Editors' Choice

Science  25 May 2012:
Vol. 336, Issue 6084, pp. 961
  1. Chemistry

    A Carbon Bond's Photo Finish

    1. Jake Yeston

    Photoinduced electron transfer is the initiating step in photosynthesis, so in a broad sense, it's been key to carbon-carbon bond formation since long before chemists (or humans more generally) arrived on the scene. Present-day synthetic organic chemistry rarely relies on that mechanism, though over the past several years its versatility has been coming into renewed focus. More specifically, catalysts such as tris(bipyridyl)ruthenium can easily lend out an electron after absorbing blue light, and substrates in the electron transfer chain often react differently than they would in a more conventional thermal context. DiRocco and Rovis apply this light-accelerated technique to one half of a dual catalytic cycle, oxidizing an amine to a more reactive iminium ion. A second catalyst—an asymmetrically substituted N-heterocyclic carbene—activates an aldehyde toward nucleophilicity in a dark portion of the cycle, ultimately linking the acyl carbon to the α carbon of the amine. The reaction couples a range of aldehydes to substituted tetrahydroisoquinolines, in many cases with enantiomeric excesses above 90%.

    J. Am. Chem. Soc. 134, 10.1021/ja3030164 (2012).

  2. Geophysics

    Yellowstone's Deep Roots

    1. Nicholas S. Wigginton

    Yellowstone National Park in the western United States, renowned for its geothermal features, including geysers and hot springs, rests on a ∼4000-km2 caldera attributed to a series of supervolcano eruptions over the past 2 million years. The volcanic and geothermal activity is caused by the presence of a hot spot currently resting below the park that migrated eastward over the course of millions of years. Conflicting geological evidence implies that the source of this hotspot volcanism is either a deep plume originating hundreds of km below Earth's surface in the lower mantle or more shallow upper mantle melting caused primarily by extension of the continental lithosphere—a process that occurs elsewhere in the western United States. Schmandt et al., analyzing data collected by the dense USArray seismic network while it was deployed across the region, addressed this debate through seismic imaging of the mantle below Yellowstone. Comparing the temperature-sensitive depth variation of mantle discontinuities at 410 and 660 km to global averages indicates the presence of a high-temperature upwelling that is vertically heterogeneous. The shallowing of the 660-km discontinuity, which marks the boundary between the upper and lower mantle, suggests that this plume-like structure originates in the lower mantle, but just how deep down remains unclear.

    Earth Planet. Sci. Lett. 10.1016/j.epsl.2012.03.025 (2012).

  3. Plant Sciences

    Shared Symbiotic Signaling

    1. Pamela J. Hines

    Symbioses of plants with Rhizobium bacteria or mycorrhizal fungi find the microbes lodged in membrane-bound compartments within the host, called symbiosomes and arbuscules, respectively. Although functionally similar, they are morphologically distinct. Shared signaling components between these two symbioses suggest that the signaling pathway governing Rhizobium-legume interactions may have been co-opted from the more common mycorrhizal fungi symbiotic pathway. Ivanov et al. have now identified two members of the VAMP72 (vesicle-associated membrane protein) family, known for their involvement in exocytosis, as critical for the formation of the membrane interface that separates Rhizobium from its host. Medicago plants in which expression of the proteins was disrupted were deficient in the development of symbiosomes and arbuscules, but other aspects of the symbiotic system, such as the root nodule and infection threads, developed normally. VAMP72 proteins localized to exocytotic vesicles in developing symbiosomes. Thus, Rhizobium bacteria and mycorrhizal fungi establish their symbioses with similar subcellular mechanisms, although the fungal symbioses remain much more widespread than the symbioses involving bacteria.

    Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1200407109 (2012).

