This Week in Science

Science  21 Feb 2020:
Vol. 367, Issue 6480, pp. 864
  1. Developmental Biology

    Putting vertebrate development on hold

    1. Beverly A. Purnell

    Fluorescence microscopy image of African turquoise killifish embryos

    CREDIT: CHI-KUO HU

    Suspended animation is an often-used device in science fiction, but it also exists in several forms in nature: hibernation, torpor, and diapause. Hu et al. studied diapause in the African turquoise killifish, a vertebrate model system (see the Perspective by Van Gilst). They found that diapause protects a complex living organism without trade-offs for future growth, fertility, and even life span. Diapause is actively regulated, with a dynamic switch to specific Polycomb complex members. One Polycomb member, CBX7, is critical for the regulation of organ genes and is involved in muscle preservation and diapause maintenance. This work illuminates the mechanisms that underlie suspended life.

    Science, this issue p. 870; see also p. 851

  2. Optomechanics

    A nanoparticle trapped and cooled

    1. Ian S. Osborne

    Cooling massive particles to the quantum ground state allows fundamental tests of quantum mechanics to be made; it would provide an experimental probe of the boundary between the classical and quantum worlds. Delić et al. laser-cooled an optically trapped solid-state object (a ∼150-nanometer-diameter silic a nanoparticle) into its quantum ground state of motion starting from room temperature. Because the object is levitated using optical forces, the experimental configuration can be switched to free fall, thereby providing a test bed for several macroscopic quantum experiments.

    Science, this issue p. 892

  3. Nanomaterials

    Larger monolayers with gold tapes

    1. Phil Szuromi

    Although the exfoliation of monolayers of materials such as transition metal dichalcogenides produces high-quality electronic materials with low defect densities, the size of the monolayers is limited to the micrometer scale. Liu et al. modified this method by creating atomically flat gold layers on polymer supports. The strong van der Waals adhesion of the gold layer allowed monolayers to be exfoliated on the centimeter scale. Multilayers could be reassembled to artificial structures, such as a MoSe2/WSe2 single-crystal bilayer with a twist angle chosen to quench intralayer exciton formation.

    Science, this issue p. 903

  4. Animal Cognition

    These bees have “seen” that before

    1. Sacha Vignieri

    Humans excel at mental imagery, and we can transfer those images across senses. For example, an object out of view, but for which we have a mental image, can still be recognized by touch. Such cross-modal recognition is highly adaptive and has been recently identified in other mammals, but whether it is widespread has been debated. Solvi et al. tested for this behavior in bumble bees, which are increasingly recognized as having some relatively advanced cognitive skills (see the Perspective by von der Emde and Burt de Perera). They found that the bees could identify objects by shape in the dark if they had seen, but not touched, them in the light, and vice versa, demonstrating a clear ability to transmit recognition across senses.

    Science, this issue p. 910; see also p. 850

  5. Atmospheric Science

    Air contaminants act differently indoors

    1. Kip Hodges

    Indoor air quality strongly affects human health, and features of the indoor environment influence exposure to contaminants. Wang et al. found that many molecules that are volatile in typical outdoor air conditions are more abundant indoors, exhibit semivolatile behaviors on surface reservoirs, and participate in dynamic surface-gas partitioning. This model may provide a better understanding of how chemicals respond to different indoor surface reservoirs and how to mitigate exposure to indoor pollutants.

    Sci. Adv. 10.1126/sciadv.aay8973 (2020).

  6. Cardiology

    Prosthetics provide room to grow

    1. Caitlin Czajka

    Children with congenital heart disease who require heart valve replacement often must undergo multiple high-risk surgeries because the replacement valve cannot grow as their heart grows. Inspired by this problem, Hofferberth et al. developed a prosthetic valve that mimics the geometry of the human venous valve, which maintains function despite large fluctuations in blood volume. The prosthesis, composed of polymeric leaflets attached to a stainless-steel stent, can be mechanically expanded using transcatheter balloon dilation to adapt to larger fluid volumes. Size-adaptable valves maintained function when implanted into growing lambs and could be mechanically expanded over 10 weeks.

