Editors' Choice

Science  06 Aug 2004:
Vol. 305, Issue 5685, pp. 754

    ECM in Sight

    More than 10% of elderly Caucasians in the United States suffer from age-related macular degeneration (AMD), an eye disorder that gradually destroys central vision and is characterized by the breakdown of light-sensing retinal cells. Previous genetic studies of an inherited form of AMD and of a macular degenerative disease resembling AMD (Malattia Leventinese) have implicated two glycoproteins—fibulin-6 and fibulin-3, respectively—that are thought to participate in the assembly and stabilization of the extracellular matrix (ECM).

    Two new studies underscore the importance of the fibulin protein family and the ECM in the pathogenesis of macular degeneration. Klenotic et al. find that fibulin-3 binds strongly in vivo to tissue inhibitor of metalloproteinases-3 (TIMP-3), a protein that suppresses ECM degradation and is itself mutated in a third type of inherited macular degeneration (Sorsby fundus dystrophy). Stone et al. report that about 2% of patients with sporadic AMD have missense mutations in the gene encoding fibulin-5. All of these mutations may disrupt the integrity or function of Bruch's membrane, a region of the eye where abnormal extracellular deposits (drusen) accumulate in patients with macular degeneration. — PAK

    J. Biol. Chem. 279, 30469 (2004); N. Engl. J. Med. 351, 346 (2004).


    Making Fusion Happen

    Cell-cell fusion is a key process that occurs during fertilization as well as during the development of a variety of tissues such as muscle and bone. Intracellular and viral fusion events are relatively well characterized in terms of mechanisms and proteins [see Koshiba et al. (p. 858, this issue) and Meeusen et al. (Science Express, 5 Aug. 2004)], yet less is known about cell-cell fusion.

    Shemer et al. examined developmental cell fusion in Caenorhabditis elegans. Previous analysis of eff-1 mutants had implicated cell fusion in establishing body and organ shape and size and in controlling cell migration. These authors find that ectopic expression of eff-1, which encodes a membrane protein, can directly promote epithelial cell fusion, as revealed by the mixing of cytoplasmic contents. In pharyngeal muscle cells, eff-1 appears to stimulate multiple microfusion events, but it is not required for cell fusion in other organs, such as the uterus. — SMH

    Curr. Biol. 10.1016/s0960982204005585 (2004).


    Seamount Dynamics

    The circulation of seawater through the ocean crust extracts heat from the volcanically produced crust and, by altering rocks, is a major control on the composition of the oceans; it also conducts nutrients to vents and springs that harbor a variety of microbes. This circulation occurs both along the hot ocean ridges and more gradually—over tens of millions of years—beyond the ridges as ocean plates move toward subduction zones. As they move, however, they accumulate sediments that retard heat and mass exchange.

    Harris et al. consider a third avenue through which seawater permeates the ocean crust. This one is associated with seamounts, which are produced volcanically but, due to their prominent topography, are not buried by sediments. Temperature and density gradients within the seamounts drive the flow of seawater. Collectively, the oceans contain about 15,000 seamounts, and thus the amount of seawater circulated through seamounts may exceed that associated with ridges. — BH

    Geology 32, 725 (2004).


    Eluting the Tag

    Fluorous tagging has become an increasingly popular means of simplifying organic separations. The basis of the technique is that, like oil and water, hydrocarbons and fluorocarbons tend not to mix. After appending fluorocarbon chains or “tags” to organic compounds, the products can be isolated from the reaction mixture because they dissolve selectively in a fluorinated solvent. In practice, the separations are often done chromatographically with a somewhat exotic fluorinated silica gel as the solid phase; a polar organic liquid phase pushes the untagged compounds through first.

    Matsugi and Curran show that the tagged and untagged compounds can also be separated using standard silica gels. The reaction mixture is deposited onto the silica, and an eluent of diethyl ether and perfluorinated hexanes (FC-72) efficiently pulls the tagged compounds through first and leaves the organic ones behind. The authors demonstrate the workup for a tin-mediated allylation and an amide coupling reaction. For the latter reaction, a single perfluorobutyl group suffices as a tag. — JSY

    Org. Lett. 10.1021/ol049040o (2004).


    A Question of Ploidy

    Eukaryotes are classically considered to be diploid, apart from a brief flirtation with haploidy during reproduction. In fact, variety in ploidy is more likely to be the rule among eukaryotes. Polyploidy is especially common in plants, where it can have spectacular morphological results; some cancerous states are linked with changes in somatic cell ploidy; and some species of sturgeon can even exhibit octoploidy.

    Nuismer and Otto contend that selection favors diploidy in host species and haploidy in parasitic species when there is a single ploidy locus. The reason is that parasites that express a narrow array of antigens or elicitors are more successful at evading the host immune system, whereas hosts with a wide variety of recognition molecules are more apt to catch invading parasites. In this scenario, alleles that increase host resistance tend to be dominant, and those that enhance parasite virulence tend to be recessive. A survey of many thousands of heterotrophic protests showed that those with parasitic lifestyles were three to four times more likely to be haploid than diploid. A striking example is the diploid parasite Trypanosoma brucei, which sequesters its large family of variant surface glycoprotein genes within haploid regions of its genome. — CA

    Proc. Natl. Acad. Sci. U.S.A. 101, 11036 (2004).


    Serendipitous Surcease

    The electrical blackout that affected the northeastern United States and southeastern Canada in August 2003 dramatically reduced the output of polluting species—sulfur dioxide (SO2), which produces fine particles, and nitrogen oxides (NOx), which produce ozone (O3)—from more than 100 power plants. This created a rare opportunity for evaluating directly the contribution of power plant emissions to the formation of regional haze and smog.

    Marufu et al. report the results of a series of measurements made from airplanes that flew over central Pennsylvania (inside the affected region) and western Maryland (outside) about 24 hours after the beginning of the blackout. Concentrations of SO2 and O3 in Pennsylvania were much lower than those measured over western Maryland earlier that day and in comparison to the same location in Pennsylvania a year earlier. Light scattering due to small particles decreased, yielding an improvement in visibility of >40 km. These observations provide a test case for assessing how well numerical models can reproduce the contributions of specific pollution sources to regional air quality. — HJS

    Geophys. Res. Lett. 31, 10.1029/2004GL019771 (2004).

  7. STKE

    Signaling Network Heterogeneity

    Irish et al. set out to determine whether the variations in the genetics and clinical phenotypes of human cancer are correlated with altered responsiveness of signaling networks. They used multiparameter flow cytometry to quantify the amounts of various phosphorylated proteins in cells from 30 acute myeloid leukemia (AML) patients, normal CD33+ cells, and the HL-60 AML and U937 lymphoma cell lines. They found substantial variation among the patient samples in the basal phosphorylation states and their responsiveness to various cytokines of transcriptional regulators (STAT1, STAT3, STAT5, and STAT6), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and the stress-activated protein kinase p38. The AML patients could be classified into four groups based on basal phosphorylation status and change upon cytokine stimulation. The frequencies of cytogenetic abnormalities, Flt3 mutation (Flt3 is a receptor tyrosine kinase, and aberrant signaling through this receptor occurs in 30% of AML patients), and resistance to chemotherapy were nonrandomly distributed across the four clusters. Hence, single-cell analysis of changes in signaling network behaviors (in contrast to focusing on changes in gene expression) may make it possible to connect cancer cell heterogeneity to network-based therapies. — NG

    Cell 118, 217 (2004).

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