Nature - The International Journal of Science / 8 February 2024

233 Open science — embrace it before it’s too late
234 Cyberattacks on knowledge institutions are increasing- what can be done?
235 Why the mental cost of a STEM career can be too high for women and people of colour
237 Research Highlights
239 Trump’s presidential push renews fears for US science
240 Black-hole observations solve cosmic-ray mystery
241 Signs of ‘transmissible’ Alzheimer’s seen in people who received growth hormone
242 Leading US particle-physics lab faces uncertain future
244 First aircraft to fly on Mars dies — but leaves a legacy of science
245 CRISPR-edited crops break new ground in Africa
246 Obesity drugs have another superpower- taming inflammation
248 The new car batteries that could power the electric vehicle revolution
252 Santorini’s volcanic past- underwater clues reveal giant prehistoric eruption
254 It’s time to admit that genes are not the blueprint for life
256 Science and government- can the power struggle ever end?
258 No ‘easy’ weight loss- don’t overlook the social cost of anti-obesity drugs
261 Correspondence
263 Mimas’s surprise ocean prompts an update of the rule book for moons
264 Stone tools in northern Europe made by Homo sapiens 45,000 years ago
266 Resting restores performance of discharged lithium-metal batteries
267 The journey to understand previously unknown microbial genes
269 Natural inhibitor found for cell death by ferroptosis
271 A break in mitochondrial endosymbiosis as a basis for inflammatory diseases
Implications of endosymbiotic origin
Remnants of the endosymbiotic origin of mitochondria
Mitochondrial signals to the cytosol
Inheritance or exaptation?
Sterile and non-sterile inflammation overlap
Endosymbiosis and autoimmunity
Emerging aspects
Outlook
Acknowledgements
Fig. 1 Pathways of molecular signal release from mitochondria.
Fig. 2 How breakdown in endosymbiosis can lead to inflammation.
Fig. 3 Did nucleic acid-sensing PRRs evolve to sense mitochondrial nucleic acids? mtDNA has been shown to be sensed by the PRRs cGAS and TLR9 while mitochondrial dsRNA can be sensed by the PRRs MDA-5 and RIG-1.
280 A recently formed ocean inside Saturn’s moon Mimas
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Fig. 1 Mimas measurements and ocean models.
Fig. 2 Mimas’s interior and orbital evolution.
Extended Data Fig. 1 Reprocessing of Mimas astrometry.
Extended Data Fig. 2 Core radius for solid model.
Extended Data Fig. 3 Sensitivity of shape parameters.
Extended Data Table 1 Estimation of Mimas gravity field.
283 Ultracold field-linked tetratomic molecules
Field-linked tetramers
Binding energy and lifetime
Association and dissociation processes
Imaging of the dissociated tetramers
Discussion
Conclusion
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Fig. 1 Electroassociation of field-linked tetramers.
Fig. 2 Tetramer binding energy and lifetime.
Fig. 3 Association and dissociation processes.
Fig. 4 Momentum distributions of the dissociated tetramers.
Extended Data Fig. 1 Dimer loss near the FL resonance.
Extended Data Fig. 2 Conditions for efficient electroassociation.
Extended Data Fig. 3 Tetramer lifetime in trap and in time-of-flight.
Extended Data Fig. 4 Hyperfine transitions of NaK molecules in the modulation spectra.
Extended Data Fig. 5 Tetramer dissociation patterns and their angular distribution.
Extended Data Fig. 6 Theoretical tetramer decay rate.
288Observation and quantification of the pseudogap in unitary Fermi gases
Observation and quantification of the pseudogap in unitary Fermi gases
Experimental scheme and set-up
Fermion spectral function
Fermion self-energy and EDCs
Summary
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Fig. 1 Experimental scheme.
Fig. 2 Microwave spectra at 0.
Fig. 3 Momentum-resolved microwave spectra at various temperatures across the superfluid transition.
Fig. 4 Temperature dependence of Δ, Γ and the EDCs.
Extended Data Fig. 1 Pair momentum distributions in the vicinity of the superfluid phase transition.
Extended Data Fig. 2 Schematic diagram for the magnetic field stabilization.
Extended Data Fig. 3 The residual 50 Hz noise and Rabi oscillations between the |3⟩ and |4⟩ hyperfine levels.
Extended Data Fig. 4 Density distribution after ballistic expansion and n(k, Δω) of the unitary Fermi gas at 0.
Extended Data Fig. 5 The contour plots of A(k, ω).
Extended Data Fig. 6 Analysis of the energy dispersion.
Extended Data Fig. 7 The evolution of EDC as a function of k for various T.
