This Week in Science

Science  17 May 2019:
Vol. 364, Issue 6441, pp. 645
  1. Development

    A tale of tadpole tail regeneration

    1. Beverly A. Purnell

    Tadpoles of the African clawed frog can sometimes regenerate severed tails.

    CREDIT: CYRIL RUOSO

    Some vertebrates, including some amphibians, show a remarkable, if sometimes restricted, ability to regenerate lost appendages. Aztekin et al. compared naturally occurring regeneration-competent and -incompetent Xenopus laevis tadpoles using single-cell messenger RNA sequencing. They identified regeneration-organizing cells (ROCs) that could coordinate tail regeneration. Relocation of ROCs from the body to the amputation plane enabled specialized wound epidermis formation and subsequent regeneration. ROCs simultaneously expressed many different ligands that can induce proliferation of different progenitor cell populations. Thus, by signaling to underlying progenitors, ROCs orchestrate the growth of a new appendage.

    Science, this issue p. 653

  2. Probe Microscopy

    Visualizing superexchange interactions

    1. Phil Szuromi

    The resolution that can be achieved in scanning probe microscopy can be greatly enhanced by absorbing a molecule such as CO on the probe tip. Czap et al. now show that this approach can be used to scan spin and magnetic properties of molecules on a surface. They adsorbed a magnetic molecule, Ni(cyclopentadienyl)2, on a silver surface and then transferred one of these molecules to a scanning tunnel microscope tip. They could then bring the tip toward the adsorbate-covered surface and map out the strength of superexchange interactions.

    Science, this issue p. 670

  3. Neuroscience

    The brain circuits of strategic decisions

    1. Peter Stern

    Primates can compute and integrate low-level decisions to make strategic adjustments to higher-level decisions. The neural substrates and mechanisms that allow this process are not known. Sarafyazd and Jazayeri performed single-cell recordings in the dorsomedial frontal cortex and the anterior cingulate cortex of monkeys. They observed that the two brain areas, which have been implicated in error monitoring and the control of adaptive behavior, processed signals involved in causal inference. The anterior cingulate acted downstream of the dorsomedial frontal cortex. It used graded evidence derived from errors in low-level processes in a decision hierarchy to select between longer-term behavioral strategies.

    Science, this issue p. eaav8911

  4. Neurodevelopment

    Brain cell transcriptomes in autism

    1. Pamela J. Hines

    Autism manifests in many ways. Despite that diversity, the disorder seems to affect specific cellular pathways, including those observed in the neocortex of patients' brains. Velmeshev et al. analyzed the transcriptomes of single brain cells, including neurons and glia, from patients with autism. Single-nucleus RNA sequencing analysis suggested that affected pathways regulate synapse function as well as neural outgrowth and migration. Furthermore, in patient samples, specific sets of genes enriched in upper-layer projection neurons and microglia correlated with clinical severity.

    Science, this issue p. 685

  5. Chemical Structure

    Dynamical refinement spots a difference

    1. Michael A. Funk

    For chiral molecules used in drugs, one isomer can have beneficial bioactivity, whereas the others are useless or even harmful. Determining the absolute configuration of molecules with chiral centers is often achieved through x-ray crystallography, but this requires relatively large crystals and high-quality data. Brázda et al. used electron diffraction to determine the absolute structure of an extremely radiation-sensitive crystal with micrometer dimensions (see the Perspective by Xu and Zou). In a strategy analogous to serial crystallography methods, many frames were combined to generate a complete dataset. Refinement incorporating dynamical effects differentiated the correct and incorrect molecular configuration.

    Science, this issue p. 667; see also p. 632

  6. Membrane Transport

    Transport control

    1. Valda Vinson

    The membrane protein P-glycoprotein protects cells by using energy from adenosine triphosphate (ATP) hydrolysis to expel chemical substances, including drugs. Inhibiting P-glycoprotein may thus ameliorate drug resistance. Structures of P-glycoprotein in the apo state and bound to substrate and inhibitor give insight into the transport mechanism, but a full picture requires access to substates in the transport cycle. Dastvan et al. used double electron electron resonance spectroscopy to show that substrates enhance transport by stabilizing an asymmetric post–ATP-hydrolysis state. By contrast, inhibitors stabilize a symmetric state that impairs transport.

