Volume 513 Issue 7519

Editorials

Staff support p.459

German research organizations need to help their workers to defend animal research.

doi: 10.1038/513459b

First response, revisited p.459

The Ebola outbreak in West Africa has starkly exposed major gaps in plans to tackle emerging infectious diseases. Lessons must be learned.

doi: 10.1038/513459a

Special interest p.460

As the Scottish referendum showed, scientists’ views can influence political debate.

doi: 10.1038/513460a

News

News Features

Ebola’s lost ward p.474

A hospital in Sierra Leone has struggled to continue its research amid the worst Ebola outbreak in history.

doi: 10.1038/513474a

News & Views

A fresh look at river flow p.490

A detailed survey of the Fraser River in Canada challenges preconceptions about how river water flows. The results call for a re-evaluation of how waterways carve through bedrock to form canyons. See Letter p.534

doi: 10.1038/513490a

Ribosome revelations p.491

Proteins are synthesized in cells by the ribosome apparatus. A report of 16 yeast ribosome structures, each bound by a different inhibitor, broadens our understanding of how drugs affect ribosome activity.

doi: 10.1038/nature13747

Window on a watery world p.493

The first definitive signs of water have been seen in the atmosphere of a Neptune-sized exoplanet, paving the way towards the search for water on smaller Earth-like planets. See Letter p.526

doi: 10.1038/513493a

Statins give bone growth a boost p.494

The development of stem-cell-based models of two diseases that cause dwarfism reveals that statins — drugs that are used to treat high levels of blood cholesterol — may also promote cartilage formation and bone growth.

doi: 10.1038/nature13750

How calcium affects oxygen formation p.495

Calcium is an essential component of the catalyst that forms oxygen from water during photosynthesis. It seems that part of calcium's job is to enable the release of oxygen from this catalyst.

doi: 10.1038/nature13753

Towards turbocharged photosynthesis p.497

The development of tobacco plants that are genetically engineered to produce a more efficient form of Rubisco, an enzyme involved in photosynthesis, marks a step towards increasing crop yields.

doi: 10.1038/nature13749

A compass for stem-cell differentiation p.498

The development of CellNet — network-biology software that determines how cell types generated in vitro relate to their naturally occurring counterparts — could improve our ability to produce desirable cells in culture.

doi: 10.1038/513498a

Articles

Asian monsoons in a late Eocene greenhouse world p.501

Asian monsoons were strongly active 40 million years ago and were enhanced by high atmospheric CO2 content. They were significantly weakened when CO2 levels decreased 34 million years ago and then reinitiated several million years later.

doi: 10.1038/nature13704

Statin treatment rescues FGFR3 skeletal dysplasia phenotypes p.507

This study reprograms fibroblasts from thanatophoric dysplasia type I (TD1) and achondroplasia (ACH) patients into induced pluripotent stem cells (iPSCs), finding that chondrogenic differentiation results in the formation of degraded cartilage; statin treatment led to significant recovery of bone growth in a mouse model of ACH.

doi: 10.1038/nature13775

Loss of oncogenic Notch1 with resistance to a PI3K inhibitor in T-cell leukaemia p.512

Mutations that dysregulate Notch1 and Ras/PI3K signalling are common in T-cell acute lymphoblastic leukaemia; here, treatment with a PI3K inhibitor is shown to induce drug resistance that is associated with downregulation of activated Notch1 signalling, suggesting that inhibition of both Notch1 and PI3K could promote drug resistance.

doi: 10.1038/nature13495

Structural basis for the inhibition of the eukaryotic ribosome p.517

Whereas previous structural investigation of ribosome inhibitors has been done using the prokaryotic ribosome, this work presents X-ray crystal structures of the yeast ribosome in complex with 16 inhibitors including eukaryotic-specific inhibitors; the inhibitors all bind the mRNA or tRNA binding sites, larger molecules appear to target specifically the first elongation cycle.

doi: 10.1038/nature13737

Letters

Water vapour absorption in the clear atmosphere of a Neptune-sized exoplanet p.526

Space telescope observations of the transmission spectrum of the extrasolar planet HAT-P-11b, which is about the same size as Neptune, reveal water vapour absorption at a wavelength of 1.4 micrometres and indicate that the planetary atmosphere is predominantly clear down to an altitude corresponding to about 1 millibar.

