Volume 522 Number 7557

Editorials

Data overprotection p.391

Draft European rules governing privacy threaten to hamper medical research.

doi: 10.1038/522391b

Hope from the Pope p.391

The Vatican has produced a timely and valuable warning on the threat of climate change that will reach a wide audience.

doi: 10.1038/522391a

Life under the ice p.392

Antarctica’s apparent barrenness hides an abundance of living organisms.

doi: 10.1038/522392a

News

News Features

Sir Paul’s cathedral p.406

When the Francis Crick Institute opens in London this year, it will be Europe’s largest biomedical research centre. Can director Paul Nurse make this gamble pay off for UK science?

doi: 10.1038/522406a

The hard science of oxytocin p.410

As researchers work out how oxytocin affects the brain, the hormone is shedding its reputation as a simple cuddle chemical.

doi: 10.1038/522410a

News & Views

Dust-poor galaxies at early times p.422

Observations of galaxies that formed early in the Universe's history reveal much lower dust levels than are found in sources from a slightly later era. It seems that galaxies underwent rapid change during a relatively short period. See Letter p.455

doi: 10.1038/522422a

Evolved protection against human prions p.423

A genetic variant of PrP, the protein that forms prions, confers protection against the human prion disease kuru by inhibiting the conversion of functional isoforms to the abnormal, disease-causing conformation. See Letter p.478

doi: 10.1038/nature14534

Precision positioning with peptides p.424

Two related peptides compete for binding to the same receptor to regulate the spacing of cells on the lower surfaces of leaves. This discovery highlights the complexity of cell signalling in plants. See Article p.439

doi: 10.1038/nature14535

The dynamics of temperature extremes p.425

Changes in the occurrence of atmospheric circulation patterns are not well understood. A study finds that these have been a big factor in observed changes in regional temperature extremes during recent decades. See Letter p.465

doi: 10.1038/522425a

Unexpected role for vitamin B2 p.427

An enzyme has been found that alters the molecular structure of vitamin B2, adding a fourth ring to its existing three-ring system. The product catalyses new types of chemistry in concert with certain other enzymes. See Letters p.497 & p.502

doi: 10.1038/nature14536

Sugar for sight p.428

Retinitis pigmentosa causes the death of cone cells, leading to blindness. A factor secreted from rod cells, RdCVF, promotes cone survival in a mouse model of the disease. It now emerges that RdCVF works by increasing glucose uptake in cones.

doi: 10.1038/522428a

Review

The changing form of Antarctic biodiversity p.431

Recent research has shown that while large fauna and flowering plants in the Antarctic are scarce, there are considerable levels of marine and terrestrial biodiversity, particularly the microbiota; what drives it, and how the Antarctic can meet conservation targets, are the subject of this review.

doi: 10.1038/nature14505

Articles

Competitive binding of antagonistic peptides fine-tunes stomatal patterning p.439

An investigation of the molecular mechanism of stomatal development and patterning finds an unexpected signalling mechanism: two signalling peptides (STOMAGEN, a positive regulator of stomatal development; and EPF2, a negative regulator of this process) use the same receptor kinase, ERECTA, to fine-tune stomatal development.

doi: 10.1038/nature14561

HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease p.444

Myocardial hypoxia activates HIF1α, which activates the splicing factor SF3B1, which mediates a splice switch of the fructose-metabolising enzyme KHK, so that the C isoform that has superior affinity for fructose is expressed in the heart—pathological heart growth and contractile dysfunction can therefore be suppressed by depleting SF3B1 or deleting KHK.

doi: 10.1038/nature14508

Letters

Galaxies at redshifts 5 to 6 with systematically low dust content and high [C ii] emission p.455

The rest-frame ultraviolet properties of galaxies during the first three billion years of cosmic time (redshift z > 4) indicate a rapid evolution in the dust obscuration of such galaxies. This evolution implies a change in the average properties of the interstellar medium, but the measurements are systematically uncertain owing to untested assumptions and the inability to detect heavily obscured regions of the galaxies. Previous attempts to measure the interstellar medium directly in normal galaxies at these redshifts have failed for a number of reasons, with two notable exceptions. Here we report measurements of the forbidden C ii emission (that is, [C ii]) from gas, and the far-infrared emission from dust, in nine typical star-forming galaxies about one billion years after the Big Bang (z ≈ 5–6). We find that these galaxies have thermal emission that is less than 1/12 that of similar systems about two billion years later, and enhanced [C ii] emission relative to the far-infrared continuum, confirming a strong evolution in the properties of the interstellar medium in the early Universe. The gas is distributed over scales of one to eight kiloparsecs, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z < 3 and being comparable in dust content to local low-metallicity systems.

