Editors' Choice

Science  16 Apr 2010:
Vol. 328, Issue 5976, pp. 286
  1. Biotechnology

    Homeostatic Engineering

    1. Gilbert Chin
    CREDIT: TITIAAN/LAMBERT SUSTRIS, 1548

    Not so many years ago, adding a heterologous set of enzymes in order to augment the biosynthetic capacity of a microbe was acknowledged as a remarkable feat of rational design. Apart from the important technical concerns of efficiency and stability, attention then turned to the greater challenge of repairing metabolic dysfunction; the goal here was not only to restore the biochemical reactions but also to place them under endogenous regulation. Kemmer et al. demonstrate how this might be achieved in mice suffering from excess uric acid, which in humans can lead to the condition commonly known as gout. Uric acid is the product of purine catabolism, and in mice, urate oxidase converts it to allantoin, which is excreted. Excess uric acid can precipitate as the sodium salt, and humans, who lack urate oxidase, cannot tolerate too much of it. Conversely, uric acid can scavenge free radicals, and a moderate amount is deemed to be beneficial. Stitching together a mini-circuit comprising a Deinococcus transcriptional repressor and promoter as well as Aspergillus urate oxidase enabled these authors to maintain serum uric acid concentration in urate oxidase–deficient mice at normal physiologic levels.

    Nat. Biotechnol. 28, 10.1038/nbt.1617 (2010).

  2. Evolution

    Sowing the Seeds of Spherulites

    1. Nicholas S. Wigginton

    The evolution of hard calcified structures such as shells and skeletons gave their bearers a selection advantage over older soft-bodied organisms. Most organisms equipped with such hard structures synthesize enzymes or other biomolecules to serve as sites for controlled crystal growth. The modern sponge Astrosclera willeyana—a living fossil related to some of the most primitive sponges—may form its simple calcite spheres via another mechanism. Within the organic matrix of these spherulites, Jackson et al. found biomarkers exclusive to the biomolecules of bacteria. This finding suggests that A. willeyana degrades the bacteria that enter its much larger cells and then uses the degradation products, rather than its own biomolecules, to nucleate calcite crystals. Bacteria on their own can form large calcified structures such as stromatolites, and did so billions of years ago; however, if sponge-like organisms ∼300 million years ago did not have the full suite of genetic machinery to direct biocalcification themselves, the harvesting of bacteria to jump-start the process would have served as an efficient evolutionary shortcut. The appearance of more sophisticated mineralization pathways, which allowed species related to modern corals to outcompete the ancient sponges that previously dominated ocean reefs, may have occurred much later.

    Geobiology 8, 10.1111/j.1472-4669.2010.00236.x (2010).

  3. Molecular Biology

    Read-Only Access

    1. Guy Riddihough

    To squeeze eukaryotic genomes into the cramped confines of the cell nucleus, DNA is packaged into nucleosomes, which are composed of octamers of histone proteins: two dimers of histones H3 and H4 and two dimers of H2A and H2B. Accessing the information stored in the genome requires that the nucleosomes be removed or shuffled out of the way and then later replaced. Assembly occurs via the interaction of dimers of H3-H4 with DNA to form a (H3-H4)2–DNA complex (the tetrasome), and then by the addition of two H2A-H2B dimers. Andrews et al. have studied the mechanism by which nucleosome assembly protein 1 (Nap1) acts to promote assembly and find that Nap1 does not affect tetrasome formation but instead binds to the H2A-H2B dimer and reduces its affinity for DNA. This is critical because histones are basic proteins and have a strong propensity for nonproductively interacting with DNA. Deletion of Nap1 in yeast results in increased levels of H2A and H2B in chromatin, without a corresponding increase in H3, supporting the idea that Nap1 protects against H2A-H2B dimers binding to DNA disobediently. The derangement of normal chromatin structure in the absence of Nap1 results in the misregulation of transcription, indicating that Nap1 chaperone activity is critical for the correct readout of information.

    Mol. Cell 37, 834 (2010).

