This Week in Science

Science  26 Sep 2003:
Vol. 301, Issue 5641, pp. 1809
  1. A Harder Look at Metals

    A particular type of a barrier to dislocation movement, the Lomer lock, has been considered to be the dominant strain-hardening mechanism for face-centered cubic (fcc) metals. Using simulations on multiple length scales, Madec et al. (p. 1879; see the Perspective by Gumbsch) propose that a previously neglected mechanism that involves the annihilation of segments of mobile dislocations with other collinear dislocations occurs more frequently and requires a higher stress to overcome.

  2. A Low-Coverage Approach to the Dog Genome

    The substantial cost of generating a high-quality draft assembly for many eukaryotic genomes has raised the question of whether a worthwhile use of finite sequencing resources would be to sample many more genomes at a lower level of coverage. Kirkness et al. (p. 1898; see the Perspective by O'Brien and Murphy) tested that possibility by generating 1.5X sequence coverage of the dog genome and using the available well-curated reference genomes to generate information about exons, comparative annotations of sequence elements, and synteny information. Dog and human genomes were more similar to each other by several measures than either was to the mouse, although the dog lineage appeared to have diverged first from the common ancestor.

  3. Exploiting DNA

    The intrinsic ability of DNA to self-assemble has been put to use for surface patterning and in protein analysis. Yan et al. (p. 1882) created a DNA tile with four-arm junctions that can couple to other four arm junctions to form a superstructure. By putting biotin into the core of the tile, the authors can template strepavidin arrays. The DNA superstructure can also be metallized to form highly conductive silver nanowires. Proteins with two antibody recognition sites can be detected by combining the sensitivity of antibody recognition with the scale-up that can achieved through the polymerase chain reaction (PCR) in immuno-PCR assays, in which antibodies are linked to a DNA marker. The detection limit and speed of these assays tend to be limited by the amount of DNA that can be attached to one antibody and the heterogeneous nature of the initial binding steps. Nam et al. (p. 1884; see the news story by Service) show that several antibodies and numerous DNA tags can be attached to gold nanoparticles to increase tagging sensitivity and that the surface attachment chemistry can be performed on magnetic latex particles. The target DNA can be fully separated from the recognition complex. In some cases, there is sufficient DNA to avoid the PCR step before DNA detection. The authors apply this method to the detection of prostate specific antigen.

  4. Clouds and Cosmic Rays

    Particle nucleation in the upper troposphere and lower stratosphere is an important step in the chain of events that produces clouds, but the mechanisms that contribute to this process are poorly understood. One possible avenue of particle nucleation is by the ionization of gas phase particles by galactic cosmic rays, which can then act as seeds for droplets. Lee et al. (p. 1886) describe observations of new particle formation in the upper troposphere and lower stratosphere, and results from a numerical model, which together show that the abundance and size distribution of these particles are consistent with production by this type of ion-induced nucleation. Hence, galactic cosmic rays appear to affect the production of aerosol particles and, in turn, Earth's radiative energy balance and climate.

  5. Silver Tracks

    Some of the world's largest silver deposits and mines are located in western Bolivia. These resources were clearly recognized by the Inca, who mined this region heavily from about 1400 A.D., and later by the Spanish. Mining and smelting accentuated the erosion and transport of metals, and Abbott and Wolfe (p. 1893) have now reconstructed a long record of metal accumulation in sediments in a lake near the mines at Cerro Rico de Potosí. The ratio of various elements in the lake core provides a fingerprint of metal processing and implies that silver was separated by smelting. There are also hints that mining may have started perhaps as early as 1000 A.D.

  6. Modular Switches

    Many proteins behave like complex switches, integrating multiple inputs to control downstream outputs. It has been thought that such switches could evolve through recombination of their modular domains. Dueber et al. (p. 1904) demonstrate this principle by showing that the actin-polymerizing activity of neuronal Wiskott-Aldrich Syndrome Protein can be reprogrammed to respond to unnatural input by replacing input domains with heterologous ones. Achieving switch diversity through this process could underlie the evolution of signaling circuits.

  7. Bypassing Inflammatory Signaling

    Tumor necrosis factor (TNF) binds to TNF receptors and stimulates inflammatory responses. In patients, an elevated level of TNF is associated with diseases such as rheumatoid arthritis, and inhibition of TNF signaling can be used to treat these diseases. Steed et al. (p. 1895) describe an approach that prevents TNF signaling. They used structure-based protein design to engineer dominant negative TNFs that form heterotrimers with native TNF and in turn prevent binding to TNF receptors. Experiments in animal models show that this approach has promise in attenuating TNF-mediated pathology in vivo.

