Volume 514 Issue 7521

Editorials

A little knowledge p.139

The significance of expertise passed on by direct contact— tacit knowledge — is moot.

doi: 10.1038/514139b

Out of Africa p.139

The Ebola outbreak in West Africa must be shut down now, or the disease will continue to spread.

doi: 10.1038/514139a

Holy cows p.140

A mass beaching of walruses in Alaska is a sign of things to come.

doi: 10.1038/514140a

News

News Features

Brains of Norway p.154

Nobel prizewinners May-Britt Moser and Edvard Moser have spent a career together near the Arctic Circle exploring how our brains know where we are.

doi: 10.1038/514154a

The big reboot p.158

As the Large Hadron Collider prepares to come back to life after a two-year hiatus, physicists are gearing up to go beyond the standard model of particle physics.

doi: 10.1038/514158a

News & Views

Art on the move p.170

Studies of stencils and paintings from prehistoric caves in Indonesia date the art to at least 39,900 years ago — around the same age as the earliest cave art previously known, 13,000 kilometres away in western Europe. See Letter p.223

doi: 10.1038/514170a

Small field with a large impact p.171

The nature of ultraluminous X-ray astronomical sources has long been unclear. The latest observations of these rare systems provide some crucial clues, but still leave theorists scratching their heads. See Letters p.198 & p.202

doi: 10.1038/514171a

Lariat lessons p.173

The spliceosome enzyme complex removes intron sequences from RNA transcripts to form messenger RNA. The crystal structure of a lasso-shaped RNA suggests a mechanism for this splicing process. See Article p.193

doi: 10.1038/nature13754

The mass of a top p.174

A measurement of the mass of the heftiest-known elementary particle, the top quark, which exists for less than a trillionth of a trillionth of a second, sheds light on the ultimate fate of our Universe, although ambiguities cloud its interpretation.

doi: 10.1038/514174a

The weighty costs of non-caloric sweeteners p.176

Analyses in mice and humans indicate that non-caloric artificial sweeteners may promote obesity-associated metabolic changes by changing the function of the bacteria that colonize the gut. See Article p.181

doi: 10.1038/nature13752

Good vibrations p.177

A newly constructed electron-energy monochromator for an atomic-resolution transmission electron microscope has resolved spectroscopic signatures of chemical-bond vibrations that are spatially highly localized. See Letter p.209

doi: 10.1038/514177a

Incipient tradition in wild chimpanzees p.178

The adoption of a new form of tool use has been observed to spread along social-network pathways in a chimpanzee community. The finding offers the first direct evidence of cultural diffusion in these animals in the wild.

doi: 10.1038/nature13759

Articles

Artificial sweeteners induce glucose intolerance by altering the gut microbiota p.181

Non-caloric artificial sweeteners (NAS), widely used food additives considered to be safe and beneficial alternatives to sugars, are shown here to lead to the development of glucose intolerance through compositional and functional changes in the gut microbiota of mice, and the deleterious metabolic effects are transferred to germ-free mice by faecal transplant; NAS-induced dysbiosis and glucose intolerance are also demonstrated in healthy human subjects.

doi: 10.1038/nature13793

Letters

An ultraluminous X-ray source powered by an accreting neutron star p.202

X-ray pulsations with an average period of 1.37 seconds have been detected from a known ultraluminous X-ray source hitherto thought to be a black hole; the pulsations instead unequivocally identify the source as an accreting magnetized neutron star ten times brighter than any previously known.

doi: 10.1038/nature13791

Large, non-saturating magnetoresistance in WTe2 p.205

The magnetoresistance effect in WTe2, a layered semimetal, is extremely large: the electrical resistance can be changed by more than 13 million per cent at very high magnetic fields and low temperatures.

doi: 10.1038/nature13763

Pleistocene cave art from Sulawesi, Indonesia p.223

Cave art from the island of Sulawesi in Indonesia, consisting of human hand stencils and animal paintings, is at least 40,000 years old, raising the question of why rock art traditions appeared at more or less the same time at opposite ends of the Late Pleistocene human world.

doi: 10.1038/nature13422

HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia p.242

β-Thalassaemia major (β-TM) is an inherited haemoglobinopathy caused by a quantitative defect in the synthesis of β-globin chains of haemoglobin, leading to the accumulation of free α-globin chains that form toxic aggregates. Despite extensive knowledge of the molecular defects causing β-TM, little is known of the mechanisms responsible for the ineffective erythropoiesis observed in the condition, which is characterized by accelerated erythroid differentiation, maturation arrest and apoptosis at the polychromatophilic stage. We have previously demonstrated that normal human erythroid maturation requires a transient activation of caspase-3 at the later stages of maturation. Although erythroid transcription factor GATA-1, the master transcriptional factor of erythropoiesis, is a caspase-3 target, it is not cleaved during erythroid differentiation. We have shown that, in human erythroblasts, the chaperone heat shock protein70 (HSP70) is constitutively expressed and, at later stages of maturation, translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. The primary role of this ubiquitous chaperone is to participate in the refolding of proteins denatured by cytoplasmic stress, thus preventing their aggregation. Here we show in vitro that during the maturation of human β-TM erythroblasts, HSP70 interacts directly with free α-globin chains. As a consequence, HSP70 is sequestrated in the cytoplasm and GATA-1 is no longer protected, resulting in end-stage maturation arrest and apoptosis. Transduction of a nuclear-targeted HSP70 mutant or a caspase-3-uncleavable GATA-1 mutant restores terminal maturation of β-TM erythroblasts, which may provide a rationale for new targeted therapies of β-TM.

doi: 10.1038/nature13614

Mechanism of Dis3l2 substrate recognition in the Lin28–let-7 pathway p.252

The structure of mouse Dis3l2 bound to an oligoU substrate shows a funnel-like substrate-binding site with the RNA being fed into the active site along a path that is distinct from that seen in the related catalytic subunit of the exosome — 12 uracils of the oligoU-tailed RNA are recognized in a complex network of interactions, suggesting the basis for target specificity.

doi: 10.1038/nature13553