This Week in Science

Science  19 Aug 2005:
Vol. 309, Issue 5738, pp. 1149
  1. Resolving Resolvase Structure and Function

    CREDIT: LI ET AL.

    The site-specific serine recombinase, resolvase, catalyzes recombination between two sites on negatively supercoiled DNA. This process requires double-strand cleavage at each site, strand exchange between the two sites, and religation. Li et al. (p. 1210, published online 30 June 2005) provide insight into how this occurs by reporting a 3.4 angstrom resolution crystal structure of a synaptic intermediate of resolvase linked to two cleaved duplex DNAs. The DNA duplexes lie on opposite sides of a tetramer of resolvase. The tetramer structure differs from a presynaptic complex between dimeric resolvase and DNA and places the catalytic serine close to the scissile phosphate. The structure supports a subunit rotation hypothesis that posits a 180° rotation of two resolvase subunits to accomplish strand exchange. A flat interface in the tetramer makes such a rotation feasible.

  2. Polymer Production

    Organic chemists have developed a wide range of techniques for linking and functionalizing small molecules that polymer chemists have exploited for creating larger molecules with controlled architectures and chain lengths. A rich toolbox is now available for making macromolecules that could not be made using standard polymerization techniques. Hawker and Wooley (p. 1200) review a number of key advances, and show how these new polymeric systems are showing promise for applications including encapsulation, drug delivery, and thin-film patterning, as well as for the study of fundamental polymer properties.

  3. Tracking a Proton Propeller

    Discovery of superacids revealed that, with a weak enough counterion, even a molecule as inert as methane could bind an extra proton. The product when methane is acidified, the CH5+ ion, has long puzzled theorists and spectroscopists alike. The hydrogen atoms seem to change places with one another too rapidly to assign the geometry and bonding mode reliably. Asvany et al. (p. 1219, published online 30 June 2005) have now measured the vibrational spectrum of CH5+ by detecting its infrared-induced reaction with CO2. Comparison with simulations supports a structure in which a CH3 tripod binds an H2 fragment through a three-centered, two-electron bond, with a barrier for exchange between these different sites of 0.3 kilocalorie per mole.

  4. Melting and Freezing

    Melting and crystallization are often easier to study in colloids, where the particles are readily visualized (see the Perspective by Pusey). Premelting can occur at the crystal surfaces below the bulk melting temperature, but this phenomenon has not been observed in the bulk itself. Alsayed et al. (p. 1207, published online 30 June 2005) studied the melting of colloidal crystals composed of microgel particles that undergo large volume changes with small changes in temperature. Premelting can occur in the bulk at grain boundaries and dislocations and depends on the interfacial free energy associated with each type of defect. The addition of impurities to a melt can stop, slow down, or accelerate the crystallization of the bulk material. The interactions between impurity and bulk are complex, because one needs to consider differences in shape and size, as well as the nature of the chemical interactions between the two materials. De Villeneuve et al. (p. 1231) examine the role of curvature in which the impurities were large colloidal particles embedded in a sea of smaller ones. The presence of impurities did not necessarily slow down crystallization, but the relative curvature did play a role in pinning grain boundaries that formed. Each impurity was surrounded by a mobile layer of small particles.

  5. Snapshots in Solution

    X-ray diffraction has long permitted chemists to map out the molecular structure of solids. Recently, short and intense x-ray pulses from synchrotrons have produced time-resolved pictures of structural rearrangements, but the samples, such as proteins, first had to be immobilized. Ihee et al. (p. 1223, published online 14 July 2005; see the Perspective by Anfinrud and Schotte) used intense 100-picosecond x-ray pulses to probe a reaction in solution. The sensitivity of x-rays for heavy atoms allowed them to follow an iodine atom in the photoinduced decomposition of diiodoethane to I2 and C2H4. Over a large solvent background, the data offer direct structural evidence for a long-hypothesized I-bridged C2H4I intermediate.

  6. Grainy Signatures

    Grains from other stars were incorporated into our solar nebula when it formed. Brandon et al. (p. 1233) obtained osmium isotope data from such grains in primitive meteorites which indicate that elements as rhenium and osmium were derived from small stars with a higher neutron density than that which formed our solar system. Furthermore, the data require that these and other grains produced in our solar system were extremely well mixed in our solar nebula when solids started forming.

  7. Strong Thin Sheets

    CREDIT: ZHANG ET AL.

    Exploiting the strength of carbon nanotubes in most applications will require their assembly into macroscopic films and fibers. Zhang et al. (p. 1215) show that by attaching a sticky sheet of paper to a forest of vertically oriented nanotubes, they can draw them into sheets that are centimeters wide and meters in length. The sheets initially take the form of a highly anisotropic electrically conducting aerogel, and can be compressed into dense, strong sheets that are only tens of nanometers thick.

  8. Why Large Size Increases Extinction Risk

    A statistical analysis of extinction risk patterns for about 4000 mammal species by Cardillo et al. (p. 1239, published online 21 July 2005; see the 22 July news story by Stokstad) has provided an explanation for why species of large body size suffer the highest risk of extinction. Sensitivity to a variety of risk-promoting factors, such as low reproductive rate and low population density, increases sharply above a threshold of around 3 kilograms. For species below this threshold, extinction risk reflects simply where species live; above it, extinction risk also reflects biological traits, so that larger species are more likely to be predisposed to decline. The disproportionate disadvantages of large size might accelerate the loss of large-mammal biodiversity in the face of environmental threats.

  9. Controlled Mobilization

    CREDIT: FLORES ET AL.

