Nature

Description

Structure of the human sodium leak channel NALCN Function of the NALCN complex Structure determination of NALCN Structure of the NALCN–FAM155A complex FAM155A: an unusual auxiliary subunit NALCN pore structure and pharmacology NALCN selectivity filter The NALCN activation gate is closed Atypical voltage-sensor domains Insight into NALCN gating Mapping pathogenic mutations Discussion Online content Fig. 1 Overall structure and function of NALCN. Fig. 2 NALCN pore, pharmacology and CTD interactions. Fig. 3 NALCN voltage-sensor domains. Fig. 4 NALCN disease-associated mutations. Extended Data Fig. 1 NALCN function in heterologous expressions systems. Extended Data Fig. 2 NALCN biochemistry and cryo-electron microscopy processing. Extended Data Fig. 3 NALCN cryo-EM map. Extended Data Fig. 4 Comparison of NALCN with NaV and CaV channel structures. Extended Data Fig. 5 NALCN structure-based sequence alignment. Extended Data Fig. 6 Extracellular pore loops, FAM155A sequence alignment (partial), and auxiliary subunit comparisons. Extended Data Fig. 7 NALCN pore volume and selectivity filter comparisons. Extended Data Fig. 8 S6 sequence alignment and NALCN π-bulge. Extended Data Fig. 9 NALCN voltage-sensor domain comparisons and features. Extended Data Fig. 10 Characterization of select CLIFAHDD and IHPRF1 mutations. Extended Data Fig. 11 Conservation analysis and potential protein interaction sites. Extended Data Table 1 Cryo-EM data collection, refinement and validation statistics. s41586-020-2530-3.pdf Structural basis for RIFIN-mediated activation of LILRB1 in malaria Online content Fig. 1 The structure of the RIFIN–LILRB1 complex. Fig. 2 A conserved binding mode among sequence-diverse LILRB1-binding RIFINs. Fig. 3 Molecular mimicry of MHC class I by a LILRB1-binding RIFIN reduces the activation of NK cells. Extended Data Fig. 1 Biophysical characterization of the variable and constant regions of RIFIN, and the RIFIN–LILRB1 complex. Extended Data Fig. 2 Surface plasmon resonance analysis of RIFIN binding to LILRB1. Extended Data Fig. 3 Analysis of the effect of RIFIN on signalling in a T-cell-based GFP-reporter system. Extended Data Fig. 4 Analysis of the sequence variability of RIFIN. Extended Data Fig. 5 Analysis of the effect of point mutations on LILRB1-binding by RIFINs. Extended Data Fig. 6 Measurement of the quantities of LILRB1 on different plasma white blood cells after fluorescent sorting. Extended Data Fig. 7 Imaging of LILRB1 and perforin in an immunological synapse model of NK cells. Extended Data Fig. 8 Analysis of quantity and colocalization of RIFIN(C223S) and RIFIN(C223S/G234R), pMHC, LILRB1 and perforin at the immunological synapse of NK cells. Extended Data Table 1 Crystallographic analysis of the RIFIN–LILRB1 complex. Extended Data Table 2 Interactions between RIFIN and LILRB1. s41586-020-2815-6.pdf RAD51-dependent recruitment of TERRA lncRNA to telomeres through R-loops Shorter telomeres recruit more TERRA Recombination factors enable TERRA recruitment TERRA forms R-loops causing telomere fragility RAD51 promotes telomeric R-loop formation Discussion Online content Fig. 1 Transgenic TERRA associates with telomeres in a manner that depends on RAD51. Fig. 2 TERRA forms R-loops in trans, inducing telomere fragility in a RAD51-dependent way. Fig. 3 RAD51 associates with TERRA and catalyses R-loop formation. Extended Data Fig. 1 Co-localization of transgenic TERRA with telomeres. Extended Data Fig. 2 TERRA associates preferentially with short telomeres. Extended Data Fig. 3 Depletion of factors regulating TERRA trafficking. Extended Data Fig. 4 Depletion of RAD51 and BRCA2, which regulate the association of TERRA with telomeres. Extended Data Fig. 5 RNaseH1-regulated formation of telomeric R-loops in trans. Extended Data Fig. 6 Transgenic TERRA expressed from plasmids induces telomere fragility. Extended Data Fig. 7 RAD51 binds TERRA and promotes R-loop formation. Extended Data Fig. 8 RAD51 catalyses the formation of canonical R-loops. Extended Data Table 1 