Extended Data Fig. 8 Temperature dependence of Δ, and Uh.
Extended Data Table 1 Temperature dependence of Δ, m*, and U.
294Evidence of superconducting Fermi arcs
Evidence of superconducting Fermi arcs
Three-dimensional band structure
Surface states on two terminations
Robust Fermi arcs from laser-ARPES
Superconductivity at the surface
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Fig. 1 3D band structure of PtBi2.
Fig. 2 Fermi arcs.
Fig. 3 Laser-ARPES.
Fig. 4 Superconducting arcs.
Extended Data Fig. 1 Fermi surface maps.
Extended Data Fig. 2 Photon energy dependence of the Fermi arcs.
Extended Data Fig. 3 3D band structure.
Extended Data Fig. 4 EDC across the Fermi arc.
Extended Data Fig. 5 Theoretical calculations of gap opening in PtBi2.
Extended Data Fig. 6 Polarization dependent datasets.
300 Stable blue phosphorescent organic LEDs that use polariton-enhanced Purcell effects
PEP and SPP dispersion engineering
Purcell effect and energy transfer rates
PHOLED performance
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Fig. 1 The PEP-enhanced Purcell effect.
Fig. 2 Polariton dispersion engineering.
Fig. 3 Optical engineering of blue PHOLEDs.
Fig. 4 Ir(dmp)3 device performance.
Fig. 5 Ir(dmp)3 device performance summary.
Extended Data Fig. 1 Molecular structural formulae of organic materials used in the EML, ETL and hosts.
Extended Data Fig. 2 Angle-resolved TM-mode reflectance of Al/BPyTP2.
Extended Data Fig. 3 Device structures used in this study.
Extended Data Fig. 4 Simulated and measured PFs for the devices studied.
Extended Data Fig. 5 Ir(dmp)3 device energy levels and performance.
Extended Data Fig. 6 Ir(cb)3 device energy levels and performance.
Table 1 Summary of Ir(dmp)3 PHOLED performance, in which device performances for control (C) and full (F) cavity devices are compared.
Extended Data Table 1 Summary of Ir(dmp)3 and Ir(cb)3 device performance.
Extended Data Table 2 Summary of stretched exponential model for Ir(dmp)3 and Ir(cb)3 devices.
306Recovery of isolated lithium through discharged state calendar ageing
Recovery of isolated lithium through discharged state calendar ageing
Discharged state capacity recovery
Operando optical cell setup
Proposed Li recovery mechanism
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Fig. 1 Capacity recovery from discharged state rest illustrated by CE and TGC data.
Fig. 2 Operando optical microscopy of Li isolation and reconnection under continuous cycling.
Fig. 3 i-Li areal comparison between rested and continuously cycled optical cells.
Fig. 4 Rest-induced SEI dissolution and overpotential reduction.
Extended Data Fig. 1 Hybrid cycling protocol and corresponding CE.
Extended Data Fig. 2 Various charging capacity hybrid cycle performance.
Extended Data Fig. 3 Various discharge current density hybrid cycle performance.
Extended Data Fig. 4 Various rest time hybrid cycle performance.
Extended Data Fig. 5 Various rest cycle number hybrid cycle performance.
Extended Data Fig. 6 Optical cell assembly and cycle performance.
Extended Data Fig. 7 Optical cell colored areal maps of isolated and recovered Li.
Extended Data Fig. 8 LFP | |Cu pouch cell and long cycle Li | |Cu half-cells cycle performance.
Extended Data Fig. 9 SEI dissolution.
Extended Data Fig. 10 NMR and XPS analysis of discharge rested SEI and electrolyte.
313 A rechargeable calcium–oxygen battery that operates at room temperature
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Fig. 1 Rechargeable Ca–O2 batteries at room temperature with CaO2 as the main discharge product.
Fig. 2 Cathode reaction of Ca–O2 batteries involves reversible two-electron O2/CaO2 chemistry.
Fig. 3 Optimized electrolyte facilitates stable operation of Ca–O2 batteries.
Fig. 4 Ca–O2 batteries are suitable for practical applications.
Extended Data Fig. 1 Characterization of CNT air cathode and cycling performance of the Ca-O2 battery.
Extended Data Fig. 2 Characterization of the discharge product in Ca-O2 batteries.
Extended Data Fig. 3 Reversibility of CaO2 formation/decomposition in Ca-O2 cell chemistry.
Extended Data Fig. 4 Characterization of Ca metal anode disassembled from Ca-O2 batteries.
Extended Data Fig. 5 Evaluation of oxidation stability of the electrolyte.
Extended Data Fig. 6 Properties of the optimized electrolyte containing DMSO.