    Tissue stem cells have the capacity to self-renew and generate differentiated cells that replace lost cells as an organism ages. Quiescent stem cells typically reside in specific microenvironments or “niches.” When needed, they begin proliferating and exit the niche, a process thought to be controlled by extracellular cues from the niche and by intrinsic genetic programs. Studying mouse models, Flores et al. (p. 1253, published online 21 July 2005) now show that epidermal stem cell mobilization is regulated by telomeres, the nucleoprotein structures at the ends of chromosomes. Short telomeres impaired mobilization, whereas overexpression of telomerase, the enzyme that synthesizes telomeres, promoted mobilization. The effect of telomeres on stem cell function could potentially explain, at least in part, their role in aging and cancer.

  10. The Smaller the Better

    Small α-proteobacteria account for about a quarter of all bacteria in the oceans. Giovannoni et al. (p. 1242) reveal that Pelagibacter, the first isolate from this clade, has the smallest genome yet observed in a free-living organism. Unlike many parasites and symbionts, Pelagibacter retains a nearly full suite of biosynthetic genes, but it shows no trace of “junk” DNA. Because of the extremely large population size, it seems that selection can act on the very small fitness costs of replicating functionless DNA. In contrast to Pelagibacter, other heterotrophic marine bacteria for which genome sequences are available have relatively large genomes.

  11. Host Factors Required for Microbial Residence

    The host cells characteristics that allow for microbial invasion and residence are less well defined than the virulence factors that allow microbe entry. Using a genome-wide screening approach, Philips et al. (p. 1251, published online 14 July 2005) identified host factors required for infection by Mycobacterium fortuitum, which divides within vacuoles. Factors fell into two main categories: those that generally affect phagocytosis (the process by which cells engulf extracellular particles) and those that cause a specific defect in mycobacterial uptake or growth. A Drosophila member of the CD36 family of scavenger receptors was specifically required for the uptake of mycobacteria. Using a similar approach, Agaisse et al. (p. 1248, published online 14 July 2005) identified host factors that affect intracellular infection by Listeria monocytogenes, a bacterial pathogen that escapes from phagocytic vacuoles and replicates within the cytosol of host cells. Several phenotypes were observed, including decreases in the percentage of host cells infected, alterations of intracellular growth rates, and changes in subcellular location of bacteria. The identified host factors spanned a wide range of cellular functions. Comparing the two studies revealed host factors that specifically affect access to the cytosol by L. monocytogenes and host pathways that are differentially required for intracellular infection by a cytosolic versus a vacuolar intracellular bacterial pathogen.

  12. Hydrogens Go Their Separate Ways

    Chemical reactions are most easily understood and predicted using the Born-Oppenheimer approximation, which treats the motion of nuclei and electrons independently. However, when electronic ground-state and excited-state surfaces overlap, the separation no longer applies. One consequence, termed the Berry or geometric phase effect, is a phase inversion in the nuclear and electronic wave functions if a molecular trajectory circles the overlap point, or conical intersection. This effect was expected to influence reaction trajectories in the collisional exchange of free and bonded atoms in the H + H2 system, but seemed to be absent when product distributions were averaged over all scattering angles. Juanes-Marcos et al. (p. 1227; see the Perspective by Clary) have used a topological analysis to account for this absence. They show that even though two reaction paths may circle the intersection, they fail to interfere with one another because the respective products are scattered in opposite directions.

  13. The Illusion of Invariance?

    There has been much interest in the search for “life-history invariants,” which are dimensionless ratios of key life-history parameters, such as life span, age at maturity, numbers of offspring produced, or size, which are found to be the same across different species or even across different higher taxa. The apparent existence of these invariants has appeared to suggest a fundamental similarity in the underlying selective forces, and the possibility of a unified life-history theory. Nee et al. (p. 1236; see the Perspective by de Jong) show that this may be a false hope, generated by an illusion of invariants that do not necessarily exist. Specifically, the regression methodology used to test for invariance gives misleading results that will always give the appearance of invariance, regardless of whether it is really there.

  14. Bacterial Contact Dependent Growth Inhibition

    Bacteria multiply by binary fission, but under certain circumstances bacteria within communities respond to their neighbors and change their physiological properties. Aoki et al. (p. 1245) now describe a growth inhibitory system in Escherichia coli that requires direct cell-to-cell contact and that may function to regulate the growth of specific cells within a differentiated bacterial population. Two genes were found to be responsible for contact-dependent growth inhibition, CdiA and CdiB, and the authors also identified a DNA region that provides immunity against growth inhibition. CdiA and CdiB belong to the two-partner secretion family of proteins. Functional homologs are present in uropathogenic E. coli and potential homologs exist in a broad range of bacteria, including many pathogens.

  15. Responding to R-Spondin

    Intestinal epithelial integrity in the gut is maintained through a delicate balance between rapid cellular proliferation, differentiation, and cell death, regulated by the Wnt/β-catenin signaling pathway. Kim et al. (p. 1256) provide evidence that a recently identified human orphan growth factor exerts a strong influence on how the β-catenin pathway regulates epithelial cell proliferation. Using an in vivo screening system, the authors found that R-spondin1 could act as a growth factor to increase crypt epithelial cell proliferation, leading to thickening and elongation of the small and large intestine. Unexpectedly, this effect appeared to operate independently of conventional stabilization of β-catenin by the Wnt protein, suggesting that another pathway may also influence β-catenin-dependent gene regulation. In a gut tumor treatment model, R-spondin1 reduced the strong cytotoxicity associated with a chemotherapeutic agent without impeding tumor growth.

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