This Week in Science

Science  19 Jun 2020:
Vol. 368, Issue 6497, pp. 1324
  1. Geophysics

    Seismic swarms show the structure

    1. Brent Grocholski

    A line marks the site of an ancient lake in a fault-rich region near Salton City, California, not far from the site of a recent seismic swarm induced by fluid injection from a deep reservoir.

    PHOTO: DAVID MCNEW/GETTY IMAGES

    Faults responsible for earthquakes are idealized into two dimensions, despite fault zones being complicated, three-dimensional structures. Ross et al. used machine learning to find 22,000 seismic events near Cahuilla, California, during a seismic swarm. They used the locations and sizes of these events to show how the complex structure of the fault interacted with natural fluid injections from below. The authors' methods highlight the complexities of one fault and suggest a way to characterize other faults around the world.

    Science, this issue p. 1357

  2. Coronavirus

    Promising antiviral protease inhibitors

    1. Valda Vinson

    With no vaccine or proven effective drug against the virus that causes coronavirus disease 2019 (COVID-19), scientists are racing to find clinical antiviral treatments. A promising drug target is the viral main protease Mpro, which plays a key role in viral replication and transcription. Dai et al. designed two inhibitors, 11a and 11b, based on analyzing the structure of the Mpro active site. Both strongly inhibited the activity of Mpro and showed good antiviral activity in cell culture. Compound 11a had better pharmacokinetic properties and low toxicity when tested in mice and dogs, suggesting that this compound is a promising drug candidate.

    Science, this issue p. 1331

  3. Metalloenzymes

    Delicate dance becomes a ballet

    1. Michael A. Funk

    The enzyme nitrogenase uses adenosine triphosphate and several unusual iron-sulfur cofactors to pump electrons into typically inert dinitrogen (N2), providing protons along the way. Previous work has shown that sulfur atoms in the iron-molybdenum cofactor (FeMoCo) are labile and suggests that replacement of one of the sulfurs by N2 is integral to the mechanism of N2 binding and reduction. Through the elimination of excess reducing agent during preparation, Kang et al. determined structures of Mo-nitrogenase in a resting conformation. Unexpectedly, they found that all three sulfurs at the outer edge of FeMoCo appear to be labile, with one subunit even having two of three sulfurs replaced by light, diatomic ligands. Biochemical and spectroscopic data indicate that the protein is active, holds tightly bound N2, and is in the expected oxidation state. These results may prompt a reassessment of the possible mechanisms of N2 reduction and the role of dynamic belt ligands in FeMoCo.

    Science, this issue p. 1381

  4. Metallurgy

    Strong and tough steel

    1. Brent Grocholski

    Ultrahard materials often do not have similarly impressive fracture toughness. Liu et al. discovered a processing route for medium manganese steel alloy in which ultrahigh strength accompanies high fracture toughness. The steel relies on both transformation-induced plasticity and delamination toughening to boost the fracture properties. The steel is composed of less expensive elements, making it a potentially inexpensive material attractive for structural applications.

    Science, this issue p. 1347

  5. Cancer Therapy

    Speedy screen for tumor therapies

    1. Leslie K. Ferrarelli

    Cell death screens using patient biopsies could be used to identify effective treatments for cancerous solid tumors. However, it takes several days to obtain results, meaning that the cells guiding treatment decisions may become molecularly distinct from those in patients. Bhola et al. developed a high-throughput method that, within 24 hours, identifies drugs that initiate cell death programs in tumor cells from freshly isolated patient biopsies. This method identified drug therapies that shrank breast and colon tumors in mice, but which would not have seemed as promising when screened in cells cultured for several days.

    Sci. Signal. 13, eaay1451 (2020).

  6. Influenza

    Resistance to influenza antibodies

    1. Valda Vinson

    Broadly neutralizing human antibodies (bnAbs) to the stem of hemagglutinin (HA), a trimeric glycoprotein found on the surface of influenza viruses, are valuable therapeutics and can guide the development of universal influenza vaccines. For their use in therapy development, it is important to understand the extent to which HA stem variants with resistance to bnAbs can develop. Wu et al. used saturation mutagenesis combined with next-generation sequencing to systematically search for resistance mutations to prototypic bnAbs in two influenza subtypes, H3 and H1. They found that the genetic barrier to resistance to stem bnAbs was low for the H3 subtype but higher for the H1 subtype. The ability of H3 to develop resistance to bnAbs presents a challenge in the development of a universal influenza vaccine.

    Science, this issue p. 1335

  7. Biodiversity Change

    Land-use change and forest biodiversity

    1. Andrew M. Sugden

    Land-use change by humans, particularly forest loss, is influencing Earth's biodiversity through time. To assess the influence of forest loss on population and biodiversity change, Daskalova et al. integrated data from more than 6000 time series of species' abundance, richness, and composition in ecological assemblages around the world. Forest loss leads to both positive and negative responses of populations and biodiversity, and the temporal lags in population and biodiversity change after forest loss can extend up to half a century. Land-use change precipitates divergent population and biodiversity change. This analysis has consequences for projections of human impact, ongoing conservation, and assessments of biodiversity change.

