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Volume 483 Issue 7391, 29 March 2012

Cancer cell lines are widely used as preclinical models to gain mechanistic and therapeutic insight. Two manuscripts in this issue describe the large-scale genetic and pharmacological characterization of human cancer cell lines. Each group characterized collections of several-hundred cell lines using different platforms and analytical methods. Their results are complementary, and confirm that many human cell lines capture the genomic diversity of their respective cancers. Initial findings include the identification of a number of potential markers of drug sensitivity and resistance. For example, Garnett et al. report an association between EWS–FLI1 gene translocations, frequently found in Ewing’s sarcoma, and sensitivity to PARP inhibitors, a class of drug currently in clinical trials for other cancer types. Barretina et al. report a possible association between SLFN11 expression and sensitivity to topoisomerase inhibitors. On the cover, dividing fibrosarcoma cells. Cover credit: Steve Gschmeissner/SPL/Corbis

Editorial

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  • Global systems for monitoring threats from flu need a radical overhaul.

    Editorial
  • In the short term, chemical fertilizers are the best way to feed Africa.

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World View

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Research Highlights

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Seven Days

  • The week in science: Global health expert may lead World Bank; Supreme Court weighs in on biotech patents; and James Cameron dives solo to the ocean’s deepest spot.

    Seven Days
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News

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News Feature

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Comment

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Books & Arts

  • Earth's climate and biosphere have always shaped one another. James F. Kasting approves of an attempt to reveal the planet's future by reading its past.

    • James F. Kasting
    Books & Arts
  • John A. Goldsmith is intrigued by the life of a linguistics giant who felt himself to be a failure.

    • John A. Goldsmith
    Books & Arts
  • Erik-Jan Bos, a philosopher at Utrecht University in the Netherlands, unearthed research gold with an Internet search. In putting together a critical edition of René Descartes' correspondence, due out in 2014, he discovered a stolen, never-before-published letter from the seventeenth-century French philosopher and mathematician. In the run-up to Descartes' 416th birthday on 31 March, Bos discusses the hazards of chasing him down.

    • Stephen Ornes
    Books & Arts
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Correspondence

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Obituary

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News & Views

  • Large panels of human cancer cell lines, profiled at the DNA, RNA and chromosomal levels and tested for sensitivity to approved and potential drugs, will accelerate the search for new cancer therapies. See Article p.570 & Letter p.603

    • John N. Weinstein
    News & Views
  • Intense laser fields can rip electrons from an atom and slam them back into it. By using intense terahertz radiation, this idea can be extended to electrons paired with 'holes' in a semiconductor. See Letter p.580

    • Rupert Huber
    News & Views
  • Anticancer 'co-clinical' trials, in which mice carrying known mutations are treated in parallel with patients enrolled in a simultaneous clinical study, could help to improve therapeutic outcome. See Letter p.613

    • Leisa Johnson
    News & Views
  • The exact origin, timing and amplitude of a rapid period of sea-level rise known as meltwater pulse 1A, about 14,500 years ago, have remained unclear. An analysis of coral samples from Tahiti delivers some answers. See Article p.559

    • Robert E. Kopp
    News & Views
  • A fossil foot found in Ethiopia suggests that human ancestors that walked on two feet and also ably climbed trees existed until 3.4 million years ago, adding evidence for locomotor diversity during early human evolution. See Article p.565

    • Daniel E. Lieberman

    Collection:

    News & Views
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Perspective

  • The hidden-reservoir explanation for the non-chondritic composition of the accessible Earth is inconsistent with the heat carried by mantle plumes, which suggests that the whole Earth is not chondritic, perhaps due to preferential loss of crusts from precursor bodies by collisional erosion during accretion.

    • Ian H. Campbell
    • Hugh St C. O’Neill
    Perspective
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Article

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Letter

  • In theory, excitons can form a coherent state like a Bose–Einstein condensate, but this is difficult to produce; it is now shown that spontaneous coherence, characteristic of a condensate, can occur in a cold exciton gas.

    • A. A. High
    • J. R. Leonard
    • A. C. Gossard
    Letter
  • Dissection of the neuronal circuit driving feeding behaviour in mice shows that suppression of the parabrachial nucleus protects against aphagia and promotes weight gain, and also that the parabrachial nucleus is an integration hub that bidirectionally modulates feeding and body weight.

    • Qi Wu
    • Michael S. Clark
    • Richard D. Palmiter
    Letter
  • Inhibition of DOT1L, the H3K79 histone methyltransferase, increases cell reprogramming and substituted for KLF4 and c-Myc, showing that chromatin-modifying enzymes act not only as facilitators but also as barriers to reprogramming.

    • Tamer T. Onder
    • Nergis Kara
    • George Q. Daley
    Letter
  • The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.

    • Jordi Barretina
    • Giordano Caponigro
    • Levi A. Garraway
    Letter
  • OTUB1 is an atypical deubiquitinating enzyme which prevents ubiquitin attachment and is important in the DNA damage pathway; structural analysis of OTUB1 in complex with an E2 ubiquitin-conjugating enzyme reveals that the ability of OTUB1 to inhibit ubiquitin chain synthesis is regulated by an allosteric feedback mechanism.

    • Reuven Wiener
    • Xiangbin Zhang
    • Cynthia Wolberger
    Letter
  • The X-ray crystal structure of the glutamate–GABA antiporter GadC is determined, revealing an inward-open conformation and providing insights into mechanism of amino acid antiport that is needed for acid resistance in bacteria.

    • Dan Ma
    • Peilong Lu
    • Yigong Shi
    Letter
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Career Brief

  • Study aims to find ways to decrease attrition of minority students.

    Career Brief
  • Michigan rules that graduate-student research assistants cannot form unions.

    Career Brief
  • Pfizer collaboration will provide opportunities to work with industry.

    Career Brief
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Feature

  • The growing field of cancer epigenetics demands computational expertise and translational research experience. Qualified practitioners are in high demand.

    • Heidi Ledford
    Feature
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Column

  • Challenging your own ideas and opinions takes more than just a change of scenery, says Andrew Peterman.

    • Andrew Peterman
    Column
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Futures

  • The path to immortality.

    • João Ramalho-Santos
    Futures
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