doi: 10.1038/nature13785

Flow in bedrock canyons p.534

A survey along the Fraser Canyon in Canada reveals complex flow dynamics involving velocity inversions and upwelling, which suggests ways to improve flow and bedrock incision modelling.

doi: 10.1038/nature13779

Island biogeography of the Anthropocene p.543

A contemporary test of the theory of island biogeography, in which species richness is determined by an island’s area and isolation, shows that geographic area is still a good positive predictor of species richness, but that geographic isolation as a negative predictor has been replaced by economic isolation.

doi: 10.1038/nature13739

A faster Rubisco with potential to increase photosynthesis in crops p.547

In photosynthetic organisms, d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the major enzyme assimilating atmospheric CO2 into the biosphere. Owing to the wasteful oxygenase activity and slow turnover of Rubisco, the enzyme is among the most important targets for improving the photosynthetic efficiency of vascular plants. It has been anticipated that introducing the CO2-concentrating mechanism (CCM) from cyanobacteria into plants could enhance crop yield. However, the complex nature of Rubisco’s assembly has made manipulation of the enzyme extremely challenging, and attempts to replace it in plants with the enzymes from cyanobacteria and red algae have not been successful. Here we report two transplastomic tobacco lines with functional Rubisco from the cyanobacterium Synechococcus elongatus PCC7942 (Se7942). We knocked out the native tobacco gene encoding the large subunit of Rubisco by inserting the large and small subunit genes of the Se7942 enzyme, in combination with either the corresponding Se7942 assembly chaperone, RbcX, or an internal carboxysomal protein, CcmM35, which incorporates three small subunit-like domains. Se7942 Rubisco and CcmM35 formed macromolecular complexes within the chloroplast stroma, mirroring an early step in the biogenesis of cyanobacterial β-carboxysomes. Both transformed lines were photosynthetically competent, supporting autotrophic growth, and their respective forms of Rubisco had higher rates of CO2 fixation per unit of enzyme than the tobacco control. These transplastomic tobacco lines represent an important step towards improved photosynthesis in plants and will be valuable hosts for future addition of the remaining components of the cyanobacterial CCM, such as inorganic carbon transporters and the β-carboxysome shell proteins.

doi: 10.1038/nature13776

Antifungal drug resistance evoked via RNAi-dependent epimutations p.555

The human fungal pathogen Mucor circinelloides develops spontaneous resistance to an antifungal drug both through mutation and through a newly identified epigenetic RNA-mediated pathway; RNA interference is spontaneously triggered to silence the fkbA gene, giving rise to drug-resistant epimutants that revert to being drug-sensitive once again when grown in the absence of drug.

doi: 10.1038/nature13575

The alarmin IL-33 promotes regulatory T-cell function in the intestine p.564

The alarmin interleukin-33 is constitutively expressed at barrier sites and released in response to tissue damage; here, the IL-33 receptor ST2 is shown to be preferentially expressed on colonic regulatory T cells, where it promotes regulatory T-cell function and adaptation to the inflammatory tissue environment.

doi: 10.1038/nature13577

Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease p.569

The CRISPR-associated protein Cas9 is an RNA-guided endonuclease that cleaves double-stranded DNA bearing sequences complementary to a 20-nucleotide segment in the guide RNA. Cas9 has emerged as a versatile molecular tool for genome editing and gene expression control. RNA-guided DNA recognition and cleavage strictly require the presence of a protospacer adjacent motif (PAM) in the target DNA. Here we report a crystal structure of Streptococcus pyogenes Cas9 in complex with a single-molecule guide RNA and a target DNA containing a canonical 5′-NGG-3′ PAM. The structure reveals that the PAM motif resides in a base-paired DNA duplex. The non-complementary strand GG dinucleotide is read out via major-groove interactions with conserved arginine residues from the carboxy-terminal domain of Cas9. Interactions with the minor groove of the PAM duplex and the phosphodiester group at the +1 position in the target DNA strand contribute to local strand separation immediately upstream of the PAM. These observations suggest a mechanism for PAM-dependent target DNA melting and RNA–DNA hybrid formation. Furthermore, this study establishes a framework for the rational engineering of Cas9 enzymes with novel PAM specificities.

doi: 10.1038/nature13579