This Week in Science

Science  10 Apr 2009:
Vol. 324, Issue 5924, pp. 143
  1. Fighting Flu


    Most current influenza vaccines elicit antibodies that target hypervariable regions on the major surface antigen hemagglutinin (HA) and interfere with binding of a specific flu strain to host cells. Recently, more broadly neutralizing antibodies have been described that raise the hope of designing more general therapies. Now Ekiert et al. (p. 246, published online 26 February) have determined crystal structures of the antigen-binding region of the broadly neutralizing human antibody CR6261 in complex with two different HAs, one from the 1918 influenza virus and the other from H5N1 avian influenza virus. The structures show how neutralization is achieved. This molecular-level understanding of the binding epitope will guide vaccine and drug-design efforts.

  2. Tallying Translation

    Messenger RNA (mRNA) abundance measurements by microarrays and, more recently, by deep sequencing have had dramatic impact on diverse areas of biology. By far the most common use of such mRNA abundance measurements is to provide an estimate of which proteins a cell is making. However, because cells use many translational control mechanisms, mRNA measurements are an imperfect proxy for protein synthesis. Ingolia et al. (p. 218, published online 12 February; see 13 February news story by Service) now present a technique for measuring translation by deep sequencing of the mRNA fragments occupied by ribosomes in living cells. This approach, ribosome profiling, allows the quantification of translation with high precision. The ribosome profiling strategy is simple, comprehensive, and can be adapted easily to other organisms.

  3. Bending Light in Air

    When ultra-intense laser pulses are shot into a dielectric, a plasma can be created with the light ionizing a channel as it travels. Under the right conditions, the light pulses can be self-focused, creating a “light bullet.” Propagating in air, this effect has been used to control lightning. So far, the trigger pulses used have resulted in the generation of plasma channels and filaments that propagate in a straight line as, perhaps, you would expect from light. Using structured light (or Airy) beams, Polynkin et al. (p. 229; see the Perspective by Kasparian and Wolf) show that the nonlinear optical effects at such high intensities can generate filaments that split from the main plasma channel, effectively sending the light bullets around bends. Possible applications of this technology include remote sensing or in the study of intense laser beams.

  4. Solomon Island Quake


    On 1 April 2007, a large magnitude 8 earthquake ruptured across a complex plate boundary in the South Pacific, revealing the dynamics of the boundary and more broadly, how strain is accommodated in the colliding plates. Furlong et al. (p. 226) describe how the earthquake ruptured where two plates containing very young oceanic crust are subducting beneath the overriding Pacific plates in two directions. Thus subduction of young crust can produce great earthquakes. Furthermore the dynamics of uplift associated with the quake implies that most of the strain before the quake was accommodated in the overriding plates.

  5. Gallium Droplet Micro-Movers

    The spontaneous motion of particles, such as Robert Brown's observation of dancing pollen particles, has long been a topic of fascination and interest. In the evaporation of arsenic from a gallium arsenide surface, gallium droplets can form and migrate. Tersoff et al. (p. 236) monitored the motion of the Ga droplets as they moved back and forth during the evaporation of hundreds of surface layers. While one might expect the droplet velocity to increase with increasing temperature, instead the authors observed a temperature at which the motion of the droplets would cease, with an increase in velocity both above and below this temperature. The motion results from the interplay between surface evaporation effects and the motion of the droplets, which prevent the evaporation of the regions they are covering.

  6. Fourfold Oxidation

    Biosynthetic pathways often rely on enzymes to append hydroxyl and thiol groups in specific locations on an already-assembled complex molecular framework, thereby preventing interference from these reactive groups at earlier stages. Inspired by this propensity, Kim et al. (p. 238; see the Perspective by Miller) adopted an analogous strategy in chemical synthesis of the fungal metabolite (+)-11,11′-dideoxyverticillin A, a dimer of alanine-tryptophan dipeptide derivatives with a sensitive bridging disulfide motif. The authors prepared the dimer framework first, and then relied on its stereochemistry to direct the simultaneous introduction of four OH groups using an experimentally optimized oxidant. The next step stereoselectively replaced all four hydroxyls with sulfur, yielding an intermediate that was easily oxidized to the final product. The efficient 10-step synthesis yielded sufficient product for crystallographic characterization.

  7. Regulated Responses to Irregular Signals

    Experiments on the effects of hormones or cytokines often compare responses of cells incubated in the presence or absence of the activating compound. But in vivo, cells experience variations in the amount of stimulus that may be irregular or pulsatile. Ashall et al. (p. 242) explored the response of the transcription factor NF-κB (a major mediator of transcriptional responses in immune function) to short pulses of exposure to the cytokine tumor necrosis factor-α (TNFα). Oscillations in the movement of the transcription factor into and out of the nucleus could be synchronized by exposure of cells to pulses of TNFα. Furthermore, whether transcription of particular genes was activated or not, depended on the frequency of stimulation and consequent timing of NFκB translocation. Cells in inflammatory tissues may experience similar changes in stimulation by TNFα, and thus respond in distinct ways, depending on the timing of the signals received in the cells.

  8. Flight Plan


    To fly with precision, flying animals need to be able to maneuver and stabilize their course and orientation immediately following a change of direction. However, the dynamics of turning are poorly understood. Hedrick et al (p. 252; see the Perspective by Tobalske) develop a framework for predicting maneuverability and stability in flying animals, then use it to predict turning dynamics of seven very different flying animals (including insects, bats, and birds). Geometrically similar animals have turning dynamics in “wingbeat time” regardless of size; fruit flies and hummingbirds both require the same number of wingbeats to finish a turn. An increase in wingbeat frequency allows animals to enhance both maneuverability and stability, two properties previously thought to be in opposition.