Oligonucleotides used herein. Extended Data Table 2 Antibodies used herein. s41586-020-2842-3.pdf Equilibrium between nascent and parental MCM proteins protects replicating genomes Defining nascent and parental MCMs MCM pools are functionally distinct MCMBP chaperones nascent MCMs Nascent MCMs delimit replisome dynamics Discussion Online content Fig. 1 Nascent MCMs continuously replenish parental MCMs in mother cells and form functionally distinct pre-RCs in daughter cells. Fig. 2 MCMBP safeguards inheritance of nascent MCMs in daughter cells. Fig. 3 MCMBP stabilizes and translocates nascent MCM3–7 to the nucleus. Fig. 4 Reduced contribution of nascent MCMs to pre-RCs accelerates replication forks and causes DNA damage. Extended Data Fig. 1 Development of tools and characterization of endogenous MCM proteins. Extended Data Fig. 2 Newly synthesized MCMs replenish the declining pool of parental MCMs. Extended Data Fig. 3 Nascent and parental MCMs are equally proficient in pre-RC formation. Extended Data Fig. 4 The inherited pools of nascent and parental MCMs display distinct unloading patterns during S phase. Extended Data Fig. 5 MCMBP associates with the CMG-independent pool of MCMs. Extended Data Fig. 6 MCMBP fosters nuclear accumulation of nascent but not parental MCMs. Extended Data Fig. 7 MCMBP possesses an autonomous NLS motif that fosters nuclear import of MCM3–7. Extended Data Fig. 8 Excess nascent MCM2 in daughter MCMBP-knockout cells does not engage in pre-RC formation in the absence of complementary MCM subunits. Extended Data Fig. 9 Reduced pre-RCs accelerate forks and trigger DNA damage without major alterations of CMG activity. Extended Data Fig. 10 Enforced deceleration of fast forks in MCMBP-deficient cells mitigates replication stress. s41586-020-2843-2.pdf DNA mismatches reveal conformational penalties in protein–DNA recognition SaMBA Mismatches enhance the binding of TFs to DNA Mismatches versus Watson–Crick mutations Mismatches prepay distortion penalty Native and non-native interactions Summary Online content Fig. 1 SaMBA measures the effects of mismatches on protein–DNA binding in high throughput. Fig. 2 The effects of DNA mismatches on TF binding. Fig. 3 DNA mismatches that exhibit geometries similar to distorted base pairs in TF-bound DNA lead to increased binding affinity. Extended Data Fig. 1 Structural deformations in TF-bound and unbound DNA. Extended Data Fig. 2 Structural characteristics of DNA mismatches. Extended Data Fig. 3 Validation and calibration of SaMBA measurements. Extended Data Fig. 4 Comparing the effects of mutations versus mismatches on TF binding. Extended Data Fig. 5 The effects of mismatches on ETS1–DNA binding. Extended Data Fig. 6 The effects of mismatches on p53–DNA binding. Extended Data Fig. 7 The effects of mismatches on TBP–DNA binding. Extended Data Fig. 8 Potential mechanisms for mismatch-enhanced TF binding. Extended Data Fig. 9 DNA mismatches in the cell. Extended Data Table 1 Data collection and refinement statistics for TBP–DNA mismatch structures. s41586-020-2672-3.pdf Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly Cytoplasm is excluded during nuclear assembly Chromosomes cluster during mitotic exit Ki-67 regulates chromosome clustering Chromosome clustering removes cytoplasm Conclusions Online content Fig. 1 Cytoplasmic macromolecules are displaced from the nucleus before the assembly of a transport-competent nuclear envelope. Fig. 2 Displacement of cytoplasm by spindle-independent chromosome clustering. Fig. 3 Ki-67 regulates chromosome clustering. Fig. 4 Ki-67-regulated chromosome clustering removes cytoplasm from the reassembling nucleus. Extended Data Fig. 1 Characterization of GEM- and L10-expressing stable cell lines. Extended Data Fig. 2 Ribosomes are excluded from the nucleus in the absence of nuclear envelope transport. Extended Data Fig. 3 Chromosomes cluster and the nucleus reassembles in spindle-less cells after the induction of mitotic exit by different experimental procedures. Extended Data Fig. 4 Chromosome clustering