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Haze cools Pluto's atmosphere p.302

Modelling suggests that Pluto's atmospheric temperature is regulated by haze, unlike the other planetary bodies in the Solar System. The finding has implications for our understanding of exoplanetary atmospheres. See Letter p.352

Robert A. West

doi: 10.1038/551302a

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Bacteria disarm host-defence proteins p.303

Infection with Shigella flexneri bacteria is a major cause of infant death. It emerges that S. flexneri evades intracellular defences by releasing a protein that triggers the destruction of members of a key family of host enzymes. See Letter p.378

John D. MacMicking

doi: 10.1038/nature24157

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Ocean hotspots of nitrogen loss p.305

Microbial activity in the sea results in a loss of bioavailable nitrogen. It emerges that the climate phenomenon called the El Niño–Southern Oscillation has a surprisingly large effect on the size of this loss.

Katja Fennel

doi: 10.1038/551305a

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Transgenic stem cells replace skin p.306

The treatment of a patient affected by an incurable genetic skin disease demonstrates the efficacy, feasibility and safety of replacing almost the whole skin using genetically corrected stem cells. See Letter p.327

Mariaceleste Aragona & Cédric Blanpain

doi: 10.1038/nature24753

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The buoyancy of Earth's deep mantle p.308

The physical nature of two regions called large low-shear-velocity provinces at the base of Earth's mantle is uncertain. A measurement of their density has implications for our understanding of mantle dynamics. See Article p.321

Barbara Romanowicz

doi: 10.1038/551308a

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The effect of conservation spending p.309

Statistical analysis of data on threatened species provides a model that can predict how rates of investment in conservation affect biodiversity under changing human population levels and agricultural and economic conditions. See Letter p.364

Hugh P. Possingham & Leah R. Gerber

doi: 10.1038/nature24158

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A broadly protective antibody p.310

A single antibody uses multiple antiviral mechanisms to block the replication of influenza B viruses in mice and ferrets. The development could inform research into improved flu vaccines.

Peter Palese

doi: 10.1038/551310a

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Review

Articles

Tidal tomography constrains Earth’s deep-mantle buoyancy p.321

An estimate of Earth’s deep-mantle buoyancy is derived from GPS-based measurements of body tide deformation and shown to be dominated by dense material possibly related to subducted oceanic plates or primordial rock.

Harriet C. P. Lau, Jerry X. Mitrovica, James L. Davis, Jeroen Tromp, Hsin-Ying Yang & David Al-Attar

doi: 10.1038/nature24452

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A single-cell survey of the small intestinal epithelium p.333

Profiling of 53,193 individual epithelial cells from the mouse small intestine identifies previously unknown cell subtypes and corresponding gene markers, providing insight into gut homeostasis and response to pathogens.

Adam L. Haber, Moshe Biton, Noga Rogel, Rebecca H. Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M. Delorey, Michael R. Howitt, Yarden Katz + et al.

doi: 10.1038/nature24489

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Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity p.340

IgA+ B cells expressing programmed death ligand 1 (PD-L1) and interleukin 10 accumulate in the inflamed livers of humans and mice with non-alcoholic fatty liver disease where they promote the progression to hepatocellular carcinoma by limiting the local activation of PD-1-expressing CD8+ T cells.

Shabnam Shalapour, Xue-Jia Lin, Ingmar N. Bastian, John Brain, Alastair D. Burt, Alexander A. Aksenov, Alison F. Vrbanac, Weihua Li, Andres Perkins, Takaji Matsutani + et al.

doi: 10.1038/nature24302

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Dynamics of P-type ATPase transport revealed by single-molecule FRET p.346

Single-molecule fluorescence resonance energy transfer is used to identify the rate-limiting step and new intermediates in the conformational cycle of the Listeria monocytogenes calcium transporter LMCA1.

Mateusz Dyla, Daniel S. Terry, Magnus Kjaergaard, Thomas L.-M. Sørensen, Jacob Lauwring Andersen, Jens Peter Andersen, Charlotte Rohde Knudsen, Roger B. Altman, Poul Nissen & Scott C. Blanchard

doi: 10.1038/nature24296

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Letters

Granular materials flow like complex fluids p.360

The relaxation dynamics of granular materials is more like that of complex fluids than that of thermal glass-forming systems, owing to the absence of the ‘cage effect’.

