The way forward is through Paris p.409

Once a solid agreement is made, the world must get to work.

doi: 10.1038/527409a

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Drugs on demand p.410

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

doi: 10.1038/527410b

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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

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Salmon approval heralds rethink of transgenic animals p.417

Long-awaited decision by US government authorizes the first genetically engineered animal to be sold as food.

doi: 10.1038/527417a

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Climate optimism builds ahead of Paris talks p.418

Emission pledges raise hopes for an international treaty.

doi: 10.1038/527418a

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Green Climate Fund faces slew of criticism p.419

First tranche of aid projects prompts concern over operations of fund for developing nations.

doi: 10.1038/nature.2015.18815

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Brazilian courts tussle over unproven cancer treatment p.420

Patients demand access to compound despite lack of clinical testing.

doi: 10.1038/527420a

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Leap-second decision delayed by eight years p.421

Some want to scrap adjustment that keeps atomic time in sync with Earth's rotation.

doi: 10.1038/nature.2015.18855

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'Digital chimp' trove preserves brains of retired apes p.422

NIH to fund a cache of brain tissue and online data in place of live-animal experimentation.

doi: 10.1038/527422a

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News Features


All together now p.425


doi: 10.1038/527425a

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The fragile framework p.427

各国は、団結して地球を守れるのだろうか? 気候変動枠組条約に関するこれまでの物語をコミックでたどる。

doi: 10.1038/527427a

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Is the 2 °C world a fantasy? p.436


doi: 10.1038/527436a

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News & Views


Genomics: Acorn worms in a nutshell p.448


doi: 10.1038/nature16315

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Circadian clocks: A receptor for subtle temperature changes p.449


doi: 10.1038/nature16316

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Imaging techniques: Super-resolution ultrasound p.451


doi: 10.1038/527451a

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Cell fate: Transition loses its invasive edge p.452


doi: 10.1038/nature16313

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Ebola: Hidden reservoirs p.453


doi: 10.1038/527453a

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Planetary science: The Moon's tilt for gold p.455


doi: 10.1038/527455a

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Blindness: Assassins of eyesight p.456


doi: 10.1038/527456a

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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

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A perisinusoidal niche for extramedullary haematopoiesis in the spleen p.466

Haematopoietic stem cells normally reside in a bone marrow niche but they are recruited to the spleen after physiological stresses; here, endothelial cells and stromal cells around sinusoidal blood vessels of the spleen are shown to secrete key niche factors to support this process.

doi: 10.1038/nature15530

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Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance p.472

An epithelial-to-mesenchymal transition (EMT) lineage-tracing system in a mouse model of breast-to-lung metastasis reveals that although some cells undergo EMT in a primary epithelial tumour, the lung metastases mainly arise from cells that have not undergone EMT; in addition, cells that have undergone EMT appear more resistant to chemotherapy.

doi: 10.1038/nature15748

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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

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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

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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

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Collisionless encounters and the origin of the lunar inclination p.492

Gravitational interactions after the Moon-forming event suggest that the current lunar inclination is the result of collisionless encounters of planetesimals with the early Moon–Earth system.

doi: 10.1038/nature16137

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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

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Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging p.499

Conventional clinical ultrasound imaging has, at best, sub-millimetre-scale resolution, but now a new ultrasound technique is demonstrated that is based on fast tracking of transient signals from a sub-wavelength contrast agent and has sufficiently high resolution to map the microvasculature deep into organs.

doi: 10.1038/nature16066

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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

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植物科学:脱水耐性のあるイネ科植物Oropetium thomaeumの単一分子塩基配列解読

Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum OPEN p.508

Oropetium thomaeum is a resurrection plant that can survive extreme water stress through desiccation to complete dryness, providing a model for drought tolerance; here, whole-genome sequencing and assembly of the Oropetium genome using single-molecule real-time sequencing is reported.

doi: 10.1038/nature15714

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Sweet and bitter taste in the brain of awake behaving animals p.512

Activation of the sweet and bitter cortical fields in awake mice evokes predetermined behavioural programs, independent of learning and experience, illustrating the hardwired and innate nature of the sense of taste.

doi: 10.1038/nature15763

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Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature p.516

A Drosophila chemosensory receptor, expressed in leg sensory neurons, is necessary for behavioural and molecular synchronization of the fly’s circadian clock to low-amplitude temperature cycles; this temperature-sensing pathway functions independently from the known temperature sensors of the fly’s antennae.

doi: 10.1038/nature16148

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Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals p.521

Fungal pathogens reorient hyphal growth towards their plant hosts in response to chemical signals; here, directed growth of the plant pathogen Fusarium oxysporum towards the roots of the tomato plant is shown to be triggered by class III peroxidases secreted by the tomato plant, with the fungal response requiring a sex pheromone receptor.

doi: 10.1038/nature15516

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Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer p.525

Deletion of Twist or Snail, two key transcription factors that induce epithelial-to-mesenchymal transition in a mouse model of pancreatic ductal adenocarcinoma leads to an increase in cell proliferation, and a greater sensitivity to the chemotherapeutic agent gemcitabine, with no effect on invasion or metastasis.

doi: 10.1038/nature16064

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ウイルス学:dsRNAウイルス内の分節化されたゲノムとRNAポリメラーゼ複合体のin situ構造

In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus p.531

This study visualizes the interior of a dsRNA virus using cryo-electron microscopy, revealing the organization of the genome of cytoplasmic polyhedrosis virus together with its transcriptional enzyme complex in both quiescent and transcribing states.

doi: 10.1038/nature15767

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Foreign DNA capture during CRISPR–Cas adaptive immunity p.535

The structure of the Cas1–Cas2 complex bound to a protospacer sequence illustrates how foreign DNA is captured and measured by bacterial proteins in preparation for integration into CRISPR loci.

doi: 10.1038/nature15760

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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

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