| 1. |
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| 2. |
- Abdalla, H., et al.
(author)
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A very-high-energy component deep in the gamma-ray burst afterglow
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 575:7783, s. 464-467
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Journal article (peer-reviewed)abstract
- Gamma-ray bursts (GRBs) are brief flashes of gamma-rays and are considered to be the most energetic explosive phenomena in the Universe(1). The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed(2). GRBs typically emit most of their energy via.-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments(3). However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive(4). Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and gamma-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
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| 3. |
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| 4. |
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| 5. |
- Aprile, E., et al.
(author)
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Observation of two-neutrino double electron capture in 124Xe with XENON1T
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 568:7753, s. 532-535
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Journal article (peer-reviewed)abstract
- Two-neutrino double electron capture (2νECEC) is a second-order weak-interaction process with a predicted half-life that surpasses the age of the Universe by many orders of magnitude. Until now, indications of 2νECEC decays have only been seen for two isotopes, 78Kr and 130Ba, and instruments with very low background levels are needed to detect them directly with high statistical significance. The 2νECEC half-life is an important observable for nuclear structure models and its measurement represents a meaningful step in the search for neutrinoless double electron capture—the detection of which would establish the Majorana nature of the neutrino and would give access to the absolute neutrino mass. Here we report the direct observation of 2νECEC in 124Xe with the XENON1T dark-matter detector. The significance of the signal is 4.4 standard deviations and the corresponding half-life of 1.8 × 1022 years (statistical uncertainty, 0.5 × 1022 years; systematic uncertainty, 0.1 × 1022 years) is the longest measured directly so far. This study demonstrates that the low background and large target mass of xenon-based dark-matter detectors make them well suited for measuring rare processes and highlights the broad physics reach of larger next-generation experiments.
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| 6. |
- Bai, Sai, et al.
(author)
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Planar perovskite solar cells with long-term stability using ionic liquid additives
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 571:7764, s. 245-250
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Journal article (peer-reviewed)abstract
- Solar cells based on metal halide perovskites are one of the most promising photovoltaic technologies(1-4). Over the past few years, the long-term operational stability of such devices has been greatly improved by tuning the composition of the perovskites(5-9), optimizing the interfaces within the device structures(10-13), and using new encapsulation techniques(14,15). However, further improvements are required in order to deliver a longer-lasting technology. Ion migration in the perovskite active layer-especially under illumination and heat-is arguably the most difficult aspect to mitigate(16-18). Here we incorporate ionic liquids into the perovskite film and thence into positive-intrinsic-negative photovoltaic devices, increasing the device efficiency and markedly improving the long-term device stability. Specifically, we observe a degradation in performance of only around five per cent for the most stable encapsulated device under continuous simulated full-spectrum sunlight for more than 1,800 hours at 70 to 75 degrees Celsius, and estimate that the time required for the device to drop to eighty per cent of its peak performance is about 5,200 hours. Our demonstration of long-term operational, stable solar cells under intense conditions is a key step towards a reliable perovskite photovoltaic technology.
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| 7. |
- Bakkeren, Erik, et al.
(author)
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Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 573:7773, s. 276-280
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Journal article (peer-reviewed)abstract
- The emergence of antibiotic-resistant bacteria through mutations or the acquisition of genetic material such as resistance plasmids represents a major public health issue(1,2). Persisters are subpopulations of bacteria that survive antibiotics by reversibly adapting their physiology(3-10), and can promote the emergence of antibiotic-resistant mutants(11). We investigated whether persisters can also promote the spread of resistance plasmids. In contrast to mutations, the transfer of resistance plasmids requires the co-occurrence of both a donor and a recipient bacterial strain. For our experiments, we chose the facultative intracellular entero-pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) and Escherichia coli, a common member of the microbiota(12). S. Typhimurium forms persisters that survive antibiotic therapy in several host tissues. Here we show that tissue-associated S. Typhimurium persisters represent long-lived reservoirs of plasmid donors or recipients. The formation of reservoirs of S. Typhimurium persisters requires Salmonella pathogenicity island (SPI)-1 and/or SPI-2 in gut-associated tissues, or SPI-2 at systemic sites. The re-seeding of these persister bacteria into the gut lumen enables the co-occurrence of donors with gut-resident recipients, and thereby favours plasmid transfer between various strains of Enterobacteriaceae. We observe up to 99% transconjugants within two to three days of re-seeding. Mathematical modelling shows that rare re-seeding events may suffice for a high frequency of conjugation. Vaccination reduces the formation of reservoirs of persisters after oral infection with S. Typhimurium, as well as subsequent plasmid transfer. We conclude that-even without selection for plasmid-encoded resistance genes-small reservoirs of pathogen persisters can foster the spread of promiscuous resistance plasmids in the gut.
