Volume 555 Issue 7694



News Features

News & Views

Precision maps for public health p.32

Researchers have produced high-resolution maps of childhood growth failure and educational attainment across Africa between 2000 and 2015, to assess progress and guide policy decisions in public health.

doi: 10.1038/d41586-018-02096-w

Qubits break the sound barrier p.33

Quantum logic gates based on trapped ions perform more accurately than solid-state devices, but have been slower. Experiments show how trapped-ion gates can be sped up, as is needed to realize a quantum computer.

doi: 10.1038/d41586-018-02402-6

A gut feeling for cellular fate p.34

A population of progenitor cells in the midgut of fruit flies undergoes differentiation in response to mechanical force. This finding marks the first time that such a phenomenon has been reported in vivo.

doi: 10.1038/d41586-018-01460-0

Quantum upside-down cake p.36

Exotic states of matter called topological superconductors have potential applications in quantum computing, but have been difficult to produce in more than one dimension. A way of overcoming this limitation has now been found.

doi: 10.1038/d41586-018-02329-y

Tight complexes from disordered proteins p.37

Charged groups on protein surfaces often take part in molecular interactions. Two unstructured proteins have been found to use charge complementarity to form a tight complex that has biologically useful kinetic properties.

doi: 10.1038/d41586-018-01694-y

A surprising chill before the cosmic dawn p.38

An experiment to estimate when stars began to form in the Universe suggests that gas temperatures just before stars appeared had fallen well below predicted limits, and that dark matter is not as shadowy as was thought.

doi: 10.1038/d41586-018-02310-9



Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source p.89

Active volcanic hotspots can tap into domains in Earth’s deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth’s interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth’s interior.

doi: 10.1038/nature25754

Circadian clock neurons constantly monitor environmental temperature to set sleep timing p.98

Circadian clocks coordinate behaviour, physiology and metabolism with Earth’s diurnal cycle. These clocks entrain to both light and temperature cycles, and daily environmental temperature oscillations probably contribute to human sleep patterns. However, the neural mechanisms through which circadian clocks monitor environmental temperature and modulate behaviour remain poorly understood. Here we elucidate how the circadian clock neuron network of Drosophila melanogaster processes changes in environmental temperature. In vivo calcium-imaging techniques demonstrate that the posterior dorsal neurons 1 (DN1ps), which are a discrete subset of sleep-promoting clock neurons, constantly monitor modest changes in environmental temperature. We find that these neurons are acutely inhibited by heating and excited by cooling; this is an unexpected result when considering the strong correlation between temperature and light, and the fact that light excites clock neurons. We demonstrate that the DN1ps rely on peripheral thermoreceptors located in the chordotonal organs and the aristae. We also show that the DN1ps and their thermosensory inputs are required for the normal timing of sleep in the presence of naturalistic temperature cycles. These results identify the DN1ps as a major gateway for temperature sensation into the circadian neural network, which continuously integrates temperature changes to coordinate the timing of sleep and activity.

doi: 10.1038/nature25740

Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel p.103

Somatic stem cells constantly adjust their self-renewal and lineage commitment by integrating various environmental cues to maintain tissue homeostasis. Although numerous chemical and biological signals have been identified that regulate stem-cell behaviour, whether stem cells can directly sense mechanical signals in vivo remains unclear. Here we show that mechanical stress regulates stem-cell differentiation in the adult Drosophila midgut through the stretch-activated ion channel Piezo. We find that Piezo is specifically expressed in previously unidentified enteroendocrine precursor cells, which have reduced proliferation ability and are destined to become enteroendocrine cells. Loss of Piezo activity reduces the generation of enteroendocrine cells in the adult midgut. In addition, ectopic expression of Piezo in all stem cells triggers both cell proliferation and enteroendocrine cell differentiation. Both the Piezo mutant and overexpression phenotypes can be rescued by manipulation of cytosolic Ca2+ levels, and increases in cytosolic Ca2+ resemble the Piezo overexpression phenotype, suggesting that Piezo functions through Ca2+ signalling. Further studies suggest that Ca2+ signalling promotes stem-cell proliferation and differentiation through separate pathways. Finally, Piezo is required for both mechanical activation of stem cells in a gut expansion assay and the increase of cytosolic Ca2+ in response to direct mechanical stimulus in a gut compression assay. Thus, our study demonstrates the existence of a specific group of stem cells in the fly midgut that can directly sense mechanical signals through Piezo.

doi: 10.1038/nature25744

Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex p.121

The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major target for the treatment of type 2 diabetes and obesity. Endogenous and mimetic GLP-1 peptides exhibit biased agonism—a difference in functional selectivity—that may provide improved therapeutic outcomes. Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Gαs heterotrimer, determined at a global resolution of 3.3 Å. At the extracellular surface, the organization of extracellular loop 3 and proximal transmembrane segments differs between our exendin-P5-bound structure and previous GLP-1-bound GLP-1 receptor structure. At the intracellular face, there was a six-degree difference in the angle of the Gαs–α5 helix engagement between structures, which was propagated across the G protein heterotrimer. In addition, the structures differed in the rate and extent of conformational reorganization of the Gαs protein. Our structure provides insights into the molecular basis of biased agonism.

doi: 10.1038/nature25773