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Volume 7 Issue 2, February 2011

Neutrophil granulocytes can fight microbes either by phagocytosis or by formation of neutrophil extracellular traps (NETs), an extracellular structure that captures and kills bacteria, fungi and parasites. Using a chemical genetics approach, Hakkim et al. identified the Raf-MEK-ERK signaling system downstream of PKC in formation of NETs. The cover image shows a group of neutrophils that have developed NETs (yellow) after contact with Shigella flexneri bacteria (blue). Cover art by Erin Dewalt, based on an image from Volker Brinkmann. Article, p75

Editorial

  • Scientists must be attentive to ensure the integrity of the published record and find new ways to facilitate scientific debate in the electronic age.

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Research Highlights

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News & Views

  • Monoubiquitylation of histone H2B is found to disrupt condensation of chemically defined chromatin fibers. A novel fluorescence-based assay is used in concert with analytical ultracentrifugation to uncover the synergistic roles of histone acetylation and ubiquitylation on chromatin dynamics.

    • Craig L Peterson
    News & Views
  • The vast majority of core structures of protein and peptide glycosylation motifs belong to either O-linked or N-linked glycans. A recent publication describes the structure and biosynthesis of an unusual S-linked glycan linkage in the antibacterial glycopeptide sublancin.

    • Róbert Šardzík
    • Peter Both
    • Sabine L Flitsch
    News & Views
  • The development of small-molecule probes for use in neural stem cells demonstrates the importance of endogenous ROS signaling in regulating in vivo phenotypes.

    • Kate S Carroll
    News & Views
  • A new quantitative proteomic approach can identify reactive cysteine residues in native proteins and distinguish them on the basis of reactivity. This resource-rich study offers a useful new technology and is a significant step toward understanding the reactivity and functions of cysteines in cells.

    • Stefano M Marino
    • Vadim N Gladyshev
    News & Views
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Brief Communication

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Article

  • Biomimetic divalent ligands based on the PDZ domain–binding motifs from the AMPA receptor auxiliary subunit Stargazin disrupt the receptor's interaction with the scaffold protein PSD-95 and show that AMPARs are stabilized at synapses by engaging in multivalent interactions with PDZ domain-containing proteins.

    • Matthieu Sainlos
    • Cezar Tigaret
    • Barbara Imperiali
    Article
  • Identifying the cellular targets of small molecules remains a central challenge of chemical biology. The application of an RNAi-based functional genomics approach permitted the clustering of drugs with related targets by 'shRNA signatures', which served as a basis set to assign modes of action to compounds with unknown targets.

    • Hai Jiang
    • Justin R Pritchard
    • Michael T Hemann
    Article
  • A new fluorescent indicator reveals that a ROS-producing NADPH oxidase generates H2O2, normally associated with pathological conditions such as neurodegeneration, in neural stem cells where it regulates Akt phosphorylation and normal cell proliferation.

    • Bryan C Dickinson
    • Joseph Peltier
    • Christopher J Chang
    Article
  • Ubiquitylated histone H2B (uH2B) is a known chromatin modification involved in transcription. Analysis of nucleosome arrays containing chemically synthesized uH2B proteins revealed that this posttranslational modification impairs chromatin fiber compaction and increases its accessibility through a mechanism distinct from other chromatin marks.

    • Beat Fierz
    • Champak Chatterjee
    • Tom W Muir
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  • Random and targeted mutagenesis of serum paraoxonase, coupled with the development of a screen that allows detection of enzymatic activity against the toxic isomer of cyclosarin, yielded a mutant enzyme capable of protecting mice from a lethal dose of this dangerous nerve agent.

    • Rinkoo D Gupta
    • Moshe Goldsmith
    • Dan S Tawfik
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