This Week in Science

Science  29 Nov 2019:
Vol. 366, Issue 6469, pp. 1090
  1. Molecular Biology

    The fitness landscape of AAV

    1. Steve Mao

    Computer-generated image of the atomic structure of adeno-associated virus

    CREDIT: SCIENCE PICTURE CO/SCIENCE SOURCE

    Adeno-associated virus (AAV) is an important gene therapy vector. Using tools from synthetic biology, Ogden et al. provide a comprehensive view of how sequence changes in capsid proteins affect AAV properties. After saturation mutagenesis of the AAV2 capsid gene, the resulting library was subjected to multiplexed phenotypic analyses, including virus production, immunity, thermostability, and biodistribution. The mutant distribution to major organs in mice revealed dominant trends affecting in vivo delivery. Moreover, the findings uncovered a viral accessory protein with a role in viral production. Finally, a model built from the capsid fitness landscape enabled machine-guided design of useful variants with much higher efficiency than random mutagenesis.

    Science, this issue p. 1139

  2. Superconductivity

    A sharp boundary in the cuprates

    1. Jelena Stajic

    Many physicists working on cuprate superconductors believe that the so-called strange metal phase in the cuprate phase diagram is associated with a quantum critical point. Within this picture, the quantum critical point gives rise to a V-shaped region in the doping-temperature phase diagram of the cuprates: the strange metal phase. Chen et al. used angle-resolved photoemission spectroscopy in the cuprate family Bi2212 to challenge this view. By taking comprehensive measurements as a function of doping and temperature—and making sure that the signal was not affected by environmental conditions—they found an incoherent strange metal phase that was sharply separated from a conventional phase by a temperature-independent vertical line in the phase diagram.

    Science, this issue p. 1099

  3. Elastocalorics

    A million times cooler

    1. Brent Grocholski

    Elastocaloric materials can be used for solid-state cooling applications because they can pump heat out of a system using a reversible phase transformation. However, many such materials fail after a small number of cycles. Hou et al. found that laser melting of elastocaloric metals can create fatigue-resistant microstructures. A nickel-titanium–based alloy could be cycled a million times and still produce a cooling of about 4 kelvin. This processing method could improve elastocaloric performance and move us closer to using these materials more widely for solid-state cooling applications.

    Science, this issue p. 1116

  4. Materials Science

    Growing polymer brushes from surfaces

    1. Marc S. Lavine

    Surface functionalization is important in a broad range of fields. One approach involves polymer brushes, where polymer chains are grafted onto a surface. Cai et al. describe the nanoscale functionalization of surfaces by exploiting the living crystallization-driven self-assembly of polyferrocenyl-based block copolymers (see the Perspective by Presa Soto). Small crystalline cylindrical micelle seeds were attached using noncovalent bonds to a variety of surfaces, including silicon wafers, graphene oxide nanosheets, and gold. Addition of dissolved unimers over the seed-coated surfaces allowed micellar brushes to grow. Protonation and postdecoration with gold and silver nanoparticles demonstrated the applicability of such modified surfaces in catalysis, as antibacterial agents, and in separation processes.

    Science, this issue p. 1095; see also p. 1078

  5. Enhancer Genomics

    Linking enhancers to disease

    1. Laura M. Zahn

    Enhancers are genomic regions that regulate gene expression, sometimes in a cell-dependent manner. However, most of our knowledge of human brain cell–type enhancers derives from studies of bulk human brain tissue. Nott et al. examined chromatin and promoter activity in cell nuclei isolated from human brains. Genetic variants associated with brain traits and disease showed cell-specific patterns of enhancer enrichment. These data indicate that Alzheimer's disease is regulated by genetic variants within microglial cells, whereas psychiatric diseases tend to affect neurons.

    Science, this issue p. 1134

  6. Microbiome

    Lactose can fuel GVHD

    1. Priscilla N. Kelly

    Allogeneic hematopoietic cell transplantation (allo-HCT) is used to treat certain hematopoietic malignancies, but patients have a risk of developing graft-versus-host disease (GVHD). Stein-Thoeringer et al. performed a large-scale analysis of more than 1300 patients treated with allo-HCT across four clinical centers (see the Perspective by Zitvogel and Kroemer). High levels of bacteria from the Enterococcus genus were associated with greater incidence of GVHD and mortality. Lactose appears to provide a substrate for Enterococcus growth, and patients with a lactose-malabsorption genotype had a greater abundance of Enterococcus. A lactose-free diet limited Enterococcus growth, reduced the severity of GVHD, and improved survival in gnotobiotic mouse models.

