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Amniote integumentary appendages constitute a diverse group of micro-organs, including feathers, hair and scales. These structures typically develop as genetically controlled units1, the spatial patterning of which emerges from a self-organized chemical Turing system2,3with integrated mechanical feedback4,5. The seemingly purely mechanical patterning of polygonal crocodile head scales provides an exception to this paradigm6. However, the nature and origin of the mechanical stress field driving this patterning remain unclear. Here, using precise in ovo intravenous injections of epidermal growth factor protein, we generate Nile crocodile embryos with substantially convoluted head skin, as well as hatchlings with smaller polygonal head scales resembling those of caimans. We then use light-sheet fluorescence microscopy to quantify embryonic tissue-layer geometry, collagen architecture and the spatial distribution of proliferating cells. Using these data, we build a phenomenological three-dimensional mechanical growth model that recapitulates both normal and experimentally modified patterning of crocodile head scales. Our experiments and numerical simulations demonstrate that crocodile head scales self-organize through compressive folding, originating from near-homogeneous skin growth with differential stiffness of the dermis versus the epidermis. Our experiments and theoretical morphospace analyses indicate that variation in embryonic growth and material properties of skin layers provides a simple evolutionary mechanism that produces a diversity of head-scale patterns among crocodilian species.

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters allele expression commitment, in support of two proposed mechanisms5,6for the regulation of aRMAE. We tested peripheral blood mononuclear cells from individuals with IEIs with shared genetic lesions but discordant clinical phenotypes for aRMAE. Among two relatives who were heterozygous for a mutation in PLCG2(delEx19), an antibody deficiency phenotype corresponds to selective mutant allele expression in B cells. By contrast, among relatives who were heterozygous for a mutation in JAK1(c.2099G>A; p.S700N), the unaffected carrier T cells predominantly expressed the wild-type JAK1allele, whereas the affected carrier T cells exhibited biallelic expression. Allelic expression bias was also documented in phenotypically discordant family members with mutations in STAT1and CARD11. This study highlights the importance of considering both the genotype and the ‘transcriptotype’ in analyses of the penetrance and expressivity of monogenic disorders.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5–7. This hampers the accuracy of global land carbon–climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9–2.0 °C] in air and 0.4 °C [CI 0.2–0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22–38%] (n= 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n= 9) and continued for at least 25 years (n= 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1–6in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.

Autonomous laboratories can accelerate discoveries in chemical synthesis, but this requires automated measurements coupled with reliable decision-making1,2. Most autonomous laboratories involve bespoke automated equipment3–6, and reaction outcomes are often assessed using a single, hard-wired characterization technique7. Any decision-making algorithms8must then operate using this narrow range of characterization data9,10. By contrast, manual experiments tend to draw on a wider range of instruments to characterize reaction products, and decisions are rarely taken based on one measurement alone. Here we show that a synthesis laboratory can be integrated into an autonomous laboratory by using mobile robots11–13that operate equipment and make decisions in a human-like way. Our modular workflow combines mobile robots, an automated synthesis platform, a liquid chromatography–mass spectrometer and a benchtop nuclear magnetic resonance spectrometer. This allows robots to share existing laboratory equipment with human researchers without monopolizing it or requiring extensive redesign. A heuristic decision-maker processes the orthogonal measurement data, selecting successful reactions to take forward and automatically checking the reproducibility of any screening hits. We exemplify this approach in the three areas of structural diversification chemistry, supramolecular host–guest chemistry and photochemical synthesis. This strategy is particularly suited to exploratory chemistry that can yield multiple potential products, as for supramolecular assemblies, where we also extend the method to an autonomous function assay by evaluating host–guest binding properties.

