This Week in Science

Science  24 May 2019:
Vol. 364, Issue 6442, pp. 746
  1. Evolutionary Biology

    How wings lost their claws

    1. Shahid Naeem,
    2. Kollen Post

    A day-old hoatzin chick has claws on its wing.

    PHOTO: AMAZON-IMAGES/ALAMY STOCK PHOTO

    As birds evolved, most lost the claws that characterize the wings of Archaeopteryx, a dinosaur from the evolutionary transition point between nonavian and avian dinosaurs. Curiously, hatchlings of the hoatzin (Opisthocomus hoazin) have similar claws on their wings but lose them by adulthood. Abourachid et al. observed the swimming and climbing movements of four fledgling hoatzins. While swimming, the chicks exhibited a synchronized motion of their wings like that of modern birds. However, the chicks climbed with the help of their claws using an alternating motion. This seeming reappearance of an ancient trait suggests greater plasticity in bird evolution than previously thought.

    Sci. Adv. 10.1126/sciadv.aat0787 (2019).

  2. Quantum Electronics

    Quantum walks on a superconducting circuit

    1. Ian S. Osborne

    Quantum walks generate large-scale quantum superposed states. This allows for classically unavailable applications, such as simulating many-body quantum systems, and also yields quantum algorithms exponentially faster than classical computation. Yan et al. demonstrate quantum walks of one and two strongly correlated microwave photons in a one-dimensional array of 12 superconducting qubits with short-range interactions. The scalability of the superconducting platform could lead to large-scale implementations and the quantum simulation of complex systems.

    Science, this issue p. 753

  3. Structural Materials

    A stronger, cooler wood

    1. Brent Grocholski

    One good way to reduce the amount of cooling a building needs is to make sure it reflects away infrared radiation. Passive radiative cooling materials are engineered to do this extremely well. Li et al. engineered a wood through delignification and re-pressing to create a mechanically strong material that also cools passively. They modeled the cooling savings of their wood for 16 different U.S. cities, which suggested savings between 20 and 50%. Cooling wood would be of particular value in hot and dry climates.

    Science, this issue p. 760

  4. Seismology

    Using earthquakes to find earthquakes

    1. Brent Grocholski

    Earthquake catalogs elucidate the behavior of faults and allow for rough estimates of when large earthquakes might occur. Cataloging small earthquakes is challenging because the small signal is often indistinguishable from noise. Ross et al. used a template-matching algorithm to find almost two million tiny earthquakes previously missed by other earthquake-logging techniques in Southern California (see the Perspective by Brodsky). This more-complete catalog can be used to better understand faults, earthquake reoccurrence, and other geophysical processes.

    Science, this issue p. 767; see also p. 736

  5. Organic Chemistry

    Markovnikov falls to chromium and titanium

    1. Jake Yeston

    Ring opening of strained triangular epoxides is a versatile method for making alcohols. However, these reactions are limited by their tendency to leave the oxygen on the more heavily substituted carbon, in accord with the Markovnikov rule. Yao et al. now show that a pair of catalysts working cooperatively can invert this selectivity pattern. A titanium catalyst pries the ring open while a chromium catalyst activates and delivers hydrogen. In an unusual mechanistic twist, the chromium complex appears to deliver a hydrogen atom, a proton, and an electron at different stages of the cycle.

    Science, this issue p. 764

  6. Conservation

    A portfolio of habitats

    1. Sacha Vignieri

    To conserve species, we must conserve their habitat. This concept is well known, but the reality is much more complex than simply conserving a particular area. Habitats are dynamic and vary across both space and time. Such variation can help to facilitate long-term persistence of species by allowing local movement in search of the best conditions. Brennan et al. clearly demonstrate the benefit of the habitat mosaic to Pacific salmon by characterizing how both climate and population productivity vary over time and space in an Alaskan river system.

    Science, this issue p. 783

  7. Antibiotic Resistance

    A race against time

    1. Caroline Ash

    Clinically relevant antimicrobial resistance is largely spread via plasmids that disperse among bacteria during conjugation. How quickly can a resistance gene be expressed after transfer? In susceptible bacterial cells, tetracycline should inhibit protein synthesis, including from the plasmid-transferred resistance gene tetA. Unexpectedly, Nolivos et al. found that TetA can be expressed despite the presence of tetracycline (see the Perspective by Povolo and Ackermann). Immediately after plasmid transfer into a cell, TetA synthesis starts because its repressor is slow to be expressed. In addition, the ubiquitous xenobiotic efflux pump AcrAB-TolC buys time for TetA translation by keeping tetracycline concentration below toxic levels.

