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A dearth of Mesozoic-aged, three-dimensional fossils hinders understanding of the origin of the distinctive skull and brain of modern (crown) birds1. Here we report Navaornis hestiaegen. et sp. nov., an exquisitely preserved fossil species from the Late Cretaceous of Brazil. The skull of Navaornisis toothless and large-eyed, with a vaulted cranium closely resembling the condition in crown birds; however, phylogenetic analyses recover Navaornisin Enantiornithes, a highly diverse clade of Mesozoic stem birds. Despite an overall geometry quantitatively indistinguishable from crown birds, the skull of Navaornisretains numerous plesiomorphies including a maxilla-dominated rostrum, an akinetic palate, a diapsid temporal configuration, a small cerebellum and a weakly expanded telencephalon. These archaic neurocranial traits are combined with a crown bird-like degree of brain flexion and a bony labyrinth comparable in shape to those of many crown birds but substantially larger. Altogether, the emergent cranial geometry of Navaornisshows an unprecedented degree of similarity between crown birds and enantiornithines, groups last sharing a common ancestor more than 130 million years ago2. Navaornisprovides long-sought insight into the detailed cranial and endocranial morphology of stem birds phylogenetically crownward of Archaeopteryx, clarifying the pattern and timing by which the distinctive neuroanatomy of living birds was assembled.

Endosymbioses have profoundly impacted the evolution of life and continue to shape the ecology of a wide range of species. They give rise to new combinations of biochemical capabilities that promote innovation and diversification1,2. Despite the many examples of known endosymbioses across the tree of life, their de novo emergence is rare and challenging to uncover in retrospect3–5. Here we implant bacteria into the filamentous fungus Rhizopus microsporusto follow the fate of artificially induced endosymbioses. Whereas Escherichia coliimplanted into the cytosol induced septum formation, effectively halting endosymbiogenesis, Mycetohabitans rhizoxinicawas transmitted vertically to the progeny at a low frequency. Continuous positive selection on endosymbiosis mitigated initial fitness constraints by several orders of magnitude upon adaptive evolution. Phenotypic changes were underscored by the accumulation of mutations in the host as the system stabilized. The bacterium produced rhizoxin congeners in its new host, demonstrating the transfer of a metabolic function through induced endosymbiosis. Single-cell implantation thus provides a powerful experimental approach to study critical events at the onset of endosymbiogenesis and opens opportunities for synthetic approaches towards designing endosymbioses with desired traits.

Interpreting diffuse intensities in electron diffraction patterns can be challenging in samples with high atomic-level complexity, as often is the case with multi-principal element alloys. For example, diffuse intensities in electron diffraction patterns from simple face-centred cubic (fcc) and related alloys have been attributed to short-range order1, medium-range order2or a variety of different {111} planar defects, including thin twins3, thin hexagonal close-packed layers4, relrod spiking5and incomplete ABC stacking6. Here we demonstrate that many of these diffuse intensities, including 1⁄3{422} and 1⁄2{311} in ⟨111⟩ and ⟨112⟩ selected area diffraction patterns, respectively, are due to reflections from higher-order Laue zones. We show similar features along many different zone axes in a wide range of simple fcc materials, including CdTe, pure Ni and pure Al. Using electron diffraction theory, we explain these intensities and show that our calculated intensities of projected higher-order Laue zone reflections as a function of deviation from their Bragg conditions match well with the observed intensities, proving that these intensities are universal in these fcc materials. Finally, we provide a framework for determining the nature and location of diffuse intensities that could indicate the presence of short-range order or medium-range order.

Kimberlites are volatile-rich, occasionally diamond-bearing magmas that have erupted explosively at Earth’s surface in the geologic past1–3. These enigmatic magmas, originating from depths exceeding 150 km in Earth’s mantle1, occur in stable cratons and in pulses broadly synchronous with supercontinent cyclicity4. Whether their mobilization is driven by mantle plumes5or by mechanical weakening of cratonic lithosphere4,6remains unclear. Here we show that most kimberlites spanning the past billion years erupted about 30 million years (Myr) after continental breakup, suggesting an association with rifting processes. Our dynamical and analytical models show that physically steep lithosphere–asthenosphere boundaries (LABs) formed during rifting generate convective instabilities in the asthenosphere that slowly migrate many hundreds to thousands of kilometres inboard of rift zones. These instabilities endure many tens of millions of years after continental breakup and destabilize the basal tens of kilometres of the cratonic lithosphere, or keel. Displaced keel is replaced by a hot, upwelling mixture of asthenosphere and recycled volatile-rich keel in the return flow, causing decompressional partial melting. Our calculations show that this process can generate small-volume, low-degree, volatile-rich melts, closely matching the characteristics expected of kimberlites1–3. Together, these results provide a quantitative and mechanistic link between kimberlite episodicity and supercontinent cycles through progressive disruption of cratonic keels.