is independent of F-actin, precedes enwrapment by the nuclear envelope and suppresses chromosome mobility. Extended Data Fig. 5 Chromosomes cluster in the presence of a mitotic spindle after flavopiridol-mediated induction of mitotic exit. Extended Data Fig. 6 Chromosome clustering is not mediated by association with BAF or removal of Ki-67. Extended Data Fig. 7 Ki-67 is required for chromosome clustering in Ki-67-knockout cells after histone overexpression or histone hyperacetylation. Extended Data Fig. 8 Ki-67 does not mediate chromosome clustering through PP1 recruitment or through H3(S10) dephosphorylation. Extended Data Fig. 9 Chromosome clustering can be artificially induced through increased adhesion between chromosomes. Extended Data Fig. 10 Clustering-deficient cells assemble a transport-competent nuclear envelope. s41586-020-2835-2.pdf Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA Online content Fig. 1 Screen to identify SpCas9 gRNAs that unsilence paternal Ube3a. Fig. 2 AAV delivery of SaCas9 and Sajw33 unsilences paternal Ube3a throughout the nervous system. Fig. 3 The SaCas9 gene therapy vector rescues phenotypes in the AS mouse model. Fig. 4 AAV integration traps Ube3a-ATS. Extended Data Fig. 1 Genomic map of Spjw33 targets and functional outcomes on Ube3a and Snord115 locus. Extended Data Fig. 2 Targeting SNORD115 unsilences paternal UBE3A in human neurons. Extended Data Fig. 3 SaCas9 vector development and testing. Extended Data Fig. 4 AAV delivery of SaCas9 and Sajw33 unsilences paternal Ube3a with no detectable AAV mediated toxicity. Extended Data Fig. 5 Expression and alternative splicing of Snord115 target genes are not affected in the brain. Extended Data Fig. 6 Single injection of AAV containing SaCas9 and Sajw33 at P1 enduringly unsilences paternal UBE3A in 17-month-old mice. Extended Data Fig. 7 Evaluation of viral transduction in tissues from injected mice and their dams. Extended Data Fig. 8 Additional behavioural assays. Extended Data Fig. 9 Analysis of mutations and AAV integration in 10-month-old mice. Extended Data Fig. 10 AAV integration disrupts Ube3a-ATS via distinct mechanisms. s41586-020-2796-5.pdf Integration of innate immune signalling by caspase-8 cleavage of N4BP1 N4BP1 as a caspase-8 cleavage substrate N4BP1 suppresses select cytokine responses Role of N4BP1 in vivo Insights into N4BP1-mediated cytokine suppression TNF licensing of TRIF-independent TLR responses Discussion Online content Fig. 1 TLR3 and TLR4 induce caspase-8-dependent cleavage of N4BP1. Fig. 2 N4BP1 suppresses cytokine responses by TRIF-independent TLRs. Fig. 3 N4bp1−/− mice develop mild inflammation and have exacerbated TLR-dependent inflammatory responses. Fig. 4 TNF-induced cleavage of N4BP1 licenses cytokine responses by TRIF-independent TLRs. Extended Data Fig. 1 Caspase-8-dependent cleavage of N4BP1. Extended Data Fig. 2 N4BP1 regulates cytokine responses and is inhibited by caspase-8. Extended Data Fig. 3 Characterization of N4bp1−/− mice. Extended Data Fig. 4 Age-dependent immune dysregulation in N4bp1−/− mice. Extended Data Fig. 5 Absence of CD3+B220+ cell population among N4bp1−/− mice, and imiquimod-induced psoriasis model. Extended Data Fig. 6 Signal transduction and RNA sequencing of N4bp1+/+ and N4bp1−/− BMDMs. Extended Data Fig. 7 Role of N4BP1 in LPS-induced transcriptional program of Mlkl−/−Casp8−/− BMDMs. Extended Data Fig. 8 TNF licenses cytokine responses by TRIF-independent TLRs and N4bp1D488A/D488A mice. Extended Data Fig. 9 Resistance of N4BP1(D488A) protein to TLR3-, TLR4-, TNF- and FASL-induced cleavage and TNF licensing in Mlkl−/− Casp8−/− BMDMs. Extended Data Fig. 10 FAS licenses cytokine responses by TRIF-independent TLRs. s41586-020-2598-9.pdf SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 Identification of S-reactive CD4+ T cells S-reactive T cells in RHDs are cross-reactive to hCoVs Activation signatures in patients with COVID-19 Discussion Online content Fig. 1 Structural domains, homology and MHC-II epitopes of the SARS-CoV-2 S protein. Fig. 