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Freshwater ecosystems are highly biodiverse1and important for livelihoods and economic development2, but are under substantial stress3. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods4,5are used to guide environmental policy6and conservation prioritization7, whereas recent proposals for target setting in freshwaters use abiotic factors8, 9, 10, 11, 12–13. However, there is evidence14, 15, 16–17that such data are insufficient to represent the needs of freshwater species and achieve biodiversity goals18,19. Here we present the results of a multi-taxon global freshwater fauna assessment for The IUCN Red List of Threatened Species covering 23,496 decapod crustaceans, fishes and odonates, finding that one-quarter are threatened with extinction. Prevalent threats include pollution, dams and water extraction, agriculture and invasive species, with overharvesting also driving extinctions. We also examined the degree of surrogacy of both threatened tetrapods and freshwater abiotic factors (water stress and nitrogen) for threatened freshwater species. Threatened tetrapods are good surrogates when prioritizing sites to maximize rarity-weighted richness, but poorer when prioritizing based on the most range-restricted species. However, they are much better surrogates than abiotic factors, which perform worse than random. Thus, although global priority regions identified for tetrapod conservation are broadly reflective of those for freshwater faunas, given differences in key threats and habitats, meeting the needs of tetrapods cannot be assumed sufficient to conserve freshwater species at local scales.

Undesired coupling to the surrounding environment destroys long-range correlations in quantum processors and hinders coherent evolution in the nominally available computational space. This noise is an outstanding challenge when leveraging the computation power of near-term quantum processors1. It has been shown that benchmarking random circuit sampling with cross-entropy benchmarking can provide an estimate of the effective size of the Hilbert space coherently available2–8. Nevertheless, quantum algorithms’ outputs can be trivialized by noise, making them susceptible to classical computation spoofing. Here, by implementing an algorithm for random circuit sampling, we demonstrate experimentally that two phase transitions are observable with cross-entropy benchmarking, which we explain theoretically with a statistical model. The first is a dynamical transition as a function of the number of cycles and is the continuation of the anti-concentration point in the noiseless case. The second is a quantum phase transition controlled by the error per cycle; to identify it analytically and experimentally, we create a weak-link model, which allows us to vary the strength of the noise versus coherent evolution. Furthermore, by presenting a random circuit sampling experiment in the weak-noise phase with 67 qubits at 32 cycles, we demonstrate that the computational cost of our experiment is beyond the capabilities of existing classical supercomputers. Our experimental and theoretical work establishes the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors.

Mountain uplift and erosion have regulated the balance of carbon between Earth’s interior and atmosphere, where prior focus has been placed on the role of silicate mineral weathering in CO2drawdown and its contribution to the stability of Earth’s climate in a habitable state1–5. However, weathering can also release CO2as rock organic carbon (OCpetro) is oxidized at the near surface6,7; this important geological CO2flux has remained poorly constrained3,8. We use the trace element rhenium in combination with a spatial extrapolation model to quantify this flux across global river catchments3,9. We find a CO2release of 68−6+18megatons of carbon annually from weathering of OCpetroin near-surface rocks, rivalling or even exceeding the CO2drawdown by silicate weathering at the global scale10. Hotspots of CO2release are found in mountain ranges with high uplift rates exposing fine-grained sedimentary rock, such as the eastern Himalayas, the Rocky Mountains and the Andes. Our results demonstrate that OCpetrois far from inert and causes weathering in regions to be net sources or sinks of CO2. This raises questions, not yet fully studied, as to how erosion and weathering drive the long-term carbon cycle and contribute to the fine balance of carbon fluxes between the atmosphere, biosphere and lithosphere2,11.

Systematic assessments of species extinction risk at regular intervals are necessary for informing conservation action1,2. Ongoing developments in taxonomy, threatening processes and research further underscore the need for reassessment3,4. Here we report the findings of the second Global Amphibian Assessment, evaluating 8,011 species for the International Union for Conservation of Nature Red List of Threatened Species. We find that amphibians are the most threatened vertebrate class (40.7% of species are globally threatened). The updated Red List Index shows that the status of amphibians is deteriorating globally, particularly for salamanders and in the Neotropics. Disease and habitat loss drove 91% of status deteriorations between 1980 and 2004. Ongoing and projected climate change effects are now of increasing concern, driving 39% of status deteriorations since 2004, followed by habitat loss (37%). Although signs of species recoveries incentivize immediate conservation action, scaled-up investment is urgently needed to reverse the current trends.

Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2–9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.

Diffuse large B cell lymphoma (DLBCL) is the most common B cell non-Hodgkin lymphoma and remains incurable in around 40% of patients. Efforts to sequence the coding genome identified several genes and pathways that are altered in this disease, including potential therapeutic targets1–5. However, the non-coding genome of DLBCL remains largely unexplored. Here we show that active super-enhancers are highly and specifically hypermutated in 92% of samples from individuals with DLBCL, display signatures of activation-induced cytidine deaminase activity, and are linked to genes that encode B cell developmental regulators and oncogenes. As evidence of oncogenic relevance, we show that the hypermutated super-enhancers linked to the BCL6, BCL2and CXCR4proto-oncogenes prevent the binding and transcriptional downregulation of the corresponding target gene by transcriptional repressors, including BLIMP1 (targeting BCL6) and the steroid receptor NR3C1 (targeting BCL2and CXCR4). Genetic correction of selected mutations restored repressor DNA binding, downregulated target gene expression and led to the counter-selection of cells containing corrected alleles, indicating an oncogenic dependency on the super-enhancer mutations. This pervasive super-enhancer mutational mechanism reveals a major set of genetic lesions deregulating gene expression, which expands the involvement of known oncogenes in DLBCL pathogenesis and identifies new deregulated gene targets of therapeutic relevance.

Comprehensive assessments of species’ extinction risks have documented the extinction crisis1and underpinned strategies for reducing those risks2. Global assessments reveal that, among tetrapods, 40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction3. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods4–7. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs6. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened—confirming a previous extrapolation8and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods—agriculture, logging, urban development and invasive species—although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles—including most species of crocodiles and turtles—require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.

A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1–4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10−4rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6and paves the way to study new quantum materials with superconducting qubits.

Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis1–3. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate4,5. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor—which binds to the same site as citrate—arrests the transport cycle of NaCT. The NaCT–inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity. Finally, the NaCT structures provide a framework for understanding how various mutations abolish the transport activity of NaCT in the brain and thereby cause epilepsy associated with mutations in SLC13A5in newborns (which is known as SLC13A5-epilepsy)6–8.

The manipulation of quantum states of light1holds the potential to enhance searches for fundamental physics. Only recently has the maturation of quantum squeezing technology coincided with the emergence of fundamental physics searches that are limited by quantum uncertainty2,3. In particular, the quantum chromodynamics axion provides a possible solution to two of the greatest outstanding problems in fundamental physics: the strong-CP (charge–parity) problem of quantum chromodynamics4and the unknown nature of dark matter5–7. In dark matter axion searches, quantum uncertainty manifests as a fundamental noise source, limiting the measurement of the quadrature observables used for detection. Few dark matter searches have approached this limit3,8, and until now none has exceeded it. Here we use vacuum squeezing to circumvent the quantum limit in a search for dark matter. By preparing a microwave-frequency electromagnetic field in a squeezed state and near-noiselessly reading out only the squeezed quadrature9, we double the search rate for axions over a mass range favoured by some recent theoretical projections10,11. We find no evidence of dark matter within the axion rest energy windows of 16.96–17.12 and 17.14–17.28 microelectronvolts. Breaking through the quantum limit invites an era of fundamental physics searches in which noise reduction techniques yield unbounded benefit compared with the diminishing returns of approaching the quantum limit.

Malaria caused by Plasmodium falciparumremains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparumparasites2, we identify P. falciparumglutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant—but not those who are susceptible—to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.

Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth’s surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth’s deep mantle and shallow crustal reservoirs, as well as Earth’s oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108and 1.3 × 1010moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth’s deep mantle than previously estimated.

