Editors' Choice

Science  16 Nov 2007:
Vol. 318, Issue 5853, pp. 1039

    How Old Is the Canyon?

    Much about the timing of formation of the Grand Canyon in Arizona remains uncertain. The process is closely tied into the history of uplift of Western North America during the Cenozoic, including even recently, as well as regional climate change. One approach toward improved understanding is to date past positions of the Colorado River as it deepened the canyon. To do this, Karlstrom et al. have taken advantage of the many volcanic fields in the western part of the canyon; some of these poured lava into the canyon during the past several million years. In fortunate cases, remnants of these flows are preserved perched on ledges or beaches in the canyon, marking past river levels. 40Ar/39Ar dating of these young flows shows that the western part of the canyon has continued to deepen by about 100 to 150 m since about 1.5 million years ago. To the east, across a major fault, the canyon has been deepening at 2 to 3 times that rate. Further dates show that this pattern of active differential uplift, facilitated by faulting, has operated over the past 5 to 6 million years and has continued to modify the canyon even geologically recently. — BH

    Geol. Soc. Am. Bull. 119, 1283 (2007).


    More than Skin Deep

    Skin fungi cause conditions ranging from flaky scalps and eczema to weeping dermatitis and invasive disease. Major culprits are the Malassezia spp., which are closely related to plant pathogenic basidiomycetes, such as Ustilago maydis. In a proteomic-genomic study, Xu et al. discovered that when Malassezia grows on the human scalp, it secretes over 50 proteins, which are generally more similar to those secreted by other skin-parasitizing fungi, such as Candida albicans, than to those of its plant parasite cousins. The secreted proteins include allergens responsible for atopic eczema, but the ones critical for the Malassezia lifestyle are lipases; these enzymes are required in order to harvest host lipids in compensation for an apparent fungal inability to synthesize fatty acids de novo. The secreted enzymes include a distinctive arsenal of extracellular hydrolases, another similarity to Candida. Furthermore, sequencing of the haploid genome revealed mating type genes and a pheromone-responsive MAP kinase module, like those found in yeast. It could be that sex promotes skin colonization and the exchange of virulence determinants. — CA

    Proc. Natl. Acad. Sci. U.S.A. 104, 10.1073/pnas.0706756104 (2007).


    A Matter of Coexistence

    Alloys such as Ge2Sb2Te5 (GST) find use in nonvolatile electronic memory and as recording media in DVDs because they undergo a fast and reversible transition between amorphous and crystalline phases with distinct optical and electronic properties. It was initially assumed that the amorphous form was simply a disordered version of the metastable cubic (rock salt) form. However, experiments on quenched thin films and simulations have given a different and often conflicting picture. Caravati et al. used ab initio molecular dynamics simulations to probe the amorphous structure. They started with metastable cubic GST with Te occupying one sublattice and Ge, Sb, or vacancies randomly occupying the other. For a quenched and annealed sample at 300 K, the calculated x-ray scattering factor was in good agreement with experimental results from the literature. The Ge and Sb atoms were mostly four-coordinate and the Te atoms mostly three-coordinate in defective octahedral-like sites, resembling cubic crystalline GST. However, about one-third of the Ge atoms occupied a tetrahedral environment, absent in the crystalline phase but supportive of the large number of homopolar Ge-Ge, Ge-Sb and Sb-Sb bonds that formed. The authors believe the coexistence of these two arrangements accounts for the rapid phase changes and strong optical contrast between the phases. — MSL

    Appl. Phys. Lett. 91, 171906 (2007).


    Come In and Take Your Coat Off

    The replication of animal viruses relies on their ability to cross a cellular membrane on their way into the host cell's cytoplasm. Simian virus 40 (SV40) is a non-enveloped DNA virus that enters cells via caveolar endocytosis, followed by vesicular transport to the endoplasmic reticulum (ER)-the entry portal of the host cell's secretory pathway-whence it crosses into the cytosol en route to the nucleus. Schelhaas et al. wondered why the viruses follow this relatively complex itinerary. They found that ER-localized enzymes that promote the isomerization of cysteines between their thiol and disulfide states were required for viral entry, and that two ER membrane proteins, Derlin-1 and Sel1L, which are known to mediate the retrotranslocation of misfolded host proteins from the ER back into the cytoplasm, were also important. Specifically, the oxidoreductase ERp57 catalyzed a rearrangement of disulfides within the capsid, resulting in a loosening of the pentamer-hexamer joints in the virus coat. Once in the cytosol, the reduced levels of calcium may promote viral capsid disassembly, facilitating release of the genome. — SMH

    Cell 131, 495 (2007).


