This Week in Science

Science  25 Oct 2019:
Vol. 366, Issue 6464, pp. 440
  1. Neurodevelopment

    Close-up of human cerebellar development

    1. Pamela J. Hines

    Fluorescence microscopy image of a developing human cerebellum


    Early on, cerebellar development shares similarities across humans, nonhuman primates, and even mice. But differences emerge while development progresses, as cellular and molecular analyses by Haldipur et al. now reveal. The rhombic lip persists longer during cerebellar development in humans than in either the mouse or the macaque and generates a pool of neuroprogenitor cells. Similarly, the ventricular zone of the human cerebellum goes a step further than that of the mouse in developing an additional proliferative layer with outer radial glia cells. Transcriptome analysis revealed detailed similarities and differences between progenitor cells of the developing human cerebellum and neocortex.

    Science, this issue p. 454

  2. Influenza

    Alternative influenza target

    1. Caroline Ash

    There is a pressing need for a broadly protective influenza vaccine that can neutralize this constantly varying, deadly virus. Stadlbauer et al. turned their attention away from the current vaccine target—the mutable hemagglutinin—and investigated an alternative, less variable virus-coat glycoprotein: neuraminidase. The authors extracted monoclonal antibodies (mAbs) from a human donor naturally infected with the H3N2 virus subtype. In mice, the mAbs were broadly protective against influenza virus A groups 1 and 2 (human, avian, and swine origin) and some influenza B viruses. These mAbs were also therapeutically effective as late as 72 hours after infection. The wide range of reactivity probably relates to the infection history of the donor, whose plasmablasts generated antibodies with long regions that insert into the active site of the neuraminidase enzyme.

    Science, this issue p. 499

  3. Social Sciences

    Measuring street protest events

    1. Aaron Clauset

    Street protests and popular marches are an important form of political expression, and how they are measured shapes our ability to understand their social significance. Fisher et al. review the growing research on protest events and crowd forming, with a focus on events following the 2016 U.S. election. They describe best-practice methods for measuring protest size and protester motivation and making such protest data publicly available in real time. Such methods help us understand who protests and why and enable better assessments of the social and political impact of protests.

    Sci. Adv. 10.1126/sciadv.aaw5461 (2019).

  4. Cell Engineering

    Tea for type 1 and type 2 diabetes

    1. Caitlin Czajka

    Cell therapy is a promising approach for treating diabetes. Yin et al. developed an elegant control system by engineering cells to respond to protocatechuic acid, a metabolite in green tea. Orally ingested protocatechuic acid regulated blood glucose by triggering secretion of insulin or a short variant of human glucagon–like peptide 1 from engineered cells implanted in mouse and nonhuman primate models of type 1 and type 2 diabetes. This study demonstrates the versatility of synthetic biology for developing remotely controlled cell-based therapies for diabetes.

    Sci. Transl. Med.11, eaav8826 (2019).

  5. Economics

    Racial bias in health algorithms

    1. Tage S. Rai

    The U.S. health care system uses commercial algorithms to guide health decisions. Obermeyer et al. find evidence of racial bias in one widely used algorithm, such that Black patients assigned the same level of risk by the algorithm are sicker than White patients (see the Perspective by Benjamin). The authors estimated that this racial bias reduces the number of Black patients identified for extra care by more than half. Bias occurs because the algorithm uses health costs as a proxy for health needs. Less money is spent on Black patients who have the same level of need, and the algorithm thus falsely concludes that Black patients are healthier than equally sick White patients. Reformulating the algorithm so that it no longer uses costs as a proxy for needs eliminates the racial bias in predicting who needs extra care.

    Science, this issue p. 447; see also p. 421

  6. Nanomaterials

    Milling corundum nanoparticles

    1. Phil Szuromi

    High-purity corundum (α-Al2O3) nanoparticles could enable applications such as more stable catalyst supports or precursors for high-strength ceramics. Milling of corundum only produces micrometer-scale particles, and direct synthesis from other aluminum oxides that would be likely starting materials, such as γ-Al2O3, fails because of the high activation barrier for converting the lattice structure of these cubic close-packed oxides. Amrute et al. show that ball milling of boehmite, γ-AlOOH, created ∼13-nanometer-diameter corundum nanoparticles of high purity through a mechanically induced dehydration reaction and by the effect of milling impacts on the surface energy of the particles.

