A hard sell p.585

Scientists must stand up for marine parks if the value of the seas is to be recognized globally.

doi: 10.1038/520585b

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Thank you for sharing p.585

Initiatives to make genetic and medical data publicly available could improve diagnostics — but they lose value if they do not share with other projects.

doi: 10.1038/520585a

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More on unicorns p.586

A newly discovered tiny dinosaur sported an intriguing structural accessory.

doi: 10.1038/525586a

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Embryo editing sparks epic debate p.593

In wake of paper describing genetic modification of human embryos, scientists disagree about ethics.

doi: 10.1038/520593a

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Canadian budget pushes applied research p.595

Plan seeks to increase government partnerships with industry but downplays basic science.

doi: 10.1038/nature.2015.17305

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Vatican convenes major climate-change meeting p.596

Religious leaders and scientists gather to discuss moral implications of global warming as Pope drafts key letter.

doi: 10.1038/520596a

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Consumer DNA firms get serious about drug development p.597

Companies race to gather large data sets in bid to find treatments based on genetics.

doi: 10.1038/520597a

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Bone DNA reveals humanity’s trek into South America p.598

Skeletons from Peru caves plot course for a single migration to the continent.

doi: 10.1038/520598a

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News Features


Collateral damage: How one misconduct case brought a biology institute to its knees p.600


doi: 10.1038/520600a

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Science in turmoil: After the Arab Spring p.604


doi: 10.1038/520604a

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News & Views


Cancer: An essential passenger with p53 p.626


doi: 10.1038/nature14390

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Immunology: Stillbirth prevented by signal blockade p.627


doi: 10.1038/520627a

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Microbiology: Malaria runs rings round artemisinin p.628


doi: 10.1038/nature14387

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Palaeoclimate: Northern push for the bipolar see-saw p.630


doi: 10.1038/520630a

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Materials science: Semiconductors grown large and thin p.631


doi: 10.1038/520631a

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A multilevel multimodal circuit enhances action selection in Drosophila p.633

Combining neural manipulation in freely behaving animals, physiological studies and electron microscopy reconstruction in the Drosophila larva identifies a complex multilsensory circuit involved in the selection of larval escape modes that exhibits a multilevel multimodal convergence architecture.

doi: 10.1038/nature14297

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Structure of the human 80S ribosome p.640

The structure of the human ribosome at high resolution has been solved; by combining single-particle cryo-EM and atomic model building, local resolution of 2.9 Å was achieved within the most stable areas of the structure.

doi: 10.1038/nature14427

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Extended hard-X-ray emission in the inner few parsecs of the Galaxy p.646

A distinct hard-X-ray emission component is reported within the central four parsecs by eight parsecs of the Galaxy; this emission is more sharply peaked toward the Galactic Centre than is the surface brightness of the soft X-ray population, and all the interpretations of this emission pose significant challenges to our understanding of stellar evolution, binary formation and cosmic-ray production in the Galactic Centre.

doi: 10.1038/nature14353

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Topological valley transport at bilayer graphene domain walls p.650

The bandgap of bilayer graphene can be tuned with an electric field and topological valley polarized modes have been predicted to exist at its domain boundaries; here, near-field infrared imaging and low-temperature transport measurements reveal such modes in gapped bilayer graphene.

doi: 10.1038/nature14364

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High-mobility three-atom-thick semiconducting films with wafer-scale homogeneity p.656

A new chemical vapour deposition method enables transition-metal dichalcogenide (TMD) monolayers to be grown directly on insulating silicon dioxide wafers, demonstrating the possibility of wafer-scale batch fabrication of high-performance devices with TMD monolayers.

doi: 10.1038/nature14417

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Precise interpolar phasing of abrupt climate change during the last ice age p.661

A new ice core from West Antarctica shows that, during the last ice age, abrupt Northern Hemisphere climate variations were followed two centuries later by a response in Antarctica, suggesting an oceanic propagation of the climate signal to the Southern Hemisphere high latitudes.

doi: 10.1038/nature14401

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Isotopic evidence for biological nitrogen fixation by molybdenum-nitrogenase from 3.2 Gyr p.666

Nitrogen is an essential nutrient for all organisms that must have been available since the origin of life. Abiotic processes including hydrothermal reduction, photochemical reactions, or lightning discharge could have converted atmospheric N2 into assimilable NH4+, HCN, or NOx species, collectively termed fixed nitrogen. But these sources may have been small on the early Earth, severely limiting the size of the primordial biosphere. The evolution of the nitrogen-fixing enzyme nitrogenase, which reduces atmospheric N2 to organic NH4+, thus represented a major breakthrough in the radiation of life, but its timing is uncertain. Here we present nitrogen isotope ratios with a mean of 0.0 ± 1.2‰ from marine and fluvial sedimentary rocks of prehnite–pumpellyite to greenschist metamorphic grade between 3.2 and 2.75 billion years ago. These data cannot readily be explained by abiotic processes and therefore suggest biological nitrogen fixation, most probably using molybdenum-based nitrogenase as opposed to other variants that impart significant negative fractionations. Our data place a minimum age constraint of 3.2 billion years on the origin of biological nitrogen fixation and suggest that molybdenum was bioavailable in the mid-Archaean ocean long before the Great Oxidation Event.