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| 8. |
- Beznosov, Pavel A., et al.
(author)
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Morphology of the earliest reconstructable tetrapod Parmastega aelidae
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 574:7779, s. 527-531
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Journal article (peer-reviewed)abstract
- The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments(1-15). The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles(2,4,16-34). All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments(5,10), and nearly 30 million years younger than the oldest known tetrapod footprints(35). Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods.
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| 9. |
- Bixby, H., et al.
(author)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Journal article (peer-reviewed)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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| 10. |
- Blacher, E., et al.
(author)
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Potential roles of gut microbiome and metabolites in modulating ALS in mice
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7770
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disorder, in which the clinical manifestations may be influenced by genetic and unknown environmental factors. Here we show that ALS-prone Sod1 transgenic (Sod1-Tg) mice have a pre-symptomatic, vivarium-dependent dysbiosis and altered metabolite configuration, coupled with an exacerbated disease under germ-free conditions or after treatment with broad-spectrum antibiotics. We correlate eleven distinct commensal bacteria at our vivarium with the severity of ALS in mice, and by their individual supplementation into antibiotic-treated Sod1-Tg mice we demonstrate that Akkermansia muciniphila (AM) ameliorates whereas Ruminococcus torques and Parabacteroides distasonis exacerbate the symptoms of ALS. Furthermore, Sod1-Tg mice that are administered AM are found to accumulate AM-associated nicotinamide in the central nervous system, and systemic supplementation of nicotinamide improves motor symptoms and gene expression patterns in the spinal cord of Sod1-Tg mice. In humans, we identify distinct microbiome and metabolite configurations-including reduced levels of nicotinamide systemically and in the cerebrospinal fluid-in a small preliminary study that compares patients with ALS with household controls. We suggest that environmentally driven microbiome-brain interactions may modulate ALS in mice, and we call for similar investigations in the human form of the disease.
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| 11. |
- Burstein, R., et al.
(author)
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Mapping 123 million neonatal, infant and child deaths between 2000 and 2017
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7778, s. 353-358
-
Journal article (peer-reviewed)abstract
- Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations. © 2019, The Author(s).
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| 12. |
- Cao, Lina, et al.
(author)
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Atomically dispersed iron hydroxide anchored on Pt for preferential oxidation of CO in H-2
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 565:7741, s. 631-635
-
Journal article (peer-reviewed)abstract
- Proton-exchange-membrane fuel cells (PEMFCs) are attractive next-generation power sources for use in vehicles and other applications(1), with development efforts focusing on improving the catalyst system of the fuel cell. One problem is catalyst poisoning by impurity gases such as carbon monoxide (CO), which typically comprises about one per cent of hydrogen fuel(2-4). A possible solution is on-board hydrogen purification, which involves preferential oxidation of CO in hydrogen (PROX)(3-7). However, this approach is challenging(8-15) because the catalyst needs to be active and selective towards CO oxidation over a broad range of low temperatures so that CO is efficiently removed (to below 50 parts per million) during continuous PEMFC operation (at about 353 kelvin) and, in the case of automotive fuel cells, during frequent cold-start periods. Here we show that atomically dispersed iron hydroxide, selectively deposited on silica-supported platinum (Pt) nanoparticles, enables complete and 100 per cent selective CO removal through the PROX reaction over the broad temperature range of 198 to 380 kelvin. We find that the mass-specific activity of this system is about 30 times higher than that of more conventional catalysts consisting of Pt on iron oxide supports. In situ X-ray absorption fine-structure measurements reveal that most of the iron hydroxide exists as Fe-1(OH)(x) clusters anchored on the Pt nanoparticles, with density functional theory calculations indicating that Fe-1(OH)(x)-Pt single interfacial sites can readily react with CO and facilitate oxygen activation. These findings suggest that in addition to strategies that target oxide-supported precious-metal nanoparticles or isolated metal atoms, the deposition of isolated transition-metal complexes offers new ways of designing highly active metal catalysts.
