This Week in Science

Science  27 Nov 2020:
Vol. 370, Issue 6520, pp. 1053
  1. Climatology

    A dangerous trend

    1. H. Jesse Smith

    East Asia, including the semiarid grasslands of Mongolia, has experienced a shift toward a hotter and drier climate in the past 20 years.

    PHOTO: MAURITIUS IMAGES GMBH / ALAMY STOCK PHOTO

    How anthropogenically driven climate change is affecting heat waves and drought is one of the most important environmental issues facing societies around the globe. Zhang et al. present a 260-year-long record of temperature and soil moisture over inner East Asia that reveals an abrupt shift to hotter and drier conditions (see the Perspective by Zhang and Fang). Extreme episodes of hotter and drier climate over the past 20 years, which are unprecedented in the earlier records, are caused by a positive feedback loop between soil moisture deficits and surface warming and potentially represent the start of an irreversible trend.

    Science, this issue p. 1095; see also p. 1037

  2. Ribosome Structure

    Quality control in mitochondria

    1. Valda Vinson

    Human mitochondria have their own genome and ribosomes called mitoribosomes that respectively encode and synthesize essential subunits of complexes that use the energy from the oxidation of metabolites to drive the synthesis of adenosine triphosphate (ATP). These complexes are key to the health of the cell. Desai et al. studied a mitoribosome-associated quality control pathway that prevents aberrant translation. They purified mitoribosomes under conditions designed to induce stalling and determined the structures of two intermediates in the rescue pathway. These structures revealed two proteins that eject the unfinished polypeptide chain and peptidyl transfer RNA from the ribosome. Their cryo–electron microscopy dataset also revealed additional states that may correspond to intermediates in the mitochondrial translation elongation cycle.

    Science, this issue p. 1105

  3. Topological Systems

    When all routes are exceptional

    1. Ian S. Osborne

    The exploration of non-Hermitian physics and parity-time symmetry have provided a route to develop a wealth of exotic physical effects. In such dissipative systems, the balance of gain and loss of the system lead to what are called exceptional points, or “sweet spots,” which relate to optimal device operation or material properties. The ability to tune the gain and loss over a range of system properties leads to exceptional arcs. Tang et al. show that systems can be designed in which the tuning of multiple parameters leads to a crossroads, or nexus, of exceptional arcs. Illustrating the effect in an acoustic system, the same properties should be attainable over various types of dissipative systems and thus provide a versatile route to fine-tune optimal performance of materials and devices.

    Science, this issue p. 1077

  4. 3D Printing

    Driving the pores away

    1. Brent Grocholski

    The formation of “keyholes” (vapor-filled depressions) during additive manufacturing leads to porosity, which degrades alloy performance, especially fracture properties, and remains a big challenge for the 3D printing of metals. Zhao et al. used high-speed x-ray imaging to take a detailed look at how keyhole formation connects to porosity in a titanium alloy. They found that instability at the keyhole tip drives pores away to get trapped in the solidification front. Understanding this process and the operating parameters under which it occurs provides a roadmap for avoiding porosity and building high-quality metal parts.

    Science, this issue p. 1080

  5. Synthetic Biology

    A logic to cell-cell recognition

    1. Valda Vinson

    There has been exciting progress in the field of cancer immunotherapy, which harnesses a patient's own immune system to kill cancer cells. However, achieving precise recognition of cancer cells remains challenging. Cells engineered with synthetic Notch (synNotch) receptors bind to specific antigens, and binding induces the expression of defined genes. Williams et al. used synNotch modules as transcriptional connectors that daisy-chain together multiple receptors. They engineered T cells that can recognize up to three target antigens expressed on or inside cancer cells and integrated these inputs to achieve NOT, AND, and OR logic. The engineered cells achieved precise recognition of targeted cancer cells.

    Science, this issue p. 1099

  6. Sex Determination

    Paternal factor specifies female wasps

    1. Beverly A. Purnell

    Not all animals have specialized sex chromosomes to determine their sex. In hymenopteran insects, for example, unfertilized eggs become males and fertilized eggs become females. Prior work showed that the paternal genome provides instruction for female development. Zou et al. identified a sex determination instructor gene, wasp overruler of masculinization, with parent-of-origin effect, in the parasitoid Nasonia vitripennis. It is only transcribed from the paternally provided genome in fertilized eggs to initiate female development. This discovery provides insights into the molecular basis and evolution of sex determination.

