This Week in Science

Science  19 Apr 2002:
Vol. 296, Issue 5567, pp. 425
  1. In Brevia

    Random integration of a retroviral vector, a common tool in gene therapy, is shown by Li et al. (p. 497) to induce leukemia in a mouse model.

  2. The Layered Look

    Theoretical studies have suggested that fluids show several layers of ordering near flat surfaces as a result of how force changes across the interface. Recent x-ray diffraction measurements have shown such ordering for relatively complex liquids. Donnelly et al. (p. 507; see the Perspective by Johnson) have used high-resolution transmission electron microscopy to provide real-space images of a much simpler system, liquid xenon confined to small cavities in aluminum. They identify density variations attributed to layering near the cavity walls. Molecular dynamics simulations show that the crystallographic structure across the entire cavity can be determined by the geometry of the cavity. As a result, xenon will be in the body-centered cubic rather than the usual face-centered cubic structure.

  3. Weeding Out the Little Guys

    In typical filtration membranes, smaller molecules preferentially pass through tortuous pathways, but if the membrane is made more selective, it becomes less permeable. Reverse-selective membranes do exist, and they allow larger molecules through preferentially due to their higher solubility in the membrane. Merkel et al. (p. 519; see the news story by Service) show that fumed silica can be used as a filler material to improve both the selectivity and permeability of a number of polymer membranes by altering the distribution of the polymer chains, creating pockets of free volume through which larger molecules can diffuse without increasing the permeability to smaller ones.

  4. Getting Connected

    In order to study the dynamics of subcellular structures, it would be useful to observe the recruitment of newly synthesized components and their subsequent fates in real time and to be able to follow this with examination at the ultrastructural level. Gaietta et al. (p. 503) have done just this by developing a fluorescent labeling technique that can discriminate old and newly synthesized gap junction proteins in living cells and that can be followed by electron microscopic analysis. New gap junction components are delivered to the edge of existing complexes, while older components are removed from the center.

  5. Electrophoretic DNA Computers

    The nature of DNA computing makes it a natural for large search problems, such as conditional Boolean logic problems that involve a large number of variables and clauses. Braich et al. (p. 499; see the Perspective by Reif) used a DNA computer to solve a 20-variable, 24-clause logic problem (a 3-conjunctive normal form formula) that was designed to have only one correct answer out of the 220 (∼1 million) possible truth assignments. Each variable was represented as true or false by two different 15-base sequences. The 300-mer DNAs that represent all possible solutions were then analyzed in an electrophoretic box with a hot stage for releasing the library and a cold stage for capturing DNAs that satisfy the first clause. The nonsatisfying strands wash out, and the process is repeated with the cold stage becoming the hot stage and a new cold stage probe inserted for the second clause. This process is repeated for all of the clauses, and the final answer is read out after PCR amplification.

  6. Nuggets from the Core

    Highly siderophile elements are concentrated in Fe-metal rich phases during melting and crystallization. Geochemists have used these elements to estimate the composition, structure, and timing of core formation. Meibom and Frei (p. 516; see the Perspective by Carlson) analyzed the Re-Os isotopic systematics from placer deposits associated with ophiolites. The high 186Os/188Os and low 187Os/188Os ratios are opposite to those of normal mantle; in fact, if these are unaltered samples of the outer core, then the inner core must have formed within 250 million years of Earth's formation.

  7. CO2 Cap for Cold Climate

    A ubiquitous feature of glacial terminations is a rise in the concentration of atmospheric CO2. Marine and atmospheric records of the stable carbon-isotopic composition of CO2 show a rapid drop in 13C/12C at the end of the last glacial period. Spero and Lea (p. 522) propose a mechanism to link the carbon isotope minima seen at the onsets of glacial terminations with Antarctic/Southern Ocean warming, changes in ocean circulation, and rises in pCO2. Their mechanism provides support for sea ice/destratification models and explains the rapid increase in atmospheric CO2 at the end of glacial cycles as being initiated by Antarctic/Southern Ocean warming.

  8. The Gold Standard

    Polymer fibers are mechanically robust and lightweight, but generally have poor optical properties. High-quality dielectric mirrors, on the other hand, are fragile and expensive to fabricate. Hart et al. (p. 510) combine the desirable attributes of polymer fibers and dielectric mirrors to form fibers that are highly reflecting. The optical properties of the fiber can be tuned during the fiber-forming process, and the reflectivity is better than gold, the standard metal used for high-quality optical instruments.

  9. Weeding Out Even Littler Guys

    The bacterial protein GlpF is an aquaporin and transports water and glycerol. Tajkhorshid et al. (p. 525) have studied the critical characteristics that govern permeability. Structures of GlpF in the presence and absence of glycerol were used for nanosecond simulations of water movements through the channel. These results led to a prediction of permeability for a GlpF mutant that, when constructed and solved, confirmed that two central asparagines block proton movement but permit water to pass.

