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Nature



Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising concl



 



Don’t let Europe’s open-science dream drift

2017-06-20

Now that the major players have agreed to the giant European Open Science Cloud, it’s time to get the project moving.



Protect funding for US earthquake early-warning system
Donald Trump’s proposed cuts to ShakeAlert puts the west coast at risk.



Heatwaves to soar above the hot air of climate politics

2017-06-20

Future generations will fear, rather than fend for, the global environment.



A year on, Brexit brings lessons in uncertainty

2017-06-20

It is more important to understand the electorate than to make predictions about the outcome of elections, says Jane Green.



SEVEN DAYS
The week in science: 16–22 June 2017.



Macron consolidates electoral victory

2017-06-19

The party of France’s recently elected president won an absolute majority in its first general elections, with an agenda that included strong support for research.



Ancient oak's youthful genome surprises biologists

2017-06-19

DNA of 234-year-old tree has few mutations, giving weight to idea that plants protect their stem cells.



China’s genomics giant to make stock-market debut
Once the world's biggest DNA sequencer for research, BGI is now looking to medical applications to boost profits.



Teeth tell tale of hippo’s quick spread across Africa

2017-06-20

Fossils from ancient hippo ancestor suggest that grass helped the animals to conquer a continent.



New concerns raised over value of genome-wide disease studies

2017-06-15

Large analyses dredge up 'peripheral' genetic associations that offer little biological insight, researchers say.



China cracks down on fake peer reviews

2017-06-20

Funding agencies announce harsh penalties and stronger policing efforts.



How sea-floor sensors could save the world from natural disasters
Geophysicists are racing to monitor underwater faults in Earth’s crust so they can provide warning of the next big earthquake and tsunami.



Track batteries degrading in real time

2017-06-21

Monitor deforming electrodes to speed development of renewable-energy storage, write Liqiang Mai, Mengyu Yan and Yunlong Zhao.



Botany: He made plants a profession

2017-06-21

Jim Endersby revisits the legacy of trailblazing botanist Joseph Dalton Hooker.



Consent: Data-sharing for indigenous peoples

2017-06-21

Broad-consent models for human studies, which leave decisions on data-sharing to the researchers, may not be appropriate for work with indigenous peoples. Making the sharing of data almost impossible is also problematic. Everyone stands to benefit from responsible data-sharing innovations that can be applied more



Philosophy: Religion's openness towards science

2017-06-21

Your Editorial suggests that Pope Francis's meeting with patients and researchers is evidence of “a new openness [of religion] towards science”, in the spirit of his 2015 encyclical Laudato si' (Nature545, 265–266;10.1038/nature.2017.219852017). This is tempered



Counterfeit drugs: Fight fake reagents with digital tools

2017-06-21

Digital technologies are emerging that could be used to stop the burgeoning market in fake research reagents that are contaminating global biomedical supply chains (see Nature545, 148–150;10.1038/545148a2017).The international counterfeit-drugs market is even more lucrative. Estimates of



Ecology: Document India's floral biodiversity

2017-06-21

This month's bicentenary of the birth of Joseph Dalton Hooker, one of the great botanical explorers of the nineteenth century, is a good time to highlight the urgent need to document India's remarkable biodiversity for conservation purposes (see also J.EndersbyNature546, 472



Sustainability: A greener culture

2017-06-21

Creative minds are shrinking research's big carbon footprint.



Women in science: Finding consensus

2017-06-21

Gender shapes US university officials' take on ways to recruit and retain women in STEM.



Memories to come

2017-06-21

Is this the real life?