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| 13. |
- Cappellini, Enrico, et al.
(author)
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Early Pleistocene enamel proteome from Dmanisi resolves Stephanorhinus phylogeny
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 574:7776, s. 103-
-
Journal article (peer-reviewed)abstract
- The sequencing of ancient DNA has enabled the reconstruction of speciation, migration and admixture events for extinct taxa(1). However, the irreversible post-mortem degradation(2) of ancient DNA has so far limited its recovery-outside permafrost areasto specimens that are not older than approximately 0.5 million years (Myr)(3). By contrast, tandem mass spectrometry has enabled the sequencing of approximately 1.5-Myr-old collagen type I-4. and suggested the presence of protein residues in fossils of the Cretaceous period(5)-although with limited phylogenetic use(6). In the absence of molecular evidence, the speciation of several extinct species of the Early and Middle Pleistocene epoch remains contentious. Here we address the phylogenetic relationships of the Eurasian Rhinocerotidae of the Pleistocene epoch(7-9), using the proteome of dental enamel from a Stephanorhinus tooth that is approximately 1.77-Myr old, recovered from the archaeological site of Dmanisi (South Caucasus, Georgia)(10). Molecular phylogenetic analyses place this Stephanorhinus as a sister group to the Glade formed by the woolly rhinoceros (Coelodonta antiquitatis) and Merck's rhinoceros (Stephanorhinus kirchbergensis). We show that Coelodonta evolved from an early Stephanorhinus lineage, and that this latter genus includes at least two distinct evolutionary lines. The genus Stephanorhinus is therefore currently paraphyletic, and its systematic revision is needed. We demonstrate that sequencing the proteome of Early Pleistocene dental enamel overcomes the limitations of phylogenetic inference based on ancient collagen or DNA. Our approach also provides additional information about the sex and taxonomic assignment of other specimens from Dmanisi. Our findings reveal that proteomic investigation of ancient dental enamel-which is the hardest tissue in vertebrates(11), and is highly abundant in the fossil record-can push the reconstruction of molecular evolution further back into the Early Pleistocene epoch, beyond the currently known limits of ancient DNA preservation.
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| 14. |
- Cardoso-Moreira, Margarida, et al.
(author)
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Gene expression across mammalian organ development
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 571:7766, s. 505-
-
Journal article (peer-reviewed)abstract
- The evolution of gene expression in mammalian organ development remains largely uncharacterized. Here we report the transcriptomes of seven organs (cerebrum, cerebellum, heart, kidney, liver, ovary and testis) across developmental time points from early organogenesis to adulthood for human, rhesus macaque, mouse, rat, rabbit, opossum and chicken. Comparisons of gene expression patterns identified correspondences of developmental stages across species, and differences in the timing of key events during the development of the gonads. We found that the breadth of gene expression and the extent of purifying selection gradually decrease during development, whereas the amount of positive selection and expression of new genes increase. We identified differences in the temporal trajectories of expression of individual genes across species, with brain tissues showing the smallest percentage of trajectory changes, and the liver and testis showing the largest. Our work provides a resource of developmental transcriptomes of seven organs across seven species, and comparative analyses that characterize the development and evolution of mammalian organs.
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| 15. |
- de Goffau, Marcus C., et al.
(author)
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Human placenta has no microbiome but can contain potential pathogens
- 2019
-
In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 572:7769, s. 329-334
-
Journal article (peer-reviewed)abstract
- We sought to determine whether pre-eclampsia, spontaneous preterm birth or the delivery of infants who are small for gestational age were associated with the presence of bacterial DNA in the human placenta. Here we show that there was no evidence for the presence of bacteria in the large majority of placental samples, from both complicated and uncomplicated pregnancies. Almost all signals were related either to the acquisition of bacteria during labour and delivery, or to contamination of laboratory reagents with bacterial DNA. The exception was Streptococcus agalactiae (group B Streptococcus), for which non-contaminant signals were detected in approximately 5% of samples collected before the onset of labour. We conclude that bacterial infection of the placenta is not a common cause of adverse pregnancy outcome and that the human placenta does not have a microbiome, but it does represent a potential site of perinatal acquisition of S. agalactiae, a major cause of neonatal sepsis.