Extended Data Fig. 7 Electrochemical performance of Ca metal anode in electrolytes with and without DMSO.
Extended Data Fig. 8 Improved Ca2+ de-solvation and Ca plating/stripping.
Extended Data Fig. 9 Electrochemical performance of Ca-O2 batteries under practical conditions.
Extended Data Fig. 10 Fabrication and electrochemical performances of fibre Ca-O2 batteries.
Extended Data Table 1 Atomic percentage (at%) of the elements observed in XPS spectra of Ca deposits in anode disassembled from our Ca-O2 batteries at different sputtering time.
Extended Data Table 2 The parameters measured by potentiostatic polarization and electrochemical impedance spectroscopy for calculating the Ca2+ transference number.
319Elevated Southern Hemisphere moisture availability during glacial periods
Elevated Southern Hemisphere moisture availability during glacial periods
Speleothem growth during glacial periods
A pervasive cool-moist glacial pattern
Extent of the cool-moist glacial pattern
Implications of a cool-moist subtropics
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Fig. 1 CMI for the three main landmasses of the Southern Hemisphere subtropics and study sites.
Fig. 2 Two new speleothem proxy records of subtropical moisture in southern Australia show a cool-moist pattern.
Fig. 3 Naracoorte fossil pollen record and moisture reconstructions confirm Naracoorte KDE pattern.
Fig. 4 Southern Hemisphere subtropical hydroclimate proxy records show a widespread cool-moist pattern.
Fig. 5 Modelled responses of Southern Hemisphere hydroclimate proxy records to Southern Hemisphere temperature.
Fig. 6 Modelled responses of Southern Hemisphere hydroclimate proxy records to hemispheric temperature show the latitudinal limits of the subtropical cool-moist pattern.
Extended Data Fig. 1 Spectral analyses shows coherence and typically small phase lags with Southern Hemisphere summer insolation.
Extended Data Fig. 2 Pollen-based quantitative climate reconstructions for Naracoorte.
Extended Data Fig. 3 Climatically sensitive plant taxa’s geographic ranges within eastern Australia.
Extended Data Fig. 4 Climatically sensitive plant taxa’s climatic ranges in summer and winter seasons.
Extended Data Fig. 5 Correlation plots of HadCM3 simulations vs.
Extended Data Fig. 6 Three subtropical lake basin hydroclimate records show a cool-moist pattern.
Extended Data Fig. 7 Hydroclimate proxy records demonstrating the equatorward and poleward limits of the subtropical cool-wet pattern.
Extended Data Fig. 8 Power spectra with red noise threshold reveal significant precessional frequencies.
Extended Data Fig. 9 Naracoorte speleothem sample thickness/diameter versus sample age confirms there is no size-based preservation bias.
Extended Data Fig. 10 Southern Hemisphere subtropical DJF and JJA precipitation (mm).
Extended Data Fig. 11 Micrographs of selected pollen and spores from Naracoorte speleothems.
Extended Data Table 1 Modern climatic data for the Naracoorte Cave Complex and the Leeuwin-Naturaliste caves in southern Australia.
327 Country-specific net-zero strategies of the pulp and paper industry
Global and national paper-related GHG emissions
Scenario analysis on future GHG emissions
National strategies towards net-zero emissions by 2050
Decarbonization options through a systems approach
Priority for energy-related measures
Sustainable and diversified sourcing
Improved waste management and recycling strategies
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Fig. 1 Global GHG emissions of paper-related sectors during 1961–2019.
Fig. 2 Total net GHG emissions of paper-related sectors in regions and countries.
Fig. 3 GHG emissions of paper-related sectors in 30 countries from 1961 to 2019.
Fig. 4 Effects of single measures and all scenarios in 30 countries.
Fig. 5 The analysis of strategies towards net-zero emissions in 2050.
Extended Data Fig. 1 System definition and GHG emissions inventory.
Extended Data Fig. 2 Diagram of global energy consumption of pulping, papermaking and printing accumulated in 1961–2019.
Extended Data Fig. 3 Global GHG emissions of all processes accumulated in 1961–2019.
Extended Data Fig. 4 Detailed information about forest carbon emissions in the first ten countries in Fig.
Extended Data Fig. 5 Net GHG emissions under three recycling measures in 30 countries when no other measures are taken.
Extended Data Fig. 6 Net GHG emissions of 30 countries in 2019 and 2050 under the BAU scenario and 16 single-measure scenarios.
Extended Data Fig. 7 Statistics of factor scenario settings of net-zero scenarios.
Extended Data Fig. 8 Distribution of net-zero scenarios by the number of best or medium measures.