  4. Biochemistry

    Locked and Loaded

    1. L. Bryan Ray

    Protein kinases that function in signaling pathways controlling cell growth and survival are potential drug targets for fighting cancer and other diseases. Predicting the actions of kinase inhibitors in cells, especially cancer cells, is difficult, however, without a detailed understanding of the normal regulation of the target enzymes. Lin et al. provide insight into how the kinase Akt reacts to inhibitors that compete with adenosine triphosphate (ATP) for binding to the active site. ATP-competitive inhibitors actually increase the phosphorylation of Akt at its activating sites. This is because in the ATP-bound (but not ADP-bound) conformation, the activating phosphorylation sites are inaccessible to phosphatases that can dephopshorylate them. Thus, when activated and bound to ATP, the enzyme is resistant to inactivation until it has catalyzed one round of phosphor ylation, at which point it becomes susceptible to inactivating phosphatases. Furthermore, the ATP-competitive inhibitor studied bound preferentially to the active form of Akt, leading the authors to propose that it might preferentially target tumor cells where Akt is highly activated, with fewer (potentially deleterious) effects on normal cells.

    Sci. Signal. 5, ra37 (2012).

  5. Cell Biology

    Cell-Cell Fusion

    1. Stella M. Hurtley

    Osteoclasts are cells that promote bone remodeling, and their hyperactivity is linked to bone-destructive disorders, including osteoporosis. Activated osteoclast precursors develop columnar actin structures, known as podosomes, which are similar to the invadopodia observed in invasive cancer cells. During osteoclast differentiation, cells can fuse with one another to create multinucleate cells. Oikawa et al. found that in osteoclastic cell cultures, a protein known to be involved in Src-induced cancer cell invadopodia production, Tks5, was also induced during osteoclastogenesis. Tyrosine phosphorylation of Tks5 by Src was required for the generation of circumferential podosomes in osteoclasts and for their fusion. Knockdown of Tks5 in osteoclasts interfered with circumferential podosome formation and cell–cell fusion, whereas polarized membrane extensions seemed to be unaffected. Tks5-expressing osteoclasts were also able to fuse with melanoma cells. Similar osteoclast–cancer cell hybrid cells have been detected in bone lesions in myeloma patients. Thus, Src-Tks5 signaling may represent a potential therapeutic target for the treatment of bone-destructive diseases and malignancies.

    J. Cell Biol. 197, 553 (2012).

  6. Economics

    No Simple Links

    1. Barbara R. Jasny

    Reported linkages of behavioral traits to particular genes indicate that political and economic attitudes might have a genetic component. To explore this possibility in more depth, Benjamin et al. analyzed genotype data from 9836 Swedish twins that had responded to a survey about their economical and political inclinations. Standard twin-based estimates of heritability indicated moderate (30 to 40%) heritability for these traits; however, another method of analysis that relied on dense single-nucleotide polymorphism (SNP) arrays found that the heritability for these traits was half of that. Overall, the authors' analyses indicated that political and economic preferences are highly polygenic, with individual SNPs contributing only small amounts to the heritability. According to the authors, future research endeavors should include larger samples, better methods of measuring economic and political phenotypes, and a focus on “behavioral phenotypes that are more biologically proximate.”

    Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1120666109 (2012).

  7. Chemistry

    Switching Hands

    1. Phil Szuromi

    Most stereoselective catalysts are designed to form just one stereoisomeric product, but there is increasing interest in catalysts that could switch the sense of the desired product through some external stimulus. Mortezaei et al. observed that the helical arrangement of two quinoline moieties in a particular polydentate ligand coordinated to copper varied depending on the metal's oxidation state. The ligand binds through the N atoms of the quinoline groups and either an O atom of a tethered methionine derivative for Cu(II) complexes or the S atom of the side chain for Cu(I) complexes. The authors went on to synthesize derivatives of these complexes in which the quinolines bear catalytic urea groups, so as to exploit the redox-driven conformational switching in control of product stereochemistry. They show that the Michael addition of diethyl malonate to trans-β-nitrostyrene occurs with ∼70% enantiomeric excess for the S and R products with the Cu(II) and Cu(I) catalysts, respectively, in acetonitrile and in the presence of base.

    J. Am. Chem. Soc. 134, 10.1021/ja302283s (2012).

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