2 SARS-CoV-2 S-reactive CD4+ T cells in patients with COVID-19 and HDs. Fig. 3 CD38, HLA-DR and Ki-67 expression in SARS-CoV-2 S-I-reactive and S-II-reactive CD4+ T cells discriminates patients with COVID-19 from RHDs. Extended Data Fig. 1 Homology of reported MHC-II epitopes in the spike glycoprotein of SARS-CoV compared with SARS-CoV-2 and endemic hCoV strains. Extended Data Fig. 2 Exemplary analyses gates and dot plots from patients with COVID-19, RHDs and HDs. Extended Data Fig. 3 Most S-I-non-reactive and S-II-non-reactive patients with COVID-19 had a critical disease stage. Extended Data Fig. 4 Repeated serology of HDs confirms unexposed status of HDs and RHDs. Extended Data Fig. 5 Expression of cytokines and differentiation markers in S-I-reactive and S-II-reactive CD40L+4-1BB+CD4+ T cells from patients with COVID-19 and RHDs. Extended Data Fig. 6 hCoV-specific IgG antibody titres in HDs and RHDs and specificity of SARS-CoV-2-reactive T cells in HDs. Table 1 Baseline characteristics of all donors. Extended Data Table 1 Reported MHC-II epitopes in the spike glycoprotein of SARS-CoV. Extended Data Table 2 Baseline characteristics of hospitalized patients with COVID-19. Extended Data Table 3 Baseline characteristics of healthy donors. Extended Data Table 4 Baseline characteristics of seven additional patients with COVID-19. s41586-020-2758-y.pdf Hippocampal CA2 sharp-wave ripples reactivate and promote social memory CA2 cells remap to a social stimulus Dorsal CA2 is needed for social memory Social memory requires CA2 SWRs CA2 SWRs replay social memory Triggered CA2 SWRs extend social memory Discussion Online content Fig. 1 Encoding of conspecifics by activity of CA2 pyramidal cells. Fig. 2 Effect of SWR disruption on social-memory consolidation. Fig. 3 Reactivation during sleep of cell ensembles that were active during prior social learning. Fig. 4 Effect of optogenetic generation of ripples on social-memory recall. Extended Data Fig. 1 Behavioural features during a social-memory task. Extended Data Fig. 2 Multiregion electrophysiological recordings. Extended Data Fig. 3 Classification of single-cell responses during a social-memory task. Extended Data Fig. 4 Classification of single-cell responses during a social-memory task. Extended Data Fig. 5 Place-cell properties of social-invariant and social-remapping cells across regions during the social-discrimination task. Extended Data Fig. 6 Object-recognition task: single-cell responses, optogenetic manipulations and reactivation properties per region. Extended Data Fig. 7 Effect of optogenetic disruption of SWRs on firing rates and field potentials, and reactivation of hippocampal cells during SWRs. Extended Data Fig. 8 Reactivation of hippocampal cells during SWRs following social learning. Extended Data Fig. 9 Strength of assembly activity during the social-memory discrimination task. Extended Data Fig. 10 Generation of CA2 ripple oscillations enhances social-memory recall. s41586-020-2860-1.pdf Parallel ascending spinal pathways for affective touch and pain Genetically defined spinal PN subsets Zonal segregation of SPB axon terminals A mechanosensory limb of the SPB pathway SPB neuronal subsets and hedonic value Discussion Online content Fig. 1 Spinal PNs that express Tacr1 and Gpr83 are largely distinct neuronal populations that innervate multiple distinct but overlapping brain regions. Fig. 2 Axons of SPB neurons that express Tacr1 and Gpr83 terminate in a zonally segregated manner within the PBNL and their strong activation produces distinct escape behaviours and autonomic responses. Fig. 3 SPB neurons that express Tacr1 and Gpr83 exhibit different responses to cutaneous stimuli, which is explained by their distinct synaptic inputs from different subtypes of primary sensory neurons. Fig. 4 SPB neurons that express Tacr1 and Gpr83 form dedicated, bilateral, non-somatotopically organized synaptic inputs to the PBNL. Fig. 5 Activation of SPB neurons that express Tacr1 and Gpr83 induces distinct affective behaviours in a manner that