The work of Berezinskii, Kosterlitz and Thouless in the 1970s1,2revealed exotic phases of matter governed by the topological properties of low-dimensional materials such as thin films of superfluids and superconductors. A hallmark of this phenomenon is the appearance and interaction of vortices and antivortices in an angular degree of freedom—typified by the classical XY model—owing to thermal fluctuations. In the two-dimensional Ising model this angular degree of freedom is absent in the classical case, but with the addition of a transverse field it can emerge from the interplay between frustration and quantum fluctuations. Consequently, a Kosterlitz–Thouless phase transition has been predicted in the quantum system—the two-dimensional transverse-field Ising model—by theory and simulation3–5. Here we demonstrate a large-scale quantum simulation of this phenomenon in a network of 1,800 in situ programmable superconducting niobium flux qubits whose pairwise couplings are arranged in a fully frustrated square-octagonal lattice. Essential to the critical behaviour, we observe the emergence of a complex order parameter with continuous rotational symmetry, and the onset of quasi-long-range order as the system approaches a critical temperature. We describe and use a simple approach to statistical estimation with an annealing-based quantum processor that performs Monte Carlo sampling in a chain of reverse quantum annealing protocols. Observations are consistent with classical simulations across a range of Hamiltonian parameters. We anticipate that our approach of using a quantum processor as a programmable magnetic lattice will find widespread use in the simulation and development of exotic materials. A large-scale programmable quantum simulation is described, using a D-Wave quantum processor to simulate a two-dimensional magnetic lattice in the vicinity of a topological phase transition.

Letter to the Editor

Embryonic stem (ES) cells, the totipotent outgrowths of bias-tocysts1,2, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages3–9. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts1,2,10or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources5,11,12; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in Ml myeloid leukaemic cells and which we have recently purified, cloned and characterized13–18. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.

ALTHOUGH some of the first observations localizing the site of protein biosynthesis to microsomes were made with Tetrahymena1, interest in protozoa has generally been overshadowed by that shown for bacteria, yeast or rat liver, as appropriate cells in which to study the mechanisms of protein synthesis. None the less, the possibilities of variation in the organization of polysomes or in genetic code assignments make these organisms of prime interest. The availability of axenic cultures of Entamoeba histolytica2, an important pathogen for man (amoebic dysentery and amoebic liver abscess), prompted us to study the polyribosomes of this organism. At present, only the trophozoite can be cultivated axenically.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein–Barr virus (EBV), is common in areas of Africa where malaria is holoendemic1. The tumour is characterized by chromosome translocations2; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 143, near the enhancer of the immunoglobulin heavy-chain locus4. Less frequent are translocations of chromosome 8 to the κ light-chain locus of chromosome 2 or to the λ light-chain locus of chromosome 225. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody6. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients7,8. Such patients are subsequently liable to develop lymphomas7,9. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a “reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites”10. We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common11.

MORE than eighty years ago, Ringer1observed that rubidium ions had effects on the frog's ventricles similar to those produced by potassium. Since then these two ions have been found to be very nearly interchangeable in a wide variety of biochemical and physiological processes2.

GOWING and Lange1recently reported that a number of herbicides (chloroalkycarboxylic acids) caused changes in colour in a wide variety of flowers. The changes reported were the disappearance of purple and red and the appearance of orange and yellow. These observations suggest that the synthesis of the carotenoid pigments may not have been affected whereas the synthesis of the anthocyanin pigments could have been inhibited. Described herein are the effects of 2,2-dichloropropionic acid (‘Dalapon’), trichloroacetic acid (TCA), and 2,3-dichloroisobutyric acid (DCIB) on the synthesis of the anthocyanins in the flowers of Salvia splendens cultivar America.

SIMILAR antiphlogistic and biochemical effects of salicylate, adrenocorticotropic hormone (ACTH) and cortisol1have stimulated interest in establishing a possible influence of salicylate on the secretion of adrenocortical hormones in man and experimental animals. Studies in dogs, guinea pigs and rats have shown a stimulatory effect of salicylate on cortisol secretion2. It has been emphasized, however, that these experiments used a dose per unit of body-weight greater than the comparable therapeutic dose in man3,4. Furthermore, an anti-rheumatic effect of salicylate has been demonstrated in a patient whose adrenocortical function had been suppressed by 9-α-fluorohydrocortisone5. In view of this conflicting evidence, the present work was designed to determine whether or not salicylate has a direct stimulatory effect on the adrenal cortex.

