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Volume 508 Issue 7494, 3 April 2014

Basal mammary tumour cells from a donor mouse (red) expressing a lineage marker (green) comingle with host-derived epithelial cells. The elongated mammary duct on the left retains a normal bilayered architecture in the absence of infiltration by the donor-derived tumour subclone. Tumours often display a complex subclonal organization. In a mouse model of breast cancer initiated by Wnt signalling, Allison Cleary et al. show that some tumours are biclonal � composed of basal and luminal clones with distinct genetic alterations. These clones cooperate to maintain tumour growth that is dependent on secretion of Wnt by the luminal cells. When Wnt production is blocked, basal cells carrying Hras mutations recruit other Wnt-producing cells to restore tumour growth, or one of the original clones may acquire alternative means of activating the pathway. These findings illuminate how complex cellular interactions in heterogeneous tumours might sway treatment outcomes. On the cover, Cover: Thomas Abrahams/Penn State Imaging Core.


  • Editorial |

    The latest instalment of the Fifth Assessment Report from the Intergovernmental Panel on Climate Change lays out the state of the world — and the challenges ahead.

  • Editorial |

    Few biology degrees still feature natural history. Is the naturalist a species in crisis?

  • Editorial |

    Above the ‘big neuroscience’ commotion, literature plays its part.

World View

  • World View |

    Given the lack of global legislation, nations should work hard to establish cross-border protections for vulnerable species, says Aaron M. Ellison.

    • Aaron M. Ellison

Research Highlights

Seven Days

  • Seven Days |

    The week in science: Court halts Japanese whaling, misconduct found in controversial stem-cell papers, and a surprising rise in autism diagnoses.


  • News |

    Crimean institutions put their future in Russia’s hands as Ukraine attempts research reforms.

    • Alison Abbott
  • News |

    Agencies face rising applications for rare-disease therapies resulting from increasingly precise disease definitions.

    • Sara Reardon
  • News |

    As hints emerge of a major weather event this year, poor data could thwart attempts to improve predictions.

    • Jeff Tollefson
  • News |

    Analysis of chemical patterns on DNA shows promise for explaining disease, but few results have yet been replicated.

    • Ewen Callaway

News Feature

  • News Feature |

    The immune system can be a powerful weapon against cancer — but researchers are still grappling with how to control it.

    • Heidi Ledford
  • News Feature |

    After years of work in the Antarctic, John Kovac and his team have captured strong evidence for a long-held theory about the Universe’s birth.

    • Ron Cowen


Books & Arts


News & Views

  • News & Views |

    The identification of the enzyme plasmin as a defence against cancer cells that have spread to the brain, and of tumour-cell serpin proteins that inhibit plasmin production, outlines a mechanism for the formation of brain metastases.

    • Janine T. Erler
  • News & Views |

    If a pregnant mouse lacks vitamin A, her offspring are born with smaller lymph nodes and have impaired immune responses as adults — a finding that adds immune development to this vitamin's list of key functions. See Letter p.123

    • Gérard Eberl
  • News & Views |

    Planets are no longer the only Solar System bodies sporting ring systems. Two dense rings have been detected encircling a Centaur object — a relatively small, icy interloper from the distant reaches of the Solar System. See Letter p.72

    • Joseph A. Burns
  • News & Views |

    A study finds that contractile cells that surround the capillary vessels of the brain control the blood supply to healthy neurons, and that their death may aggravate brain injury by strangling vessels. See Article p.55

    • Daniel M. Greif
    • Anne Eichmann
  • News & Views |

    Simulations of Earth's growth show a correlation between the timing of the Moon's formation and the amount of mass that Earth accreted afterwards. This relationship provides a way of measuring the age of our planet. See Letter p.84

    • John Chambers
  • News & Views |

    Widespread genetic heterogeneity in cells of human tumours poses a question: what prevents the fittest clone from taking over? A demonstration of interdependence between distinct clones might shed light on this puzzle. See Letter p.113

    • Kornelia Polyak
    • Andriy Marusyk


  • Article |

    Neuronal activity relaxes pericytes, leading to capillary dilation and increased blood flow, before arterioles dilate, suggesting that pericytes initiate blood-oxygen-level-dependent (BOLD) functional imaging signals; pericytes constrict and die in rigor in ischaemia, which will cause a long-lasting blood flow decrease after stroke, and damage the blood–brain barrier.

    • Catherine N. Hall
    • Clare Reynell
    • David Attwell
  • Article |

    High-resolution structures of the Photorhabdus luminescens TcA toxin subunit and the entire Tc toxin complex reveal important new insights into Tc complex structure and function.

    • Dominic Meusch
    • Christos Gatsogiannis
    • Stefan Raunser
  • Article |

    A new high-throughput sequencing method to determine mRNA poly(A)-tail length enabled studies of individual RNAs across species and developmental stages to investigate the role of poly(A) length in translational regulation; the relationship between poly(A) length and translational efficiency shown in early embryo systems does not occur later in development, a finding that explains different regulatory consequences of microRNAs acting at different developmental times.