    Science, this issue p. 689

  7. Chemical Physics

    Bonding's outer limit

    1. Jake Yeston

    In a Rydberg state, an atom has been very nearly, but not quite, ionized. This puts the electron relatively far from the nucleus, and two atoms in such a state can thus form a rather long-range bond. Hollerith et al. observed this phenomenon in fine detail by exciting pairs of ultracold rubidium atoms along the diagonal of an optical lattice. The authors resolved the vibrational state structure spectroscopically and showed that the Rydberg dimers manifested bond lengths exceeding 700 nanometers.

    Science, this issue p. 664

  8. Cancer

    The secret life of cediranib

    1. Yevgeniya Nusinovich

    Anti-angiogenic agents are used to inhibit the formation of new blood vessels that supply nutrients and oxygen to tumors. However, recent findings suggest that they can have additional anticancer effects. The antiangiogenic drug cediranib can sensitize tumors to poly(ADP-ribose) polymerase (PARP) inhibitors, which normally target tumors with defective DNA repair. Kaplan et al. determined that cediranib damages tumors both by interrupting their blood supply, inducing hypoxi a, and by directly affecting pathways involved in DNA repair, sensitizing cancer cells to PARP inhibitors.

    Sci. Transl. Med. 11, eaav4508 (2019).

  9. Immunology

    Recall responses by human NK cells

    1. Ifor Williams

    One of the traditional dividing lines separating innate and adaptive immunity is the restriction of immune memory to adaptive immune cells. However, accumulating evidence in animal models has suggested that memory responses can be evoked in natural killer (NK) cells. Nikzad et al. asked whether human NK cells also exhibit memory responses. They analyzed NK cells recovered from humanized mice and NK cells found in the viral antigen-challenged skin of adult volunteers who had chickenpox as children. Antigen-specific recall responses by human NK cells were observed in both experimental systems. Thus, human NK memory responses contribute to host protection after vaccinations or natural infections.

    Sci. Immunol. 4, eaat8116 (2019).

  10. Cancer

    Supporting tumor suppression

    1. L. Bryan Ray

    The protein PTEN is a phosphatase and tumor suppressor whose activity is often decreased in human cancers. Thus, reactivating such a protein could potentially be an effective therapy against cancer. Lee et al. identified a ubiquitin E3 ligase (WWP1) as a PTEN-interacting protein that modifies PTEN and inhibits its tumor suppressive activity (see the Perspective by Parsons). Depletion of WWP1 increased dimerization and membrane recruitment of PTEN. A natural compound found to be a pharmacological inhibitor of WWP1 inhibited tumor growth in a mouse model of prostate cancer. Thus, reactivation of the tumor suppressor PTEN may provide a strategy for battling tumors.

    Science, this issue p. eaau0159; see also p. 633

  11. Metamaterials

    Dynamic metasurfaces

    1. Ian S. Osborne

    Optical metasurfaces have opened an entirely new field in the quest to manipulate light. Optical metasurfaces can locally impart changes to the amplitude, phase, and polarization of propagating waves. To date, most of these metasurfaces have been passive, with the optical properties largely set in the fabrication process. Shaltout et al. review recent developments toward time-varying metasurfaces and explore the opportunities that adding dynamic control can offer in terms of actively controlling the flow of light.

    Science, this issue p. eaat3100

  12. Cellular Neuroscience

    Local translation in presynaptic terminals

    1. Stella M. Hurtley

    Proteins carry out most of the functions in cells, including neurons, which are one of the most morphologically complex cell types in the body. This poses challenges for how proteins can be supplied to remote regions where connections (synapses) are made with other neurons. One solution to the neuron protein-supply problem involves the local synthesis of proteins from messenger RNA (mRNA) molecules located at or near synapses. Hafner et al. used RNA sequencing methods and superresolution microscopy to show that axon terminals contain hundreds of mRNA molecules as well as the machinery needed for protein synthesis. Furthermore, the axon terminals were able to use these components to make proteins that participate in synaptic transmission.

    Science, this issue p. eaau3644

  13. Outer Solar System

    New Horizons flies past MU69

    1. Keith T. Smith

    After flying past Pluto in 2015, the New Horizons spacecraft shifted course to encounter (486958) 2014 MU69, a much smaller body about 30 kilometers in diameter. MU69 is part of the Kuiper Belt, a collection of small icy bodies orbiting in the outer Solar System. Stern et al. present the initial results from the New Horizons flyby of MU69 on 1 January 2019. MU69 consists of two lobes that appear to have merged at low speed, producing a contact binary. This type of Kuiper Belt object is mostly undisturbed since the formation of the Solar System and so will preserve clues about that process.

