This Week in Science

Science  01 Apr 2016:
Vol. 352, Issue 6281, pp. 48
  1. Ice Sheets

    Sensitive ice sheets

    1. H. Jesse Smith

    Increasing carbon dioxide levels could destabilize the Antarctic Ice Sheet

    PHOTO: © RGB VENTURES/SUPERSTOCK/ALAMY STOCK PHOTO

    Why did the Antarctic Ice Sheet begin to grow 34 million years ago, and what does that have to do with us? Galeotti et al. studied a marine sediment core recovered from just off the coast of Antarctica (see the Perspective by Lear and Lunt). The ice sheet did not begin to grow until atmospheric CO2 concentrations had dropped to below around 600 parts per million. Indeed, the ice sheet was unstable when CO2 was higher. As modern atmospheric CO2 concentrations continue their rise, a shift back to an unstable Antarctic Ice Sheet could increase harmful rises in sea level.

    Science, this issue p. 76; see also p. 34

  2. Obesity

    Cell-free DNA and adipose tissue inflammation

    1. Philip Yeagle

    Obesity can induce chronic inflammation and subsequent insulin resistance (type 2 diabetes), but how this happens has been a nagging question. Nishimoto et al. found that degenerating adipocytes (fat cells) release DNA (known as cell-free DNA or cfDNA) that attracts macrophages to the adipose tissue, thus initiating or exacerbating inflammation. Toll-like receptor 9 was involved in recognizing the cfDNA. Genetic deletion of the receptor reduced both macrophage accumulation in adipose tissue and insulin resistance. Thus, the receptor may represent a therapeutic target for obesity-related diseases.

    Sci. Adv. 2, 10.1126.sciadv.01332 (2016).

  3. Mitochondrial Disease

    Thriving on a breath of low oxygen

    1. Paula A. Kiberstis

    Mitochondrial diseases are debilitating and largely untreatable. Most are caused by genetic mutations that impair the mitochondrial respiratory chain, which generates cellular energy. Because these diseases do not affect all tissues equally, it is thought that endogenous mechanisms exist that can help cells cope with mitochondrial defects. Jain et al. identified the hypoxia response, a mechanism that helps cells adapt when oxygen is limited, as a potent suppressor of mitochondrial dysfunction (see the Perspective by Shoubridge). Mouse models of the mitochondrial disease Leigh syndrome showed fewer symptoms and a dramatically extended life span when raised in a hypoxic environment.

    Science, this issue p. 54; see also p. 31

  4. Flow Chemistry

    Drug manufacturing in a fridge-sized box

    1. Jake Yeston

    Commodity chemicals tend to be manufactured in a continuous fashion. However, the preparation of pharmaceuticals still proceeds batch by batch, partly on account of the complexity of their molecular structures. Adamo et al. now present an apparatus roughly the size of a household refrigerator that can synthesize and purify pharmaceuticals under continuous-flow conditions (see the Perspective by Martin). The integrated set of modules can produce hundreds to thousands of accumulated doses in a day, delivered in aqueous solution.

    Science, this issue p. 61; see also p. 44

  5. Immune Regulation

    Long noncoding RNAs in inflammation

    1. Kristen L. Mueller

    Growing evidence suggests that long noncoding RNAs (lncRNAs) are important modulators of gene expression. Castellanos-Rubio et al. identified a lncRNA, lnc13, that suppresses inflammatory gene expression in macrophages (see the Perspective by Huarte). Lnc13 interacts with proteins that regulate chromatin accessibility. Stimulating macrophages with a cell wall component from bacteria decreased expression of lnc13 and increased the expression of several inflammatory genes. Decreased levels of lnc13 in intestinal tissue from individuals with celiac disease hint that lnc13 may also play a role in the pathogenesis of immune-mediated diseases.

    Small-intestine damage in celiac patient biopsy

    PHOTO: LAB OF SANKAR GHOSH/COLUMBIA UNIVERSITY MEDICAL CENTER

    Science, this issue p. 91; see also p. 43

  6. Conflict Behavior

    How to win a fish fight

    1. Peter Stern

    When to cease aggression and escape is an important decision that fighting animals must make. Chou et al. characterized the role of two nuclei in a brain area of the zebrafish called the dorsal habenula (dHb) during social aggression (see the Perspective by Desban and Wyart). Silencing the lateral dHb reduced the likelihood of winning a fight, whereas silencing the medial dHb increased the likelihood of winning. Thus, these two nuclei antagonistically control the threshold for surrender.