Effects of a ketamine metabolite on synaptic NMDAR function

2017-06-21

arising from P. Zanos et al. Nature533, 481–486 (2016); doi:10.1038/nature17998Clinical data have demonstrated rapid and sustained antidepressant effects of ketamine, a noncompetitive NMDAR (N-methyl-d-aspartate receptor) antagonist. Recently, Zanos et al. claimed that the



Zanos et al. reply

2017-06-21

Replying to K. Suzuki et al. Nature546, http://dx.doi.org/10.1038/nature22084 (2017)In the accompanying Comment, Suzuki et al. confirmed our previous findings that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) does not functionally inhibit the NMDAR at



Correction

2017-06-21

The Spotlight article 'The genetic microscope' (Nature545, S25–S27; 2017) said that Orit Rozenblatt-Rosen was an associate director at the Klarman Cell Observatory. In fact, she is the scientific director there.



Vision: These retinas are made for walkin'

2017-06-07

Measurements of the activity of neurons called direction-selective ganglion cells in the mouse retina explain how visual motion encoded by the eye maps onto body movements such as walking. See Article p.492



Particle physics: No sign of asymmetry in the strong force

2017-06-14

The strong force binds the constituents of nuclei together. Differences between the force's fundamental interactions and their mirror images were thought to have been observed in heavy-ion collisions, but new data challenge this picture.



50 & 100 Years Ago

2017-06-21

50 Years AgoIndividual plants of the amphibious buttercup species Ranunculus flabellaris Raf. are known to produce leaves of differing morphologies in response to different environments. Leaves produced in the aquatic phase are highly dissected, while terrestrially produced leaves are less dissected or simply



Bacterial pathogens: A spoonful of sugar could be the medicine

2017-06-14

Pili are filamentous bacterial structures that promote adhesion to host cells. It emerges that a small molecule that inhibits this adhesion can prevent colonization of the mouse gut by a pathogenic bacterium. See Letter p.528



Genomics: The feline line

2017-06-21

A study of ancient cat DNA that uses samples from different times and from around the world provides insights into the spread and evolution of these enigmatic creatures. Writing in Nature Ecology & Evolution, Ottoni et al. report their investigation of more than



Quantum physics: Interactions propel a magnetic dance

2017-06-21

A combination of leading-edge techniques has enabled interaction-induced magnetic motion to be observed for pairs of ultracold atoms — a breakthrough in the development of models of complex quantum behaviour. See Letter p.519



Neuroinflammation: Synapses pruned in lupus

2017-06-14

Lupus is an autoimmune disease that can cause brain dysfunction. Studies in mouse models of lupus find that interferon proteins can cause the brain's immune cells to trim the synaptic connections between neurons. See Letter p.539



Climate science: Clouds unfazed by haze

2017-06-21

The extent to which aerosols affect climate is highly uncertain. Observations of clouds interacting with aerosols from a volcanic eruption suggest that the effect is much smaller than was once feared. See Article p.485



Strong constraints on aerosol–cloud interactions from volcanic eruptions

2017-06-22

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify



A retinal code for motion along the gravitational and body axes

2017-06-07

Self-motion triggers complementary visual and vestibular reflexes supporting image-stabilization and balance. Translation through space produces one global pattern of retinal image motion (optic flow), rotation another. We examined the direction preferences of direction-sensitive ganglion cells (DSGCs) in flattened mouse retinas in vitro. Here we



Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer

2017-06-07

The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to



Structure of the human multidrug transporter ABCG2

2017-05-29

ABCG2 is a constitutively expressed ATP-binding cassette (ABC) transporter that protects many tissues against xenobiotic molecules. Its activity affects the pharmacokinetics of commonly used drugs and limits the delivery of therapeutics into tumour cells, thus contributing to multidrug resistance. Here we present the structure of



