This Week in Science

Science  16 Feb 2018:
Vol. 359, Issue 6377, pp. 756
  1. Influenza

    Investigating flu vaccine effectiveness

    1. Lindsey Pujanandez

    Studying samples after flu vaccination suggests that immunological memory cells reside outside the vasculature.

    CREDIT: (PHOTO) AP PHOTO/CAROLYN KASTER

    Seasonal influenza vaccines have been recommended for decades, but studies focused on antigen-specific lymphocytes in humans are sparse. Koutsakos et al. examined longitudinal samples of influenza-vaccinated individuals to determine what responses generate protective immunity. Vaccination could induce circulating T follicular helper memory cells, antibody-secreting cells, and memory B cells, but it did not seem to affect other types of lymphocytes. Existing antibodies against influenza at the time of vaccination dampened these responses. The authors probed different tissues for influenza memory B cells, which they found outside the circulation. Better targeting of these cells might improve influenza vaccine efficacy.

    Sci. Transl. Med. 10, eaan8405 (2018).

  2. Biochemistry

    How lipopolysaccharides bridge the gap

    1. Stella M. Hurtley

    The outer membrane of Gram-negative bacteria is composed of lipopolysaccharide, a large glycolipid that prevents drugs from entering the cells. Disrupting lipopolysaccharide assembly hypersensitizes bacteria to antibiotics. Sherman et al. used biochemical tools to observe lipopolysaccharide transport. Seven proteins, which are conserved in all Gram-negative bacteria, appear to form a protein bridge that uses adenosine triphosphate to power transport of lipopolysaccharide from one membrane to another. The ability to monitor intermembrane transport of lipopolysaccharide will help in efforts to develop and characterize inhibitors.

    Science, this issue p. 798

  3. Cancer

    SNF'ing out antitumor immunity

    1. Paula A. Kiberstis

    Immune checkpoint inhibitors induce durable tumor regressions in some, but not all, cancer patients. Understanding the mechanisms that determine tumor sensitivity to these drugs could potentially expand the number of patients who benefit (see the Perspective by Ghorani and Quezada). Pan et al. discovered that tumor cells in which a specific SWI/SNF chromatin remodeling complex had been experimentally inactivated were more sensitive to T cell–mediated killing. The cells were more responsive to interferon-γ, leading to increased secretion of cytokines that promote antitumor immunity. Miao et al. examined the genomic features of tumors from patients with metastatic renal cell carcinoma who had been treated with immune checkpoint inhibitors. Tumors harboring inactivating mutations in PBRM1, which encodes a subunit of the same SWI/SNF complex, were more likely to respond to the drugs.

    Science, this issue p. 770, p. 801; see also p. 745

  4. Microbiology

    CRISPR-Cas accelerates phage evolution

    1. Trudy Morrison

    Despite the growing use of the CRISPR-Cas system for targeted mutagenesis, little attention has been paid to understanding the basic biology of this defense system in bacteria-phage relationships. Rao et al. suggest that the system is a driver of phage, and perhaps bacterial, evolution. The authors characterized phage escape mutants restricted by high- and low-restriction spacers. Although the frequency of phage mutants that escaped high-restriction sequences was predictably low, the mutation frequency of phages that escaped low-restriction sequences was extremely high, about six orders of magnitude greater than spontaneous mutation frequencies.

    Sci. Adv. 10.1126/sciadv.aar4134 (2018).

  5. Structural Immunology

    Recognizing danger signals

    1. Valda Vinson

    In the classical complement pathway, the C1 initiation complex binds to danger patterns on the surface of microbes or damaged host cells and triggers an immune response. Immunoglobulin G (IgG) antibodies form hexamers on cell surfaces that have high avidity for the C1 complex. Ugurlar et al. used cryo–electron microscopy to show how a hexamer of C1 complexes interacts with the IgG hexamer. Structure-guided mutagenesis revealed how C1 is activated to trigger an immune response.

    Science, this issue p. 794

  6. Applied Physics

    It's a wrap

    1. Marc S. Lavine

    Whether an object has a regular or irregular shape, wrapping it with a thin film can be challenging. Kumar et al. released droplets of oil above thin polymer sheets floating on water (see the Perspective by Amstad). With sufficient impact force, the polymer wrapped around the droplet with near perfect seams. The shape of the resulting enclosed drop depended on the shape of the sheet initially placed at the air-liquid interphase.

    Science, this issue p. 775; see also p. 743

  7. Quantum Optics

    Forming photonic bound states

    1. Ian S. Osborne

    Photons do not naturally interact with each other and must be coaxed into doing so. Liang et al. show that a gas of Rydberg atoms—a cloud of rubidium atoms excited by a sequence of laser pulses—can induce strong interactions between propagating photons. The authors could tune the strength of the interaction to make the photons form dimer and trimer bound states. This approach should prove useful for producing novel quantum states of light and quantum entanglement on demand.

