Editorials
Moves to create a multi-speed Internet could push science into the slow lane.
doi: 10.1038/d41586-017-07842-0
Japan needs a better way to assess whether research reactors are safe to re-open.
doi: 10.1038/d41586-017-08464-2
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
News
Lawsuit alleges that the institution mishandled complaints about cognitive scientist Florian Jaeger.
doi: 10.1038/d41586-017-08235-z
Geneticists analyse DNA from preserved pup, more than 80 years after the last of its kind died.
doi: 10.1038/d41586-017-08368-1
Large study suggests acupuncture could help women stick with unpleasant cancer treatments.
doi: 10.1038/d41586-017-08309-y
Worries over the cost of an education spill over into protests.
doi: 10.1038/d41586-017-07879-1
Government researcher Ricardo Villalba stands accused of shaping a study to benefit mining interests.
doi: 10.1038/d41586-017-08236-y
News Features
Nature investigates how many papers really end up without a single citation.
doi: 10.1038/d41586-017-08404-0
News & Views
As pluripotent stem cells become primed to give rise to all bodily cell types, they begin to form the amniotic cavity in which the mammalian fetus will grow. A checkpoint that gates this transition has now been identified.
doi: 10.1038/d41586-017-07436-w
Dense stellar remnants called white dwarfs are often found in binary star systems. Satellite observations suggest a previously unknown way in which a white dwarf can draw material from its companion star.
doi: 10.1038/d41586-017-08286-2
The molecule 19,20-dihydroxydocosapentaenoic acid, formed by the metabolism of a fatty acid involved in normal brain function, promotes the development of a diabetes-associated form of blindness in a mouse model.
doi: 10.1038/d41586-017-07678-8
The evolutionarily conserved enzyme RNA polymerase III is a driver of protein synthesis and cell growth. It emerges that partial suppression of this essential enzyme extends lifespan in yeast, roundworms and flies.
doi: 10.1038/d41586-017-07435-x
A geological record reveals that the Aurora sector of the Antarctic Ice Sheet showed contrasting responses to past periods of atmospheric warmth. The findings might help to predict the ice sheet’s response to modern warming.
doi: 10.1038/d41586-017-08285-3
Manipulation of host-cell metabolism is an essential aspect of viral replication cycles. Viral co-option of a cellular long non-protein-coding RNA has now been found to be a key step in this process.
doi: 10.1038/d41586-017-07692-w
Articles
Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.
doi: 10.1038/nature25143
Amyloid-β peptide proteopathies disrupt mitochondria, and restoring mitochondrial proteostasis reduces protein aggregation in animal models of amyloid-β disease.
doi: 10.1038/nature25016
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
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
Letters
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
Miniature hydrogel compartments in scalable stacked and folded geometries were used to prepare a contact-activated artificial electric organ.
doi: 10.1038/nature24670
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
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
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
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
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
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
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
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
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
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
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
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