This Week in Science

Science  27 Sep 2019:
Vol. 365, Issue 6460, pp. 1414
  1. Liquid Crystals

    Knot all that it seems

    1. Marc S. Lavine

    Optical micrograph of a self-assembled lattice of knots in a chiral liquid crystal


    Although for some, knots are merely a frustration caused by poorly tied shoelaces, interest in knots in physical systems spans many disciplines, including fluid and optical vortices, Skyrmion states, liquid crystals, excitable media, polymers, proteins, DNA, and even chemical molecules. Tai and Smalyukh describe the creation of localized knotted structures in cholesteric liquid crystals using electric fields (see the Perspective by Alexander). The knots are topologically distinct from the host medium and diffuse and organize like colloidal particles, forming regular crystalline arrangements.

    Science, this issue p. 1449; see also p. 1377

  2. Thermoelectrics

    Lower-cost thermoelectrics

    1. Brent Grocholski

    Thermoelectric materials convert heat to electricity, making them attractive for heat harvesting or cooling applications. However, many high-performance thermoelectrics are made of expensive or toxic materials. He et al. found that a material composed of primarily tin and sulfur could be optimized to have relatively good thermoelectric properties. Introducing about 10% selenium to tin sulfide helped tune these properties by electronic band manipulation. This material is a step toward more earth-abundant, less toxic, and lower-cost thermoelectrics than the telluride-based materials currently in use.

    Science, this issue p. 1418

  3. Cancer Therapy

    Refining precision medicine

    1. Leslie K. Ferrarelli

    Unlike most colorectal cancer patients with mutations in the KRAS gene, those with the Gly13→Asp (G13D) mutation respond to blockade of epidermal growth factor receptor (EGFR). Using a systems biology approach, McFall et al. showed that EGFR-mediated activation of wild-type KRAS depended on whether the mutant KRAS inhibited the tumor suppressor neurofibromin 1 (NF1). Because the KRAS G13D mutant did not inhibit NF1, EGFR signaling still activated wild-type KRAS in KRAS G13D cells and drove tumor growth. These findings underscore how precision medicine could benefit from a systems-level analysis of patients.

    Sci. Signal. 12, eaaw8288 (2019).

  4. Particle Physics

    Looking for an exotic decay

    1. Jelena Stajic

    Neutrinos—elementary fermionic particles with no electrical charge—defy the standard model of particle physics by having a tiny, but nonzero mass. One explanation for their properties is that they are Majorana fermions, which are particles equal to their antiparticles. If neutrinos were Majorana fermions, a process called neutrinoless double-β decay would become possible: an unstable nucleus could decay by turning two of its neutrons into protons with the emission of two electrons but no antineutrinos. The GERDA Collaboration searched for this decay in a particular isotope of germanium. Housed deep underground to reduce the background signal, the experiment did not detect the elusive process but did place improved boundaries on its half-life.

    Science, this issue p. 1445

  5. Synthetic Biology

    Sounding out mammalian cells

    1. Valda Vinson

    Live cell imaging allows us to observe cellular processes in real time. Most methods rely on light, and the poor penetration of light into tissues limits their application. Ultrasound penetrates tissues, and cellular reporters that respond to ultrasound have been developed recently. These reporters are air-filled protein structures that provide buoyancy in the bacteria they are derived from, but when surrounded by a fluid medium, they reflect sound waves. Farhadi et al. achieved expression from multiple genes to create these complex structures in mammalian cells. In addition to optimizing reporter production and detection, they visualize cells in a proof-of-principle experiment in mouse tumor xenografts.

    Science, this issue p. 1469

  6. Plant Ecology

    Habitat connectivity enhances diversity

    1. Andrew M. Sugden

    Fragmentation of ecosystems leads to loss of biodiversity in the remaining habitat patches, but retaining connecting corridors can reduce these losses. Using long-term data from a large, replicated experiment, Damschen et al. show quantitatively how these losses are reduced. In their pine savanna system, corridors reduced the likelihood of plant extinction in patches by about 2% per year and increased the likelihood of patch colonization by about 5% per year. These benefits continued to accrue over the course of the 18-year experiment. By the end of monitoring, connected patches had 14% more species than unconnected patches. Restoring habitat connectivity may thus be a powerful technique for conserving biodiversity, and investment in connections can be expected to magnify conservation benefit.