Extended Data Fig. 9 Carbon intensity of energy consumption in S2 and S3 across 30 countries from 1961 to 2019.
Extended Data Fig. 10 Analytical framework of forest carbon emissions estimation.
Extended Data Table 1 The grouping principles by difficulty of net-zero achievement for 30 countries.
Extended Data Table 2 The setting of factors in scenario analysis.
335 Predator mass mortality events restructure food webs through trophic decoupling
Trophic biomass responses
Community structural responses
Community biomass dynamics
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Fig. 1 Food-web biomass responses to predator removals, resource pulses and MMEs.
Fig. 2 Community-wide biomass, density and functional trait responses to predator removals, resource pulses and MMEs.
Fig. 3 Distinct zooplankton and microalgal community biomass trajectories after predator removals, resource pulses and MMEs.
Extended Data Fig. 1 Time series of mean zooplankton and microalgae density following ecological perturbations.
Extended Data Fig. 2 Time series of mean zooplankton body size and microalgae biovolume following ecological perturbations.
Extended Data Fig. 3 Time series of mean biomass across five major zooplankton families following ecological perturbations.
Extended Data Fig. 4 Time series of mean biomass across five major microalgae phyla following ecological perturbations.
Extended Data Fig. 5 Time series of mean density across five major zooplankton families following ecological perturbations.
Extended Data Fig. 6 Time series of mean density across five major microalgae phyla following ecological perturbations.
Extended Data Fig. 7 Time series of mean body size across five major zooplankton families following ecological perturbations.
Extended Data Fig. 8 Time series of mean biovolume across two major microalgae phyla following ecological perturbations.
Extended Data Fig. 9 Raw biomass estimates during sample periods before ecological perturbations were induced (i.
Extended Data Fig. 10 Raw (non-smoothed) and smoothed biomass estimates following ecological perturbations.
341 Homo sapiens reached the higher latitudes of Europe by 45,000 years ago
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Fig. 1 Stratigraphy with location of H.
Fig. 2 Chronological comparison of Ranis with selected contemporary sites and directly dated human remains.
Fig. 3 Bayesian phylogenetic tree of the newly reconstructed mtDNA genomes with previously published ancient and recent modern human mtDNA genomes constructed with BEAST2.
Extended Data Fig. 1 Ranis site plan and main West profile of the 2016–2022 excavation.
Extended Data Fig. 2 Map of Ranis with the location of the newly identified hominin specimens and selected lithic artefacts.
Extended Data Fig. 3 Chronological site model of 2016-2022 material from Ranis.
Extended Data Fig. 4 Protein deamidation for all hominin specimens in Ranis.
Extended Data Fig. 5 Proteomic coverage for the seven hominin bone specimens analysed with SPIN.
Extended Data Table 1 Hominin specimens identified in Ranis.
347 A dedicated hypothalamic oxytocin circuit controls aversive social learning
One-day defeat induces avoidance and fear
Winner cues drive loser aVMHvlOXTR cells
The aVMHvlOXTR response is specific to social contexts
Avoidance expression requires aVMHvlOXTR cells
Social avoidance learning requires OXTR
The SOR provides oxytocin to aVMHvlOXTR cells
Oxytocin facilitates synaptic potentiation
Noxious stimuli activate SOROXT cells
SOROXT cells boost social avoidance learning
Discussion
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Fig. 1 aVMHvlOXTR cells in male mice show increased responses to aggressors after defeat.
Fig. 2 aVMHvlOXTR cells bidirectionally modulate social avoidance.
Fig. 3 OXTRs in the aVMHvl are essential for defeat-induced social avoidance learning.
Fig. 4 The SOR is the primary source of oxytocin for aVMHvlOXTR cells.
Fig. 5 SOROXT cells are activated by noxious stimuli.
Fig. 6 SOROXT cells are essential for social avoidance learning.
Extended Data Fig. 1 One-day 10-min social defeat is sufficient to induce social avoidance of winner-like conspecifics.
Extended Data Fig. 2 Defeated animals do not avoid conspecifics with genetic backgrounds different from the aggressor.
Extended Data Fig. 3 The relationship between OXTR and defeat-induced c-Fos and Esr1 in the VMHvl.
Extended Data Fig. 4 aVMHvlOXTR cells increase responses to the aggressor after defeat in male mice.
Extended Data Fig. 5 Female aVMHvlOXTR cells increase responses to the aggressor after defeat.
Extended Data Fig. 6 aVMHvlOXTR cells increase response to the aggressor after defeat in female mice.