Binquan Kou, Yixin Cao, Jindong Li, Chengjie Xia, Zhifeng Li, Haipeng Dong, Ang Zhang, Jie Zhang, Walter Kob & Yujie Wang

doi: 10.1038/nature24062

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Reductions in global biodiversity loss predicted from conservation spending p.364

Empirical two-part models describe the relationship between conservation spending, human development pressures and biodiversity loss and can inform sustainable development strategies by predicting the effects of financing decisions on future biodiversity losses.

Anthony Waldron, Daniel C. Miller, Dave Redding, Arne Mooers, Tyler S. Kuhn, Nate Nibbelink, J. Timmons Roberts, Joseph A. Tobias & John L. Gittleman

doi: 10.1038/nature24295

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Parallel palaeogenomic transects reveal complex genetic history of early European farmers p.368

In European Neolithic populations, the arrival of farmers prompted admixture with local hunter-gatherers over many centuries, resulting in distinct signatures in each region due to a complex series of interactions.

Mark Lipson, Anna Szécsényi-Nagy, Swapan Mallick, Annamária Pósa, Balázs Stégmár, Victoria Keerl, Nadin Rohland, Kristin Stewardson, Matthew Ferry, Megan Michel + et al.

doi: 10.1038/nature24476

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Locomotor speed control circuits in the caudal brainstem p.373

In the mouse caudal brainstem, functionally distinct neuronal subpopulations, which are distinguishable by neurotransmitter identity, connectivity and location, regulate locomotion parameters.

Paolo Capelli, Chiara Pivetta, Maria Soledad Esposito & Silvia Arber

doi: 10.1038/nature24064

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BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation p.384

The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases. Knockdown of BCAT1 in leukaemia cells caused accumulation of αKG, leading to EGLN1-mediated HIF1α protein degradation. This resulted in a growth and survival defect and abrogated leukaemia-initiating potential. By contrast, overexpression of BCAT1 in leukaemia cells decreased intracellular αKG levels and caused DNA hypermethylation through altered TET activity. AML with high levels of BCAT1 (BCAT1high) displayed a DNA hypermethylation phenotype similar to cases carrying a mutant isocitrate dehydrogenase (IDHmut), in which TET2 is inhibited by the oncometabolite 2-hydroxyglutarate. High levels of BCAT1 strongly correlate with shorter overall survival in IDHWTTET2WT, but not IDHmut or TET2mut AML. Gene sets characteristic for IDHmut AML were enriched in samples from patients with an IDHWTTET2WTBCAT1high status. BCAT1high AML showed robust enrichment for leukaemia stem-cell signatures, and paired sample analysis showed a significant increase in BCAT1 levels upon disease relapse. In summary, by limiting intracellular αKG, BCAT1 links BCAA catabolism to HIF1α stability and regulation of the epigenomic landscape, mimicking the effects of IDH mutations. Our results suggest the BCAA–BCAT1–αKG pathway as a therapeutic target to compromise leukaemia stem-cell function in patients with IDHWTTET2WT AML.

Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert + et al.

doi: 10.1038/nature24294

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A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair p.389

A signalling mechanism in human cells for sensing DNA damage induced by alkylation involves ubiquitin-dependent recruitment of the alkylation repair complex ASCC to the vicinity of the damage and co-localization with transcription and splicing factors.

Joshua R. Brickner, Jennifer M. Soll, Patrick M. Lombardi, Cathrine B. Vågbø, Miranda C. Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E. Sullender, Elyse Blazosky + et al.

doi: 10.1038/nature24484

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Structure and assembly of the Ebola virus nucleocapsid p.394

Application of cryo-electron tomography and subtomogram averaging to determine the structure of the Ebola virus nucleocapsid within intact viruses and recombinant nucleocapsid-like assemblies.

William Wan, Larissa Kolesnikova, Mairi Clarke, Alexander Koehler, Takeshi Noda, Stephan Becker & John A. G. Briggs

doi: 10.1038/nature24490

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