This Week in Science

Science  20 Sep 2019:
Vol. 365, Issue 6459, pp. 1260
  1. Paleontology

    Extinction leads to restructuring

    1. Sacha Vignieri

    Artist's rendering of a woolly mammoth. Such animals shaped Pleistocene ecosystems.

    CREDIT: DANIEL ESKRIDGE/ALAMY STOCK PHOTO

    By most accounts, human activities are resulting in Earth's sixth major extinction event, and large-bodied mammals are among those at greatest risk. Loss of such vital ecosystem components can have substantial impacts on the structure and function of ecological systems, yet fully understanding these effects is challenging. Tóth et al. looked at the loss of large-bodied mammals in the Pleistocene epoch to identify potential community assembly effects. They found that the demise of large mammals led to a restructuring and a shift from biotic to abiotic drivers of community structure. Understanding past changes may help predict the community-level effects of the extinctions we are currently driving.

    Science, this issue p. 1305

  2. Protein Folding

    Catch and release

    1. Valda Vinson

    Chaperones are essential for proper protein folding inside cells, but their interactions with client proteins are difficult to study because they are dynamic. Jiang et al. used nuclear magnetic resonance spectroscopy to look at how the chaperones Hsp70 and Hsp40 work together in the client binding and release cycle. Hsp40 alters the folding properties of the client protein, perhaps unfolding a non-native state, by binding dynamically through multiple binding sites. Hsp70 binding to Hsp40 displaces the unfolded client. The released protein may either fold to its native state, or be rebound for another chaperone cycle.

    Science, this issue p. 1313

  3. Topological Matter

    Magnetic Weyl semimetals

    1. Jelena Stajic

    Weyl semimetals (WSMs)—materials that host exotic quasiparticles called Weyl fermions—must break either spatial inversion or time-reversal symmetry. A number of WSMs that break inversion symmetry have been identified, but showing unambiguously that a material is a time-reversal-breaking WSM is tricky. Three groups now provide spectroscopic evidence for this latter state in magnetic materials (see the Perspective by da Silva Neto). Belopolski et al. probed the material Co2MnGa using angle-resolved photoemission spectroscopy, revealing exotic drumhead surface states. Using the same technique, Liu et al. studied the material Co3Sn2S2, which was complemented by the scanning tunneling spectroscopy measurements of Morali et al. These magnetic WSM states provide an ideal setting for exotic transport effects.

    Science, this issue p. 1278, p. 1282, p. 1286; see also p. 1248

  4. Tumor Immunology

    Priming responses to checkpoint blockade

    1. Anand Balasubramani

    Activation of intracellular DNA sensing has been proposed as a means to promote antitumor immunity, but molecules that regulate sensing of intracellular RNAs have received less attention. Heidegger et al. found that expression of the RNA sensor RIG-I in tumor cells plays a vital role in promoting responsiveness to an immune checkpoint therapy in mouse models of cancer. The authors used engineered melanoma cell lines to map the relative importance of various pathways in regulating antitumor immunity and responsiveness to checkpoint blockade. Activation of RNA sensing may be useful to increase the immunogenicity of poorly immunogenic tumors.

    Sci. Immunol. 4, eaau8943 (2019).

  5. HIV

    Taking RV144 beyond Thailand

    1. Lindsey Pujanandez

    The RV144 vaccine trial in Thailand is based on the only HIV vaccine to show efficacy against HIV infection to date. Gray et al. designed the HIV Vaccine Trials Network 097 trial to test this regimen in South Africa, where clade C HIV circulates. Examining immune protective responses previously identified in the RV144 trial, the authors found the vaccine to be even more immunogenic in South Africans, and the magnitude of protective antibody responses was greater compared with RV144. The RV144 regimen or others like it may therefore be protective in areas where clade C HIV is endemic.

    Sci. Transl. Med. 11, eaax1880 (2019).

