Editors' Choice

Science  22 Jul 2005:
Vol. 309, Issue 5734, pp. 536

    Eddies and the Seesaw

    1. H. Jesse Smith

    A series of warm episodes, each lasting several thousand years, occurred in Antarctica between 90,000 and 30,000 years ago. These events correlated with rapid climate oscillations in the Arctic, with Antarctica warming while the Arctic was cooling or already cold. This bipolar seesaw is thought to have been driven by changes in the strength of the deep overturning circulation in the North Atlantic Ocean, but some have questioned how completely that process can account for the fine details of Antarctic warming events.

    Keeling and Visbeck offer an explanation that builds upon earlier suggestions that include the effects of shallow-water processes as well as deep ones. They suggest that changes in the surface salinity gradient across the Antarctic Circumpolar Current were caused by the melting of icebergs discharged from the Arctic, which allowed increased heat transport to Antarctica by ocean eddies. This mechanism produces Antarctic warming of the magnitude observed in ice core records. — HJS

    Quat. Sci. Rev. 10.1016/j/quascirev.2005.04.005 (2005).


    Combichem Sensors

    1. Phil D. Szuromi

    The design of fluorescent chemosensors that can be used to detect metal ions often begins by identifying a molecule with an appropriate metal-binding specificity and then derivatizing the compound so that binding initiates a fluorescent signal. However, once the binding scaffold is set, synthetic routes to fluorescent derivatives may be few.

    Mello and Finney have approached the problem from the opposite direction by using fluorescence to screen combinatorial libraries. They took advantage of cases where binding of a metal ion restricts torsional motion between aryl groups and hence favors an extended aromatic network. A 2,6-biaryl-4-vinylpyridine core bound to a resin support was functionalized with identical arms that consisted of an amino acid and an acyl end group. Screening an initial library of 198 such compounds with a variety of mono- and divalent cations, they identified a fluorophore that bound Hg2+ with an affinity of about 1.8 × 10−6 M−1, which is about an order of magnitude greater than the affinity of K+ for 18-crown-6 ether. — PDS

    J. Am. Chem. Soc. 10.1021/ja043682p (2005).


    Outside Influences

    1. Paula A. Kiberstis

    One of the current concepts in cancer research is that tumor epithelial cells do not grow in isolation, but in the context of a stromal microenvironment that can be permissive or nonpermissive for malignancy. Although this hypothesis was proposed many years ago, only recently have microenvironmental influences on tumorigenesis been explored at the level of specific cell types and signaling molecules.

    Two papers focus on the cellular microenvironment in breast cancer. Radisky et al. describe a cascade of signaling events triggered in mouse mammary epithelial cells that are exposed to matrix metalloproteinase-3 (MMP-3), a stromal enzyme that is overexpressed in human breast cancer and that has been shown to confer tumorigenic potential to normal epithelial cells. These signaling events culminate in the production of reactive oxygen species (ROS) that damage DNA and cause genomic instability in the epithelial cells. Hu et al. investigated whether stromal cells in human breast cancer undergo genomic modifications that might influence stromal cell gene expression during tumorigenesis. An assay of genome-wide methylation revealed that epigenetic changes occur in stromal cells in a tumor stage- and cell type-specific manner, supporting the idea that the dialogue between tumor cells and microenvironment evolves as tumors progress. — PAK

    Nature 436, 123 (2005); Nat. Genet. 10.1038/ng1596 (2005).


    What's in a Name?