Extended Data Fig. 7 Defeat experience enhances aggressor cue-induced c-Fos in aVMHvlOXTR cells during subsequent encounters.
Extended Data Fig. 8 No change in excitability of aVMHvlOXTR cells one day after defeat.
Extended Data Fig. 9 aVMHvlOXTR cells do not respond to non-social aversive odors.
Extended Data Fig. 10 aVMHvlOXTR cells do not respond to non-social aversive cues or noxious somatosensory stimuli in head-fixed animals.
Extended Data Fig. 11 Behavior changes induced by optogenetic activation of aVMHvlOXTR and SOROXT cells.
Extended Data Fig. 12 SOROXT affects aVMHvl cell activity by activating OXTR, not glutamatergic synaptic transmission.
Extended Data Fig. 13 Overlap between OXT and defeat-induced c-Fos.
Extended Data Fig. 14 SOROXT cells do not increase responses to aggressors after defeat in male mice.
Extended Data Fig. 15 SOROXT cells in female mice are activated by noxious stimuli.
357 Hypoblast from human pluripotent stem cells regulates epiblast development-
Naive hPSC-induced hypoblast by GATA6
Hypoblast induced by signalling molecules
FGF/BMP for hypoblast specification
Generation of bilaminoids
Epiblast progression via TB-secreted IL-6
Mesoderm-like cells emerge in bilaminoids
Single-cell transcriptomics of bilaminoids
Anterior–posterior axis formation in bilaminoids
nHyCs support epiblast progression
Lineage specification in bilaminoids
Discussion
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Fig. 1 Naive hPSC differentiation into the PDGFRA+ hypoblast by GATA6 overexpression.
Fig. 2 Essential signalling for human hypoblast specification.
Fig. 3 Naive hPSCs and nHyCs generate bilaminoids.
Fig. 4 TB enhances epiblast progression through IL-6 paracrine signalling.
Fig. 5 Global gene expression profiles of individual cells in bilaminoids.
Fig. 6 Bilaminoids recapitulate human pregastrulation.
Extended Data Fig. 1 Naïve and Primed hPSCs and GATA6 overexpression.
Extended Data Fig. 2 Transcriptome analysis after GATA6 overexpression in naïve and primed G6-PDGFRA+ cells.
Extended Data Fig. 3 Naïve hPSCs differentiate into hypoblast lineage with 7F without GATA6 overexpression.
Extended Data Fig. 4 Surface markers and signalling molecules of human hypoblast cells.
Extended Data Fig. 5 Signalling for hypoblast specification differs between humans and mice.
Extended Data Fig. 6 Bilaminoids generated by naïve hPSCs and nHyC.
Extended Data Fig. 7 Trophoblast enhances epiblast progression.
Extended Data Fig. 8 Global gene expression profiles and anterior-posterior axis formation of bilaminoids.
Extended Data Fig. 9 LAMB1 knockout nHyC and gene expression profiles of bilaminoids.
Extended Data Fig. 10 Bilaminoids on D9 and interspecies chimaera assays.
367Modelling post-implantation human development to yolk sac blood emergence
Modelling post-implantation human development to yolk sac blood emergence
Epiblast and hypoblast codevelopment
Intra- and/or extra-embryonic scRNA trajectories
Specification of amniotic ectoderm
Anterior hypoblast and posterior domain
Yolk sac mesoderm and blood progenitors
Yolk sac-like haematopoiesis
Cell composition of haematopoietic waves
Discussion
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Fig. 1 Engineering codevelopment of embryonic and extra-embryonic endoderm tissues.
Fig. 2 Amniotic cavity formation and expansion.
Fig. 3 Anterior hypoblast domain and posterior pole in heX-embryoids.
Fig. 4 Haematopoietic lineages and haematopoietic foci structures in the heX-embryoids.
Fig. 5 Haematopoietic programme characterization in heX-embryoids.
Extended Data Fig. 1 Fate acquisition, sorting, and symmetry breaking following GATA6 induction.
Extended Data Fig. 2 Lumen development and optimization within WT cluster.
Extended Data Fig. 3 Single Cell RNA-seq analysis and clustering per day (day 0 to 5).
Extended Data Fig. 4 Hypergeometric statistical comparison of heX-embryoid time points to human and NHP embryo data.
Extended Data Fig. 5 Merged clustering of RNA-seq Day 0 – Day 5 of the embryoids.
Extended Data Fig. 6 Amnion and anteroposterior domains.
Extended Data Fig. 7 Identification of endothelial/hematopoietic populations in heX-embryoids.
Extended Data Fig. 8 GATA6-hi supplementation and structure of hematopoietic foci.
