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How poverty affects the brain p.150

An unprecedented study in Bangladesh could reveal how malnutrition, poor sanitation and other challenges make their mark on child development.

doi: 10.1038/547150a

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News & Views

Sensing past the quantum limit p.164

Quantum physics ultimately constrains how well sensors of position, speed and acceleration can perform. A hybrid quantum system that avoids these constraints could give rise to improved sensor technologies. See Letter p.191

Christopher G. Baker & Warwick P. Bowen

doi: 10.1038/547164a

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Precision T-cell therapy targets tumours p.165

The T cells of the immune system can destroy tumours, but their activation can be inefficient. Vaccines that exploit tumour mutations elicit robust T-cell responses to tumours, with potential clinical benefits. See Letters p.217 & p.222

Cornelis J. M. Melief

doi: 10.1038/nature23093

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Arctic plants take up mercury vapour p.167

Trace elements are enriched in plants by natural processes, human activities or both. An analysis of mercury in Arctic tundra vegetation offers fresh insight into the uptake of trace metals from the atmosphere by plants. See Letter p.201

William Shotyk

doi: 10.1038/547167a

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A liquid reservoir for silent chromatin p.168

The protein HP1 mediates compaction of DNA into a repressive structure called heterochromatin. Analysis reveals that HP1 has liquid-like properties, offering a fresh perspective on genome organization. See Letters p.236 & p.241

Adam Klosin & Anthony A. Hyman

doi: 10.1038/nature23089

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Taming tangled tau p.170

The protein tau forms abnormal filamentous aggregates called tangles in the brains of people with neurodegeneration. Structures of two such filaments offer pathways to a deeper understanding of Alzheimer's disease. See Article p.185

David S. Eisenberg & Michael R. Sawaya

doi: 10.1038/nature23094

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Bile ducts regenerated p.171

The development of a protocol for isolating and expanding the cell population that lines bile ducts has enabled the in vitro generation of bioengineered ducts. These can replace native bile ducts when transplanted into mice.

Ludi Zhang & Lijian Hui

doi: 10.1038/547171a

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Articles

Fine-mapping inflammatory bowel disease loci to single-variant resolution p.173

Results of fine-mapping 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals and several new fine-mapping methods.

Hailiang Huang, Ming Fang, Luke Jostins, Maša Umićević Mirkov, Gabrielle Boucher, Carl A. Anderson, Vibeke Andersen, Isabelle Cleynen, Adrian Cortes, François Crins + et al.

doi: 10.1038/nature22969

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The extracellular matrix protein agrin promotes heart regeneration in mice p.179

The extracellular matrix protein agrin promotes cardiac regeneration in adult mice after myocardial infarction; it modulates cardiac differentiation and proliferation by interacting with the dystrophin–glycoprotein complex, Yap and ERK-mediated signalling.

Elad Bassat, Yara Eid Mutlak, Alex Genzelinakh, Ilya Y. Shadrin, Kfir Baruch Umansky, Oren Yifa, David Kain, Dana Rajchman, John Leach, Daria Riabov Bassat + et al.

doi: 10.1038/nature22978

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Cryo-EM structures of tau filaments from Alzheimer’s disease p.185

High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease.

Anthony W. P. Fitzpatrick, Benjamin Falcon, Shaoda He, Alexey G. Murzin, Garib Murshudov, Holly J. Garringer, R. Anthony Crowther, Bernardino Ghetti, Michel Goedert & Sjors H. W. Scheres

doi: 10.1038/nature23002

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Letters

Quantum back-action-evading measurement of motion in a negative mass reference frame p.191

By coupling a mechanical object to an ensemble of atomic spins with negative effective mass, the object’s position can be measured without the usual quantum back-action perturbation of its momentum.

