This Week in Science

Science  19 Feb 2021:
Vol. 371, Issue 6531, pp. 793
  1. Conservation

    No waters left untouched

    1. Sacha Vignieri

    Fish such as brook trout have contributed to phylogenetic dissimilarity in rivers in which they are introduced as exotic species.


    We are increasingly aware of human impacts on biodiversity across our planet, especially in terrestrial and marine systems. We know less about fresh waters, including large rivers. Su et al. looked across such systems globally, focusing on several key measures of fish biodiversity. They found that half of all river systems have been heavily affected by human activities, with only very large tropical river basins receiving the lowest levels of change. Fragmentation and non-native species have also led to the homogenization of rivers, with many now containing similar species and fewer specialized lineages.

    Science, this issue p. 835

  2. Surface Chemistry

    Joint strategy for surface chemistry

    1. Yury Suleymanov

    Recent advances in the development of tip-based microscopy have led to angstrom-scale spatial resolution, but no technique provides univocal characterization of the structural and chemical heterogeneities of surface species. Using a model system of pentacene derivatives on the Ag(110) surface, Xu et al. show that the combination of scanning tunneling microscopy, atomic force microscopy, and tip-enhanced Raman scattering provides the electronic, structural, and chemical information sufficiently correlated for an unambiguous characterization of the different—but structurally similar—chemical species and their interaction with the metal surface with single-bond resolution. The proposed multitechnique approach could find wide application in fundamental studies of heterogeneous catalysis and surface chemistry in general.

    Science, this issue p. 818

  3. Soft Robots

    Walk this way

    1. Michael M. Lee

    Pneumatic soft robots generally require an assortment of electronically controlled, bulky components such as pumps and valves to achieve legged locomotion. Drotman et al. simplified the design of walking soft robots by using fluidic circuits, rather than electronic circuits, to achieve locomotion. Specifically, a soft ring oscillator produces movement by generating rhythmic motions analogous to biological central pattern generator neural circuits found in nature.

    Sci. Robot. 6, eaay2627 (2021).

  4. Thermoelectrics

    Distorted thermal properties

    1. Brent Grocholski

    Thermoelectric devices can convert waste heat into electricity, providing one path for improving energy efficiency. Jiang et al. leveraged entropy engineering to synthesize a single-phase high-entropy alloy with attractive thermoelectric properties. By increasing the number of elements in the alloy, the resulting disorder helps to stabilize against breakdown into multiple phases. The disordered and distorted crystal lattice suppresses thermal transport while maintaining the electrical properties, which boosts the heat-conversion efficiency of the material.

    Science, this issue p. 830

  5. Coronavirus

    Targeting sarbecoviruses

    1. Valda Vinson

    As we continue to battle the COVID-19 pandemic, we must confront the possibility of new pathogenic coronaviruses emerging in humans in the future. With this in mind, Rappazzo et al. isolated antibodies from a survivor of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), used yeast display libraries to introduce diversity into these antibodies, and then screened for binding to SARS-CoV-2. One of the affinity-matured progeny strongly neutralized SARS-CoV-2, SARS-CoV, and two SARS-related viruses from bats. In addition, this antibody bound to the receptor-binding domains from a panel of sarbecoviruses, suggesting broader activity, and provided protection against SARS-CoV and SARS-CoV-2 in mouse models.

    Science, this issue p. 823

  6. Coronavirus

    Mapping antibody escape in SARS-CoV-2

    1. Valda Vinson

    Several antibodies are in use or under development as therapies to treat COVID-19. As new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants emerge, it is important to predict whether they will remain susceptible to antibody treatment. Starr et al. used a yeast library that covers all mutations to the SARS-CoV-2 receptor-binding domain that do not strongly disrupt binding to the host receptor (ACE2) and mapped how these mutations affect binding to three leading anti–SARS-CoV-2 antibodies. The maps identify mutations that escape antibody binding, including a single mutation that escapes both antibodies in the Regeneron antibody cocktail. Many of the mutations that escape single antibodies are circulating in the human population.

    Science, this issue p. 850

  7. Mitoribosome

    Making the energy makers

    1. Di Jiang

    Within a mitochondrion, the powerhouse of eukaryotic cells, synthesis of the specialized transmembrane proteins of the electron transport chain is performed by dedicated mitoribosomes. The mechanism by which mitoribosomes couple protein synthesis with membrane insertion is poorly understood. Itoh et al. determined structures of the human mitoribosome during nascent chain synthesis while bound to its membrane insertase. These structures revealed a series of coordinated conformational changes within the polypeptide exit tunnel. The gating mechanism offers a fundamental molecular insight into how membrane proteins are synthesized in human mitochondria.