    • Alexander O. Subtelny
    • Stephen W. Eichhorn
    • David P. Bartel


  • Letter |

    In combination with sympathetic cooling of translational degrees of freedom (leading to Coulomb crystallization), cooling of the rotational degrees of freedom of magnesium hydride ions using a helium buffer gas leads to temperatures in a tunable range from 60 kelvin down to about 7 kelvin for a single ion, the lowest such temperature so far recorded.

    • A. K. Hansen
    • O. O. Versolato
    • M. Drewsen
  • Letter |

    The resonant interaction between γ-ray photons and an ensemble of nuclei with a periodically modulated resonant transition frequency can be used to control the waveforms of the photons coherently; for example, individual γ-ray photons can be converted into a coherent, ultrashort pulse train or into a double pulse.

    • Farit Vagizov
    • Vladimir Antonov
    • Olga Kocharovskaya
  • Letter |

    A large number of N-body simulations of the giant-impact phase of planet formation, combined with the measured concentrations of highly siderophile elements in Earth’s mantle, reveal that the Moon must have formed at least 40 million years after the condensation of the first solids of the Solar System.

    • Seth A. Jacobson
    • Alessandro Morbidelli
    • David C. Rubie
  • Letter |

    CA2 neuron inactivation leads to a severe deficit in social memory, while having little effect on other well-known hippocampal functions such as contextual or spatial memory.

    • Frederick L. Hitti
    • Steven A. Siegelbaum
  • Letter |

    This study finds that triple-negative breast cancers (TNBC) show an increased basal level of endoplasmic reticulum stress and activation of the XBP1 branch of the unfolded protein response; furthermore, XBP1 promotes tumour formation of TNBC cell lines by interacting with and regulating HIF1α.

    • Xi Chen
    • Dimitrios Iliopoulos
    • Laurie H. Glimcher
  • Letter |

    New apparatus is used to maintain proliferating cancer cells in low-glucose conditions, demonstrating that mitochondrial oxidative phosphorylation (OXPHOS) is essential for optimal proliferation in these conditions; the most sensitive cell lines are defective in OXPHOS upregulation and may therefore be sensitive to current antidiabetic drugs that inhibit OXPHOS.

    • Kıvanç Birsoy
    • Richard Possemato
    • David M. Sabatini
  • Letter |

    Patients with melanomas carrying an activating BRAF mutation respond to treatment with BRAF inhibitors although resistance to the inhibitor usually emerges; this resistance is shown to arise through increased expression of receptor tyrosine kinases such as EGFR; however, these changes decrease cell fitness and during a break from inhibitor treatment these cells are selected against, revealing that some patients who acquire EGFR expression may benefit from inhibitor re-treatment after a drug holiday.

    • Chong Sun
    • Liqin Wang
    • Rene Bernards

Technology Feature

  • Technology Feature |

    Beams of charged particles can treat cancer more safely and effectively than X-rays. Physicists and biomedical researchers are working to refine the technology for wider use.

    • Vivien Marx



  • Feature |

    Promising results in cancer immunotherapy offer growing opportunities — and challenges — in translational research.

    • Rachel Bernstein


  • Q&A |

    Solar System findings help geochemist to return to China to launch planetary-chemistry lab.

    • Virginia Gewin

Career Brief


  • Futures |

    Science fiction in 200 characters or less.

Brief Communications Arising


  • Outlook |

    Unravelling the mystery of verbal dysfunction in schizophrenia could yield clues to the nature of the disease.

    • David Noonan
  • Outlook |

    A massive research collaboration is revealing hundreds of genes underlying schizophrenia risk, and may point the way to targeted treatments.

    • Jessica Wright
  • Outlook |

    Researchers have made good progress with animal tests for cognition. The next step is to devise a rodent model for drug development.

    • Alla Katsnelson
  • Outlook |

    Schizophrenia debilitates not just by psychosis but by depriving people of the ability to feel pleasure.

    • Elie Dolgin
  • Outlook |

    Paying attention to risk factors and warning signs could avert some cases of schizophrenia — or at least better prepare people for what's to come.

    • Michele Solis
  • Outlook |

    Schizophrenia patients in developing countries seem to fare better than their Western counterparts. Researchers are keen to find out why.

    • T. V. Padma
  • Outlook |

    People with schizophrenia show signs of accelerated ageing — a phenomenon that could lead researchers to a deeper understanding of the disease.

    • Emily Anthes
  • Outlook |

    Failures in the development of schizophrenia treatments don't justify the dramatic overhaul now being proposed, says Stephen R. Marder.

    • Stephen R. Marder
  • Outlook |

    The more we study the genetics of schizophrenia, says Steven E. Hyman, the more daunting — and exciting — are the challenges we see ahead.

    • Steven E. Hyman

Nature Outlook

  • Nature Outlook |


    About one in every one hundred people must endure the psychosis, disorientation, and social withdrawal that define schizophrenia. While there is still no effective treatment in development, scientists are learning more about the genetic and biochemical basis of this severe disorder. It is hoped that this new knowledge will one day result in new treatments that will let people living with schizophrenia lead more normal lives.

Nature Briefing

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