    Science, this issue p. eaaw9771

  14. Sugar Chemistry

    Sweet spot for making oligosaccharides

    1. Michael A. Funk

    Sugars pose a challenge for chemists: how to string together functional group–rich building blocks that can adopt multiple conformations. Two papers in this issue used sugar building blocks constrained by a macrocyclic linker to encourage formation of a specific glycosidic linkage (see the Perspective by Pohl). Ikuta et al. used glucose building blocks containing a linker that changes the sugar conformation to synthesize cyclic oligomers with only three or four units. The linker changes the conformation of the glucose monomers, enabling them to come together despite the strain in the final structure. Komura et al. prepared sialic acid building blocks with a linker that allows for selective formation of the α-anomeric linkage with a range of nucleophiles. They synthesized dimers of sialic acid with many different linkages and a pentamer with four α(2,8) linkages. This method enabled chemical synthesis of components of mammalian glycans involved in brain development, cell adhesion, and immune response.

    Science, this issue p. 674, p. 677; see also p. 631

  15. Organic Chemistry

    Excising an olefin

    1. Jake Yeston

    Plants produce an abundance of structurally complex terpene compounds that are useful precursors to pharmaceuticals and other fine chemicals. However, the carbon frameworks of these compounds constrain the available pathways for diversification. Smaligo et al. now show that successive treatment with ozone, an iron oxidant, and a hydrogen-atom donor can cleanly cleave pendant olefins from terpenes and related compounds (see the Perspective by Caille). Breaking the bond between saturated and double-bonded carbon centers offers a direct route to desirable chiral intermediates from readily available, inexpensive precursors.

    Science, this issue p. 681; see also p. 635

  16. Auditory Neuroscience

    Machine learning improves hearing aids

    1. Aaron Clauset,
    2. Kollen Post

    A key challenge in improving assistive hearing devices is isolating and separating different voices in noisy or crowded settings. This task is especially difficult without prior exposure to the voices of interest and without knowing which voice to amplify. Han et al. used deep attractor networks—a powerful machine-learning technique—to project unfamiliar mixed audio signals into a high-dimensional space to separate signals from independent speakers. Comparing these separated sources with auditory cortical responses of a user allowed the method to determine and amplify the attended voice. The approach was as accurate as methods trained with clean audio sources and may thus enable hearing-impaired users to communicate more naturally in complex social environments.

    Sci. Adv. 10.1126/sciadv.aav6134 (2019).

  17. Inflammasomes

    BCAPing inflammasome activation

    1. Erin Williams

    The phosphoinositide 3-kinase adaptor protein BCAP (B cell adapter for PI 3-kinase) limits macrophage responses to stimulation of Toll-like receptors. Inflammasomes are multiprotein complexes that activate the protease caspase-1 to process the proinflammatory cytokine interleukin-1β (IL-1β). Carpentier et al. identified a distinct role for BCAP in preventing excessive activation of inflammasomes. In macrophages, BCAP reduced active caspase-1 levels, IL-1β release, and cell death after exposure to the toxin nigericin or after bacterial infection. BCAP delayed caspase-1 activation by inflammasomes, and loss of BCAP promoted bacterial clearance in mice.

    Sci. Signal. 12, eaau0615 (2019).

  18. Protein Design

    Designed to respond

    1. Valda Vinson

    Protein design has achieved success in finding sequences that fold to very stable target structures. Protein function, however, often requires conformational dynamics. Boyken et al. describe designed proteins that undergo conformational transitions in response to pH. They designed helical oligomers in which histidines are positioned in hydrogen-bond networks at the interfaces, with complimentary hydrophobic packing around the networks. Lowering the pH protonated the histidine, disrupting the oligomers. After endocytosis into low-pH compartments in cells, the designed proteins disrupted endosomal membranes.

    Science, this issue p. 658

  19. Aging

    Agents for healthful aging

    1. Gemma Alderton

    During aging, senescent cells—dysfunctional noncycling cells—accumulate. This accumulation is associated with numerous diseases, including osteoarthritis and cancer. In a Perspective, van Deursen discusses the preclinical evidence from mice showing that selectively eliminating senescent cells using targeted senolytic drugs can improve longevity and prevent or reduce age-associated disease. Such drugs are now moving into clinical trials, but we still need to understand much more about senescent cells.

    Science, this issue p. 636