This Week in Science

Science  05 Jun 2009:
Vol. 324, Issue 5932, pp. 1239
  1. Signaling Signature in Situ


    Upon activation, signaling proteins trigger response pathways, but knowing when and where they are activated within animals has been difficult. Kamiyama and Chiba (p. 1338) describe an in vivo bioprobe imaging technology that reveals the restricted pattern for endogenous activities of a ubiquitously expressed signaling protein Cdc42 within individual cells and in whole animals. Genetic experiments confirmed that it is the activation within individual cells and tissues, not simply the protein's presence, which defines its function during development.

  2. Two Ways to Redox Regulation

    Eukaryotic cells control the redox environment within their cytoplasm to be generally reducing. However, the endoplasmic reticulum provides an oxidizing environment for secretory and membrane proteins. In addition, a subcompartment of mitochondria—the powerhouses of the cell—also generates an oxidizing environment for constituent and itinerant proteins. Riemer et al. (p. 1284) review the current understanding of both eukaryotic redox machineries and highlight their implications for the biogenesis and regulation of protein function, focusing on the impact of these systems on health and disease.

  3. Coordinating Response to Stress

    Sirtuin 1 (Sirt1) (a protein deacetylase implicated in aging), senses the metabolic state of the cell and modulates the activity of substrate proteins that in turn regulate cellular transcriptional responses. In response to hypoxia, cells activate the transcription factor hypoxia-inducible factor 2 alpha (HIF-2α), which promotes adaptive responses. Dioum et al. (p. 1289; see the Perspective by Guarente) discovered a link between these two important cellular stress response systems—HIF-2α is a substrate of Sirt1. Direct interaction between Sirt1 and HIF-2α results in deacetylation of HIF-2α and enhances its transcriptional activity. In mice lacking Sirt1, the ability of HIF-2α to promote synthesis of the growth factor erythropoietin is diminished. Thus, the regulation of HIF-2α helps to coordinate responses of cells to various stresses.

  4. Extending Platinum Catalysts


    Platinum performs extremely well as a catalyst for the oxygen-reduction reaction that runs under highly acidic conditions in proton-exchange membrane fuel cells, but is expensive. One strategy for reducing costs is to increase the surface area of the platinum. Lim et al. (p. 1302, published online 14 May) describe a simple chemical route, in which Pt ions in solution are reduced onto Pd seed crystals, which creates faceted Pt nanocrystals with a high area owing to their dendritic architecture. On a Pt mass basis, these catalysts are several times more active than conventional Pt catalysts.

  5. War and Peace?

    Modern behavior, including the development of advanced tools, musical instruments, and art, seems to have arisen in humans in stages. The earliest hints are seen in Africa about 70 to 90,000 years ago, but later in Europe about 45,000 years ago. An ongoing discussion centers on the origins and significance of human prosociality. During early human development, could the benefits of altruistic behavior have outweighed its costs (see the Perspective by Mace)? Bowles (p. 1293) constructed a model of conflict between groups of humans and extracted estimates of the critical parameters from archaeological and ethnographic data sets. Provocatively, it appears that warfare might have enhanced the emergence and persistence of altruistic behavior. Powell et al. (p. 1298) present a population model that shows that the development of modern behaviors may rely on the attainment of critical population densities and migratory patterns required for stable cultural transmission. The model is consistent with genetic inferences of population dynamics in Africa and Europe and suggests that these cultural changes may not solely reflect increased cognitive evolution.

  6. Mergers and Acquisitions

    The crystallization of small molecules or polymers is often described in terms of a nucleation stage, where initial clusters form, followed by a distinct growth stage. Growth can come from the addition of unbound molecules, or through “Ostwald ripening” where larger crystals grow at the expense of smaller ones due to thermodynamic effects. Zheng et al. (p. 1309) studied the growth of platinum nanocrystals inside a transmission electron microscope using a special liquid cell, allowing observation of crystal growth in situ. Both monomer addition to growing particles and the coalescence of two particles were observed. The specific growth mechanism appeared to be governed by the size of each of the particles. The combination of growth processes makes it possible for an initially broad distribution of particles to narrow into an almost uniform one.

  7. Growing Graphene

    The highest quality graphene samples, single-atom-thick layers of carbon, are suspended flakes exfoliated from graphite, but these samples are very small in size (square micrometers). For many electronics applications, larger areas are needed. Li et al. (p. 1312, published online 7 May) show that graphene grows in a self-limiting way on copper films as large-area sheets (one square centimeter) from methane through a chemical vapor deposition process. The films, which are mainly one layer in thickness, can be transferred to other substrates and have electron mobilities as high as 4300 square centimeters per volt second.

