This Week in Science

Science  07 Mar 2008:
Vol. 319, Issue 5868, pp. 1303
  1. Toward Designer Antibiotics


    In the past few years, there has been an alarming increase in the number of methicillin-resistant Staphylococcus aureus (MRSA) infections occurring in hospitals and in the community. Liu et al. (p. 1391, published online 14 February) suggest an antibiotic approach that targets the pigment staphyloxanthin that, besides giving S. aureus its golden color, provides resistance to killing by the host immune system. Early steps in staphyloxanthin biosynthesis resemble those in cholesterol biosynthesis and an enzyme involved in pigment biosynthesis, CrtM (dehydrosqualene synthase), is structurally similar to human squalene synthase (SQS). Inhibitors of SQS were screened for activity against CrtM, and the structures of CrtM bound to three compounds that inhibited pigment formation in vitro were examined. One of these inhibitors, which has been through initial human clinical trials as a cholesterol-lowering agent, increased the susceptibility of S. aureaus to killing by the innate immune system.

  2. Reconciling Sea-Level Changes

    Estimates of global sea level during the Cretaceous period vary widely and sometimes are difficult to reconcile with the geological record of widespread continental flooding that occurred then. In order to remove some of those contradictions, Müller et al. (p. 1357) incorporate marine geophysical data into reconstructions of ocean basin volumes to show that global sea level was between 175 and 235 meters higher during the Cretaceous, when climate was much warmer than it is today. Moreover, by using a mantle convection model to incorporate the effect of the dynamic topography of the East Coast of North America associated with the movement of the subducted Fallaron plate, some different sea-level reconstructions can be reconciled that had seemed to be mutually exclusive.

  3. Rings Around Rhea?

    Rhea, one of Saturn's largest moons, lies outside of the main rings of the planet and is heavily cratered. As described by Jones et al. (p. 1380; see the news story by Kerr), Cassini recently flew by Rhea and was able to detect a depletion in ionized particles and electrons in Saturn's magnetotail downstream of Rhea out to several radii of the moon. Analysis of the data and the geometry of the depletion imply that Rhea may have a ring system formed from dust lofted from the moon by impacts that caused the observed depletions.

  4. Model Citizens?

    Much has been made of the prosocial force of altruistic punishment in human societies—the willingness of some individuals to incur personal costs in order to coerce others into behaving in a cooperative fashion. Herrmann et al. (p. 1362; see the cover and the Perspective by Gintis) describe a large data set collected from university students across a range of societies. The frequency and extent of behaviors that were antisocial in nature—where individuals who had been punished would react by punishing the cooperators—was correlated with previous survey data measuring the social norms of civic cooperation and rule of law in these same societies. Cross-societal variation of this antisocial punishment was associated with cross-societal variation in cooperative behavior and was more prevalent in societies with weaker social norms.

  5. Grand Canyon Dates

    The incision history of the Grand Canyon has been an unsettled issue, in part because common dating methods that rely on the analysis of basalt flows and travertine do not provide any information on samples older than about 1 million years. In order to overcome this limitation, Polyak et al. (p. 1377; see the Perspective by Atkinson and Leeder) take advantage of technical advances in uranium-lead dating methods to date cave mammillaries, a type of speleothem that forms only in caves at or near the depth of the water table. Because these structures are common throughout the canyon, the authors could construct a history of its incision that extends back 17 million years for much of the length of the canyon.

  6. Changing Stiffness with Solvents


    The sea cucumber can rapidly and reversibly alter the stiffness of its inner dermis. Capadona et al. (p. 1370) created a material that mimics these properties by combining a rubber copolymer and cellulose nanofibers taken from tunicates. Addition of a hydrogen-bonding solvent causes the fibers to segregate. This process can be reversed upon removal of the solvent, which causes a reaggregation of the fibers to form a percolating network. By interfering with the cellulose network in this way, the stiffness of the composite can be altered by a factor of 40.

  7. Seeing Over the Optical Event Horizon

    The event horizon of a gravitational black hole represents a point of no return—particles inside this boundary, including photons, cannot escape. However, the direct observation of the event horizon and the possibility of verifying the proposed theoretical properties appear remote. Looking to lab-based analogies that may describe the underlying physics, Philbin et al. (p.1367; see the news story by Cho) report to have found a connection between light propagation in optical fibers and black hole physics. They report on the observation of an optical event horizon and probe some of the expected properties, such as frequency shifting of probe light. The authors also propose a scenario for observing Hawking radiation.