    Science, this issue p. 485

  7. Biogeography

    Earthworm distribution in global soils

    1. Andrew M. Sugden

    Earthworms are key components of soil ecological communities, performing vital functions in decomposition and nutrient cycling through ecosystems. Using data from more than 7000 sites, Phillips et al. developed global maps of the distribution of earthworm diversity, abundance, and biomass (see the Perspective by Fierer). The patterns differ from those typically found in aboveground taxa; there are peaks of diversity and abundance in the mid-latitude regions and peaks of biomass in the tropics. Climate variables strongly influence these patterns, and changes are likely to have cascading effects on other soil organisms and wider ecosystem functions.

    Science, this issue p. 480; see also p. 425

  8. Ferroelectrics

    Flexible ferroelectrics

    1. Brent Grocholski

    High-quality ferroelectric materials, which polarize in response to an electric field, are usually oxides that crack when bent. Dong et al. found that high-quality membranes of barium titanate are surprisingly flexible and super-elastic. These films accommodate large strains through dynamic evolution of nanodomains during deformation. This discovery is important for developing more robust flexible devices.

    Science, this issue p. 475

  9. Renewable Energy

    A multifaceted future for wind power

    1. Jake Yeston

    Modern wind turbines already represent a tightly optimized confluence of materials science and aerodynamic engineering. Veers et al. review the challenges and opportunities for further expanding this technology, with an emphasis on the need for interdisciplinary collaboration. They highlight the need to better understand atmospheric physics in the regions where taller turbines will operate as well as the materials constraints associated with the scale-up. The mutual interaction of turbine sites with one another and with the evolving features of the overall electricity grid will furthermore necessitate a systems approach to future development.

    Science, this issue p. eaau2027

  10. Microbiota

    One world, one health

    1. Caroline Ash

    As people increasingly move to cities, their lifestyles profoundly change. Sonnenburg and Sonnenburg review how the shift of recent generations from rural, outdoor environments to urbanized and industrialized settings has profoundly affected our biology and health. The signals of change are seen most strikingly in the reduction of commensal microbial taxa and loss of their metabolic functions. The extirpation of human commensals is a result of bombardment by new chemicals, foodstuffs, sanitation, and medical practices. For most people, sanitation and readily available food have been beneficial, but have we now reached a tipping point? How do we “conserve” our beneficial symbionts and keep the pathogens at bay?

    Science, this issue p. eaaw9255

  11. Immunology

    Commensals rule the MAITrix

    1. Seth Thomas Scanlon

    Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT cells recognize microbial small molecules presented by the major histocompatibility complex class Ib molecule MR1. MAIT cells are absent in germ-free mice, and the mechanisms by which microbiota control MAIT cell development are unknown (see the Perspective by Oh and Unutmaz). Legoux et al. show that, in mice, development of MAIT cells within the thymus is governed by the bacterial product 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil, which rapidly traffics from the mucosa to the thymus, where it is captured by MR1 and presented to developing MAIT cells. Constantinides et al. report that MAIT cell induction only occurs during a limited, early-life window and requires exposure to defined microbes that produce riboflavin derivatives. Continual interactions between MAIT cells and commensals in the skin modulates tissue repair functions. Together, these papers highlight how the microbiota can direct immune cell development and subsequent function at mucosal sites by secreting compounds that act like self-antigens.

    Science, this issue p. 494, p. eaax6624; see also p. 419

  12. Plant Biology

    Plant thirst quenched without water

    1. Pamela J. Hines

    Drought causes many billions of dollars of annual losses to farmers worldwide. Central to a plant's water use efficiency are signaling pathways regulated by the hormone abscisic acid and its receptors. Vaidya et al. screened a pool of candidate small molecules and used structure-guided design to optimize the function of an abscisic acid receptor agonist (see the Perspective by Phillips and Sussman). Application of the agonist protected Arabidopsis, wheat, and tomato from underwatering.

    Science, this issue p. eaaw8848; see also p. 416

  13. Innate Immunity

    NODs require S-palmitoylation to signal

    1. Stella M. Hurtley

    The compartmentalization of proteins within the cell is essential for their function. The addition of lipid molecules redistributes proteins to the cell surface or to membrane-bound organelles. Working in transgenic mice and in tissue cultured cells, Lu et al. found that nucleotide oligomerization domain–like receptors 1 and 2 (NOD1 and NOD2), two proteins responsible for detecting bacterial products, required lipid modifications for their recruitment to the cell membrane and function. The specific modification, palmitoylation at a cysteine thiol, was mediated by the enzyme ZDHHC5. Loss of ZDHHC5 or removal of key modification residues in NOD1 and NOD2 abolished their function, compromising antibacterial responses. Human variants of NOD2 display altered palmitoylation, which could help to explain many inflammatory conditions, such as irritable bowel syndrome.

