Editors' Choice

Science  09 Mar 2018:
Vol. 359, Issue 6380, pp. 1115
  1. Proteostasis

    Gumming up the works

    1. Stella M. Hurtley

    Poly-GA aggregate within a neuron

    CREDIT: Q. GUO ET AL., CELL 172, 696 (2018)

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that has been linked to toxic aggregates of poly-Gly-Ala (poly-GA) peptides generated by aberrant translation of an expanded nucleotide repeat sequence. Proteasomes are cytosolic molecular machines involved in the degradation of misfolded and aggregated proteins. Guo et al. used cryo–electron tomography to examine the molecular architecture of poly-GA aggregates in situ in intact neurons. The peptide aggregates formed twisted ribbons that clumped together and that were surrounded by proteasomes trapped in their normally transient substrate-processing conformation. The extent of proteasome accumulation was such that the ability of the remaining proteasomes within the neuron to perform their normal housekeeping functions was likely to be impaired, potentially explaining the neuronal pathologies observed in ALS.

    Cell 172, 696 (2018).

  2. Neuroscience

    Speed representation in the brain

    1. Peter Stern

    Speed- and direction-responsive neurons in the medial entorhinal cortex and the hippocampus form a major component of the mammalian space representation system. There are long-range GABAergic projections between these two brain regions. Some of these inputs originate from parvalbumin-expressing inhibitory neurons. However, it has not been shown whether the parvalbumin cells projecting to the hippocampus are speed cells. Ye et al. used extracellular recording, optogenetic tagging, and immunohistochemistry to investigate whether, and how, speed-responsive cells in the entorhinal cortex and hippocampus are functionally connected. The majority of medial entorhinal speed cells were fast-spiking, the hippocampus received direct input from such cells, and GABAergic long-range projections to the hippocampus originated almost exclusively from parvalbumin-positive neurons. This indicates that hippocampus-projecting speed cells are part of this subpopulation.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1720855115 (2018).

  3. Glass Transition

    A simple theory for simple glass

    1. Brent Grocholski

    A microscopic image of glass made from a metallic alloy

    CREDIT: AN SCHROERS, YALE

    Glasses have many important industrial applications, yet understanding the changes that occur over the wide range of time and length scales of the glass transition remains a challenge. Hansen et al. performed simultaneous neutron scattering and dielectric spectroscopy measurements that allowed dynamic observations to be made over an impressive 14 orders of magnitude. Unexpectedly, for van der Waals fluids, they found identical dynamics across this massive time scale at different state points in the phase diagram. This finding dramatically simplifies the theory that describes these fluids, which include technologically important materials such as metallic glasses.

    Nat. Commun. 10.1038/s41467-017-02324-3 (2018).

  4. Signal Transduction

    Protein kinase signaling without phosphorylation

    1. L. Bryan Ray

    Protein kinases usually propagate signals by phosphorylating substrate molecules. Goncharov et al. find a different mechanism for the protein kinase RIP2 (receptor interacting protein 2) in inflammatory signaling. RIP2 acts in the innate immune system to signal the detection of bacterial infection. The authors found that inhibitors of RIP2's protein kinase activity prevented signaling not by reducing autophosphorylation (no other substrates for the kinase are known) but rather by inhibiting interaction of RIP2 with the ubiquitin ligase XIAP (x-linked inhibitor of apoptosis). Ubiquitination of RIP2 by XIAP was in turn required for proper signaling. This unusual mechanism, whereby dimerization of RIP2 appears to alter protein interactions rather than kinase activity to propagate a signal, could provide a therapeutic target for inflammatory diseases in which such signaling is inappropriately activated.

    Mol. Cell 10.1016/j.molcel.2018.01.016 (2018).

  5. Batteries

    A solid electrolyte

    1. Marc S. Lavine

    In an electrochemical cell, the electrolyte has the role of separating and shuttling ions to produce a current. A good electrolyte thus should have high ionic conductivity and good thermal and electrochemical stability, although many in use do not have all these attributes. For example, solid electrolytes can show greater stability, but they are often poorer conductors. Joos et al. consider a deep eutectic solvent, in which the combination of two compounds radically lowers the melting temperature, immobilized within a silica matrix to form a gel. This material was easily processed, had decent ionic conductivity and thermal stability up to 130°C, and was successfully cycled in a Li/LiFePO4 cell.

    Chem. Mater. 10.1021/acs.chemmater.7b03736 (2018).

  6. Education

    Scientific reasoning on paper

    1. Melissa McCartney

    Helping students develop skills in both critical thinking and scientific reasoning is fundamental to science education. However, the relationship between these two constructs remains largely unknown. Dowd et al. examined this issue by investigating how students' critical thinking skills related to scientific reasoning in the context of undergraduate thesis writing. The authors used the BioTAP rubric to assess scientific reasoning and the California Critical Thinking Skills Test to assess critical thinking. Results support the role of inference in scientific reasoning in writing, while also revealing other aspects of scientific reasoning (epistemological considerations and writing conventions) not related to critical thinking. In considering future implications for instruction, the authors suggest that further research into the impact of interventions focused on specific critical thinking skills (i.e., inference) for improved science reasoning in writing is needed.

    CBE Life Sci. Educ. 10.1187/cbe.17-03-0052 (2018).

  7. Framework Morphology

    Mesocrystal morphogenesis

    1. Phil Szuromi

    Control of the formation of mesoscale crystals of metalorganic framework (MOF) compounds can offer ways to control their reactivity and sorption properties and create more elaborate structures. Hwang et al. show that a copolymer with two hydrophilic blocks—polyethylene oxide and polymethylmethacrylate—modulates the crystal formation of a MOF in which zinc cations and bdc (benzene-1,4-dicarboxylic acid) linkers form two-dimensional sheets connected by a second ligand that act as pillars. The copolymer kinetically favors metastable hexagonal crystal polymorphs. After partial removal of the copolymer with methanol soaking, the crystals transform into more stable tetragonal crystals.

    J. Am. Chem. Soc. 10.1021/jacs7b12633 (2018).