Volume 512 Number 7512

Editorial

Home-brew tests need regulation p.5

A US proposal to regulate medical diagnostics from individual labs reflects the tests’ growing complexity. Such guidance should be welcomed, not resisted.

doi: 10.1038/512005a

News

News Features

THE ROBO-CHEMIST p.20

The race is on to build a machine that can synthesize any organic compound. It could transform chemistry.

doi: 10.1038/512020a

News & Views

Seeds of selective nanotube growth p.30

'Seed' molecules have been made that enable synthesis of just one kind of single-walled carbon nanotube, rather than a mixture of species. This paves the way for the preparation of pure samples of any nanotube species. See Letter p.61

doi: 10.1038/512030a

Directions for the drivers p.31

A comparison of colorectal cancer and normal cells from 103 patients identifies dozens of genes that are differently expressed in tumour cells as a result of altered regulation of transcription. See Letter p.87

doi: 10.1038/nature13649

Alzheimer's disease under strain p.32

Two studies of amyloid-β protein aggregates, which cause Alzheimer's disease, find that different conformations of the aggregates can define different strains of the disorder, drawing parallels with prion diseases.

doi: 10.1038/512032a

Portrait of a doomed star p.34

Some stars explode in thermonuclear supernovae, but understanding of why this occurs comes mainly from indirect clues. Now, the progenitor of a member of a strange class of such explosions may have been detected directly. See Letter p.54

doi: 10.1038/512034a

Early treatment may not be early enough p.35

Giving monkeys antiretroviral therapy from just three days after exposure to simian immunodeficiency virus does not prevent a subsequent rebound of viral replication, suggesting that viral reservoirs are established early. See Letter p.74

doi: 10.1038/nature13647

Tooth structure re-engineered p.36

Mice deficient in the EDA protein lack normal tooth features. Restoring EDA in embryonic teeth at increasing doses has now been found to recover these dental features in a stepwise pattern that mimics evolution. See Article p.44

doi: 10.1038/nature13651

Articles

Convergence of terrestrial plant production across global climate gradients p.39

Net primary production is affected by temperature and precipitation, but whether this is a direct kinetic effect on plant metabolism or an indirect ecological effect mediated by changes in plant age, plant biomass or growing season length is unclear — this study develops metabolic scaling theory to be able to answer this question and applies it to a global data set of plant productivity, concluding that it is indirect effects that explain the influence of climate on productivity, which is characterized by a common scaling relationship across climate gradients.

doi: 10.1038/nature13470

Replaying evolutionary transitions from the dental fossil record p.44

Gradual changes that occur to mammalian tooth morphology across evolutionary time were modeled in vitro and in vivo by modulation of signalling pathways in the mouse, and computer modelling was used to provide further analysis of the parameters influencing tooth morphology.

doi: 10.1038/nature13613

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide p.49

The crystal structures of thalidomide and its derivatives bound to the E3 ligase subcomplex DDB1–CRBN are shown; these drugs are found to have dual functions, interfering with the binding of certain cellular substrates to the E3 ligase but promoting the binding of others, thereby modulating the degradation of cellular proteins.

doi: 10.1038/nature13527

Letters

Controlled synthesis of single-chirality carbon nanotubes p.61

Present preparation methods fail to meet fully the demand for structurally pure single-walled carbon nanotubes; surface-catalysed cyclodehydrogenation reactions are now shown to convert precursor molecules deposited on a platinum(111) surface into ultrashort nanotube seeds that can then be grown further into defect-free and structurally pure single-walled carbon nanotubes of single chirality.

doi: 10.1038/nature13607

Neuropathy of haematopoietic stem cell niche is essential for myeloproliferative neoplasms p.78

Myeloproliferative neoplasms are caused by mutations in the haematopoietic stem cell (HSC) compartment, and here the authors show that the HSC niche contributes to the pathogenesis; sympathetic innervation of mesenchymal stem cells (MSCs) is reduced in the bone marrow of patients, which leads to reduced MSC numbers and increased mutant HSC expansion, and restoring sympathetic regulation of MSCs with neuroprotective/sympathomimetic drugs prevents mutant HSC expansion.

doi: 10.1038/nature13383

Putative cis-regulatory drivers in colorectal cancer p.87

Examination of allele-specific expression identifies 71 genes with excess somatic cis-regulatory effects in colorectal cancer (CRC), and 1,693 and 948 expression quantitative trait loci (eQTLs) in normal samples and tumours, respectively (with 36% of tumour eQTLs exclusive to CRC); tumour-specific eQTLs are more enriched for low CRC genome-wide association study P values and accumulate more somatic mutations than shared eQTLs, suggesting a role as germline-derived cancer regulatory drivers.

doi: 10.1038/nature13602

Enhancer loops appear stable during development and are associated with paused polymerase p.96

A high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis shows that although local regulatory interactions are frequent, long-range interactions are also very common; unexpectedly, most interactions appear unchanged between tissues and across development and are formed prior to gene expression, indicating that transcription initiates from preformed enhancer–promoter loops, which are associated with paused polymerase.

doi: 10.1038/nature13417

Visualizing the kinetic power stroke that drives proton-coupled zinc(ii) transport p.101

The proton gradient is a principal energy source for respiration-dependent active transport, but the structural mechanisms of proton-coupled transport processes are poorly understood. YiiP is a proton-coupled zinc transporter found in the cytoplasmic membrane of Escherichia coli. Its transport site receives protons from water molecules that gain access to its hydrophobic environment and transduces the energy of an inward proton gradient to drive Zn(ii) efflux. This membrane protein is a well-characterized member of the family of cation diffusion facilitators that occurs at all phylogenetic levels. Here we show, using X-ray-mediated hydroxyl radical labelling of YiiP and mass spectrometry, that Zn(ii) binding triggers a highly localized, all-or-nothing change of water accessibility to the transport site and an adjacent hydrophobic gate. Millisecond time-resolved dynamics reveal a concerted and reciprocal pattern of accessibility changes along a transmembrane helix, suggesting a rigid-body helical re-orientation linked to Zn(ii) binding that triggers the closing of the hydrophobic gate. The gated water access to the transport site enables a stationary proton gradient to facilitate the conversion of zinc-binding energy to the kinetic power stroke of a vectorial zinc transport. The kinetic details provide energetic insights into a proton-coupled active-transport reaction.

doi: 10.1038/nature13382