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| 16. |
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| 17. |
- Flannick, Jason, et al.
(author)
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Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7759, s. 71-76
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Journal article (peer-reviewed)abstract
- Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10−3) and candidate genes from knockout mice (P = 5.2 × 10−3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000–185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
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| 18. |
- Fridman, Jonas, et al.
(author)
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Climatic controls of decomposition drive the global biogeography of forest-tree symbioses
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569, s. 404-408
-
Journal article (peer-reviewed)abstract
- The identity of the dominant root-associated microbial symbionts in a forest determines the ability of trees to access limiting nutrients from atmospheric or soil pools(1,2), sequester carbon(3,4) and withstand the effects of climate change(5,6). Characterizing the global distribution of these symbioses and identifying the factors that control this distribution are thus integral to understanding the present and future functioning of forest ecosystems. Here we generate a spatially explicit global map of the symbiotic status of forests, using a database of over 1.1 million forest inventory plots that collectively contain over 28,000 tree species. Our analyses indicate that climate variables-in particular, climatically controlled variation in the rate of decomposition-are the primary drivers of the global distribution of major symbioses. We estimate that ectomycorrhizal trees, which represent only 2% of all plant species(7), constitute approximately 60% of tree stems on Earth. Ectomycorrhizal symbiosis dominates forests in which seasonally cold and dry climates inhibit decomposition, and is the predominant form of symbiosis at high latitudes and elevation. By contrast, arbuscular mycorrhizal trees dominate in aseasonal, warm tropical forests, and occur with ectomycorrhizal trees in temperate biomes in which seasonally warm-and-wet climates enhance decomposition. Continental transitions between forests dominated by ectomycorrhizal or arbuscular mycorrhizal trees occur relatively abruptly along climate-driven decomposition gradients; these transitions are probably caused by positive feedback effects between plants and microorganisms. Symbiotic nitrogen fixers-which are insensitive to climatic controls on decomposition (compared with mycorrhizal fungi)-are most abundant in arid biomes with alkaline soils and high maximum temperatures. The climatically driven global symbiosis gradient that we document provides a spatially explicit quantitative understanding of microbial symbioses at the global scale, and demonstrates the critical role of microbial mutualisms in shaping the distribution of plant species.
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| 19. |
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| 20. |
- Grill, G., et al.
(author)
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Mapping the world's free-flowing rivers
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 569:7755, s. 215-221
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Journal article (peer-reviewed)abstract
- Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.
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| 21. |
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| 22. |
- Harrison, John A., et al.
(author)
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Dams : weigh pros and cons case by case
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 568:7751, s. 171-171
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Journal article (pop. science, debate, etc.)
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| 23. |
- Heywood, I., et al.
(author)
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Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7773, s. 235-237
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Journal article (peer-reviewed)abstract
- The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.
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| 24. |
- Izzo, L., et al.
(author)
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Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 565:7739, s. 324-
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Journal article (peer-reviewed)abstract
- Long gamma-ray bursts are associated with energetic, broad-lined, stripped-envelope supernovae(1,2) and as such mark the death of massive stars. The scarcity of such events nearby and the brightness of the gamma-ray burst afterglow, which dominates the emission in the first few days after the burst, have so far prevented the study of the very early evolution of supernovae associated with gamma-ray bursts(3). In hydrogen-stripped supernovae that are not associated with gamma-ray bursts, an excess of high-velocity (roughly 30,000 kilometres per second) material has been interpreted as a signature of a choked jet, which did not emerge from the progenitor star and instead deposited all of its energy in a thermal cocoon(4). Here we report multi-epoch spectroscopic observations of the supernova SN 2017iuk, which is associated with the gamma-ray burst GRB 171205A. Our spectra display features at extremely high expansion velocities (around 115,000 kilometres per second) within the first day after the burst(5,6). Using spectral synthesis models developed for SN 2017iuk, we show that these features are characterized by chemical abundances that differ from those observed in the ejecta of SN 2017iuk at later times. We further show that the high-velocity features originate from the mildly relativistic hot cocoon that is generated by an ultra-relativistic jet within the gamma-ray burst expanding and decelerating into the medium that surrounds the progenitor star(7,8). This cocoon rapidly becomes transparent(9) and is outshone by the supernova emission, which starts to dominate the emission three days after the burst.