The bony palate diagnoses the two deepest clades of extant birds: Neognathae and Palaeognathae1–5. Neognaths exhibit unfused palate bones and generally kinetic skulls, whereas palaeognaths possess comparatively rigid skulls with the pterygoid and palatine fused into a single element, a condition long considered ancestral for crown birds (Neornithes)3,5–8. However, fossil evidence of palatal remains from taxa close to the origin of Neornithes is scarce, hindering strong inferences regarding the ancestral condition of the neornithine palate. Here we report a new taxon of toothed Late Cretaceous ornithurine bearing a pterygoid that is remarkably similar to those of the extant neognath clade Galloanserae (waterfowl + landfowl). Janavis finalidens, gen. et sp. nov., is generally similar to the well-known Mesozoic ornithurine Ichthyornisin its overall morphology, although Janavisis much larger and exhibits a substantially greater degree of postcranial pneumaticity. We recovered Janavisas the first-known well-represented member of Ichthyornithes other than Ichthyornis, clearly substantiating the persistence of the clade into the latest Cretaceous9. Janavisconfirms the presence of an anatomically neognathous palate in at least some Mesozoic non-crown ornithurines10–12, suggesting that pterygoids similar to those of extant Galloanserae may be plesiomorphic for crown birds. Our results, combined with recent evidence on the ichthyornithine palatine12, overturn longstanding assumptions about the ancestral crown bird palate, and should prompt reevaluation of the purported galloanseran affinities of several bizarre early Cenozoic groups such as the ‘pseudotoothed birds’ (Pelagornithidae)13–15.

CD4+T cell differentiation requires metabolic reprogramming to fulfil the bioenergetic demands of proliferation and effector function, and enforce specific transcriptional programmes1–3. Mitochondrial membrane dynamics sustains mitochondrial processes4, including respiration and tricarboxylic acid (TCA) cycle metabolism5, but whether mitochondrial membrane remodelling orchestrates CD4+T cell differentiation remains unclear. Here we show that unlike other CD4+T cell subsets, T helper 17 (TH17) cells have fused mitochondria with tight cristae. T cell-specific deletion of optic atrophy 1 (OPA1), which regulates inner mitochondrial membrane fusion and cristae morphology6, revealed that TH17 cells require OPA1 for its control of the TCA cycle, rather than respiration. OPA1 deletion amplifies glutamine oxidation, leading to impaired NADH/NAD+balance and accumulation of TCA cycle metabolites and 2-hydroxyglutarate—a metabolite that influences the epigenetic landscape5,7. Our multi-omics approach revealed that the serine/threonine kinase liver-associated kinase B1 (LKB1) couples mitochondrial function to cytokine expression in TH17 cells by regulating TCA cycle metabolism and transcriptional remodelling. Mitochondrial membrane disruption activates LKB1, which restrains IL-17 expression. LKB1 deletion restores IL-17 expression in TH17 cells with disrupted mitochondrial membranes, rectifying aberrant TCA cycle glutamine flux, balancing NADH/NAD+and preventing 2-hydroxyglutarate production from the promiscuous activity of the serine biosynthesis enzyme phosphoglycerate dehydrogenase (PHGDH). These findings identify OPA1 as a major determinant of TH17 cell function, and uncover LKB1 as a sensor linking mitochondrial cues to effector programmes in TH17 cells.

Global integrated reporting is essential if the planet is to achieve net-zero emissions.