    Science, this issue p. 1341

  8. Electrochemistry

    Cutting it close for radical coupling

    1. Jake Yeston

    In principle, electrochemistry is an ideal method for radical coupling: One precursor oxidized at the anode pairs up with a counterpart that has been reduced at the cathode. The trouble is that either or both coupling partners might not stay stable long enough to meet in the middle. Mo et al. resolved this issue by closely spacing the electrodes in a microfluidics platform (see the Perspective by Liu et al.). They showcase coupling of dicyanobenzene as the cathodic radical precursor with a variety of oxidatively generated partners.

    Science, this issue p. 1352; see also p. 1312

  9. Forest and Climate

    Risks to mitigation potential of forests

    1. Andrew M. Sugden

    Much recent attention has focused on the potential of trees and forests to mitigate ongoing climate change by acting as sinks for carbon. Anderegg et al. review the growing evidence that forests' climate mitigation potential is increasingly at risk from a range of adversities that limit forest growth and health. These include physical factors such as drought and fire and biotic factors, including the depredations of insect herbivores and fungal pathogens. Full assessment and quantification of these risks, which themselves are influenced by climate, is key to achieving science-based policy outcomes for effective land and forest management.

    Science, this issue p. eaaz7005

  10. Evolution

    The origins of pollination

    1. Gemma Alderton

    Which came first, the flower or pollinating insects? Fossil evidence and molecular analyses using chloroplast DNA sequencing give conflicting estimates about when flowering plants first appeared, which has implications for how pollinating insects arose. In a Perspective, van der Kooi and Ollerton discuss the data and the possible explanations for the evolution of these interdependent species.

    Science, this issue p. 1306

  11. Solar Cells

    Perovskite decomposition in detail

    1. Phil Szuromi

    Solar cells are subject to heating when operating in sunlight, and the organic components of hybrid perovskite solar cells, especially the commonly used methylammonium cation, can undergo thermal decomposition. Encapsulation can limit decomposition by bringing such reactions to equilibrium and can prevent exposure to damaging ambient moisture. Shi et al. examined several encapsulation schemes for perovskite films and devices by probing volatile products with gas chromatography–mass spectrometry (see the Perspective by Juarez-Perez and Haro). Pressure-tight polymer/glass stack encapsulation was effective in suppressing gas transfer and allowed solar cells containing methylammonium to pass harsh moisture and thermal cycling tests.

    Science, this issue p. eaba2412; see also p. 1309

  12. Neuroscience

    Ensemble activity and perception

    1. Peter Stern

    The mechanisms by which sensory percepts are encoded in neural ensembles are still incompletely understood. Chong et al. used single-spot optogenetic stimulation to control neuronal activity in mouse olfactory glomeruli in space and time. Animals were trained to recognize a learned activity pattern that was likely perceived as a specific odor. The authors then systematically varied the activity patterns by changing either the activated glomeruli or the timing between activation of glomeruli to evaluate their impact on odor recognition. Glomeruli that were activated early during the synthetic odor contributed more to odor recognition than glomeruli that were subsequently activated. This approach allows neuroscience to explain how features combine in complex patterns to generate perception.

    Science, this issue p. eaba2357

  13. Neuroscience

    Secrets of Meissner corpuscles

    1. Peter Stern

    The Meissner corpuscle, a mechanosensory end organ, was discovered more than 165 years ago and has since been found in the glabrous skin of all mammals, including that on human fingertips. Although prominently featured in textbooks, the function of the Meissner corpuscle is unknown. Neubarth et al. generated adult mice without Meissner corpuscles and used them to show that these corpuscles alone mediate behavioral responses to, and perception of, gentle forces (see the Perspective by Marshall and Patapoutian). Each Meissner corpuscle is innervated by two molecularly distinct, yet physiologically similar, mechanosensory neurons. These two neuronal subtypes are developmentally interdependent and their endings are intertwined within the corpuscle. Both Meissner mechanosensory neuron subtypes are homotypically tiled, ensuring uniform and complete coverage of the skin, yet their receptive fields are overlapping and offset with respect to each other.

    Science, this issue p. eabb2751; see also p. 1311

  14. Coronavirus

    Mobile symptom tracking

    1. Caroline Ash

    The rapidity with which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads through a population is defying attempts at tracking it, and quantitative polymerase chain reaction testing so far has been too slow for real-time epidemiology. Taking advantage of existing longitudinal health care and research patient cohorts, Drew et al. pushed software updates to participants to encourage reporting of potential coronavirus disease 2019 (COVID-19) symptoms. The authors recruited about 2 million users (including health care workers) to the COVID Symptom Study (previously known as the COVID Symptom Tracker) from across the United Kingdom and the United States. The prevalence of combinations of symptoms (three or more), including fatigue and cough, followed by diarrhea, fever, and/or anosmia, was predictive of a positive test verification for SARS-CoV-2. As exemplified by data from Wales, United Kingdom, mathematical modeling predicted geographical hotspots of incidence 5 to 7 days in advance of official public health reports.

