This Week in Science

Science  04 Mar 2011:
Vol. 331, Issue 6021, pp. 1109
  1. Whittling Away at Graphene Layers


      When graphene is used in device applications, it is often supported on a substrate. The support interaction can alter the conductivity of graphene. Dimiev et al. (p. 1168; see the Perspective by Gunlycke and Sheehan) report a chemical route for removing a single graphene layer from various forms of graphene and related materials, such as graphene oxide. They coat graphene with a thin layer of zinc—which can be patterned on the surface—and then dissolve it with dilute hydrochloric acid, which removes the graphene layer.

    1. Netting Pancreatic Cancer Genes

        Pancreatic neuroendocrine tumors (PanNETs) are aggressive human cancers that often develop silently and progress to untreatable metastatic disease prior to diagnosis. Using an exome sequencing strategy to identify recurrent somatic mutations in PanNETs, Jiao et al. (p. 1199, published online 20 January; see the Perspective by Elsässer et al.) find that the most commonly mutated genes, affecting nearly 45% of the tumors, encode proteins implicated in chromatin remodeling. About 15% of the tumors had mutations altering the mammalian target of rapamycin (mTOR) signaling pathway. mTOR inhibitors are already being tested as cancer therapies, so the mutational status of the PanNETs could help to identify which patients are most likely to respond to these drugs.

      1. Join the Queue

          Many pathogenic Gram-negative bacteria use type III secretion systems to transfer bacterial effector proteins into eukaryotic cells (see the Perspective by Stamm and Goldberg). The core structure is the 3.5-millidalton needle complex (NC) that is organized as rings in the inner and outer bacterial membranes with a needle filament extending out of the cell. Based on cryo-electron microscopy, Schraidt and Marlovits (p. 1192) reconstructed a subnanometer structure of the NC from Salmonella typhimurium that revealed a 24-fold symmetry for the inner rings and a 15-fold symmetry for the outer rings.

          Type III secretion systems work together with a family of translocase proteins, which need to deliver several bacterial effectors to the same target cell in a temporally regulated manner. Lara-Tejero et al. (p. 1188, published online 3 February) describe a mechanism by which the Salmonella type III secretion system sorts its substrates prior to secretion. A cytoplasmic sorting platform is assembled that is sequentially loaded with the appropriate secreted proteins in a process facilitated by customized chaperones.

        1. Hungry Horses

            The evolution of horses in the Cenozoic—the last 65 million years—is one of the best-studied prolonged vertebrate radiations. Their evolution is in part thought to be related to changes in available food, and the abrasiveness of that food, as grasslands expanded. Mihlbachler et al. (p. 1178) used measures of the wear on fossil horse teeth, which have an excellent fossil record, to trace these changes. Most horse populations show relatively low wear, suggesting that dietary pressures were overall low. However, there are several episodes of higher wear in some species, especially during the Miocene, 23 to 5 million years ago, before the appearance of a group of horses with a markedly high crown.

          1. A Visible Sawtooth

              Radio frequency (RF) generators can be programmed to emit many differently shaped oscillatory patterns, from sinusoidal waves associated with single frequencies to square and sawtooth shapes that emerge when frequencies spanning multiple octaves are mixed. Analogous manipulation of optical fields is rather more challenging, because laser sources cannot usually produce many mutually coherent components spaced octaves apart. Chan et al. (p. 1165, published online 20 January; see the Perspective by Yavuz) have now succeeded in preparing optical sawtooth and square wave pulses by assembling discrete combs of five harmonics, from the blue to the mid-infrared, derived through Raman shifting in a hydrogen cell and demonstrate a method for characterizing such waveforms based on linear cross-correlation.

            1. Sizing Signals

                CREDIT: L. LE GOFF AND T. LECUIT

                Growth regulation of the Drosophila wing imaginal disc critically depends on the Decapentaplegic (Dpp) morphogen gradient. How a graded Dpp signal is interpreted by cells to control homogeneous tissue growth remains unclear. Wartlick et al. (p. 1154; see the Perspective by Le Goff and Lecuit) address this question by measuring the spatial and temporal changes of Dpp concentration and signaling activity during the disc growth phase and by quantifying cell proliferation parameters in the discs. Both modeling and experimental findings suggest that both Dpp concentration and signaling gradients scale with tissue size so that, on average, the onset of mitosis occurs when Dpp signaling levels have increased by 50% since the beginning of the cell cycle.

              1. Tangents to Vector Transmission

                  A variety of human parasites complete part of their lifecycle in insect vectors and must achieve a balance between prolonging parasite survival and investment in transmission stages. Matthews (p. 1149) reviews common themes among a broad group of vector-borne parasites and highlights areas of recent progress, ranging from the different factors that influence a parasite's development in its vector, to the different routes that parasites take as they passage through the insect, to the challenges they face from immune responses and sudden environmental shifts. The combined effect of these processes may result in low rates of insect infection—but not low enough to hinder insect-born human diseases such as sleeping sickness, malaria, and dengue.

