Editors' Choice

Science  28 Oct 2011:
Vol. 334, Issue 6055, pp. 434
  1. Geology

    Volcanic Vetting

    1. Brooks Hanson

    The eruption of Eyjafjallajökull in Iceland in 2010 disrupted air travel across large parts of Europe. Just recently, a series of earthquakes has occurred beneath Katla, which has produced much larger historical eruptions. Ash from even modest volcanic eruptions can be preserved as fine layers in lake and bog sediments, and along with historical records, can provide information on likely recurrence rates. Swindles et al. provide a synthesis of these records, improved by recent dating, microscopic identification of thin ash deposits in the sedimentary sequences, and in some cases chemical fingerprinting of ash to sources. The integrated record, which is probably still missing some events, implies that ash from Icelandic eruptions spread across northern Europe on average about every 50 years during the past 1500 years, and a bit less frequently earlier. In a separate study, Taddeucci et al. examined the fallout of ash from Eyjafjallajökull and show, through direct high-speed videos and simulations, that fine-ash aggregated within the cloud, accelerating its fallout. This effect increased the amount of fine ash particles close to the vent but depleted the downstream ash cloud of fine particles by about a factor of 10. This process should be considered in modeling ash clouds, as commented on by Rose and Durant, and in assessing local health effects from eruptions.

    Geology 39, 887; 891; 895 (2011).

  2. Development

    Palate Development Revealed

    1. Beverly A. Purnell

    Disruptions of cellular migration, proliferation, differentiation, and apoptosis during development can lead to serious defects. Cleft lip and/or palate, a defect seen in 1 in 700 live births, occur when the plates in the roof of the mouth do not join correctly during embryonic development. Previous work has shown that the mutation of several genes, including WNT, FGF, P63, and IRF6, result in clefting in humans and mice, but how these pathways interact to regulate this process is not well understood. Ferretti et al. now show that cephalic ectoderm-specific deletion of Pbx, which encodes a transcription factor, in mice results in cleft lip and palate. Pbx binds to a specific regulatory element of Wnt9b-Wnt3, which is known to regulate p63. The genetic module Pbx-Wnt-p63, along with downstream Irf6, specifies correct embryonic apoptosis, and misregulation of these elements led to craniofacial defects. Clefting could be repaired by ectopically expressing Wnt in the ectoderm of Pbx mutant mice. Because there are many conserved developmental pathways among mammals, this mouse model will probably be useful to elucidating the mechanisms underlying cleft lip and/or palate in humans.

    Dev. Cell. 21, 627 (2011).

  3. Biochemistry

    Cutting to Size

    1. Valda Vinson
    CREDIT: DUBOIS ET AL., J. BIOL. CHEM. 286, 35562 (2011)

    For proteins and peptides synthesized on the ribosome, proteolytic cleavage is a common activation mechanism. Two papers extend this mechanism to nonribosomally synthesized peptides and peptide-polyketide hybrids, natural products of interest in drug development. Reimer et al. identified a gene, xcnG, in the biosynthetic gene cluster for production of the antibiotic xenocoumacin from Xenorhabdus nematophila. An xcnG deletion mutant did not synthesize xenocoumacin but did synthesize pre-xenocoumacin compounds. A pre-xenocoumacin compound added to Escherichia coli cells that expressed full-length xcnG was cleaved to give a xenocoumacin precursor. Homologs of xcnG were identified in other biosynthetic gene clusters. Dubois et al. independently investigated one such homolog, ClpB, an atypical biosynthetic protein in E. coli. They determined the structure of the periplasmic domain and showed that it belongs to a family of serine peptidases. C1pB showed peptidase activity, and mutagenesis experiments confirmed the importance of active site residues in cytopathic activity. Homologs to XCNG and ClpB included larger proteins with ABC export domains, suggesting that inactive prodrugs might be secreted and synchronously cleaved for activation.

    Nat. Chem. Biol. 7, 10.1038/NCHEMBIO.688 (2011); J. Biol. Chem. 286, 35562 (2011).

