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CancerDestiny from density p.490

The identification of a signalling protein that regulates the accumulation of fat and connective tissue in breasts may help to explain why high mammographic density is linked to breast-cancer risk. It may also provide a marker for predicting this risk.

Victoria L. Seewaldt

doi: 10.1038/490490a

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Earth scienceSigns of instability p.491

The finding that pools of gas hydrates — compounds that trap natural gas emissions — in ocean sediments are deeper than expected implies that the hydrates are destabilizing, and might release gigatonnes of methane. See Letter p.527

Juergen Mienert

doi: 10.1038/490491a

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Structural biologySnapshot of an activated peptide receptor p.492

Developing therapeutic drugs that target peptide receptors is challenging. The structure of one of these G-protein-coupled receptors, NTS1, activated and bound to a peptide, provides an excellent starting point. See Article p.508

Felix Hausch & Florian Holsboer

doi: 10.1038/nature11634

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GeneticsThe inner life of proteins p.493

A quantitative analysis shows that epistasis — the fact that genetic background determines whether a mutation is beneficial, deleterious or inconsequential — is the main factor regulating evolution at the level of proteins. See Letter p.535

Günter P. Wagner

doi: 10.1038/490493a

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CosmologyInfrared light from wandering stars p.494

An explanation has been proposed for the observed excess of cosmic light at infrared wavelengths. It invokes stars that are cast into the dark-matter haloes of their parent galaxies during powerful galaxy collisions. See Letter p.514

Andrea Ferrara

doi: 10.1038/490494a

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Articles

A map of rice genome variation reveals the origin of cultivated rice p.497

Crop domestications are long-term selection experiments that have greatly advanced human civilization. The domestication of cultivated rice (Oryza sativa L.) ranks as one of the most important developments in history. However, its origins and domestication processes are controversial and have long been debated. Here we generate genome sequences from 446 geographically diverse accessions of the wild rice species Oryza rufipogon, the immediate ancestral progenitor of cultivated rice, and from 1,083 cultivated indica and japonica varieties to construct a comprehensive map of rice genome variation. In the search for signatures of selection, we identify 55 selective sweeps that have occurred during domestication. In-depth analyses of the domestication sweeps and genome-wide patterns reveal that Oryza sativa japonica rice was first domesticated from a specific population of O. rufipogon around the middle area of the Pearl River in southern China, and that Oryza sativa indica rice was subsequently developed from crosses between japonica rice and local wild rice as the initial cultivars spread into South East and South Asia. The domestication-associated traits are analysed through high-resolution genetic mapping. This study provides an important resource for rice breeding and an effective genomics approach for crop domestication research.

Xuehui Huang, Nori Kurata, Xinghua Wei, Zi-Xuan Wang, Ahong Wang, Qiang Zhao, Yan Zhao, Kunyan Liu, Hengyun Lu, Wenjun Li + et al.

doi: 10.1038/nature11532

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Compensatory dendritic cell development mediated by BATF–IRF interactions p.502

The AP1 transcription factor Batf3 is required for homeostatic development of CD8α+ classical dendritic cells that prime CD8 T-cell responses against intracellular pathogens. Here we identify an alternative, Batf3-independent pathway in mice for CD8α+ dendritic cell development operating during infection with intracellular pathogens and mediated by the cytokines interleukin (IL)-12 and interferon-γ. This alternative pathway results from molecular compensation for Batf3 provided by the related AP1 factors Batf, which also functions in T and B cells, and Batf2 induced by cytokines in response to infection. Reciprocally, physiological compensation between Batf and Batf3 also occurs in T cells for expression of IL-10 and CTLA4. Compensation among BATF factors is based on the shared capacity of their leucine zipper domains to interact with non-AP1 factors such as IRF4 and IRF8 to mediate cooperative gene activation. Conceivably, manipulating this alternative pathway of dendritic cell development could be of value in augmenting immune responses to vaccines.

Roxane Tussiwand, Wan-Ling Lee, Theresa L. Murphy, Mona Mashayekhi, Wumesh KC, Jörn C. Albring, Ansuman T. Satpathy, Jeffrey A. Rotondo, Brian T. Edelson, Nicole M. Kretzer + et al.

doi: 10.1038/nature11531

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Structure of the agonist-bound neurotensin receptor p.508

Neurotensin (NTS) is a 13-amino-acid peptide that functions as both a neurotransmitter and a hormone through the activation of the neurotensin receptor NTSR1, a G-protein-coupled receptor (GPCR). In the brain, NTS modulates the activity of dopaminergic systems, opioid-independent analgesia, and the inhibition of food intake; in the gut, NTS regulates a range of digestive processes. Here we present the structure at 2.8 Å resolution of Rattus norvegicus NTSR1 in an active-like state, bound to NTS8–13, the carboxy-terminal portion of NTS responsible for agonist-induced activation of the receptor. The peptide agonist binds to NTSR1 in an extended conformation nearly perpendicular to the membrane plane, with the C terminus oriented towards the receptor core. Our findings provide, to our knowledge, the first insight into the binding mode of a peptide agonist to a GPCR and may support the development of non-peptide ligands that could be useful in the treatment of neurological disorders, cancer and obesity.

Jim F. White, Nicholas Noinaj, Yoko Shibata, James Love, Brian Kloss, Feng Xu, Jelena Gvozdenovic-Jeremic, Priyanka Shah, Joseph Shiloach, Christopher G. Tate + et al.

doi: 10.1038/nature11558

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