Metal–organic frameworks (MOFs) are useful synthetic materials that are built by the programmed assembly of metal nodes and organic linkers1. The success of MOFs results from the isoreticular principle2, which allows families of structurally analogous frameworks to be built in a predictable way. This relies on directional coordinate covalent bonding to define the framework geometry. However, isoreticular strategies do not translate to other common crystalline solids, such as organic salts3–5, in which the intermolecular ionic bonding is less directional. Here we show that chemical knowledge can be combined with computational crystal-structure prediction6(CSP) to design porous organic ammonium halide salts that contain no metals. The nodes in these salt frameworks are tightly packed ionic clusters that direct the materials to crystallize in specific ways, as demonstrated by the presence of well-defined spikes of low-energy, low-density isoreticular structures on the predicted lattice energy landscapes7,8. These energy landscapes allow us to select combinations of cations and anions that will form thermodynamically stable, porous salt frameworks with channel sizes, functionalities and geometries that can be predicted a priori. Some of these porous salts adsorb molecular guests such as iodine in quantities that exceed those of most MOFs, and this could be useful for applications such as radio-iodine capture9–12. More generally, the synthesis of these salts is scalable, involving simple acid–base neutralization, and the strategy makes it possible to create a family of non-metal organic frameworks that combine high ionic charge density with permanent porosity.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics1,2, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital–community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences. We estimate that between June 2020 and March 2021 between 95,000 and 167,000 inpatients acquired SARS-CoV-2 in hospitals (1% to 2% of all hospital admissions in this period). Analysis of time series data provided evidence that patients who themselves acquired SARS-CoV-2 infection in hospital were the main sources of transmission to other patients. Increased transmission to inpatients was associated with hospitals having fewer single rooms and lower heated volume per bed. Moreover, we show that reducing hospital transmission could substantially enhance the efficiency of punctuated lockdown measures in suppressing community transmission. These findings reveal the previously unrecognized scale of hospital transmission, have direct implications for targeting of hospital control measures and highlight the need to design hospitals better equipped to limit the transmission of future high-consequence pathogens.

Moons potentially harbouring a global ocean are tending to become relatively common objects in the Solar System1. The presence of these long-lived global oceans is generally betrayed by surface modification owing to internal dynamics2. Hence, Mimas would be the most unlikely place to look for the presence of a global ocean3. Here, from detailed analysis of Mimas’s orbital motion based on Cassini data, with a particular focus on Mimas’s periapsis drift, we show that its heavily cratered icy shell hides a global ocean, at a depth of 20–30 kilometres. Eccentricity damping implies that the ocean is likely to be less than 25 million years old and still evolving. Our simulations show that the ocean–ice interface reached a depth of less than 30 kilometres only recently (less than 2–3 million years ago), a time span too short for signs of activity at Mimas’s surface to have appeared.

Human society is dependent on nature1,2, but whether our ecological foundations are at risk remains unknown in the absence of systematic monitoring of species’ populations3. Knowledge of species fluctuations is particularly inadequate in the marine realm4. Here we assess the population trends of 1,057 common shallow reef species from multiple phyla at 1,636 sites around Australia over the past decade. Most populations decreased over this period, including many tropical fishes, temperate invertebrates (particularly echinoderms) and southwestern Australian macroalgae, whereas coral populations remained relatively stable. Population declines typically followed heatwave years, when local water temperatures were more than 0.5 °C above temperatures in 2008. Following heatwaves5,6, species abundances generally tended to decline near warm range edges, and increase near cool range edges. More than 30% of shallow invertebrate species in cool latitudes exhibited high extinction risk, with rapidly declining populations trapped by deep ocean barriers, preventing poleward retreat as temperatures rise. Greater conservation effort is needed to safeguard temperate marine ecosystems, which are disproportionately threatened and include species with deep evolutionary roots. Fundamental among such efforts, and broader societal needs to efficiently adapt to interacting anthropogenic and natural pressures, is greatly expanded monitoring of species’ population trends7,8.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France5,6.

Generation of silicic magmas leads to emplacement of granite plutons, huge explosive volcanic eruptions and physical and chemical zoning of continental and arc crust1–7. Whereas timescales for silicic magma generation in the deep and middle crust are prolonged8, magma transfer into the upper crust followed by eruption is episodic and can be rapid9–12. Ages of inherited zircons and sanidines from four Miocene ignimbrites in the Central Andes indicate a gap of 4.6 Myr between initiation of pluton emplacement and onset of super-eruptions, with a 1-Myr cyclicity. We show that inherited zircons and sanidine crystals were stored at temperatures <470 °C in these plutons before incorporation in ignimbrite magmas. Our observations can be explained by silicic melt segregation in a middle-crustal hot zone with episodic melt ascent from an unstable layer at the top of the zone with a timescale governed by the rheology of the upper crust. After thermal incubation of growing plutons, large upper-crustal magma chambers can form in a few thousand years or less by dike transport from the hot-zone melt layer. Instability and disruption of earlier plutonic rock occurred in a few decades or less just before or during super-eruptions.

