Editors' Choice

Science  06 Jan 2006:
Vol. 311, Issue 5757, pp. 16

    A Little Light Work

    1. Stella M. Hurtley

    The interactions of proteins with other proteins (or ligands) and the regulation of protein activity by conformational changes are fundamental aspects of how a wide range of enzymes, signaling proteins, and ion channels function. Volgraf et al. describe the design of a channel that can be turned on (at 380 nm) and off (at 500 nm) by light. Using structure-based design, the authors covalently linked to the ligand-binding domain of the ionotropic glutamate receptor a light-sensitive azobenzene derivative with an appended agonist. Photoisomerization (from trans to cis) brings the agonist within striking distance of the ligand-binding site and triggers a conformational change that closes the channel within milliseconds. This approach can be used in future designs of light-operated switches incorporated into a variety of proteins either in electrophysiological settings or in nanodevices. — SMH

    Nat. Chem. Biol. 10.1038/nchembio756 (2005).


    Stronger Nanocomposites

    1. Marc S. Lavine

    The use of hydroxyapatite (HAP) in load-bearing orthopedic implants has been limited by its sintering behavior and mechanical properties. Reinforcing agents have been added to make composites, but only HAP-polymer blends have achieved clinical application. For metal and ceramic reinforcing agents, high particle loadings are required, but this reduces the bioactivity. Furthermore, at high loadings of metallic particles, thermal mismatch is an issue, whereas for ceramics, high loading requires high sintering temperatures that degrade HAP.

    Using a previously developed nanocrystalline HAP, Ahn et al. employed a colloidal technique to add small amounts of zirconia to HAP. Optimal Vickers hardness was obtained for loadings as small as 1.5 weight %, which increased the bending strength by about 30%. Adding the Zr during the precipitation of the HAP achieved an intimate mixing, and the Zr acted as seed nuclei for HAP crystallization. A further benefit was that the composites could be fully sintered under relatively mild conditions, preserving the nanocrystalline grain size of the HAP particles, which have higher bioactivity than coarser-grained ones. — MSL

    J. Am. Ceram. Soc. 88, 3374 (2005).


    Attracting a Blood Supply

    1. Beverly A. Purnell

    Tissue growth and repair require the generation of new blood vessels through the process of angiogenesis. Because cell death and angiogenesis have been shown to be related, Weihua et al. examined whether apoptotic cells are involved in initiating the angiogenic response. When apoptotic tumor cells were cultured with endothelial cells, the nonproliferating endothelial cells began sprouting toward the apoptotic cells. As cells go through apoptosis, they display an increase in fixed negative charge on the cell surface, and endothelial cell sprouting was stimulated by this electrostatic interaction. — BAP

    Cancer Res. 65, 11529 (2005).


    Fertilizing Forests with CO2

    1. H. Jesse Smith

    One of the biggest obstacles to predicting how much climate will be affected by increasing concentrations of atmospheric CO2 is not knowing how much additional carbon uptake from the terrestrial biosphere, stimulated by higher CO2 concentrations, might occur. This sequestration could slow the rate of warming by a significant amount, at least in the short term, so it is important to understand how forests in particular will react to the CO2 “fertilizer” added by fossil fuel burning.

    Norby et al. report results from an experiment in which forest stands were exposed to an artificially enhanced level of CO2 and their net primary productivity (NPP)—the net fixation of C by green plants into organic matter—was determined. NPP increased by an average of 23% over a broad range of productivity when CO2 was enriched to a level of 550 parts per million (ppm), approximately 170 ppm above today's value and around what it is expected to be by the end of the 21st century. This study thereby provides a foundation on which questions about more specific and subtle responses of ecosystems to CO2 fertilization, such as how this additional C is allocated and retained in plants and how the availability of other growth-limiting resources might affect NPP, can be addressed. — HJS

    Proc. Natl. Acad. Sci. U.S.A. 102, 18052 (2005).


    Unexpected Pairing

    1. Jake S. Yeston

    It is well known that when chiral compounds crystallize, they often associate preferentially as like enantiomers or as racemic pairs. This property underlies Pasteur's pioneering elucidation of molecular chirality in tartaric acid, and it has since become a useful purification technique for extracting a homochiral sample from a mixture that is enriched in one enantiomer. However, the phenomenon is commonly attributed to the packing forces pertaining in tightly confined crystals; an analogous effect that would lead to loose aggregation in solution has been less well-studied.

    Soloshonok has found that a trifluoromethyl group at a chiral center can have a surprisingly strong effect in inducing such aggregation during chromatography. Samples of a chiral CF3-substituted benzamide derivative were eluted on ordinary, achiral silica gel, and initial enrichment of 67% in one enantiomer induced fractionation into a mostly racemic portion and a portion >99.9% enriched in the major isomer. Systematic variation of the compound's substituents implicated the CF3 group as the critical factor, and further studies confirmed a similar effect in chromatography of several CF3-substituted alcohols. — JSY

    Angew. Chem. Int. Ed. 10.1002/anie.200503373 (2005).


    FinGering the Merchandise

    1. Gilbert J. Chin

    Remarkable advances in the application of physical methods to biological systems have yielded a bumper crop of achievements taken to the nth degree, such as atomic-resolution models of enormously complicated macromolecular assemblies and real-time tracking of single molecules within live cells. It is, however, not yet feasible to do both at once, which would allow for the spatiotemporal visualization of protein-protein interactions at the scale of individual amino acid residues, and current approaches have relied on bioinformatics and laborious experimental trials.

    Molecular dynamics simulations provide a way to look at these events, and Isgro and Schulten confirm previous results and uncover new ones in their analysis of the nuclear transport factor β-importin and phenylalanineglycine (FG) repeat-containing peptides; the latter are stand-ins for the nucleoporins, components of the nuclear pore complex that mediates the passage of large molecules (10 to 40 nm in diameter) across the nuclear membrane. FG binding sites on transport factors have been identified in structural and biochemical studies, and proposals for how the nucleoporins gate entry into the nucleus are based on multiple semi-strong sites (1 to 100 nM affinity) that turn the pore into an examination room where import cargoes can be palpated and then accepted or rejected. — GJC

    Structure 13, 1869 (2005).

  7. STKE

    This Week: Getting Lean with Leptin

    1. Nancy R. Gough

    Treatment of lean rats with the hormone leptin depleted fat from adipocytes, which of course has raised considerable interest in the possibility of using leptin as a treatment for obesity. However, failure of the hormone to reverse obesity has shown that metabolic regulation needs to be understood better in order to take advantage of its potential therapeutic benefits. Wang et al. therefore designed experiments to uncover how white adipocytes are able to store triglycerides at the same time as they secrete leptin at concentrations that, when experimentally administered to lean rats, would block adipogenesis. They identified two mechanisms by which adipocytes from rats fed a 60% fat diet become resistant to leptin. Within 6 days after exposure to the high-fat diet, there was a large increase in the expression of mRNA encoding SOCS3 (suppressor of cytokine signaling 3), an inhibitor of leptin signaling through its receptor (Lepr-b); after several weeks, the level of mRNA encoding Lepr-b decreased. The authors conclude that a high-fat diet causes resistance to leptin signaling in adipocytes and that the hypertrophy and hyperplasia that cause obesity can only occur if such mechanisms allow the adipocytes to ignore the extracellular leptin concentrations to which they are exposed. They further speculate that a period of starvation of patients might reduce such a blockade and allow a beneficial response to leptin therapy in obese patients. — NRG

    Proc. Natl. Acad. Sci. U.S.A. 102, 18011 (2005).