This Week in Science

Science  14 Apr 2017:
Vol. 356, Issue 6334, pp. 149
  1. Immunotherapy

    Targeting nonviral antigens in viral-driven cancer

    1. Priscilla N. Kelly

    Colored electron microscopy image of a human cervical cancer cell

    CREDIT: STEVE GSCHMEISSNER/SCIENCE SOURCE

    Adoptive cell transfer harnesses a patient's own T cells to destroy cancer. The strategy can successfully treat epithelial tumors driven by human papillomavirus (HPV), but it remains unclear why only some patients respond. Stevanović et al. examined the antitumor T cell response associated with HPV+ cervical cancers that underwent complete regression. Unexpectedly, reactive T cells were not directed against virally associated antigens, but rather against cancer germline antigens or neoantigens not previously recognized by the immune system. These findings counter the widely held belief that T cell responses against viral antigens are responsible for therapeutic effects in HPV-driven cancers.

    Science, this issue p. 200

  2. Planetary Geology

    Hydrothermal processes on Enceladus

    1. Keith T. Smith

    Saturn's moon Enceladus has a subsurface ocean covered by a layer of ice. Some liquid escapes into space through cracks in the ice, which is the source of one of Saturn's rings. In October 2015, the Cassini spacecraft flew directly through the plume of escaping material and sampled its chemical composition. Waite et al. found that the plume contains molecular hydrogen, H2, a sign that the water in Enceladus' ocean is reacting with rocks through hydrothermal processes (see the Perspective by Seewald). This drives the ocean out of chemical equilibrium, in a similar way to water around Earth's hydrothermal vents, potentially providing a source of chemical energy.

    Science, this issue p. 155; see also p. 132

  3. Solar Cells

    Transporter layers for greater stability

    1. Phil Szuromi

    Although perovskite solar cells (PSCs) can have power conversion efficiencies exceeding 20%, they can have limited stability under ultraviolet irradiation. This is in part because the mesoporous TiO2 used as an electron-transporting layer can photocatalyze unwanted reactions in the perovskite layer. Shin et al. report a low-temperature colloidal method for depositing La-doped BaSnO3 films as a replacement for TiO2 to reduce such ultraviolet-induced damage. Solar cells retained over 90% of their initial performance after 1000 hours of full-Sun illumination.

    Science, this issue p. 167

  4. Organic Chemistry

    Stitching a belt out of carbon rings

    1. Jake Yeston

    If you had a molecular scalpel, you could slice a carbon nanotube twice against the long axis to excise a loop of fused phenyl rings. Of course, knives don't come that small. Instead, Povie et al. succeeded in stitching together such a nanometer-scale belt in bottom-up fashion from molecular components, using consecutive Wittig reactions (see the Perspective by Siegel). The belt of 12 edge-sharing rings could ultimately be a first step toward more precisely controlled bottom-up syntheses of extended nanotubes.

    Science, this issue p. 172; see also p. 135

  5. Zika Virus

    One antibody for all and all antibodies for one

    1. Caroline Ash

    Antibodies against related flaviviruses such as dengue (DENV) and West Nile (WNV) can cross-react with Zika virus (ZIKV) and could thereby increase disease severity. Bardina et al. tested whether DENV and WNV antibodies from humans, or even yellow fever vaccination, could enhance ZIKV infection. In a mouse model, low titers of DENV and WNV antibodies enhanced ZIKV viremia, especially in the spinal cord and testes, whereas high titers remained protective. Generally, WNV antibodies were less disease-enhancing than DENV antibodies, and, in macaques, yellow fever vaccination had very little effect.

    Science, this issue p. 175

  6. Structural Biology

    Nucleosomes in contact

    1. Valda Vinson

    Dinucleosome complexes form during eukaryotic cell replication.

    CREDIT: KATO ET AL.

    In eukaryotic cells, genomic DNA must be compacted to fit inside the nucleus. A key player in DNA packaging is the nucleosome, which comprises a segment of DNA wrapped around an octamer of histone proteins. During replication and transcription, nucleosomes must reposition themselves on the DNA. In this process, nucleosomes can collide to form a dinucleosome. Kato et al. report a high-resolution crystal structure of a dinucleosome. One of the octamers has lost a histone dimer so that the dinucleosome comprises an octamer and a hexamer. The structure may represent an intermediate during chromatin remodeling.

    Science, this issue p. 205

  7. Defaunation

    Quantifying hunting-induced defaunation

    1. Sacha Vignieri

    As the human population grows and increasingly encroaches on remaining wildlife habitat, hunting threatens many species. Benítez-López et al. conducted a large-scale meta-analysis of hunting trends and impacts across the tropics (see the Perspective by Brashares and Gaynor). Bird and mammal populations were considerably lower in areas where hunting occurred. Although commercial hunting and proximity to roads and urban centers were the most damaging factors, all hunting had worrying impacts, even in protected areas. Protection and alternative approaches for sustainable subsistence hunting must be implemented soon if we are to prevent further, rapid defaunation.