    Science, this issue p. 1115

  7. Marine Robotics

    Deep dive

    1. Michael M. Lee

    Researchers launch Clio, an autonomous deep-ocean exploration and sample-collection vehicle.

    PHOTO: CPAUL LETHABY BERMUDA INSTITUTE OF OCEAN SCIENCES

    Mapping the ocean's biochemistry will lead to a better understanding of Earth's biogeochemical cycles. Breier et al. developed an untethered autonomous underwater vehicle, which they named Clio, to map vertical profiles of the water column through high-resolution sensor surveys and sample-return missions. Clio could controllably descend through the water column at a rate of 0.8 meters per second with a maximum depth of 6000 meters. In 2019, Clio was deployed to map 1144 kilometers of the Sargasso Sea to a depth of 1000 meters.

    Sci. Robot. 5 abc7104 (2020).

  8. Drugs

    Helping asthmatics breathe better

    1. Wei Wong

    β2-adrenoreceptor agonists used for acute relief of airway constriction in asthmatic patients become less effective with repeated use because of receptor desensitization. They also increase the risk of death. Using cells, lung slices, and mouse models of asthma, Wang et al. showed that osthole, a compound derived from a traditional Chinese medicine, promoted airway relaxation through mechanisms other than activating β2-adrenoreceptors. These results suggest that variants of osthole could be developed to induce bronchodilation without desensitizing receptors or increasing the risk of death.

    Sci. Signal. 13, eaax0273 (2020).

  9. Synthetic Biology

    Engineering immune responses

    1. Gemma Alderton

    Cytokines mediate various immune responses and have potential as drugs to treat cancer and other diseases. However, cytokines have diverse and competing roles; although some cytokine therapies are approved, they come with side effects and their efficacy can be limited. In a Perspective, Li and Lim discuss the synthetic biology approaches to engineering better cytokine-based drugs. They discuss improving on naturally occurring cytokines, engineering cytokine-signaling circuits for use with engineered cell therapies, and the possibility of designing cytokines that do not exist naturally. If efficacious, such approaches could improve the potency of cytokines as drugs and add to our understanding of cytokine-based communication.

    Science, this issue p. 1034

  10. Protein Modeling

    Understanding what drives proteins

    1. Valda Vinson

    Computational molecular physics (CMP) aims to leverage the laws of physics to understand not just static structures but also the motions and actions of biomolecules. Applying CMP to proteins has required either simplifying the physical models or running simulations that are shorter than the time scale of the biological activity. Brini et al. reviewed advances that are moving CMP to time scales that match biological events such as protein folding, ligand unbinding, and some conformational changes. They also highlight the role of blind competitions in driving the field forward. New methods such as deep learning approaches are likely to make CMP an increasingly powerful tool in describing proteins in action.

    Science, this issue p. eaaz3041

  11. Neurogenomics

    An in vivo analysis of autism risk genes

    1. Laura M. Zahn

    CRISPR targeting in vivo, especially in mammals, can be difficult and time consuming when attempting to determine the effects of a single gene. However, such studies may be required to identify pathological gene variants with effects in specific cells along a developmental trajectory. To study the function of genes implicated in autism spectrum disorders (ASDs), Jin et al. applied a gene-editing and single-cell–sequencing system, Perturb-Seq, to knock out 35 ASD candidate genes in multiple mice embryos (see the Perspective by Treutlein and Camp). This method identified networks of gene expression in neuronal and glial cells that suggest new functions in ASD-related genes.

    Science, this issue p. eaaz6063; see also p. 1038

  12. Coronavirus

    Profiling coronaviruses

    1. Valda Vinson

    Among the coronaviruses that infect humans, four cause mild common colds, whereas three others, including the currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), result in severe infections. Shrock et al. used a technology known as VirScan to probe the antibody repertoires of hundreds of coronavirus disease 2019 (COVID-19) patients and pre–COVID-19 era controls. They identified hundreds of antibody targets, including several antibody epitopes shared by the mild and severe coronaviruses and many specific to SARS-CoV-2. A machine-learning model accurately classified patients infected with SARS-CoV-2 and guided the design of an assay for rapid SARS-CoV-2 antibody detection. The study also looked at how the antibody response and viral exposure history differ in patients with diverging outcomes, which could inform the production of improved vaccine and antibody therapies.

