Editors' Choice

Science  30 Mar 2018:
Vol. 359, Issue 6383, pp. 1481
  1. Solar System

    Searching the solar system with pulsars

    1. Keith T. Smith

    Radio waves from pulsars can be used to detect objects in the solar system, such as Mars (shown).

    PHOTO: NASA/JPL-CALTECH/MALIN SPACE SCIENCE SYSTEMS

    Pulsar timing arrays (PTAs) monitor the arrival times of radio pulses from numerous pulsars to search for shifts caused by passing long-wavelength gravitational waves. Reaching the necessary level of precision requires correcting the data for small perturbations in Earth's orbit owing to the other planets in our solar system. Guo et al. have switched that process around: Instead of correcting for known planets, they show that PTAs can be used to search for undiscovered massive bodies in the solar system. Existing PTAs should be sufficient to recover the known planets and measure their masses, but more sensitive PTAs will be required to search the outer solar system for objects such as the proposed Planet Nine.

    Mon. Not. R. Astron. Soc. 475, 3644 (2018).

  2. Cancer

    Blood biomarkers for melanoma therapy

    1. Priscilla N. Kelly

    Immunotherapy using checkpoint inhibitors has dramatically improved melanoma treatment response. However, only a subset of patients show durable remissions. Hong et al. studied circulating tumor cells (CTCs) from the blood of 49 melanoma patients to identify biomarkers that may predict therapeutic outcomes. They developed a two-part test, wherein an RNA digital PCR (polymerase chain reaction) gene signature was combined with microfluidic enrichment for CTCs. A reduced CTC score within the first 7 weeks of therapy correlated with progression-free survival and overall survival in the small cohort studied. Liquid biopsy strategies may provide a means to distinguish which patients are the best candidates for immunotherapy using checkpoint blockade.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1719264115 (2018).

  3. Immunology

    A bat's STING is less potent

    1. Seth Thomas Scanlon

    Bat immune responses to viruses are compromised.

    PHOTO: MERLIN D. TUTTLE/SCIENCE SOURCE

    Bats have evolved enhanced oxidative phosphorylation pathways in response to the increased metabolic demands of flight. One effect of this is DNA damage and release. Additionally, bats serve as reservoirs for a multitude of viruses, which raises the question of how these animals are able to tune cytosolic DNA sensing and innate immune activation. Xie et al. report that STING (stimulator of interferon genes)—the main adaptor in several DNA-sensing pathways—is mutated in bats at the serine-358 residue, which is critical for downstream interferon (IFN) activation. They found that bat STING was less effective at inducing IFN production and viral inhibition. These findings add to previous work showing bat-specific changes in other DNA sensors such as AIM2, IFI16, and TLR9 that elicit more harmonious immune responses to pathogens.

    Cell Host Microbe 23, 297 (2018).

  4. Neuroscience

    We choose what we want to hear

    1. Peter Stern

    To make sense of the outside world, the brain must organize and group information that arrives at our sensory organs. Can we consciously influence this perception process? Billig et al. measured brain activity while subjects listened to sequences of pure tones that could be interpreted as individual sounds or as an integrated percept. Listeners indicated when their perception changed between these two interpretations. These changes were associated with changes in auditory cortex activity. Participants could also consciously control how many objects they perceived in an ambiguous auditory scene. This led to similar changes in neural activity. Listeners can thus use attention not only to enhance the representation of a subset of sounds, but also to intentionally alter the number of distinct objects heard.

    J. Neurosci. 38, 2844 (2018).

  5. Cell Biology

    Right time, right speed, right size

    1. Stella M. Hurtley

    Centrioles are microtubule-based organelles composed of an archetypal cylindrical arrangement of tubulin. Centrioles duplicate when a daughter centriole grows from the side of the mother, but it has been unclear how daughters grow to the right size. Aydogan et al. used live-cell imaging to quantify the dynamics of daughter centriole assembly in developing Drosophila embryos. They found that Polo-like kinase 4 (Plk4) promoted incorporation of a centriole component, Sas-6, into the proximal end of the growing daughter at a linear rate during the early S phase. However, growth abruptly stopped when centrioles reached the correct size in the mid- to late S phase. Plk4 is a “suicidal” enzyme that promotes its own degradation, and it acted as a homeostatic clock to set the size of centrioles: The higher the centriolar Plk4 activity, the faster the centrioles would grow, but the faster Plk4 would become degraded and centriole growth would cease.

    J. Cell Biol. 10.1083/jcb.201801014 (2018).

  6. Structural Biology

    A scaffold for small proteins

    1. Michael A. Funk

    Reconstruction of atomic-resolution structures in cryo–electron microscopy is limited by the ability to select, align, and average individual particles in the underlying images. Small biomolecules pose a particular challenge because they are hard to distinguish from the surrounding amorphous ice. Liu et al. combined a large, computationally designed protein cage with a small, modular domain containing a protein-binding surface that can be evolved separately to bind other small proteins for structure determination. The cage serves as a rigid scaffold that allows for accurate particle selection and alignment. The 17-kDa protein-binding domain was well resolved in the electron density maps at near-atomic resolution.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1718825115 (2018).

  7. Organic Chemistry

    Enacting a program's plans for synthesis

    1. Jake Yeston

    How does a chemist plan a synthesis? In principle, it is an exercise in breaking down the targeted product into smaller pieces that look feasible to stitch together. Computer programs that offer such advice on the basis of a set of reaction precedents have been around for decades, but they have seldom proven broadly useful. Klucznik et al. now report a validation test of their Chematica program, which charts a course to products by using reactivity rules coded by human experts. Eight compounds were targeted, and all of them were successfully prepared in accord with routes devised by the software, often with improved yields relative to prior routes.

    Chem 4, 522 (2018).