Editors' Choice

Science  24 Feb 2017:
Vol. 355, Issue 6327, pp. 809
  1. Mast Cells

    DNA methylation curbs mast cell response

    1. Priscilla Kelly

    DNMT3A is important for preventing mast cell overactivity.


    Mast cells are white blood cells that are perhaps best known for their role in allergic responses and asthma. Leoni et al. now show that the enzyme DNMT3A limits mast cell activity following acute and chronic inflammation. Using mice deficient in DNMT3A, the authors found exaggerated mast cell responses to skin allergy. Inactivation of DNMT3A was associated with increased cytokine production, enhanced mast cell degranulation, and aberrant expression of the IQGAP2 scaffold protein. A number of hematological disorders have been associated with mutations in DNA methylation enzymes, and the current studies highlight a broader role for containing immune responses.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1616420114 (2017).

  2. RNA Design

    An old motif with new specificity

    1. Valda Vinson

    RNA aptamers bind to small molecules and, in the context of adjacent regulatory domains, can control cellular processes. Synthetic RNA aptamers can be selected against a target, but it is difficult to integrate these artificial sensors into cells. Porter et al. started with scaffolds derived from two different riboswitches and a ribozyme that all contain a recurrent motif. They made libraries designed to maintain the structure, but with sufficient diversity to select sequences that would bind precursors of serotonin and dopamine. They obtained a diverse set of aptamers that selectively bind their target and can be coupled to a fluorophore binding domain for readout. The suite of aptamers could potentially be combinatorially coupled to communication modules to rapidly screen for sequences with a required activity.

    Nat. Chem. Biol. 10.1038/NCHEMBIO.2278 (2017).

  3. Stress Response

    How tissues can take the heat

    1. Laura M. Zahn

    Heat shock proteins (HSPs) show a generally conserved stress response, interacting with specific chaperone proteins to maintain cellular homeostasis. However, studies of the heat shock response (HSR) tend to be performed in unicellular organisms or tissue culture. To test whether the HSR is global or tissue-specific, Ma et al. examined HSR and specificity in muscle and intestine in Caenorhabditis elegans. They observed that the tissue specificity of the HSR was determined by the ratio of the specific proteome of each tissue relative to associated HSP chaperone proteins. On the basis of these findings, the authors suggest that some tissue-specific human disease may be explained by similar mechanisms.

    G3 10.1534/g3.116.038232 (2017).

  4. Active Galaxies

    A supermassive black hole awakes

    1. Keith M. Smith

    Every large galaxy hosts a supermassive black hole at its center, which grows by consuming passing gas or stars. Most are quiescent, but when the black hole is feeding, an accretion disk forms, causing the galaxy nucleus to shine brightly as a quasar. Gezari et al. have discovered a bright quasar in a galaxy that was previously in an unremarkable quiescent state. As the black hole began feeding, the nucleus brightened by at least a factor of 10 in about a year. Such a rapid switch-on is unexpected, challenging theories of how quickly accretion disks can change state.

    Astrophys. J. 10.3847/1538-4357/835/2/144 (2017).

  5. Development

    Polarity reversal during tissue remodeling

    1. Megan Eldred

    The epithelial-mesenchymal transition occurs when epithelial cells lose apicobasal polarity and cell-cell contacts and migrate into surrounding tissues as mesenchymal cells. Migration is crucial for gastrulation, neural tube formation, and cancer metastasis. However, the mechanisms underlying loss of polarity and cell movement are poorly understood. Burute et al. show that the centrosome position in epithelial cells changes from the periphery to the center of mesenchymal cells. The change in cell organization results in the transition from apicobasal polarity to front-rear polarity that precedes cell migration. Micropatterned cell culture showed that the mechanism is cell-intrinsic and governed by microtubule reorganization but is not influenced by neighboring cells.

    J. Dev. Cell. 10.1016/j.devcel.12.004 (2016).

  6. Electrochemistry

    CO2 reduction off base

    1. Phil Szuromi

    The electrochemical reduction of CO2 can yield a range of products, including aldehydes, acids, and alcohols, as well as hydrogen formed by the competing hydrogen evolution reaction (HER) at the high cathodic potentials used. Birdja and Koper show in studies with boron-doped diamond electrodes that aldehydes are the direct product of CO2 reduction and that primary alcohols and carboxylic acids form through Cannizzaro-type disproportionation (thus, methanol and formic acid form from formaldehyde). These reactions are unexpected because they require base, but the HER creates OH− as a by-product, so regions near the electrode can be at high pH. Such reactions are inhibited in buffered electrolytes, which the authors recommend to sort out direct and indirect product formation mechanisms.

    J. Am. Chem. Soc. 10.1021/jacs.6b12008 (2016).

  7. Evolution

    How animals sense CO2 in blood

    1. Julia Fahrenkamp-Uppenbrink

    Chickens and other warm-blooded animals may share the same internal carbon dioxide sensor.


    High carbon dioxide levels in blood can be lethal to animals, so it is crucial that the body regulates the regular excretion of CO2. De Wild et al. hypothesized that the protein Connexin 26 plays a key role in sensing CO2 levels in warm-blooded animals. The authors exposed Connexin 26 from four different organisms—human, chicken, rat, and mole rat—to rising levels of CO2. They found that the sensitivity of the protein to CO2 matched the organism's tolerance of CO2. Connexin 26 may thus be a universal CO2 sensor in warm-blooded animals.

    Proc. R. Soc. B 10.1098/rspb.2016.2723 (2017).

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