doi: 10.1038/nature14180

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An epigenome-wide association study of total serum immunoglobulin E concentration p.670

A survey of epigenetic associations between serum immunoglobulin E concentrations indicating allergy and methylation at CpG islands in families and a population sample has revealed associations at 36 loci that harbour genes encoding proteins including eosinophil products and phospholipid inflammatory mediators.

doi: 10.1038/nature14125

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A circuit mechanism for differentiating positive and negative associations p.675

Neurons in the basolateral amygdala projecting to canonical fear or reward circuits undergo opposing changes in synaptic strength following fear or reward conditioning, and selectively activating these projection-target-defined neural populations causes either negative or positive reinforcement, respectively.

doi: 10.1038/nature14366

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NIK1-mediated translation suppression functions as a plant antiviral immunity mechanism p.679

A new mechanism that plants use to combat begomoviruses—one of the most pathogenic groups of plant viruses, causing severe disease in major crops worldwide—is uncovered: plants inhibit the transcription of genes associated with the translational apparatus, thus causing a general reduction in protein synthesis.

doi: 10.1038/nature14171

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A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria p.683

Artemisinins are key anti-malarial drugs, but artemisinin resistance has been increasing; this study identifies the molecular target of artemisinins as phosphatidylinositol-3-kinase and increase of the lipid product phosphatidylinositol-3-phosphate induces resistance in Plasmodium falciparum.

doi: 10.1038/nature14412

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Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus p.688

Two second-generation attenuated Ebola virus vaccines based on recombinant vesicular stomatitis virus protect macaques against infection with a recent Ebola virus isolate from Guinea.

doi: 10.1038/nature14428

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Mutant MHC class II epitopes drive therapeutic immune responses to cancer p.692

The authors show that a large fraction of tumour mutations is immunogenic and predominantly recognized by CD4+ T cells; they use these data to design synthetic messenger-RNA-based vaccines specific against tumour mutations, and show that these can reject tumours in mice.

doi: 10.1038/nature14426

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TP53 loss creates therapeutic vulnerability in colorectal cancer p.697

TP53, a well-known tumour suppressor gene that encodes p53, is frequently inactivated by mutation or deletion in most human tumours. A tremendous effort has been made to restore p53 activity in cancer therapies. However, no effective p53-based therapy has been successfully translated into clinical cancer treatment owing to the complexity of p53 signalling. Here we demonstrate that genomic deletion of TP53 frequently encompasses essential neighbouring genes, rendering cancer cells with hemizygous TP53 deletion vulnerable to further suppression of such genes. POLR2A is identified as such a gene that is almost always co-deleted with TP53 in human cancers. It encodes the largest and catalytic subunit of the RNA polymerase II complex, which is specifically inhibited by α-amanitin. Our analysis of The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) databases reveals that POLR2A expression levels are tightly correlated with its gene copy numbers in human colorectal cancer. Suppression of POLR2A with α-amanitin or small interfering RNAs selectively inhibits the proliferation, survival and tumorigenic potential of colorectal cancer cells with hemizygous TP53 loss in a p53-independent manner. Previous clinical applications of α-amanitin have been limited owing to its liver toxicity. However, we found that α-amanitin-based antibody–drug conjugates are highly effective therapeutic agents with reduced toxicity. Here we show that low doses of α-amanitin-conjugated anti-epithelial cell adhesion molecule (EpCAM) antibody lead to complete tumour regression in mouse models of human colorectal cancer with hemizygous deletion of POLR2A. We anticipate that inhibiting POLR2A will be a new therapeutic approach for human cancers containing such common genomic alterations.

doi: 10.1038/nature14418

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Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9 p.702

Crystal structures of three forms of Toll-like receptor (TLR) 9 — unliganded or bound either to immune stimulatory CpG-containing DNA or inhibitory DNA — together reveal the molecular basis of TLR9 activation.

doi: 10.1038/nature14138

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The octahaem MccA is a haem c–copper sulfite reductase p.706

Sulfite-reducing microbes couple the reduction of sulfite to the generation of a proton motive force that sustains organismic growth; here, two X-ray crystal structures are solved of MccA, a c-type cytochrome enzyme with eight haem groups that catalyses the six-electron reduction of sulfite to sulfide at a novel haem–copper active site.

doi: 10.1038/nature14109

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