This Week in Science

Science  25 Oct 2002:
Vol. 298, Issue 5594, pp. 699
  1. In Brevia

    Continuous cycling in the polymerase chain reaction (PCR) amplification of DNA has been achieved by Krishnan et al. (p. 793) by using convection to shuttle the reaction volume through temperature zones associated with denaturation and annealing.

  2. Shear Surprise

    The elastic modulus of a material is a measure of how much tensile force is required to deform a sample and should generally be a good predictor of shear strength. However, first-principles calculations by Ogata et al. (p. 807) show that because of differences in atomic bonding, aluminum, which has a lower modulus than copper, can undergo larger strains before yielding and thus has the greater shear strength. External pressure is also shown to harden or soften the metals, depending on the crystal direction of the applied force, contrary to the common wisdom that such effects should be negligible.

  3. Mediterranean Air Pollution

    A large, international field measurement campaign—MINOS, the Mediterranean Intensive Oxidant Study—was conducted in 2001 to investigate anthropogenic contributions to environmental stresses affecting rainfall, ecosystems, agriculture, and drinking water supplies. Atmospheric chemistry-transport model simulations suggest that summertime tropospheric ozone is enhanced across the entire Mediterranean basin and contribute substantially to the radiative forcing of climate. Lelieveld et al. (p. 794) used a coastal station in north Crete and two aircraft to measure a wide range of gases, aerosols, radiation, and meteorological parameters. They conclude that European pollution of the Mediterranean lower troposphere has a strong impact on air quality and climate, particularly during summer, and that pollution in the free troposphere is largely determined by intercontinental transport, with upper tropospheric pollution from Asia by monsoons sometimes reaching into the stratosphere.

  4. Magnetic Evolution in Manganites

    The colossal magnetoresistance effect, in which the material's resistance drops rapidly in response to an applied magnetic field, is currently being developed for the applications in memory elements. Despite the complex phase diagram of such materials, a picture is developing based on the seeding, growth, and percolation of magnetic domains to explain the results. However, such an interpretation has so far relied on indirect experiments. Using magnetic force microscopy, Zhang et al. (p. 805) present direct evidence supporting the above scenario, but surprisingly find that the domains evolve at temperatures far away from the transition region.

  5. Second Time Around

    Secondary organic aerosols particles form in the atmosphere through gas-phase reactions of volatile organic compounds associated with photochemical oxidant cycles. These aerosols have potentially negative health effects, contribute to the formation of visibility-reducing haze, and affect Earth's radiative balance. Jang et al. (p. 814) report that the formation of acidic surfaces on atmospheric organic aerosols can lead to large increases in secondary organic aerosol mass. Their experimental observations confirm that inorganic acids, such as sulfuric acid, catalyze particle-phase heterogeneous reactions of atmospheric organic carbonyl species. These reactions lead to a large increase in secondary organic aerosol mass and help stabilize the organic layers as the particles age. Climate models that do not take these reactions into account will likely underpredict radiative forcing caused by aerosols.

  6. Robotic Eyes

    Windblown dust may carry minerals such as iron that are often the limiting nutrient of productivity in many areas of the world ocean. Bishop et al. (p. 817) describe results obtained with a new generation of robotic ocean sensors. They deployed 3000 autonomous profiling floats, which can function for years at a time, in the North Pacific just prior to the storms that swept dust from the Gobi desert across the Pacific Ocean in April and May 2001. They present observations of biomass variability between the surface and 1000 meters depth that show a likely biotic response to fertilization of high nutrient-low chlorophyll waters by iron and other micronutrients in the Asian dust.

  7. High But Not Dry

    The peopling of the New World after deglaciation appears to have followed patterns that reflect the response of early settlers to environmental conditions. Nuñez et al. (p. 821; see the Perspective by Dillehay) describe the discovery and survey of many new early sites in the Atacama Desert region of northern Chile at elevations exceeding 4000 meters. Most of the sites are concentrated in caves or around paleolakes. Settlement of the region about 13,000 years ago apparently coincided with a change from arid to humid conditions, and sites were abandoned starting about 9500 years ago when aridity returned.

  8. Transcriptional Networks and Their Relatives

    Living cells are the product of gene expression programs involving regulated transcription of thousands of genes. Lee et al. (p. 799) used immunoprecipitation and microarray studies to build a global analysis of transcriptional regulatory networks in Saccharomyces cerevisiae. Patterns observed were characterized as motifs that were then combined by an automatic process into a network structure. Such transcriptional regulation represents a network of interactions, and similar networks underlie apparently unrelated systems such as food webs and electronic circuits. To examine their fundamental design features, Milo et al. (p. 824; see the Perspective by Oltvai and Barabási) looked at local organizing principles of networks, expressed as motifs of how different interactors are joined, that occurred at more than random frequencies. Motifs shared by food webs had features that were not shared by transcription networks from yeast and from Escherichia coli or by electronic circuits, although similarities were seen in information-processing circuits.

  9. Digital Programming

    Digit duplications (polydactyly) are seen in mice with defects in the transcription factor Gli3, and excess digits can be induced by ectopic expression of Sonic Hedgehog (Shh) in mouse limb buds. It was previously thought that the Gli3 mutant phenotype was caused by ectopic Shh expression. Using mouse genetics and molecular analyses, te Welscher et al. (p. 827) examine the relative mechanisms for Shh and Gli3 in limb patterning. When Shh function was eliminated, the digits were severely truncated, whereas loss of Gli3 function caused polydactyly. Mouse embryos lacking both Shh and Gli3 were polydactylous. Digits can form by two completely different mechanisms, one of which is SHH dependent and another that is SHH independent (represented by the GLI3 mutation). Thus, a major function of SHH is to counteract the repressive action of GLI3.