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| 25. |
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| 26. |
- Ji, Cheng, et al.
(author)
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Ultrahigh-pressure isostructural electronic transitions in hydrogen
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 573:7775, s. 558-562
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Journal article (peer-reviewed)abstract
- High-pressure transitions are thought to modify hydrogen molecules to a molecular metallic solid and finally to an atomic metal(1), which is predicted to have exotic physical properties and the topology of a two-component (electron and proton) superconducting superfluid condensate(2,3). Therefore, understanding such transitions remains an important objective in condensed matter physics(4,5). However, measurements of the crystal structure of solid hydrogen, which provides crucial information about the metallization of hydrogen under compression, are lacking for most high-pressure phases, owing to the considerable technical challenges involved in X-ray and neutron diffraction measurements under extreme conditions. Here we present a single-crystal X-ray diffraction study of solid hydrogen at pressures of up to 254 gigapascals that reveals the crystallographic nature of the transitions from phase I to phases III and IV. Under compression, hydrogen molecules remain in the hexagonal close-packed (hcp) crystal lattice structure, accompanied by a monotonic increase in anisotropy. In addition, the pressure-dependent decrease of the unit cell volume exhibits a slope change when entering phase IV, suggesting a second-order isostructural phase transition. Our results indicate that the precursor to the exotic two-component atomic hydrogen may consist of electronic transitions caused by a highly distorted hcp Brillouin zone and molecular-symmetry breaking.
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| 27. |
- Kardol, Paul
(author)
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Soil nematode abundance and functional group composition at a global scale
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572
-
Journal article (peer-reviewed)abstract
- Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 +/- 0.64 x 10(20) nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.
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| 28. |
- Kemaladewi, Dwi U, et al.
(author)
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A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7767, s. 125-130
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Journal article (peer-reviewed)abstract
- Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. MDC1A is caused by mutations in LAMA2 that lead to nonfunctional laminin-α2, which compromises the stability of muscle fibres and the myelination of peripheral nerves. Transgenic overexpression of Lama1, which encodes a structurally similar protein called laminin-α1, ameliorates muscle wasting and paralysis in mouse models of MDC1A, demonstrating its importance as a compensatory modifier of the disease1. However, postnatal upregulation of Lama1 is hampered by its large size, which exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. We modulate expression of Lama1 in the dy2j/dy2j mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter. When pre-symptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. However, for many disorders it is important to investigate the therapeutic window and reversibility of symptoms. In muscular dystrophies, it has been hypothesized that fibrotic changes in skeletal muscle are irreversible. However, we show that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy2j/dy2j mice with apparent hindlimb paralysis and muscle fibrosis. Collectively, our data demonstrate the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.
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| 29. |
- Korablev, Oleg, et al.
(author)
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No detection of methane on Mars from early ExoMars Trace Gas Orbiter observations
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 568, s. 517-520
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Journal article (peer-reviewed)abstract
- The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today1. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations2,3,4,5. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere6,7, which—given methane’s lifetime of several centuries—predicts an even, well mixed distribution of methane1,6,8. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections2,4. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater4 would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally.
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| 30. |
- Lambo, Sander, et al.
(author)
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The molecular landscape of ETMR at diagnosis and relapse
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 576, s. 274-280
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Journal article (peer-reviewed)abstract
- Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2–4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.
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| 31. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 32. |
- Lindgren, Johan, et al.
