Volume 529 Number 7587

Editorials

In praise of parks p.437

Our affection for national parks is well founded, but many more areas need protection.

doi: 10.1038/529437b

Digital intuition p.437

A computer program that can outplay humans in the abstract game of Go will redefine our relationship with machines.

doi: 10.1038/529437a

Found out p.438

Self-doubt is a pernicious affliction that can overwhelm researchers.

doi: 10.1038/529438a

News

News Features

Slaughter of the song birds p.452

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

News & Views

The domestication of Cas9 p.468

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

Fluorescent boost for voltage sensors p.469

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

A lizard that generates heat p.470

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

Small RNA with a large impact p.472

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 mystery of globular clusters p.473

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

A mechanism for myelin injury p.474

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

Technological leap for sweat sensing p.475

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

Articles

Letters

Formation of new stellar populations from gas accreted by massive young star clusters p.502

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

No iron fertilization in the equatorial Pacific Ocean during the last ice age p.519

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

Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia p.523

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

Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity p.532

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

A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter p.537

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