Bureaucratic drag dents Japan’s nuclear science p.147

Japan needs a better way to assess whether research reactors are safe to re-open.

doi: 10.1038/d41586-017-08464-2

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Loss of net neutrality could harm research p.147

Moves to create a multi-speed Internet could push science into the slow lane.

doi: 10.1038/d41586-017-07842-0

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How to avoid glib interdisciplinarity p.148

To make progress on the grand challenges, authors, reviewers and editors must take the time to respect each others’ expertise and blind spots.

doi: 10.1038/d41586-017-08465-1

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Nine researchers sue University of Rochester over sexual-harassment allegations p.155

Lawsuit alleges that the institution mishandled complaints about cognitive scientist Florian Jaeger.

doi: 10.1038/d41586-017-08235-z

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Tasmanian tiger genome offers clues to its extinction p.156

Geneticists analyse DNA from preserved pup, more than 80 years after the last of its kind died.

doi: 10.1038/d41586-017-08368-1

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US graduate students in uproar over proposed tax hike p.157

Worries over the cost of an education spill over into protests.

doi: 10.1038/d41586-017-07879-1

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Acupuncture in cancer study reignites debate about controversial technique p.157

Large study suggests acupuncture could help women stick with unpleasant cancer treatments.

doi: 10.1038/d41586-017-08309-y

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Argentinian geoscientist faces criminal charges over glacier survey p.158

Government researcher Ricardo Villalba stands accused of shaping a study to benefit mining interests.

doi: 10.1038/d41586-017-08236-y

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News Features


The science that’s never been cited p.162


doi: 10.1038/d41586-017-08404-0

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News & Views


Developmental biology: Early embryos kept in check p.178


doi: 10.1038/d41586-017-07436-w

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Astrophysics: Stellar cannibalism in fits and starts p.179


doi: 10.1038/d41586-017-08286-2

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Vascular biology: A dark side to omega-3 fatty acids p.180


doi: 10.1038/d41586-017-07678-8

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Ageing: Longer life through an odd Pol enzyme p.182


doi: 10.1038/d41586-017-07435-x

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Palaeoglaciology: Antarctic ice dynamics in warm climates p.183


doi: 10.1038/d41586-017-08285-3

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Infection: Viruses hijack a long non-coding RNA p.184


doi: 10.1038/d41586-017-07692-w

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Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity p.187

Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.

doi: 10.1038/nature25143

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Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4 p.194

Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.

doi: 10.1038/nature25016

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Electron cryo-microscopy structure of a human TRPM4 channel p.200

The structure of the Ca2+-activated, non-selective ion channel TRPM4 bound to the agonist Ca2+ and a modulator decavanadate, solved using electron cryo-microscopy.

doi: 10.1038/nature24674

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Structures of the calcium-activated, non-selective cation channel TRPM4 p.205

Electron cryo-microscopy structures of mouse TRPM4, a calcium-activated, non-selective cation channel, in the apo and ATP-bound states.

doi: 10.1038/nature24997

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Magnetically gated accretion in an accreting ‘non-magnetic’ white dwarf p.210

A weak magnetic field regulates magnetically gated accretion of gas from a companion star onto the white dwarf in the binary system MV Lyrae, previously labelled as a ‘non-magnetic’ system.

doi: 10.1038/nature24653

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An electric-eel-inspired soft power source from stacked hydrogels p.214

Miniature hydrogel compartments in scalable stacked and folded geometries were used to prepare a contact-activated artificial electric organ.

doi: 10.1038/nature24670

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Force loading explains spatial sensing of ligands by cells p.219

The formation of cellular adhesion complexes is important in normal and pathological cell activity, and is determined by the force imposed by the combined effect of the distribution of extracellular matrix molecules and substrate rigidity.

doi: 10.1038/nature24662

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Initiation and long-term instability of the East Antarctic Ice Sheet p.225

Geophysical and geological data reveal increased ice-sheet variability and surface meltwater—possibly analogous to future conditions—offshore of the Aurora subglacial basin of East Antarctica during warm climate intervals of the past 50 million years.

doi: 10.1038/nature25026

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Large emissions from floodplain trees close the Amazon methane budget p.230

Methane fluxes from the stems of Amazonian floodplain trees indicate that the escape of soil gas through wetland trees is the dominant source of methane emissions in the Amazon basin.

