Editorials
Our affection for national parks is well founded, but many more areas need protection.
doi: 10.1038/529437b
A computer program that can outplay humans in the abstract game of Go will redefine our relationship with machines.
doi: 10.1038/529437a
Self-doubt is a pernicious affliction that can overwhelm researchers.
doi: 10.1038/529438a
News
Deep-learning software defeats human professional for first time.
doi: 10.1038/529445a
Pet project hunts genetic links to behaviour by polling owners on their companions’ quirks.
doi: 10.1038/529446a
Some welcome his latest report as a fresh way to solve a black-hole conundrum; others are unsure of its merits.
doi: 10.1038/529448a
But it is unclear how well the results match the condition in humans.
doi: 10.1038/529449a
Local expertise is required to provide detailed emissions reports.
doi: 10.1038/529450a
Warming in the Pacific Ocean helps to shatter past records, and could bring even faster temperature rises.
doi: 10.1038/nature.2016.19216
News Features
Songbirds are a culinary delicacy in Cyprus — but catching and eating them is illegal. Even so, the practice is on the rise and could be threatening rare species.
doi: 10.1038/529452a
It may not be sexy, but quality assurance is becoming a crucial part of lab life.
doi: 10.1038/529456a
News & Views
The enzyme Cas9 is used in genome editing to cut selected DNA sequences, but it also creates breaks at off-target sites. Protein engineering has now been used to make Cas9 enzymes that have minimal off-target effects. See Article p.490
doi: 10.1038/529468a
The development of a voltage sensor in which a microbial rhodopsin protein is fused with a fluorescent protein enables the neuronal activity of single cells in live animals to be measured with unprecedented speed and accuracy.
doi: 10.1038/529469a
Birds and mammals generate heat to regulate body temperature, but most non-avian reptiles cannot. The discovery of endothermy during the reproductive period of a tegu lizard sheds light on the evolution of this characteristic.
doi: 10.1038/529470a
A simultaneous comparison of the RNA molecules expressed by Salmonella bacteria and human cells during infection reveals how a bacterial small RNA alters the transcript profiles of both the bacteria and the host cells. See Article p.496
doi: 10.1038/nature16872
The discovery of multiple stellar populations — formed at different times — in several young star clusters adds to the debate on the nature and origin of such populations in globular clusters from the early Universe. See Letter p.502
doi: 10.1038/529473a
The cells that insulate neuronal processes with a myelin membrane sheath are damaged during stroke. Data now show that an influx of calcium ions mediated by the TRPA1 protein contributes to myelin injury. See Letter p.523
doi: 10.1038/nature16865
Sweat analysis is an ideal method for continuously tracking a person's physiological state, but developing devices for this is difficult. A wearable sweat monitor that measures several biomarkers is a breakthrough. See Letter p.509
doi: 10.1038/529475a
Perspective
Targets for reducing atmospheric carbon dioxide are related to regional changes in climate extremes rather than to changes in global mean temperature, in order to convey their urgency better to individual countries.
doi: 10.1038/nature16542
Articles
A computer Go program based on deep neural networks defeats a human professional player to achieve one of the grand challenges of artificial intelligence.
doi: 10.1038/nature16961
A high-fidelity variant of Streptococcus pyogenes CRISPR–Cas9 is reported that lacks detectable off-target events as assessed by genome-wide break capture and targeted sequencing methods.
doi: 10.1038/nature16526
Using dual RNA-seq technology to profile RNA expression simultaneously in the bacterial pathogen Salmonella and its host during infection reveals molecular phenotypes of small noncoding RNAs in the infection process.
doi: 10.1038/nature16547
Letters
Three massive star clusters in the Magellanic Clouds show clear evidence of burst-like star formation that occurred a few hundred million years after their initial formation era; such clusters could have accreted sufficient gas to form new stars while orbiting in their host galaxies’ gaseous disks throughout the period between their initial and more recent bursts of star formation.
doi: 10.1038/nature16493
Quantum entanglement is thought to offer great promise for improving measurement precision; now a spin-squeezing implementation with cold atoms offers levels of sensitivity unavailable with any competing conventional method, sensing microwave induced rotations a factor of 70 beyond the standard quantum limit.