Christoffer B. Møller, Rodrigo A. Thomas, Georgios Vasilakis, Emil Zeuthen, Yeghishe Tsaturyan, Mikhail Balabas, Kasper Jensen, Albert Schliesser, Klemens Hammerer & Eugene S. Polzik

doi: 10.1038/nature22980

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Tundra uptake of atmospheric elemental mercury drives Arctic mercury pollution p.201

A two-year study of mercury deposition in the Arctic finds that the main source of mercury is gaseous elemental mercury, which is deposited throughout the year and leads to very high soil mercury levels.

Daniel Obrist, Yannick Agnan, Martin Jiskra, Christine L. Olson, Dominique P. Colegrove, Jacques Hueber, Christopher W. Moore, Jeroen E. Sonke & Detlev Helmig

doi: 10.1038/nature22997

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The pyrite-type high-pressure form of FeOOH p.205

The pyrite-type high-pressure form of FeOOH is predicted from first principles, and found experimentally to be stable under the conditions at the base of the mantle, with implications for transport of water within Earth’s deep interior.

Masayuki Nishi, Yasuhiro Kuwayama, Jun Tsuchiya & Taku Tsuchiya

doi: 10.1038/nature22823

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Pre-oral gut contributes to facial structures in non-teleost fishes p.209

In contrast to the prevailing belief that the gut begins with the mouth and continues backwards from there, this work shows that substantial areas of the faces of ray-finned fishes originate from the pre-oral gut or endoderm.

Martin Minarik, Jan Stundl, Peter Fabian, David Jandzik, Brian D. Metscher, Martin Psenicka, David Gela, Adriana Osorio-Pérez, Lenin Arias-Rodriguez, Ivan Horácek + et al.

doi: 10.1038/nature23008

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Nutrient sensing modulates malaria parasite virulence p.213

Malaria parasites use a sensing mechanism to moderate their growth in response to the nutrient content of their host.

Liliana Mancio-Silva, Ksenija Slavic, Margarida T. Grilo Ruivo, Ana Rita Grosso, Katarzyna K. Modrzynska, Iset Medina Vera, Joana Sales-Dias, Ana Rita Gomes, Cameron Ross MacPherson, Pierre Crozet + et al.

doi: 10.1038/nature23009

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An immunogenic personal neoantigen vaccine for patients with melanoma p.217

The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity.

Patrick A. Ott, Zhuting Hu, Derin B. Keskin, Sachet A. Shukla, Jing Sun, David J. Bozym, Wandi Zhang, Adrienne Luoma, Anita Giobbie-Hurder, Lauren Peter + et al.

doi: 10.1038/nature22991

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Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer p.222

The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma.

Ugur Sahin, Evelyna Derhovanessian, Matthias Miller, Björn-Philipp Kloke, Petra Simon, Martin Löwer, Valesca Bukur, Arbel D. Tadmor, Ulrich Luxemburger, Barbara Schrörs + et al.

doi: 10.1038/nature23003

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Allelic reprogramming of 3D chromatin architecture during early mammalian development p.232

A low-input Hi-C method is used to show that chromatin organization is markedly relaxed in pre-implantation mouse embryos after fertilization and that the subsequent maturation of 3D chromatin architecture is surprisingly slow.

Zhenhai Du, Hui Zheng, Bo Huang, Rui Ma, Jingyi Wu, Xianglin Zhang, Jing He, Yunlong Xiang, Qiujun Wang, Yuanyuan Li + et al.

doi: 10.1038/nature23263

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Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin p.236

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context.

Adam G. Larson, Daniel Elnatan, Madeline M. Keenen, Michael J. Trnka, Jonathan B. Johnston, Alma L. Burlingame, David A. Agard, Sy Redding & Geeta J. Narlikar

doi: 10.1038/nature22822

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Phase separation drives heterochromatin domain formation p.241

HP1a can nucleate into foci that display liquid properties during the early stages of heterochromatin domain formation in Drosophila embryos, suggesting that the repressive action of heterochromatin may be mediated in part by emergent properties of phase separation.

Amy R. Strom, Alexander V. Emelyanov, Mustafa Mir, Dmitry V. Fyodorov, Xavier Darzacq & Gary H. Karpen

doi: 10.1038/nature22989

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