    Sci. Transl. Med. 12, eaay4006 (2020).

  7. Structural Biology

    Choosing the drug to fit the protein

    1. Valda Vinson

    Many approved drugs bind to G protein–coupled receptors (GPCRs). A challenge in targeting GPCRs is that different ligands preferentially activate different signaling pathways. Two papers show how biased signaling arises for the angiotensin II type 1 receptor that couples to two signaling partners (G proteins and arrestins). Suomivuori et al. used large-scale atomistic simulations to show that coupling to the two pathways is through two distinct GPCR conformations and that extracellular ligands favor one or the other conformation. Wingler et al. present crystal structures of the same receptor bound to ligands with different bias profiles. These structures show conformational changes in and around the binding pocket that match those observed in simulations. This work could provide a framework for the rational design of drugs that are more effective and have fewer side effects.

    Science, this issue p. 881, p. 888

  8. Topological Matter

    Quantum anomalous Hall goes intrinsic

    1. Jelena Stajic

    Quantum anomalous Hall effect—the appearance of quantized Hall conductance at zero magnetic field—has been observed in thin films of the topological insulator Bi2Se3 doped with magnetic atoms. The doping, however, introduces inhomogeneity, reducing the temperature at which the effect occurs. Two groups have now observed quantum anomalous Hall effect in intrinsically magnetic materials (see the Perspective by Wakefield and Checkelsky). Serlin et al. did so in twisted bilayer graphene aligned to hexagonal boron nitride, where the effect enabled the switching of magnetization with tiny currents. In a complementary work, Deng et al. observed quantum anomalous Hall effect in the antiferromagnetic layered topological insulator MnBi2Te4.

    Science, this issue p. 900, p. 895; see also p. 848

  9. Regenerative Medicine

    Next steps in heart disease cell therapy

    1. Gemma Alderton

    Almost 20 years ago, the first trials that implanted stem cells into the heart were carried out. The aim of those trials, and many since, has been to regenerate lost heart muscle to recover function after a heart attack. However, numerous cell therapy strategies using adult stem cells have not shown efficacy in patients, despite positive preclinical experiments in animal models. In a Perspective, Murry and MacLellan discuss the reasons underlying this lack of success in the clinic, including lack of stem cell engraftment and survival. An emerging strategy to overcome these problems is the use of pluripotent stem cells, which have demonstrated long-term engraftment and regeneration in preclinical studies. The authors discuss the future hurdles that need to be overcome to successfully develop this cell therapy.

    Science, this issue p. 854

  10. Plant Ecology

    The pervasive power of mycorrhizas

    1. Andrew M. Sugden

    Associations between plants and symbiotic fungi—mycorrhizas—are ubiquitous in plant communities. Tedersoo et al. review recent developments in mycorrhizal research, revealing the complex and pervasive nature of this largely invisible interaction. Complex networks of mycorrhizal hyphae connect the root systems of individual plants, regulating nutrient flow and competitive interactions between and within plant species, controlling seedling establishment, and ultimately influencing all aspects of plant community ecology and coexistence.

    Science, this issue p. eaba1223

  11. Immunogenomics

    Thymus development, cell by cell

    1. Laura M. Zahn

    The human thymus is the organ responsible for the maturation of many types of T cells, which are immune cells that protect us from infection. However, it is not well known how these cells develop with a full immune complement that contains the necessary variation to protect us from a variety of pathogens. By performing single-cell RNA sequencing on more than 250,000 cells, Park et al. examined the changes that occur in the thymus over the course of a human life. They found that development occurs in a coordinated manner among immune cells and with their developmental microenvironment. These data allowed for the creation of models of how T cells with different specific immune functions develop in humans.

