This Week in Science

Science  18 Sep 2020:
Vol. 369, Issue 6510, pp. 1443
  1. Archaeology

    Horses were not domesticated in Anatolia

    1. Mark Aldenderfer

    Modern horses in Anatolia, such as this wild herd, are descended from ancestors introduced from outside the region.

    PHOTO: GUIMARAES ET AL., SCI. ADV. 10.1126/SCIADV.ABB0030 (2020)

    The domestication of the horse was one of the most consequential innovations in human history and led to profound changes in the economic, political, and social structures of prehistoric Eurasia. However, when, where, and how many times horses were domesticated remains an open question. Anatolia has been proposed as an early center of domestication because of the long history of exploitation of equids there. Using advanced paleogenomic methods, Guimaraes et al. tested this hypothesis on archaeological samples of equids from 14 sites from central Anatolia across a temporal span from about 8000 to 1000 BCE. They determined that the ancient wild horses of the region were never domesticated and identified the introduction of nonlocal and already domesticated horse lineages around 2000 BCE.

    Sci. Adv. 10.1126/sciadv.abb0030 (2020).

  2. Microbiome

    Inosine modulates antitumor immunity

    1. Priscilla N. Kelly

    Checkpoint blockade immunotherapy harnesses the immune system to kill cancer cells and has been used with great success to treat certain tumors, but not all cancer patients respond. The efficacy of checkpoint blockade immunotherapy has been shown to depend on the presence of distinct, beneficial bacteria residing in the gut of patients, but how the microbiome mediates such beneficial effects is unclear. Mager et al. found that specific bacteria produce a metabolite called inosine that enhances the effect of checkpoint blockade immunotherapy (see the Perspective by Shaikh and Sears). In mouse models, inosine, together with proinflammatory stimuli and immunotherapy, strongly enhanced the antitumor capacities of T cells in multiple tumor types, including colorectal cancer, bladder cancer, and melanoma.

    Science, this issue p. 1481; see also p. 1427

  3. Structural Biology

    How ribosomes are made

    1. Valda Vinson

    The formation of eukaryotic ribosomes is a complex process that starts with transcription of a large precursor RNA that assembles into a large 90S preribosome, which matures to finally give the 40S small subunit of the ribosome. Cheng et al. and Du et al. give insight into this process, using cryo–electron microscopy to look at intermediates along the pathway. Together, these studies reveal how a cast of molecular players act to coordinate the compositional and structural changes that transform the 90S preribosome into a pre-40S subunit.

    Science, this issue p. 1470, p. 1477

  4. Plastic Pollution

    A mess of plastic

    1. H. Jesse Smith

    It is not clear what strategies will be most effective in mitigating harm from the global problem of plastic pollution. Borrelle et al. and Lau et al. discuss possible solutions and their impacts. Both groups found that substantial reductions in plastic-waste generation can be made in the coming decades with immediate, concerted, and vigorous action, but even in the best case scenario, huge quantities of plastic will still accumulate in the environment.

    Science, this issue p. 1515, p. 1455

  5. Surface Chemistry

    Nature of the molecule-surface encounter

    1. Yury Suleymanov

    Adsorption is an important initial step in all heterogeneous chemical processes. However, detailed adsorption dynamics are complex and challenging to follow experimentally. Using the fact that vibrationally excited carbon monoxide molecules can be trapped on the Au(111) surface with all degrees of freedom being equilibrated except the vibrational ones, Borodin et al. show that the vibrational relaxation time can serve as an internal clock to follow the microscopic pathways of adsorption and equilibration on the surface. On the basis of molecular beam experiments and theoretical modeling of this prototypical system, the authors reveal the intricate interplay between physisorption and chemisorption states. These observed characteristics are relevant to many other heterogeneous systems.

    Science, this issue p. 1461

  6. Water Structure

    Supercooled water structures

    1. Phil Szuromi

    Water displays a number of anomalous properties that are further enhanced in its supercooled state, but experimental studies at ambient pressure must obtain data before the onset of rapid crystallization at temperatures below ∼240 kelvin. Kringle et al. obtained infrared spectra of supercooled water films at temperatures between 135 and 235 kelvin that formed for a few nanoseconds by ultrafast heating and cooling. Supercooled water thermally equilibrates before crystallization above 170 kelvin, and over the range of temperatures studied, the structure of water was shown to be a linear combination of a high-density and a low-density liquid.

    Science, this issue p. 1490

  7. Stellar Evolution

    Complex stellar winds from evolved stars

    1. Keith T. Smith

    Stars less than eight times the mass of the Sun end their lives as planetary nebulae, structures of ionized gas thrown off by the star and heated by the exposed stellar core. Planetary nebulae are often bipolar in shape or contain complex morphological features such as rings or spirals. Decin et al. observed the stellar winds of 14 stars during their asymptotic giant branch (AGB) phase of stellar evolution, which immediately precedes the planetary nebula phase. They found morphologies in the AGB winds similar to planetary nebulae and demonstrated that they are produced by the influence of a binary companion on the AGB wind.