    Science, this issue p. eabd4250

  13. Transcription

    Dephosphorylating RNA polymerase II

    1. Di Jiang

    Transcription in metazoans requires coordination of multiple factors to control the progression of polymerases and the integrity of their RNA products. Zheng et al. identified a new dual-enzyme complex called INTAC, which is composed of protein phosphatase 2A (PP2A) core enzyme and the multisubunit RNA endonuclease Integrator. Structural and functional studies show that INTAC functions as a noncanonical PP2A holoenzyme that dephosphorylates the C-terminal domain of RNA polymerase II to attenuate transcription. This study provides a direct connection between PP2A-mediated dephosphorylation and transcriptional regulation, two fundamental cellular processes.

    Science, this issue p. eabb5872

  14. Cell Biology

    Tension where multiple cells meet

    1. Beverly A. Purnell

    Cells exist in varying environments and must respond to specific stimuli. During development, epithelial cells need to rapidly reorganize under tension without compromising epithelial integrity. Yu et al. demonstrate that Drosophila epithelial cells achieve this by transiently stabilizing adhesion at tricellular junctions where three cells meet (see the Perspective by Raghavan and Vasioukhin). The conserved adhesion regulator Canoe/Afadin is recruited to tricellular junctions under tension within seconds and dissociates when tension is released through a mechanism that requires Abl-dependent tyrosine phosphorylation. These results identify an in vivo mechanotransduction pathway that dynamically couples tricellular adhesion with physiological forces, allowing cells to rapidly modulate their behavior in response to mechanical changes in their environment.

    Science, this issue p. eaba5528; see also p. 1036

  15. Fundamental Physics

    Testing physics using the hydrogen atom

    1. Yury Suleymanov

    Discrepancy between the proton radius determined from hydrogen and muonic hydrogen spectroscopy data, the so-called “proton radius puzzle,” has been a focus of the physics community for more than a decade now. Using two-photon ultraviolet frequency comb spectroscopy below 1 kilohertz, Grinin et al. report a high-precision measurement of the 1S-3S transition frequency in atomic hydrogen (see the Perspective by Ubachs). Combining this measurement with the data for the 1S-2S transition, the authors obtained the Rydberg constant with improved accuracy and an independent value for the proton charge radius that favors the data from muonic hydrogen. However, the present frequency value differs from the one obtained previously using a different spectroscopic technique, leaving the puzzle still unresolved.

    Science, this issue p. 1061; see also p. 1033

  16. Forest Ecology

    Limits to the growing season

    1. Andrew M. Sugden

    The length of the growing season in temperate forests has been increasing under recent climate change because of earlier leaf emergence and later leaf senescence. However, Zani et al. show that this trend might be reversed as increasing photosynthetic productivity begins to drive earlier autumn leaf senescence (see the Perspective by Rollinson). Using a combination of experimental, observational, and modeling studies based on European forest trees, the researchers conclude that leaf senescence will advance by 3 to 6 days by the end of the 21st century rather than lengthening by 1 to 3 weeks as current phenological models have predicted. In turn, this predicted phenological pattern will limit the capacity of temperate forests to mitigate climate change through carbon uptake.

    Science, this issue p. 1066; see also p. 1030

  17. Chemical Physics

    Roaming dynamics in real time

    1. Yury Suleymanov

    Roaming is distinct from conventional reaction channels because of the unusual geometries that chemical systems use to bypass the minimum energy pathway. It is a relatively new phenomenon that is usually determined in experiments through spectroscopic characterization of the roaming products. Using a combination of time-resolved Coulomb explosion imaging and quasiclassical trajectory analysis, Endo et al. report real-time observation of individual fragments of the prototypical reaction of deuterated formaldehyde (D2CO) dissociation as they roam on ultrafast time scales. They show that roaming not only occurs several orders of magnitude earlier than previously expected but also that it can terminate in a radical (D + DCO) rather than the well-known molecular (D2 + CO) product channel.