    1. Gilbert J. Chin

    The human pathogen Staphylococcus aureus exhibits a golden hue, which comes from a carotenoid that is made by joining two molecules of farnesyl pyrophosphate, a reaction that is catalyzed by dehydrosqualene synthase (encoded by the gene crtM). Liu et al.have looked closely at this bacterium and find that its pigment is in fact a defensive weapon. Deleting crtM changed S. aureus color from gold to pale yellow and increased its sensitivity to being killed by reactive oxygen species (ROS). Conversely, adding this gene to another human pathogen, Streptococcus pyogenes, enhanced its color as well as its resistance to singlet oxygen. Survival of crtM-deleted S. aureus when challenged by human neutrophils or by whole blood from mice and humans was much lower than for wild-type bacteria. Protection could be conferred by an inhibitor of NADPH oxidase, which generates ROS; this was consistent with no difference in the survival of mutant and wild-type bacteria when cocultured with blood from a patient with chronic granulomatous disease (CGD; caused by NADPH oxidase deficiency) or from a mouse model of human CGD. Taken together, these results suggest that inhibition of carotenoid synthesis may render S. aureus more susceptible to host immune defenses. — GJC

    J. Exp. Med. 10.1084/jem.20050846 (2005).


    Fouling Deliberately

    1. Marc S. Lavine

    An ongoing problem in water purification is the fouling of membranes by particulates (such as clay, silt, or algae) and by natural organic matter (NOM), which comes from the biological degradation of plants and humus. NOM typically consists of molecules in the range of 1 to 2 kD, but can form aggregates of much larger size. It has not been clear which components of NOM are responsible for fouling, although it is known that more hydrophobic membranes are more susceptible.

    Clark et al.turn this problem on its head by using a hydrophobic polymer as the basis for a new adsorbent material that can be used to pretreat water. Polysulfone, a common membrane material, was dissolved in an organic solvent mixture and then injected into water, which is not a solvent for the polymer. The polysulfone formed particles with a diameter around 50 nm, which then rapidly clustered into micrometer-sized colloidal aggregates with large surface area. When added to local drinking water, the aggregates adsorbed only a small fraction of the NOM from the water, but these molecules were the ones responsible for most of the fouling of a 20-kD filtration membrane. — MSL

    Langmuir 10.1021/la050186l (2005).


    Sizing Rings

    1. Jake S. Yeston

    Over the past hundred years, chemists have developed numerous methods to squeeze molecules into tight, small rings, despite the inherent strain this places on bond angles. Large rings have little or no strain, but their synthesis poses a different challenge—the ends of long strands must be coaxed to form a loop, instead of linking end-to-end to yield linear oligomers.

    Hori et al.used π-stacking interactions to help achieve this goal. They prepared a precursor resembling a double key-chain: An oligomer of -OCH2CH2O- was capped at both ends by palladium centers complexed to cyclic ligands comprising seven aromatic groups. Adding water to a solution of this compound in dimethyl sulfoxide led to its dimerization, presumably driven by stacking of the large aromatic rings. After they had been brought together, the cyclic ligands became catenated by means of their reversible coordination to Pd, resulting in a very large ring of 238 atoms. — JSY

    Angew. Chem. Int. Ed. 10.1002/anie.200501559 (2005).

  7. STKE

    NO Deadly Signal

    1. L. Bryan Ray

    Reminiscent of mild-mannered Clark Kent, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has an alter ego with potent and deadly effects. When translocated to the nucleus, GAPDH has been associated with transcriptional regulation, and Hara et al.present results implicating it in cell death. Screening for proteins that interact with GAPDH turned up Siah1, a ubiquitin ligase. In transfected cells, GAPDH moved to the nucleus, an effect that required the nuclear localization signal of Siah1. In human embryonic kidney cells undergoing apoptosis in response to staurosporine, GAPDH underwent modification via S-nitrosylation (a consequence of increased intracellular nitric oxide), which enhanced its association with Siah1. In a macrophage cell line undergoing apoptosis in response to lipopolysaccharide, GAPDH became S-nitrosylated and associated with endogenous Siah1, and this complex moved to the nucleus. All of these effects could be blocked by an inhibitor of the nitric oxide—generating enzyme iNOS (inducible nitric oxide synthase). Exactly how nuclear Siah1 promotes apoptosis remains to be explored, but its action appears to require its RING finger domain, indicating that Siah1-mediated ubiquitination and consequent degradation of nuclear proteins is one likely mechanism. — LBR

    Nat. Cell Biol. 7, 665 (2005).

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