  8. Genetic Perils of Aging

    Genomic instability plays a critical role in the development of cancer and other age-related diseases. One manifestation of increasing genomic instability with age—and a common genetic alteration in tumors—is loss of heterozygosity (LOH). LOH involves the mutational loss of a normal allele of a gene and renders the cell either hemizygous or homozygous for the deleterious allele. Do yeast suffer the same increased genomic instability with age as do higher organisms? McMurray and Gottschling (p. 1908; see the Perspective by Sinclair) have addressed this question by monitoring LOH as a proxy for instability in both yeast “mother” cells and their “daughters.” Genome instability in the daughter cells increased with the age of the mother, and the genomic integrity of the mother was maintained relative to the daughters. The onset of the genomic instability depended on alterations in the mother cell's life span.

  9. A Very Early Role for Ecdysone

    During the Drosophila life cycle, the steroid hormone ecdysone regulates cell shape changes and movements associated with metamorphosis. Kozlova and Thummel (p. 1911) report that this hormone also acts at an earlier point of the life cycle to establish the body plan of the early larva. This earlier pulse of hormone appears to arise from the amnioserosa, the presumed equivalent of the vertebrate placenta, which suggests a parallel between the two tissues as a critical source of hormone during development.

  10. Letting Go Only Reluctantly

    The bacteriophage λ encodes an exonuclease that digests one strand of a double-stranded DNA substrate. Three enzyme monomers form a toroidal trimer that can digest several thousand nucleotides before letting go of the DNA. No external energy is required, so hydrolysis of the phosphodiester bond must be sufficient to power movement of the enzyme for long distances (tenths of micrometers). Using single-molecule techniques, Perkins et al. (p. 1914) examined the kinetics of this enzyme and found that individual molecules move at the rate of about 10 to 15 nucleotides per second, with pauses of variable duration and location. The strongest pause site on an M13 viral DNA substrate occurred at the sequence GGCGA, which may explain why the recombination frequency at the left end of the λ genome is less than that at the right end.

  11. How Salmonella Staples Actin

    The Salmonella invasion protein A (SipA) is a crucial virulence determinant that plays a role in remodeling the actin cytoskeleton when Salmonella invades its mammalian host cells. Lilic et al. (p. 1918) describe a mechanistic model of SipA activity based on the crystal structure of SipA and electron microscopic analysis. The virulence factor binds and polymerizes host actin through a mechanism termed a “molecular staple.” The SipA protein forms a globular domain, and two nonglobular “arms” that tether actin subunits on separate strands within an actin filament stabilize the filament by stapling it together.

  12. Immunity That Runs Skin Deep

    Immunity to infections of the skin has long been regarded as the domain of Langerhans cells, the specialized dendritic cells (DCs) resident in the skin epidermis. Using a mouse model of herpes simplex virus (HSV) infection, Allan et al. (p. 1925; see the Perspective by Serbina and Pamer) now challenge this accepted view. Langerhans cells were defined as CD8?low/-ve cells capable of migrating out of the epidermis to the draining lymph nodes of the skin. However, these cells were distinct from the high CD8α+ DCs responsible for stimulating HSV-specific T cells after HSV skin infection. These unexpected results cast Langerhans cells in a new, but as yet unidentified, role in maintaining skin immunity.

  13. Solar Climate Connections

    A better understanding of the role of solar forcing on climate during the Holocene and connections of climate in different regions is emerging from comparisons of detailed climate reconstructions. Hu et al. (p. 1890) constructed a high-resolution record of climate variations in the North Pacific region from analyses of lake sediments from coastal Alaska. They show that periodic variations in the hydrological cycle and ecosystems there are similar to cycles of solar activity and to climate in the North Atlantic. This evidence that small variations in insolation have played an important role in determining climate cycles in two distant locations underscores the role of climate cycles that occur on time scales longer than those of modern instrumental records, and suggests that these cycles can be incorporated into models in order better to predict future climate variability.

  14. Promoting Interference

    In RNA interference, aberrant (double-stranded) RNA is first cleaved into small 21- to 25-nucleotide-long fragments by the RNAse-III enzyme Dicer. These small RNAs are then taken up by the RNA-initiated silencing complex (RISC), which uses them in the second step to identify the RNA targeted for destruction. How these two steps are linked has been a mystery. Liu et al. (p. 1921) have purified the dicing activity from Drosophila cells and shown that it consists of Dicer-2 and the newly discovered protein R2D2. R2D2 is related to the Caenorhabditis elegans protein RDE-4, which is also involved in RNAi, and both contain RNA-binding domains. The Dicer-2-R2D2 complex binds the 21 to 25 nucleotide fragments and is involved in delivering them to the RISC complex, allowing it to locate the RNA target and direct its destruction.

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