    Science, this issue p. 1143; see also p. 1077

  7. HIV

    Early to treat, early to thrive

    1. Lindsey Pujanandez

    Timing of antiretroviral therapy (ART) initiation for HIV can influence viral-reservoir seeding and also the immune response. However, this has not been well characterized in neonatal HIV infection. To discern how ART affects neonates, Garcia-Broncano et al. studied infants from Botswana who were placed on ART hours or months after birth. Early initiation of therapy reduced seeding of the viral reservoir and also modulated natural killer cell and T cell responses to HIV. Thus, immediate ART initiation—earlier than the current guidelines of a few weeks—could provide real benefit to infants with HIV.

    Sci. Transl. Med. 11, eaax7350 (2019).

  8. Tumor Immunotherapy

    New cell therapy fights brain tumors

    1. Sarah M. Fortune

    An adoptive cellular therapy that expands clonal T cells could help fight deadly heterogeneous brain tumors, medulloblastoma, and glioblastoma. Working in mice, Flores et al. used dendritic cells expressing tumor RNA to expand polyclonal T cells that quickly react against a variety of different antigens within different brain tumors. Promising results were also obtained in a patient with recurrent medulloblastoma. Although previous adoptive T cell therapies have proven effective against several advanced cancers, the current method could provide patients with effective T cell therapy for brain tumors.

    Sci. Adv. 10.1126/sciadv.aav9879 (2019).

  9. Neuroscience

    Brain anatomy revealed in startling detail

    1. Peter Stern

    The mammalian cerebral cortex is an enormously complex network of neuronal processes that are long and thin, branching, and extremely densely packed. This high packing density has made the reconstruction of cortical neuronal networks challenging. Motta et al. used advanced automated imaging and analysis tools to reconstruct with high spatial resolution the morphological features of 89 neurons and their connections in the mouse barrel cortex. The reconstruction covered an area more than two orders of magnitude larger than earlier neuroanatomical mapping attempts. This approach revealed information about the connectivity of inhibitory and excitatory synapses of corticocortical as well as excitatory thalamocortical connections.

    Science, this issue p. eaay3134

  10. Seismology

    Marine observations with optics

    1. Brent Grocholski

    Placing sensors on the seafloor is difficult, but a sensor network has huge potential for observing processes occurring both below and above the seafloor. Lindsey et al. measured acoustic vibrations collected by attaching a laser to the Monterey Accelerated Research System's subsea optical fiber during a maintenance period (see the Perspective by Jousset). Acoustic waves were monitored by changes in laser light along the cable. The observations from just a few days allowed mapping of an unknown fault system and detection of several dynamic processes in the water column above.

    Science, this issue p. 1103; see also p. 1076

  11. Quantum Materials

    Controlling quantum defects in graphene

    1. Ian S. Osborne

    The development of quantum technologies relies on the ability to fabricate and engineer materials with robust quantum properties. The controlled introduction of defects in semiconductors is one of the most promising platforms under development. With the capability to precisely position point defects (five-membered rings) in the graphene honeycomb lattice, Lombardi et al. explored recent theoretical work suggesting that such defects should display enhanced quantum properties (see the Perspective by von Kugelgen and Freedman). The spin-bearing properties of the defects and the engineered control of their interactions open up exciting possibilities for graphene-based spintronics and quantum electronics.

    Science, this issue p. 1107; see also p. 1070

  12. Chemical Physics

    Glimpsing an exchange of partners

    1. Jake Yeston

    When two diatomic molecules collide, they can sometimes swap partners. For instance, two potassium-rubidium (KRb) molecules can produce K2 and Rb2. The four-atom intermediate formed upon collision is typically too scarce and short-lived to spot, even using ultrafast techniques. Hu et al. circumvented this problem by studying the reaction at temperatures approaching 0 kelvin. Using a combination of mass spectrometry and velocity-map imaging, the authors directly characterized the ionized K2Rb2 complex as well as the reactant and product populations.