  10. Live Long and Reproduce

    Insulin and other insulin-like growth factors signal through a pathway that involved phosphatidynlinositol 3-kinase and the forkhead transcription factors. This pathway is a critical regulator of life-span and reproduction in many organisms. Dillin et al. (p. 830) have now determined that in the nematode Caenorhabditis elegans, life-span can be regulated through this pathway only in the adult and reproduction only in the developmental phases. Thus, the long-standing notion that life-span can be lengthened only at the expense of reproductive fitness is almost certainly false.

  11. Power Gliding

    The role of the motor protein myosin A in the pathogenesis of Toxoplasma gondii has been examined by Meissner et al. (p. 837), who regulated the expression of a target protein to maintain the possibility of parasite propagation in the presence of a mutation of a gene required for invasion and parasite growth. They confirmed that myosin A is required to power the invasion of host cells and is a virulence factor in a mouse model system.

  12. Strong Bones via Tailored Hormones

    Interest in alternative preventive strategies against bone loss has intensified in light of the recent announcement of risks associated with hormone replacement therapy. Previous cell culture studies showed that estrogen and androgen protect bone through a mechanism distinct from the DNA-mediated mechanism underlying their effects on reproductive organs. Kousteni et al. (p. 843; see the news story by Miller) now show that a synthetic compound (estren) that mimics these “nongenotropic” effects can increase bone mass in estrogen- or androgen-deficient mice without adverse effects on reproductive organs.

  13. A Gentler Treatment for Stroke

    Although N-methyl-D-aspartate (NMDA) receptors play an important role in stroke, simply blocking them would lead to many unwanted side effects. Aarts et al. (p. 846) suggest a novel approach to treat ischemic brain injury without blocking NMDA receptors. They constructed peptides that bind to molecular domains governing the interaction of NMDA receptors with the postsynaptic density protein PSD-95. Normal synaptic activity and the subsequent postsynaptic calcium influx remain intact but deleterious downstream neurotoxic signaling events are inhibited.

  14. Taking the Heat

    Many industrial chemical reactions are catalyzed by small metal particles supported on oxide surfaces. Often these catalysts are deactivated by sintering, the agglomeration of smaller particles into larger ones at high temperatures, but the theoretical models for predicting sintering are either empirical or based on simplistic models for particle energetics. Campbell et al. (p. 811), using calorimetric data for lead particles on magnesium oxide, developed a model for metal nanoparticle energetics. They then apply this model to reproduce the distribution of gold nanoparticles on titanium oxide that they measured in ion scattering experiments. This model should prove useful in predicting long-term sinter rates of supported catalysts.

  15. β-Arrestin Regulation of Cyclic AMP Signaling

    A molecular understanding of the spatio-temporal regulation of various intracellular signals has revealed how tightly controlled this process can be. For example, the intracellular second messenger adenosine 3',5'-monophosphate (cAMP) is generated in response to the activation of some G protein-coupled receptors, and cAMP microdomains are thought to be generated by the rate and location of cAMP degradation by phosphodiesterases (PDEs). The cAMP signals generated by activated β2-adrenergic receptors are quenched when the cytosolic molecule β-arrestin associates with and desensitizes the receptors from further agonist stimulation. Perry et al. (p. 834) now report that β-arrestins not only blunt the rate of cAMP generation but also promote cAMP degradation by recruiting PDEs to activated receptors at the plasma membrane. This coordinated activity may allow β-arrestins to restrict the extent of cAMP-dependent activities at the cell surface.

  16. Winding a Two-Hour Clock

    The reiterated structures of the vertebrate axial skeleton and muscles are derived from the metameric structure of somites. It has been shown that messenger RNAs (mRNAs) of Notch signaling molecules such as Hes1 oscillate in 2-hour cycles during somite segmentation. However, the molecular mechanism of such oscillation remains unknown. Hirata et al. (p. 840) now describe the oscillation of Hes1 mRNA and protein in cultured cells after serum treatment. This oscillation requires Hes1 protein synthesis and degradation and relies on the negative autoregulation of Hes1 mRNA synthesis by Hes1 protein. Hence, this work indicates that Hes1 represents a 2-hour cycle clock gene. Furthermore, because Hes1 oscillation occurs in many cell types, this clock may apply to several biological processes as well as to somite segmentation.

  17. Making Space for Cancer Therapy

    Antitumor immunity can be elicited either by stimulating T lymphocytes in vivo by “vaccination” with tumor antigens, or by transferring tumor-specific T cells to patients. Limitations in generating favorable antitumor responses have been encountered in both settings, either because of a failure to overcome prevailing immune tolerance to the tumor antigens, or because of poor engraftment of adoptively transferred lymphocytes. Dudley et al. (p. 850; see the 20 September news story by Couzin) have now combined nonmyeloablative conditioning with the transfer of expanded autologous tumor-reactive T cells, to treat patients with metastatic melanoma that had proven otherwise poorly responsive to conventional treatment regimes. Several recipients displayed clinical signs of antitumor response and two showed highly significant cancer regression, which correlated with the persistence of lymphocytes with strong tumor reactivity. Although some caution must be exercised in the use of autologous tumor-reactive T cells because of the possibility of associated autoimmune pathologies, these results represent an encouraging development in the use of immunotherapy as a treatment for certain types of cancer.