Although circumstantial evidence supports enhanced Toll-like receptor 7 (TLR7) signalling as a mechanism of human systemic autoimmune disease1–7, evidence of lupus-causing TLR7gene variants is lacking. Here we describe human systemic lupus erythematosus caused by a TLR7gain-of-function variant. TLR7 is a sensor of viral RNA8,9and binds to guanosine10–12. We identified a de novo, previously undescribed missense TLR7Y264Hvariant in a child with severe lupus and additional variants in other patients with lupus. The TLR7Y264Hvariant selectively increased sensing of guanosine and 2',3'-cGMP10–12, and was sufficient to cause lupus when introduced into mice. We show that enhanced TLR7 signalling drives aberrant survival of B cell receptor (BCR)-activated B cells, and in a cell-intrinsic manner, accumulation of CD11c+age-associated B cells and germinal centre B cells. Follicular and extrafollicular helper T cells were also increased but these phenotypes were cell-extrinsic. Deficiency of MyD88 (an adaptor protein downstream of TLR7) rescued autoimmunity, aberrant B cell survival, and all cellular and serological phenotypes. Despite prominent spontaneous germinal-centre formation in Tlr7Y264Hmice, autoimmunity was not ameliorated by germinal-centre deficiency, suggesting an extrafollicular origin of pathogenic B cells. We establish the importance of TLR7 and guanosine-containing self-ligands for human lupus pathogenesis, which paves the way for therapeutic TLR7 or MyD88 inhibition.

About half of the anthropogenic CO2emissions remain in the atmosphere and half are taken up by the land and ocean1. If the carbon uptake by land and ocean sinks becomes less efficient, for example, owing to warming oceans2or thawing permafrost3, a larger fraction of anthropogenic emissions will remain in the atmosphere, accelerating climate change. Changes in the efficiency of the carbon sinks can be estimated indirectly by analysing trends in the airborne fraction, that is, the ratio between the atmospheric growth rate and anthropogenic emissions of CO2(refs. 4–10). However, current studies yield conflicting results about trends in the airborne fraction, with emissions related to land use and land cover change (LULCC) contributing the largest source of uncertainty7,11,12. Here we construct a LULCC emissions dataset using visibility data in key deforestation zones. These visibility observations are a proxy for fire emissions13,14, which are — in turn — related to LULCC15,16. Although indirect, this provides a long-term consistent dataset of LULCC emissions, showing that tropical deforestation emissions increased substantially (0.16 Pg C decade−1) since the start of CO2concentration measurements in 1958. So far, these emissions were thought to be relatively stable, leading to an increasing airborne fraction4,5. Our results, however, indicate that the CO2airborne fraction has decreased by 0.014 ± 0.010 decade−1since 1959. This suggests that the combined land–ocean sink has been able to grow at least as fast as anthropogenic emissions.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3through two different implosion concepts4–7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

The output of the retina is organized into many detector grids, called ‘mosaics’, that signal different features of visual scenes to the brain1–4. Each mosaic comprises a single type of retinal ganglion cell (RGC), whose receptive fields tile visual space. Many mosaics arise as pairs, signalling increments (ON) and decrements (OFF), respectively, of a particular visual feature5. Here we use a model of efficient coding6to determine how such mosaic pairs should be arranged to optimize the encoding of natural scenes. We find that information is maximized when these mosaic pairs are anti-aligned, meaning that the distances between the receptive field centres across mosaics are greater than expected by chance. We tested this prediction across multiple receptive field mosaics acquired using large-scale measurements of the light responses of rat and primate RGCs. ON and OFF RGC pairs with similar feature selectivity had anti-aligned receptive field mosaics, consistent with this prediction. ON and OFF RGC types that encode distinct features have independent mosaics. These results extend efficient coding theory beyond individual cells to predict how populations of diverse types of RGC are spatially arranged.

