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Volume 500 Issue 7461, 8 August 2013

The cover represents a rendering of 7 of 950 neurons reconstructed in a piece of mouse retina and their mutual contacts (cyan spheres, 112 of 579,724 contacts) together with their contact matrix (see page 168). Three papers in this issue use the retina as a model for mapping neuronal circuits from the level of individual synaptic contacts to the long-range scale of dendritic interactions. Helmstaedter et al. used electron microscopy to map a mammalian retinal circuit of close to a thousand neurons. The work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations. The other two groups studied the detection of visual motion in the Drosophila visual system � a classic neural computation model. Takemura et al. used semi-automated electron microscopy to reconstruct the basic connectome (8,637 chemical synapses among 379 neurons) of Drosophilas optic medulla. Their results reveal a candidate motion detection circuit with a wiring plan consistent with direction selectivity. Maisak et al. used calcium imaging to show that T4 and T5 neurons are divided into specific subpopulations responding to motion in four cardinal directions, and are specific to ON� versus OFF� edges, respectively.(Cover: Julia Kuhl & Winfried Denk)

Editorial

  • Editorial |

    The possibility that H7N9 avian influenza may evolve sufficiently to cause a pandemic has scientists turning again to controversial research —they must be careful how they justify the risks taken.

  • Editorial |

    Scientists should give donors more information about how their biospecimens are used.

World View

  • World View |

    Maximizing access to research data will greatly benefit science, and users can help to establish universal principles on how to do it, says Martin Bobrow.

    • Martin Bobrow

Research Highlights

Seven Days

  • Seven Days |

    The week in science: Archaeologists open double coffin at Grey Friars, tissue engineers serve up lab-grown hamburger, and MIT releases report on Aaron Swartz case.

News

News Feature

Comment

  • Comment |

    Kathy L. Hudson and Francis S. Collins discuss how and why the US National Institutes of Health worked with the family of Henrietta Lacks, the unwitting source of the HeLa cell line, to craft an agreement for access to HeLa genome data.

    • Kathy L. Hudson
    • Francis S. Collins
  • Comment |

    Recycling, renewables and a reinvigorated domestic energy market will allow China to lead the world in low-carbon development, say Zhu Liu and colleagues.

    • Zhu Liu
    • Dabo Guan
    • Jianguo Liu

Books & Arts

Correspondence

News & Views

  • News & Views |

    Such is the brain's complexity that even small neural circuits contain hundreds of neurons making thousands of connections. Connectivity and optical analyses provide close-up views of two such circuits. See Articles p.168 , p.175 & Letter p.212

    • Richard H. Masland
  • News & Views |

    Data obtained by the Cassini spacecraft show that the plume of ice particles at the south pole of Saturn's moon Enceladus is four times brighter when the moon is farthest away from the planet than when it is closest. See Letter p.182

    • John Spencer
  • News & Views |

    Metabolic processes are regulated by the relative need for the end product, but this control mechanism may fail if demand is very low. A safety mechanism that copes with low demand has been discovered in bacteria. See Letter p.237

    • Athel Cornish-Bowden
  • News & Views |

    A comparison of regulatory DNA sequences in humans, macaques and mice during embryonic limb development reveals thousands of sites of enhanced regulatory activity that are likely to have driven the evolution of our characteristic anatomy.

    • Paul Flicek
  • News & Views |

    The ice sheets retreated 10,000 years ago during a peak in solar radiation, but this peak was no larger than previous ones. A modelling study suggests why the ice sheets were unusually vulnerable to melting at that time. See Letter p.190

    • Shawn J. Marshall
  • News & Views |

    Two new Jurassic fossils yield conflicting reconstructions of the mammalian tree. These divergent genealogies have profoundly different implications for the origin and early diversification of mammals. See Article p.163 & Letter p.199

    • Richard L. Cifelli
    • Brian M. Davis

Article

  • Article |

    Haramiyids were Mesozoic era animals that until now have been identified only from their distinctive teeth, and are thought to be related to the better-known multituberculates: here the authors describe a haramiyid that is very primitive in terms of its jaw and ankle characteristics, suggesting a lack of relationship to the multituberculates.

    • Chang-Fu Zhou
    • Shaoyuan Wu
    • Zhe-Xi Luo
  • Article |

    Improved electron microscopy methods are used to map a mammalian retinal circuit of close to 1,000 neurons; the work reveals a new type of retinal bipolar neuron and suggests functional mechanisms for known visual computations.

    • Moritz Helmstaedter
    • Kevin L. Briggman
    • Winfried Denk
  • Article |

    Reconstruction of a connectome within the fruitfly visual medulla, containing more than 300 neurons and over 8,000 chemical synapses, reveals a candidate motion detection circuit; such a circuit operates by combining displaced visual inputs, an operation consistent with correlation based motion detection.