(author)
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Fossil insect eyes shed light on trilobite optics and the arthropod pigment screen
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 573:7772, s. 122-125
-
Journal article (peer-reviewed)abstract
- Fossilized eyes permit inferences of the visual capacity of extinct arthropods1–3. However, structural and/or chemical modifications as a result of taphonomic and diagenetic processes can alter the original features, thereby necessitating comparisons with modern species. Here we report the detailed molecular composition and microanatomy of the eyes of 54-million-year-old crane-flies, which together provide a proxy for the interpretation of optical systems in some other ancient arthropods. These well-preserved visual organs comprise calcified corneal lenses that are separated by intervening spaces containing eumelanin pigment. We also show that eumelanin is present in the facet walls of living crane-flies, in which it forms the outermost ommatidial pigment shield in compound eyes incorporating a chitinous cornea. To our knowledge, this is the first record of melanic screening pigments in arthropods, and reveals a fossilization mode in insect eyes that involves a decay-resistant biochrome coupled with early diagenetic mineralization of the ommatidial lenses. The demonstrable secondary calcification of lens cuticle that was initially chitinous has implications for the proposed calcitic corneas of trilobites, which we posit are artefacts of preservation rather than a product of in vivo biomineralization4–7. Although trilobite eyes might have been partly mineralized for mechanical strength, a (more likely) organic composition would have enhanced function via gradient-index optics and increased control of lens shape.
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| 33. |
- Lloyd-Price, Jason, et al.
(author)
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Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
- 2019
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 569:7758, s. 655-661
-
Journal article (peer-reviewed)abstract
- Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
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| 34. |
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| 35. |
- Mach, Katharine J., et al.
(author)
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Climate as a risk factor for armed conflict
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 571:7764, s. 193-197
-
Journal article (peer-reviewed)abstract
- 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.
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| 36. |
- McFiggans, Gordon, et al.
(author)
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Secondary organic aerosol reduced by mixture of atmospheric vapours
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 565:7741, s. 587-593
-
Journal article (peer-reviewed)abstract
- Secondary organic aerosol contributes to the atmospheric particle burden with implications for air quality and climate. Biogenic volatile organic compounds such as terpenoids emitted from plants are important secondary organic aerosol precursors with isoprene dominating the emissions of biogenic volatile organic compounds globally. However, the particle mass from isoprene oxidation is generally modest compared to that of other terpenoids. Here we show that isoprene, carbon monoxide and methane can each suppress the instantaneous mass and the overall mass yield derived from monoterpenes in mixtures of atmospheric vapours. We find that isoprene 'scavenges' hydroxyl radicals, preventing their reaction with monoterpenes, and the resulting isoprene peroxy radicals scavenge highly oxygenated monoterpene products. These effects reduce the yield of low-volatility products that would otherwise form secondary organic aerosol. Global model calculations indicate that oxidant and product scavenging can operate effectively in the real atmosphere. Thus highly reactive compounds (such as isoprene) that produce a modest amount of aerosol are not necessarily net producers of secondary organic particle mass and their oxidation in mixtures of atmospheric vapours can suppress both particle number and mass of secondary organic aerosol. We suggest that formation mechanisms of secondary organic aerosol in the atmosphere need to be considered more realistically, accounting for mechanistic interactions between the products of oxidizing precursor molecules (as is recognized to be necessary when modelling ozone production).
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| 37. |
- Melnyk, Charles
(author)
-
Mobile PEAR transcription factors integrate positional cues to prime cambial growth
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 565, s. 490-494
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Journal article (peer-reviewed)abstract
- Apical growth in plants initiates upon seed germination, whereas radial growth is primed only during early ontogenesis in procambium cells and activated later by the vascular cambium(1). Although it is not known how radial growth is organized and regulated in plants, this system resembles the developmental competence observed in some animal systems, in which pre-existing patterns of developmental potential are established early on(2,3). Here we show that in Arabidopsis the initiation of radial growth occurs around early protophloem-sieve-element cell files of the root procambial tissue. In this domain, cytokinin signalling promotes the expression of a pair of mobile transcription factors-PHLOEM EARLY DOF 1 (PEAR1) and PHLOEM EARLY DOF 2 (PEAR2)-and their four homologues (DOF6, TMO6, OBP2 and HCA2), which we collectively name PEAR proteins. The PEAR proteins form a short-range concentration gradient that peaks at protophloem sieve elements, and activates gene expression that promotes radial growth. The expression and function of PEAR proteins are antagonized by the HD-ZIP III proteins, well-known polarity transcription factors(4)-the expression of which is concentrated in the more-internal domain of radially non-dividing procambial cells by the function of auxin, and mobile miR165 and miR166 microRNAs. The PEAR proteins locally promote transcription of their inhibitory HD-ZIP III genes, and thereby establish a negative-feedback loop that forms a robust boundary that demarks the zone of cell division. Taken together, our data establish that during root procambial development there exists a network in which a module that links PEAR and HD-ZIP III transcription factors integrates spatial information of the hormonal domains and miRNA gradients to provide adjacent zones of dividing and more-quiescent cells, which forms a foundation for further radial growth.