Our understanding of the earliest stages of crown bird evolution is hindered by an exceedingly sparse avian fossil record from the Mesozoic era. The most ancient phylogenetic divergences among crown birds are known to have occurred in the Cretaceous period1–3, but stem-lineage representatives of the deepest subclades of crown birds—Palaeognathae (ostriches and kin), Galloanserae (landfowl and waterfowl) and Neoaves (all other extant birds)—are unknown from the Mesozoic era. As a result, key questions related to the ecology4,5, biogeography3,6,7and divergence times1,8–10of ancestral crown birds remain unanswered. Here we report a new Mesozoic fossil that occupies a position close to the last common ancestor of Galloanserae and fills a key phylogenetic gap in the early evolutionary history of crown birds10,11. Asteriornis maastrichtensis, gen. et sp. nov., from the Maastrichtian age of Belgium (66.8–66.7 million years ago), is represented by a nearly complete, three-dimensionally preserved skull and associated postcranial elements. The fossil represents one of the only well-supported crown birds from the Mesozoic era12, and is the first Mesozoic crown bird with well-represented cranial remains. Asteriornis maastrichtensisexhibits a previously undocumented combination of galliform (landfowl)-like and anseriform (waterfowl)-like features, and its presence alongside a previously reported Ichthyornis-like taxon from the same locality13provides direct evidence of the co-occurrence of crown birds and avialan stem birds. Its occurrence in the Northern Hemisphere challenges biogeographical hypotheses of a Gondwanan origin of crown birds3, and its relatively small size and possible littoral ecology may corroborate proposed ecological filters4,5,9that influenced the persistence of crown birds through the end-Cretaceous mass extinction.

Immediately after birth, newborn babies experience rapid colonization by microorganisms from their mothers and the surrounding environment1. Diseases in childhood and later in life are potentially mediated by the perturbation of the colonization of the infant gut microbiota2. However, the effects of delivery via caesarean section on the earliest stages of the acquisition and development of the gut microbiota, during the neonatal period (≤1 month), remain controversial3,4. Here we report the disrupted transmission of maternal Bacteroidesstrains, and high-level colonization by opportunistic pathogens associated with the hospital environment (including Enterococcus, Enterobacterand Klebsiellaspecies), in babies delivered by caesarean section. These effects were also seen, to a lesser extent, in vaginally delivered babies whose mothers underwent antibiotic prophylaxis and in babies who were not breastfed during the neonatal period. We applied longitudinal sampling and whole-genome shotgun metagenomic analysis to 1,679 gut microbiota samples (taken at several time points during the neonatal period, and in infancy) from 596 full-term babies born in UK hospitals; for a subset of these babies, we collected additional matched samples from mothers (175 mothers paired with 178 babies). This analysis demonstrates that the mode of delivery is a significant factor that affects the composition of the gut microbiota throughout the neonatal period, and into infancy. Matched large-scale culturing and whole-genome sequencing of over 800 bacterial strains from these babies identified virulence factors and clinically relevant antimicrobial resistance in opportunistic pathogens that may predispose individuals to opportunistic infections. Our findings highlight the critical role of the local environment in establishing the gut microbiota in very early life, and identify colonization with antimicrobial-resistance-containing opportunistic pathogens as a previously underappreciated risk factor in hospital births.

Research findings on the relationship between climate and conflict are diverse and contested. Here we assess the current understanding of the relationship between climate and conflict, based on the structured judgments of experts from diverse disciplines. These experts agree that climate has affected organized armed conflict within countries. However, other drivers, such as low socioeconomic development and low capabilities of the state, are judged to be substantially more influential, and the mechanisms of climate–conflict linkages remain a key uncertainty. Intensifying climate change is estimated to increase future risks of conflict. Climate has affected organized armed conflict within countries, and intensifying climate change is estimated to increase future risks of conflict, although other drivers are substantially more influential and the mechanisms of climate–conflict linkages remain uncertain.

The skull of living birds is greatly modified from the condition found in their dinosaurian antecedents. Bird skulls have an enlarged, toothless premaxillary beak and an intricate kinetic system that includes a mobile palate and jaw suspensorium. The expanded avian neurocranium protects an enlarged brain and is flanked by reduced jaw adductor muscles. However, the order of appearance of these features and the nature of their earliest manifestations remain unknown. The Late Cretaceous toothed bird Ichthyornis disparsits in a pivotal phylogenetic position outside living groups: it is close to the extant avian radiation but retains numerous ancestral characters1–3. Although its evolutionary importance continues to be affirmed3–8, no substantial new cranial material of I. disparhas been described beyond incomplete remains recovered in the 1870s. Jurassic and Cretaceous Lagerstätten have yielded important avialan fossils, but their skulls are typically crushed and distorted9. Here we report four three-dimensionally preserved specimens of I. dispar—including an unusually complete skull—as well as two previously overlooked elements from the Yale Peabody Museum holotype, YPM 1450. We used these specimens to generate a nearly complete three-dimensional reconstruction of the I. disparskull using high-resolution computed tomography. Our study reveals that I. disparhad a transitional beak—small, lacking a palatal shelf and restricted to the tips of the jaws—coupled with a kinetic system similar to that of living birds. The feeding apparatus of extant birds therefore evolved earlier than previously thought and its components were functionally and developmentally coordinated. The brain was relatively modern, but the temporal region was unexpectedly dinosaurian: it retained a large adductor chamber bounded dorsally by substantial bony remnants of the ancestral reptilian upper temporal fenestra. This combination of features documents that important attributes of the avian brain and palate evolved before the reduction of jaw musculature and the full transformation of the beak.

DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation. Here we demonstrate that human cells have a previously unrecognized signalling mechanism for sensing damage induced by alkylation. We find that the alkylation repair complex ASCC (activating signal cointegrator complex) relocalizes to distinct nuclear foci specifically upon exposure of cells to alkylating agents. These foci associate with alkylated nucleotides, and coincide spatially with elongating RNA polymerase II and splicing components. Proper recruitment of the repair complex requires recognition of K63-linked polyubiquitin by the CUE (coupling of ubiquitin conjugation to ER degradation) domain of the subunit ASCC2. Loss of this subunit impedes alkylation adduct repair kinetics and increases sensitivity to alkylating agents, but not other forms of DNA damage. We identify RING finger protein 113A (RNF113A) as the E3 ligase responsible for upstream ubiquitin signalling in the ASCC pathway. Cells from patients with X-linked trichothiodystrophy, which harbour a mutation in RNF113A, are defective in ASCC foci formation and are hypersensitive to alkylating agents. Together, our work reveals a previously unrecognized ubiquitin-dependent pathway induced specifically to repair alkylation damage, shedding light on the molecular mechanism of X-linked trichothiodystrophy.

Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with metastatic melanoma. Unfortunately, the efficacy of these treatments is often countered by the acquisition of drug resistance. Here we investigated the molecular mechanisms that underlie acquired resistance to BRAFi and to the combined therapy. Consistent with previous studies, we show that resistance to BRAFi is mediated by ERK pathway reactivation. Resistance to the combined therapy, however, is mediated by mechanisms independent of reactivation of ERK in many resistant cell lines and clinical samples. p21-activated kinases (PAKs) become activated in cells with acquired drug resistance and have a pivotal role in mediating resistance. Our screening, using a reverse-phase protein array, revealed distinct mechanisms by which PAKs mediate resistance to BRAFi and the combined therapy. In BRAFi-resistant cells, PAKs phosphorylate CRAF and MEK to reactivate ERK. In cells that are resistant to the combined therapy, PAKs regulate JNK and β-catenin phosphorylation and mTOR pathway activation, and inhibit apoptosis, thereby bypassing ERK. Together, our results provide insights into the molecular mechanisms underlying acquired drug resistance to current targeted therapies, and may help to direct novel drug development efforts to overcome acquired drug resistance.

Melanoma of the skin is a common cancer only in Europeans, whereas it arises in internal body surfaces (mucosal sites) and on the hands and feet (acral sites) in people throughout the world. Here we report analysis of whole-genome sequences from cutaneous, acral and mucosal subtypes of melanoma. The heavily mutated landscape of coding and non-coding mutations in cutaneous melanoma resolved novel signatures of mutagenesis attributable to ultraviolet radiation. However, acral and mucosal melanomas were dominated by structural changes and mutation signatures of unknown aetiology, not previously identified in melanoma. The number of genes affected by recurrent mutations disrupting non-coding sequences was similar to that affected by recurrent mutations to coding sequences. Significantly mutated genes included BRAF, CDKN2A, NRAS and TP53 in cutaneous melanoma, BRAF, NRAS and NF1 in acral melanoma and SF3B1 in mucosal melanoma. Mutations affecting the TERT promoter were the most frequent of all; however, neither they nor ATRX mutations, which correlate with alternative telomere lengthening, were associated with greater telomere length. Most melanomas had potentially actionable mutations, most in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways. The whole-genome mutation landscape of melanoma reveals diverse carcinogenic processes across its subtypes, some unrelated to sun exposure, and extends potential involvement of the non-coding genome in its pathogenesis.