    Science, this issue p. 1111

  13. Neuroscience

    Keeping tabs on bad experiences

    1. Peter Stern

    Identifying the neural basis underlying how we acquire, process, and store negative experiences could help the search for effective treatments for mood disorders. Szőnyi et al. used a range of neuroscientific tools to elucidate the role of a specific neural circuit that originates in the median raphe region of the murine brainstem (see the Perspective by Ikemoto). A subpopulation of excitatory neurons projected to aversive brain areas and received recurrent feedback from the lateral habenula and convergent feedback from a range of fear-related circuitry. These neurons were activated by aversive stimuli, and artificial stimulation promoted aversion or anxiety-related behavior. This group of cells thus plays a pivotal role in a network that helps to mediate aversive motivation.

    Science, this issue p. eaay8746; see also p. 1071

  14. Magnonics

    Toward magnonic devices

    1. Jelena Stajic

    The field of magnonics aims to use spin waves (SWs) and their associated quasiparticles—magnons—as carriers of information. Compared with the movement of charge in conventional electronics, a major advantage of SWs is reduced Joule heating. However, SWs are trickier to direct and control. Two groups now go a step further toward magnon-based devices. Han et al. show that in multilayer films, domain walls can be used to change the phase and magnitude of a spin wave. Wang et al. demonstrate how magnon currents can be used to switch the magnetization of an adjacent layer.

    Science, this issue p. 1121, p. 1125

  15. Biochemistry

    CTP hydrolysis organizes chromosomes

    1. Steve Mao

    The bacterial DNA parS centromere recruits the ParB protein to the bacterial chromosome. Soh et al. found that the widespread family of ParB proteins not only bind DNA but also bind and hydrolyze cytidine triphosphate (CTP) (see the Perspective by Funnell). ParB CTP hydrolysis is stimulated by parS and regulates the spreading of ParB protein to the parS flanking regions, which is crucial for organizing the bacterial chromosome. The cytidine triphosphatase domain is conserved in a large variety of protein sequences, suggesting its potential roles in other cellular processes.

    Science, this issue p. 1129; see also p. 1072

  16. Protein Folding

    A pathway for helical membrane proteins

    1. Valda Vinson

    Membrane proteins are inserted into cell membranes while they are being translated and may fold concurrently into their secondary and tertiary structures. Choi et al. describe a single-molecule force microscopy technique that allowed them to monitor folding of helical membrane proteins in vesicles and bicelles. Two helical membrane proteins, the Escherichia coli rhomboid protease GlpG and the human β2-adrenergic receptor, both folded from the N to the C terminus, with structures forming in units of helical hairpins. In the cell, this would allow these proteins to begin folding while being translated.

    Science, this issue p. 1150

  17. Immunology

    Microbiota influence vaccine responses

    1. Gemma Alderton

    Responses to vaccines can be variable, and recent findings suggest a potential explanation may lie in the influence of gut microbiota. In a Perspective, Pulendran discusses how systematic analyses of vaccination responses—for example, to the influenza vaccine—are revealing insights into vaccine responses and the importance of the gut microbiota in forming immunogenicity to infectious disease. This has implications for vaccine design and for stratifying individuals according to likely vaccine response.

    Science, this issue p. 1074

  18. T Cells

    Charting MAIT cell development

    1. Ifor Williams

    Mucosal-associated invariant T (MAIT) cells are a distinct subset of T cells that recognize vitamin B metabolites presented by major histocompatibility complex class I–related protein (MR1). Koay et al. used bulk and single-cell RNA sequencing and flow cytometric analysis to characterize the development of murine and human MAIT cells. In addition to providing a clearer picture of MAIT cell development in the thymus, the studies uncovered several molecules that play key roles in regulating this process. Genetic inactivation experiments in mice confirmed the functions some of these molecules—including SAP, SATB1, CXCR6, and CCR7—in regulating MAIT cell development.

    Sci. Immunol. 4, eaay6039 (2019).

  19. Innate Immunity

    A convergence for RNA and DNA sensing

    1. Erin Williams

    In response to cytosolic DNA, cyclic GMP-AMP synthase (cGAS) initiates a type I interferon response. Hu et al. found that endogenous cGAS bound to the nucleotide helicase G3BP1, which is involved in stress-granule formation. After DNA stimulation of human cells, cGAS associated in an RNA-dependent manner with G3BP1 and was found in cytoplasmic foci that also contained messenger RNA and the RNA-dependent kinase PKR. Formation of cytoplasmic cGAS condensates necessary for DNA-stimulated type I interferon production required G3BP1 and PKR activity.

    Sci. Signal. 12, eaav7934 (2019).

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