This Week in Science

Science  25 Sep 2020:
Vol. 369, Issue 6511, pp. 1579
  1. Immune Systems

    Reconfiguring an immune response

    1. Sacha Vignieri

    A female anglerfish of the species Haplophryne mollis supports a dorsally fused male fish, an arrangement requiring immune system changes.


    The deep sea is a vast and generally empty environment. Finding a mate can thus be difficult. In response to this situation, one group of deep-sea denizens, the anglerfishes, have evolved a system in which males attach to females, in some cases permanently, through fusion of tissues and connection of circulatory systems. Such attachment greatly challenges the immune systems of the fish. Swann et al. found that these challenges have been met by the evolution of increasingly reduced immune responses among anglerfish species, including the loss of what have been considered essential vertebrate responses. These shifts suggest that vertebrate immune systems may be more flexible over evolutionary time than was previously thought.

    Science, this issue p. 1608

  2. Protein Design

    Logic at the cell surface

    1. Valda Vinson

    A major challenge in medical interventions is to target only diseased cells. Although there are biomarkers characteristic of certain cancers, for example, it is unlikely that a single marker can specify a particular cell type. Lajoie et al. addressed this problem by designing protein switches called Co-LOCKR that bind to antigens on the cell surface and activate through a conformational change only when there is a precise combination of antigens. They designed switches that can perform AND, OR, and NOT logic. On the path toward applying this technology, they used Co-LOCKR to direct chimeric antigen receptor T cells to tumor cells expressing specific antigens.

    Science, this issue p. 1637

  3. Coronavirus

    A dynamic viral spike

    1. Valda Vinson

    Efforts to protect human cells against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the trimeric spike (S) protein. Several structures have shown a stabilized ectodomain of the spike in its prefusion conformation. Cai et al. now provide insight into the structural changes in the S protein that result in the fusion of the viral and host cell membranes. They purified full-length S protein and determined cryo–electron microscopy structures of both the prefusion and postfusion conformations. These structures add to our understanding of S protein function and could inform vaccine design.

    Science, this issue p. 1586

  4. Coronavirus

    Modeling SARS-CoV-2 in mice

    1. Priscilla N. Kelly

    Among the research tools necessary to develop medical interventions to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, high on the list are informative animal models with which to study viral pathogenesis. Gu et al. developed a mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia. Adaptation of this viral strain in the mouse appeared to be dependent on a critical amino acid change, Asn501 to Tyr (N501Y), within the receptor-binding domain of the viral spike protein. The new mouse model was used to study neutralizing antibodies and a vaccine candidate against the virus.

    Science, this issue p. 1603

  5. Graphene

    Making metallic ribbons

    1. Jelena Stajic

    In its usual two-dimensional form, graphene does not have an energy gap in its electronic structure. However, one-dimensional ribbons made of the material are semiconducting and making them metallic is tricky. Rizzo et al. developed a strategy for synthesizing metallic graphene nanoribbons and demonstrated their metallicity using scanning tunneling spectroscopy. These metallic graphene nanoribbons may be useful for exploring exotic quantum phases in a single dimension.

    Science, this issue p. 1597

  6. Chemical Physics

    Duality of roaming mechanism in H2CO

    1. Yury Suleymanov

    The phenomenon of roaming in chemical reactions (that is, bypassing the minimum energy pathway from unlikely geometries) has attracted a great deal of attention in the chemical reaction dynamics community over the past decade and still demonstrates unexpected results. Using velocity-map imaging of state-selected H2 products of H2CO photodissociation, Quinn et al. discovered the bimodal structure of rotational distribution of the other product fragment, CO. Quasiclassical trajectories showed that this bimodality originates from two distinctive reaction pathways that proceed by the trans or cis configuration of O–C–H⋯H, leading to high or low rotational excitations of CO, respectively. Whether such a mechanism is present in the many other chemical reactions for which roaming reaction pathways have been reported is yet to be determined.

