This Week in Science

Science  20 Nov 2020:
Vol. 370, Issue 6519, pp. 926
  1. Neuroscience

    Threat detection starts in the eyes

    1. Takaki Komiyama

    Neural circuits in the retina help mice and other animals detect looming threats, such as a lunging predator.

    PHOTO: IMAGE SOURCE/GETTY IMAGES

    When a mouse sees something that quickly becomes larger in its visual field, perhaps indicating an attacking predator, it runs. Kim et al. identified a small group of neurons in the mouse retina that selectively respond to such looming visual stimuli and are required for innate defensive behaviors in response. These neurons perform this specific computation by integrating inputs from nearby neurons in a selective manner. Thus, neural circuits within the eyes, even before the information reaches the brain, perform specific computations to mediate innate, evolutionarily conserved behaviors.

    Sci. Adv. 10.1126/sciadv.abc9920 (2020).

  2. Antibiotic Resistance

    PBT2 pumps up polymyxins

    1. Melissa Norton

    Bacterial resistance to antibiotics is a growing worldwide problem, and Enterobacterales with resistance to the polymyxin class of antibiotics are a critical threat. De Oliveira et al. repurposed a hydroxyquinoline compound called PBT2, currently in phase 2 clinical trials for neurodegenerative diseases, to break polymyxin antibiotic resistance in four different Gram-negative pathogens, including Klebsiella pneumoniae and Pseudomonas aeruginosa. In vitro, treatment with PBT2 disrupted the abundance of zinc and iron in the resistant bacteria, whereas in immunocompetent septic mice, PBT2 combined with polymyxins resulted in improved survival with reduced bacterial dissemination. These findings, although exciting, need to be confirmed in humans.

    Sci. Transl. Med. 12, eabb3791 (2020).

  3. Developmental Biology

    Functional screen for microcephaly genes

    1. Beverly A. Purnell

    Genetic screens are widely used to identify regulators in biological processes. Human screens are currently limited to two-dimensional cell cultures, which lack the ability to score tissue-dependent gene function. Esk et al. combined CRISPR-Cas9 screening with barcoded cellular lineage tracing to enable loss-of-function screening in three-dimensional human cerebral organoid tissue. By testing microcephaly candidate genes, the endoplasmic reticulum was found to control extracellular matrix protein secretion regulating tissue integrity and brain size. This genetic screen in human brain tissue implicates multiple pathways in microcephaly and provides a tool for systematic testing of genes in organoids.

    Science, this issue p. 935

  4. Water Phases

    Liquid-liquid transitions under pressure

    1. Phil Szuromi

    Theoretical simulations suggest that deeply supercooled water undergoes a transition between high- and low-density forms, but this transition is difficult to study experimentally because it occurs under conditions in which ice crystallization is extremely rapid. Kim et al. combined x-ray lasers for rapid structure determination with infrared femtosecond pulses for rapid heating of amorphous ice layers formed at about 200 kelvin. The heating process created high-density liquid water at increased pressures. As the layer expanded and decompressed, low-density liquid domains appeared and grew on time scales between 20 nanoseconds and 3 microseconds, which was much faster than competing ice crystallization.

    Science, this issue p. 978

  5. Stellar Astrophysics

    A relic star cluster under the floor

    1. Keith T. Smith

    Globular clusters (GCs) are gravitationally bound assemblies of thousands to millions of stars that orbit in the outskirts of large galaxies. GCs consist of old stars with low metallicity containing low proportions of chemical elements heavier than hydrogen and helium. However, GCs appear to have a minimum metallicity, known as the floor, implying that at least some of those elements were required for their formation. Larsen et al. have found a GC in the nearby Andromeda Galaxy with a metallicity beneath the floor. This unexpected discovery will inform models of GC formation and incorporation into galaxies.

