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Volume 472 Issue 7341, 7 April 2011

Organogenesis relies on the orchestration of many cellular interactions to create the collective cell behaviours needed to shape developing tissues. Yoshiki Sasai and colleagues have developed a three-dimensional cell-culture system in which floating clusters of mouse embryonic stem cells can successfully organize themselves into a layered structure resembling the optic cup, a pouch-like structure that develops into the inner and outer layers of the retina during embryogenesis. In further 3D culture, the optic cup forms fully stratified retinal tissue as seen in the postnatal eye. This approach might have important implications for stem-cell therapy for retinal repair. The optic cup shown on the cover was generated from multi-photon images of an optic cup formed in vitro.


  • Editorial |

    Those who want to build a better future for Scotland should resist cuts to an innovative scheme that helps its universities to compete with larger rivals elsewhere.

  • Editorial |

    A partnership to encourage sustainable farming in Brazil may not be as green as it seems.

  • Editorial |

    The latest Indian tiger census demonstrates welcome methodological rigour.

World View

  • World View |

    One impact of Japan's nuclear crisis is a dim but definite echo of Chernobyl, says Jim Smith — decades of caesium-137.

    • Jim Smith

Research Highlights

Seven Days


News Feature

  • News Feature |

    The country's vast, education-hungry population could supply the next generation of the world's scientists — but only if it can teach them.

    • Anjali Nayar


  • Comment |

    This month marks 50 years since Yuri Gagarin first ventured into space in the Vostok 1 mission, and 30 years since NASA's first shuttle flight. As the shuttle Endeavour prepares for its final flight, seven experts outline what NASA's priorities need to be.

  • Comment |

    The Massachusetts Institute of Technology has been an innovator of university funding models, says David Kaiser. Its 150-year history holds lessons for today.

    • David Kaiser
  • Comment |

    As resistance mushrooms, governments must make development of new antibiotics financially viable for industry, say Matthew A. Cooper and David Shlaes.

    • Matthew A. Cooper
    • David Shlaes

Books & Arts


News & Views

  • News & Views |

    A common dietary component that some people even take as a supplement is converted by the gut microbiota to harmful metabolites linked to heart disease. This finding has cautionary implications. See Article p.57

    • Kimberly Rak
    • Daniel J. Rader
  • News & Views |

    An innovative technique has been developed to manufacture graphene transistors that operate at radio frequencies and low temperatures. The process brings the devices closer to applications. See Letter p.74

    • Frank Schwierz
  • News & Views |

    Generation of complex organs in vitro is a major challenge in regenerative medicine. But it is not an impossible one: an entire synthetic retina has now been generated from embryonic stem cells. See Article p.51

    • Robin R. Ali
    • Jane C. Sowden
  • News & Views |

    The energy released by capsizing icebergs can be equal to that of small earthquakes — enough to create ocean waves of considerable magnitude. Should such 'glacial tsunamis' be added to the list of future global-warming hazards?

    • Anders Levermann
  • News & Views |

    A consequence of Darwin's 'principle of divergence' is that loss of species can harm the functioning of ecosystems. A study of algal communities in artificial streams suggests that he was right. See Letter p.86

    • Andy Hector
  • News & Views |

    There are well-established links between the reproductive system, metabolism and skeletal growth. But it comes as a surprise that the skeleton — more specifically, the bone hormone osteocalcin — modulates fertility.

    • Sonya M. Schuh-Huerta
    • Renee A. Reijo Pera
  • News & Views |

    Independent lines of evidence suggest that the first stars, which ended the cosmic dark ages, came in pairs rather than singly. This could change the prevailing view that the early Universe had a Swiss-cheese-like appearance.

    • Zoltán Haiman
  • News & Views |

    A three-dimensional mechanical model of the Tibetan crust explains both the first-order features of GPS surface velocities and the contrast in the types of earthquake between northern and southern Tibet. See Letter p.79

    • Jeffrey T. Freymueller


  • Article |

    Organogenesis relies on the orchestration of many cellular interactions to create the collective cell behaviours that progressively shape developing tissues. Using a three-dimensional embryonic stem cell culture system, this study successfully generated neural retinal tissues that formed a fully stratified neural retinal structure with all the major components located in their proper spatial location as seen during optic-cup development in vivo. This approach might have important implications for stem cell therapy for retinal repair.

    • Mototsugu Eiraku
    • Nozomu Takata
    • Yoshiki Sasai
  • Article |

    This paper shows that gut flora can influence cardiovascular disease, by metabolizing a dietary phospholipid. Using a metabolomics approach it is found that plasma levels of three metabolites of dietary phosphatidylcholine—choline, betaine and TMAO—are associated with increased risk of cardiovascular disease in humans. The gut flora is known to have a role in TMAO formation from choline, and this paper shows that dietary choline supplementation enhances macrophage foam cell formation and lesion formation in atherosclerosis-prone mice, but not if the gut flora are depleted with antibiotics.

    • Zeneng Wang
    • Elizabeth Klipfell
    • Stanley L. Hazen
  • Article |

    The streptococcal M1 protein can cause vascular leakage and tissue injury and these pathologies are dependent on its interaction with host fibrinogen and subsequent activation of neutrophils. This study presents the structural basis for this process.

    • Pauline Macheboeuf
    • Cosmo Buffalo
    • Partho Ghosh


  • Letter |

    In atomic systems, electromagnetically induced transparency (EIT) has been the subject of much experimental research, as it enables light to be slowed and stopped. This study demonstrates EIT and tunable optical delays in a nanoscale optomechanical device, fabricated by simply etching holes into a thin film of silicon. These results indicate significant progress towards an integrated quantum optomechanical memory, and are also relevant to classical signal processing applications: at room temperature, the system can be used for optical buffering, amplification and filtering of microwave-over-optical signals.