    Science, this issue p. 180; see also p. 136

  8. Physiology

    A target for preventing kidney damage

    1. Annalisa VanHook

    Proteinuria, the appearance of protein in the urine, results when podocytes in the kidney are damaged. Rinschen et al. found that the activation of the transcriptional coactivator YAP and the expression of YAP target genes preceded proteinuria in rats with chemically induced nephrosis. YAP activity can be stimulated by mechanical stress, and activation of YAP in cultured podocytes depended on the stiffness of the substrate. A YAP inhibitor ameliorated proteinuria and damage-induced mechanosignaling in the nephrotic rat kidneys.

    Sci. Signal. 10, eaaf8165 (2017).

  9. Social Sciences

    The negative impact of EU enlargement

    1. Aaron Clauset

    National borders and restrictions on immigration can strongly hinder international scientific work. Arrieta et al. used detailed data on scientific productivity, collaboration, and mobility before and after the 2004 enlargement of the European Union (EU) to estimate the impact of EU integration on cross-border collaborations. The results suggest that the 12 new EU nations would have experienced higher rates of cross-border collaboration without integration. This effect is driven by high-skill migration to Western EU nations through cross-border competition for the newly mobile scientists.

    Sci. Adv. 10.1126.sciadv.1602232 (2017).

  10. Organic Chemistry

    Stitching one alkyl group to another

    1. Jake Yeston

    Chemical reactions such as Heck and Suzuki coupling facilitate access to an enormous range of relatively flat molecules. This geometrical constraint is associated with the comparative ease of linking together aryl and alkenyl carbons. Choi and Fu review recent developments in forming bonds between the more abundant alkyl carbon centers that underlie diverse molecules with complex three-dimensional structures. Nickel catalysis in particular has emerged as a powerful method to access individual mirror-image isomers selectively and thereby tune the biological properties of the targeted products.

    Science, this issue p. eaaf7230

  11. Natural Hazards

    An earthquake with a dozen faults

    1. Brent Grocholski

    The 2016 moment magnitude (Mw) 7.8 Kaikōura earthquake was one of the largest ever to hit New Zealand. Hamling et al. show with a new slip model that it was an incredibly complex event. Unlike most earthquakes, multiple faults ruptured to generate the ground shaking. A remarkable 12 faults ruptured overall, with the rupture jumping between faults located up to 15 km away from each other. The earthquake should motivate rethinking of certain seismic hazard models, which do not presently allow for this unusual complex rupture pattern.

    Science, this issue p. eaam7194

  12. Developmental Biology

    In vitro embryogenesis

    1. Beverly A. Purnell

    Pluripotent embryonic stem cells (ESCs) can differentiate into any adult cell type; however, aggregates of these cells do not mimic embryonic architecture when grown in culture. To see whether mouse ESCs and their extraembryonic counterparts, trophoblast stem cells (TSCs), can recapitulate normal development, Harrison et al. combined ESCs and TSCs in an extracellular matrix culture (see the Perspective by Pera). The resultant “ETS-embryos” displayed considerable resemblance to normal embryos, even specifying mesoderm and primordial germ cells at the boundary between embryonic and extraembryonic compartments. These ETS-embryos are a genetically tractable tool for studying mammalian embryogenesis.

    Science, this issue p. eaal1810; see also p. 137

  13. Geophysics

    Crustal rock strength from outer space

    1. Brent Grocholski

    The response of crustal rock to stresses is challenging to estimate yet vital for determining risks from events such as earthquakes. Moore et al. take advantage of the recent Mw 7.1 Kumamoto earthquake in Japan to determine the rheology of crustal rocks in the region. The observed inversion of the crustal strain rates demonstrates that certain areas have stiff rock and others (e.g., under the Aso volcanic complex) have much weaker rock. The results match up with expectations, which means that the method can successfully measure rock properties over a wide range of strength and large spatial and temporal scales.

    Science, this issue p. 163

  14. Cognitive Science

    Machines learn what people know implicitly

    1. Gilbert Chin

    AlphaGo has demonstrated that a machine can learn how to do things that people spend many years of concentrated study learning, and it can rapidly learn how to do them better than any human can. Caliskan et al. now show that machines can learn word associations from written texts and that these associations mirror those learned by humans, as measured by the Implicit Association Test (IAT) (see the Perspective by Greenwald). Why does this matter? Because the IAT has predictive value in uncovering the association between concepts, such as pleasantness and flowers or unpleasantness and insects. It can also tease out attitudes and beliefs—for example, associations between female names and family or male names and career. Such biases may not be expressed explicitly, yet they can prove influential in behavior.