    Science, this issue p. 970

  6. Zika Virus

    Domesticating Zika virus

    1. Caroline Ash

    A feeding female Aedes aegypti mosquito, the primary species that transmits Zika virus

    PHOTO: B. G. THOMSON/SCIENCE SOURCE

    Why hasn't Zika virus (ZIKV) disease caused as much devastation in Africa, its continent of origin, as it has in the Americas? Outside of Africa, this flavivirus is transmitted by a ubiquitous mosquito subspecies, Aedes aegypti aegypti, which emerged from the African forerunner subspecies A. aegypti formosus and acquired a preference for human blood and a peridomestic lifestyle. Now, this subspecies colonizes many intertropical cities, aided by climate change and human trash. Aubry et al. tested 14 laboratory mosquito colonies for their relative susceptibility to ZIKV. Quantitative trait locus mapping showed differences on chromosome 2 between mosquitoes from Gabon and Guadeloupe. Mouse infection experiments revealed that African mosquitoes transmitted a smaller virus inoculum than the South American insects. Increased susceptibility coupled with the ability of A. aegypti aegypti to breed in any discarded object containing water has amplified the problematic nature of this virus as it has circumnavigated the world.

    Science, this issue p. 991

  7. Coronavirus

    A strong cocktail against SARS-CoV-2

    1. Valda Vinson

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the trimeric spike protein that decorates the virus and binds the ACE2 receptor. Antibodies against the spike that neutralize viral infection have potential as therapeutics. Tortorici et al. describe two very potent antibodies, S2E12 and S2M11. Electron microscopy structures characterized the binding and showed that S2E12 traps the spike in a conformation that cannot bind ACE2. Both antibodies protected hamsters against SARS-CoV-2 challenge and may be useful in antibody cocktails to combat the virus and prevent the development of resistance.

    Science, this issue p. 950

  8. Geophysics

    Finding the Emperor's head

    1. Brent Grocholski

    Volcanic island and seamount chains form from deep-seated plumes of hot material upwelling through the mantle. The most famous of these is the Hawaiian-Emperor seamount chain. However, a large volcanic structure associated with a plume head that should precede the chain has long been missing. Wei et al. finally identified the likely location of this structure in the mantle under eastern Russia. The structure was likely subducted 20 million to 30 million years ago, and the location helps constrain several geodynamic processes.

    Science, this issue p. 983

  9. Coronavirus

    Tackling other infectious diseases

    1. Gemma Alderton

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has pushed drug discovery and clinical testing to a pace previously considered impossible. In a Perspective, Gupta discusses how the structure of drug development for coronavirus disease 2019 (COVID-19) can be implemented to treat other infectious diseases that kill millions globally each year. By focusing research, implementing operational efficiencies, and ensuring large-scale financing, the author suggests that extensive drug development pipelines can be built to tackle other severe infections.

    Science, this issue p. 913

  10. Fire Ecology

    Fire's growing impacts on ecosystems

    1. Andrew M. Sugden

    Fire has played a prominent role in the evolution of biodiversity and is a natural factor shaping many ecological communities. However, the incidence of fire has been exacerbated by human activity, and this is now affecting ecosystems and habitats that have never been fire prone or fire adapted. Kelly et al. review how such changes are already threatening species with extinction and transforming terrestrial ecosystems and discuss the trends causing changes in fire regimes. They also consider actions that could be taken by conservationists and policy-makers to help sustain biodiversity in a time of changing fire activity.

    Science, this issue p. eabb0355

  11. Virology

    Riding the calcium waves

    1. Stella M. Hurtley

    Rotavirus causes severe diarrhea and vomiting in children worldwide, yet how infection causes these diseases remains poorly understood. A leading theory is that virus-infected cells secrete paracrine signaling molecules that dysregulate epithelial cells. Chang-Graham et al. found that rotavirus-infected cells trigger cell-to-cell signaling that manifests as intercellular calcium waves (see the Perspective by Stanifer and Boulant). This signal results from the repeated release of adenosine 5′-diphosphate by rotavirus-infected cells. This release activates receptors on nearby uninfected cells, resulting in a calcium signal. The intercellular calcium waves activate chloride and serotonin secretion, which contributes to diarrhea and vomiting. Blocking this paracrine signal could represent a target for antidiarrheal pharmacotherapy.