    Back to Basics

    Nitrogenase enzymes use an elaborate metal cluster to catalyze the reduction of dinitrogen to ammonia under remarkably mild conditions. Two questions about this process continue to puzzle researchers: What are the elementary steps underlying the scission of the nitrogen triple bond, and how is the cluster that guides these steps assembled? Curatti et al. shed light on the latter question by reconstituting from purified components a system for in vitro synthesis of the cluster—which contains 7 Fe, 9 S, Mo, homocitrate, and one as-yet unidentified light atom and is called the FeMo cofactor. Of 11 nitrogen fixation (Nif) proteins previously shown to be involved in FeMo cofactor biosynthesis, they find that NifB, NifEN, and NifH are key. NifB assembles ferrous iron, sulfide, and S-adenosylmethionine into the NifB cofactor (a precursor of the FeMo cofactor) under reducing conditions; NifEN pushes the synthesis one step further by converting the NifB cofactor into the VK cluster, to which molybdate and homocitrate are then added in a NifH-dependent fashion. The other Nif proteins are thought to supply the relevant forms of Fe, S, and Mo under in vivo conditions and also to protect labile intermediates. The catalytic competency of the synthesized FeMo cofactor (whose structure is still unknown) was confirmed by its ability to combine with apo-NifDK into a holoenzyme that reduced nitrogen. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 104, 17626 (2007).


    Extending Networks

    Many desirable materials properties tend to have tradeoffs. For example, engineered cross-linked polymer networks can have high tensile strength, but though lighter than metals, they have much poorer extensibility—their rigidity causes them to fail after a small increase in length. Some proteins, such as the muscle protein titin, do combine high strength and elasticity, in part because they have a modular structure that unfolds upon deformation. Kushner et al. mimicked this property in their design for cross-links in a poly(n-butyl acrylate) network. Side chains that could form four hydrogen bonds also carried long-chain terminal olefinic groups, which through ring-closing metathesis formed flexible covalent links between the hydrogen bonding pairs (much like the safety chain on a car trailer), providing two levels of chain cross-linking. Compared to a control material with a poly(ethylene glycol) cross-link, the tensile strength increased by 700% for similar elongations at a cross-link density of 6%. — PDS

    J. Am. Chem. Soc. 129, 10.1021/ja0742176 (2007).

  7. STKE

    A New Angiogenesis Weapon

    Tumors need blood, and they secrete angiogenic molecules such as vascular endothelial growth factor (VEGF) to encourage new blood vessels to form. Although an antibody directed against VEGF (αVEGF) can prolong life when given in conjunction with chemotherapy to individuals with certain cancers, inhibiting VEGF signaling can elicit adverse side effects and switch on alternative angiogenic mechanisms in tumor cells. Noting that placental growth factor (PlGF, a VEGF family member) is not required for normal development of the vasculature but has been implicated in pathological angiogenesis, Fischer et al. investigated the effect on tumors of an antibody directed against PlGF (αPlGF). In a mouse model, αPIGF by itself inhibited the growth or metastasis of melanoma and of colon and pancreatic carcinomas, and enhanced inhibition of tumor growth by the chemotherapeutic agents gemcitabine and cyclophosphamide, as well as the anticancer effects of an antibody directed against the VEGF receptor (αVEGFR). The processes inhibited included tumor angiogenesis and lymphangiogenesis, as well as the recruitment of proangiogenic macrophages. On the other hand, αPlGF did not turn on the expression of proangiogenic genes, nor did it mimic or enhance αVEGFR-dependent side effects; indeed, pregnant mice treated with αPlGF delivered litters of healthy pups. Thus, the authors hope that αPlGF might represent a useful addition to the anticancer armamentarium. — EMA

    Cell 131, 463 (2007).

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