    Science, this issue p. 1592

  7. Alcohol Addiction

    Tipsy microglia binge on synapses

    1. Leslie K. Ferrarelli

    Alcohol abuse has detrimental cognitive and behavioral consequences. Binge drinking is associated with anxiety in humans and, in mice, activates resident phagocytic immune cells in the brain called microglia. Socodato et al. found that a binge-drinking protocol in male mice induced microglia to selectively scavenge excitatory synapses between neurons in the prefrontal cortex. The loss of these connections did not cause neuronal death during the study but instead depressed neurotransmission and increased anxiety-like behaviors in the mice.

    Sci. Signal. 13, eaba5754 (2020).

  8. Climate Change

    Antarctic ice sheet melting and climate

    1. Kip Hodges

    The massive West Antarctic Ice Sheet (WAIS) is now melting at an accelerated rate in response to anthropogenic greenhouse gas emissions, and exactly how this will affect global climate remains poorly understood. Widely available predictive global climate models do not adequately account for ice sheet physics. Using a newly developed model that incorporates ice sheet thermodynamics, Rogstad et al. explored the potential effects of WAIS melting on the global climate. Their model not only predicts a significantly greater increase in subsurface ocean temperatures near the WAIS margins than earlier models but also suggests that simultaneous decreases in air and ocean surface temperature, as well as expanded sea ice, will delay previously predicted increases in global warming by several decades.

    Sci. Adv. 10.1126/sciadv.aaz1169 (2020).

  9. Immunology

    Immunology through a human lens

    1. Priscilla N. Kelly

    The coronavirus disease 2019 (COVID-19) pandemic has underscored the critical need to better understand the human immune system and how to unleash its power to develop vaccines and therapeutics. Much of our knowledge of the immune system has accrued from studies in mice, yet vaccines and drugs that work effectively in mice do not always translate into humans. Pulendran and Davis review recent technological advances that have facilitated the study of the immune system in humans. They discuss new insights and how these can affect the development of drugs and vaccines in the modern era.

    Science, this issue p. eaay4014

  10. Structural Biology

    Dissecting membrane dislocation

    1. Stella M. Hurtley

    Mistargeting and misinsertion of membrane proteins causes proteostasis stress and dysfunction of intracellular organelles, which can lead to disease. McKenna et al. found that a conserved orphan P-type adenosine triphosphatase (ATPase) transporter removes misinserted transmembrane segments from the endoplasmic reticulum (ER). Functional reconstitutions and cryo–electron microscopy structures show how this ATPase selectively extracts mitochondrial proteins that are mistargeted to the ER and transmembrane segments that are inserted in the wrong orientation. This work identifies polypeptides as a new class of P-type ATPase substrates and defines a new protein quality-control mechanism at the ER.

    Science, this issue p. eabc5809

  11. Prebiotic Chemistry

    Mapping primordial reaction networks

    1. Jake Yeston

    Chemists seeking to understand the origins of life have published a wide range of reactions that may have yielded the building blocks of proteins, nucleic acids, and lipids from simple precursors. Wołos et al. scoured the literature to document each such reaction class and then wrote software that applied the reactions first to the simplest compounds such as cyanide, water, and ammonia, and then iteratively to each successive generation of products. The resulting network predicted a variety of previously unappreciated routes to biochemically relevant compounds, several of which the authors validated experimentally.

    Science, this issue p. eaaw1955

  12. Neuroscience

    Basic principles of bird and mammal brains

    1. Peter Stern

    Mammals can be very smart. They also have a brain with a cortex. It has thus often been assumed that the advanced cognitive skills of mammals are closely related to the evolution of the cerebral cortex. However, birds can also be very smart, and several bird species show amazing cognitive abilities. Although birds lack a cerebral cortex, they do have pallium, and this is considered to be analogous, if not homologous, to the cerebral cortex. An outstanding feature of the mammalian cortex is its layered architecture. In a detailed anatomical study of the bird pallium, Stacho et al. describe a similarly layered architecture. Despite the nuclear organization of the bird pallium, it has a cyto-architectonic organization that is reminiscent of the mammalian cortex.