    Science, this issue p. 1497

  8. Cancer Immunology

    PD-1 keeps immune and tumor cells apart

    1. John F. Foley

    When cytotoxic T cells enter tumors and become tumor-infiltrating lymphocytes (TILs), they lose their ability to kill target tumor cells. TILs in this state express inhibitory receptors, including programed cell death protein-1 (PD-1), which are engaged in the tumor environment. Ambler et al. found that the suppressed cells had impaired cytoskeletal rearrangements and a decreased ability to form productive contacts with their targets. Blocking PD-1 signaling in vivo, but not in vitro, reversed these defects, stabilized the interactions between tumor cells and TILs, and improved cell killing.

    Sci. Signal. 13, eaau4518 (2020).

  9. Urban Ecology

    Imprints of racism

    1. Sacha Vignieri

    Cities create challenging environments for many nonhuman species, and the presence of nonhumans in cities influences the health and well-being of the humans with which they share the environment. Distinct urban conditions are created by landscape modification, but the history of this transformation is not equal across urban environments. Schell et al. review how systematic racist practices such as residential segregation, enacted in part through redlining, have led to an unequal distribution of “nature” within cities. These inequities continue to play out in both the ecological processes of cites and the welfare of their residents.

    Science, this issue p. eaay4497

  10. Neurodevelopment

    Insights from big data

    1. Pamela J. Hines

    The billions of neurons that make up the adult brain are organized into domains and circuits during development. High-resolution measurements such as those enabled by single-cell molecular profiling have revealed unexpected cellular diversity. Genomic tools are lending insight into mechanisms behind neurodevelopmental disorders. Briscoe and Marèn review the insights gained as big data analyses are applied to neurodevelopmental questions.

    Science, this issue p. eaaz8627

  11. Neuroscience

    Magic for animals

    1. Gemma Alderton

    Magical effects such as sleight-of-hand and distraction techniques can be informative about human cognition and blind spots in perception. Can this psychology of magic be applied to animals? In a Perspective, Garcia-Pelegrin et al. discuss how some animals, especially corvid birds such as magpies and jays, already use some techniques common to magic effects. The authors propose that experiments using magic effects with animals could reveal information about their cognition and perception and may provide exciting insights about the animal mind.

    Science, this issue p. 1424

  12. Inflammasomes

    The MTOC is “speck”-tacular

    1. Seth Thomas Scanlon

    Inflammasome complexes are formed in response to pathogen-associated molecules. They initiate both the maturation of inflammatory cytokines and pyroptosis, a type of programmed cell death. One notable feature for inflammasome activation is the formation of a single supramolecular punctum (or “speck”) in each affected cell. However, the location and mechanism of speck formation is poorly understood. Magupalli et al. report that for NLRP3- and pyrin-mediated inflammasomes, their assembly and downstream functions occur at the microtubule-organizing center (MTOC). This process requires the dynein adaptor HDAC6, which is also a central player in aggresome formation and autophagosomal degradation at the MTOC. This work links several important cellular processes and provides clues for how inflammasomes are efficiently regulated.

    Science, this issue p. eaas8995

  13. Developmental Biology

    Setting the tempo for development

    1. Beverly A. Purnell

    Many animals display similarities in their organization (body axis, organ systems, and so on). However, they can display vastly different life spans and thus must accommodate different developmental time scales. Two studies now compare human and mouse development (see the Perspective by Iwata and Vanderhaeghen). Matsuda et al. studied the mechanism by which the human segmentation clock displays an oscillation period of 5 to 6 hours, whereas the mouse period is 2 to 3 hours. They found that biochemical reactions, including protein degradation and delays in gene expression processes, were slower in human cells compared with their mouse counterparts. Rayon et al. looked at the developmental tempo of mouse and human embryonic stem cells as they differentiate to motor neurons in vitro. Neither the sensitivity of cells to signals nor the sequence of gene-regulatory elements could explain the differing pace of differentiation. Instead, a twofold increase in protein stability and cell cycle duration in human cells compared with mouse cells was correlated with the twofold slower rate of human differentiation. These studies show that global biochemical rates play a major role in setting the pace of development.

    Science, this issue p. 1450, p. eaba7667; see also p. 1431

  14. Coronavirus

    Better relaxing lockdown together

    1. Caroline Ash

    Even during a pandemic, all countries—even islands—are dependent in one way or another on their neighbors. Without coordinated relaxation of nonpharmaceutical interventions (NPIs) among the most closely connected countries, it is difficult to envisage maintaining control of infectious viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ruktanonchai et al. used mobility data from smartphones to estimate movements between administrative units across Europe before and after the implementation of NPIs for coronavirus disease 2019 (COVID-19). Modeling disease dynamics under alternative scenarios of countries releasing NPIs, in particular stay-at-home orders, showed that if countries do not coordinate their NPIs when they relax lockdown, resurgence of disease occurs sooner. Coordination of on-off NPIs would significantly increase their effectiveness at reducing transmission across Europe.

