This Week in Science

Science  31 Aug 2018:
Vol. 361, Issue 6405, pp. 888
  1. Yellow Fever

    Arbovirus risk in Brazil

    1. Caroline Ash

    Yellow fever is moving from the forests to the cities.

    PHOTO: AMI VITALE/GETTY IMAGES

    Despite the existence of an effective vaccine for yellow fever, there are still almost 80,000 fatalities from this infection each year. Since 2016, there has been a resurgence of cases in Africa and South America—and this at a time when the vaccine is in short supply. The worry is that yellow fever will spread from the forests to the cities, because its vector, Aedes spp. mosquitoes, are globally ubiquitous. Faria et al. integrate genomic, epidemiological, and case distribution data from Brazil to estimate patterns of geographic spread, the risks of virus exposure, and the contributions of rural versus urban transmission (see the Perspective by Barrett). Currently, the yellow fever epidemic in Brazil seems to be driven by infections acquired while visiting forested areas and indicates spillover from susceptible wild primates.

    Science, this issue p. 894; see also p. 847

  2. Induced Seismicity

    Seismic limits for hard and soft rock

    1. Brent Grocholski

    Induced earthquakes from oil, gas, and geothermal energy exploration projects can damage infrastructure and concern the public. However, it remains unclear how far away from an injection site an earthquake can still be triggered. Goebel and Brodsky looked at 18 different earthquake-producing injection sites around the world to address this issue. Injecting fluid into softer layers increased the range for seismic hazard, whereas harder basement rock better confined the fluid. These findings should be considered when regulating and managing projects with the potential to induce seismicity.

    Science, this issue p. 899

  3. Solar Cells

    Perovskite/CIGS tandem cells

    1. Phil Szuromi

    Tandem solar cells can boost efficiency by using more of the available solar spectrum. Han et al. fabricated a two-terminal tandem cell with an inorganicorganic hybrid perovskite top layer and a Cu(In,Ga)Se2 (CIGS) bottom layer. Control of the roughness of the CIGS surface and the use of a heavily doped organic hole transport layer were crucial to achieve a 22.4% power conversion efficiency. The unencapsulated tandem cells maintained almost 90% of their efficiency after 500 hours of operation under ambient conditions.

    Science, this issue p. 904

  4. Genome Structure

    The structure of the genome

    1. Valda Vinson

    Beyond the sequence of the genome, its three-dimensional structure is important in regulating gene expression. To understand cell-to-cell variation, the structure needs to be understood at a single-cell level. Chromatin conformation capture methods have allowed characterization of genome structure in haploid cells. Now, Tan et al. report a method called Dip-C that allows them to reconstruct the genome structures of single diploid human cells. Their examination of different cell types highlights the tissue dependence of three-dimensional genome structures.

    Science, this issue p. 924

  5. Ecology

    Fisheries management and human adaptation

    1. Philippa J. Benson

    Finding effective ways to mitigate the future impacts of climate change on fisheries is critical. Previous efforts have not incorporated alternative human responses to climate change. These could limit or exacerbate ecosystem changes that affect fish stocks and population locations. Gaines et al. analyzed four fisheries management approaches that address fish stock–productivity adaptation and/or range-shift adaptation. They then applied these management scenarios to 915 species stocks worldwide. Implementing proactive and adaptive fishery management approaches would bring about higher global profits (154%), harvest (34%), and biomass (60%) as compared with strategies reflecting no management changes. Addressing both range shifts and productivity changes lead to greater benefits as compared with targeting one challenge alone.

    Sci. Adv. 10.1126/sciadv.aao1378 (2018).

  6. Pain

    A dual-targeting painkiller

    1. Mattia Maroso

    Opioids are among the most effective treatments for severe pain. Their pain-relieving effects are mediated by activation of the mu opioid receptor (MOR). Unfortunately, selective MOR agonists induce diverse side effects, including respiratory depression, tolerance, hyperalgesia, and dependence. Recently, activation of the nociceptin/orphanin FQ peptide receptor (NOR) has been reported to enhance MOR agonist–induced analgesia without producing side effects. Ding et al. developed a bifunctional MOR/NOR agonist called AT-121, which showed potent analgesic effects in nonhuman primates without inducing hyperalgesia, respiratory depression, or dependence. Bifunctional MOR/NOR agonists might thus represent a safe and effective pharmacological tool for treating severe pain.

    Sci. Transl. Med. 10, eaar3483 (2018).

  7. Molecular Motors

    Tiny cargos ferried along a track

    1. Michael A. Funk

    Control of molecules at the nanometer scale requires motors that convert potential energy into movement. Qing et al. designed a small molecule that could hop along a track of cysteine residues within a membrane-embedded protein pore. The direction of processive movement along the track was reversible, driven by an applied potential across the membrane. Cargos were attached to a carrier motor, and their position and chemical identity read out from changes in the current through the pore. These features enabled repeat observations of a single molecule as it moved back and forth on the track.

    Science, this issue p. 908

  8. Climate Change

    Warming, crops, and insect pests

    1. Andrew M. Sugden

    Crop responses to climate warming suggest that yields will decrease as growing-season temperatures increase. Deutsch et al. show that this effect may be exacerbated by insect pests (see the Perspective by Riegler). Insects already consume 5 to 20% of major grain crops. The authors' models show that for the three most important grain crops—wheat, rice, and maize—yield lost to insects will increase by 10 to 25% per degree Celsius of warming, hitting hardest in the temperate zone. These findings provide an estimate of further potential climate impacts on global food supply and a benchmark for future regional and field-specific studies of crop-pest-climate interactions.