    Science, this issue p. 783

  8. Neuroscience

    A way to prevent generalized seizures?

    1. Peter Stern

    Temporal lobe epilepsy is the most common form of epilepsy in adults. Patients have spontaneous seizures and risk developing serious cognitive impairment. Bui et al. studied an animal model of temporal lobe epilepsy (see the Perspective by Scharfman). Selective optogenetic inhibition of dentate gyrus mossy cells increased the likelihood of electrographic seizures generalizing to full behavioral convulsive seizures. Activation of mossy cells reduced the likelihood. Thus, the activity of mossy cells might serve to inhibit seizure propagation.

    Science, this issue p. 787; see also p. 740

  9. Atmospheric Chemistry

    Air pollution evolution

    1. H. Jesse Smith

    Transport-derived emissions of volatile organic compounds (VOCs) have decreased owing to stricter controls on air pollution. This means that the relative importance of chemicals in pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products has increased. McDonald et al. show that these volatile chemical products now contribute fully one-half of emitted VOCs in 33 industrialized cities (see the Perspective by Lewis). Thus, the focus of efforts to mitigate ozone formation and toxic chemical burdens need to be adjusted.

    Science, this issue p. 760; see also p. 744

  10. Organic Chemistry

    Left- or right-handed C–H bond activation

    1. Jake Yeston

    Although organic compounds consist mostly of carbon and hydrogen atoms, strategies for chemical synthesis have traditionally targeted the handful of more reactive interspersed oxygens, nitrogens, and halogens. Modifying C–H bonds directly is a more appealing approach, but selectivity remains a challenge. Saint-Denis et al. review recent progress in using transition metal catalysis to break just one of two mirror-image C–H bonds and then append a more complex substituent in its place. Ligand design has proven crucial to differentiate these otherwise similar bonds in a variety of molecular settings.

    Science, this issue p. eaao4798

  11. Evolutionary Ecology

    Estimating the predictability of evolution

    1. Laura M. Zahn

    Evolution results from expected effects, such as selection driving alleles toward fixation, and stochastic effects, such as unusual environmental variation and genetic drift. To determine the potential to predict evolutionary change, Nosil et al. examined three naturally occurring morphs of stick insects (see the Perspective by Reznick and Travis). They wanted to determine which selective parameters could be used to foresee changes, despite varying environmental conditions. One morph fit a model of negative frequency-dependent selection, likely owing to predation, but changes in other morph frequencies remained unpredictable. Thus, for specific cases, we can forecast short-term changes within populations, but evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions.

    Science, this issue p. 765; see also p. 738

  12. Peptide Modification

    Protein backbone, broken and mended

    1. Michael A. Funk

    Small, posttranslationally modified peptides are produced by microorganisms as antimicrobial agents or to communicate with neighboring cells. Alterations to the peptide backbone can change the structure of peptides or introduce reactive chemical moieties. Morinaka et al. characterized a bacterial enzyme that excises the side chain and α-carbon of a tyrosine residue from a short peptide, leaving behind an α-ketoamide. This backbone functional group is found in some protease inhibitors and is a valuable handle for bio-orthogonal chemistry. The enzyme accepts peptide substrates with a short recognition motif, suggesting that it could be used to generate libraries of modified peptides.

    Science, this issue p. 779

  13. Ecosystem Services

    Many, many more pollinators needed

    1. Sacha Vignieri

    Numerous studies have shown that biodiversity is necessary for ecosystem function. The majority of these, however, have taken place at relatively small experimental scales. Winfree et al. looked across more than 3000 square kilometers for relationships between biodiversity and crop pollination (see the Perspective by Kremen). The number of wild bee species required for successful pollination rapidly increased with spatial scale, largely owing to variation in the species present across sites and the degree to which the most abundant species played a role. In the end, more than an order of magnitude more species than predicted by smaller-scale experiments were required for full ecosystem functioning.

    Science, this issue p. 791; see also p. 741

  14. Development

    A primitive role for ATF6

    1. Leslie K. Ferrarelli

    The unfolded protein response (UPR) preserves endoplasmic reticulum (ER) homeostasis in mature cells. However, inactivating mutations in the UPR-associated transcription factor ATF6 cause congenital vision defects, suggesting a developmental role for ATF6 as well. Kroeger et al. found that ATF6 was critical to stem cell differentiation into the mesodermal lineage, in part by promoting ER expansion during cell differentiation. Activating ATF6 in cultured stem cells resulted in the generation of functional vascular endothelial cells, suggesting a potential strategy to facilitate mesodermal tissue production for research or therapy.

    Sci. Signal. 11, eaan5785 (2018).