Extended Data Fig. 9 Hematopoietic foci in heX-embryoids.
Extended Data Fig. 10 Hematopoietic cell composition in heX-embryoids.
Extended Data Fig. 11 heX-embryoid formation from hiPSCs to model human early post-implantation development in vitro.
Extended Data Fig. 12 heX-embryoid development, passaging, cryostorage as well as engineering in a separate iPSC line.
377 Functional and evolutionary significance of unknown genes from uncultivated taxa
A curated catalogue of novel gene families
Functional predictions
Hypothesis-driven functional validations
Density of novel families per genome
Synapomorphies in uncultivated taxa
Habitat distribution of novel families
Discovery of new biomarkers
Discussion
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Fig. 1 Gene family discovery pipeline and general statistics.
Fig. 2 Distribution of FESNov gene families confidently linked to KEGG pathways.
Fig. 3 FESNov gene families are spread across the entire microbial phylogeny, covering a variety of habitats.
Fig. 4 FESNov synapomorphic gene families found at high-level taxonomic rank.
Fig. 5 FESNov gene families contribute to CRC predictive power and include biomarkers for the disease.
Extended Data Fig. 1 Swimming chemotaxis assay of Escherichia coli W3110 strain expressing NOV3845Y.
Extended Data Fig. 2 Antimicrobial activity of NOVOQR9B peptide.
Extended Data Fig. 3 Structural similarity of NOV5WD8W with the copper metallochaperone CusF.
Extended Data Fig. 4 Schematic representation of the genomic context of four transmembrane FESNov gene families in Patescibacteria genomes.
Extended Data Fig. 5 Correlation between FESNov gene families mobility and ecological dispersion.
Extended Data Fig. 6 Number of FESNov gene families confined to each taxonomic rank.
Extended Data Fig. 7 Separation of habitats and human gut populations with FESNov families and KO relative abundances.
Extended Data Fig. 8 Examples of the genomic context of FESNov families over-abundant in CRC samples.
Extended Data Fig. 9 Performance of predictors built upon the relative abundance matrices of both FESNov gene families and KEGG Orthologs (KOs) families.
385 Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques
Study design
Mucosal and peripheral humoral responses
Mucosal and peripheral T cell responses
Protective efficacy
Histopathology
Lung transcriptomics and cytokines
Discussion
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Fig. 1 Study outline.
Fig. 2 Mucosal and peripheral SARS-CoV-2 NAb responses.
Fig. 3 Mucosal and peripheral IgA spike-specific binding antibody responses.
Fig. 4 Mucosal and peripheral T cell responses.
Fig. 5 Viral loads after SARS-CoV-2 BQ.
Fig. 6 Transcriptomics and cytokine analyses in the BAL.
Extended Data Fig. 1 Comparison of week 4 immune responses in BAL.
Extended Data Fig. 2 Mucosal and peripheral IgA spike-specific binding antibody responses by ECLA.
Extended Data Fig. 3 Mucosal and peripheral IgG spike-specific binding antibody responses by ELISA.
Extended Data Fig. 4 Mucosal and peripheral IgG spike-specific binding antibody responses by ECLA.
Extended Data Fig. 5 Sample flow cytometry gating.
Extended Data Fig. 6 Anamnestic SARS-CoV-2 neutralizing antibody responses following SARS-CoV-2 BQ.
Extended Data Fig. 7 Immune correlates of protection.
Extended Data Fig. 8 Histopathology.
Extended Data Fig. 9 Fibrosis scores.
Extended Data Fig. 10 Additional transcriptomics analyses in the BAL.
392 Prevention of respiratory virus transmission by resident memory CD8+ T cells
CD8+ TRM cells limit the transmission window
IFNγ is required to limit transmission
TRM cells limit susceptibility to infection
IFNγ alters epithelial cell programming
CD8+ TRM cells can provide durable protection
Discussion
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Fig. 1 Respiratory tract CD8+ TRM cells can limit transmission of respiratory viruses.
Fig. 2 IFNγ signalling has an essential role in preventing transmission of respiratory viruses.
Fig. 3 Respiratory tract CD8+ TRM cells protect against viral propagation following transmission through IFNγ.
Fig. 4 IFNγ signalling induces antiviral gene expression and increases antigen presentation in nasal cavity epithelial cells.
Fig. 5 The number of respiratory tract CD8+ TRM cells is strongly linked to protection from transmission.
Extended Data Fig. 1 Distribution and characterization of tissue-resident Sendai-specific CD8+ T cells limit following intranasal and intraperitoneal infection with recombinant influenza virus.
Extended Data Fig. 2 Sendai-luciferase bioluminescence strongly correlates with viral titer.