    Science, this issue p. 916; see also p. 846

  9. Cancer

    Looping together genes in cancer

    1. Paula A. Kiberstis

    A subset of human cancers are characterized by aberrant fusion of two specific genes. In some cases, the activity of the resultant fusion protein drives tumor growth. Most fusion genes in cancer appear to arise from simple reciprocal chromosomal translocations. Anderson et al. found that the characteristic fusion gene in a bone and soft tissue tumor called Ewing sarcoma is produced by a far more complicated mechanism (see the Perspective by Imielinski and Ladanyi). In nearly half of the tumors examined, the fusion gene was created by the formation of dramatic genomic loops that disrupt multiple genes. These complex rearrangements occur in early replicating and transcriptionally active regions of the genome and are associated with poor prognosis.

    Science, this issue p. eaam8419; see also p. 848

  10. Signal Transduction

    Dynamics of cell signaling and decoding

    1. L. Bryan Ray

    Defects in cellular signaling pathways, like those in some cancer cells, are often thought to result in increased or decreased steady-state signals that promote or inhibit cell proliferation. But Bugaj et al. show that dynamic changes in the duration or frequency of a signal can also alter cellular responses (see the Perspective by Kolch and Kiel). They took precise control of signaling in cultured human or mouse cells with a light-controlled mechanism for activating and inactivating the guanosine triphosphate Ras. Known cancer mutations in components of the Ras-activated signaling pathway or inhibitors of particular pathway components altered signal timing and readouts. The modified dynamics changed transcriptional outcomes and could inappropriately support cell proliferation. The ability to probe responses of signaling networks in this way may enhance understanding of biological regulation and reveal new therapeutic targets.

    Science, this issue p. eaao3048; see also p. 844

  11. Biotechnology

    Lineage tracing in mouse using CRISPR

    1. Steve Mao

    A homing guide RNA (hgRNA) that directs CRISPR-Cas9 to its own DNA locus can diversify its sequence and act as an expressed genetic barcode. Kalhor et al. engineered a mouse line carrying 60 independent loci of hgRNAs, thus generating a large number of unique barcodes in various embryonic and extraembryonic tissues in fully developed mice. This method demonstrates lineage tracing from the very first branches of the development tree up to organogenesis events and was used to elucidate embryonic brain patterning.

    Science, this issue p. eaat9804

  12. Organometallics

    Carbonyls in the s block

    1. Jake Yeston

    Conventional wisdom in chemistry distinguishes transition metals from other elements by their use of d orbitals in bonding. Wu et al. now report that alkaline earth metals can slide their electrons from s- to d-orbital bonding motifs as well (see the Perspective by Armentrout). Calcium, strontium, and barium all form coordination complexes with a cubic arrangement of eight carbonyl ligands and an 18-electron valence shell. The compounds were characterized in frozen neon matrices by vibrational spectroscopy and in gas phase by mass spectrometry.

    Science, this issue p. 912; see also p. 849

  13. Climate Change

    Future predictions from paleoecology

    1. Andrew M. Sugden

    Terrestrial ecosystems will be transformed by current anthropogenic change, but the extent of this change remains a challenge to predict. Nolan et al. looked at documented vegetational and climatic changes at almost 600 sites worldwide since the last glacial maximum 21,000 years ago. From this, they determined vegetation responses to temperature changes of 4° to 7°C. They went on to estimate the extent of ecosystem changes under current similar (albeit more rapid) scenarios of warming. Without substantial mitigation efforts, terrestrial ecosystems are at risk of major transformation in composition and structure.

    Science, this issue p. 920

  14. Evolution

    Venoms yield their secrets

    1. Julia Fahrenkamp-Uppenbrink

    Venoms can be deadly but, in the right hands, can perform important therapeutic functions. Research into potential drug leads from venoms has, however, been hampered by an inability to study venoms from animals that are small, rare, or difficult to maintain in the laboratory. In a Perspective, Holford et al. highlight recent studies that have used genomics and other omics technologies to study venoms from a wide range of organisms, shedding light on the evolutionary biology of venoms. The work is also providing important leads for the development of therapeutics and eco-friendly insecticides.

    Science, this issue p. 842

  15. Cell Death

    Casting NETs

    1. Anand Balasubramani

    Gasdermin D (GSDMD), a pore-forming protein, has emerged as a key downstream effector in pyroptosis, a form of cell death induced by intracellular lipopolysaccharide. Sollberger et al. found that GSDMD was activated in neutrophils during the generation of neutrophil extracellular traps (NETs). NETs are composed of chromatin and antimicrobial proteins and are cast by dying neutrophils in a process termed NETosis. While carrying out a chemical screen to identify molecules that block NETosis, the authors identified a pyrazolo-oxazepine scaffold–based molecule that binds GSDMD. Chen et al. also report a role for GSDMD in NETosis, and Rathkey et al. report necrosulfonamide to be an inhibitor of GSDMD.

    Sci. Immunol. 3, eaar6689, eaar6676, eaat2738 (2018).

  16. GPCR Signaling

    Melatonin meets diabetes

    1. John F. Foley

    Some of the single-nucleotide polymorphisms associated with type 2 diabetes occur in the gene that encodes the melatonin receptor MT2, a G protein–coupled receptor (GPCR). Karamitri et al. measured the spontaneous and melatonin-stimulated signaling of 40 different MT2 variants. MT2 variants with defective melatonin-stimulated G protein signaling and reduced spontaneous β-arrestin recruitment were associated with the greatest risk for type 2 diabetes. These data may aid in developing specific type 2 diabetes treatments based on a patient's MT2 variant.

    Sci. Signal. 11, eaan6622 (2018).

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