    Science, this issue p. 460

  14. Structural Biology

    Complex regulation

    1. Valda Vinson

    The protein kinase mTORC1 controls cellular growth in response to external signals. In the presence of nutrients, it localizes on the surface of the lysosome, where it is activated. The Raptor domain of mTORC1 binds to a complex comprising the protein Ragulator and a heterodimer of the Rag guanosine triphosphatase, which can adopt four different nucleotide conformations depending on nutrient availability. Rogala et al. determined the structure of the Raptor-Rag-Ragulator complex at 3.2-angstrom resolution by cryo–electron microscopy. The structure shows why Raptor binds only to a specific nucleotide conformation of the Rag heterodimer and suggests a model for how mTORC1 would dock onto the lysosomal surface, which is a key step in its activation.

    Science, this issue p. 468

  15. Mutation

    Genetic background affects variation

    1. Laura M. Zahn

    Robustness, or the effect of mutations on fitness, can affect the evolutionary trajectory of a species. By introducing a large number of deleterious mutations into many different genetic backgrounds of yeast, Johnson et al. found that, for many mutations, the more fit the background, the larger the deleterious effect of the mutation (see the Perspective by Miller). A more-fit lineage is thus less tolerant to deleterious mutations, whereas less-fit lineages can tolerate more mutations. This observation supports a tendency toward diminishing returns for beneficial mutations, which has been shown to influence patterns of adaptation.

    Science, this issue p. 490; see also p. 418

  16. Structural Biology

    Coupled transport

    1. Valda Vinson

    Cation-chloride cotransporters move chloride and cations across the cell membrane and are important in regulating cell volume and setting the chloride concentration inside the cell. Mutations lead to serious diseases, such as epilepsy. Liu et al. present the structure of the human potassium-chloride cotransporter KCC1, as determined by cryo–electron microscopy. Based on the structure, functional studies, and molecular dynamics simulations, they propose an ion transport model. The structure provides a framework for interpreting disease-related mutations in potassium-chloride cotransporters.

    Science, this issue p. 505

  17. Tumor Immunology

    Interior tumor views

    1. Christiana N. Fogg

    Previous studies indicate that a high frequency of intratumoral neutrophils is associated with a poor clinical prognosis. Si et al. used microscopy and imaging techniques to examine how intratumoral interactions between tumor-associated neutrophils (TANs) and tumor-infiltrating lymphocytes (TILs) can affect TIL function. They localized functional cell subsets, which were then used to identify hotspots of TAN-TIL interactions within tumors. Some of these TANs had a distinct phenotype, and their physical association with TILs reduced antitumor functions of those TILs.

    Sci. Immunol. 4, eaaw9159 (2019).

  18. Immunometabolism

    Metabolic quiescence for B cell maturity

    1. Erin Williams

    Transitional B cell precursors mature into follicular B cells, which are involved in antibody responses. Farmer et al. discovered a metabolic checkpoint in this developmental process. Compared with transitional B cells, mouse and human follicular B cells were metabolically quiescent and had increased activation of the kinase AMPK and increased levels of the cell surface ectoenzymes CD39 and CD73, which generate extracellular adenosine. Transitional human B cells that expressed CD73 or were exposed to an AMPK agonist preferentially acquired a follicular B cell phenotype.

    Sci. Signal. 12, eaaw5573 (2019).

  19. Spin Physics

    Coherent surface spin manipulation

    1. Phil Szuromi

    Spin-based quantum information processing requires coherent spin manipulation. Yang et al. demonstrate coherent control of surface titanium and iron atom spins on a magnesium oxide surface with a magnetic scanning tunneling microscope tip. Arbitrary sequences of fast electrical pulses delivered to the top induced large electric fields. These fields drove metal-atom movement, which then modulated the tip-atom exchange interaction to create an oscillating effective magnetic field. Advanced spin-control protocols such as Ramsey fringes and Hahn spin echoes revealed quantum dynamics, such as coherent oscillations in a titanium atom dimer assembled on the surface with the tip.

    Science, this issue p. 509

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