thermodynamic properties and electrical response (for example, by binding electrons into superconducting Cooper pairs)1,2,3. The physics of lattice phonons and elasticity is absent in simulators of quantum solids constructed of neutral atoms in periodic light potentials:

Canonical CRISPR–Cas systems provide adaptive immunity against mobile genetic elements1. However, type I-F, I-B and V-K systems have been adopted by Tn7-like transposons to direct RNA-guided transposon insertion2,3,4,5,6,7. Type V-K CRISPR-associated transposons rely on the pseudonuclease Cas12k, the transposase TnsB, the AAA+ ATPase TnsC and the zinc-finger protein TniQ7, but the molecular mechanism

Pathogens use virulence factors to inhibit the immune system1. The guard hypothesis2,3 postulates that hosts monitor (or ‘guard’) critical innate immune pathways such that their disruption by virulence factors provokes a secondary immune response1. Here we describe a ‘self-guarded’ immune pathway in human monocytes, in which guarding and guarded functions are combined in one protein. We find that this

Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host–microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from

Aviation and shipping currently contribute approximately 8% of total anthropogenic CO2 emissions, with growth in tourism and global trade projected to increase this contribution further1–3. Carbon-neutral transportation is feasible with electric motors powered by rechargeable batteries, though challenging if not impossible for long-haul commercial travel, particularly air travel4. A promising solution

Amorphous–amorphous transformations under pressure are generally explained by changes in the local structure from low- to higher-fold coordinated polyhedra1,2,3,4. However, as the notion of scale invariance at the critical thresholds has not been addressed, it is still unclear whether these transformations behave similarly to true phase transitions in related crystals and liquids. Here we report ab