Volume 520 Number 7549

Editorials

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

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

More on unicorns p.586

A newly discovered tiny dinosaur sported an intriguing structural accessory.

doi: 10.1038/525586a

News

News Features

After the Arab Spring p.604

Four years after revolutions shook governments in North Africa and the Middle East, scientists face an uncertain future.

doi: 10.1038/520604a

News & Views

An essential passenger with p53 p.626

Deletion of the TP53 gene, an event seen in colorectal cancers, often occurs with co-deletion of a gene that encodes an enzyme subunit governing gene transcription. This creates a vulnerability ripe for therapeutic development. See Letter p.697

doi: 10.1038/nature14390

Stillbirth prevented by signal blockade p.627

Bacterial infections during pregnancy can cause fetal death. The identification of a cell-signalling pathway induced during infection that recruits dangerous immune cells to the placenta may open up avenues to prevent this.

doi: 10.1038/520627a

Malaria runs rings round artemisinin p.628

In parts of southeast Asia, malaria parasites are showing resistance to the active ingredient in artemisinin-based antimalarial drugs. Delineation of a cell-signalling pathway might help to explain this phenomenon. See Letter p.683

doi: 10.1038/nature14387

Northern push for the bipolar see-saw p.630

Antarctic ice-core data show that abrupt changes of climate in the Northern Hemisphere in the last glacial period preceded associated shifts in Antarctica by about 200 years — indicating an oceanic coupling process. See Letter p.661

doi: 10.1038/520630a

Semiconductors grown large and thin p.631

Atomically thin layers of semiconductors called transition-metal dichalcogenides have been grown uniformly on the square-centimetre scale — paving the way for the ultimate miniaturization of electronic applications. See Letter p.656

doi: 10.1038/520631a

Articles

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

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

Letters

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

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

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

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

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

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