The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.

Demographers must work together so that officials can produce numbers all can trust.

The fossil record traces the origin of the modern bird skull as birds evolved from their dinosaurian ancestors. Now the discovery of a bizarre fossil reveals a surprising diversion during this process of facial transformation.

A range of techniques, including high-speed photography and image intensification, are used to study the collapse of cavities by shock waves. Of particular interest are the shape changes of the cavity and the production of luminescence at 'hot spots' in the gas. The relevance of the research to cavitation damage, explosive initiation, and medical uses of acoustic waves is discussed.

Recent work on superstring theories has prompted interest in ‘shadow matter’, exotic matter which interacts only gravitationally with normal matter. Green and Schwarz1,2have shown that the only anomaly-free type 1 superstring theories are those with gauge group SO32. Gross et al.3have constructed a superstring theory resulting in a gauge group E8×E8. Such a theory could result, at low energies, in the existence of two sectors: an ‘observed’ sector associated with all familiar particles and interactions, and another ‘hidden’ sector, previously discussed in various low-energy super-symmetry models (see, for example, ref. 4 and references therein). The particles of the hidden E8sector couple only through gravitational interactions with ordinary matter. Kolb, Seckel and Turner5have explored some of the astrophysical and cosmological implications of the existence of such shadow matter. We demonstrate here that if, in the early Universe, an inflationary phase6–8is associated with the breaking of one of the symmetries in the E8×E8theory, this strongly constrains the physics of both sectors if shadow matter is to be the missing mass in the Universe.

The lifetimes of both positive and negative relativistic (γ = 29.33) muons have been measured in the CERN Muon Storage Ring with the results τ+= 64.419 (58) µs, τ−= 64.368 (29) µs The value for positive muons is in accordance with special relativity and the measured lifetime at rest: the Einstein time dilation factor agrees with experiment with a fractional error of 2×10−3at 95% confidence. Assuming special relativity, the mean proper lifetime for μ−is found to be τ0−= 2.1948(10) µs the most accurate value reported to date. The agreement of this value with previously measured values of τ0+confirms CPT invariance for the weak interaction in muon decay.

The nonapeptide bradykinin (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) and the decapeptide kallidin (Lys-bradykinin) are released during tissue damage and cause vasodilation, increased vascular permeability, altered gut motility and pain1–4. Accordingly, they have been implicated in several pathological processes, including carcinoid tumours and postgastrectomy dumping syndrome. Symptoms of these two syndromes include flushing, light-headedness, headaches and diarrhoea5–9. Increased blood levels of bradykinin5,7–9and kallikrein9, the bradykinin-releasing enzyme, have been noted in such patients and may explain these symptoms. However, while kinin-forming and -destroying activity has been noted in the gut10–14, bradykinin itself has not been directly demonstrated. Moreover, while bradykinin influences gut motility and electrical activity15,25,26, most clinical diarrhoea is due to ion and fluid secretion into the gut lumen rather than altered motility16. We describe here specific bradykinin receptors in intestinal mucosa and muscle. We also report that bradykinin and several peptide analogues potently stimulate chloride secretion in the gut with a peptide specificity indicative of specific receptor interactions. These findings suggest a physiological and a pathological role for kinins in intestinal function. Throughout this report the term kinin will indicate both bradykinin and kallidin activities since in several cases the true active form is unknown.

Controlled high speed fracture of conducting solids can provide a feasible method of breaking alternating currents at zero current.

A key element in the absorption of salt and water by various epithelia is the presence, in the apical or brush border membrane, of a mechanism for directly coupling the inward movements of Na+and Cl−(ref. 1). In this way the downhill gradient for Na+from lumen to cell, which is maintained by the cell's Na+/K+pump, can provide the energy for cellular accumulation and transepithelial transport of Cl−. A requirement for K+at the serosal surface of the epithelium has long been accepted as essential to the operation of the Na+/K+pump and therefore to salt absorption. Until very recently, however, the effect of luminal K+on NaCl absorption has not been explored. We show here that luminal K+stimulates NaCl absorption in the intestine of a marine teleost, the winter flounder, Pseudopleuronectes americanus. Furthermore, K+uptake across the brush border membrane depends on the presence of both Na+and Cl−in the bathing medium and is inhibited by furosemide, which also inhibits the coupled uptake of Na+and Cl−(ref. 2). Thus, flounder intestine seems to have a Na+−K+−Cl−co-transport system similar to that demonstrated in erythrocytes3–5, cultured tumour cells6, cultured kidney cells7and squid giant axon8. Electrophysiological studies of the thick ascending limb of Henlé's loop in mammalian kidney9and the diluting segment in amphibian kidney10also indicate that luminal K+is required for salt absorption. Co-transport of Na+, K+and Cl−may therefore be characteristic of a variety of cells and tissues, including salt-absorbing epithelia.