    Science, this issue p. 1478

  7. Immunogenomics

    Immune landscape of the human kidney

    1. Laura M. Zahn

    Single-cell RNA sequencing has begun to shed light on the full cellular diversity of specific organs. However, these studies rarely examine organ-specific immune cells. Stewart et al. sequenced healthy adult and fetal kidney samples at a single-cell level to define the heterogeneity in epithelial, myeloid, and lymphoid cells. From this dataset, they identified zonation of cells, with relevance to disease and the varied perturbations that occur in different tumor settings. This profiling of the human kidney generates a comprehensive census of existing cell populations that will help inform the diagnosis and treatment of kidney-related diseases.

    Science, this issue p. 1461

  8. Vaccines

    Hinting at a herpes vaccine

    1. Christiana N. Fogg

    A vaccine for genital herpes does not currently exist, despite the prevalence of this sexually transmitted disease. Previous attempts to make vaccines against herpes simplex virus 2 (HSV-2) included trials with protein subunit vaccine candidates that delayed infection onset but were not protective. Awasthi et al. describe a vaccine candidate that is composed of nucleoside-modified mRNA in lipid nanoparticles that encodes the HSV-2 glycoproteins C, D, and E. This trivalent vaccine protected mice and guinea pigs from developing genital lesions and reduced viral shedding. Neutralizing antibody and CD4+ T cell responses were detected in immunized mice. These results suggest that an mRNA-based HSV-2 vaccine may have potential for further preclinical development.

    Sci. Immunol. 4, eaaw7083 (2019).

  9. Human Genomics

    Genetic roots of multiple sclerosis

    1. Laura M. Zahn

    The genetics underlying who develops multiple sclerosis (MS) have been difficult to work out. Examining more than 47,000 cases and 68,000 controls with multiple genome-wide association studies, the International Multiple Sclerosis Genetics Consortium identified more than 200 risk loci in MS (see the Perspective by Briggs). Focusing on the best candidate genes, including a model of the major histocompatibility complex region, the authors identified statistically independent effects at the genome level. Gene expression studies detected that every major immune cell type is enriched for MS susceptibility genes and that MS risk variants are enriched in brain-resident immune cells, especially microglia. Up to 48% of the genetic contribution of MS can be explained through this analysis.

    Science, this issue p. eaav7188; see also p. 1383

  10. Metabolism

    Microbial entrainment of metabolism

    1. Caroline Ash

    The metabolism of mammals is synchronized to daily cycles relating to sleep and mealtimes. It is not surprising that the gut microbiota, which aids in digestion, should also display daily cycling. Kuang et al. found that the gut microbiota can mediate daily cycles epigenetically (see the Perspective by Bishehsari and Keshavarzian). The microbiota induces rhythmic expression of histone deacetylase 3 (HDAC3) in epithelial cells of the small intestine, but not those of the colon. HDAC3 expression drives oscillations in intestinal metabolic gene expression, especially for nutrient transport and lipid metabolism. HDAC3 also directly activates estrogen-related receptor α, which promotes lipid absorption. Consequently, mice that lack a gut microbiota lack daily regulation of their metabolism and become obese on high-fat chow. Disruption of HDAC3 cycling could be an explanation for human obesity associated with antibiotic damage to the microbiota and with sleep disruption caused by jet lag and nighttime working.

    Science, this issue p. 1428; see also p. 1379

  11. Structural Biology

    Responding to the cold

    1. Valda Vinson

    Mint tastes cool because the active component, menthol, activates the receptor and calcium channel TRPM8, which also responds to cold temperatures. Previous structures have revealed the architecture of TRPM8 and how it binds ligands but not its gating mechanism. Diver et al. determined structures of avian TRPM8 in ligand-free, antagonist-bound, and calcium-bound states using cryo–electron microscopy at resolutions between 3.0 and 3.6 angstroms. They observed a closed state in the presence of antagonist and that large conformational changes are required to form the desensitized state in the presence of calcium. Understanding how ligands affect channel gating may facilitate drug design.

    Science, this issue p. 1434

  12. Superconductivity

    Tweaking the Hubbard model

    1. Jelena Stajic

    Modeling high-temperature superconductivity (HTS) remains extremely challenging. Many researchers believe that the simplest model that captures HTS is the Hubbard model, which accounts for interactions and allows for electrons to hop from one site of a lattice to another. However, even just determining whether the ground state of this model supports superconductivity is tricky. Jiang and Devereaux undertook an extensive computational study based on a method known as density matrix renormalization group. They found that for a particular concentration of empty lattice sites, superconductivity indeed appears as a long-range state, but only if electrons are allowed to hop to sites that are next to their immediate neighbors on the lattice.

