This Week in Science

Science  12 Dec 2008:
Vol. 322, Issue 5908, pp. 1605
  1. Contagious Rule-Breaking

    CREDIT: KEES KEIZER

    When people see that others clearly disobey a social norm, it will increase the observers' readiness to disobey this particular norm as well (thinking “Everyone else does it, so why shouldn't I?”). But will the fact that other people disobey a particular norm make it more likely that an observer will disobey different social norms, even laws? Keizer et al. (p. 1681, published online 20 November) performed six natural field experiments in Groningen, Netherlands, in which observers had to choose to obey or disobey different social norms after observing visual disorder (such as littering or graffiti), or hearing fireworks go off when prohibited. The willingness to disobey social rules was, indeed, observed to increase when there were signs of social disorder around, and the presence of graffiti more than doubled the number of people littering and stealing.

  2. Transporter Mechanics

    Secondary transporters catalyze the movement of substrates across cellular membranes by coupling substrate passage to ion gradients. Recently described structures have provided insight into how transport occurs through alternate opening and closing of inward and outward facing cavities. Now, Singh et al. (p. 1655; see the Perspective by Diallinas) present extensive structural and functional studies on LeuT, a model for the pharmacologically important class of neurotransmitter:sodium symporters. Incoming amino acids transiently bind to gating residues that are only accessible in the open-to-out conformation. The amino acid then moves to the primary binding site, allowing formation of the occluded state with substrates, but sterically preventing its formation in the case of larger competitive inhibitors like tryptophan. The occluded state then isomerizes to an open-to-in conformation to allow release of substrate to the cytoplasm.

  3. Assemble, Inject, React, Reform

    Self-assembly of molecules on surfaces often occurs through weak interactions, and the reactivity of the constituent molecules usually remains unchanged. Maksymovych et al. (p. 1664) report an unusual example of altered reactivity for dimethyldisulfide (CH3SSCH3) molecules that self-assemble into long chains on single-crystal gold surfaces (up to 15 molecules long). When the tip of a scanning tunneling microscope injects an electron into one end of the chain, not only does the S-S bond in the molecule on the end of the chain break, but the reaction propagates down the chain. The end fragments remain isolated, and the interior fragments reassemble with new partners back into CH3SSCH3 molecules. Theoretical calculations indicate the barrier to this chain reaction is very low, which helps to explain how it competes successfully against energy relaxation processes.

  4. Cancer Epigenetics 101

    CREDIT: VARAMBALLY ET AL.

    Proteins that methylate histones play a key role in regulating gene expression through a so-called “epigenetic” mechanism that involves alterations in chromatin structure rather than sequence changes in DNA. The histone methyltransferase EZH2 (enhancer of zeste homolog 2) is overexpressed in a subset of human cancers, especially in cancers that have metastasized. Varambally et al. (p. 1695, published online 13 November) now show that expression of EZH2 is normally inhibited by a specific microRNA, miR-101. This regulatory mechanism appears to be disrupted during prostate cancer progression when tumors lose miR-101 by genomic deletion. By virtue of its regulation of EZH2, miR-101 may thus exert control over epigenetic pathways active in cancer cells.

  5. Dynamic Calcium

    Permanent burial of calcium carbonate in marine sediments is the major, long-term sink of atmospheric CO2 that balances volcanic CO2 emissions and keeps the concentration of CO2 in the atmosphere mostly within a well-defined but variable range. Griffith et al. (p. 1671) present data on the isotopic composition of Ca in seawater, showing that it varied considerably over the past 28 million years. Major changes occurred in the concentration of Ca in seawater, with the largest excursion corresponding to a climate transition marked both by carbon and oxygen isotopes, which underscores the links between climate and marine geochemical cycles.

  6. Sumatran Earthquake

    The huge moment magnitude (Mw) 9.2 earthquake that struck Sumatra in December 2004, producing a devastating tsunami, ruptured the western end of a major plate boundary. Two subsequent earthquakes ruptured progressively eastward sections, including a Mw 8.4 earthquake in September 2004. The area to the east last ruptured in two great earthquakes in 1797 and 1833. Quakes are associated with local uplift of several meters, which expose shallow corals. Sieh et al. (p. 1674) have accurately dated bands in these corals to reconstruct the quake history. Major quakes occurred in the 1300s and again, about 200 years later. With the known quakes, this record implies that major quakes in this region appear in a series of events about 200 years apart.