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| 38. |
- Mäkinen, Taija
(author)
-
Neurobiology : A Drain At The Base Of The Brain
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7767, s. 34-35
-
Journal article (other academic/artistic)abstract
- A set of lymphatic vessels that wrap around the base of the mouse brain have been shown to drain fluid from the brain into the peripheral lymphatic system, and to exhibit a decline in function with ageing.
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| 39. |
- Newton, P. T., et al.
(author)
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A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 567:7747
-
Journal article (peer-reviewed)abstract
- Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification(1). However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth(1,2), but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
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| 40. |
- Nielsen, Jens B, 1962
(author)
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METABOLISM: A stress-coping strategy for yeast cells
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7768, s. 184-185
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Journal article (other academic/artistic)abstract
- Stressed yeast cells take up the amino acid lysine and reprogram their metabolism to free up supplies of a stress-relieving molecule. Lysine uptake therefore increases the tolerance of yeast cells to stress. See LETTER P.249
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| 41. |
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| 42. |
- Nyström, Magnus, et al.
(author)
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Anatomy and resilience of the global production ecosystem
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 575, s. 98-108
-
Journal article (peer-reviewed)abstract
- Much of the Earth's biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated 'keystone actors' such as multinational corporations.
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| 43. |
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| 44. |
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| 45. |
- Sikora, M., et al.
(author)
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The population history of northeastern Siberia since the Pleistocene
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 570:7760
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Journal article (peer-reviewed)abstract
- Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas.
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| 46. |
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| 47. |
- Skiniemi, Sannako, et al.
(author)
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Death from within
- 2019
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 570:7762, s. 449-450
-
Journal article (other academic/artistic)abstract
- Some bacteria naturally transfer pieces of their DNA within and between species. Such a piece of DNA has been engineered to act as a molecular 'Trojan horse' that unleashes a toxin to selectively kill antibiotic-resistant Vibrio cholerae bacteria.
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| 48. |
- Sukonina, Valentina, et al.
(author)
-
FOXK1 and FOXK2 regulate aerobic glycolysis.
- 2019
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 566, s. 279-283
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Journal article (peer-reviewed)abstract
- Adaptation to the environment and extraction of energy are essential for survival. Some species have found niches and specialized in using a particular source of energy, whereas others-including humans and several other mammals-have developed a high degree of flexibility1. A lot is known about the general metabolic fates of different substrates but we still lack a detailed mechanistic understanding of how cells adapt in their use of basic nutrients2. Here we show that the closely related fasting/starvation-induced forkhead transcription factors FOXK1 and FOXK2 induce aerobic glycolysis by upregulating the enzymatic machinery required for this (for example, hexokinase-2, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in the mitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit of pyruvate dehydrogenase phosphatase 1 this leads to increased phosphorylation of the E1α regulatory subunit of the pyruvate dehydrogenase complex, which in turn inhibits further oxidation of pyruvate in the mitochondria-instead, pyruvate is reduced to lactate. Suppression of FOXK1 and FOXK2 induce the opposite phenotype. Both in vitro and in vivo experiments, including studies of primary human cells, show how FOXK1 and/or FOXK2 are likely to act as important regulators that reprogram cellular metabolism to induce aerobic glycolysis.
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| 49. |
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| 50. |
- Thompson, Deborah J, et al.
(author)
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Genetic predisposition to mosaic Y chromosome loss in blood
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 575, s. 652-657
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Journal article (peer-reviewed)abstract
- Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.
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