    Science, this issue p. 778; see also p. 737

  8. Structural Biology

    A GPCR seen in the active state

    1. L. Bryan Ray

    G protein–coupled receptors (GPCRs) are exceptionally good targets for drug development. Warne et al. describe four crystal structures of complexes of a GPCR—the β1-adrenergic receptor—in its active state. They used nanobodies (recombinant variable domains of heavy-chain antibodies) and engineered G protein to stabilize the β1-adrenergic receptor bound to a full agonist, two partial agonists, and a weak partial agonist. Comparison of these structures to the inactive state elucidates how agonist binding is altered in the active conformation.

    Science, this issue p. 775

  9. Gene Therapy

    Vectors in stealth mode

    1. Mattia Maroso

    Gene therapy using adeno-associated virus (AAV) vectors has shown safety and efficacy in hemophilia. However, AAV vectors have limitations hindering their efficacy in some patients. The use of lentiviral vectors (LVs) has been explored as a possible alternative; however, preclinical data reported low transduction efficacy, possibly owing to fast clearance by phagocytes. Milani et al. developed a shielded LV able to escape phagocytosis by expressing the phagocytosis inhibitor CD47 on its surface. Upon intravenous administration in monkeys, the LVs showed high transduction efficacy without signs of toxicity. Thus, LV-mediated gene therapy might be an effective strategy for treating hemophilia.

    Sci. Transl. Med. 11, eaav7325 (2019).

  10. Protein Engineering

    Exploring a range of signaling

    1. Valda Vinson

    Cytokines are small proteins that bind to the extracellular domains of transmembrane receptors to activate signaling pathways inside the cell. They often act by dimerizing their receptors, and changes in dimer orientation of the extracellular domains can change the signaling output. Mohan et al. systematically explored this tuning effect by designing a series of dimer ligands for the erythropoietin receptor in which they varied the distance and angle between monomers. The topology affected the strength of activation and differentially affected different pathways, which raises the potential for exploiting such ligands in medicinal chemistry.

    Science, this issue p. eaav7532

  11. Mitochondrial DNA

    Heteroplasmy incidence in mitochondrial DNA

    1. Laura M. Zahn

    In humans, mitochondrial DNA (mtDNA) is predominantly maternally inherited. mtDNA is under selection to prevent heteroplasmy—the transmission of multiple genetic variants into the next generation. Wei et al. explored human mtDNA sequences to determine mtDNA genome structure, selection, and transmission. Whole-genome sequencing revealed that about 45% of individuals carry heteroplasmic mtDNA sequences at levels greater than 1% of their total mtDNA. Furthermore, studies of more than 1500 mother-offspring pairs indicated that the female line selected which mtDNA variants were passed on to children. This effect was influenced by the mother's nuclear genetic background. Thus, mtDNA is under selection at specific loci in the human germ line.

    Science, this issue p. eaau6520

  12. Immunology

    A crystal-clear ingredient for allergy?

    1. Seth Thomas Scanlon

    Charcot-Leyden crystals (CLCs) are formed from the eosinophil granule protein galectin-10 (Gal10) and found in severe eosinophil-associated diseases like asthma and chronic rhinosinusitis. Whether CLCs actively contribute to disease pathogenesis is unknown. Persson et al. found that lab-grown Gal10 crystals are biosimilar to CLCs (see the Perspective by Allen and Sutherland). When given to mice, the crystals acted as a type 2 adjuvant, mimicking many of the features of human asthma. In contrast, a Gal10 mutein unable to crystallize had no effect. Antibodies against epitopes crucial for Gal10 autocrystallization could dissolve both in vitro–generated Gal10 crystals and patient-derived CLCs. Furthermore, these anti-Gal10 antibodies reversed the effects of Gal10 crystals in a humanized mouse model of asthma, suggesting a potential therapeutic approach for crystallopathies more broadly.

    Science, this issue p. eaaw4295; see also p. 738

  13. Neuroscience

    What inhibits the inhibitors?