  8. Defeating the Cuckoo

    Brood parasite-host interactions show ongoing antagonistic coevolution. What mediates rapid behavioral changes that do not reflect genetic change? Davies and Welbergen (p. 1318) show that reed warblers learn from their neighbors to behave aggressively toward models of the parasitic common cuckoo. Furthermore, reed warblers seem to be predisposed to learn to respond to cuckoos as enemies: Hosts that witnessed neighbors mobbing a harmless parrot model did not increase their aggression toward a cuckoo model. Thus, birds have templates for threats, and relevant antithreat behaviors can be turned on or off depending on social experience.

  9. Hox Clocks

    Homeobox or Hox genes are historically significant for demonstrating evolutionary conservation and homology in developmentally important genes. In addition, in many species, the Hox genes are fundamental to the organization of the embryo. Modifications in the regulation of their colinear, temporal activation may represent a way of altering their expression patterns and to elaborate body plans during evolution. Soshnikova and Duboule (p. 1320) now report highly dynamic modifications of chromatin marks along with progressive Hox gene activation during axial extension in the mouse. This work supports the proposal that the “Hox clock” may be controlled, at least in part, by epigenetic mechanisms.

  10. Starving T Cells


    The TH17 lineage of CD4+ helper T cells, characterized by the ability to secrete IL-17, is an important mediator of inflammation and autoimmunity. Dampening the responses of these cells or inhibiting their differentiation is of great therapeutic interest. Sundrud et al. (p. 1334; see the Perspective by Blander and Amsen) now show that the small molecule halofuginone inhibits the differentiation of TH17 cells but not other CD4+ T cell helper lineages both in vitro and in a mouse model of multiple sclerosis. This selective inhibition was mediated by activation of the amino acid starvation response. Amino acid depletion mimicked the effects of halofuginone, whereas excess amino acids rescued TH17 differentiation. The results highlight the importance of amino acid metabolism in regulating inflammation.

  11. Rhes-olving Huntington's Disease?

    Huntington's disease (HD) is caused by a single dominant mutation of huntingtin (Htt), a protein that occurs in all tissues of the body and that is uniformly distributed throughout the brain. How mutant Htt (mHtt) selectively damages striatal neurons with negligible alterations elsewhere has been a mystery. Subramaniam et al. (p. 1327) show that Rhes, a small G protein very highly localized to the striatum, binds mHtt and augments its neurotoxicity. Rhes promotes sumoylation of mHtt, leading to its disaggregation and augmented cytotoxicity. The findings establish how mHtt selectively kills cells in the striatum and suggest that Rhes-Htt binding might provide a therapeutic target.

  12. Dissecting VWF's Thrombogenic Potential

    Von Willebrand factor (VWF) is secreted from cells in an ultralarge form (ULVWF) in response to thrombogenic stimuli. Shear forces expose a binding site for platelets, enabling formation of a hemostatic plug. The thrombogenic potential of VWF correlates with its length and is regulated by proteolytic cleavage of the A2 domain. Zhang et al. (p. 1330; see the Perspective by Gebhardt and Rief) now combine single molecule data and polymer dynamics theory to show that shear forces in the circulation are sufficient to unfold the A2 domain and allow cleavage of multimers with more than about 200 monomers. The A2 domain may thus represent the “shear bolt” of VWF, unfolding when multimers experience high forces to allow cleavage and down-regulation of thrombogenic potential.

  13. Forbidden Crystals

    In crystalline materials, a unit cell is replicated in space through a series of rotations, inversions, and reflections. In order to fully fill space, only certain rotational symmetries are allowed. Quasicrystals contain aperiodic tilings of two or more basic shapes that allow these forbidden rotation symmetries. A number of quasicrystalline materials have been synthesized in the lab, including a number of aluminum alloys. Bindi et al. (p. 1306) examined samples of the mineral khatyrkite, with a nominal composition of (Cu,Zn)Al2. A number of quasicrystalline grains with composition similar to synthetically formed materials were observed. Thus, quasicrystals can form in nature under geological conditions.

  14. Superconducting Limits

    An electron wave function extends in three dimensions. Pairing up into Cooper pairs and reducing the temperatures can induce superconductivity in a material. How robust is an inherently three-dimensional effect when the dimensions are restricted? Qin et al. (p. 1314, published online 30 April) looked at the thickness dependence of superconductivity in thin lead films. In contrast to earlier, less direct measurements, superconductivity was robust, even down to films of only two monolayers.

  15. Transcriptional Repressor Dissected

    Living organisms have quality-control mechanisms to eliminate proteins damaged by environmental stresses. In the model organism Bacillus subtilis, the transcriptional repressor CtsR controls the expression of genes that are key to the heat-shock response. CtsR is activated by the kinase McsB to allow transcription of stress response genes, however, the mechanism of activation is unclear. Fuhrmann et al. (p. 1323) now describe structural and biochemical studies showing that McsB inhibits DNA binding of CtsR by specifically phosphorylating arginine residues in its DNA binding domain. This study provides a basis for exploring a potential wider role of arginine phosphorylation in prokaryotic and eukaryotic transcriptional regulation.

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