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n= 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P= 0.001; RFS, 64% versus 32% at 2 years, P= 0.021). The findings were validated in several additional cohorts2–4of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n= 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P= 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P= 0.0006 and P= 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P= 0.018 and P= 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P= 0.021 and P< 0.0001). Together, these results have important implications for therapy.

Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1–3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6–9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h−1g−1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control.

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10–20% (14–24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.

Interactions govern the flow of information and the formation of correlations between constituents of many-body quantum systems, dictating phases of matter found in nature and forms of entanglement generated in the laboratory. Typical interactions decay with distance and thus produce a network of connectivity governed by geometry—such as the crystalline structure of a material or the trapping sites of atoms in a quantum simulator1,2. However, many envisioned applications in quantum simulation and computation require more complex coupling graphs including non-local interactions, which feature in models of information scrambling in black holes3–6and mappings of hard optimization problems onto frustrated classical magnets7–11. Here we describe the realization of programmable non-local interactions in an array of atomic ensembles within an optical cavity, in which photons carry information between atomic spins12–19. By programming the distance dependence of the interactions, we access effective geometries for which the dimensionality, topology and metric are entirely distinct from the physical geometry of the array. As examples, we engineer an antiferromagnetic triangular ladder, a Möbius strip with sign-changing interactions and a treelike geometry inspired by concepts of quantum gravity5,20–22. The tree graph constitutes a toy model of holographic duality21,22, in which the quantum system lies on the boundary of a higher-dimensional geometry that emerges from measured correlations23. Our work provides broader prospects for simulating frustrated magnets and topological phases24, investigating quantum optimization paradigms10,11,25,26and engineering entangled resource states for sensing and computation27,28.

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1–6, an inverse Hall angle that varies as temperature squared7–9and a linear-in-field magnetoresistance10–13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant ‘Planckian’ dissipators.

Genetic recombination arises during meiosis through the repair of DNA double-strand breaks (DSBs) that are created by Spo11, a topoisomerase-like protein1,2. Spo11 DSBs form preferentially in nucleosome-depleted regions termed hotspots3,4, yet how Spo11 engages with its DNA substrate to catalyse DNA cleavage is poorly understood. Although most recombination events are initiated by a single Spo11 cut, here we show in Saccharomyces cerevisiaethat hyperlocalized, concerted Spo11 DSBs separated by 33 to more than 100 base pairs also form, which we term ‘double cuts’. Notably, the lengths of double cuts vary with a periodicity of 10.5 base pairs, which is conserved in yeast and mice. This finding suggests a model in which the orientation of adjacent Spo11 molecules is fixed relative to the DNA helix—a proposal supported by the in vitro DNA-binding properties of the Spo11 core complex. Deep sequencing of meiotic progeny identifies recombination scars that are consistent with repair initiated from gaps generated by adjacent Spo11 DSBs. Collectively, these results revise our present understanding of the mechanics of Spo11-DSB formation and expand on the original concepts of gap repair during meiosis to include DNA gaps that are generated by Spo11 itself.

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3–5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDecould reduce the net warming impact of CO2and CH4emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2per hectare per year, until WTDeis less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDeis within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDein all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

Dire wolves are considered to be one of the most common and widespread large carnivores in Pleistocene America1, yet relatively little is known about their evolution or extinction. Here, to reconstruct the evolutionary history of dire wolves, we sequenced five genomes from sub-fossil remains dating from 13,000 to more than 50,000 years ago. Our results indicate that although they were similar morphologically to the extant grey wolf, dire wolves were a highly divergent lineage that split from living canids around 5.7 million years ago. In contrast to numerous examples of hybridization across Canidae2,3, there is no evidence for gene flow between dire wolves and either North American grey wolves or coyotes. This suggests that dire wolves evolved in isolation from the Pleistocene ancestors of these species. Our results also support an early New World origin of dire wolves, while the ancestors of grey wolves, coyotes and dholes evolved in Eurasia and colonized North America only relatively recently.