    Science, this issue p. 87; see also p. 42

  7. Stellar Evolution

    Discovery of an oxygen white dwarf

    1. Keith T. Smith

    The vast majority of stars will eventually evolve into a white dwarf, a small, hot, and extremely dense object made of leftover material from the star's core. Stellar evolution theory suggests that white dwarfs should be mostly made of helium, carbon, or oxygen, but even a tiny amount of hydrogen or helium floats to the surface and hides the underlying composition. Kepler et al. searched through thousands of white dwarf spectra and discovered one that has an atmosphere dominated by oxygen, with no contamination by hydrogen or helium (see the Perspective by Gänsicke). This pristine object confirms the long-postulated theory and will be an important test case for stellar evolution.

    Science, this issue p. 67; see also p. 37

  8. Mammalian Germ Cells

    Mouse oocytes receive sister cell factors

    1. Beverly A. Purnell

    Mammalian mature oocytes, the largest cells in the body, are capable of programming and reprogramming embryogenesis. Only about 20% of developing mouse germ cells become oocytes. Lei and Spradling show that organelles and the cytoplasm move through intercellular connections between sister germ cells in mouse fetal ovaries to enrich oocyte cytoplasm just before oocytes arrest to form the ovarian reserve (see the Perspective by Pepling). Similar transfers occur during oogenesis in many invertebrate and lower vertebrate species, possibly providing oocytes their special properties for programming embryo development.

    Science, this issue p. 95; see also p. 35

  9. Pain

    “WNK”ing away chronic pain

    1. Nancy R. Gough

    WNK1 is a kinase found in the spinal cord's dorsal horn, which transmits pain signals from the periphery to the brainstem. Mutations in the HSN2 exon in the gene encoding WNK1 cause a neuropathy that results in loss of touch, temperature, and pain sensation. Kahle et al. found that mice lacking this alternatively spliced variant of WNK1 were protected from pain hypersensitivity in an injury-induced model of neuropathic pain. The pain-transmitting nerves in these mice were inhibited by the neurotransmitter GABA, unlike those in control mice. Thus, drugs that inhibit WNK1-dependent signaling might reduce injury-induced neuropathic pain.

    Sci. Signal. 9, ra32 (2016).

  10. Cell Death Pathways

    Apoptosis, necrosis, and pyroptosis

    1. Stella M. Hurtley

    The routes to cell death are many, and distinguishing which path a particular cell may have taken remains a challenge. Wallach et al. review current understanding of how programmed necrotic cell death contributes to inflammation.

    Science, this issue p. 10.1126/science.aaf2154

  11. Nonhuman Genomics

    Improving on the gorilla genome

    1. Laura M. Zahn

    Access to complete, high-quality genomes of nonhuman primates will also help us understand human biology. Gordon et al. used long-read sequencing technology to improve genome data on our close relative the gorilla. Sequencing from a single individual decreased assembly fragmentation and recovered previously missed genes and noncoding loci. Mapping short-read sequences from additional gorillas helped reconstruct a “pan” gorilla sequence documenting genetic variation. Comparison with human genomes revealed species-specific differences ranging in size from one to thousands of bases in length, including some that are likely to affect gene regulation.

    Science, this issue p. 10.1126/science.aae0344

  12. Synthetic Biology

    Programming circuitry for synthetic biology

    1. L. Bryan Ray

    As synthetic biology techniques become more powerful, researchers are anticipating a future in which the design of biological circuits will be similar to the design of integrated circuits in electronics. Nielsen et al. describe what is essentially a programming language to design computational circuits in living cells. The circuits generated on plasmids expressed in Escherichia coli required careful insulation from their genetic context, but primarily functioned as specified. The circuits could, for example, regulate cellular functions in response to multiple environmental signals. Such a strategy can facilitate the development of more complex circuits by genetic engineering.

