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Volume 463 Issue 7280, 28 January 2010

For most of human evolutionary history, before the advent modern running shoes, humans ran either barefoot or in minimal shoes. A comparison of the biomechanics of habitually shod versus habitually barefoot runners suggests that running barefoot is not only comfortable but may also help avoid some impact-related stress injuries. On the cover, the feet of Kenyan adolescents who have never worn shoes and run up to 20 km a day. Their feet are healthy and strong - and until recently, everyone’s feet looked like this. Photo: Adam Daoud.



  • Editorial |

    By opening up its database of potential malaria drugs, GlaxoSmithKline has blazed a path that other pharmaceutical companies should follow.

  • Editorial |

    The reporting of candidate biomarkers for disease must be rigorous to drive translational research.

  • Editorial |

    British scientists must adopt a positive tone if they hope to protect their gains in funding.

Research Highlights

Journal Club



News Feature

  • News Feature |

    Scientists are struggling to make sense of the expanding scientific literature. Corie Lok asks whether computational tools can do the hard work for them.

    • Corie Lok
  • News Feature |

    The surprising discovery of methane in Mars's atmosphere could be a sign of life there. Researchers are now working out how to find its source, reports Katharine Sanderson.

    • Katharine Sanderson
  • News Feature |

    Alan Ashworth took a cancer drug from Petri dish to patients in near record speed. Daniel Cressey meets a biologist who is evangelical about translational research.

    • Daniel Cressey



  • Opinion |

    Geoengineering studies of solar-radiation management should begin urgently, argue David W. Keith, Edward Parson and M. Granger Morgan — before a rogue state decides to act alone.

    • David W. Keith
    • Edward Parson
    • M. Granger Morgan

Books & Arts

  • Books & Arts |

    A volume of essays celebrating 350 years of Britain's Royal Society highlights the continuing gulf between science and the public, says John Gribbin.

    • John Gribbin
  • Books & Arts |

    A restored imperial theatre in China reveals how Western techniques of visual perspective brought by the Jesuits were adopted by an eighteenth-century Chinese emperor, explains Martin Kemp.

    • Martin Kemp

News & Views

  • News & Views |

    Detailed analyses of foot kinematics and kinetics in barefoot and shod runners offer a refined understanding of bipedalism in human evolution. This research will also prompt fresh studies of running injuries.

    • William L. Jungers
  • News & Views |

    TH2 growth factors, which are involved in allergy and in defence against parasites, are produced by many different cell types, including a newly identified population found in fat-associated lymph clusters in the abdomen.

    • Warren Strober
  • News & Views |

    As a rule of thumb, carbon–carbon bonds are not easily broken. But a tungsten complex has been found to break a particularly strong carbon–carbon bond, opening up fresh opportunities for organic synthesis.

    • Alan S. Goldman
  • News & Views |

    Damaged lysosomes, the principal degradative organelles, can kill a cell. A stress-induced protein controls lysosome stability, providing a potential target to treat lysosome-related diseases and cancer.

    • Ibolya Horváth
    • László Vígh
  • News & Views |

    A probabilistic analysis of climate variation during the period AD 1050–1800 refines available estimates of the influence of temperature change on the concentration of carbon dioxide in the atmosphere.

    • Hugues Goosse
  • News & Views |

    The curvature of cellular membranes is generated by proteins and lipids. A synthetic experimental system allows the interplay between protein- and lipid-generated bending mechanisms to be studied directly.

    • Michael M. Kozlov

News and Views Q&A

  • News and Views Q&A |

    The race is on to build a computer that exploits quantum mechanics. Such a machine could solve problems in physics, mathematics and cryptography that were once thought intractable, revolutionizing information technology and illuminating the foundations of physics. But when?

    • Emanuel Knill


  • Editorial |

    • Deepa Nath
    • Ritu Dhand
    • Angela K. Eggleston

Review Article


  • Article |

    Age-associated changes in stem cell supportive niche cells are shown to deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment.