    Science, this issue p. 846

  8. Paleoenvironment

    Reversing the field

    1. H. Jesse Smith

    Do terrestrial geomagnetic field reversals have an effect on Earth's climate? Cooper et al. created a precisely dated radiocarbon record around the time of the Laschamps geomagnetic reversal about 41,000 years ago from the rings of New Zealand swamp kauri trees. This record reveals a substantial increase in the carbon-14 content of the atmosphere culminating during the period of weakening magnetic field strength preceding the polarity switch. The authors modeled the consequences of this event and concluded that the geomagnetic field minimum caused substantial changes in atmospheric ozone concentration that drove synchronous global climate and environmental shifts.

    Science, this issue p. 811

  9. Neuroscience

    No ligand needed for learning

    1. Leslie K. Ferrarelli

    In addition to its role in stimulating appetite, the hormone ghrelin and its receptor, GHS-R1a, are implicated in cognition. Ribeiro et al. found a role for ghrelin-independent GHS-R1a signaling in learning in mice. Treating mice with an inverse agonist of GHS-R1a impaired spatial and contextual memory formation. Thus, the use of ghrelin receptor–blocking therapies, which have been proposed for treating metabolic disorders, acromegaly, cancer, and alcoholism, may also have cognitive side effects.

    Sci. Signal. 14, eabb1953 (2021).

  10. Stem Cells

    The origins of tissue regeneration

    1. Gemma Alderton

    Tissue turnover is maintained by a stem cell pool, but stem cells in some tissues can be highly sensitive to damage. When stem cells are ablated, how is the stem cell pool and the rest of the tissue regenerated? In a Perspective, Shivdasani et al. discuss the evidence that differentiated cells can dedifferentiate and become stem cells that enable tissue recovery from damage. Understanding these processes is important because cancer is largely considered to originate from stem cells. The finding that differentiated cells can acquire stem cell characteristics raises questions about how cancers are initiated.

    Science, this issue p. 784

  11. Plant Science

    New pathways in plants and microbes

    1. Pamela J. Hines

    Plants and microbes have interacted through evolution in ways that shaped diversity and helped plants colonize land. Delaux and Schornack review how insights from a range of plant and algal genomes reveal sustained use through evolution of ancient gene modules as well as emergence of lineage-specific specializations. Mosses, liverworts, and hornworts have layered innovation onto existing pathways to build new microbial interactions. Such innovations may be transferrable to crop plants with an eye toward building a more sustainable agriculture.

    Science, this issue p. eaba6605

  12. Evolution

    A recipe for new genes

    1. Laura M. Zahn

    Most lineages contain evolutionarily novel genes, but their origin is not always clear. Cosby et al. investigated the origin of families of lineage-specific vertebrate genes (see the Perspective by Wacholder and Carvunis). Fusion between transposable elements (TEs) and host gene exons, once incorporated into the host genome, could generate new functional genes. Examination of KARABINER, a bat gene that arose through this process, shows how the retention of part of the TE within this gene allows the transcribed protein to bind throughout the genome and act as a transcriptional regulator. Thus, TEs interacting within their host genome provide the raw material to generate new combinations of functional domains that can be selected upon and incorporated within the hierarchical cellular network.

    Science, this issue p. eabc6405; see also p. 779

  13. Bacterial Genomics

    Bacterial cell gene expression

    1. Laura M. Zahn

    Single-cell genomics in bacteria has lagged relative to in eukaryotes because of their tough bacterial cell walls, low messenger RNA content, and lack of many posttranscriptional modifications. To tackle this challenge, Kuchina et al. developed microbial split-pool ligation transcriptomics, or microSPLiT, a single-cell sequencing method for both Gram-negative and Gram-positive bacteria. Sequencing both Escherichia coli and Bacillus subtilis showed differences in the heat shock response. Examining B. subtilis transcriptional patterns revealed that a small fraction of cells grown in laboratory medium express a myo-inositol catabolism pathway, which the cell could use in nonlaboratory environments, thus highlighting how microSPLiT can identify rare cellular states.

    Science, this issue p. eaba5257

  14. Antibiotic Resistance

    The many roads to resistance

    1. Laura M. Zahn

    Antibiotic resistance arising from mutation is common among pathogenic bacteria. However, this process is not well understood, and most of the mutations that have been identified to confer resistance do so by modification of the intracellular target or enzymes that can disable the antibacterial compound within the cell. Screening for the evolution of resistance at different temperatures, Lopatkin et al. found that mutations that affect microbial metabolism can result in antibiotic resistance (see the Perspective by Zampieri). These mutations targeted central carbon and energy metabolism and revealed novel resistance mutations in core metabolic genes, expanding the known means by which pathogenic microbes can evolve resistance.

    Science, this issue p. eaba0862; see also p. 783

  15. DNA Origami

    Orienting origami binding

    1. Phil Szuromi

    Directing self-assembly for devices will require placing nanocomponents not only in the correct position on a surface but also in particular orientations. Gopinath et al. designed an asymmetric DNA origami, a “small moon” shape that binds to lithographically patterned sites on silica to within 3° of a target orientation angle. The authors were able to position and orient a molecular dipole within the resonant mode of an optical cavity. More than 3000 DNA origami were arranged in a single fabrication step in 12 different orientations to create a simple polarimeter.

