Editors' Choice

Science  25 Apr 2003:
Vol. 300, Issue 5619, pp. 551

    Pièces de Résistance

    1. Paula A. Kiberstis

    Because many chemotherapeutic drugs kill tumor cells by inducing apoptosis (programmed cell death), cellular resistance to apoptosis is thought to be a major factor limiting drug efficacy. Elucidation of the molecular factors that determine whether a tumor will be sensitive or resistant to chemotherapy-induced apoptosis may ultimately enable oncologists to optimize therapies for individual cancer patients.

    Complementary laboratory and clinical studies by Bergamaschi et al. and Irwin et al. highlight the interactive role of the tumor suppressor protein p53 and its paralog p73 in the apoptotic response to chemotherapy. Their results reveal that specific mutations in p53, when present in combination with a common allelic variant at codon 72 of p53, can confer resistance to drug-induced apoptosis via inhibition of p73 function. Along with the implications for prediction of chemotherapeutic response, these findings raise the possibility that therapeutic modulation of p73 levels may offset the development of drug resistance in certain human cancers.—PAK

    Cancer Cell 3, 387; 403 (2003).


    Staying Single and Coupled

    1. Ian S. Osborne

    In cavity quantum electrodynamics (QED) the ideal experimental system is a single atom trapped in a cavity and coupled strongly to a single photon. Although much progress has been reported in attaining this goal, the length of time the atoms remain trapped in the cavity has generally been only several hundreds of microseconds. For the study of light-matter interactions or for potential applications in quantum computation and communication, this may be too brief a period. McKeever et al. describe work in which the residence time can be extended. Using a far-off resonance dipole trap, they are able to hold a single cesium atom for 2 to 3 s within the cavity while preserving the strong coupling to a single photon. Their setup allows them to monitor the number of atoms in the cavity and to visualize them dropping out of the cavity region one at a time.—ISO

    Phys. Rev. Lett. 90, 133602 (2003).


    Recognizing a "True" Tit

    1. Sherman J. Suter

    Even novice birdwatchers have little trouble distinguishing between members of the families Corvidae (jays and crows) and Paridae (tits and chickadees). The former are medium to large in size, have strong feet and stout bills, and have predominantly black or blue plumages. The latter are small, have short, conical bills, and usually have black or brown caps and throats or short crests. Although clearly not typical, Hume's ground jay (Pseudopodoces humilis), a drab bird of the rocky steppes of the Tibetan Plateau, has long been recognized as the smallest corvid.

    Two previous anatomical studies have questioned this classification, and James et al. present phylogenetic analyses of comparative osteology, the nuclear c-myc gene, and the mitochondrial cytochrome b gene. Together, these data identify Pseudopodoces as a parid. Its taxonomic position has been obscured by adaptations to a treeless habitat (including pale, cryptic plumage, a long, decurved beak for probing in the ground, and long legs for hopping locomotion). This result confirms the continuing need for careful phylogenetic work even in such intensely studied taxa as birds.—ShJS

    Ibis 145, 185 (2003).


    Snip Snip

    1. Stella M. Hurtley

    A key enzyme involved in Alzheimer's disease is known as γ-secretase. This protein complex acts as an aspartyl protease and cleaves the β-amyloid precursor protein (APP) to release amyloid β-peptide (Aβ). Several distinct membrane proteins have been identified as contributing to γ-secretase activity. Edbauer et al. have defined the minimal set of molecular components sufficient for γ-secretase activity by reconstituting this activity in yeast, chosen because it lacks any sign of γ-secretase activity and does not encode homologs of the putative γ-secretase component proteins. Human presenilin, nicastrin, APH-1, and PEN-2 together produced a holoenzyme that could faithfully reproduce β-amyloid precursor cleavage in intact yeast cells and, after detergent extraction and immunoprecipitation, in vitro.—SMH

    Nature Cell Biol. 10.1038/ncb960 (2003).