  4. Molecular Biology

    Remote Enhancement

    1. Helen Pickersgill

    Rescuing spa function by moving it closer.

    CREDIT: SWANSON ET AL., DEV. CELL 18, 359 (2010)

    The temporal and cell type–specific regulation of gene expression relies in part on enhancers, which are noncoding regions of the genome that control tissue-specific expression of a gene sometimes located hundreds of kilobases away. Enhancers recruit regulatory proteins to decondense chromatin and promote the assembly of transcription machinery at genes. Swanson et al. have dissected the 350-bp sparkling (spa) enhancer that controls expression of the dPax2 gene, which specifies cone cell fate in the developing Drosophila eye. The spa enhancer has been shown to consist of 12 binding sites that recruit four regulatory proteins, the combination of which was thought to be sufficient to activate gene expression. By analyzing mutated versions of a synthetic spa enhancer in vivo, the authors have identified additional regulatory regions that are required for gene expression. One of these regions was required only when the enhancer was located 846 bp upstream of the promoter, but not at 121 bp, which suggests that other enhancers may contain similar hidden remote-control regions that work at a distance. Rearranging the regulatory elements in spa switched its cell-type specificity. Thus, both distance and the order of regulatory regions enable enhancers to fine-tune gene expression, revealing more levels of complexity than previously appreciated.

    Dev. Cell 18, 359 (2010).

  5. Chemistry

    A Precatalytic Cycle

    1. Phil Szuromi

    When metal particles are deposited or formed on oxides for catalytic applications, the goal is to create small clusters that expose as many surface atoms as possible. One method of limiting surface adsorption is atomic layer deposition, which restricts deposition by requiring the system to undergo cycles of stoichiometric reactions. For the formation of palladium (Pd) particles on silica gel supports, Lu and Stair report a cycle of three reactions that occur at low temperatures (below 110°C) and yield highly uniform particles with an average size of 1 nm. Pd is deposited on a limited number of surface sites as an ion complex, coordinated by hexafluoroacetylacetonate ligands. A second step deposits an alumina or titania precursor, and a third step adsorbs water in order to form the oxides. This cycle is repeated over as many as 15 cycles, and then the protective Pd ligands are removed by reaction with formalin at 200°C. CO chemisorption studies showed that successive cycles do not interfere with the accessibility of the Pd clusters to reactants.

    Angew. Chem. Int. Ed. 49, 2547 (2010).

  6. Cell Biology

    Natural Skin Care

    1. Stella M. Hurtley

    The skin acts as one of our primary defenses, protecting our organs and tissues from a dry and often hostile environment. During development, fibroblast growth factors (FGFs) and their receptors (FGFRs) help to produce and maintain a robust epidermis. Yang et al. generated mutant mice that lacked FGFR1, FGFR2, or both. Mice lacking keratinocyte FGFR1 appeared normal throughout development; those lacking keratinocyte FGFR2, however, had a reduced number of hairs and no sebaceous glands. Mice lacking both receptors displayed a more severe phenotype: As they aged, hair was lost, and the outer layer of the skin—the dermis—underwent fibrosis as a consequence of an increased inflammatory response. The tight junctions that hold skin cells together were also down-regulated in the mutant mice, which correlated with an impairment of epidermal barrier function.

    J. Cell Biol. 188, 935 (2010).

  7. Climate Science

    A Long Slow March

    1. H. Jesse Smith

    Among the most important responses to rising temperatures is accelerating rates of melting of the world's ice sheets and glaciers. Nowhere has that melting been more evident than in southern Greenland, where for the past decade or more, ice mass loss has occurred at an increasing rate. Now the mass loss so apparent in the south is spreading up the northwest coast, as would be expected. Khan et al. use two independent techniques—gravity measurements from the GRACE satellites and GPS measurements of bedrock elevations adjacent to the ice sheet—to construct a self-consistent record which shows that ice mass loss in northwest Greenland probably began to pick up speed in 2005. Detailed pictures of the evolution of ice sheets should lead to better predictions of other phenomena such as sea-level rise.

    Geophys. Res. Lett. 37, L06501 (2010).