    Science, this issue p. eabc5534

  13. Spectroscopy

    Nonlinear x-ray spectroscopy

    1. Yury Suleymanov

    The extension of nonlinear optics to the x-ray spectral domain is a promising direction in the development of x-ray spectroscopy. Although theoretical concepts of nonlinear x-ray spectroscopy were developed decades ago, scientists still struggle to implement them because of the elusive nature of nonlinear effects. Eichmann et al. now present atomic momentum spectroscopy (AMS), which is based on the detection of the scattered atom after momentum transfer from x-ray photons (see the Perspective by Pfeifer). The authors show how AMS can observe stimulated x-ray Raman scattering signals at the neon K edge on a single-atom level and distinguish them from other competing processes. These results pave the way for future nonlinear x-ray spectroscopy methods for the study of x-ray–matter interactions.

    Science, this issue p. 1630; see also p. 1568

  14. Solar Cells

    Operating in wet conditions

    1. Phil Szuromi

    The high efficiency of the complex organic molecule Spiro-OMeTAD as a hole-transporting material for perovskite solar cells requires the use of hygroscopic dopants that decrease stability. Jeong et al. synthesized hydrophobic fluorinated analogs of Spiro-OMeTAD as hole-transporting materials that have favorable shifting of the electronic state for hole extraction and used them to fabricate perovskite solar cells. A champion device had a certified power conversion efficiency of 24.8% and an open-circuit voltage near the Shockley-Queisser limit. These devices could maintain more than 87% of the original power conversion efficiency under 50% relative humidity for more than 500 hours.

    Science, this issue p. 1615

  15. Ocean Temperature

    The heat is on

    1. H. Jesse Smith

    Anthropogenic climate change is causing not only more episodes of historically high air temperatures but also more frequent spells of unusually increased ocean temperatures. Marine heatwaves, defined as periods of anonymously high regional surface ocean temperatures, have also become common in recent decades. Laufkötter et al. show that the frequency of these events has already increased more than 10-fold because of anthropogenic global warming, making marine heatwaves, which typically occurred once in hundreds to thousands of years in preindustrial times, likely to occur on an annual to decadal basis if the global average air temperature rises by 3°C.

    Science, this issue p. 1621

  16. Immunometabolism

    Fumarate targets pyroptosis

    1. Seth Thomas Scanlon

    A form of inflammatory cell death called pyroptosis depends on the caspase-mediated cleavage of gasdermin D (GSDMD), the fragments of which assemble into permeability pores that then kill the cell. The mechanisms regulating this important cellular process are not yet fully understood. Humphries et al. now report that the tricarboxylic acid cycle intermediate fumarate can act as an inhibitor of pyroptosis (see the Perspective by Pickering and Bryant). Both endogenous fumarate and exogenously delivered dimethyl fumarate (DMF) convert the cysteines in GSDMD to S-(2-succinyl)-cysteines (a process called succination) to prevent its interaction with caspases and subsequent processing and activation. Administration of DMF to mice alleviated inflammation in models of multiple sclerosis and familial Mediterranean fever. These findings may explain the efficacy of DMF as a treatment for multiple sclerosis and other inflammatory diseases and offer insights into future anti-inflammatory drug design.

    Science, this issue p. 1633; see also p. 1564

  17. Consciousness

    Consciousness shared

    1. Sacha Vignieri

    Humans have tended to believe that we are the only species to possess certain traits, behaviors, or abilities, especially with regard to cognition. Occasionally, we extend such traits to primates or other mammals—species with which we share fundamental brain similarities. Over time, more and more of these supposed pillars of human exceptionalism have fallen. Nieder et al. now argue that the relationship between consciousness and a standard cerebral cortex is another fallen pillar (see the Perspective by Herculano-Houzel). Specifically, carrion crows show a neuronal response in the palliative end brain during the performance of a task that correlates with their perception of a stimulus. Such activity might be a broad marker for consciousness.