  7. Cytoskeleton and Substrate Stiffness

    Substrate stiffness is sensed by cells and affects motility, morphology, and cell fate. Linking molecules between filamentous (F)-actin and the extracellular substrate are thought to act as “clutches” that transmit traction forces and slow F-actin retrograde flow. Chan and Odde (p. 1687; see the Perspective by Aratyn-Schaus and Gardel) now consider the effect of substrate stiffness by modeling both the clutch molecules and the substrate as Hookean springs. The model suggests that substrate stiffness-dependent changes in clutch dynamics result in higher retrograde flow rates with lower traction forces on stiff substrates, and lower retrograde flow rates on soft substrates. As predicted, in embryonic chick forebrain neurons, a switch in F-actin dynamics was observed at an elastic modulus of about 1 kilopascal.

  8. Threading a Molecular Needle

    CREDIT: DEUTMAN ET AL.

    Threading the eye of a needle is often challenging, even when using two hands. Deutman et al. (p. 1668) have explored the mechanism of a molecular analog of this process, in which a linear polymer (thread) and macrocycle must find one another with no outside assistance. Somewhat surprisingly, rates picked up at intermediate lengths—a 22-atom chain threaded more rapidly than a 7-atom chain—before slowing down again into the more expected length dependence of a point-to-point hopping mechanism for extended chains. This effect appears to stem from the capacity of the intermediate length chains to bind first to the exterior of the macrocycle, after which they can bend around and into the opening. Consistent with such a mechanism, enhancing this external binding affinity increased the rate further.

  9. Genes, Triglycerides, and Heart Health

    High blood levels of triglycerides, a major form of dietary fat, have been linked to human heart disease. To identify genes that contribute to interindividual differences in the body's handling of dietary triglycerides, Pollin et al. (p. 1702) performed a genome-wide association study of volunteers from the Lancaster Amish population whose blood triglyceride levels had been measured before and after consumption of a milkshake. Individuals with the lowest levels of blood triglycerides were found to be heterozygous carriers of a null mutation in the gene encoding an inhibitor of triglyceride hydrolysis, called apolipoprotein C-III (apoC-III). These individuals, who produce half the normal amount of apoC-III, also had a favorable cholesterol profile and coronary calcification score, suggesting that they are less likely to develop cardiovascular disease.

  10. Invariant Chain Migration Control

    The spatiotemporal regulation of the immune response remains largely unknown. Now Faure-André et al. (p. 1705; see the Perspective by Lukacs-Kornek and Turley) show that the invariant chain, a key regulator of antigen processing and presentation by MHC class II molecules, also controls the intrinsic migratory capacity of dendritic cells. In a study of the behavior of dendritic cells taken from mouse models on microfabricated surfaces using time-lapse imaging, the invariant chain caused dendritic cells to enter a discontinuous migration mode that alternated between low- and high-motility phases. This regulation of dendritic cell migration by the invariant chain results from its association with the actin-based motor protein, Myosin II. This use of common regulators for antigen processing and cell motility may provide dendritic cells with a way to coordinate the two functions in time and space.

  11. Corralling the Cajal

    The eukaryotic cell nucleus does not contain membrane bound organelles, nevertheless the nucleoplasm is not a homogeneous medium. The nucleoplasm is compartmentalized into a range of highly dynamic structures, including many small foci, which serve to localize intranuclear functions. How are such structures generated and maintained? Kaiser et al. (p. 1713, published online 23 October) analyzed the assembly of the Cajal body, which is involved in the biogenesis and recycling of small nuclear ribonucleoproteins. Individual Cajal body proteins and RNAs were tethered to chromatin and used as “baits” for other Cajal body components. All were able to nucleate the de novo formation of authentic Cajal bodies, with similar kinetics. Thus, assembly of this nuclear body does not occur in a linear, hierarchical manner.

  12. Shaping Up

    The shoot apical meristem of plants is responsible for the upward growth of the plant. This small group of stem cells also leads to lateral branches and to flowering structures. Hamant et al. (p. 1650; see the Perspective by Mulder; see the cover) analyzed the forces patterning the microtubule network, which seems to guide development of the cell wall. The microtubule network and the signaling by the plant hormone, auxin, both affect how the shoot apical meristem functions. Theoretical calculations of stresses in the meristem and during primordium outgrowth paralleled the pattern of microtubules. Interventions involving ablation of individual cells to change the stress pattern confirmed that microtubule networks generally follow the pattern of physical stresses imposed on the cells.

  13. A Golden Route to Dyes

    Brightly colored azobenzene derivatives are important components of dyes, and their efficient photoisomerization behavior has been exploited in molecular device research. However, synthesis of the compounds—two aryl rings bridged by an N=N group—has generally relied on stoichiometric oxidations that generate copious, sometimes toxic, by-products. Grirrane et al. (p. 1661) have found that gold nanoparticles supported on titania act as highly selective catalysts for the direct preparation of these colorful molecules from aniline derivatives and oxygen. Moreover, the same catalyst is known to induce clean reduction of nitroaromatics to anilines, presenting an alternative route to azobenzenes from this second class of precursors through a two-step reduction-oxidation sequence in a single vessel.

