Volume 527 Number 7576

Editorials

Care for the carers p.7

Researchers should add their voices to the effort to stop attacks on health workers in war zones.

doi: 10.1038/527007b

Ills of the system p.7

Reform is long overdue for Germany’s archaic medical-education system, which puts undue pressure on students and contaminates the scientific literature.

doi: 10.1038/527007a

Smooth operator p.8

A tribute to the nineteenth-century polymath whose algebra lets you search the Internet.

doi: 10.1038/527008a

News

News Features

The big baby experiment p.22

A London lab is deploying every technology it can to understand infant brains, and what happens when development goes awry.

doi: 10.1038/527022a

News & Views

Australia at the crossroads p.40

A modelling study argues that comprehensive policy change could limit Australia's environmental pollution while maintaining a materials-intensive path to economic growth. But other paths are worth considering. See Article p.49

doi: 10.1038/527040a

Droplets leap into action p.41

What could cause a water droplet to start bouncing on a surface? It seems that a combination of evaporation and a highly water-repellent surface induces droplet bouncing when ambient pressure is reduced. See Letter p.82

doi: 10.1038/527041a

Light on leptin link to lipolysis p.43

Cutting-edge experiments show that the hormone leptin, which is secreted by fat cells, promotes fat loss by activating the release of catecholamine signalling molecules from neurons wrapped around the fat cells.

doi: 10.1038/527043a

Electrical signalling goes bacterial p.44

The discovery that potassium ion channels are involved in electrical signalling between bacterial cells may help to unravel the role of ion channels in microbial physiology and communication. See Article p.59

doi: 10.1038/nature15641

Quantum sound waves stick together p.45

A sensitive cold-ion experiment probes sound at the level of phonons, the fundamental quantum units of vibration. It shows that phonons mix in such a way that they can be classified as 'bosonic' particles, like photons. See Letter p.74

doi: 10.1038/527045a

Expression feels two pulses p.46

Single-cell analyses reveal that combinatorial changes in the intracellular locations of transcription factors can tune the expression of the factors' target genes in response to environmental stimuli. See Article p.54

doi: 10.1038/nature15634

Articles

Combinatorial gene regulation by modulation of relative pulse timing p.54

Many gene-regulatory proteins have been shown to activate in pulses, but whether cells exploit the dynamic interaction between pulses of different regulatory proteins has remained unexplored; here single-cell videos show that yeast cells modulate the relative timing between the pulsatile transcription factors Msn2 and Mig1—a gene activator and a repressor, respectively—to control the expression of target genes in response to diverse environmental conditions.

doi: 10.1038/nature15710

Ion channels enable electrical communication in bacterial communities p.59

Ion channels in bacterial biofilms are shown to conduct long-range electrical signals within the biofilm community through the propagation of potassium ions; as predicted by a simple mathematical model, potassium channel gating is shown to coordinate metabolic states between distant cells via electrical communication.

doi: 10.1038/nature15709

Architecture of the mammalian mechanosensitive Piezo1 channel p.64

Piezo1, a mechanosensitive cation channel, senses shear stress of blood flow for proper blood vessel development, regulates red blood cell function and controls cell migration and differentiation; here a trimeric architecture of this novel class of ion channel is reported, suggesting that Piezo1 may use its peripheral propeller-like ‘blades’ as force sensors to gate the central ion-conducting pore.

doi: 10.1038/nature15247

Letters

Hong–Ou–Mandel interference of two phonons in trapped ions p.74

The Hong–Ou–Mandel effect is a quantum phenomenon that involves the interference of bosonic particles and demonstrates their indistinguishability; this effect has been demonstrated previously for photons and neutral atoms, and is now demonstrated for phonons, using a system of trapped ions that are promising building blocks for quantum computers.

doi: 10.1038/nature15735

The genetic sex-determination system predicts adult sex ratios in tetrapods p.91

An analysis of 344 species of tetrapods (birds, mammals, reptiles and amphibians) shows that taxa in which the female is heterogametic tend to have a more male-biased sex ratio; the mechanisms driving the association are unclear, but sex-determination systems are likely to have important consequences for the social behaviour and demography of tetrapods.

doi: 10.1038/nature15380

Autophagy mediates degradation of nuclear lamina p.105

In response to cancer-associated stress, autophagy machinery mediates degradation of nuclear lamina components in mammals, suggesting that cells might degrade nuclear components to prevent tumorigenesis.

doi: 10.1038/nature15548

Conformational control of DNA target cleavage by CRISPR–Cas9 p.110

Cas9 is an RNA-guided DNA endonuclease that targets foreign DNA for destruction as part of a bacterial adaptive immune system mediated by clustered regularly interspaced short palindromic repeats (CRISPR). Together with single-guide RNAs, Cas9 also functions as a powerful genome engineering tool in plants and animals, and efforts are underway to increase the efficiency and specificity of DNA targeting for potential therapeutic applications. Studies of off-target effects have shown that DNA binding is far more promiscuous than DNA cleavage, yet the molecular cues that govern strand scission have not been elucidated. Here we show that the conformational state of the HNH nuclease domain directly controls DNA cleavage activity. Using intramolecular Förster resonance energy transfer experiments to detect relative orientations of the Cas9 catalytic domains when associated with on- and off-target DNA, we find that DNA cleavage efficiencies scale with the extent to which the HNH domain samples an activated conformation. We furthermore uncover a surprising mode of allosteric communication that ensures concerted firing of both Cas9 nuclease domains. Our results highlight a proofreading mechanism beyond initial protospacer adjacent motif (PAM) recognition and RNA–DNA base-pairing that serves as a final specificity checkpoint before DNA double-strand break formation.

doi: 10.1038/nature15544

Crystal structure of the RNA-dependent RNA polymerase from influenza C virus p.114

The X-ray crystal structure of influenza C virus polymerase, captured in a closed, pre-activation confirmation, is solved at 3.9 Å resolution; comparison with previous RNA-bound structures reveals large conformational changes associated with RNA binding and activation, and illustrates the notable flexibility of the influenza virus RNA polymerase.

doi: 10.1038/nature15525