This Week in Science

Science  26 Sep 2008:
Vol. 321, Issue 5897, pp. 1737
  1. Rethinking Cancer Metastasis

    CREDIT: KATRINA PODSYPANINA

    Most human cancer deaths are caused by metastasis, in which cancer cells spread from the primary tumor to new sites in the body. Because metastatic cells must successfully negotiate a series of complex steps, including survival in the bloodstream and establishment in a foreign tissue environment, metastasis has been viewed as a late event in cancer progression. Podsypanina et al. (p. 1841, published online 28 August; see the Perspective by Klein) suggest that the metastatic process may begin earlier than previously thought. Normal mouse mammary cells were genetically manipulated to allow the timing of oncogene expression to be experimentally controlled and injected into the bloodstream of mice. Surprisingly, in the absence of oncogene expression, normal mammary cells were capable of traveling to and surviving in the lungs for up to 16 weeks, although they did not initiate aggressive growth until after oncogene activation. Thus, metastases might arise from disseminated normal (premalignant) cells that remain clinically silent until genetic changes render them malignant.

  2. DNA Templates for Nanomachinery

    The precise and complementary base pair matching in DNA has increasingly led to its use as a building or templating material in the assembly of nanoscale objects like particles or wires, or for the decoration of particles and wires with metals or other molecules. Aldaye et al. (p. 1795) review recent developments in the use of DNA as a precise positional tool for complex material assembly. Developments have moved from simple one-dimensional templating to two and three dimensions, with scope for dynamically changing the shape or size of an object, or the fabrication of nanomachines.

  3. Cancer Genomes: From Chaos Comes Order?

    Identification of the genes altered in cancer cells is critical for understanding how the disease arises and for designing more effective diagnostic tests and therapies (see 5 September news story by Kaiser). Parsons et al. (p. 1807, published online 4 September) and Jones et al. (p. 1801, published online 4 September) catalog the numerous genomic alterations that help turn normal cells into two of the deadliest human cancers: glioblastoma multiforme (the most common type of brain cancer) and pancreatic cancer. Although for each cancer type, the specific genomic alterations varied from tumor to tumor, the altered genes affected a limited number of cellular signaling pathways and regulatory processes, suggesting that these are the pathways that go awry and lead to the disease. Of particular interest in the glioblastoma study was the discovery of recurrent mutations in the active site of isocitrate dehydrogenase 1, encoded by the IDH1 gene. In this small study, IDH1 mutations were more prevalent in glioblastomas from younger patients and in “secondary” glioblastomas, and they were associated with a better prognosis.

  4. Martian Dynamo

    CREDIT: STANLEY ET AL.

    One surprise from recent spacecraft observations of Mars is that its crust in the southern hemisphere is strongly magnetized, but not so in the northern hemisphere. This pattern seems similar to the major crustal difference on Mars in that the northern hemisphere is relatively smooth, at a much lower elevation, and younger. Mars now lacks an active dynamo. Stanley et al. (p. 1822; see the news story by Lawler and the Perspective by Langlais and Amit) show through numerical models that if the heat flow were lower across the core-mantle boundary in the northern hemisphere, as might be expected from any mechanism producing the crustal dichotomy, the resulting geomagnetic field might not be a dipole but be concentrated just in the south. Such a dynamo would also affect Mars' atmospheric evolution because only part of the planet would be strongly shielded from the solar wind.

  5. Working Together to Get the Job Done

    Bob tries to make a call to Alice but finds that the line is too noisy. Picking up his second phone (he's a very busy builder), he finds that line is also too noisy and so gives up trying to contact her. With two bad lines, Bob wouldn't be able to make that phone call, at least using the classical communication channels of his provider. Had he had access to quantum communication channels, Smith and Yard (p. 1812, published online 21 August; see the Perspective by Oppenheim) show theoretically that the situation is quite different. Two quantum channels, each with zero capacity to transmit information independently, will allow information to be carried across them when used together. Not only of theoretical interest, this counterintuitive result may be of practical use in the design of quantum communication networks.

  6. Dissecting a Disordered Material

    Graphite oxide was first prepared almost 150 years ago, but the functionalization of the graphite is not uniform, which has hampered efforts to characterize it. This material is now of interest as a precursor for the formation of graphene, which has potentially useful electronic properties. Cai et al. (p. 1815) have now prepared graphite oxide from graphite with varying degrees of 13C-labeling (up to almost 100%). The labeled product allowed much higher resolution in solid-state nuclear magnetic resonance studies and excluded some of the potential models for the chemical bonding network of this material.

  7. Sodium's Nonlinear Response

    The influence of solvent rearrangements on chemical reactions in solution is often modeled using the linear response approximation, which essentially dictates that all starting configurations that equilibrate to a given final state do so with the same dynamics. Bragg et al. (p. 1817; see the Perspective by Stratt) show that the approximation comes up short for the formation of neutral sodium-electron ion pairs in tetrahydrofuran. Equilibration is twice as fast when the reaction proceeds by reduction of a Na+ precursor than when Na is oxidized. The breakdown can be attributed to the large size differences between the cation, anion, and neutral, which substantially alter the extent of necessary solvent cavity rearrangements in each case.

