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Volume 510 Issue 7506, 26 June 2014

Aspergillus versicolor fungus conidiophore and spores, stained with pactophenol cotton blue. Infection with Gram-negative pathogens bearing metallo-β-lactamases such as NDM-1 and VIM is a growing public health problem and threatens the use of penicillin, cephalosporin and carbapenem antibiotics to treat infections. Here, Gerard Wright and colleagues report a screen for naturally produced inhibitors of NDM-1 in an extensive collection of DMSO-dissolved natural product extracts derived from environmental microorganisms. One extract (from A. versicolor) exhibited a particularly potent anti-NDM-1 activity and was identified as aspergillomarasmine A (AMA), a natural product first reported some 50 years ago associated with leaf wilting. AMA is a rapid and potent inhibitor of both NDM-1 and VIM-2, and the authors find that AMA fully restores antibiotic efficacy in vitro and in vivo against bacterial pathogens possessing either VIM- or NDM-type resistance genes. AMA is non-toxic and well tolerated, making it a realistic prospect as an antibiotic adjuvant. Cover: Dennis Kunkel Microscopy, Inc./Visuals Unlimited/Corbis.

Editorial

  • Editorial |

    An accident with anthrax demonstrates that pathogen research always carries a risk of release — and highlights the need for rigorous scrutiny of gain-of-function flu studies.

  • Editorial |

    Measures of research impact are improving, but universities should be wary of their limits.

  • Editorial |

    Environmentalists are divided over whether it is possible to have a ‘good’ Anthropocene.

World View

Research Highlights

Seven Days

  • Seven Days |

    The week in science: Chemist fined over burns death in lab; gravitational-waves team admits dust problems; and West African Ebola outbreak worsens.

News

Correction

News Feature

Comment

  • Comment |

    Debates over oil-sands infrastructure obscure a broken policy process that overlooks broad climate, energy and environment issues, warn Wendy J. Palen and colleagues.

    • Wendy J. Palen
    • Thomas D. Sisk
    • Ken P. Lertzman
  • Comment |

    Fifty years ago, John Bell made metaphysics testable, but quantum scientists still dispute the implications. Howard Wiseman proposes a way forward.

    • Howard Wiseman

Books & Arts

  • Books & Arts |

    Roger D. Launius is perplexed by a biography of Neil Armstrong that profiles the missions, not the man.

    • Roger D. Launius

Correspondence

Obituary

News & Views

  • News & Views |

    A means of verifying that nuclear warheads to be dismantled are genuine items has been proposed that potentially reveals no information to an inspector about the design of the weapons. Two experts explain the ins and outs of the method and its implications for arms-control policy. See Article p.497

    • John Finney
    • James M. Acton
  • News & Views |

    A naturally occurring fungal compound has been found to restore the susceptibility of bacteria to a class of antibiotic that is currently considered to be our last defence against serious infections. See Article p.503

    • Djalal Meziane-Cherif
    • Patrice Courvalin
  • News & Views |

    Published results of the gravitational constant, a measure of the strength of gravity, have failed to converge. An approach that uses cold atoms provides a new data point in the quest to determine this fundamental constant. See Letter p.518

    • Stephan Schlamminger
  • News & Views |

    Enzymes that attach amino acids to transfer RNAs during protein synthesis must recognize both substrates specifically. Crystal structures reveal a mechanism that explains the RNA specificity for one such system. See Article p.507

    • Oscar Vargas-Rodriguez
    • Karin Musier-Forsyth
  • News & Views |

    A method has been invented for determining nanoscale variations in the distribution of electric charge on surfaces. It has so far been used to examine specific inorganic materials, but could find widespread applications in imaging.

    • J. Marty Gregg
    • Amit Kumar
  • News & Views |

    Many enzymes form 'assembly lines' containing a series of catalytic modules. Visualization of how the structure of a module shifts during catalysis provides a clearer idea of how such enzymes work. See Article p.512 & Letter p.560

    • Peter F. Leadlay

Review Article

  • Review Article |

    N-heterocyclic carbenes are powerful tools in organic chemistry, with many commercially important applications; this overview describes their properties and potential uses.

    • Matthew N. Hopkinson
    • Christian Richter
    • Frank Glorius

Article

  • Article |

    Future rounds of nuclear arms control would ideally involve direct inspection of nuclear warheads using procedures that give inspectors high confidence about the authenticity of submitted nuclear items yet give no information about their design; this is now shown to be achievable using zero-knowledge protocols in neutron imaging of nuclear warheads.

    • Alexander Glaser
    • Boaz Barak
    • Robert J. Goldston
  • Article |

    The emergence of Gram-negative pathogens resistant to carbapenem antibiotics is a global health concern and carbapenem resistance often arises through acquisition of β-lactamase enzymes; this study identifies the natural fungal product aspergillomarasmine A as a metallo-β-lactamase inhibitor and a potential treatment to tackle carbapenem resistance.

    • Andrew M. King
    • Sarah A. Reid-Yu
    • Gerard D. Wright
  • Article |

    Polyketide synthases are multidomain enzymes that produce polyketides, which form the basis of many therapeutic agents; here, electron cryo-microscopy is used to establish the structure of a bacterial full-length module, and to elucidate the structural basis of both intramodule and intermodule substrate transfer.

    • Somnath Dutta
    • Jonathan R. Whicher
    • Georgios Skiniotis

Letter

Feature

  • Feature |

    Early-career researchers who help to organize conferences develop crucial skills that go beyond just booking speakers.

    • Cameron Walker

Q&A

Career Brief

Futures

Outlook

  • Outlook |

    • Brian Owens
  • Outlook |

    Stroke is a public-health problem that tends to affect poorer countries more and leaves richer countries with ballooning medical costs. Yet it is often preventable. By Zoë Corbyn.

    • Zoë Corbyn
  • Outlook |

    Simply lowering blood pressure would reduce the risk of both stroke and age-related cognitive impairment, says Walter J. Koroshetz.

    • Walter J. Koroshetz
  • Outlook |

    The key to stroke recovery is to coax the brain cells to heal without creating more damage in the process. A clever delivery system may just do the trick.

    • Hannah Hoag
  • Outlook |

    Interactive devices are helping people who have had a stroke to regain their motor function.

    • Moheb Costandi
  • Outlook |

    Strokes can shatter a person's identity and make it difficult to find the light. But there are ways to help patients cope.

    • Sujata Gupta
  • Outlook |

    'Covert' strokes are a leading cause of dementia — and their incidence will rise in step with that of vascular risk factors, says Antoine M. Hakim.

    • Antoine M. Hakim

Nature Outlook

  • Nature Outlook |

    Stroke

    Stroke is the second most common cause of death worldwide, yet it can often be prevented. Each year, some 17 million people worldwide will have a stroke and almost 6 million of them will die. Research seeks to guide rehabilitation, to help maintain brain function after a stroke, and to develop treatments to repair the physical damage caused by the condition.

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