Volume 533 Number 7601

Editorials

The nuclear option p.7

China is vigorously promoting nuclear energy, but its pursuit of reprocessing is misguided.

doi: 10.1038/533007b

Lessons from the Ancient One p.7

The final stages of a dispute over an ancient Native American skeleton signal the need for clearer oversight of such human remains.

doi: 10.1038/533007a

Fat lot of good p.8

Humans' exceptional ability to burn through calories fuels our evolution.

doi: 10.1038/533008a

News

News Features

Nine years of censorship p.26

Canadian scientists are now allowed to speak out about their work — and the government policy that had restricted communications.

doi: 10.1038/533026a

News & Views

Clockwork at the atomic scale p.38

Design rules for exotic materials known as polar metals have been put into practice in thin films. The findings will motivate studies of how a phenomenon called screening can be manipulated to generate new phases in metals. See Letter p.68

doi: 10.1038/nature17890

Evolved to overcome Bt-toxin resistance p.39

Insects readily evolve resistance to insecticidal proteins that are introduced into genetically modified crop plants. Continuous directed evolution has now been used to engineer a toxin that overcomes insect resistance. See Article p.58

doi: 10.1038/nature17893

Guilt by genetic association p.40

Certain sequence variants of the α-synuclein gene are linked to the risk of Parkinson's disease. An analysis of these variants using gene-editing technology provides a possible explanation for this increased risk. See Letter p.95

doi: 10.1038/nature17891

Mum's microbes boost baby's immunity p.42

The microorganisms that colonize pregnant mice have been shown to prime the innate immune system in newborn offspring, preparing them for life in association with microbes.

doi: 10.1038/nature17895

Ubiquitination without E1 and E2 enzymes p.43

A protein in the pathogenic bacterium Legionella pneumophila has been found to attach the modifying molecule ubiquitin to human proteins, using a mechanism that, surprisingly, does not involve cellular E1 and E2 enzymes. See Letter p.120

doi: 10.1038/nature17888

Elusive transition spotted in thorium p.44

The highly precise atomic clocks used in science and technology are based on electronic transitions in atoms. The discovery of a nuclear transition in thorium-229 raises hopes of making nuclear clocks a reality. See Article p.47

doi: 10.1038/533044a

Articles

Direct detection of the 229Th nuclear clock transition p.47

Direct detection of the 229Th nuclear clock transition has been achieved, placing direct constraints on transition energy and half-life; these results are a step towards a nuclear clock, nuclear quantum optics and a nuclear laser.

doi: 10.1038/nature17669

Letters

Resolved atomic lines reveal outflows in two ultraluminous X-ray sources p.64

Ultraluminous X-ray sources are thought to be powered by accretion onto a compact object; now the discovery of X-ray emission lines and blueshifted absorption lines in the high-resolution spectra of ultraluminous X-ray sources NGC 1313 X-1 and NGC 5408 X-1 shows that in each case the compact object is surrounded by powerful winds with an outflow velocity of about 0.2 times that of light.

doi: 10.1038/nature17417

Polar metals by geometric design p.68

Ab initio calculations are used to identify the structural conditions under which a polar state in metals might be stabilized; this information is used to guide the experimental realization of new room-temperature polar metals.

doi: 10.1038/nature17628

Machine-learning-assisted materials discovery using failed experiments p.73

Failed chemical reactions are rarely reported, even though they could still provide information about the bounds on the reaction conditions needed for product formation; here data from such reactions are used to train a machine-learning algorithm, which is subsequently able to predict reaction outcomes with greater accuracy than human intuition.

doi: 10.1038/nature17439

Scalable and sustainable electrochemical allylic C–H oxidation p.77

An electrochemical C–H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity is described; it uses inexpensive and readily available materials and represents a scalable allylic C–H oxidation that could be adopted in large-scale industrial settings without substantial environmental impact.

doi: 10.1038/nature17431

Chondritic xenon in the Earth’s mantle p.82

High-precision analysis of magmatic gas from the Eifel volcanic area in Germany suggests that the light xenon isotopes reflect a chondritic primordial component that differs from the precursor of atmospheric xenon, consistent with an asteroidal origin for the volatile elements in the Earth’s mantle.

doi: 10.1038/nature17434

Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression p.95

Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis. It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types. Furthermore, single nucleotide polymorphism (SNP)-specific changes in transcription factor binding are correlated with heritable alterations in chromatin state and considered a major mediator of sequence-dependent regulation of gene expression. Here we describe a novel strategy to functionally dissect the cis-acting effect of genetic risk variants in regulatory elements on gene expression by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells. By generating a genetically precisely controlled experimental system, we identify a common Parkinson’s disease associated risk variant in a non-coding distal enhancer element that regulates the expression of α-synuclein (SNCA), a key gene implicated in the pathogenesis of Parkinson’s disease. Our data suggest that the transcriptional deregulation of SNCA is associated with sequence-dependent binding of the brain-specific transcription factors EMX2 and NKX6-1. This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes.

doi: 10.1038/nature17939

Unique human immune signature of Ebola virus disease in Guinea p.100

Fatal Ebola virus disease is characterized by a high proportion of CD4+ and CD8+ T cells expressing the inhibitory molecules CTLA-4 and PD-1, correlating with high virus load; individuals who survive the infection exhibit lower expression of these inhibitory molecules and generate Ebola-specific CD8+ T cells, suggesting that dysregulation of the T cell response is a key component of Ebola virus disease pathophysiology.

doi: 10.1038/nature17949

Ubiquitination independent of E1 and E2 enzymes by bacterial effectors p.120

An unprecedented mechanism of ubiquitination that is independent of E1 and E2 enzymes, instead relying on activation of ubiquitin by ADP-ribosylation, and which is mediated by members of the SidE effector family encoded by the bacterial pathogen Legionella pneumophila, establishes that ubiquitination can be carried out by a single enzyme.

doi: 10.1038/nature17657