RECENT publications1,2reporting the induction of leukæmia in mice by cell-free extracts have reawakened general interest in the role of viruses as oncogenic agents and, as a corollary, in the metabolic alterations induced by these agents. It has been shown in this laboratory that alterations in host cell metabolism induced by virus can be detected very soon after infection3. The current investigation was undertaken to see if analogous effects could be observed in vivo using one of the viruses inducing tumours. The agent investigated here was that described by Friend2as producing a Leukæmia in mice, characterized by splenomegaly and an accumulation in the spleen of stem cells. The basic experiments were performed as follows: 150 mice were infected i.v. with 0.2 ml. of a cell-free filtrate from spleens of mice carrying the infection. 150 control mice received the same amount of cell-free filtrate prepared from normal spleen. Beginning the day after inoculation of the virus, and at the intervals thereafter indicated in Fig. 1, six infected and six control mice were selected at random and given intraperitoneal injection of 5 µc. of phosphorus-32. 3 hr. later the spleens of these animals were removed, weighed, dried in pre-weighed planchets, reweighed, the radioactivity determined, and expressed as c.p.m./mgm. dry tissue. The averaged wet-weights of the spleens from a typical experiment as well as the averaged c.p.m./mgm. dry spleen are given in Fig. 1. As part of the same experiment, on the fifth day some of the control and the infected mice received 300 r. of total body X-irradiation. The results for weight and radioactivity of the spleens of these mice examined on subsequent days are also included in Fig. 1.

A DESIRABLE experimental condition for the study of metabolic effects of viruses on living organisms is that all or nearly all the cells be infected and that they be infected approximately simultaneously so that any metabolic changes can reasonably be expected to take place at about the same time throughout the cell population. This condition can readily be achieved with bacteriophages and their hosts, and a great deal of valuable work has been done with this system1,2. It has been virtually impossible to approximate to the necessary conditions with animal viruses and their intact hosts. The closest approximation has been achieved in the work with eggs; but complications introduced by host influences must be considered. As a result, our knowledge of metabolic changes induced in animal cells by animal viruses is limited. With the present emergence of tissue-culture techniques as an almost standardized procedure and the availability of animal virus suspensions of high titre, it has become feasible to undertake quantitative metabolic studies with animal viruses, and to relate any observed effects with virus growth. The present preliminary report is a summary of work on the effect of Type III poliomyelitis virus (Saukett strain) on some aspects of the metabolism of monkey kidney tissue culture; specifically, the effects of the virus on glycolysis and on the uptake by the tissue of glycine-2-carbon-14.

INFECTION of the Hevea rubber tree by Oidium heveae is common in Malaya but is not regarded as a major pathological problem; in Ceylon, however, the fungus can produce serious loss of crop yields and the problem is of economic importance1. Oidium heveae is most prominent in Malaya at the time of refoliation after ‘wintering’ of the trees, when it may cause a secondary leaf-fall. It is only at this time that Oidium is found on leaves exposed to full sun. Throughout the year it may be found on young plants but only when these are shaded, and then never sufficiently seriously to cause defoliation. A small number of poorly developed colonies of Oidium heveae are usual on the leaves of plants grown in our plant-house2as the glass and framework of the house provide light shade. During the study of the micro-nutrient-deficiency symptoms of Hevea brasiliensis grown in sand culture within this house, a striking relationship between the susceptibility to severe Oidium heveae attack and the zinc status of the plants was noticed. This relationship was not noted for the copper- or molybdenum-deficient plants grown simultaneously and in the same environmental conditions as the zinc-deficient plants. Our observations were thus made on plants grown under glass and were derived from one experiment only; the results, however, were so well marked that their significance should be quickly tested and evaluated in countries where Oidium heveae attack is of major concern.

AMONG the organisms frequently encountered in investigations of freshwater habitats are members of the genus Scenedesmus. Species are delimited on the basis of the size and shape of the cells, as well as position and number of spines, if present. Although Smith1in his monograph of the genus shows some variation in these characters, one can, with some degree of confidence, identify species quite easily.

IN a letter in your last issue (p. 414) upon the vitality of seeds, “N. E. P.” states that Prof. Judd in his address to the Geological Association (I presume he means the Geological Society) was reported to have said: “The botanist cites the germination of seeds, taken from ancient Egyptian tombs, as a striking illustration of how long life may remain dormant in the vegetable world.” This appears to be a remarkable assertion to emanate from such an eminent scientific man as Prof. Judd, for if he really did make this statement one would think he must have some good proof quite incontrovertible. I must admit I am sceptical, and do not place credence in the statements that have been made by certain people, that wheat or barley, which is frequently found in the ancient tombs of Egypt, could possibly germinate after the lapse, say, of 3000 years.

THE association of certain serological types of Bact. coli type I with infantile diarrhœa has been described by many investigators, particularly in Great Britain1–4. Identification of these strains has been based on the serological identification of the somatic O, the surface K and the flagellar H antigens5,6. Kauffmann subdivides the K antigens into three types, capsular A, thermolabile L and B; when heated, the B antigen retains its antibody-binding capacity, but loses its agglutinability.