doi: 10.1038/nature24639

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A compositional tipping point governing the mobilization and eruption style of rhyolitic magma p.235

Measurements of the composition-dependent viscosity of rhyolitic magma reveal a tipping point that changes the physical properties of the melt and controls the transition between effusive and explosive eruptions.

doi: 10.1038/nature24488

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Pluripotent state transitions coordinate morphogenesis in mouse and human embryos p.239

Exit of epiblasts from an unrestricted naive pluripotent state is required for epithelialization and generation of the pro-amniotic cavity in mouse embryos and for amniotic cavity formation in human embryos and human embryonic stem cells.

doi: 10.1038/nature24675

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Moving beyond microbiome-wide associations to causal microbe identification p.244

Triangulation of microbe–phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes of disease, which may be applicable to human microbiome studies.

doi: 10.1038/nature25019

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Inhibition of soluble epoxide hydrolase prevents diabetic retinopathy p.248

A product of the soluble epoxide hydrolase enzyme, 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP), is implicated in the pathogenesis of diabetic retinopathy; levels of 19,20-DHDP increase in the retinas of mice and humans with diabetes, and inhibition of its production can rescue vascular abnormalities in a mouse model of the disease.

doi: 10.1038/nature25013

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免疫学:Runx3は非リンパ組織と腫瘍におけるCD8+ T細胞常在性をプログラムする

Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours p.253

Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis. Runx3 was required to establish TRM cell populations in diverse tissue environments, and supported the expression of crucial tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Furthermore, we show that human and mouse tumour-infiltrating lymphocytes share a core tissue-residency gene-expression signature with TRM cells that is associated with Runx3 activity. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ tumour-infiltrating lymphocytes failed to accumulate in tumours, resulting in greater rates of tumour growth and mortality. Conversely, overexpression of Runx3 enhanced tumour-specific CD8+ T cell abundance, delayed tumour growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of TRM cell differentiation, these results provide insight into the signals that promote T cell residency in non-lymphoid sites, which could be used to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

doi: 10.1038/nature24993

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A non-canonical Notch complex regulates adherens junctions and vascular barrier function p.258

The transmembrane domain of NOTCH1 plays a key role in the assembly of adherens junctions and the non-transcriptional regulation of vascular permeability that links transcriptional programs with adhesive and cytoskeletal remodelling.

doi: 10.1038/nature24998

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RNA polymerase III limits longevity downstream of TORC1 p.263

RNA polymerase III is a key evolutionarily conserved regulator of longevity that may have potential as a therapeutic target for age-related conditions.

doi: 10.1038/nature25007

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piRNA-mediated regulation of transposon alternative splicing in the soma and germ line p.268

A new mechanism of pre-mRNA splicing regulation is revealed that is mediated by piRNA pathway components and is dependent on heterochromatin histone modifications.

doi: 10.1038/nature25018

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KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase p.273

Histone modifications, such as the frequently occurring lysine succinylation, are central to the regulation of chromatin-based processes. However, the mechanism and functional consequences of histone succinylation are unknown. Here we show that the α-ketoglutarate dehydrogenase (α-KGDH) complex is localized in the nucleus in human cell lines and binds to lysine acetyltransferase 2A (KAT2A, also known as GCN5) in the promoter regions of genes. We show that succinyl-coenzyme A (succinyl-CoA) binds to KAT2A. The crystal structure of the catalytic domain of KAT2A in complex with succinyl-CoA at 2.3 Å resolution shows that succinyl-CoA binds to a deep cleft of KAT2A with the succinyl moiety pointing towards the end of a flexible loop 3, which adopts different structural conformations in succinyl-CoA-bound and acetyl-CoA-bound forms. Site-directed mutagenesis indicates that tyrosine 645 in this loop has an important role in the selective binding of succinyl-CoA over acetyl-CoA. KAT2A acts as a succinyltransferase and succinylates histone H3 on lysine 79, with a maximum frequency around the transcription start sites of genes. Preventing the α-KGDH complex from entering the nucleus, or expression of KAT2A(Tyr645Ala), reduces gene expression and inhibits tumour cell proliferation and tumour growth. These findings reveal an important mechanism of histone modification and demonstrate that local generation of succinyl-CoA by the nuclear α-KGDH complex coupled with the succinyltransferase activity of KAT2A is instrumental in histone succinylation, tumour cell proliferation, and tumour development.

doi: 10.1038/nature25003

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