    Science, this issue p. eabc3621; see also p. 909

  12. Photosynthesis

    Green to the core

    1. Michael A. Funk

    Light from the Sun powers most life on today's Earth in some way. The core of the photosynthetic apparatus where charge separation occurs, the reaction center (RC), is thought to have originated a single time and diverged, yielding new kinds of complexes adapted to different tasks and environments. Chen et al. now present an important missing puzzle piece in our understanding of the evolution of RCs: a cryo–electron microscopy structure of the homodimeric type I RC from a green sulfur bacterium bound to a light-harvesting protein. The observed cofactor and pigment arrangement explain biochemical features of this RC and will aid in our understanding of how a single ancestral RC gave rise to the range of structures and functions seen in RCs today.

    Science, this issue p. eabb6350

  13. Neurodegeneration

    Two ways to get tangled?

    1. Stella M. Hurtley

    Neurodegeneration in Alzheimer's disease dementia is associated with neurofibrillary tangles composed of aggregated tau protein. Darwich et al. describe an additional form of autosomal-dominant dementia with neurofibrillary tangles linked to a hypomorph mutation in valosin-containing protein (VCP). VCP was found to disaggregate pathologic tau, and the hypomorph mutation increased tau accumulation in cells and mice. These findings highlight the role of protein turnover in maintaining neuronal health and suggest that VCP may provide a therapeutic target for Alzheimer's disease.

    Science, this issue p. eaay8826

  14. Wildlife Disease

    Climate change alters disease risks

    1. Caroline Ash

    Climate change appears to be provoking changes in the patterns and intensity of infectious diseases. For example, when conditions are cool, amphibians from warm climates experience greater burdens of infection by chytrid fungus than hosts from cool regions. Cohen et al. undertook a global metanalysis of 383 studies to test whether this “thermal mismatch” hypothesis holds true over the gamut of host-pathogen relationships. The authors combined date and location data with a selection of host and parasite traits and weather data. In the resulting model, fungal disease risk increased sharply under cold abnormalities in warm climates, whereas bacterial disease prevalence increased sharply under warm abnormalities in cool climates. Warming is projected to benefit helminths more than other parasites, and viral infections showed less obvious relationships with climate change.

    Science, this issue p. eabb1702

  15. Neurodevelopment

    Unlocking retinal regeneration in mice

    1. Pamela J. Hines

    Zebrafish can regenerate damaged retinal tissue, but mice cannot. Hoang et al. found that tracking changes in gene expression and chromatin accessibility upon injury revealed clues as to why retinal glial cells in zebrafish could generate new neurons but the same cell type in mice could not. In zebrafish, activated Müller glial cells shift into a proliferative phase, whereas in mice, a genetic network returns the glial cells to quiescence. A few transcription factors enforce quiescence in the mouse, and disruption of these allowed Müller glia to proliferate and generate new neurons after retinal injury.

    Science, this issue p. eabb8598

  16. Developmental Biology

    Cells and the path of least resistance

    1. Beverly A. Purnell

    For processes encompassing proper embryonic development, adult homeostasis, tumor cell dissemination, and immunity, certain cells must translocate from their site of origin. Migrating cells navigate physical features of their microenvironment; however, the in vivo importance of tissue topography for pathfinding is mostly unknown. Studying fruit flies, Dai et al. used border cells within the ovarian egg chamber to study path selection. Live imaging, genetics, mathematical modeling, and simulations showed that tissue microtopography provides an energetically favorable path of least resistance, whereas chemoattractants supply orthogonal guidance information and cell-cell adhesion contributes traction. The results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many.

    Science, this issue p. 987

  17. Immunology

    Maternal IgE activates fetal mast cells

    1. Priscilla N. Kelly

    Mast cells (MCs) are immune cells that participate in allergic reactions through their activation by immunoglobulin E (IgE) antibodies. MCs arise early during mammalian development, but it is unclear whether IgE-mediated activation occurs in fetal tissues and what the source of IgE stimulation is. Msallam et al. show that human and mouse fetal MCs can be sensitized by IgE of maternal origin, which crosses the placental barrier through the fetal neonatal Fc receptor (see the Perspective by Rothenberg). Prenatal maternal sensitization conferred transient allergen sensitivity after birth and resulted in the development of postnatal skin and airway inflammation in the offspring after their first exposure to allergen. Thus, both maternal IgE and fetal MCs may influence mother-to-child transmission of allergic disease during gestation.