A massive, dead disk galaxy in the early Universe

2017-06-21

At redshift z = 2, when the Universe was just three billion years old, half of the most massive galaxies were extremely compact and had already exhausted their fuel for star formation. It is believed that they were formed in intense nuclear starbursts and that they ultimately grew into the most massive local elliptical galaxies seen today, through mergers with minor companions, but validating this picture requires higher-resolution observations of their centres than is currently possible. Magnification from gravitational lensing offers an opportunity to resolve the inner regions of galaxies. Here we report an analysis of the stellar populations and kinematics of a lensed z = 2.1478 compact galaxy, which—surprisingly—turns out to be a fast-spinning, rotationally supported disk galaxy. Its stars must have formed in a disk, rather than in a merger-driven nuclear starburst. The galaxy was probably fed by streams of cold gas, which were able to penetrate the hot halo gas until they were cut off by shock heating from the dark matter halo. This result confirms previous indirect indications that the first galaxies to cease star formation must have gone through major changes not just in their structure, but also in their kinematics, to evolve into present-day elliptical galaxies.



A giant planet undergoing extreme-ultraviolet irradiation by its hot massive-star host

2017-06-05

The amount of ultraviolet irradiation and ablation experienced by a planet depends strongly on the temperature of its host star. Of the thousands of extrasolar planets now known, only six have been found that transit hot, A-type stars (with temperatures of 7,300–10,000 kelvin), and no planets are known to transit the even hotter B-type stars. For example, WASP-33 is an A-type star with a temperature of about 7,430 kelvin, which hosts the hottest known transiting planet, WASP-33b (ref. 1); the planet is itself as hot as a red dwarf star of type M (ref. 2). WASP-33b displays a large heat differential between its dayside and nightside, and is highly inflated–traits that have been linked to high insolation. However, even at the temperature of its dayside, its atmosphere probably resembles the molecule-dominated atmospheres of other planets and, given the level of ultraviolet irradiation it experiences, its atmosphere is unlikely to be substantially ablated over the lifetime of its star. Here we report observations of the bright star HD 195689 (also known as KELT-9), which reveal a close-in (orbital period of about 1.48 days) transiting giant planet, KELT-9b. At approximately 10,170 kelvin, the host star is at the dividing line between stars of type A and B, and we measure the dayside temperature of KELT-9b to be about 4,600 kelvin. This is as hot as stars of stellar type K4 (ref. 5). The molecules in K stars are entirely dissociated, and so the primary sources of opacity in the dayside atmosphere of KELT-9b are probably atomic metals. Furthermore, KELT-9b receives 700 times more extreme-ultraviolet radiation (that is, with wavelengths shorter than 91.2 nanometres) than WASP-33b, leading to a predicted range of mass-loss rates that could leave the planet largely stripped of its envelope during the main-sequence lifetime of the host star.



Microscopy of the interacting Harper–Hofstadter model in the two-body limit

2017-06-21

The interplay between magnetic fields and interacting particles can lead to exotic phases of matter that exhibit topological order and high degrees of spatial entanglement. Although these phases were discovered in a solid-state setting, recent innovations in systems of ultracold neutral atoms—uncharged atoms that do not naturally experience a Lorentz force—allow the synthesis of artificial magnetic, or gauge, fields. This experimental platform holds promise for exploring exotic physics in fractional quantum Hall systems, owing to the microscopic control and precision that is achievable in cold-atom systems. However, so far these experiments have mostly explored the regime of weak interactions, which precludes access to correlated many-body states. Here, through microscopic atomic control and detection, we demonstrate the controlled incorporation of strong interactions into a two-body system with a chiral band structure. We observe and explain the way in which interparticle interactions induce chirality in the propagation dynamics of particles in a ladder-like, real-space lattice governed by the interacting Harper–Hofstadter model, which describes lattice-confined, coherently mobile particles in the presence of a magnetic field. We use a bottom-up strategy to prepare interacting chiral quantum states, thus circumventing the challenges of a top-down approach that begins with a many-body system, the size of which can hinder the preparation of controlled states. Our experimental platform combines all of the necessary components for investigating highly entangled topological states, and our observations provide a benchmark for future experiments in the fractional quantum Hall regime.



Improved maize reference genome with single-molecule technologies

2017-06-12

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.



Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist

2017-06-14

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually. Despite effective antibiotic therapy, 30–50% of patients experience recurrent UTIs. In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections. UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs. UPEC isolates encode up to 16 distinct chaperone-usher pathway pili, and each pilus type may enable colonization of a habitat in the host or environment. For example, the type 1 pilus adhesin FimH binds mannose on the bladder surface, and mediates colonization of the bladder. However, little is known about the mechanisms underlying UPEC persistence in the gut. Here, using a mouse model, we show that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, we show that targeting FimH with M4284, a high-affinity inhibitory mannoside, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without notably disrupting the structural configuration of the gut microbiota. By selectively depleting intestinal UPEC reservoirs, mannosides could markedly reduce the rate of UTIs and recurrent UTIs.



Multilineage communication regulates human liver bud development from pluripotency

2017-06-14

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development. We find that liver bud hepatoblasts diverge from the two-dimensional lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark three-dimensional liver buds against fetal and adult human liver single-cell RNA sequencing data, and find a striking correspondence between the three-dimensional liver bud and fetal liver cells. We use a receptor–ligand pairing analysis and a high-throughput inhibitor assay to interrogate signalling in liver buds, and show that vascular endothelial growth factor (VEGF) crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.



Microglia-dependent synapse loss in type I interferon-mediated lupus

2017-06-14

Systemic lupus erythematosus (SLE) is an incurable autoimmune disease characterized by autoantibody deposition in tissues such as kidney, skin and lungs. Notably, up to 75% of patients with SLE experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and, in rare cases, psychosis—collectively this is referred to as central nervous system (CNS) lupus. In some cases, certain autoantibodies, such as anti-NMDAR or anti-phospholipid antibodies, promote CNS lupus. However, in most patients, the mechanisms that underlie these symptoms are unknown. CNS lupus typically presents at lupus diagnosis or within the first year, suggesting that early factors contributing to peripheral autoimmunity may promote CNS lupus symptoms. Here we report behavioural phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signalling. Furthermore, we show that type I IFN stimulates microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. These findings and our observation of increased type I IFN signalling in post-mortem hippocampal brain sections from patients with SLE may instruct the evaluation of ongoing clinical trials of anifrolumab, a type I IFN-receptor antagonist. Moreover, identification of IFN-driven microglia-dependent synapse loss, along with microglia transcriptome data, connects CNS lupus with other CNS diseases and provides an explanation for the neurological symptoms observed in some patients with SLE.



Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge

2017-06-14

Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.



BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation

2017-06-14

BRCA1-associated protein 1 (BAP1) is a potent tumour suppressor gene that modulates environmental carcinogenesis. All carriers of inherited heterozygous germline BAP1-inactivating mutations (BAP1+/−) developed one and often several BAP1−/− malignancies in their lifetime, mostly malignant mesothelioma, uveal melanoma, and so on. Moreover, BAP1-acquired biallelic mutations are frequent in human cancers. BAP1 tumour suppressor activity has been attributed to its nuclear localization, where it helps to maintain genome integrity. The possible activity of BAP1 in the cytoplasm is unknown. Cells with reduced levels of BAP1 exhibit chromosomal abnormalities and decreased DNA repair by homologous recombination, indicating that BAP1 dosage is critical. Cells with extensive DNA damage should die and not grow into malignancies. Here we discover that BAP1 localizes at the endoplasmic reticulum. Here, it binds, deubiquitylates, and stabilizes type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), modulating calcium (Ca2+) release from the endoplasmic reticulum into the cytosol and mitochondria, promoting apoptosis. Reduced levels of BAP1 in BAP1+/− carriers cause reduction both of IP3R3 levels and of Ca2+ flux, preventing BAP1+/− cells that accumulate DNA damage from executing apoptosis. A higher fraction of cells exposed to either ionizing or ultraviolet radiation, or to asbestos, survive genotoxic stress, resulting in a higher rate of cellular transformation. We propose that the high incidence of cancers in BAP1+/− carriers results from the combined reduced nuclear and cytoplasmic activities of BAP1. Our data provide a mechanistic rationale for the powerful ability of BAP1 to regulate gene–environment interaction in human carcinogenesis.