    Science, this issue p. 183; see also p. 133

  15. Plant Science

    Refined understanding of the preprophase band

    1. Pamela J. Hines

    Because plant cells do not move, plant tissues are constructed according to how they place the divisions of their constituent cells. Schaefer et al. found a mutation in the model plant Arabidopsis that abolishes a visible precursor of cell division, the preprophase band. Despite loss of the band—previously thought essential to define the division plane—the general orientations of cell division planes in the roots of these plants were normal. However, individual division orientations showed more variance than normal. Thus, the preprophase band serves to focus and refine the final orientation of the nascent cell division plane.

    Science, this issue p. 186

  16. Single-Cell Genomics

    Making an unbiased library

    1. Valda Vinson

    Sequencing the genome of single cells gives insight into issues such as cell-to-cell heterogeneity and genome instability. Key to single-cell sequencing techniques are whole-genome amplification (WGA) methods that provide sufficient DNA for next-generation sequencing. Current WGA methods have been hampered by low accuracy and spatial resolution of gene copy numbers and by low amplification fidelity. Chen et al. report an improved single-cell WGA method, Linear Amplification via Transposon Insertion (LIANTI). The DNA is randomly fragmented by Tn5 transposition of a transposon that includes a T7 promoter, which allows linear amplification. The authors used the method to determine the spectrum of single-nucleotide variations in a single human cell after ultraviolet radiation.

    Science, this issue p. 189

  17. Structural Biology

    Coupling transcription and translation

    1. Valda Vinson

    In bacteria, the transcription of DNA into mRNA by RNA polymerase is coupled to the translation of that mRNA into protein by the ribosome. How this coupling is achieved has been unclear. Kohler et al. show that RNA polymerase and the ribosome from Escherichia coli can form a so-called expressome complex. Electron microscopy structural analysis, together with functional experiments, revealed details of the coupled complex. The coupling could allow translation to prevent transcriptional pausing, backtracking, and termination.

    Science, this issue p. 194

  18. Size Control

    How the flagellum knows when to stop

    1. Stella M. Hurtley

    The bacterial flagellum is important in bacterial pathogenesis and biofilm formation. It is a rotary nanomotor that allows bacteria to propel themselves through liquids and across surfaces. Researchers interested in nanoscale robotics use the bacterial flagellum as a model for a machine that self-assembles on the nanoscale. Cohen et al. examined exactly how the flagellum precisely measures its shaft so that it spans, but does not extend beyond the edge of, the periplasm. The growing flagellum uses a mechanism by which it “senses” when it hits the outer membrane and stops growing. Changing the width of the periplasmic space by remodeling a particular lipid changed the length of the flagellar shaft.

    Science, this issue p. 197

  19. Emerging Infections

    The evolving Ebola virus host response

    1. Lindsey Pujanandez

    Although the Ebola virus sporadically causes outbreaks in humans, there is a relative paucity of information regarding the dynamics of the immune response in patients. During the recent outbreak, a health-care worker with severe Ebola virus disease was evacuated to the NIH Clinical Center, where he received supportive care and had longitudinal blood samples drawn up to almost a year after infection. Kash et al. performed transcriptomic analyses on these blood samples. This revealed how the patient's body responded to the virus through the different phases of infection and recovery and could be compared with clinical symptoms and viral loads. These valuable data provide insights into Ebola pathogenesis and could help guide future treatments.

    Sci. Transl. Med. 9, eaai9321 (2017).

  20. Organic Electronics

    Adding a twist for enhanced performance

    1. Ian S. Osborne

    The efficiency of organic light-emitting diodes (OLEDs) is fundamentally governed by the ratio of emissive singlet to dark triplet excitons that are formed from spin-polarized electron and hole currents within the material. Typically, this has set an upper limit of 25% internal quantum efficiency for OLEDs. Di et al. manipulated the ratio of spin states through a modification of process chemistry. They introduced a rotation of the molecular structure, which inverted the spin-state energetics and enhanced OLED performance.

    Science, this issue p. 159

  21. Immune Regulation

    Regulatory T cells sans FoxP3

    1. Anand Balasubramani

    Although expression of FoxP3 is largely synonymous with T regulatory (Treg) cell identity in mice, type 1 regulatory T cells (TR1) are an exception. TR1 cells produce interleukin-10 but are FoxP3-negative. In comparison with FoxP3-positive Treg cells, the development and functions of TR1 cells are poorly understood. Zhang et al. report that TR1 cells play a critical regulatory role after allogeneic bone marrow transplantation (BMT) in mice and use this model to delineate the molecular circuits driving commitment to the TR1 lineage. By documenting the presence of TR1 cells after BMT in humans, they propose that modulation of TR1 cells could be a therapeutic approach for increasing BMT success rates in the clinic.

    Sci. Immunol. 2, eaah7152 (2017).

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