  4. Neuroscience

    Alcohol's Toll on the Brain

    1. Lisa D. Chong

    Toll-like receptor 4 (TLR4) is expressed by immune cells and controls the expression of genes related to the inflammatory response to pathogens. Wu et al. report that TLR4 and MyD88 (an adaptor protein that acts downstream of TLR4) are also involved in alcohol-induced behavioral changes in mice, implicating an inflammatory response in the brain to alcohol exposure. The duration of acute alcohol-induced sedation and impaired motor activity was reduced in mice lacking TLR4 or MyD88, and these mice recovered motor control more quickly than wild-type animals. Pharmacological inhibition of TLR4 before alcohol exposure also resulted in attenuated behavioral responses to alcohol. Analysis of hippocampal cells isolated from mice showed that alcohol increased the expression of IkBα (an inhibitor of the proinflammatory transcription factor NF-kB), an effect that depended on the presence of TLR4 or MyD88. Thus, a specific immune signaling pathway may be involved in a neuroinflammatory mechanism that controls behavioral responses to alcohol. These observations add to previous reports that in response to alcohol, TLR4 controls glial cell activity and cognitive functions in mice.

    Br. J. Pharmacol. 10.1111/j.1476-5381.2011.01572.x (2011).

  5. Biomedicine

    Surveying the Damage

    1. Paula A. Kiberstis

    Cellular macromolecules such as proteins, lipids, and DNA undergo an increase in oxidative damage with aging, and this damage can have a cascade effect. Oxidation of membrane lipids, for example, produces a reactive product called malondialdehyde (MDA), which can then form adducts with normal cellular proteins, creating new epitopes that are recognized by the immune system, potentially inducing an inflammatory response. A new study presents a plausible model for how these molecular events contribute to age-related macular degeneration (AMD), a form of blindness affecting over 30 million people worldwide. Weismann et al. now show that the immunoregulatory protein complement factor H (CFH) binds MDA with high affinity and blocks MDA-induced inflammation in mice. Interestingly, a variant form of CFH that is associated with an elevated risk of AMD in humans was found to have a lower affinity for MDA. Thus CFH, which is one of the most abundant proteins in plasma, protects mammals from oxidative stress by virtue of its interaction with a specific product of oxidative damage; disruption of this interaction appears to underlie AMD and conceivably other age-related inflammatory diseases.

    Nature 478, 76 (2011).

  6. Physics

    Error Corrected Interferometry

    1. Ian S. Osborne

    Optical interferometers can probe an object at high resolution through its effect on their interference pattern. Neutrons also have an associated wavelength—the de Broglie wavelength— which is very much smaller than any optical wavelength and can in principle provide information on an atomic size scale. However, neutron interferometers are susceptible to low-frequency mechanical vibrations of the interferometer itself. Pushin et al. show that ideas based on error correction protocols used in quantum information science can be carried over to suppress such effects of environmental noise. They show that the formation of decoherence-free subspaces (DFSs), special states in which the system is manipulated in such a way as to protect it from the surrounding environment, can be formed by carefully designing the setup of the system. In this case, they use a figure-eight interferometer carved into a single ingot of silicon instead of the usual two-arm interferometer setup and show that a DFS formed at the center of the interferometer suppresses the effect of environmental noise.

    Phys. Rev. Lett. 107, 150401 (2011).

  7. Economics

    Advantage: Women

    1. Melissa McCartney

    The Internet transformed communication between coauthors by eliminating the transfer of data by mail and allowing for more interdepartmental collaboration. Using women in political science as a case study, Butler and Butler ran a series of regressions on data from three influential journals in the discipline to test the effect of the Internet on coauthorship rates. Although a strict causal interpretation is not possible, the analysis showed that the Internet disproportionately affected women in two ways: through increasing the rate at which women coauthor relative to their male counterparts and through an increase in the number of women accepting jobs in departments with fewer women faculty. These trends may reverse existing gender inequities and possibly have a multiplier effect. Whether these gender effects hold across academic disciplines and how academia can best capitalize on them are open questions.

    Econ. Educ. Rev. 30, 665 (2011).

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