BNT162b2, a nucleoside-modified mRNA formulated in lipid nanoparticles that encodes the SARS-CoV-2 spike glycoprotein (S) stabilized in its prefusion conformation, has demonstrated 95% efficacy in preventing COVID-191. Here we extend a previous phase-I/II trial report2by presenting data on the immune response induced by BNT162b2 prime–boost vaccination from an additional phase-I/II trial in healthy adults (18–55 years old). BNT162b2 elicited strong antibody responses: at one week after the boost, SARS-CoV-2 serum geometric mean 50% neutralizing titres were up to 3.3-fold above those observed in samples from individuals who had recovered from COVID-19. Sera elicited by BNT162b2 neutralized 22 pseudoviruses bearing the S of different SARS-CoV-2 variants. Most participants had a strong response of IFNγ+or IL-2+CD8+and CD4+T helper type 1 cells, which was detectable throughout the full observation period of nine weeks following the boost. Using peptide–MHC multimer technology, we identified several BNT162b2-induced epitopes that were presented by frequent MHC alleles and conserved in mutant strains. One week after the boost, epitope-specific CD8+T cells of the early-differentiated effector-memory phenotype comprised 0.02–2.92% of total circulating CD8+T cells and were detectable (0.01–0.28%) eight weeks later. In summary, BNT162b2 elicits an adaptive humoral and poly-specific cellular immune response against epitopes that are conserved in a broad range of variants, at well-tolerated doses.

Meiotic processes are potentially dangerous to genome stability and could be disastrous if activated in proliferative cells. Here we show that two key meiosis-defining proteins, the topoisomerase Spo11 (which forms double-strand breaks) and the meiotic cohesin Rec8, can dismantle centromeres. This dismantlement is normally observable only in mutant cells that lack the telomere bouquet, which provides a nuclear microdomain conducive to centromere reassembly1; however, overexpression of Spo11 or Rec8 leads to levels of centromere dismantlement that cannot be countered by the bouquet. Specific nucleosome remodelling factors mediate centromere dismantlement by Spo11 and Rec8. Ectopic expression of either protein in proliferating cells leads to the loss of mitotic kinetochores in both fission yeast and human cells. Hence, while centromeric chromatin has been characterized as extraordinarily stable, Spo11 and Rec8 challenge this stability and may jeopardize kinetochores in cancers that express meiotic proteins.

Expansion of anthropogenic noise and night lighting across our planet1,2is of increasing conservation concern3–6. Despite growing knowledge of physiological and behavioural responses to these stimuli from single-species and local-scale studies, whether these pollutants affect fitness is less clear, as is how and why species vary in their sensitivity to these anthropic stressors. Here we leverage a large citizen science dataset paired with high-resolution noise and light data from across the contiguous United States to assess how these stimuli affect reproductive success in 142 bird species. We find responses to both sensory pollutants linked to the functional traits and habitat affiliations of species. For example, overall nest success was negatively correlated with noise among birds in closed environments. Species-specific changes in reproductive timing and hatching success in response to noise exposure were explained by vocalization frequency, nesting location and diet. Additionally, increased light-gathering ability of species’ eyes was associated with stronger advancements in reproductive timing in response to light exposure, potentially creating phenological mismatches7. Unexpectedly, better light-gathering ability was linked to reduced clutch failure and increased overall nest success in response to light exposure, raising important questions about how responses to sensory pollutants counteract or exacerbate responses to other aspects of global change, such as climate warming. These findings demonstrate that anthropogenic noise and light can substantially affect breeding bird phenology and fitness, and underscore the need to consider sensory pollutants alongside traditional dimensions of the environment that typically inform biodiversity conservation.

Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity1and stabilizing the climate of the Earth2. Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO2—30% of the total CO2increase in the atmosphere, or 14% of total emissions, since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically.

An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18–55 years of age. Two doses of 1–50 µg of BNT162b1 elicited robust CD4+and CD8+T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-µg dose) to 3.5-fold (50-µg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+and CD4+T cell expansion. Interferon-? was produced by a large fraction of RBD-specific CD8+and CD4+T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.

In March 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1, a pandemic. With rapidly accumulating numbers of cases and deaths reported globally2, a vaccine is urgently needed. Here we report the available safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study (ClinicalTrials.gov identifier NCT04368728) among 45 healthy adults (18–55 years of age), who were randomized to receive 2 doses—separated by 21 days—of 10 µg, 30 µg or 100 µg of BNT162b1. BNT162b1 is a lipid-nanoparticle-formulated, nucleoside-modified mRNA vaccine that encodes the trimerized receptor-binding domain (RBD) of the spike glycoprotein of SARS-CoV-2. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. A second vaccination with 100 µg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-µg dose. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second dose. Geometric mean neutralizing titres reached 1.9–4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR. These results support further evaluation of this mRNA vaccine candidate.