depends on stimulus intensity. Extended Data Fig. 1 Generation of CreERT2 mouse lines for genetic labelling of anterolateral pathway neurons and Flp mouse lines for labelling of primary sensory neurons. Extended Data Fig. 2 Comparative analysis of the Gpr83+, Tacr1+ and Tac1+ SPB populations. Extended Data Fig. 3 Tacr1+ and Gpr83+ spinal PNs that innervate the posterior thalamus, midbrain or pons are distinct populations. Extended Data Fig. 4 Strong axon terminal stimulation of Tacr1+ and Gpr83+ SPB neurons produces distinct locomotor behaviours. Extended Data Fig. 5 Physiological response properties of Tacr1+ and Gpr83+ SPB neurons. Extended Data Fig. 6 Simultaneous inhibition of the synaptic outputs of both Tacr1+ and Gpr83+ SPB neurons attenuates nocifensive behaviours in response to noxious cutaneous stimuli. Extended Data Fig. 7 Gpr83+ and Tacr1+ SPB neurons receive strong synaptic inputs from Mrgprd+ polymodal non-peptidergic sensory neurons and weak, sparse, and polysynaptic inputs from distinct primary sensory neurons, and exhibit distinct dendritic morph Extended Data Fig. 8 Anatomical analyses of axonal projections of anterolateral pathway PNs innervating the PBNL and the inferior olivary complex. Extended Data Fig. 9 Photostimulation of either Tacr1+ or Gpr83+ SPB neuron axon terminals promotes rostral grooming, and produces distinct behaviours in instrumental conditioning assays. Extended Data Fig. 10 Summary of two parallel ascending SPB pathways and a phylogenetic tree of structurally-related GPCR family proteins. s41586-020-2873-9.pdf Dense sampling of bird diversity increases power of comparative genomics Online content Fig. 1 Newly sequenced genomes densely cover the bird tree of life. Fig. 2 Improved orthologue distinction and detection of lineage-specific sequences. Fig. 3 Denser phylogenomic sequencing increases the power to detect selective constraints. Extended Data Fig. 1 Sampling and processing of the 363 genomes. Extended Data Fig. 2 Distribution of transposable elements. Extended Data Fig. 3 Patterns of the presence and absence of 5 visual opsins in 363 bird species. Extended Data Fig. 4 GC content and codon use. Extended Data Fig. 5 Overview of the pipelines for identifying genomic regions. Extended Data Fig. 6 Gene tree for copies of the growth hormone gene GH. Extended Data Fig. 7 Identification of lineage-specific sequences. Extended Data Fig. 8 The evolution of songbirds was associated with the loss of the cornulin gene. Extended Data Fig. 9 Acceleration and conservation scores. Extended Data Fig. 10 Distribution of acceleration and conservation scores. s41586-020-2871-y.pdf Progressive Cactus is a multiple-genome aligner for the thousand-genome era Progressive Cactus Evaluation on simulated data Effect of the guide tree Effect of assembly quality on alignment 600-way amniote alignment Discussion Online content Fig. 1 The alignment process within Progressive Cactus. Fig. 2 Comparing alignments of varying numbers of simulated genomes using Progressive Cactus. Fig. 3 Analysing the 600-way amniote alignment. Fig. 4 Comparing Cactus and MULTIZ alignment coverage. Extended Data Fig. 1 Results from improved paralogue filtering. Extended Data Fig. 2 Methods of adding a genome to a Progressive Cactus alignment. Extended Data Fig. 3 Analysing insertions, deletions and L1PA6 repeats in the 600-way alignment. Table 1 Aggregate statistics for the 600-way alignment. Extended Data Table 1 Adding a new genome to an alignment of simulated genomes. Extended Data Table 2 Alignment similarity between four alignments of the same 48 avian genomes with different guide trees. s41586-020-2816-5.pdf Dense and pleiotropic regulatory information in a developmental enhancer Mutational scanning of the E3N enhancer Most mutations alter gene expression Mutational scanning maps binding sites Mutations drive pleiotropic expression E3N architecture may constrain evolution Discussion Online content Fig. 1 Most nucleotide mutations in E3N alter gene expression. Fig. 2 Mutational scanning identifies