Editors' Choice

Science  13 Jan 2006:
Vol. 311, Issue 5758, pp. 147

    Lifting a Switch

    1. Gilbert J. Chin

    Two-component systems enable microbes to respond to environmental conditions. Signal transduction begins when a dimeric integral membrane protein senses an external signal, and one of the monomers phosphorylates the other on a histidine residue. Thisphosphoryl group is then transferred to the cytosolic response regulator protein, which initiates changes in gene expression. Salmonella typhimurium PhoPQ promotes virulence of this pathogen in humans, and the activity of the sensor component PhoQ can be repressed by divalent cations, such as calcium and magnesium.

    Cho et al. describe the structure of the external domain of PhoQ, with four monomers in the asymmetric unit of the crystal. They find that two of the monomers associate in a fashion similar to what would be expected for the in vivo PhoQ dimer and that together they display a planar surface rich in acidic residues. Biochemical and structural experiments pinpoint at least three calcium-binding sites per monomer on this surface, which would allow the dimer to lie flat on top of the negatively charged head groups of the lipid bilayer. This positioning leads the authors to propose that displacement of the divalent ions (for instance, by cationic antibiotic peptides) would trigger a lever-like movement of the sensor domain up off of the membrane surface, thereby turning on the kinase. — GJC

    J. Mol. Biol. 10.1016/j.jmb.2005.12.032 (2005).


    Stress and Immunity

    1. Stephen J. Simpson

    Our psychological states influence our physical health, not least through their effects on the immune system. Nevertheless, how the nervous and immune systems interact in the context of stress or depression remains an open question. Wheway et al. have investigated the role of neuropeptide Y (NPY), a regulator produced by sympathetic nerves that innervate secondary lymphoid organs. T cells lacking the NPY receptor Y1 responded considerably more vigorously to activation in culture than did Y1-positive T cells. This hyperreactivity was evidenced as an increase in the severity of pathology caused by activating these cells in a mouse model of colitis. In contrast, Y1-deficient mice were themselves relatively resistant to inflammation induced by activated T helper-1 cells, reflecting an apparent defect in dendritic cell (DC) function. One explanation for these seemingly divergent results is that NPY mediates distinct effects on different cells of the immune system. Thus, although T cells can be impeded directly through Y1 receptor signaling, they can also be stimulated indirectly through NPY-assisted activation of the antigen (Ag)-presenting cell function. The mechanistic basis of this dichotomy may further understanding of the neuroimmune interface and yield therapeutic benefits. — SJS

    J. Exp. Med. 202, 1527 (2005).


    Pulling into a Rest Stop

    1. Gilbert J. Chin

    The recent explosion of research on the interaction of small RNAs with messenger RNAs (mRNAs), which can lead either to cleavage of the double-stranded RNA complex or to translational repression, has intersected with studies of the life cycles of mRNAs, which in some cases spend part of their time in cytoplasmic processing bodies in a translationally dormant state, before degradation or reactivation. Beliakova-Bethell et al. have observed that the protein and RNA components of the yeast retrovirus-like element Ty3 congregate in cytoplasmic foci that also contain nascent virus-like particles. These sites turn out to be a way station for other proteins already shown to reside in processing bodies, among them Dhh1, a helicase that is involved in translational represssion and is required for Ty3 retrotransposition. Hence it appears that the demands of assembling proteins onto an RNA genome may be facilitated by the translational stasis imposed within processing bodies. — GJC

    RNA 12, 94 (2006).


    Powered by Hydrogen

    1. Brooks Hanson

    The evidence for earliest life on Earth comes not from fossils but from shifts in the carbon isotopes of preserved and altered carbonate minerals or rocks. In younger rocks, possible isolated bacterial fossils have been described. The metabolism of these early fossils has been uncertain, and some have suggested that they resemble cyanobacteria, implying at least some oxygenic photosynthesis and a rapid and early evolution of this biochemical pathway. One of the earliest indicators of more widespread life is in 3.4-billion-year-old rocks in Australia that contain abundant layered carbonaceous matter interpreted to be fossil microbial photsynthetic mats.