Substantial research over the past two decades has established that extracellular matrix (ECM) elasticity, or stiffness, affects fundamental cellular processes, including spreading, growth, proliferation, migration, differentiation and organoid formation. Linearly elastic polyacrylamide hydrogels and polydimethylsiloxane (PDMS) elastomers coated with ECM proteins are widely used to assess the role of stiffness, and results from such experiments are often assumed to reproduce the effect of the mechanical environment experienced by cells in vivo. However, tissues and ECMs are not linearly elastic materials—they exhibit far more complex mechanical behaviours, including viscoelasticity (a time-dependent response to loading or deformation), as well as mechanical plasticity and nonlinear elasticity. Here we review the complex mechanical behaviours of tissues and ECMs, discuss the effect of ECM viscoelasticity on cells, and describe the potential use of viscoelastic biomaterials in regenerative medicine. Recent work has revealed that matrix viscoelasticity regulates these same fundamental cell processes, and can promote behaviours that are not observed with elastic hydrogels in both two- and three-dimensional culture microenvironments. These findings have provided insights into cell–matrix interactions and how these interactions differentially modulate mechano-sensitive molecular pathways in cells. Moreover, these results suggest design guidelines for the next generation of biomaterials, with the goal of matching tissue and ECM mechanics for in vitro tissue models and applications in regenerative medicine.

Technologies such as batteries, biomaterials and heterogeneous catalysts have functions that are defined by mixtures of molecular and mesoscale components. As yet, this multi-length-scale complexity cannot be fully captured by atomistic simulations, and the design of such materials from first principles is still rare1–5. Likewise, experimental complexity scales exponentially with the number of variables, restricting most searches to narrow areas of materials space. Robots can assist in experimental searches6–14but their widespread adoption in materials research is challenging because of the diversity of sample types, operations, instruments and measurements required. Here we use a mobile robot to search for improved photocatalysts for hydrogen production from water15. The robot operated autonomously over eight days, performing 688 experiments within a ten-variable experimental space, driven by a batched Bayesian search algorithm16–18. This autonomous search identified photocatalyst mixtures that were six times more active than the initial formulations, selecting beneficial components and deselecting negative ones. Our strategy uses a dexterous19,20free-roaming robot21–24, automating the researcher rather than the instruments. This modular approach could be deployed in conventional laboratories for a range of research problems beyond photocatalysis.

Primary immunodeficiency (PID) is characterized by recurrent and often life-threatening infections, autoimmunity and cancer, and it poses major diagnostic and therapeutic challenges. Although the most severe forms of PID are identified in early childhood, most patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease, allergy is prevalent and up to 10% develop lymphoid malignancies1–3. Consequently, in sporadic (or non-familial) PID genetic diagnosis is difficult and the role of genetics is not well defined. Here we address these challenges by performing whole-genome sequencing in a large PID cohort of 1,318 participants. An analysis of the coding regions of the genome in 886 index cases of PID found that disease-causing mutations in known genes that are implicated in monogenic PID occurred in 10.3% of these patients, and a Bayesian approach (BeviMed4) identified multiple new candidate PID-associated genes, including IVNS1ABP. We also examined the noncoding genome, and found deletions in regulatory regions that contribute to disease causation. In addition, we used a genome-wide association study to identify loci that are associated with PID, and found evidence for the colocalization of—and interplay between—novel high-penetrance monogenic variants and common variants (at the PTPN2and SOCS1loci). This begins to explain the contribution of common variants to the variable penetrance and phenotypic complexity that are observed in PID. Thus, using a cohort-based whole-genome-sequencing approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans.

Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved challenging1. Atlantic subduction zones are a valuable endmember when studying this deep water cycle because hydration in Atlantic lithosphere, produced by slow spreading, is expected to be highly non-uniform2. Here, as part of a multi-disciplinary project in the Lesser Antilles volcanic arc3, we studied boron trace element and isotopic fingerprints of melt inclusions. These reveal that serpentine—that is, hydrated mantle rather than crust or sediments—is a dominant supplier of subducted water to the central arc. This serpentine is most likely to reside in a set of major fracture zones subducted beneath the central arc over approximately the past ten million years. The current dehydration of these fracture zones coincides with the current locations of the highest rates of earthquakes and prominent low shear velocities, whereas the preceding history of dehydration is consistent with the locations of higher volcanic productivity and thicker arc crust. These combined geochemical and geophysical data indicate that the structure and hydration of the subducted plate are directly connected to the evolution of the arc and its associated seismic and volcanic hazards.

Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1–4. Radioactive molecules—in which one or more of the atoms possesses a radioactive nucleus—can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7–9in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research.