    Science, this issue p. eaay3224

  12. Vaccines

    Pitching cGAMP as a vaccine strategy

    1. Seth Thomas Scanlon

    One strategy to address the variable effectiveness of many influenza vaccines is to induce antiviral resident memory T cells, which can mediate cross-protection against multiple substrains (heterosubtypic immunity). Unfortunately, such vaccines typically use attenuated active viruses, which may be unsafe for certain populations. Wang et al. report a vaccine using an inactivated virus that effectively induced heterosubtypic immunity in both mice and ferrets (see the Perspective by Herold and Sander). They coadministered the virus with 2′,3′-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), a potent activator of the innate immune system, encapsulated in pulmonary surfactant–biomimetic liposomes. This adjuvant was taken up by alveolar epithelial cells, whose activation resulted in effective antiviral T cell and humoral immune responses without accompanying immunopathology.

    Science, this issue p. eaau0810; see also p. 852

  13. Structural Biology

    Architecture of human BAF complex

    1. Steve Mao

    The SWI/SNF family chromatin remodelers regulate chromatin and transcription. The protein complexes BAF and PBAF are mammalian SWI/SNF remodelers that play essential functions in diverse developmental and physiological processes. He et al. determined the structure of the human BAF complex, which contains three modules that bind the nucleosome on the top, bottom, and side, making this nucleosome-recognition pattern distinct from other chromatin remodelers. Mutations in BAF that are frequently associated with human cancer cluster into a nucleosome-interacting region. This structure provides a framework for understanding the BAF-mediated chromatin remodeling mechanism and its dysregulation in cancer.

    Science, this issue p. 875

  14. Atmospheric Methane

    Small burden from old sources

    1. H. Jesse Smith

    Methane is a potent greenhouse gas with large natural sources, reservoirs, and sinks. Dyonisius et al. found that methane emissions from old, cold-region carbon reservoirs like permafrost and methane hydrates were minor during the last deglaciation (see the Perspective by Dean). They analyzed the carbon isotopic composition of atmospheric methane trapped in bubbles in Antarctic ice and found that methane emissions from those old carbon sources during the warming interval were small. They argue that this finding suggests that methane emissions in response to future warming likely will not be as large as some have suggested.

    Science, this issue p. 907; see also p. 846

  15. Enzyme Regulation

    Evolution of a kinase allosteric site

    1. Michael A. Funk

    Enzyme activity is often regulated by conformational changes coupled to binding of an effector at an allosteric site, a feature especially important for enzymes involved in signaling cascades. Hadzipasic et al. studied the origins of allosteric regulation of Aurora A, a kinase involved in progression of the eukaryotic cell cycle. Aurora A is allosterically regulated through the binding of an effector protein named TPX2, which also targets the kinase to spindle microtubules. By reconstructing ancestor kinase sequences, they found that TPX2 bound to an early Aurora A but had very weak activation that was gradually strengthened by evolution of an allosteric network within the kinase. An evolutionary advantage from localizing the active protein at the mitotic spindle may have driven the development of this regulatory mechanism.

    Science, this issue p. 912

  16. Cancer

    Treatments from the dark kinome

    1. Leslie K. Ferrarelli

    Ovarian cancer is frequently fatal because it is difficult to detect and challenging to treat. Using cell lines and patient tumors, Kurimchak et al. analyzed the functional kinome of high-grade serous ovarian carcinoma (HGSOC) and identified a kinase called MRCKA as being important for HGSOC cell survival and tumor growth. Decreasing abundance of this kinase or inhibiting its activity killed HGSOC cells but led to activation of other survival-promoting kinases in the remaining cells, which could be targeted by cotreating cells with a different kinase inhibitor or platinum-based chemotherapy.

    Sci. Signal. 13, eaax8238 (2020).

  17. Biocatalysis

    Enzymes lock in planar chirality

    1. Michael A. Funk

    Molecules with very large rings—macrocycles—are often conformationally constrained, and some exhibit planar chirality when substituents of the ring cannot rotate freely. Restricted rotation is generally valued in macrocycles because it can hold the molecule in functional conformations. Using a well-established lipase enzyme, Gagnon et al. developed a synthesis of planar chiral macrocycles with handles that can be easily functionalized. Computational docking suggests how using an enzyme as the catalyst for sequential acylation reactions can impart the observed stereochemistry.

    Science, this issue p. 917

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