    Science, this issue p. 1362

  15. Measles

    Older origins of measles virus

    1. Caroline Ash

    Animal domestication by humans is thought to have given many pathogens an opportunity to invade a new host, and measles is one example of this. However, there is controversy about when measles emerged in humans, because the historical descriptions of measles are relatively recent (late ninth century CE). The controversy has persisted in part because ancient RNA is thought to be a poor target for molecular clock techniques. Düx et al. have overcome the ancient RNA challenge by sequencing a measles virus genome obtained from a museum specimen of the lungs of child who died in 1912 (see the Perspective by Ho and Duchêne). The authors used these and other more recent sequencing data in a Bayesian molecular clock–modeling technique, which showed that measles virus diverged from rinderpest virus in the sixth century BCE, indicating an early origin for measles possibly associated with the beginnings of urbanization.

    Science, this issue p. 1367; see also p. 1310

  16. Chemical Ecology

    A plant-herbivore information “arms race”

    1. Andrew M. Sugden

    The consumption of plants by herbivores has driven the evolution of many diverse plant defense chemicals to which herbivores have constantly adapted. The transmission of chemical information at the community level is less known but important given the plethora of plant and herbivore species, especially in tropical communities. Zu et al. propose an information “arms race” approach to explain plant-herbivore chemical communication at the community level (see the Perspective by Solé). To test their conceptual framework, they used field data of herbivore-plant interactions and plant–volatile organic compound associations in a tropical dry forest. Their approach provides an understanding of the functioning and persistence of systems where individuals send and receive information in the form of signals to which other individuals react and, in turn, affect the behavior of other participants in these systems.

    Science, this issue p. 1377; see also p. 1315

  17. Immunometabolism

    Inflammaging? Blame T cells!

    1. Seth Thomas Scanlon

    Mitochondrial dysfunction in various tissues is a prominent characteristic of age-related deterioration, but it is unclear how mitochondrial dysfunction in particular cell types contributes to this process. Desdín-Micó et al. generated mice with T cells that were specifically deficient in a mitochondrial DNA–stabilizing protein. These animals exhibited multiple features associated with aging, including neurological, metabolic, muscular, and cardiovascular impairments. The defective T cells initiated an inflammatory program similar to that observed in older animals, a process called “inflammaging.” Blocking the cytokine tumor necrosis factor–α or administering precursors of the cofactor nicotinamide adenine dinucleotide restored many of these symptoms of senescence. These findings may potentially inform future therapies for age-associated diseases, as well as cachexia and cytokine-release syndrome.

    Science, this issue p. 1371

  18. Phase Separation

    Drug partitioning in nuclear condensates

    1. Valda Vinson

    There is increasing interest in the function of phase-separated biomolecular condensates in cells because of their distinct properties and expanding roles in important biological processes. Klein et al. considered the fate of small-molecule therapeutics in the context of nuclear condensates (see the Perspective by Viny and Levine). They show that certain antineoplastic drugs have physicochemical properties that cause them to concentrate preferentially in condensates, both in vitro and in cancer cells. This property influences drug activity, and protein mutations that alter condensate formation can lead to drug resistance. Optimizing condensate partitioning may be valuable in developing improved therapeutics.

    Science, this issue p. 1386; see also p. 1314

  19. Vaccines

    Tempting T cells

    1. Lindsey Pujanandez

    Strategies to induce T cell responses during vaccination are difficult to execute. Esposito et al. tested a vaccine that uses the major histocompatibility complex class II invariant chain (Ii), which is important for antigen presentation to T cells, as an adjuvant in healthy volunteers. The so-called “prime-boost” strategy involved viral vectors and nonstructural antigens from hepatitis C virus. Inclusion of Ii boosted the magnitude and breadth of the T cell response. Work in a mouse vaccination model demonstrated that the Ii adjuvant enhanced proteasomal degradation of the vaccine antigens. This promising platform could be used to “tempt” T cells into vaccine responses, potentially resulting in successful vaccines for diseases that cannot be treated with conventional, antibody-driven vaccine protection.

    Sci. Transl. Med. 12, eaaz7715 (2020).

  20. Allergy

    Finding contributors to allergy control

    1. Ifor Williams

    House dust mites (HDMs) are a major source of aeroallergens that trigger human allergic responses, including asthma. To characterize the heterogeneity of human CD4+ T helper (TH) cell responses to HDM antigens, Seumois et al. stimulated blood T cells with HDM peptides and isolated the freshly activated T cells for single-cell RNA sequencing. One TH cell subset was more frequent in individuals without HDM allergy. These cells may function to restrain allergic T helper 2 (TH2) cell responses. Individuals with both HDM allergy and asthma were enriched for interleukin-9–producing TH2 cells. These findings provide a basis for designing more precise approaches to thwart pathogenic TH cell responses contributing to allergic asthma.

    Sci. Immunol. 5, eaba6087 (2020).

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