    Science, this issue p. eabd6179

  16. Protein Design

    Building a barrel

    1. Valda Vinson

    Computational design offers the possibility of making proteins with customized structures and functions. The range of accessible protein scaffolds has expanded with the design of increasingly complex cytoplasmic proteins and, recently, helical membrane proteins. Vorobieva et al. describe the successful computational design of eight-stranded transmembrane β-barrel proteins (TMBs). Using an iterative approach, they show the importance of negative design to prevent off-target structures and gain insight into the sequence determinants of TMB folding. Twenty-three designs satisfied biochemical screens for a TMB structure, and two structures were experimentally validated by nuclear magnetic resonance spectroscopy or x-ray crystallography. This is a step toward the custom design of pores for applications such as single-molecule sequencing.

    Science, this issue p. eabc8182

  17. Coronavirus

    How to hold down transmission

    1. Caroline Ash

    Early in 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission was curbed in many countries by imposing combinations of nonpharmaceutical interventions. Sufficient data on transmission have now accumulated to discern the effectiveness of individual interventions. Brauner et al. amassed and curated data from 41 countries as input to a model to identify the individual nonpharmaceutical interventions that were the most effective at curtailing transmission during the early pandemic. Limiting gatherings to fewer than 10 people, closing high-exposure businesses, and closing schools and universities were each more effective than stay-at-home orders, which were of modest effect in slowing transmission.

    Science, this issue p. eabd9338

  18. Protein Engineering

    Moving targets of neurotoxins

    1. Di Jiang

    Proteases that cleave protein targets at specific sequences control many biological functions. The ability to reprogram proteases to cleave new sequences of our choosing would enable new therapeutic and biotechnological applications. Blum et al. report a laboratory evolution method to rapidly evolve proteases that cut new protein sequences and lose their ability to cut nontarget sequences (see the Perspective by Stenmark). Using this method, they evolved botulinum neurotoxin proteases, an important class of enzymes used in patients, to selectively cleave new targets, including a protein unrelated to those natively cleaved by these proteases. This work establishes a powerful approach to generate proteases with tailor-made specificities.

    Science, this issue p. 803; see also p. 782

  19. Tissue Repair

    Organoids regenerate human bile ducts

    1. Priscilla N. Kelly

    Bile ducts carry bile from the liver and gall bladder to the small intestine, where it aids digestion. Cholangiocytes are epithelial cells that line bile ducts and modify bile as its transported through the biliary tree. Chronic liver diseases involving cholangiocytes account for a large fraction of liver failure and the need for liver transplantation. Because liver donors are in short supply, Sampaziotis et al. used organoid technology to develop a cell-based therapy using human tissue (see the Perspective by Kurial and Willenbring). Cholangiocyte organoids were transplanted into the intrahepatic ducts of deceased human donor livers undergoing ex vivo normothermic perfusion. The livers could be maintained for up to 100 hours, and the transplanted organoids engrafted, exhibited function, and could repair bile ducts.

    Science, this issue p. 839; see also p. 786

  20. Alzheimer's Disease

    Controlling amyloid in brain and vessels

    1. Mattia Maroso

    The genetic variant ε4 of the apolipoprotein E gene (APOE) is associated with increased risk of developing Alzheimer's disease (AD). In AD, amyloid-β forms deposits in the brain parenchyma (amyloid plaques) and in the cerebral vasculature (cerebral amyloid angiopathy, CAA). Immunotherapy targeting human APOE has reduced brain amyloid-β deposits in mice. Xiong et al. used a mouse model with both amyloid plaques and CAA and evaluated the effects of the anti–human APOE antibody HAE4. The treatment reduced both parenchymal amyloid-β plaques and CAA without vascular complications, whereas an antibody targeting amyloid-β exacerbated CAA-related microhemorrhages. The results suggest that HAE4 may provide therapeutic effects on amyloid removal in AD while protecting the cerebrovasculature.

    Sci. Transl. Med. 13, eabd7522 (2021).

  21. Innate Immunity

    Teamwork for T cells

    1. Dan A. Erkes

    The location and interaction of innate immune cells in lymph nodes contribute to the induction of T cell responses, yet the exact cells that contribute are unclear. Using advanced imaging techniques to characterize the spatial arrangement of innate and adaptive immune cells during Toll-like receptor agonist–induced inflammation, Leal et al. show that lymph node–resident dendritic cells (DCs) and inflammatory monocytes cooperate to induce T cell responses. These DCs migrate to the T cell zone and present antigen to T cells. Circulating monocytes enter the lymph nodes through high endothelial venules and become spatially polarized in the T cell zone, consequently inducing distinct inflammatory microenvironments and effector T cell subsets. Thus, DCs and monocytes in the lymph node T cell zone work together to induce T cell responses.

    Sci. Immunol. 6, eabb9435 (2021).

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