    Science, this issue p. 941; see also p. 907

  18. Materials Science

    Feeling temperature and touch

    1. Marc S. Lavine

    The range of receptors in our skin make it possible to sense when we are touching an object and also gives us a general sense of the temperature of that object. Achieving this in an artificial skin-like material has been a challenge because most of the approaches for sensing touch are themselves temperature sensitive. You et al. studied the ion relaxation dynamics in a conductive elastomeric film (see the Perspective by Liu). They show that the ion relaxation time can be used as a strain-insensitive intrinsic variable for detecting temperature and the capacitance can be used as a temperature-insensitive extrinsic variable for sensing the strain, thus decoupling the two so that their signals do not interfere with each other.

    Science, this issue p. 961; see also p. 910

  19. Materials Science

    A soft touch

    1. Marc S. Lavine

    Measuring the force it takes for a hand to grasp an object requires sensors to be placed on the fingertips, but these sensors will interfere with or affect how much force ends up being applied. Lee et al. developed a nanomesh sensor built from a series of electrospun materials (see the Perspective by Liu). Using a robotic tester, they show that this device can repeatably detect the pressure involved in gripping an object. They also show that the sensors can be attached to human fingers and that this does not affect the force used to grasp an object.

    Science, this issue p. 966; see also p. 910

  20. Surface Science

    Telegraphing molecules

    1. Phil Szuromi

    Scanning tunneling microscope (STM) tips have long been used to manipulate atoms and molecules through direct interactions. Civita et al. now show that at cryogenic temperatures, the bias voltage from an STM tip can propel a large organic molecule, dibromoterfluorene, long distances—tens of nanometers along straight tracks on the flat silver (111) surface (see the Perspective by Esch and Lechner). This electrostatic effect requires the molecule to be oriented along the track, and derivatives lacking bromide groups would change direction. In a dual-tip setup, changing the bias voltage sent and received molecules between two specific points about 60 nanometers apart.

    Science, this issue p. 957; see also p. 912

  21. Antifungal Discovery

    Prospecting for antifungal molecules

    1. Michael A. Funk

    Marine bacteria produce a plethora of natural products that often have unusual chemical structures and corresponding reactivity, which sometimes translate into a valuable biological function. Zhang et al. used a metabolomic screen to zero in on microbial strains from the microbiome of a sea squirt that produces a high diversity of chemical structures. They then screened these molecules for inhibition of fungi (see the Perspective by Cowen). A polycyclic molecule dubbed turbinmicin possessed potent antifungal activity against the multidrug-resistant fungal pathogens Candida auris and Aspergillus fumigatus. Preliminary mechanism-of-action and mouse toxicity studies suggest that this molecule works though a fungus-specific pathway and is well tolerated at therapeutic doses.

    Science, this issue p. 974; see also p. 906

  22. Cancer Therapy

    Unmasking sensitivity to chemotherapy

    1. Leslie K. Ferrarelli

    Although the activity of the epidermal growth factor receptor (EGFR) pathway is increased in triple-negative breast cancers (TNBCs), these tumors are generally insensitive to EGFR inhibitors. Cruz-Gordillo et al. found that insensitivity to the EGFR inhibitor erlotinib was due to the prosurvival protein Mcl-1. MCL1 expression in TNBC cells was promoted by the ELP family of transcription-elongation regulators, particularly ELP4. These findings suggest that combining erlotinib with an Mcl-1 inhibitor might be effective in TNBC patients.

    Sci. Signal. 13, eabb9820 (2020).

  23. Dendritic Cells

    Distinct dendritic cell responses

    1. Claire Olingy

    Dendritic cells (DCs) are critical for activating naïve T cells by presenting antigens and providing costimulation, processes that are enhanced by cytokine signals from the surrounding environment. Girard et al. used single-cell proteogenomics and flow cytometry to examine cell type–specific responses of human peripheral blood monocyte and DC subsets to type I interferon. Interferon-β induced maturation of the recently identified CD1c+ CD5 DC3 subset, which was characterized by distinct expression of the costimulatory molecule GITRL, a tumor necrosis factor family ligand, and driven by nuclear factor κB signaling. These results identify conserved and cell type–specific features of the type I interferon response of human mononuclear phagocyte subsets, including the molecular signals that monocytes and DCs may leverage to instruct T cells.

    Sci. Immunol. 5, eabe0347 (2020).

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