Editors' Choice

Science  08 May 2015:
Vol. 348, Issue 6235, pp. 645
  1. Myeloid Cells

    A role for macrophages in Rett syndrome

    1. Kristen L. Mueller

    Mutations in meningeal macrophages may contribute to the generation of Rett syndrome

    PHOTO: J. C. CRONK ET AL. IMMUNITY 42, 4 (21 APRIL 2015) © 2015 ELSEVIER INC.

    Scientists previously implicated microglia, a macrophage subset in the brain, in the pathogenesis of the neurodegenerative disease Rett syndrome. To better understand how microglia and other types of macrophages might contribute to the development of the disease, Cronk et al. examined MECP2-deficient mice. Multiple types of macrophages express MECP2 in normal mice, and several of these populations, including microglia, are lost in MECP2-deficient mice. MECP2 regulated a pro-inflammatory gene expression signature in macrophages. When the authors selectively reexpressed MECP2 in macrophages, they were able to extend the lives of MECP2-deficient mice, which suggests that macrophages probably contribute to disease pathogenesis.

    Immunity 42, 679 (2015).

  2. Protein Binding

    Methyl-C binding may explain Rett late onset

    1. Guy Riddihough

    Girls with Rett syndrome develop normally for the first 1 or 2 years of life before suffering from progressive neurological problems, perhaps due to mutations in methyl-CpG–binding protein 2 (MeCP2). Chen et al. analyzed the binding of MeCP2 to genomic DNA in the mouse brain and found that before birth, MeCP2 binds predominantly to methylated CG sequences. After birth, there is an increase in the genome of methylated C in a non-CG context (mCH). MeCP2 binds to many of these mCH sites, which are enriched in genes with neuronal functions. MeCP2 binding modulates the transcription of these genes, some of which are implicated in Rett syndrome, potentially explaining the late onset of the disease.

    Proc. Natl. Acad. Sci. U.S.A. doi/10.1073/pnas.1505909112 (2015).

  3. Neuroscience

    Sleeping while awake

    1. Monika S. Magon

    Sleep deprivation affects our behavior and performance. Bernardi et al. demonstrate the connection between task-specific performance decrease and local sleep in relevant parts of the human brain. During 24 hours of wakefulness, individuals participated in driving simulations and executive function exercises. Their task-related abilities, such as visuomotor control and response inhibition, were tested alongside electroencephalography (EEG) recordings and functional magnetic resonance imaging (fMRI). Local EEG theta waves, normally observed during sleep, coincided with times of slower movements, visual inaccuracies, and decreased impulse control. The fMRI scans exposed cognitive fatigue in the form of regional neuronal disconnections in the task-relevant brain areas in addition to the general deficiencies.

    J. Neurosci. 35, 4487 (2015)

  4. Physics

    Tilting the field to expose a fraction

    1. Jelena Stajic

    In extremely clean, flat, and cold conductors, turning on an external magnetic field can produce the so-called quantum Hall effect (QHE), with the voltage across the sample exhibiting plateaus. The plateaus reflect the discrete energy levels of electrons in a magnetic field and can sometimes appear when only part of the level is filled: the fractional QHE. The most exotic of these states have filling factors with even denominators and may be useful in topological quantum computing. Falson et al. observed even-denominator states with filling factors 3/2 and 7/2 at the interface of MgZnO and ZnO. Interestingly, one of the states was only observable when the researchers tilted the magnetic field from the normal to the sample.

    Nat. Phys. 11, 347 (2015).

  5. Ecology

    Thirty new fly species in Los Angeles

    1. Julia Fahrenkamp-Uppenbrink

    Six of 30 new fly species discovered in Los Angeles

    PHOTO: KELSEY BAILEY

    Urban environments are not usually considered to be rich in biodiversity; surveys of urban biodiversity often report limited and declining numbers of species. Hartop et al. show that they can nevertheless yield surprises, at least when it comes to insect diversity. Studying thousands of samples from private backyards in Los Angeles, CA, the authors have discovered 30 previously unknown species of Megaselia flies. Possible reasons for this unexpected diversity may be the wide range of geography in the Los Angeles area and the introduction of invasive species via its large container ports. It remains unclear, however, whether this diversity represents native or invasive species.

    Zootaxa 10.11646/zootaxa.3941.4.1 (2015).

  6. Medicinal Chemistry

    Proteins take steps to bind larger ligands

    1. Valda Vinson

    In medicinal chemistry, optimizing the binding of a small molecule to a protein target often involves incremental changes to the small molecule. The design process may involve simulations of how a series of molecules binds to the target, but there is little experimental data to inform this analysis. Merski et al. determined the structures of eight benzene compounds, each differing by a single methyl group, binding to the model protein T4 lysozyme. Instead of gradually changing structure, T4 lysozyme transitions between three conformations with different-sized ligand-binding sites. A search of the protein data bank revealed other examples of discrete changes in response to ligand size. Modeling such discrete conformations may be important in drug design.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1500806112 (2015).

  7. Flow Chemistry

    Round and round with a precious catalyst

    1. Jake Yeston

    When manufacturing pharmaceuticals, it is crucial to make just one of two possible mirror-image structures. Soluble precious metal catalysts can facilitate that objective, but they're often hard to collect and reuse after the reaction is over. O'Neal et al. present a laboratory-scale flow and filtration protocol to keep a ruthenium hydrogenation catalyst in continuous use for 24 hours. A membrane incorporated into the flow apparatus retains the catalyst in the reaction loop while releasing the product, all the while withstanding hydrogen pressure and a strongly basic co-catalyst. Less than 200 parts per billion of ruthenium escapes into the product stream.

    ACS Catal. 5, 2615 (2015).

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