Acyclovir (9-[2-hydroxyethoxymethyl]guanine or ACV) is a nucleoside analogue with considerable potential for the treatment of herpes simplex virus (HSV) infections in man1,2. Two virus-coded enzymes are important in the mechanism of action of this drug: thymidine kinase (TK) which initiates its activation by converting it to the monophosphate3and DNA polymerase whose action is inhibited by ACV triphosphate4. Changes in either gene may confer resistance5–7, but all reported mutations in the TK gene have resulted in failure of the resistant virus to induce appreciable levels of the enzyme. Such TK−mutants arise readily in tissue culture systems8,9where the enzyme is non-essential for virus replication10, but in animals they show considerably reduced pathogenicity and neurovirulence7,11–14. We now describe the isolation of a resistant mutant which induces a TK of altered substrate specificity and we show that this virus retains pathogenicity for mice with only a slight attenuation of neurovirulence.

An unexpected phenomenon emerges from the model equations governing single-mode homogeneously broadened lasers. We have identified conditions analytically under which the laser output can be made to switch from low to high (or high to low) intensity through a small variation in the parameters of the medium, for example, the pump rate. Our results are distinct from those involving transitions at a 'second laser threshold' to regions of testability, multistability and chaos1,2. The transition described here arises from the inclusion in our analysis of fluctuating forces in the medium3. A similar scheme can be used to describe a familiar transition in physics—the Curie–Weiss ferromagnetic transition.

A major objective in total rock Rb–Sr isotope studies of relatively homogeneous igneous or high-grade metamorphic gneisses is to obtain as wide a range of 87Rb/86Sr ratios as possible, so that the resultant isochron may be well defined1. This is often achieved by collecting samples at some distance from each other. Recent studies2–6have shown that primary Rb–Sr isotopic systems can be profoundly disturbed, and even completely reset, in response even to low-grade secondary deformations and/or mineral alterations, and in three cases2–4isochron diagrams based on regionally collected samples have been shown to yield linear arrays corresponding to apparent ages intermediate between the true ages of the primary and secondary events. The evidence we present here shows that it is also possible for well defined intermediate isochron apparent ages to be produced where this sampling technique is used on rock suites which show evidence of only minor secondary alteration effects. An isochron so produced is geologically meaningless, that is, the apparent age is unrelated to any geological event.

The cosmic X-ray background has been found to be anisotropic. It is interpreted as being made up of two components: an isotropic background, possibly of extragalactic origin, and an anomalous emission, perhaps located within the Galaxy.

ACCIDENTAL contamination is an abiding anxiety for all who work with scrapie agent and the possibility of false positive results is well recognized1. Few, however, have sought to evaluate this risk experimentally. In the light of the report by Morris et al.2, we have examined the role of close physical contact and animal house fomites (sawdust, droppings, scrapers, and so on) in the establishment of the disease in normal animals.

‘ICRF 159’, a new cytostatic agent, blocks the entry of cultured human lymphocytes into mitosis and arrests dividing cells in prophase and early metaphase.

MANY of the properties of metals are satisfactorily accounted for in terms of relatively simple models. The cohesive energy even of pure metals presents problems, however, and any experimental evidence that helps with an understanding of the behaviour of the conduction electrons is valuable.

LYMPHOID cells from a highly inbred parental strain of rat injected into F1hybrids derived from that strain and another inbred strain provoke a reaction, characterized among other manifestations by a hyperplasia of the recipients' spleen and other lymphoid tissues1. A striking splenic enlargement can also be produced in the chick embryo by intravenous injection of adult chicken spleen cells, or peripheral white blood cells2. The splenomegaly in both instances is due to an attack by the inoculated immunologically competent cells directed against a host incapable of reacting against them3–5. The splenomegaly is part of a more generalized graft versus host (GVH) reaction and reduction of the degree of splenomegaly is therefore a measure of the inhibition of the GVH reaction6,7.