a Hth binding site associated with a changed evolutionary phenotype. Fig. 3 Ubx mutations often simultaneously change levels, timing, and locations of E3N expression. Fig. 4 E3N enhancer architecture may constrain evolution. Extended Data Fig. 1 Distribution of mutations in the E3N enhancer library. Extended Data Fig. 2 An automated platform for fixing, staining, and imaging Drosophila embryos. Extended Data Fig. 3 Methods of image and data analysis. Extended Data Fig. 4 Single base pair mutations and E3N conservation. Extended Data Fig. 5 Testing additional Hth-Exd motifs in E3N. Extended Data Fig. 6 The effects of Ubx affinity on morphology. Extended Data Fig. 7 Extensive pleiotropic effects across the E3N enhancer. Extended Data Fig. 8 Cuticle preps from 60 Drosophila species across approximately 100 million years of evolution. s41586-020-2867-7.pdf Slower decay of landfalling hurricanes in a warming world Decay timescale τ τ and sea surface temperature Additional factors Concluding remarks Online content Fig. 1 Effect of SST on the decay of North Atlantic landfalling hurricanes. Fig. 2 Effect of SST on the decay of simulated landfalling hurricanes. Fig. 3 Effect of hurricane motion on the decay of North Atlantic landfalling hurricanes. Extended Data Fig. 1 Analysis of North Atlantic landfalling hurricanes. Extended Data Fig. 2 Analysis of North Atlantic landfalling hurricanes. Extended Data Fig. 3 Effect of various factors on τ. Extended Data Fig. 4 Computational simulations. Extended Data Fig. 5 Sensitivity tests with axisymmetric simulations. Extended Data Fig. 6 Hurricane size and SST. Extended Data Fig. 7 A simple model of a landfalling hurricane. Extended Data Table 1 Parameters for computational simulations. Extended Data Table 2 Statistical significance of the relationship between two variables. Extended Data Table 3 Smoothing and robustness of results. s41586-020-2869-5.pdf  Anatomy of cage formation in a two-dimensional glass-forming liquid Online content Fig. 1 The experimental system and responses to local perturbations. Fig. 2 Excitation properties are non-monotonic in packing density. Fig. 3 Particle displacements for different packing fractions. Extended Data Fig. 1 Details of laser-beam setup. Extended Data Fig. 2 Static and dynamic properties of the quiescent system. Extended Data Fig. 3 Influence of laser-pulse duration on excitation pattern. Extended Data Fig. 4 The non-monotonic response of the system is independent of the laser intensity. Extended Data Fig. 5 Excitation patterns for different laser intensities. s41586-020-2892-6.pdf Ultra-sensitive and resilient compliant strain gauges for soft machines Online content Fig. 1 SCARS sensor overview. Fig. 2 Demonstration of sensor sensitivity and robustness. Fig. 3 The effect of off-axis loading and design parameters on sensor performance. Fig. 4 Demonstration of a textile-based sensor-integrated sleeve for hand motion detection. Extended Data Fig. 1 CFPC fabrication and characterization. Extended Data Fig. 2 Sensor fabrication and resistance measurement. Extended Data Fig. 3 Sensor resilience to adverse conditions, off-axis deformations, strain rate and textile coupling. Extended Data Fig. 4 Experimental setup for initial curvature and twist characterizations. Extended Data Fig. 5 Sensor analytical model. Extended Data Fig. 6 Sensor sleeve design and testing. Extended Data Fig. 7 Taxonomy of compliant, resistive sensing mechanisms. Extended Data Table 1 Motion capture trial protocol. Extended Data Table 2 Selected hand motion tracking and classification model architectures. Extended Data Table 3 Comparison table of compliant strain sensor mechanisms. s41586-020-2868-6.pdf Correlated insulating states at fractional fillings of moiré superlattices Dielectric sensing with excitons Correlated insulating states Energy ordering and critical temperature Quantum effects Online content Fig. 1 Optical sensing of charge gaps using a van der Waals heterostructure platform. Fig. 2 An abundance of insulating states and their energy