  8. Getting the Balance Wrong

    Cancer development lies in the balance between tumor-suppressing activities and tumor-promoting activities. Halazonetis et al. (p. 1352) review the accumulating evidence that oncogenes, which force cells into rapid cycles of cell division that lead to cancer, cause errors in DNA replication and accumulation of damaged DNA. Cells that detect problems with DNA replication can signal through the p53 tumor suppressor protein and delay cell cycle progression. Mutations in p53 that are very common in cancer cells presumably bypass this barrier to tumorigenesis.

  9. Toward Designer Enzymes

    The creation of “designer enzymes” with new activities remains a challenge. Jiang et al. (p. 1387) take a step in this direction by computationally designing a retroaldolase that, in a multistep reaction, catalyzes the breaking of a carbon-carbon bond in a nonnatural substrate. Seventy-two designs representing four different catalytic motifs and 10 different scaffolds were examined. Active-site designs that used charged side-chain networks to mediate proton transfer were less successful than simpler designs that used a water molecule. Close agreement between two crystal structures and the corresponding design models validated the design procedure; however, the catalytic proficiency of the designed proteins remains far from that of natural enzymes.

  10. Toward a Designer GAS Vaccine


    M proteins are antigenically variable cell-surface virulence factors of group A Streptococcus (GAS). This organism is an important cause of human illness and notably provokes the autoimmune disease rheumatic fever. McNamara et al. (p. 1405) examined a fragment of M1 that binds to host fibrinogen and promotes inflammation. The M1 protein consists of α-helical coiled coils bearing distinctive structural features that impart irregularity and instability to the coiled coil. These features mimic muscle myosin and tropomyosin, which may explain postinfection autoimmune responses. Mice immunized with a mutant, stabilized M protein exhibited reduced harmful inflammation without compromising protective immune responses.

  11. Fine-Scale Analysis of Human Variation

    Two reports examine patterns of human recombination that underlie some of the significant variation that exists among humans. Coop et al. (p. 1395, published online 31 January) genotyped individuals in a Hutterite population and identified the fine scale of recombination events between generations. Kong et al. (p. 1398, published online 31 January) examined parents in the Icelandic population to identify a gene associated with recombination frequency. Together, these studies point to a genomic region affecting the variation in recombination levels among individuals.

  12. Directly Modulating Glucose Homeostasis

    The concentration of glucose in the bloodstream is regulated by glucose itself along with the hormones insulin and glucagon. Glucagon stimulates gluconeogenesis in part by regulating phosphorylation of a transcriptional coactivator known as cyclic adenosine monophosphate response element-binding protein 2 (CRTC2). Dentin et al. (p. 1402; see the Perspective by Birnbaum) found that high concentrations of circulating glucose also regulate CRTC2, but do so through stimulation of the hexosamine biosynthetic pathway and consequent O-linked glycosylation of the same serine residue in CRTC2 that is modified by phosphorylation.

  13. Core Aerosol Issues

    The formation of new aerosol particles begins with the formation of nanometer-scale condensation nuclei, but this crucial step in the formation of aerosols, which affects atmospheric processes such as cloud formation, has been difficult to understand in detail, mainly because the tools needed to generate the relevant particles nanometer size-range have been unavailable. Winkler et al. (p. 1374) have made tungsten oxide nanoparticles nearly as small as molecules, and then use these particles in different charge states to investigate activation and growth of n-propanol aerosols on these particles, as well as on positive and negative ions. Their observations on the role of size, charge, and nucleation should allow a more accurate description of cluster activation and illuminate the role of organic compounds in new atmospheric particle formation.

  14. Plants Going TOPLESS

    The plant hormone auxin is a key regulator of proper plant development. Failure to properly respond to auxin leads to the inability to develop a root and vasculature during Arabidopsis embryogenesis. Szemenyei et al. (p. 1384, published online 7 February) now show that TOPLESS is an integral cofactor required for proper auxin response through the AUX/IAA pathway. These data provide insight into the mechanism by which auxin-mediated transcription directs plant development.

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