    1. Peter Stern

    In the hippocampus, each memory trace is encoded by a specific subset of pyramidal cells. The other pyramidal cells must be actively excluded from the memory encoding process by inhibition, which is done by selective dendrite-targeting interneurons. Szőnyi et al. found that γ-aminobutyric acid–releasing (GABAergic) cells located in a small region in the brain stem called the nucleus incertus project to the hippocampus. The nucleus incertus again is innervated by several regions that respond to salient stimuli. Its GABAergic cells preferentially inhibit the dendrite-targeting interneurons in the hippocampus. The nucleus incertus is thus a central mediator between brain regions that are highly responsive to salient stimuli and the hippocampal circuitry involved in memory formation.

    Science, this issue p. eaaw0445

  14. Industrial Catalysis

    More-efficient heating

    1. Phil Szuromi

    Large-scale production of hydrogen through steam reforming directly produces CO2 as a side product. In addition, the heating of reactors through fossil-fuel burning contributes further CO2 emissions. One problem is that the catalyst bed is heated unevenly, which renders much of the catalyst effectively inactive. Wismann et al. describe an electrical heating scheme for a metal tube reactor that improves the uniformity of heating and catalyst usage (see the Perspective by Van Geem et al.). Adoption of this alternative approach could affect CO2 emissions by up to approximately 1% of global emissions.

    Science, this issue p. 756; see also p. 734

  15. Optical Metrology

    Superoscillatory displacement metrology

    1. Ian S. Osborne

    The resolving power of light (or other waveforms, for that matter) is typically limited to about half the wavelength. However, multiple interference of waves gives rise to subwavelength “hotspots” in the phase owing to what is termed superoscillation of the wave field. Yuan and Zheludev used a specially designed metasurface to interfere laser light (wavelength λ = 800 nm) and created a superoscillatory ruler comprising these hotspots. They demonstrated the ability to measure displacements of around λ/800 while operating at a wavelength of 800 nm. They then showed theoretically that resolving powers of around λ/4000, i.e., atomic-scale displacements, may be possible. The technique should prove useful to metrology applications requiring precision measurements.

    Science, this issue p. 771

  16. Enzymology

    Divergent protein kinase

    1. Caroline Ash

    SidJ is a protein produced by Legionella pneumophila that orchestrates this intracellular pathogen's establishment within the host cell. SidJ prevents lysosome fusion with the vacuole, within which the bacterium resides and replicates. SidJ also modulates the toxicity of the SidE family ubiquitin ligases that catalyze phosphoribosyl-linked host protein ubiquitination. Black et al. discovered that SidJ is activated by host calmodulin. Furthermore, although SidJ has a pseudokinase fold, it does not phosphorylate SidE proteins but polyglutamylates them instead. The in vivo relevance of this mechanism for bacterial infectivity was verified in the natural reservoir host Acanthamoeba castellanii.

    Science, this issue p. 787

  17. Emerging Infections

    mRNA-based passive immunotherapy

    1. Ifor Williams

    Passive transfer of neutralizing antibodies can protect against disease caused by chikungunya virus, an emerging mosquito-borne pathogen. However, effective treatment of chikungunya-infected patients with symptomatic disease using antibodies will require identification of high-potency immunoglobulins and an efficient platform for delivering them to patients. Kose et al. screened immortalized human B cells from a chikungunya survivor and identified a monoclonal immunoglobulin G (IgG) antibody with exceptional neutralizing capacity. Intravenous injection of a lipid nanoparticle–encapsulated mRNA molecule encoding this antibody protected mice against viral infection and virus-associated arthritis. It also induced protective concentrations of serum antibody in macaques. These preclinical results pave the way for translational clinical trials of mRNA-based passive immunotherapy for human chikungunya infection.

    Sci. Immunol. 4, eaaw6647 (2019).

  18. Immunology

    IRF2 induces gasdermin D for pyroptosis

    1. John F. Foley

    Inflammasome activation triggers the cleavage of the protein gasdermin D. The N-terminal fragments oligomerize and form pores in the plasma membrane, leading to the release of the inflammatory cytokine interleukin-1β (IL-1β) and cell death by pyroptosis. Kayagaki et al. found that loss of the transcriptional regulator IRF2 reduced gasdermin D levels in mice and in human cells, resulting in decreases in IL-1β secretion and pyroptosis in response to inflammasome activation. Thus, like gasdermin D, IRF2 might also be a therapeutic target for the treatment of sepsis and other inflammasome-mediated diseases.

    Sci. Signal. 12, eaax4917 (2019).