    • Shane R. Mayack
    • Jennifer L. Shadrach
    • Amy J. Wagers
  • Article |

    GNF-2 is a recently discovered, selective allosteric Bcr–Abl inhibitor. Solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry are now used to show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. The results show that the combination of allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.

    • Jianming Zhang
    • Francisco J. Adrián
    • Nathanael S. Gray
  • Article |

    The γ-carboxylation of many blood coagulation factors relies on the generation of vitamin K hydroquinone by the enzyme vitamin K epoxide reductase (VKOR), of which the anticoagulant warfarin is an inhibitor. Here, the X-ray crystal structure of a bacterial homologue of VKOR is presented; the results have implications for the mechanism of action of mammalian VKOR and explain how mutations can cause warfarin resistance.

    • Weikai Li
    • Sol Schulman
    • Tom A. Rapoport


  • Letter |

    Long duration γ-ray bursts mark the explosive death of some massive stars and are a rare sub-class of type Ibc supernovae. To date, central-engine-driven supernovae have been discovered exclusively through their γ-ray emission, yet it is expected that a larger population goes undetected. The discovery of luminous radio emission from the seemingly ordinary type Ibc supernova SN 2009bb, which requires a substantial relativistic outflow powered by a central engine, is now reported.

    • A. M. Soderberg
    • S. Chakraborti
    • M. A. P. Torres
  • Letter |

    Type Ic supernovae have drawn attention since 1998 owing to their sparse association with long duration γ-ray bursts (GRBs). Although the GRB central engine generates ultra-relativistic jets, no relativistic outflows have yet been found in type Ib/c supernovae explosions. Here, radio observations reveal a mildly relativistic expansion in a nearby type Ic supernova, SN 2007gr.

    • Z. Paragi
    • G. B. Taylor
    • B. Paczyński
  • Letter |

    In the study of high-transition-temperature (high-Tc) copper oxide superconductors, a fundamental question is what symmetries are broken when the pseudogap phase sets in below a temperature T*. A large in-plane anisotropy of the Nernst effect is now observed in a high-Tc copper oxide superconductor that sets in precisely at T* throughout the doping phase diagram. It is concluded that the pseudogap phase is an electronic state that strongly breaks four-fold rotational symmetry.

    • R. Daou
    • J. Chang
    • Louis Taillefer
  • Letter |

    The transformation of petroleum-derived feedstocks into useful chemicals often requires controllable cleavage of C–H or C–C bonds. There are many examples of achieving this through the oxidative addition of C–H bonds to metal centres, but analogous transformations of C–C bonds are rare. Here, using a tungsten centre and exploiting the formation of an unusual chelating ligand, a strong C–C bond is cleaved; other metal centres with suitable ancillary ligands could perform the same function.

    • Aaron Sattler
    • Gerard Parkin
  • Letter |

    Anthropogenic global warming is likely to be amplified by positive feedback from the global carbon cycle; however, the magnitude of the climate sensitivity of the global carbon cycle, and thus of its positive feedback strength, is under debate. By combining a probabilistic approach with an ensemble of proxy-based temperature reconstructions and pre-industrial CO2 data from three ice cores, this climate sensitivity is now shown to be much smaller than previously thought.

    • David C. Frank
    • Jan Esper
    • Fortunat Joos
  • Letter |

    Although humans have engaged in long-distance running either barefoot or with minimal footwear for most of human evolutionary history, the modern running shoe was not invented until the 1970s. Here, runners who habitually run in sports shoes are shown to run differently to those who habitually run barefoot, with the latter often landing on the fore-foot rather than the rear-foot. This strike pattern may have evolved to protect from some of the impact-related injuries now experienced by runners.

    • Daniel E. Lieberman
    • Madhusudhan Venkadesan
    • Yannis Pitsiladis
  • Letter |

    Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. The sequencing of the male-specific region of the Y chromosome (MSY) in the chimpanzee and comparison between the MSYs of the two species now reveals that they differ radically in sequence structure and gene content, indicating rapid evolution over the past 6 million years.