    Science, this issue p. 1465

  15. Quantum Systems

    Dressed for coherence

    1. Ian S. Osborne

    Solid-state qubits based on the electron spin of defects in silicon carbide or diamond provide a robust and versatile architecture for developing quantum technologies. The longer the lifetime of a spin, the more manipulations and quantum calculations can be performed, making for a more powerful quantum computational platform. Miao et al. show that by dressing the spins associated with the divacancy in silicon carbide with microwave photons, the lifetime can be extended by several orders of magnitude into milliseconds (see the Perspective by Hemmer). The technique effectively creates a quiet space for the qubit, thereby protecting it from magnetic, electric, and temperature fluctuations. This approach could be applicable to other architectures and provide a universal route to protecting qubits.

    Science, this issue p. 1493; see also p. 1432

  16. Coronavirus

    Stabilizing the prefusion SARS-CoV-2 spike

    1. Valda Vinson

    The development of therapeutic antibodies and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is focused on the spike (S) protein that decorates the viral surface. A version of the spike ectodomain that includes two proline substitutions (S-2P) and stabilizes the prefusion conformation has been used to determine high-resolution structures. However, even S-2P is unstable and difficult to produce in mammalian cells. Hsieh et al. characterized many individual and combined structure-guided substitutions and identified a variant, named HexaPro, that retains the prefusion conformation but shows higher expression than S-2P and can also withstand heating and freezing. This version of the protein is likely to be useful in the development of vaccines and diagnostics.

    Science, this issue p. 1501

  17. Coronavirus

    A steric block to SARS-CoV-2

    1. Valda Vinson

    In response to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the immune system makes antibodies, many of which target the spike protein, a key player in host cell entry. Antibodies that potently neutralize the virus hold promise as therapeutics and could inform vaccine design. Lv et al. report a humanized monoclonal antibody that protected against SARS-CoV-2 in a mouse model. The cryo–electron microscopy structure, together with biochemical, cellular, and virological studies, showed that the antibody acts by binding to the receptor-binding domain of the spike and blocking its attachment to the host receptor.

    Science, this issue p. 1505

  18. Ocean Warming

    Hearing the heat

    1. H. Jesse Smith

    Most of the excess heat that causes global warming is absorbed by the oceans. Quantifying that heat increase is challenging because it requires many different temperature measurements over both the vertical and horizontal extent of the oceans. Wu et al. report success in this effort through the use of a different method: They inferred temperature changes from sound waves generated by repeating earthquakes (see the Perspective by Wunsch). The travel time of these earthquakes from source to receiver reflects changes in the average water temperature that they encounter. This technique should substantially enhance our ability to monitor ocean warming.

    Science, this issue p. 1510; see also p. 1433

  19. Microbiota

    Microbiota protect the kidneys

    1. Caroline Ash

    Chronic kidney disease (CKD) afflicts millions of people globally. The first-line treatment for CKD is dietary intervention, so there may be a gut microbiota–associated component. Lobel et al. investigated the mechanistic links between the microbiota and protein intake, because the protein metabolites indole and indoxyl sulfate are known uremic toxins (see the Perspective by Pluznick). The authors used a mouse model of CKD precipitated by a paucity of the dietary sulfur–containing amino acids methionine and cysteine. Bacterial metabolism of sulfur-containing amino acids modulated indole production by sulfide inhibition of the enzyme tryptophanase, thus abrogating uremic toxicity by this metabolite in this model system.

    Science, this issue p. 1518; see also p. 1426

  20. Myeloid Cells

    A sympathetic tumor response

    1. Christiana N. Fogg

    The sympathetic nervous system (SNS) has been shown to regulate immune responses through various mechanisms. Nevin et al. now show that ablation of SNS signaling can suppress tumor immunity, and this is caused by disruption in α-adrenergic signaling that is needed for myeloid cell maturation. In tumor-bearing mice, this disruption promoted the accumulation of immature myeloid-derived suppressor cells, which allowed for tumor growth. In the absence of intact SNS signaling, these cells also promoted the expansion of regulatory T cells. These results provide insight into the contributions of SNS signaling in innate and adaptive immunity, particularly in the context of tumor immunity.

    Sci. Immunol. 5, eaay9368 (2020).

  21. Metabolism

    How to mete out metformin

    1. Catherine A. Charneski

    Metformin is the drug most commonly used to treat type 2 diabetes, though not all patients respond to it and others do not tolerate it at all. García-Calzón et al. analyzed genome-wide methylation in the blood of drug-naïve patients who were recently diagnosed with type 2 diabetes. They found that methylation at specific loci was associated with future metformin response or tolerance across multiple cohorts. These epigenetic markers may have theranostic potential regarding which patients should receive metformin.

    Sci. Transl. Med. 12, eaaz1803 (2020).

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