ordering in a WSe2/WS2 moiré heterostructure. Fig. 3 Temperature dependence of the correlated insulating states. Extended Data Fig. 1 Additional doping-dependence data and analysis for the control device. Extended Data Fig. 2 Assignment of the filling factor of the insulating states. Extended Data Fig. 3 Results from different regions of the device. Extended Data Fig. 4 Results from a different device. Extended Data Fig. 5 Analysis of the −1/3 and −2/3 states. Extended Data Fig. 6 First derivative of data shown in Fig. Extended Data Fig. 7 Optical response of the WSe2/WS2 moiré superlattice. Extended Data Fig. 8 Contour plots of additional gate-dependent reflection contrast spectrum at higher temperatures. Extended Data Fig. 9 Transition temperature to the charge-ordered state (simulation). Extended Data Table 1 Comparison between model and experiment for the transition temperature of the charge-ordered states at fillings ν = 1/7, 1/4, 1/3, 2/5 and 1/2. s41586-020-2878-4.pdf The baryon density of the Universe from an improved rate of deuterium burning Online content Fig. 1 The S factor of the D(p,γ)3He reaction. Fig. 2 Likelihood distribution of the baryon density and baryon-to-photon ratio. Fig. 3 Likelihood contours (at 68%, 95% and 99% confidence levels) on the Neff versus Ωbh2 plane. Extended Data Fig. 1 Typical γ-ray spectrum obtained underground with the high-purity germanium detector at proton beam energy Ep = 50 keV. Extended Data Fig. 2 Typical γ-ray spectrum taken at proton beam energy Ep = 395 keV. Extended Data Fig. 3 Sensitivity of the primordial deuterium abundance to the D(p,γ)3He reaction cross-section as a function of centre-of-mass energy. Table 1 Mean values and 68% confidence level ranges for Ωbh2 (with relative uncertainties δ) and Neff. Extended Data Table 1 Astrophysical S factors for the D(p,γ)3He reaction at the measured centre-of-mass energies. Extended Data Table 2 Thermonuclear reaction rate for the D(p,γ)3He reaction. s41586-020-2846-z.pdf Bennu’s near-Earth lifetime of 1.75 million years inferred from craters on its boulders Online content Fig. 1 Craters are observed on Bennu’s boulders in images and laser altimetry data. Fig. 2 The maximum crater size on a boulder depends on boulder strength. Fig. 3 Bennu’s boulders are relatively weak and have short lifetimes in the main asteroid belt. Fig. 4 The surface exposure age of Bennu’s metre-size boulders is ~1. Extended Data Fig. 1 Examples of boulders with craters and OLA profiles of the craters. Extended Data Table 1 Summary of OLA crater profile measurements for a subset of boulders with crater size close to the maximum allowable before disruption. Extended Data Table 2 Locations of boulders with flat faces that exhibit multiple impact craters on their surface. s41586-020-2876-6.pdf A comparative genomics multitool for scientific discovery and conservation Designing a comparative-genomics multitool Comparative power of 240 species Biological insights from additional assemblies Speciation Protection from cancer Convergent evolution of venom Informing biodiversity conservation strategies Rapid assessment of species infection risk Genetic diversity and extinction risk Resources for biodiversity conservation Whole-genome alignment Next steps Conclusion Online content Fig. 1 The Zoonomia Project brings the fraction of eutherian families that are represented by at least one assembly to 83%. Fig. 2 Genetic diversity varies across IUCN conservation categories. Fig. 3 The Zoonomia alignment doubles the fraction of the human genome predicted to be under purifying selection at single-base-pair resolution. Extended Data Fig. 1 Notable traits in non-human mammals. Extended Data Fig. 2 Sample collection can be challenging, and sequencing methods must be selected to handle the sample quality. Extended Data Table 1 The Zoonomia Project data includes 132 genome assemblies. Extended Data Table 2 Power to detect constraint across datasets. Extended Data Table 3 Diversity statistics are not correlated with other species-level phenotypes.