    • Jennifer F. Hughes
    • Helen Skaletsky
    • David C. Page
  • Letter |

    Innate immune responses are important in the early phases of infection; for example, natural killer cells are innate lymphocytes that rapidly exhibit cytotoxic activities against virus-infected cells and produce various cytokines. Here, a new type of innate lymphocyte is found in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells, termed FALC (fat-associated lymphoid cluster) cells, produce TH2 cytokines and support B1 cells.

    • Kazuyo Moro
    • Taketo Yamada
    • Shigeo Koyasu
  • Letter |

    In human tumours, complex cell interactions in the tumour and its microenvironment are thought to have an important role in tumorigenesis and cancer progression. In a genetically well-defined model system in Drosophila, clones of cells bearing different mutations are now shown to cooperate to promote tumour growth and invasion. This interaction involves JNK signalling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines.

    • Ming Wu
    • José Carlos Pastor-Pareja
    • Tian Xu
  • Letter |

    Heat shock protein 70 (Hsp70) is a molecular chaperone which, by inhibiting lysosomal membrane permeabilization, promotes the survival of stressed cells. Hsp70 is now shown to stabilize lysosomes by binding to an anionic phospholipid, BMP, resulting in stimulation of acid sphingomyelinase (ASM) activity. Notably, the decreased ASM activity and lysosomal stability seen in patients with Niemann–Pick disease can be corrected by treatment with recombinant Hsp70.

    • Thomas Kirkegaard
    • Anke G. Roth
    • Marja Jäättelä
  • Letter |

    After fertilization in mammals, the maternal and paternal genomes undergo epigenetic reprogramming to prepare for the transition from germ cell to somatic cell transcription programs. One of the events that takes place is the demethylation of the paternal genome. To identify the factors involved in this process, a live cell imaging system is now used to monitor the paternal DNA methylation state in zygotes; Elp3, a component of the elongator complex, is found to have an important role.

    • Yuki Okada
    • Kazuo Yamagata
    • Yi Zhang
  • Letter |

    The increasing cost of energy and concerns about the environment have emphasized the need to find new sources of fuel, with the microbial production of high-energy fuels a promising approach. Here, Escherichia coli is engineered to produce more complex biofuels — fatty esters (biodiesel), fatty alcohols and waxes — directly from simple sugars. Some cells are further engineered to express hemicellulases, a step towards producing these compounds directly from hemicellulose.

    • Eric J. Steen
    • Yisheng Kang
    • Jay D. Keasling
  • Letter |

    Progenitor cells sustain the capacity of self-renewing tissues for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation is one potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through cell divisions. The DNA methyltransferase 1 and other regulators of DNA methylation are now shown to be essential for epidermal progenitor cell function.

    • George L. Sen
    • Jason A. Reuter
    • Paul A. Khavari
  • Letter |

    Distinguishing self from non-self is a vital function for immune systems to repel invaders without inducing autoimmunity. One system, which protects bacteria and archaea from invasion by phage and plasmid DNA, involves clustered, regularly interspaced, short palindromic repeat (CRISPR) loci. Here, in Staphylococcus epidermidis, the mechanism of CRISPR self/non-self discrimination is defined.

    • Luciano A. Marraffini
    • Erik J. Sontheimer


Careers Q&A

  • Careers Q&A |

    Chemist Richard Zare is winner of the 2010 Priestley Medal and the 2009 Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring.

    • Virginia Gewin


  • News |

    Number of domestic researchers draws level with Europe and the United States.

    • Gene Russo

Career Brief

  • Career Brief |

    University benefits should include housework help, study suggests.

  • Career Brief |

    Booklet offers tips to help animal researchers avoid action by activists.

  • Career Brief |

    Bangalore institute uses fellowship to entice young international researchers.



  • Insight |

    Building a Cell

    A cell is a self-organizing and self-replicating machine. The genome contains the instructions for building this highly complex machine, but how this information is accessed, read and interpreted depends on the cell type and its stage of development. Our understanding of how cellular organization and function are regulated in this way is now rapidly improving.

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