Extended Data Fig. 3 Contact mice that show no indication of transmission by bioluminescence also fail to develop a Sendai-specific T cell response.
Extended Data Fig. 4 Number of SenNP-specific CD8+ TRM in knockout mouse strains following immunization.
Extended Data Fig. 5 Immunization does not alter influx of NK cells and monocytes following Sendai virus transmission.
Extended Data Fig. 6 Sendai-specific TRM numbers and assessment of transmission under different immunization strategies at 1- and 6-months post-immunization.
Extended Data Fig. 7 High viral burden in index mice does not correlate with increased viral burden in contact mice.
Extended Data Fig. 8 Pre-existing immunity to related influenza strains limits the efficacy of protective T cell immunity induced by LAIV-SenNP immunization but can be overcome by Ad-SenNP immunization.
Extended Data Fig. 9 Heterologous influenza prime-boost does not improve the durability of respiratory tract TRM.
401 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis
DHCR7 is a proferroptotic gene
7-DHC is an antiferroptotic metabolite
7-DHC blocks phospholipid peroxidation
Truncated phospholipids drive cell lysis
7-DHC accumulation increases cell fitness
Discussion
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Fig. 1 Identification and impact of DHCR7 deficiency on ferroptosis.
Fig. 2 7-DHC accumulation suppresses ferroptosis.
Fig. 3 7-DHC acts to suppress (phospho)lipid peroxidation.
Fig. 4 Phospholipid truncated species contribute to ferroptosis execution.
Fig. 5 Impact of 7-DHC accumulation on lymphoma growth.
Extended Data Fig. 1 Lipidomic characterization of DHCR7-deficient cells.
Extended Data Fig. 2 DHCR7 deficiency impact on ferroptosis and other cell death modalities.
Extended Data Fig. 3 Characterization of HT1080 DHCR7-deficient clonal cell line.
Extended Data Fig. 4 Impact of 7-DHC accumulation on ferroptosis.
Extended Data Fig. 5 Influence of cholesterol low conditions on the antiferroptotic activity of the 7-DHC/DHCR7 axis.
Extended Data Fig. 6 Role of B-ring unsaturated sterol in ferroptosis.
Extended Data Fig. 7 Impact and consequence of 7-DHC on phospholipid peroxidation.
Extended Data Fig. 8 Impact of ferroptosis inhibitors on oxidant mediated liposomal rupture.
Extended Data Fig. 9 Role of truncated phospholipid in membrane permeability.
Extended Data Fig. 10 Conjugation at the omega position affects ferroptosis sensitivity.
Extended Data Fig. 11 Impact of 7-DHC accumulation on BL growth.
Extended Data Fig. 12 Impact of DHCR7 loss in vivo.
411 7-Dehydrocholesterol dictates ferroptosis sensitivity
Distal cholesterol biosynthesis regulates ferroptosis
7-DHC suppresses ferroptosis
7-DHC suppresses phospholipid peroxidation
7-DHC regulates tumour ferroptosis
7-DHC protects the kidneys from IRI
Discussion
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Fig. 1 The genes involved in distal cholesterol synthesis differentially regulate ferroptosis.
Fig. 2 7-DHC suppresses ferroptosis.
Fig. 3 7-DHC shields plasma and mitochondria membranes from autoxidation.
Fig. 4 Targeting 7-DHC biosynthesis regulates cancer cell sensitivity to ferroptosis.
Fig. 5 7-DHC attenuates IRI in vivo.
Extended Data Fig. 1 Identification of distal CB pathway including CYP51A1, MSMO1, EBP and SC5D as ferroptosis suppressors.
Extended Data Fig. 2 The distal cholesterol biosynthesis genes regulates ferroptosis.
Extended Data Fig. 3 Distal CB pathway regulates ferroptosis independent of cholesterol and known ferroptosis defence system.
Extended Data Fig. 4 7-DHC suppresses ferroptosis.
Extended Data Fig. 5 7-DHC is a general suppressor of ferroptosis.
Extended Data Fig. 6 7-DHC protects against phospholipid peroxidation.
Extended Data Fig. 7 Regulation of 7-DHC level during ferroptosis.
Extended Data Fig. 8 Targeting 7-DHC biosynthesis regulates cancer cell sensitivity to ferroptosis.
Extended Data Fig. 9 7-DHC promotes metastasis.
Extended Data Fig. 10 Cariprazine protects IRI in vivo.
419 Reverse metabolomics for the discovery of chemical structures from humans
Reverse metabolomics
Acyl amide and ester searches
Analysis of bile amidates
Validation of the IBD association
Microbial production of bile amides
Conclusion
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Fig. 1 Overview of reverse metabolomics and the synthetic strategies used to obtain standards for MS/MS in this work.