  8. Modeling Ocean Circulation

    Hydrothermal systems along ocean ridges help control the chemistry of the oceans and alter and hydrate the upper oceanic crust; this, in turn, returns water to the Earth's mantle at subduction zones. Hydrothermal systems also foster deep ocean ecosystems. Observations seem to indicate that although ocean ridges are broadly linear, outflows are spaced out along them. Comou et al. (p. 1825) have developed a three-dimensional numerical model of this flow to help reveal the dynamics. Their model shows that optimizing heat transfer causes the flows to self-organize into narrow pipe-like upflows, spaced about 500 m apart, fed by zones of warm downflow that recirculate up to a quarter of the heat.

  9. Cystic Fibrosis Remodeled

    CREDIT: DAVID K. MEYERHOLZ

    Cystic fibrosis (CF) is caused by mutational disruption of CFTR, a gene encoding an ion channel required for chloride- and bicarbonate-mediated fluid secretion in epithelia and for salt absorption in many organs. Two decades of intense research on CFTR has not yet translated into new clinical therapies, in part because mice—the traditional animal model for human disease research—do not develop the full spectrum of pathologies seen in human CF. To address this problem, Rogers et al. (p. 1837) have inactivated the CFTR gene in pigs, an animal that shares many anatomical and physiological features of humans. Newborn pigs lacking CFTR developed many of the gastrointestinal pathologies seen in infants with CF, including intestinal obstruction and abnormalities of the pancreas, liver, and gallbladder, and their nasal epithelia showed defects in chloride transport. These results, while still preliminary, suggest that the pig model may be a valuable tool for testing new therapies for CF.

  10. From the Minds of Babes

    Human babies between 8 months and a year of age cannot perform certain cognitive tasks. In one of these, called the A-not-B error, an object is hidden under a container and the infant repeatedly reaches for it. Then the experimenter hides the object under a different container, in full view of the infant, but the baby still looks under the first container to find it. Topál et al. (p. 1831) propose a new explanation for this error, suggesting that the socially intense “teaching” interaction that usually accompanies the repeated hiding of the object under the first container ensures strong association of the object with that location. When the object is hidden without any communication between the experimenter and the infant, the baby's error rate is reduced. Previous explanations for the phenomenon suggested that it was due to the immaturity of the infant's executive motor control or his or her limited cognitive capacities.

  11. The Agony of Defeat

    Auctioneers take advantage of human nature to increase the sale prices of items. But are they banking on the successful bidder's enjoyment of winning, or are they instead relying on the bidder's aversion to losing? Two sides of the same coin, one might say, but Delgado et al. (p. 1849; see the Perspective by Maskin) argue that it is the latter that drives the phenomenon known as overbidding. When participating in an auction, brain areas sensitive to loss became active. When the authors modified the ground rules of the auction so as to emphasize the potential for loss, without altering the basic possibility of winning, the tendency to overbid was magnified.

  12. Old Rocks

    Some of the oldest rocks on Earth seem to have had a relative excess of the short-lived isotope 146Sm, which led to a preserved excess (relative to other Nd isotopes) in its daughter, 142Nd, compared to other rocks on Earth. These data implied that Earth's mantle fractionated during the first few hundred million years of the planet's formation. O'Neil et al. (p. 1828; see the news story by Kerr) have now found rocks along Hudson Bay, Canada, showing a relative deficit of 142Nd, suggesting that the complementary reservoir also led to volcanic rocks on Earth's surface. In addition, the data define an array with a slope implying an age of 4.28 billion years ago for these rocks, which, if a valid age, would make them the oldest known rocks on Earth.

  13. Recognition Receptor Revealed

    In jawed vertebrates, immunoglobulin genes undergo recombination of variable, diverse, and joining gene segments to give a wide diversity of antibodies that recognize foreign antigens. The mechanism for antigen recognition in jawless vertebrates is quite different, involving variable lymphocyte Receptors (VLRs) that achieve diversity by combinatorial assembly of leucine-rich repeat (LRR) gene cassettes. The structural basis for antigen specificity has been well studied for immunoglobulins, but the mode of antigen recognition by VLRs had not been determined. Now Han et al. (p. 1834) have determined the crystal structure of a lamprey VLR bound to antigen. The VLR forms a solenoid structure, and the antigen is bound to the concave surface that contains variable regions of LRR sequence. A variable loop in the C-terminal module also plays a role in recognition. VLRs structurally resemble Toll-like receptors (TLRs) that play specialized roles in pathogen recognition in the mammalian innate immune system; however, we will have to await more structures of VLR and TLR complexes to clarify their evolutionary relationship.

  14. Your True Colors

    In human social interactions, it is not uncommon to draw inferences about hidden characteristics (attitudes, beliefs, or behavioral norms) on the basis of observable markers that may bear no fundamental connection to the underlying quantity but have become associated with specific groups over time. For instance, individuals sporting insignia of the Boston Red Sox or Manchester United may be classified as friends (or foes, if one should happen to be a New York Yankees or Chelsea fan). Although much research has been devoted to how a member of one cultural or ethnic group views other in-group and out-group members, less is known about the process by which symbolic markers come to be used as signals to define group membership. Efferson et al. (p. 1844) have designed a laboratory-based economic game in which subjects were free to associate arbitrary markers with varying payoffs. Cultural groups (those in which members had adopted the same marker) and consequent ingroup favoritism developed only when the marker was both predictive of behavior in the game as well as changeable over time.