Volume 527 Number 7579

Editorials

Drugs on demand p.410

Controversy in Brazil over access to a purported cancer cure could set a harmful precedent.

doi: 10.1038/527410b

Built on trust p.410

Written agreements between parties in research collaborations are not a sign of a lack of faith.

doi: 10.1038/527410a

News

News Features

All together now p.425

After 25 years of negotiations, all countries are finally set to take steps to limit global warming. A special issue examines the path to the Paris climate summit, and the road beyond.

doi: 10.1038/527425a

The fragile framework p.427

A Nature comic examines the 25-year quest for a climate treaty. Can nations unite to save Earth’s climate?

doi: 10.1038/527427a

Is the 2 °C world a fantasy? p.436

Countries have pledged to limit global warming to 2 °C, and climate models say that is still possible. But only with heroic — and unlikely — efforts.

doi: 10.1038/527436a

News & Views

Acorn worms in a nutshell p.448

The genome sequences of two members of the hemichordate group of marine invertebrates bring the evolution of their relatives, including vertebrates, into sharper focus. See Article p.459

doi: 10.1038/nature16315

A receptor for subtle temperature changes p.449

The protein IR25a is best known for its role as an odour receptor in flies, but an analysis reveals that it also acts to synchronize the circadian clock by sensing small temperature fluctuations. See Letter p.516

doi: 10.1038/nature16316

Super-resolution ultrasound p.451

By infusing blood vessels with gas-filled microbubbles and using rapid ultrasound imaging to detect the bubbles, super-resolution imaging of an entire vessel system has been achieved in a rat brain. See Letter p.499

doi: 10.1038/527451a

Transition loses its invasive edge p.452

Two studies provide evidence that epithelial tumour cells do not need to transition to a mesenchymal-cell state to form metastases, but that this process does contribute to drug resistance. See Article p.472 & Letter p.525

doi: 10.1038/nature16313

Hidden reservoirs p.453

West Africa's Ebola epidemic continues to reveal surprises. Although the animal species that originally passed the virus to people remains a mystery, a virus reservoir and persistent disease have been identified in some human survivors.

doi: 10.1038/527453a

The Moon's tilt for gold p.455

The Moon's current orbit is at odds with theories predicting that its early orbit was in Earth's equatorial plane. Simulations now suggest that its orbit was tilted by gravitational interactions with a few large bodies. See Letter p.492

doi: 10.1038/527455a

Assassins of eyesight p.456

A molecular cascade involving the transcription factor SIX6 and its target gene p16INK4a causes the death of neurons that link the eye to the brain. This discovery deepens our understanding of a common form of blindness, glaucoma.

doi: 10.1038/527456a

Articles

Hemichordate genomes and deuterostome origins OPEN p.459

Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).

doi: 10.1038/nature16150

Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65 p.477

Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, ‘ogerin’, as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.

doi: 10.1038/nature15699

Letters

Extremely metal-poor stars from the cosmic dawn in the bulge of the Milky Way p.484

The first stars and their immediate successors should be found today in the central regions (bulges) of galaxies; old, metal-poor stars have now been found in the Milky Way bulge, including one star with an iron abundance about 10,000 times lower than that of the Sun without noticeable carbon enhancement, making it possibly the oldest known star in the Galaxy.

doi: 10.1038/nature15747

Ubiquitous time variability of integrated stellar populations p.488

The number of long-period variable stars in a stellar population is directly related to their lifetime, which is difficult to predict from first principles; here a time-dependent stellar population model is constructed that includes the effects of long-period variable stars, and is applied to the galaxy M87.

doi: 10.1038/nature15731

Type-II Weyl semimetals p.495

A new type of topological semimetal is described, which contains so-called type-II Weyl fermions and has very different properties to standard Weyl semimetals, owing to the existence of an open Fermi surface rather than a point-like one in the vicinity of Weyl points; WTe2 is predicted to be one such semimetal.

doi: 10.1038/nature15768

Extra adsorption and adsorbate superlattice formation in metal-organic frameworks p.503

Metal-organic frameworks (MOFs) have a high internal surface area and widely tunable composition, which make them useful for applications involving adsorption, such as hydrogen, methane or carbon dioxide storage. The selectivity and uptake capacity of the adsorption process are determined by interactions involving the adsorbates and their porous host materials. But, although the interactions of adsorbate molecules with the internal MOF surface and also amongst themselves within individual pores have been extensively studied, adsorbate–adsorbate interactions across pore walls have not been explored. Here we show that local strain in the MOF, induced by pore filling, can give rise to collective and long-range adsorbate–adsorbate interactions and the formation of adsorbate superlattices that extend beyond an original MOF unit cell. Specifically, we use in situ small-angle X-ray scattering to track and map the distribution and ordering of adsorbate molecules in five members of the mesoporous MOF-74 series along entire adsorption–desorption isotherms. We find in all cases that the capillary condensation that fills the pores gives rise to the formation of ‘extra adsorption domains’—that is, domains spanning several neighbouring pores, which have a higher adsorbate density than non-domain pores. In the case of one MOF, IRMOF-74-V-hex, these domains form a superlattice structure that is difficult to reconcile with the prevailing view of pore-filling as a stochastic process. The visualization of the adsorption process provided by our data, with clear evidence for initial adsorbate aggregation in distinct domains and ordering before an even distribution is finally reached, should help to improve our understanding of this process and may thereby improve our ability to exploit it practically.

doi: 10.1038/nature15734

Endoperoxide formation by an α-ketoglutarate-dependent mononuclear non-haem iron enzyme p.539

Many peroxy-containing secondary metabolites have been isolated and shown to provide beneficial effects to human health. Yet, the mechanisms of most endoperoxide biosyntheses are not well understood. Although endoperoxides have been suggested as key reaction intermediates in several cases, the only well-characterized endoperoxide biosynthetic enzyme is prostaglandin H synthase, a haem-containing enzyme. Fumitremorgin B endoperoxidase (FtmOx1) from Aspergillus fumigatus is the first reported α-ketoglutarate-dependent mononuclear non-haem iron enzyme that can catalyse an endoperoxide formation reaction. To elucidate the mechanistic details for this unique chemical transformation, we report the X-ray crystal structures of FtmOx1 and the binary complexes it forms with either the co-substrate (α-ketoglutarate) or the substrate (fumitremorgin B). Uniquely, after α-ketoglutarate has bound to the mononuclear iron centre in a bidentate fashion, the remaining open site for oxygen binding and activation is shielded from the substrate or the solvent by a tyrosine residue (Y224). Upon replacing Y224 with alanine or phenylalanine, the FtmOx1 catalysis diverts from endoperoxide formation to the more commonly observed hydroxylation. Subsequent characterizations by a combination of stopped-flow optical absorption spectroscopy and freeze-quench electron paramagnetic resonance spectroscopy support the presence of transient radical species in FtmOx1 catalysis. Our results help to unravel the novel mechanism for this endoperoxide formation reaction.

doi: 10.1038/nature15519