  6. Neuroscience

    A brain pathway for active forgetting

    1. Peter Stern

    Sleep affects memories via several mechanisms. Izawa et al. identified a possible new pathway in the brain: REM sleep–active hypothalamic melanin-concentrating hormone (MCH)–producing neurons, which, among others, project to the hippocampus. Surprisingly, genetic ablation of MCH neurons increased memory performance in mice. Conversely, pharmacogenetic activation of MCH neurons impaired memory. In vitro physiological experiments showed that activation of MCH fibers in hippocampal slices suppressed spiking activity of pyramidal cells. These findings indicate that the MCH pathway may become a target for memory modulation.

    Science, this issue p. 1308

  7. Signal Transduction

    Worms yield opioid receptor insight

    1. L. Bryan Ray

    The µ-opioid receptor (MOR) is the target of pain-reducing drugs, including morphine and the potent synthetic opioid fentanyl. Better understanding of the receptor system is needed to suppress potentially deadly side effects and manage addiction potential. Wang et al. used a screen in the worm Caenorhabditis elegans to find genes that influenced MOR function (see the Perspective by Mercer Lindsay and Scherrer). They found another receptor called GPR139, loss of which enhanced effects of morphine in mice but reduced withdrawal effects. GPR139 could be a target to improve safety or efficacy of opioid therapy.

    Science, this issue p. 1267; see also p. 1246

  8. Biotechnology

    Tracking nucleic acids in living cells

    1. Steve Mao

    Fluorescence in situ hybridization (FISH) is a powerful molecular technique for detecting nucleic acids in cells. However, it requires cell fixation and denaturation. Wang et al. found that CRISPR-Cas9 protects guide RNAs from degradation in cells only when bound to target DNA. Taking advantage of this target-dependent stability switch, they developed a labeling technique, named CRISPR LiveFISH, to detect DNA and RNA using fluorophore-conjugated guide RNAs with Cas9 and Cas13, respectively. CRISPR LiveFISH improves the signal-to-noise ratio, is compatible with living cells, and allows tracking real-time dynamics of genome editing, chromosome translocation, and transcription.

    Science, this issue p. 1301

  9. Climate Change

    The need to stabilize global climate

    1. Andrew M. Sugden

    Climate change will be the greatest threat to humanity and global ecosystems in the coming years, and there is a pressing need to understand and communicate the impacts of warming, across the perspectives of the natural and social sciences. Hoegh-Guldberg et al. review the climate change–impact literature, expanding on the recent report of the Intergovernmental Panel on Climate Change. They provide evidence of the impacts of warming at 1°, 1.5°, and 2°C—and higher—for the physical system, ecosystems, agriculture, and human livelihoods. The benefits of limiting climate change to no more than 1.5°C above preindustrial levels would outweigh the costs.

    Science, this issue p. eaaw6974

  10. Hydrology

    River restoration guided by research

    1. Julia Fahrenkamp-Uppenbrink

    Human activities have altered the flow regimes of many of Earth's rivers, with negative impacts on biodiversity, water quality, and ecological processes. In a Review, Palmer and Ruhi explain how restoration designs now attempt to mimic ecologically important aspects of natural flow regimes, guided by insights into how variations in flow affect biota and ecosystem processes. To be successful, such efforts must go beyond accounting for flood pulses to restore natural flow variability and achieve hydrological connectivity between a river and its surroundings.

    Science, this issue p. eaaw2087

  11. Development

    Identifying terminal nematode cells

    1. Laura M. Zahn

    Single-cell RNA sequencing provides the power to identify the developmental trajectory of an organism. However, identifying the temporal lineage of cell development can be difficult without large-scale analyses. Packer et al. sequenced more than 80,000 cells from embryos of the roundworm Caenorhabditis elegans to determine the expression of genes directing the development of terminal cell types. Because all somatic cells in a C. elegans individual have been mapped, the authors are able to connect gene expression with cell lineages over time during development, noting stark transitions in some cases.

    Science, this issue p. eaax1971

  12. One Health

    Livestock antibiotic resistance

    1. Caroline Ash

    Most antibiotic use is for livestock, and it is growing with the increase in global demand for meat. It is unclear what the increase in demand for antibiotics means for the occurrence of drug resistance in animals and risk to humans. Van Boeckel et al. describe the global burden of antimicrobial resistance in animals on the basis of systematic reviews over the past 20 years (see the Perspective by Moore). There is a clear increase in the number of resistant bacterial strains occurring in chickens and pigs. The current study provides a much-needed baseline model for low- and middle-income countries and provides a “one health” perspective to which future data can be added.