  9. Synonymous, Not the Same

    The genetic code is redundant—many of the 20 common amino acids can be coded for by more than one codon, known as synonymous codons—which means that different DNA sequences can code for the same protein sequence. Synonymous codon usage has been thought to be determined by the abundances of iso-accepting transfer RNAs, which can play an important role in either increasing the efficiency or the accuracy of protein synthesis by the ribosome. To test this idea, Kudla et al. (p. 255) created 154 synonymous variants of the green fluorescent protein gene. Rather than synonymous codon usage playing a dominant role in overall translational efficiency, instead, the secondary structure of the messenger RNA, especially at its 5′-end, was most critical. Thus, with regard to protein synthesis, initiation of translation rather than elongation, is limiting for gene expression.

  10. Mosquito Immune Mediation

    Mosquitoes are vectors of numerous human and animal diseases, including malaria. Approaches that enhance or otherwise alter the natural defense mechanisms of mosquitoes could help to reduce or eliminate their competence as vectors of disease. Proteins containing leucine-rich repeats (LRIM1 and APL1C) are known to mediate immune responses in the mosquito, Anopheles gambiae, against the malaria parasite, Plasmodium berghei. Povelones et al. (p. 258, published online 5 March) used gene silencing to show that these proteins produce an immune cascade together with a complement-like protein, binding to the surface of the parasite targeting it for destruction. LRIM1 and APL1C are members of an extensive family of secreted leucine-rich repeat containing proteins that are unique to mosquitoes.

  11. The Enzymology of Brain Cancer

    Many human gliomas (a type of brain tumor) harbor somatic mutations in two genes encoding isocitrate dehydrogenases (IDHs). By structural modeling and biochemical analyses, Zhao et al. (p. 261; see the Perspective by Pollard and Ratcliffe) show that tumor-associated mutations in IDH1 lead to a loss of enzyme activity in a dominant manner through the formation of catalytically inactive heterodimers. Expression of mutant IDH1 reduces formation of the enzyme product, α-ketoglutarate, and enhances the expression of hypoxia-inducible factor-1α (HIF-1α), a subunit of a transcription factor that helps cells to survive and grow when oxygen levels are low. Thus, the IDH1 gene is likely to function as a tumor suppressor that, when inactivated by mutation, facilitates tumor growth through effects on the HIF-1 pathway.

  12. Monitoring the Mantle

    Strong seismic anisotropy is observed at the base of the Earth's mantle and is attributed to deformation. But it has not been clear which mineral is mostly responsible. High-pressure, high-temperature experiments on post-perovskite, the dominant mineral in the mantle, have implied that it is not sufficiently anisotropic. Marquardt et al.(p. 224) have conducted experiments on ferropericlase [(Mg,Fe)O] and show that its anisotropy increases dramatically across a pressure-induced iron-spin transition in the deep mantle. The data support the idea that ferropericlase is the origin of the deep seismic anisotropy and help in mapping flow in the deep mantle.

  13. Flexible Wires and Organic Photovoltaics

    Organic photovoltaic solar cells trade off the high efficiency of single-crystal silicon cells for lower costs, but the active region of the cell that generates electron and hole carriers is not the only part of the cell that can limit performance and cost. In flat-panel devices, the transparent oxide electrodes can limit the mobility of charge carriers. Lee et al. (p. 232, published online 12 March) present a design in which the active organic materials (a conducting polymer and a fullerene derivative that contact one another through interdigitation) are coated on a thin metal wire electrode and the counterelectrode (a thinner wire coated in a silver film to provide good electrical contact) that is then wrapped around the primary electrode and also coated with a transparent polymer. Although the counterelectrode can shadow the active region, this effect appears to be compensated by the optics of polymer fiber; the efficiency, at ∼3%, is similar to flat-panel implementations.

  14. Sex in Leishmania

    Leishmaniasis, a neglected disease that causes high morbidity among impoverished human populations, is caused by kinetoplastid Leishmania parasites. Kinetoplastids are notoriously diverse, yet thought to be largely clonal. Akopyants et al. (p. 265; see the Perspective by Miles et al.) provide direct evidence for genetic exchange between Leishmania parasites occurring in the insect vector, involving the inheritance of a full set of chromosomes from each parent, and uniparental inheritance of maxicircle kDNA (which is equivalent to mitochondrial DNA). These findings illuminate our understanding of the mechanisms underlying the extensive inter- and intraspecies diversity of Leishmania, and will allow classical genetic approaches to identify genes controlling important traits such as virulence and drug resistance.

  15. Vanishingly Ubiquitous Plankton

    Micromonas pusilla is a globally distributed photosynthetic picoeukaryote (less than 2 micrometers), which thrives from tropical to polar ecosystems. Worden et al. (p. 268; see the Perspective by Archibald) compare two strains within the purported single “species” and find far greater genome variability than anticipated—not just in gene complements, but at the most fundamental levels, such as in the capacity for RNA-processing. Micromonas is important to global carbon cycles, not only as a primary producer but also because of its relationship to the progenitors of land-plants. As ocean conditions shift, ubiquitous ocean organisms such as Micromonas promise to serve as reporters of ecological transitions.

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