    Science, this issue p. 1424

  13. Exoplanets

    A small star hosts a big planet

    1. Keith T. Smith

    M dwarfs, the most common type of star, are low-mass objects that emit most of their faint light in the near-infrared, making it difficult to detect any orbiting exoplanets. Morales et al. have observed the nearby M dwarf GJ 3512 in the optical and near-infrared (see the Perspective by Laughlin). Periodic variations in the star's radial velocity show that it hosts a gas giant exoplanet on an eccentric orbit. The authors use simulations to show that such a large exoplanet around such a small star has implications for models of planet formation.

    Science, this issue p. 1441; see also p. 1382

  14. Plasmonics

    Probing protein-nanorod aggregates

    1. Phil Szuromi

    The interaction of proteins with nanoparticles can enhance circular dichroism signals and provide a route for sensitive biodetection. However, ensemble measurements are insufficient for resolving the origin of plasmon-coupled circular dichroism (PCCD). Zhang et al. used single-particle circular differential scattering spectroscopy along with correlated tomographic reconstruction and electromagnetic simulations to study individual aggregates of bovine serum albumin and gold nanorods (see the Perspective by Kim and Kotov). Aggregates contribute to PCCD activity through formation of plasmonic hotspots, but single nanoparticles do not contribute. The protein does not function simply as a chiral chromophore but enables assembly of the chiral nanorod-protein complexes.

    Science, this issue p. 1475; see also p. 1378

  15. Applied Physics

    A hole flatland

    1. Jelena Stajic

    When two distinct materials are placed on top of each other, the difference in polarization between the two layers can induce charge carriers at the interface. Many such two-dimensional (2D) electron gases have been observed, but engineering a 2D hole gas without the help of doping has been much trickier. Chaudhuri et al. used molecular beam epitaxy to grow a layer of gallium nitride on top of aluminum nitride without introducing dopants. This approach resulted in a high-density 2D hole gas at the interface in this technologically relevant system.

    Science, this issue p. 1454

  16. Sex Determination

    Making males in a fruit fly pest

    1. Beverly A. Purnell

    The Mediterranean fruit fly or Medfly (Ceratitis capitata) is a global and highly destructive fruit pest. Meccariello et al. identified the master gene for male sex determination on the Y chromosome of Medfly and named it Maleness-on-the-Y (MoY) (see the Perspective by Makki and Meller). Flies of each sex were transformed into the other sex by genetic manipulation, and crosses of transformed files generated male and female progeny. MoY is functionally conserved in the olive fruit fly and in the invasive oriental fruit fly. This discovery has potential for insect genetic control based on mass release of sterile males and future strategies based on gene drive.

    Science, this issue p. 1457; see also p. 1380

  17. Reproductive Biology

    Understanding fertility in young and old

    1. Beverly A. Purnell

    Fertility in humans follows a U-curve, with low rates in both teenagers and women of advancing maternal age (mid-30s and above). Gruhn et al. found that this distinct shape originates from chromosomal errors in human eggs, which result in genomic imbalance and pregnancy loss. The error types and chromosomes affected in the young and advanced age groups were different, suggesting that two distinct chromosome-based mechanisms balance risk associated with pregnancy and evolutionary fitness as women enter and exit their reproductive life span. The authors show that chromosome structure erodes only with advancing age, acting as a “molecular clock” for reproductive senescence.

    Science, this issue p. 1466

  18. Immunology

    Escalating responses to DNA

    1. Gemma Alderton

    Numerous DNA sensors exist in cells to detect viral and microbial infection, as well as nonphysiological cytosolic DNA. These detection systems activate immune signaling pathways to respond to infection, but why are so many DNA sensors needed? In a Perspective, Emming and Schroder propose that DNA sensors, including a newly identified nuclear sensor, function in a tiered system that can adjust the cellular response according to the amount of detected intracellular DNA. Cellular and immune responses can therefore be scaled, from low-level inflammation to immunogenic cell death, according to the threat posed by an infection.

    Science, this issue p. 1375

  19. Pulmonary Fibrosis

    The strange case of IL-11

    1. Mattia Maroso

    In idiopathic pulmonary fibrosis (IPF), chronic activation of invasive fibroblasts causes fibrotic scar formation in the lungs. Patients with IPF present with progressive breathing difficulty, pulmonary hypertension, and respiratory failure. The pathophysiological mechanisms remain unclear. Interleukin-11 (IL-11) has been shown to participate in kidney and cardiac fibrosis; however, conflicting data suggest IL-11 can either be pro- or antifibrotic. Ng et al. report that in patients with IPF, IL-11 was up-regulated in invasive lung fibroblasts. In vitro and in vivo experiments demonstrated that IL-11 exerted profibrotic effects by driving fibroblast activation. Targeting IL-11 with a neutralizing antibody had therapeutic effects in a mouse model of established pulmonary fibrosis.

    Sci. Transl. Med. 11, eaaw1237 (2019).

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