    Tice and Lowe have examined the geochemistry of these early mats in order to decipher their origin and likely metabolism. The reduced oxidation state of iron and trace elements, notably cerium, indicates that the water column was highly anoxic. Tice and Lowe argue that uranium mobility was controlled by carbonate, not by oxygen as has been proposed. Together these data imply that the mats represent anoxygenic photosynthesis and a metabolism based on hydrogen gas as the source of electrons. — BH

    Geology 34, 37 (2006).


    Beading a Band

    1. Marc S. Lavine

    Plastic deformation in semicrystalline or amorphous materials is often restricted to very thin shear bands. For metallic glasses, these bands are particularly important because the associated work-softening leads to a plastic instability in tension that limits the potential of these materials as structural materials. Despite the appearance of liquid-like features at fracture surfaces, there is some controversy over the local temperature rise at the bands.

    Lewandowski and Greer use a fusible coating and find that the local temperature can reach as high as a few thousand Kelvin over a few nanoseconds. Specimens were coated with a thin film of tin, which formed hemispherical beads when heated. By measuring the half-width of the beads or their volumes, the authors were able to calculate the enthalpy required to form the beads, and thus the local temperature flux during specimen deformation. The same calculations, however, predict that the shear bands should be much larger than the 10 to 20 nm typically observed. Thus, the authors conclude that although local heating is important in understanding the changes that take place at the bands, the thickness of the bands is controlled by local structural changes, such as the formation of nanocrystals and voids. — MSL

    Nat. Mater. 5, 15 (2006).


    Coated Catalysts

    1. Phil D. Szuromi

    One cause of deactivation in heterogeneous catalysts is that the metallic nanoparticles can aggregate over time, leading not only to a loss of active surface but also to less favorable electronic or support interactions that depend on particle size. Jiang and Gao have explored the use of hyperbranched polymers for encapsulating palladium nanoparticles in the context of supported catalysts, in this case by functionalizing the channels in mesoporous silica SBA-15 with polyamidoamine dendrimers. The selectivity of hydrogen-ation of allyl alcohol to 1-propanol increased for generations three and four of the dendrimer versus generations one and two, and the formation of acetone was about a factor of 4 lower for the generation-three catalyst versus Pd supported on alumina. The catalysts retained their activity after several rounds of reuse or after storage for 1 month under ambient conditions. — PDS

    J. Am. Chem. Soc. 10.1021/ja056424g (2005).

  7. STKE

    Not Recognizing Ourselves

    1. Elizabeth M. Adler

    Toll-like receptors (TLRs) recognize conserved motifs in microbial molecules, enabling them to initiate immune responses against pathogens. Whereas most TLRs are found on the cell surface, those that recognize bacterial and viral nucleic acids are inside. Barton et al. investigated the functional importance of the endosomal localization of TLR9, a TLR that is activated by DNA containing unmethylated CpG motifs, which occur frequently in bacterial and viral DNA. Immunofluorescence analysis of chimeric receptors containing the transmembrane or cytosolic domains of TLR9 or TLR4 (which is found on the plasma membrane) revealed that localization depended on the transmembrane domain. TLR9N4C, a chimeric receptor made of the TLR9 ectodomain and the TLR4 cytosolic and transmembrane domains, localized to the cell surface. Dendritic cells expressing TLR9N4C responded to CpG DNA as effectively as cells expressing TLR9 did. However, dendritic cells expressing TLR9N4C, unlike those expressing TLR9, failed to respond to herpes simplex virus; moreover, macrophages expressing TLR9N4C, but not macrophages expressing TLR9, were stimulated by exposure to extracellular mammalian DNA. Thus, the authors propose that the intracellular localization of TLR9 may be critical to prevent it seeing self DNA. — EMA

    Nat. Immunol. 7, 49 (2006).

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