    Science, this issue p. 1626; see also p. 1567

  18. Y Evolution

    Y chromosome evolution in Neanderthals

    1. Laura M. Zahn

    The genomes of archaic hominins have been sequenced and compared with that of modern humans. However, most archaic individuals with high-quality sequences available have been female. Petr et al. performed targeted sequencing of the paternally inherited Y chromosomes from three Neanderthals and two Denisovans (see the Perspective by Schierup). Comparisons with available archaic and diverse modern human Y chromosomes indicated that, similar to the maternally inherited mitochondria, the human and Neanderthal Y chromosomes were more closely related to each other compared with the Denisovan Y chromosome. This result supports the conclusion that interbreeding between early humans and Neanderthals and selection replaced the more ancient Denisovian-like Y chromosome and mitochondria in Neanderthals.

    Science, this issue p. 1653; see also p. 1565

  19. Osteoarthritis

    Remediating malalignment

    1. Caitlin Czajka

    Joint alignment affects cartilage and bone degeneration in osteoarthritis. Haberkamp et al. studied site-specific differences in cartilage and bone damage in patients with knee osteoarthritis. They found that varus malalignment (a deviation of the axial alignment of the lower leg) caused reduced load on the lateral compartment of the knee, whereas there was a compensatory increase in medial load, particularly in patients with high body mass index. These results help to map the spatial structural changes in cartilage and bone that occur during varus knee osteoarthritis and highlight the potential therapeutic utility of load redistribution.

    Sci. Transl. Med. 12, eaba9481 (2020).

  20. Parasite Genetics

    Schistosome biology illuminated

    1. Laura M. Zahn

    Schistosomiasis is caused by a parasitic flatworm about which little is known. Therefore, options to combat human disease caused by schistosome infection are limited. To aid in our quest to develop treatments, two studies undertook molecular investigations of the parasite Schistosoma mansoni. By generating a single-cell atlas, Wendt et al. identified the developmental trajectory of the flatworm, including the blood-feeding gut required for its survival in the host. From these data, they found a gene required for gut development that, when knocked out through RNA interference, confers reduced pathology in infected mice. Wang et al. performed a large-scale RNA interference survey of S. mansoni and identified an essential pair of protein kinases that can be targeted by approved pharmacological intervention (see the Perspective by Anderson and Duraisingh). These molecular investigations add to our understanding of the schistosome parasite and provide biological information that may help to combat this neglected tropical disease.

    Science, this issue p. 1644, p. 1649; see also p. 1562

  21. Artificial Intelligence

    An Olympic curling robot

    1. Michael M. Lee

    The Olympic sport of curling is played on an ice sheet that is prone to changes throughout a match. The uncertain conditions of the ice sheet add further complexity to the game, beyond the prerequisites of accurate throwing and strategic thinking, making it a difficult sport to master and a challenging problem to solve for roboticists. Won et al. developed a curling robot, which they called Curly, that uses an adaptive deep reinforcement learning framework to react to past errors and adapt its throws to the current ice sheet conditions. Curly demonstrated human-like performance by winning three out of four matches against top-ranked human curling teams.

    Sci. Robot. 5, eabb9764 (2020).

  22. Neuroimmunology

    Cerebrospinal fluid snapshot

    1. Christiana N. Fogg

    The central nervous system features mechanisms to protect against untoward inflammation while allowing immune surveillance for pathogens. Pappalardo et al. profiled T cells in the cerebrospinal fluid (CSF) of healthy individuals and patients with multiple sclerosis (MS) using single-cell RNA and T cell receptor sequences to define central nervous system immune homeostasis. In healthy individuals, clonally expanded CSF T cells were largely distinct from those found in the blood, with effector, interferon-γ, and tissue adaptation signatures, whereas CSF T cells from patients with MS differed from healthy controls, with a gene expression signature consistent with increased activation and cytotoxicity. These findings provide insight into the distinct immune environment in the CSF under normal and disease-associated conditions.

    Sci. Immunol. 5, eabb8786 (2020).

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