    Science, this issue p. 10.1126/science.aac7341

  13. Colloidal Ordering

    Competing forces drive ordering

    1. Marc S. Lavine

    The power and beauty of liquid crystals come from their tendency to order loosely over long length scales. This ordering can be tweaked using external fields, or via tailored boundary conditions, or embedded objects. Mundoor et al. deposited luminescent nanorods into a liquid crystal solvent (see the Perspective by Blanc). This caused a competition between local electrostatic interactions and the elastic ordering of the liquid crystal. The nanorods ordered into a triclinic structure not otherwise attainable. The authors further adjusted the structure using external fields.

    Science, this issue p. 69; see also p. 40

  14. Electrocatalysis

    A lanthanide boost for platinum

    1. Phil Szuromi

    High loadings of precious platinum are needed for automotive fuel cells, because the kinetics of the oxygen reduction reaction (ORR) are relatively slow. Escudero-Escribano et al. studied a series of platinum alloys with lanthanides and alkaline earth elements. When the surfaces were leached to leave pure platinum, they developed compressive strain that boosted the ORR activity—up to a factor of 6 for terbium. Enthalpy effects helped to stabilize these alloys under operating conditions.

    Science, this issue p. 73

  15. Organic Chemistry

    Beyond textbook SN2 chemistry

    1. Julia Fahrenkamp-Uppenbrink

    In one of best-studied organic reactions, a negatively charged ion such as chlorine replaces another atom or group of atoms in an organic molecule. According to the traditional understanding of this SN2 reaction, pre- and post-reaction complexes form, and the configuration at the carbon that binds the ion is inverted during the reaction. In a Perspective, Xie and Hase highlight recent studies that have revealed a host of other mechanisms in the gas-phase SN2 reaction. In some of these mechanisms, the configuration of the resulting molecule is not inverted. The dominant mechanism depends on the nature of the reactants and on the reaction conditions. For one SN2 reaction, 28 different mechanisms have been found.

    Science, this issue p. 32

  16. Atmospheric Methane

    Getting a rise out of agriculture

    1. H. Jesse Smith

    Methane, a powerful and important greenhouse gas, has been accumulating nearly uninterruptedly in the atmosphere for the past 200 years, with the exception of a mysterious plateau between 1999 and 2006. Schaefer et al. measured methane's carbon isotopic composition in samples collected over the past 35 years in order to constrain the cause of the pause. Lower thermogenic emissions or variations in the hydroxyldriven methane sink caused the plateau. Thermogenic emissions didn't resume to cause the subsequent rise. Instead, the ongoing rise is most likely due to biogenic sources, most notably agriculture.

    Science, this issue p. 80

  17. Climate Change

    Birds populations allied in abundance

    1. Sacha Vignieri

    Changes in climate can cause populations of species to decline, to increase, or to remain steady. Stephens et al. looked across species of common birds in Europe and the United States. Despite many differences between the two regions, expectations about how a species might respond to climate change did predict actual responses. Species predicted to benefit from increasing temperatures, or their associated effects, tended to increase, whereas those predicted to be negatively affected declined. Thus, even across widely varying ecological conditions and communities, climate change can be expected to alter population sizes.

    Science, this issue p. 84

  18. Inflammation

    Guarding inflammation

    1. Angela Colmone

    The innate immune system is genetically hardwired in each of us to protect against infection. Mutations in these protective genes can lead to uncontrolled inflammation and disease. Masters et al. describe a family with a hereditary autoinflammatory disease caused by a mutation in the pathogen sensor pyrin. This mutation disrupts pyrin regulation so that it acts as if it detects pathogens, even in their absence, leading to proinflammatory interleukin-1β production. Indeed, inhibiting this interleukin in one patient eliminated the disease. Thus, pyrin regulation can guard against destructive autoinflammation in humans.

    Sci. Transl. Med. 8, 332ra45 (2016).

  19. Immunology

    Dialing down allergic responses

    1. Kristen L. Mueller

    Immunity to parasites and worms, termed type 2 immunity, is a double-edged sword. The same immune cells that keep these pests at bay can go awry, causing allergy and asthma. Chan et al. found that an enzyme called TYRO3, a receptor tyrosine kinase, dampens type 2 immunity in mice and humans. Worm infection or an allergic stimulus caused T cells to express PROS1, which bound to TYRO3 on dendritic cells and inhibited proinflammatory mediator production.

    Science, this issue p. 99

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