  10. Cellular Invasions

    In order to infect a cell, a virus must first gain entry. Pelkmans et al. (p. 535) examined how simian virus 40 (SV40) enters via membrane specializations known as caveolae. The virus stimulates the internalization of the caveolae, which requires the breakdown of an actin meshwork. The virus-loaded caveolae bind to the free actin, which forms comet-like tails that propel the loaded caveolae farther into the cell.

  11. The Heart of Eicosanoid Action

    The roles of prostacyclin (PGI2) and thromboxane (TxA2) in the pathogenesis of cardiovascular disease have been debated for over 30 years. Cheng et al. (p. 539; see the Perspective by Vane) show that PGI2 modulates platelet-vascular interactions in vivo and limits the deleterious vascular proliferative response to TxA2. In contrast to aspirin, which suppresses both PGI2 and TxA2, the recently introduced cyclooxygenase-2 (COX-2) inhibitors suppress PGI2 only. The interplay between PGI2 and TxA2 could be the molecular basis of the cardiovascular complications that have been seen in some patients who have substituted COX-2 inhibitors for aspirin.

  12. Taking an In-Depth View

    Recent advances in three-dimensional (3D) optical microscopy have greatly improved imaging for medical histopathology and developmental genetics. Sharpe et al. (p. 541; see the cover) now report a noninvasive, virtual sectioning technology for larger specimens (up to 15 millimeters in diameter), called optical projection tomography (OPT). This technique can produce high-resolution 3D images of both fluorescent and nonfluorescent specimens.

  13. Malaria Drug Regulation

    Antifolate drugs have been used against malaria for decades; however, no one has fully understood the basis for their selectivity. Zhang and Rathod (p. 545; see the Perspective by Goldberg) have now identified a key contribution. Antifolates target a bifunctional enzyme in the parasite called dihydrofolate reductase-thymidylate synthase. In humans, these activities reside in two separate proteins, and antifolates interfere with binding of the cognate messenger RNA (mRNA), disrupting the normal regulation of enzyme levels. Thus, continued translation produces more enzyme, counteracting drug inhibition. In the parasite, mRNA binding occurs far from the active site; therefore, translation stops, and drug action is not thwarted.

  14. Complexes Within Complexes

    When a cellular protein is no longer needed, a proteasomal complex is often used to degrade the unneeded protein. However, proteasomal subunits are now known to be active in nuclear excision repair and transcription elongation. Gonzalez et al. (p. 548; see the Perspective by Ottosen et al.) use biochemical and genetic analyses to demonstrate that the transcriptional activator Gal4 recruits the 19S, but not the 20S, proteasome particle to a target gene.

  15. Rare Lineage

    A small subset of T lymphocytes express markers characteristic of natural killer (NK) cells and has been shown to regulate adaptive immune responses. Compared with conventional T cells, the development of these NKT cells is poorly understood, although it is known that they are positively selected by major histocompatibility complex-like CD1 ligands within the thymus. Benlagha et al. (p. 553; see the Perspective by MacDonald) used tetramer staining to characterize NKT cell precursors in wild-type populations of thymocytes and track their emigration from the thymus into peripheral tissues. The NK phenotype displayed by these cells actually occurred after these cells exited the thymus. More striking was a progression from expression of the cytokine interleukin-4 to interferon-γ, which may reflect distinct mechanisms of immune regulation mediated by these cells.

  16. Superplumes as Heat Conduits

    Seismic tomography has imaged two large regions of lower-than-average velocity in the lower mantle in the central Pacific Ocean and near southern Africa, and these features are correlated with hot spot tracks and two major gravity field anomalies at the surface. These structures, the Hawaiian and African superplumes, may represent the rise of hotter-than-average material from the core to the crust, yet there is no robust evidence for these superplumes in the upper mantle. Now, Romanowicz and Gung (p. 513) show that seismic waves are attenuated in the upper mantle directly above these two superplume regions, creating two prominent hotter-than-average conduits that affect heat flux from the core and dynamics throughout Earth's interior.

  17. Damage Control

    In the nematode Caenorhabditis elegans, activation of a member of the so-called “forkhead” family of transcription factors can cause an increase in life-span of the organism, perhaps by promoting resistance to oxidative damage or other forms of stress. Tran et al. (p. 530) examined the role of mammalian forkhead family member FOXO3a in stress responses and found that activation of the transcription factor caused a delay in the cell cycle and promoted repair of damaged DNA. Analysis of the transcriptional profile of cells expressing activated FOXO3a revealed a group of genes implicated in cellular stress responses and DNA repair. The results indicate that forkhead transcription factors are key regulators of stress responses in mammals as well as in worms and could conceivably influence organismal life-span in this manner.

  18. Persistently Interfering

    RNA interference (RNAi), in which short, double-stranded RNAs of 21 to 25 nucleotides result in the destruction of messenger (and other) RNAs bearing homologous sequences, has become a powerful tool in the experimental manipulation of gene expression. Results have already demonstrated the efficacy of transiently knocking down or knocking out gene expression in mammalian cells using RNAi. Brummelkamp et al. (p. 550) have now developed a vector system that can direct the persistent synthesis of small, interfering RNAs in mammalian cells and can efficiently suppress gene expression for months.

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