doi: 10.1038/nature14500

Linking high harmonics from gases and solids p.462

High-harmonic generation in zinc oxide illuminated by an intense, pulsed, mid-infrared laser is found to involve a recollision effect in which electrons recollide with holes causing harmonics to be emitted, a process similar to that which occurs in atomic systems.

doi: 10.1038/nature14517

Contribution of changes in atmospheric circulation patterns to extreme temperature trends p.465

This study identifies statistically significant trends in mid-atmospheric circulation patterns that partially explain observed changes in extreme temperature occurrence over Eurasia and North America; although the underlying cause of circulation pattern trends remains uncertain, most extreme temperature trends are shown to be consistent with thermodynamic warming.

doi: 10.1038/nature14550

PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal p.474

Many acute and chronic anaemias, including haemolysis, sepsis and genetic bone marrow failure diseases such as Diamond–Blackfan anaemia, are not treatable with erythropoietin (Epo), because the colony-forming unit erythroid progenitors (CFU-Es) that respond to Epo are either too few in number or are not sensitive enough to Epo to maintain sufficient red blood cell production. Treatment of these anaemias requires a drug that acts at an earlier stage of red cell formation and enhances the formation of Epo-sensitive CFU-E progenitors. Recently, we showed that glucocorticoids specifically stimulate self-renewal of an early erythroid progenitor, burst-forming unit erythroid (BFU-E), and increase the production of terminally differentiated erythroid cells. Here we show that activation of the peroxisome proliferator-activated receptor α (PPAR-α) by the PPAR-α agonists GW7647 and fenofibrate synergizes with the glucocorticoid receptor (GR) to promote BFU-E self-renewal. Over time these agonists greatly increase production of mature red blood cells in cultures of both mouse fetal liver BFU-Es and mobilized human adult CD34+ peripheral blood progenitors, with a new and effective culture system being used for the human cells that generates normal enucleated reticulocytes. Although Ppara−/− mice show no haematological difference from wild-type mice in both normal and phenylhydrazine (PHZ)-induced stress erythropoiesis, PPAR-α agonists facilitate recovery of wild-type but not Ppara−/− mice from PHZ-induced acute haemolytic anaemia. We also show that PPAR-α alleviates anaemia in a mouse model of chronic anaemia. Finally, both in control and corticosteroid-treated BFU-E cells, PPAR-α co-occupies many chromatin sites with GR; when activated by PPAR-α agonists, additional PPAR-α is recruited to GR-adjacent sites and presumably facilitates GR-dependent BFU-E self-renewal. Our discovery of the role of PPAR-α agonists in stimulating self-renewal of early erythroid progenitor cells suggests that the clinically tested PPAR-α agonists we used may improve the efficacy of corticosteroids in treating Epo-resistant anaemias.

doi: 10.1038/nature14326

A naturally occurring variant of the human prion protein completely prevents prion disease p.478

This study looks at a polymorphism of the human prion protein gene, which results in a G-to-V substitution at residue 127, in transgenic mice expressing different human prion proteins, finding that mice heterozygous for the G127V polymorphism are resistant to both kuru and classical CJD prions, but there is some transmission of variant CJD prions; most remarkable, however, is that mice homozygous for V127 are completely resistant to all prion strains.

doi: 10.1038/nature14510

New cofactor supports α,β-unsaturated acid decarboxylation via 1,3-dipolar cycloaddition p.497

The bacterial ubiD and ubiX or the homologous fungal fdc1 and pad1 genes have been implicated in the non-oxidative reversible decarboxylation of aromatic substrates, and play a pivotal role in bacterial ubiquinone (also known as coenzyme Q) biosynthesis or microbial biodegradation of aromatic compounds, respectively. Despite biochemical studies on individual gene products, the composition and cofactor requirement of the enzyme responsible for in vivo decarboxylase activity remained unclear. Here we show that Fdc1 is solely responsible for the reversible decarboxylase activity, and that it requires a new type of cofactor: a prenylated flavin synthesized by the associated UbiX/Pad1. Atomic resolution crystal structures reveal that two distinct isomers of the oxidized cofactor can be observed, an isoalloxazine N5-iminium adduct and a N5 secondary ketimine species with markedly altered ring structure, both having azomethine ylide character. Substrate binding positions the dipolarophile enoic acid group directly above the azomethine ylide group. The structure of a covalent inhibitor–cofactor adduct suggests that 1,3-dipolar cycloaddition chemistry supports reversible decarboxylation in these enzymes. Although 1,3-dipolar cycloaddition is commonly used in organic chemistry, we propose that this presents the first example, to our knowledge, of an enzymatic 1,3-dipolar cycloaddition reaction. Our model for Fdc1/UbiD catalysis offers new routes in alkene hydrocarbon production or aryl (de)carboxylation.

doi: 10.1038/nature14560