    Science, this issue p. 1072

  18. Conservation Genetics

    Survival of the most variable

    1. Sacha Vignieri

    As more species become highly threatened because of human activity, there has been an increasing push to understand how best to reintroduce or translocate individuals from wild or captive populations. Suggestions have varied from choosing individuals from the most environmentally similar regions to choosing those that might have the best ability to adapt to new environments. Scott et al. used long-term data collected during translocations of Mojave Desert tortoises, including animals formerly kept as pets, to test these questions. Although the overall rates of survival for all tortoises at the site (both reintroduced and native) were extremely low, translocated individuals with the highest heterozygosity survived at much higher rates than those determined to be similar to the target population.

    Science, this issue p. 1086

  19. Coronavirus

    Structure of a vaccine candidate

    1. Valda Vinson

    Much effort is being targeted at developing vaccines that will provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A trimeric spike protein that decorates the virus is a primary target of the host immune system and the focus of vaccine development. Bangaru et al. present the structure of a leading vaccine candidate: a full-length spike protein with some modifications aimed at enhancing stability that is formulated in polysorbate 80 detergent. The study confirms that the full-length immunogen is in a stable prefusion conformation and provides a basis for understanding immune responses to the vaccine.

    Science, this issue p. 1089

  20. Coronavirus

    A beneficial cocktail

    1. Valda Vinson

    Since the start of the coronavirus disease 2019 (COVID-19) pandemic, considerable effort has gone into generating and characterizing neutralizing antibodies that could be used as therapeutics. Studies in humanized mice and convalescent humans led to the development of a cocktail of two potent antibodies that simultaneously bind to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and prevent the virus from entering host cells. Baum et al. evaluated the efficacy of this cocktail, REGN-COV2, in rhesus macaques, which may model mild disease, and in golden hamsters, which present more severe symptoms. The antibody cocktail provided benefits in both models when administered either prophylactically or therapeutically and is currently in clinical trials.

    Science, this issue p. 1110

  21. Neuroimmunology

    Regulatory IgA response

    1. Ifor Williams

    Multiple sclerosis (MS) is associated with the production of oligoclonal immunoglobulin G (IgG) antibodies within the central nervous system (CNS), but less is known about the status of IgA-producing cells. Pröbstel et al. detected clonally expanded IgA+ cells in cerebrospinal fluid and tissue adjacent to areas of active MS-associated demyelination. Recombinant IgA antibodies assembled from the cloned antibody genes bound to surface antigens found on multiple bacterial phyla but did not cross-react with brain tissue. Recruitment of gut-associated IgA+ B cells and plasma cells to the CNS is a potential biomarker of disease activity in MS.

    Sci. Immunol. 5, eabc7191 (2020).

  22. Alzheimer's Disease

    Understanding protein trafficking defects

    1. Mattia Maroso

    Alzheimer's disease (AD) is characterized by abnormal protein accumulation in the extracellular milieu in the brain. The endosomal pathway is responsible for proteolytic cleavage and secretion of proteins, and recent data have shown that a defective endosomal pathway contributes to AD pathogenesis. However, which proteins are affected by defective endosomal pathways is still unclear. Simoes et al. performed proteomic analysis in cerebrospinal fluid from mice with defective endosomal trafficking and in patients with AD and showed that the expression of two transmembrane proteins, APLP1 and CHL, was increased and correlated with tau expression. The results provide valuable insights regarding the effect of endosomal trafficking alterations in AD.

    Sci. Transl. Med. 12, eaba6334 (2020).

  23. Water Resources

    Missing freshwater found off Hawai'i

    1. Kip Hodges

    Freshwater resources are limited on oceanic islands, and their scarcity complicates sustainability efforts. Attias et al. identified an important new freshwater resource in the submarine environment offshore of the island of Hawai'i. Previous studies suggested that as much as 40% of water input to the onshore aquifer is missing and unavailable for use. The salinity of seawater makes it more electrically conductive than freshwater, and electromagnetic imaging surveys off the coast of Hawai'i revealed large quantities of freshwater in deep submarine sediments just offshore. These alternative water resources improve the prospects of sustainable water extraction for Hawai'i, and the authors speculate that the same mechanism may operate on other volcanic islands.

    Sci. Adv. 10.1126/sciadv.abd4866 (2020).

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