Fig. 2 Repository-scale analysis of public MS data.
Fig. 3 IBD association of new conjugated bile acids.
Fig. 4 Bile acid conjugations observed in HMP isolates cultured in fecal growth medium containing CA and DCA.
Extended Data Fig. 1 Representative fragmentation of standard vs observed MS/MS in public data with key fragment ions shown.
Extended Data Fig. 2 Results of MASST searches for N-acyl amides.
Extended Data Fig. 3 Results of MASST searches for acyl esters.
Extended Data Fig. 4 Analysis of synthetic conjugated bile acid mixtures.
Extended Data Fig. 5 Independent validation of new conjugated bile acids in PRISM human IBD cohort.
Extended Data Fig. 6 Overview of conjugated bile acids in iHMP2 human IBD cohort.
Extended Data Fig. 7 PXR activity of conjugated bile acids.
Extended Data Fig. 8 LC-IMS-MS Analysis of Bacterial Cultures.
427Transport and inhibition mechanisms of human VMAT2
Transport and inhibition mechanisms of human VMAT2
Function and architecture of VMAT2
5-HT recognition by VMAT2
Titratable residues within the cavity
Molecular dynamics simulations of 5-HT binding
Essential role of E312 and R189
Inhibition of VMAT2 by reserpine
VMAT2 inhibition by TBZ
VMAT2 inhibition by KET
State transitions of VMAT2
Discussion
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Fig. 1 Functional characterization and structure of human VMAT2.
Fig. 2 Structural basis of 5-HT recognition by VMAT2.
Fig. 3 Structural basis of VMAT2 inhibition by reserpine.
Fig. 4 Structural basis of VMAT2 inhibition by TBZ.
Fig. 5 Structural basis of VMAT2 inhibition by KET.
Fig. 6 Structural basis of VMAT2 state transitions.
Extended Data Fig. 1 Purification of human VMAT2.
Extended Data Fig. 2 Cryo-EM analysis of human VMAT25HT.
Extended Data Fig. 3 Cryo-EM data processing of VMAT2RES.
Extended Data Fig. 4 Cryo-EM data processing of VMAT2TBZ and VMAT2KET.
Extended Data Fig. 5 Structures of VMAT2 in three distinct states.
Extended Data Fig. 6 Comparison of the hydrogen bond network of VMAT2 in different states.
Extended Data Fig. 7 MD simulation of 5HT binding to the lumen-facing VMAT2.
Extended Data Fig. 8 Sequence alignment of SLC18 transporters.
Extended Data Fig. 9 Function and transport model of VMAT2.
Extended Data Table 1 Cryo-EM data collection, refinement and validation statistics.
435 De novo design of high-affinity binders of bioactive helical peptides
Design of peptide-binding scaffolds
Designing binders using Hallucination
Design refinement with RFdiffusion
De novo binder design using RFdiffusion
Human versus machine problem solving
Design of protein biosensors
Enrichment for LC–MS/MS detection
Discussion
Online content
Fig. 1 Design strategies for binding helical peptides.
Fig. 2 Peptide binder optimization with RFdiffusion.
Fig. 3 De novo peptide binder design with RFdiffusion.
Fig. 4 Application of designed binders to sensing and detection.
Extended Data Fig. 1 Low affinity RFjoint-Inpainted binders for NPY and GCG using extended parametric designs.
Extended Data Fig. 2 Additional binders made using threading and redesign.
Extended Data Fig. 3 Hallucinated Bid binders are stable and bind Bid peptide with high affinity.
Extended Data Fig. 4 Partial diffusion increases designability of native proteins.
Extended Data Fig. 5 PTH and GCG binders designed with RFdiffusion.
Extended Data Fig. 6 LC-MS/MS chromatograms for PTH and GCG binders.
Extended Data Table 1 Amino acid sequences of peptide binders.
Extended Data Table 2 Crystallographic data collection and refinement.
443 Organize your –80 °C freezer to save time and prevent frozen fingertips
444 How a peer network made my worst day as a grad student bearable
448 I started fossil hunting in my 60s — now I have more than 2,000 pieces
e4 Author Correction- Short tRNA anticodon stem and mutant eRF1 allow stop codon reassignment
e5 Author Correction- Aerial additive manufacturing with multiple autonomous robots
e6 Author Correction- R-loop-derived cytoplasmic RNA–DNA hybrids activate an immune response
e7 Publisher Correction- Intermediate conformations of CD4-bound HIV-1 Env heterotrimers