    Raindrops and Roses

    1. Phil D. Szuromi

    It might seem that every small object imaginable has been levitated in a laser trap, and liquid droplets are one of the favorite things that have been used. Since 1975, when Ashkin and Dziedzic trapped a glycerol droplet, a variety of viscous liquid droplets have been captured, although with fairly low efficiencies (below 10%). Water droplets, however, have been difficult to control in this fashion, yet this capability would be extremely valuable for the study of the formation of water droplets and reactions within them. Magome et al. decided not to try to extract a water droplet from the liquid phase, but to grow one in the gas phase instead. They placed an ammonium chloride nucleation center in an infrared laser beam, and water droplets grew from supersaturated vapor to a diameter of 11 m before falling out of the trap; with a 5-mW laser, the efficiency was 46%.—PDS

    J. Phys. Chem. B 10.1021/jp034336h (2003).


    An Old Salt's Tale

    1. Stewart Wills

    About 6 million years ago, the Mediterranean Sea began to dry up—an event marked in the rock record by substantial evaporite deposits, some sitting directly atop deep-water sediments such as black shales. This “Messinian salinity crisis,” during which the Mediterranean became an evaporitic lake for a million years, apparently stemmed from closure of the narrow Atlantic-Mediterranean seaway. This closure is usually attributed to climate-driven sea level fall at the end of the Miocene, though recent studies have emphasized a possible role for tectonics as well.

    Roveri et al. limn that tectonic role for the Mio-Pliocene Vena del Gesso basin, the record of which is exposed in rocks in the Italian Apennines. Integrating field and subsurface data, they show that evaporite precipitation there was tightly controlled by pre-Messinian and Messinian tectonic events that isolated the basin. They also establish that some shallow-water Messinian evaporites may have been transported by gravity sliding into adjacent areas and onto deeper-water deposits, near the close of the salinity crisis. The supposedly abrupt transition from deep-water shales to shallow-water evaporites that marked the beginning of the Messinian event may thus be partly a tectonic artifact, and the sea level drop that precipitated the salinity crisis may have been far smaller than generally thought.—SW

    Geol. Soc. Am. Bull. 115, 387 (2003).


    Seeing Red

    1. Phil D. Szuromi

    Aggregation immunoassays can be used to detect molecules that present more than one antibody-binding site. In the presence of the target molecule, latex particles bearing anti-target immunoglobin G's (IgGs) will form aggregates that can be detected as changes in solution turbidity. However, such assays are not so useful for direct detection of molecules in blood, given its absorption in the visible regime. Hirsch et al. present a different approach for measuring aggregation: The latex particles are replaced by core-shell metal nanoparticles that can be detected in the near-infrared through their characteristic plasmon resonance. Aggregation diminishes the strength of the plasmon peak. They can quantitate rabbit IgG at the nanogram-per-milliliter level in whole blood in about 10 min.—PDS

    Anal. Chem. 10.1021/ac0262210 (2003).


    Of T Cells and Tolls

    1. Stephen J. Simpson

    Leprosy occurs as distinct clinical phenotypes, with more resistant patients presenting localized skin lesions and susceptible individuals afflicted with a systemically disseminated form of the disease. Clear differences in the magnitude and type of immune response correlate with these two forms, suggesting a direct immunological influence on how the disease advances.

    Krutzik et al. show that Toll-like receptors (TLRs) of the innate immune system are differentially activated in response to the leprosy bacillus, Mycobacterium leprae. Cellular activation by killed M. leprae required TLR2 but could be intensified by coexpression of TLR1, suggesting dual contributions from TLR2 homodimers and TLR1-TLR2 heterodimers. Two potential lipoprotein ligands for these TLRs, identified from a genome-wide scan of M. leprae, also elicited a response. Activation by a synthetic form of one of these ligands and TLR1-TLR2 expression were both enhanced by T helper cell type 1 (TH1)-associated cytokine, but diminished by TH2 cytokines. Increased TLR expression in leprosy skin lesions from resistant patients, who are known to express elevated levels of TH1 cytokines, was also apparent. Thus, the modulation of TLR expression and activation by cytokines may determine immunological status and clinical outcome in this disease.—SJS

    Nature Med. 10.1038/nm864 (2003).