SOME of the morphological changes in the brain which are found both in the light and electron microscopes in the relatively young mouse or rat with scrapie are also present in the normal animal in old age1. These include enlargement and increased aurophilia of astroglia, presence of amyloid bodies, occurrence of closely orientated tubules within axis cylinders, and the occurrence of intranuclear inclusion bodies2. Recently, too, plaques resembling those found in senile brains have been reported in the scrapie mouse (H. Fraser and M. Bruce, demonstration at the Pathological Society of Great Britain and Ireland, July 1972). It would appear that the disease process has brought forward in time many of the features normally found in old age. Similar ageing changes have not, however, been reported in other organs, perhaps because no study has been specifically directed towards them.

IMMUNOCHEMICAL techniques involving humoral antibody have long been used in elucidating the structural relationships of proteins and small antigenic molecules. Development of a quantitative technique for sensitized lymphocytes with high discriminatory capacity in respect to closely related antigens has made it possible to use these cells to assess structural requirements for antigenicity1–3. When sensitized lymphocytes are brought into contact with specific antigen a material is liberated which lowers the electrophoretic mobility of normal guinea-pig macrophages. The change in cell mobility can be measured in a Zeiss cytopherometer. This assay has been used in the study of several experimental and human autoimmune diseases to give an accurate and quantitative assessment of the cellular immune response1,4.

RESEARCH into scrapie, an enigma of veterinary medicine which may embody principles of considerable interest for human disease, commonly involves demonstration of agent activity or its titration. A great step forward was made by Chandler1when he showed the disease could be produced in mice, and biological titration in these animals is currently widely employed. This takes 6–8 months. From a recent study of multiple sclerosis, with which scrapie has been linked2, we were led into an immunological study of scrapie itself. We found that brain or spleen from a scrapie mouse when injected into a guinea-pig (adult Hartley) led to the appearance of blood lymphocytes which were more highly sensitized to scrapie brain or spleen than to normal brain or spleen.

BELOUSOV1reported that the ratio [Ce(IV)]/[Ce(III)] undergoes repeated temporal oscillations in a stirred sulphuric acid solution containing bromate ion and malonic acid. Busse2and Zaikin and Zhabotinsky3reported that spatial bands of alternating oxidizing and reducing character propagated through an unstirred solution if it were initially subject to a concentration gradient. Existence of these bands was demonstrated by the redox indicator ferroin (the 1,10-phenanthroline complex of ferrous ion), and bands could be generated in the absence of cerium ions if indicator were present, because the ferroin indicator itself serves as an oxidation-reduction couple in the absence of cerium ions.

INTEREST in leptonic resonances has been generated recently by both experimental and theoretical investigations1,2. Anomalies in bubble chamber data have indicated a possible π±μŦ resonance of mass ≈ 429 MeV and width <15 MeV in the final state of both vp→πμp interactions and K0L→πμv decays1. Theoretical estimates of the effects of such a resonance have been made (S. C. Chhajlany and S. Pakvasa, unpublished), and it has been suggested (S. Barshay, unpublished) that the low measured limit on the rate for K0L→μ+μ−(refs. 3 and 4) could be a consequence of an interfering πμ intermediate state. Studies of finite quantum field theory with an indefinite metric suggest (E. C. G. Sudarshan, unpublished) that leptonic resonances, if they exist, could manifest themselves in γe, πe, πμ and πν channels.

IT has been found that blood lymphocytes from patients suffering from malignant neoplasia (even in an early stage) are sensitized to a basic protein1(encephalitogenic factor, EF) derived from human brain2. They react even more markedly (but to a strikingly similar degree) with a basic protein derived from a variety of human tumours3. During a visit to Dr Carnegie's laboratory some months ago one of us (E. J. F.) was shown the complementary structure of the serotonin molecule and the antigenic determinant (since published4) and realized that since the electrophoretic method1depends on interaction of EF with sensitized lymphocytes, structures complementary to the EF determinant might be able to mask it and so block the reaction.