  14. Impact Cratering

    Impact cratering is a dominant geologic process throughout the solar system and is our primary means to date surfaces and view the interiors of nearby planets. Understanding how deformation occurs during an impact is critical to these interpretations. Recently, drilling into the Bosumtwi Crater, a large crater in eastern Africa, has provided a view through the core of a large impact structure. Ferrière et al. (p. 1678) combine these data with a numerical model of impacts to reconstruct the pre-impact geology and calculate how the shock from the impact propagated. Together the data imply that the central uplift in the crater resulted from brittle deformation.

  15. Meiosis in the Making

    Diploid organisms, including humans, have two sets of chromosomes in every somatic cell. Sexual organisms must necessarily make haploid gametes—sperm and eggs with only one set of chromosomes—so that the diploid state is maintained when gametes fuse to form an embryo. The specialized cell division process that generates gametes is known as meiosis and is initiated by the extrinsic factor retinoic acid. Lin et al. (p. 1685) show that the mouse RNA-binding protein DAZL (Deleted in azoospermia-like) acts as a complementary intrinsic factor in the initiation of meiosis in a newly posited germ cell-cell state—the meiosis-competent gonocyte. Thus, meiotic initiation in mammals is governed by the cell intrinsic competence factor DAZL and the extrinsic inducing signal, retinoic acid.

  16. Coiled-Coil and Dynein Dynamics

    Dyneins are molecular motors that move various cargos toward the minus-end of microtubules with motility powered by ATP hydrolysis. Unlike kinesin and myosin, where the polymer binding site and catalytic site are within one domain, in dynein a ring of AAA+ ATPase domains is separated from the microtubule binding domain (MTBD) by a 15-nanometer coiled-coil. Now Carter et al. (p. 1691; see the Perspective by Amos) have determined the structure of the MTBD and a portion of the coiled-coil and investigated the effect of lengthening or shortening the coiled-coil on motility. Their results support a mechanism in which the ATPase domain and MTBD communicate through a shift in coiled-coil registry and surprisingly suggest that the MTBD, rather than the ATPase domain, determines the direction of movement.

  17. The Mechanisms Behind Cognitive Enhancement

    Neurophysiological models of cognitive control have hypothesized an important role for the locus coeruleus, in which the functional state of this nucleus in the brain stem modulates an organism's behavioral state to promote adaptive functioning. Electrophysiological studies in primates have shown that states of low-tonic, high-phasic neuronal activity in the locus coeruleus are optimal for task-oriented exploitative modes of functioning, while a shift toward greater tonic but less phasic activity favors less task-oriented, exploratory behavioral states. To increase locus coeruleus autoreceptor activation, Minzenberg et al. (p. 1700) administered modafinil, a known cognitive enhancing drug, which inhibits norepinephrine reuptake in the brain, to subjects during functional magnetic resonance imaging. This pharmacologic intervention promoted a shift from tonic to phasic mode of locus coeruleus activity, as well as coordinated activity between the locus coerules and the prefrontal cortex, in keeping with predictions from the model of the modulatory role of locus coeruleus activity on cortical function and cognition.

  18. Ancient ESCRT to Division

    The ESCRT (endosomal sorting complex required for transport) proteins in eukaryotes mediate a range of processes involving manipulation of cellular membranes including viral budding, endosome trafficking, and membrane abscission in the final stages of cytokinesis in higher eukaryotic cells. Samson et al. (p. 1710, published online 13 November) reveal that ESCRT proteins are not restricted to eukaryotes but are additionally found in the crenarchaeal kingdom of the archaeal domain of life. The archaeal ESCRTs are cell cycle regulated, localize to the mid-cell in dividing cells, and expression of mutant components interferes with cell division in these prokaryotic organisms. Thus crenarchaeal ESCRTs are key components of the archaeal cell division machinery.

  19. Airy Silence

    Several large noncoding (nc) RNAs are known to play a role regulating imprinted gene expression in mammals—where either the maternally derived or the paternally derived gene in the diploid genome is shut down. The Air ncRNA is involved in silencing a series of imprinted genes in cis on mouse chromosomes 17. Nagano et al. (p. 1717, published online 6 November) show that the imprinted mouse gene cluster falls within an Air RNA expression domain in the nucleus. Furthermore, the Air RNA is found to bind to the promoter of one of the imprinted target genes, Slc22a3, and acts to recruit the histone methyltransferase G9a to the promoter. G9a di- and trimethylates nucleosomes on histone H3 lysine 9, a repressive chromatin mark, and shuts down gene expression.

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