Editors' Choice

Science  04 Mar 2005:
Vol. 307, Issue 5714, pp. 1377

    Reducing Nitrogen

    1. Phillip D. Szuromi

    The formation of stable and well-defined inorganic clusters often requires the presence of chelating organic ligands. Rather et al. report using an organic reaction to drive the formation of a hydroxyl-bridged Ga13 cluster. The oxidation of nitrosobenzene to nitrobenzene can be coupled to the reduction of nitrate, and using Ga(NO3)3 as the source of nitrate yields as a product the compound [Ga133-OH)62-OH)18(H2O)24](NO3)15, in which the N: Ga stoichiometry has been reduced from 3:1 to 15:13. Unlike related Al13 clusters, which have a modified Keggin ion structure, x-ray crystallography reveals that the Ga13 cluster is similar to ligand-stabilized clusters in that it has an octahedral Ga core, which is bridged by hydroxyl groups to six Ga cations that are, in turn, surrounded by six hydrated Ga ions. All together, this cluster forms a disklike structure about 1 nm thick and about 2 nm in diameter. — PDS

    J. Am. Chem. Soc. 10.1021/ja043520t (2005).


    Doubly Active Protease

    1. Stephen J. Simpson

    Evasion of host immune responses is a common defensive strategy used by viruses and is clearly illustrated by the ability of hepatitis C virus (HCV) to cause chronic liver infection. HCV achieves evasion, in part, through expression of the NS3/4A protease, which interrupts the induction of α/β interferon (IFN) gene expression by interferon regulatory factor 3 (IRF3).

    Two studies identify the targets of NS3/4A, and both pathways are shown to be pivotal in IRF3 induction. Li et al. observed that the Toll-like receptor 3 (TLR3) adapter protein TRIF was cleaved by NS3/4A in an in vitro assay system. This was sufficient to prevent the induction of IFN-β by an activating ligand of TLR3. Furthermore, compromising TLR3 signaling was found to be sufficient to permit the cellular replication of HCV RNA. Foy et al. determined that the retinoic acid-inducible gene I (RIG-I) signaling pathway was disrupted by NS3/4A, again leading to loss of IRF3 induction of IFN-β The development of NS3/4A inhibitors may help guide improved therapeutic intervention in HCV infection. — SJS

    Proc. Natl. Acad. Sci. U.S.A. 102, 2992; 2986 (2005).


    A Fourth Musketeer

    1. Lisa D. Chong

    In eukaryotic cells, the enzymatic activities of RNA polymerases I, II, and III produce ribosomal RNA (rRNA), messenger RNA, and transfer RNA (and 5S rRNA), respectively. However, the genome sequence of Arabidopsis thaliana revealed that another RNA polymerase might exist, and Onodera et al. provide evidence for a functional RNA polymerase IV (Pol IV). Mutant plants lacking RPD1 and RPD2, genes encoding the two largest subunits of the putative Pol IV, were still viable, but higher order heterochromatin assembly into centromeres was disrupted. Generally, an increase in cytosine methylation favors the formation of condensed heterochromatin. In rpd2 plants, cytosine methylation of the pericentromeric 5S rRNA gene clusters was low, and these clusters did not cycle from a decondensed transcriptionally active state into inactive heterochromatin. Because small interfering RNAs (siRNAs) complementary to 5S rRNA genes were also reduced, the authors suggest that Pol IV affects amplification of siRNAs that direct DNA methylation (of their corresponding genes) and hence promote the organization of condensed nuclear chromocenters. — LDC

    Cell 10.1016/S0092867405001510 (2005).


    Fast and Accurate

    1. Julia Fahrenkamp-Uppenbrink

    Methods for detecting explosives in a range of settings, such as airports, should be highly sensitive, highly specific, and applicable to nonvolatile and thermally unstable substances. Furthermore, they should be fast and not require much sample preparation. Current methods do not measure up; they involve manual sample transfer and are not ideal for detecting nonvolatile or thermally unstable substances.

    Takáts et al. show that the recently developed desorption electrospray ionization (DESI) method meets these requirements. An electrospray is directed onto a surface bearing the analyte, and the resulting secondary ions are collected and analyzed by mass spectrometry. Subnanogram amounts of several explosives, including TNT, can be detected on a variety of surfaces such as paper, skin, and metal. Analysis takes just a few seconds, and no sample preparation is required. — JFU

    Chem. Commun. 10.1039/b418697d (2005).


    Freedom to Associate

    1. Gilbert J. Chin

    The power-generating capacity of mitochondria is based on redox reactions (in complexes I, II, III, and IV) that establish an electrochemical gradient of protons, which is used to make ATP (in complex V). The redox reactions utilize the mobile electron carriers ubiquinone and cytochrome C, and considerations of catalytic flux as well as sequestration of reactive intermediates (not to mention membrane morphology and integrity) have led to the view that these complexes might associate into supercomplexes. Dudkina et al. provide electron microscopic evidence that in plant mitochondria, a 1.5-megadalton conglomerate of complex I and dimeric complex III exists. This observation fits nicely with recent human genetics studies that have linked mutations in genes coding subunits in one mitochondrial complex with functional or structural deficiencies in another. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.0408870102 (2005).


    Greasing the Color Switch

    1. Marc S. Lavine

    Spirooxazine and chromene are photochromic dye molecules that undergo a reversible color change when subject to irradiation. Switching between clear and colored states requires that half of the molecule undergo an approximately 90° rotation. In solution, switching and unswitching are fast processes, but when these molecules are embedded in a host matrix, the unswitching or color fade times are significantly longer and are strongly influenced by the viscosity of the matrix. Although a matrix with a lower glass transition temperature could be used to mitigate this problem, this would then compromise other properties of the lens.

    Evans et al. have come up with a solution that was inspired by drug and gene delivery, where sensitive peptides or oligonucleotides are protected by a polymer conjugate. In this application, they covalently linked their dye molecules to low-glass transition temperature oligomers, such as poly(dimethylsiloxane) and poly(ethyleneglycol), which then shield the dye from the lower-viscosity matrix material. The attached oligomers do not alter the electronic character of the dyes, but they do act to lubricate the twisting motion, so that the color fade times were reduced by 40 to 99%. — MSL

    Nature Mater. 10.1038/nmat1326 (2005).

  7. STKE

    The Big Picture of Synaptic Phosphorylation

    1. L. Bryan Ray

    Collins et al. have used advances in mass spectrometry and strategies to enrich phosphopeptides in cell extracts to carry out a proteomic analysis of phosphorylation events in synaptosomes (synaptic terminals) from the mouse brain. Although phosphorylation events are known to be important in synaptic signaling and have been studied extensively, these results suggest that traditional studies have barely scratched the surface. Of the almost 300 phosphorylation sites identified, 92% had not been described previously. Many proteins exhibited multiple phosphorylation sites (as many as 30), so the 300 sites were distributed among only 79 proteins, half of which were not known to be phosphorylated before.

    The authors used peptide arrays along with literature mining and bioinformatic analysis to assign kinases likely to target these sites. Most substrates appear to be targets of multiple kinases; one group of kinases appears to phosphorylate their target proteins at multiple sites, and another appears to hit just one site per substrate. A relatively small number of kinases appears to account for much of the phosphorylation observed. In fact, nine kinases appear to be responsible for more than 250 of the phosphorylation sites. — LBR

    J. Biol. Chem. 280, 5972 (2005).