PTEN counteracts FBXL2 to promote IP3R3- and Ca2+-mediated apoptosis limiting tumour growth

2017-06-14

In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the ‘quasisynaptical’ feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca2+ release results in mitochondrial Ca2+ overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca2+-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca2+ influx into mitochondria. FBXL2-knockdown cells and FBXL2-insensitive IP3R3 mutant knock-in clones display increased cytosolic Ca2+ release from the endoplasmic reticulum and sensitization to Ca2+-dependent apoptotic stimuli. The phosphatase and tensin homologue (PTEN) gene is frequently mutated or lost in human tumours and syndromes that predispose individuals to cancer. We found that PTEN competes with FBXL2 for IP3R3 binding, and the FBXL2-dependent degradation of IP3R3 is accelerated in Pten−/− mouse embryonic fibroblasts and PTEN-null cancer cells. Reconstitution of PTEN-null cells with either wild-type PTEN or a catalytically dead mutant stabilizes IP3R3 and induces persistent Ca2+ mobilization and apoptosis. IP3R3 and PTEN protein levels directly correlate in human prostate cancer. Both in cell culture and xenograft models, a non-degradable IP3R3 mutant sensitizes tumour cells with low or no PTEN expression to photodynamic therapy, which is based on the ability of photosensitizer drugs to cause Ca2+-dependent cytotoxicity after irradiation with visible light. Similarly, disruption of FBXL2 localization with GGTi-2418, a geranylgeranyl transferase inhibitor, sensitizes xenotransplanted tumours to photodynamic therapy. In summary, we identify a novel molecular mechanism that limits mitochondrial Ca2+ overload to prevent cell death. Notably, we provide proof-of-principle that inhibiting IP3R3 degradation in PTEN-deregulated cancers represents a valid therapeutic strategy.



Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage

2017-05-31

Cpf1 is an RNA-guided endonuclease that is emerging as a powerful genome-editing tool. Here we provide insight into its DNA-targeting mechanism by determining the structure of Francisella novicida Cpf1 with the triple-stranded R-loop generated after DNA cleavage. The structure reveals the machinery involved in DNA unwinding to form a CRISPR RNA (crRNA)–DNA hybrid and a displaced DNA strand. The protospacer adjacent motif (PAM) is recognized by the PAM-interacting domain. The loop-lysine helix–loop motif in this domain contains three conserved lysine residues that are inserted in a dentate manner into the double-stranded DNA. Unzipping of the double-stranded DNA occurs in a cleft arranged by acidic and hydrophobic residues facilitating the crRNA–DNA hybrid formation. The PAM single-stranded DNA is funnelled towards the nuclease site through a mixed hydrophobic and basic cavity. In this catalytic conformation, the PAM-interacting domain and the helix–loop–helix motif in the REC1 domain adopt a ‘rail’ shape and ‘flap-on’ conformations, respectively, channelling the PAM strand into the cavity. A steric barrier between the RuvC-II and REC1 domains forms the ‘septum’, separating the displaced PAM strand and the crRNA–DNA hybrid, avoiding DNA re-annealing. Mutations in key residues reveal a mechanism linking the PAM and DNA nuclease sites. Analysis of the Cpf1 structures proposes a singular working model of RNA-guided DNA cleavage, suggesting new avenues for redesign of Cpf1.



Addendum: The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

2017-06-21

Nature537, 50–56 (2016); doi:10.1038/nature19323Figure 1 of our original Article illustrated that treatment with aducanumab reduced human brain amyloid-β plaques in a dose-dependent fashion as measured by florbetapir positron emission tomography (PET) imaging. The figure gave the