    • Shin-ya Takemura
    • Arjun Bharioke
    • Dmitri B. Chklovskii

Letter

  • Letter |

    The plume at the south pole of Enceladus is several times brighter when that moon is near the apocentre of its eccentric orbit around Saturn than when it is near its orbital pericentre, showing that more material appears to be escaping from beneath Enceladus’ surface at times when models predict its fissures should be under tension.

    • M. M. Hedman
    • C. M. Gosmeyer
    • M. R. Showalter
  • Letter |

    Quantum fluctuations of a laser are transferred onto the motion of a mechanical resonator and interfere with the fluctuations of the light reflected from the resonator, leading to ‘squeezed’ light with optical noise suppressed below the standard quantum limit.

    • Amir H. Safavi-Naeini
    • Simon Gröblacher
    • Oskar Painter
  • Letter |

    Comprehensive climate and ice-sheet models show that insolation and internal feedbacks between the climate, the ice sheets and the lithosphere–asthenosphere system explain the 100,000-year period on which the Northern Hemisphere ice sheets grow and shrink.

    • Ayako Abe-Ouchi
    • Fuyuki Saito
    • Heinz Blatter
  • Letter |

    Suggestions that haramiyids were related to multituberculates are substantiated with the first discovery of a haramiyid skeleton from the Jurassic period of China; recalibrating evolutionary relationships, this finding means that the lineage leading to placentals and marsupial mammals was distinct in the Triassic period, more than 200 million years ago.

    • Xiaoting Zheng
    • Shundong Bi
    • Jin Meng
  • Letter |

    A computational analysis of the ability of a metabolic reaction network to synthesize all biomass from a single source of carbon and energy shows that when such networks are required to be viable on one particular carbon source, they are typically also viable on multiple other carbon sources that were not targets of selection.

    • Aditya Barve
    • Andreas Wagner
  • Letter |

    Haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain shows that HeLa is relatively stable in terms of point variation; integration of several data sets reveals strong, haplotype-specific activation of the proto-oncogene MYC by the human papilloma virus type 18 genome, and enables the relationship between gene dosage and expression to be examined.

    • Andrew Adey
    • Joshua N. Burton
    • Jay Shendure
  • Letter |

    This study uses calcium imaging to show that T4 and T5 neurons are divided in specific subpopulations responding to motion in four cardinal directions, and are specific to ON versus OFF edges, respectively; when either T4 or T5 neurons were genetically blocked, tethered flies walking on air-suspended beads failed to respond to the corresponding visual stimuli.

    • Matthew S. Maisak
    • Juergen Haag
    • Alexander Borst
  • Letter |

    A new approach has been developed in order to achieve the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells in a three-dimensional culture: this process, which mimics normal development and produces cells that have functional characteristics of mechanosensitive hair cells, is hoped to provide further insights into inner ear development and disorder.

    • Karl R. Koehler
    • Andrew M. Mikosz
    • Eri Hashino
  • Letter |

    Vitamin C is a direct regulator of Tet enzyme activity and DNA methylation fidelity in mouse ES cells; addition of vitamin C promotes Tet activity, increases 5-hydroxymethlycytosine (5hmC) and DNA demethylation of many gene promoters, upregulates demethylated germline genes, and induces a state that more closely approximates that of the inner cell mass of the blastocyst.

    • Kathryn Blaschke
    • Kevin T. Ebata
    • Miguel Ramalho-Santos
  • Letter |

    This study identifies 17 strains of human-derived Clostridia capable of inducing the accumulation and functional maturation of regulatory T cells; it is suggested that these strains may be useful candidates for the future development of oral bacterial therapeutics to treat human inflammatory disorders.

    • Koji Atarashi
    • Takeshi Tanoue
    • Kenya Honda
  • Letter |

    Here, the authors identify a previously unknown regulatory strategy used by Escherichia coli to control end-product levels of the pyrimidine biosynthetic pathway: this involves feedback regulation of the near-terminal pathway enzyme UMP kinase, with accumulation of UMP prevented by its degradation to uridine through UmpH, a phosphatase with a previously unknown function.

    • Marshall Louis Reaves
    • Brian D. Young
    • Joshua D. Rabinowitz

Corrigendum

Erratum

Feature

  • Feature |

    Researchers can get visibility and connections by putting their data online — if they go about it in the right way.

    • Richard Van Noorden

Q&A

  • Q&A |

    Researcher's interest in climate change gets him into international policy negotiation.

    • Virginia Gewin

Futures

  • Futures |

    An unexpected guest.

    • Milo James Fowler
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