    • A. H. Safavi-Naeini
    • T. P. Mayer Alegre
    • O. Painter
  • Letter |

    An attractive method to fabricate graphene transistors is transferring high-quality graphene sheets to a suitable substrate. This study identifies diamond-like carbon as a new substrate for graphene devices. It is attractive as few sources for scattering are expected at the interface that may lead to deterioration of device properties. Graphene transistors operating at radio frequencies with cutoff as high as 155 GHz and with scalable gate length are demonstrated. Unlike conventional semiconductor devices, the high-frequency performance of the graphene devices exhibits little temperature dependence down to 4.3 K, providing a much larger operation window than conventional devices.

    • Yanqing Wu
    • Yu-ming Lin
    • Phaedon Avouris
  • Letter |

    This study shows that the contrast in tectonic regime between primarily strike-slip faulting in northern Tibet and dominantly normal faulting in southern Tibet requires mechanical coupling between the upper crust of southern Tibet and the underthrusting Indian crust. Such coupling is inconsistent with the presence of active ‘channel flow’ beneath southern Tibet, and indicates that the Indian crust retains its strength as it underthrusts the plateau.

    • Alex Copley
    • Jean-Philippe Avouac
    • Brian P. Wernicke
  • Letter |

    This study reports on laboratory-strength measurements of fault core materials from a drill hole located northwest of Parkfield, California, near the southern end of a creeping zone of the San Andreas fault. It is found that the fault is profoundly weak at this location and depth, owing to the presence of the smectite clay mineral saponite—one of the weakest phyllosilicates known. These findings provide strong evidence that deformation of the mechanically unusual creeping portions of the San Andreas fault system is controlled by the presence of weak minerals rather than by high fluid pressure or other proposed mechanisms.

    • David A. Lockner
    • Carolyn Morrow
    • Stephen Hickman
  • Letter |

    More diverse stream communities have increased uptake of nutrients, including nitrate, a major pollutant, but the mechanism is little understood. This study manipulated algal species diversity in stream mesocosms with different flow habitats and disturbance regimes. Nitrogen uptake increased linearly with species richness, but when niche structure was experimentally removed the relationship disappeared.

    • Bradley J. Cardinale
  • Letter |

    Although it is known that tumours are genetically heterogeneous it has so far been difficult to dissect this heterogeneity at a single cell level. This paper combines whole-genome amplification and next-generation sequencing of flow-sorted nuclei from breast tumours to investigate their population structure and evolution. In contrast to gradual models of tumour progression, the results indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.

    • Nicholas Navin
    • Jude Kendall
    • Michael Wigler


  • Letter |

    Although it has been known for some time that rodent mating depends on many social and chemical cues, very little is known about the molecular and cellular mechanisms underlying such behaviour. Here it is shown that serotonergic neuron signalling seems to stabilize sexual preference, with the loss of the neurotransmitter serotonin causing indiscriminate mating behaviour in male mice.

    • Yan Liu
    • Yun’ai Jiang
    • Yi Rao
  • Letter |

    Even brief neuronal activity can result in long-term potentiation of synapses, which is associated with enlargement of dendritic spines on the neuron at the receiving end of neurotransmission. Using live imaging of fluorescently tagged signalling proteins in individual dendritic spines, this study shows that transient activation of the Ca2+/calmodulin-dependent kinase is translated into short-term versus long-term and long-range (dendritic) versus short-range (spine-confined) signalling, depending on which small GTPase of the Rho family is activated. The technique is bringing the study of the cellular bases of learning and memory down to the nanometre scale.

    • Hideji Murakoshi
    • Hong Wang
    • Ryohei Yasuda
  • Letter |

    The maintenance and regeneration of the epithelium of the adult bladder is poorly understood yet it is a clinically relevant process during urinary tract infections and bladder cancer. This study provides insight into the cellular and molecular mechanisms underlying the regenerative response to injury within the mammalian urinary bladder. Upon injury by bacterial infection or chemical agents, a Shh and Wnt signalling feedback circuit between basal cells of the urothelium and the stromal cells that underlie them leads to regenerative proliferation of the bladder epithelia.

    • Kunyoo Shin
    • John Lee
    • Philip A. Beachy
  • Letter |

    The transcription of repetitive elements such as retrotransposons is normally repressed, to prevent their unchecked dissemination throughout the genome. This study shows that heat stress induces the transcription of the ONSEN retroelement. The accumulation of ONSEN is suppressed by small interfering RNAs. When siRNAs were absent, new ONSEN insertions were found in the progeny of heat-stressed plants, having transposed during differentiation. These results imply a memory of stress that can be counteracted by siRNAs.

    • Hidetaka Ito
    • Hervé Gaubert
    • Jerzy Paszkowski
  • Letter |

    Long intergenic non-coding RNAs (lincRNAs) have been implicated in both gene silencing and activation, and could be a means for long-range control of gene expression. Here a lincRNA termed HOTTIP is identified at the 5′ tip of the HOXA locus that coordinates the activation of multiple 5′ HOXA genes. Chromosomal looping brings HOTTIP into the proximity of its target genes, where it seems to be required to facilitate histone H3 lysine 4 trimethylation and gene transcription.

    • Kevin C. Wang
    • Yul W. Yang
    • Howard Y. Chang


  • Feature |

    San Diego's diverse corporate science portfolio offers opportunities for open-minded scientists hoping to escape stagnation in academia.

    • Karen Kaplan


  • Column |

    It's easy to give in to procrastination — but Hugh Kearns and Maria Gardiner offer some tips for getting your drive back.

    • Hugh Kearns
    • Maria Gardiner


  • Futures |

    A structured revolution.

    • Liz Williams

Brief Communications Arising

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