    Science, this issue p. eaaw1944; see also p. 1251

  13. Topological Matter

    The topology of line nodes

    1. Jelena Stajic

    Band structure degeneracies in topological materials can take the form of lines or even chains of interconnected loops. Wu et al. study theoretically these nodal lines and how they evolve as the system parameters are varied. They focus on a class of materials that have weak spin-orbit coupling and that respect a combination of inversion- and time-reversal symmetry. Noncommutative topological charges are associated with nodal lines in such materials that place constraints on the configurations of these lines. Calculations indicate that elemental scandium under strain may provide a test system for this unconventional topology.

    Science, this issue p. 1273

  14. Surface Chemistry

    An 18-member carbon ring

    1. Phil Szuromi

    Carbon's allotropes include molecular species such as C60 and C70 fullerenes. Kaiser et al. now report the assembly of a large carbon ring, cyclo[18]carbon, from organic precursors whose reactivity was controlled by adsorbing them on a sodium chloride surface at 5 kelvin (see the Perspective by Maier). Manipulation, with an atomic force microscope tip, of a cyclocarbon oxide molecule, C24O6, led to elimination of carbon monoxide molecules and formation of the desired all-carbon ring. High-resolution imaging revealed alternating single and triple bonds versus an all-double-bond structure.

    Science, this issue p. 1299; see also p. 1245

  15. Life History

    The decline of resistance in old age

    1. Caroline Ash

    Infection, immunity, and demography are rarely measured simultaneously, despite being intertwined. Froy et al. measured an immune marker of resistance to infection by worm parasites (helminths) in Soay sheep off the remote Atlantic island of St. Kilda (see the Perspective by Gaillard and Lemaître). They used a library of 2000 blood samples from 800 known individuals that have been left to run wild and unmanaged. Resistance declines as the sheep age, which reduces a sheep's chances of surviving the winter. Helminths are an important component of many natural systems, including humans, and may thus become an increasing burden on health with age.

    Science, this issue p. 1296; see also p. 1244

  16. Plant Science

    Flood-resistance from gene regulation

    1. Pamela J. Hines

    Some plants tolerate flooding better than others. Reynoso et al. compared gene regulatory networks activated by flooding in rice, which is adapted to flooding, with those in species less adapted to flooding. Flood-related gene regulation was characterized according to chromatin accessibility as well as transcription. Although flood response circuitry is evident in dryland species as well, its activation is greater in wetland rice.

    Science, this issue p. 1291

  17. Immunology

    Tumors metabolically paralyze T cells

    1. John F. Foley

    The cytokine transforming growth factor–β (TGF-β) suppresses both immune and tumor cells. Dimeloe et al. found that TGF-β from tumor effusions suppressed the antitumor activity of CD4+ T cells by inhibiting their production of the inflammatory cytokine interferon-γ (IFN-γ). The effects of TGF-β were mediated by Smad proteins in the mitochondria and led to decreased mitochondrial respiration. Indeed, IFN-γ production by CD4+ T cells was suppressed by inhibiting a mitochondrial electron transport chain complex. These data suggest that TGF-β suppresses antitumor immunity by metabolically paralyzing T cells.

    Sci. Signal. 12, eaav3334 (2019).

  18. Neuroscience

    How learning to read changes the brain

    1. Kelly LaMarco

    Learning to read requires fine-tuning of perceptual and cognitive abilities and is thought to depend, in part, on an orthographically sensitive brain region in the visual cortex. Hervais-Adelman et al. conducted a large-scale functional magnetic resonance imaging study with individuals of varying degrees of literacy to test whether this brain region takes over cortical territory from neighboring areas of the brain. By examining cortical responses to orthographic and nonorthographic stimuli, they found that literacy enhances early visual responses rather than contracting the extent of tissue sensitive to other visual categories. The brain areas responsible for visual processing thus develop a dual representational capacity.

    Sci. Adv. 10.1126/sci adv.aax0262 (2019).