doi: 10.1038/nature16176
By merging plastic-based skin sensors with silicon integrated circuits, a flexible, wearable perspiration analysis system is presented that measures skin temperature and the metabolites and electrolytes in human sweat and analyses the information in situ.
doi: 10.1038/nature16521
Here we report a lithium-ion all-climate battery that very efficiently heats itself up in extremely cold environments by diverting current through a strip of metal foil to generate heat of resistance and then reverts to normal high-power operation.
doi: 10.1038/nature16502
Core isotope measurements in the equatorial Pacific Ocean reveal that although atmospheric dust deposition during the last ice age was higher than today’s, the productivity of the equatorial Pacific Ocean did not increase; this may have been because iron-enabled greater nutrient consumption, mainly in the Southern Ocean, reduced the nutrients available in the equatorial Pacific Ocean, and hence also productivity there.
doi: 10.1038/nature16453
The myelin sheaths wrapped around axons by oligodendrocytes are crucial for brain function. In ischaemia myelin is damaged in a Ca2+-dependent manner, abolishing action potential propagation. This has been attributed to glutamate release activating Ca2+-permeable N-methyl-d-aspartate (NMDA) receptors. Surprisingly, we now show that NMDA does not raise the intracellular Ca2+ concentration ([Ca2+]i) in mature oligodendrocytes and that, although ischaemia evokes a glutamate-triggered membrane current, this is generated by a rise of extracellular [K+] and decrease of membrane K+ conductance. Nevertheless, ischaemia raises oligodendrocyte [Ca2+]i, [Mg2+]i and [H+]i, and buffering intracellular pH reduces the [Ca2+]i and [Mg2+]i increases, showing that these are evoked by the rise of [H+]i. The H+-gated [Ca2+]i elevation is mediated by channels with characteristics of TRPA1, being inhibited by ruthenium red, isopentenyl pyrophosphate, HC-030031, A967079 or TRPA1 knockout. TRPA1 block reduces myelin damage in ischaemia. These data suggest that TRPA1-containing ion channels could be a therapeutic target in white matter ischaemia.
doi: 10.1038/nature16519
The role of mitochondria in haematopoietic stem-cell maintenance has not been examined in detail; here mitofusin 2, which modulates mitochondrial fusion and tethering of endoplasmic reticulum to the mitochondria, is shown to be necessary for the maintenance of haematopoietic stem cells with extensive lymphoid potential.
doi: 10.1038/nature16500
The transcription factor Foxo1 is shown to be involved in the determination of distinct subsets of regulatory T (Treg) cells, and the differentiation of activated phenotype Treg cells is associated with the repression of the Foxo1-dependent transcriptional program; constitutively active Foxo1 expression triggers depletion of activated Treg cells in peripheral tissues and leads to CD8 T-cell-mediated autoimmunity and anti-tumour immunity.
doi: 10.1038/nature16486
Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules. Intracellular antigenic peptides are transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune system. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumour development. To escape immune surveillance, some viruses have evolved strategies either to downregulate TAP expression or directly inhibit TAP activity. So far, neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. Here we describe the cryo-electron microscopy structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. Here we show that the 12 transmembrane helices and 2 cytosolic nucleotide-binding domains of the transporter adopt an inward-facing conformation with the two nucleotide-binding domains separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the endoplasmic reticulum, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host.
doi: 10.1038/nature16506
Structural details of how oncogenic human papilloma viruses induce cancer by targeting the tumour suppressor p53 for ubiquitin-mediated degradation.
doi: 10.1038/nature16481
The first structure of fully active HOIP of the RBR family of RING-type E3 ligases in its transfer complex with an E2~ubiquitin conjugate provides insights into its mechanism of action, including the ideal alignment of the E2 and E3 catalytic centres for ubiquitin transfer and the allosteric regulation of the RBR family.
doi: 10.1038/nature16511
The first high-resolution, cryo-electron microscopy structure of mammalian RNA polymerase II, in the form of a transcribing complex comprising DNA template and RNA transcript.
doi: 10.1038/nature16482