                1. Space Rock History Revealed

                    Calcium, aluminum-rich inclusions (CAIs) in meteorites are thought to be the oldest solids in the solar system, preserving clues to events that happened in the early solar nebula, before planets or other solids formed. Simon et al. (p. 1175) measured oxygen isotope variations within a CAI from the CV3 Allende meteorite. Both the inclusion's core and its rim show systematic variations in relative abundances of oxygen isotopes that approach the range that has been observed for all solids formed in the solar system. The observations imply that, as it formed, this CAI experienced distinct isotopic environments, possibly because it was transported through different regions of the solar nebula.

                  1. Dissecting the Centriole

                      In most animal cells, centrioles template the nine microtubule doublets in cilia and flagella and constitute the core of the centrosome—the microtubule-organizing center. An early stage of centriole assembly is formation of a central hub with nine spokes. SAS-6 is a protein component of this hub and, based on structural studies, van Breugel et al. (p. 1196, published online 27 January) show that recombinant SAS-6 can self-assemble into a cartwheel-like structure. Mutagenesis results are consistent with the observed interactions being important in centriole assembly.

                    1. Wrap and Slide

                        CREDIT: Q. GAN ET AL.

                        In rotaxanes, a central building block in the burgeoning field of nanometer-scale synthetic machines, a molecular ring can shuttle back and forth along a molecular rod but is kept from falling off by bulky stopper groups at each end. Gan et al. (p. 1172) have designed a variant of this motif in which the ring is replaced by a tightly wound helix. Because the unwinding rate is relatively slow, the helix can slide between binding sites on the rod, despite topologically remaining an open structure. This strategy confers flexibility on the assembly process, which no longer requires kinetically delicate ring-closing and/or stopper-addition reactions.

                      1. Improving Old Memories

                          Can memory be improved? In vivo experiments using pharmacological inhibition of the enzyme protein kinase Mζ (PKMζ) in the insular cortex have shown that long-term conditioned taste aversion memory can be blocked. Now, Shema et al. (p. 1207) show that overexpression of PKMζ in the rat insular cortex enhances memory, including memory that was formed long before the enzyme was overexpressed. The enhancement appears to affect more than a single memory. Thus, modulation of PKMζ can alter memories, even months after the initial encoding.

                        1. Exploiting Ancient Seas

                            Early colonizers of the New World exploited its wide variety of meat resources—many archeological sites show evidence of hunting of megafauna and smaller animals. Early evidence for widespread marine sustenance has been observed primarily in South America. Erlandson et al. (p. 1181) now describe sites in the California Northern Channel Islands that show exploitation of marine food for an extended period of time about 12,000 years ago. At that time, these islands were still several kilometers offshore, requiring boat travel to reach them. A variety of tools show evidence of hunting of marine birds, mammals, shellfish, and fish.

                          1. Made to Move

                              Dynein is a large cytoskeletal motor protein, evolved from ring-shaped AAA+ adenosine triphosphatases, that moves along microtubules to perform functions such as powering the beating of cilia and transporting intracellular cargo. A long coiled-coil stalk connects the AAA+ ring to the microtubule-binding site. Carter et al. (p. 1159, published online 17 February; see the Perspective by Spudich) describe the structure of a dimer of motor domains of yeast cytoplasmic dynein. The structure suggests how conformational changes in the ring associated with adenosine triphosphate binding and hydrolysis might be relayed through the coiled coil to the microtubule-binding domain, leading to a model for the mechanism of motility.

                            1. Break It Down, Sweep It Out

                                Why do some bacteria and viruses cause disease on certain plant species but not on others? Fan et al. (p. 1185) analyzed the resistance mechanisms that keep some strains of Pseudomonas syringae from infecting the plant Arabidopsis. The analysis pointed to a three-gene bacterial operon, sax. Analysis of the plant defense compounds identified an isothiocyanate, a breakdown product of aliphatic glucosinolates, as the key. Similar compounds can also contribute to defenses against insect herbivores. It seems that bacteria can cause the plant to release these defensive compounds. In turn, successful bacterial pathogens use the sax operon to evade the plant's defenses by producing an efflux system that pumps the toxic agent out of the bacteria.

                              1. A Closer Look at Immune Memory

                                  One of the hallmarks of the adaptive immune system is the formation of long-lived memory B lymphocytes, which provide protection against reinfection. Tracking the generation, maintenance, and function of memory B cells during an endogenous immune response is difficult, however, because of the low numbers of antigen-specific cells. Pape et al. (p. 1203, published online 10 February) now describe an enrichment technique that overcomes this hurdle. Using this technique revealed that the endogenous memory B cell response results in the generation of two antigen-specific populations. One population underwent affinity maturation and immunoglobulin (Ig) isotype switching from IgM to IgG, IgE, or IgA, resulting in higher-affinity Ig. The other population maintained expression of IgM and persisted in higher numbers for longer times. Thus, short-term memory responses are dominated by isotype switched memory B cells and long-term memory is provided by IgM-expressing memory B cells.

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