This Week in Science

Science  24 Mar 2017:
Vol. 355, Issue 6331, pp. 1277
  1. Distant Galaxies

    Identifying the hosts of quasar absorbers

    1. Keith T. Smith

    More than 60 antennas form the Atacama Large Millimeter/Submilimeter Array.

    CREDIT: NATIONAL GEOGRAPHIC CREATIVE/ALAMY STOCK PHOTO

    If the line of sight from Earth to a distant quasar passes through foreground material, some of the quasar's light is absorbed. If a galaxy-sized quantity of gas intervenes, it forms a damped Lyman-α system (DLA), visible as absorption lines in the quasar spectrum. Using the Atacama Large Millimeter/Submillimeter Array, Neeleman et al. observed two quasars with known DLAs. They detected emission from gas and dust in two foreground galaxies associated with the DLAs and were able to measure their star-formation rates. Combining these different tracers of DLAs will help us understand how galaxies evolved in the early universe.

    Science, this issue p. 1285

  2. Cell Signaling

    Cell projections set up pigment pattern

    1. Beverly A. Purnell

    Macrophages eliminate dead or dying cells and identify and destroy invading microbes. However, they also exhibit nonimmune functions in development and homeostasis. Eom and Parichy show that macrophages are essential for postembryonic remodeling during adult pigment stripe formation in zebrafish (see the Perspective by Guilliams). Pigment cells relay signal-containing vesicles via cellular projections from one class of cell to another. Without macrophages, this signal relay fails, and adult stripes are disorganized.

    Science, this issue p. 1317; see also p. 1258

  3. Metallurgy

    Nanograined metals avoid going soft

    1. Brent Grocholski

    The Hall-Petch relationship links a metal's increasing hardness with decreasing grain size, but it breaks down when grains become very small. This is unfortunate because nanograined metals could otherwise be extremely hard. Hu et al. found a way to circumvent this problem in a set of nickel-molybdenum alloys. They altered the molybdenum composition and annealed the samples at just the right temperature, which stabilized the grain boundaries in their nanograined samples. This allowed hardness to keep increasing with decreasing grain size, which could provide a route for designing superhard coatings.

    Science, this issue p. 1292

  4. Catalysis

    Metal-oxide synergy

    1. Phil Szuromi

    The hydrogenation of carbon dioxide is a key step in the industrial production of methanol. Catalysts made from copper (Cu) and zinc oxide (ZnO) on alumina supports are often used. However, the actual active sites for this reaction—Zn-Cu bimetallic sites or ZnO-Cu interfacial sites—are debated. Kattel et al. studied model catalysts and found that ZnCu became as active as ZnO/Cu only after surface oxidation formed ZnO. Theoretical studies favor a formate intermediate pathway at a ZnO-Cu interface active site.

    Science, this issue p. 1296

  5. Psychology

    Using “you” to generalize from me to others

    1. Gilbert Chin

    Sometimes “you” is used when addressing another person, but in many situations, “you” is used to indicate anyone or everyone—the generic “you.” Orvell et al. studied the underlying psychological function of the generic “you.” When asked to write about a past negative experience, people were more likely to distance themselves and derive meaning from the experience if tasked with using the generic “you” rather than the first-person pronoun “I.”

    Science, this issue p. 1299

  6. Dengue Virus

    Estimating transmission chains for dengue

    1. Caroline Ash

    Structural model of the dengue virus

    CREDIT: RAMON ANDRADE/SCIENCE SOURCE

    Dengue virus (DENV) causes a large number of asymptomatic infections, so surveillance captures only a fraction of cases. Salje et al. developed a method for identifying the number of transmission chains of DENV from sequence data and serology. They found that sequential transmission of DENV typically occurs between households in the same neighborhood. Within high-density urban localities, such as Bangkok, there are surprisingly few transmission chains. This results in epidemic spikes within a regional background of endemicity. Large urban settings may thus act as a source of diverse viruses that can be transported elsewhere.

    Science, this issue p. 1302

  7. Immunological Memory

    Helping T cells feel at home in the liver

    1. Angela Colmone

    Liver-resident T cells defend against infections such as malaria and hepatitis B virus. McNamara et al. found that liver-resident CD8+ T cells up-regulate LFA-1 and that LFA-1–ICAM-1 interactions are critical for T cell patrolling of the hepatic sinusoids. Moreover, in the absence of LFA-1, CD8+ T cells did not form liver-resident memory populations in mice, even after the animals were infected with the parasite that causes malaria (Plasmodium) or lymphocytic choriomeningitis virus. Thus, LFA-1 expression acts as a sort of invisible fence, allowing the liver-resident memory T cells free rein within the boundaries of the liver.

    Sci. Immunol. 2, eaaj1996 (2017).

  8. Neuroscience

    Why pain and stress lead to depression

    1. Leslie K. Ferrarelli

    Chronic stress or pain is associated with the development of depression. Descalzi et al. examined gene expression changes in the brain in mouse models of nerve injury– or chronic stress–induced depression. They found some common changes in the expression of genes encoding signaling pathway components that also occur in patients with depression, anxiety, and pain. Analysis of knockout mice suggested that the molecular changes may be the result of global changes in chromatin acetylation.

    Sci. Signal. 10, eaaj1549 (2017).

  9. Cancer Etiology

    Cancer and the unavoidable R factor

    1. Paula A. Kiberstis

    Most textbooks attribute cancer-causing mutations to two major sources: inherited and environmental factors. A recent study highlighted the prominent role in cancer of replicative (R) mutations that arise from a third source: unavoidable errors associated with DNA replication. Tomasetti et al. developed a method for determining the proportions of cancer-causing mutations that result from inherited, environmental, and replicative factors (see the Perspective by Nowak and Waclaw). They found that a substantial fraction of cancer driver gene mutations are indeed due to replicative factors. The results are consistent with epidemiological estimates of the fraction of preventable cancers.

    Science, this issue p. 1330; see also p. 1266

  10. Volcanology

    Making magma chambers from mush

    1. Brent Grocholski

    Shallow magma chambers either erupt as volcanoes or solidify as intrusive magma bodies. These magma bodies are traditionally considered to be long-lived and dominated by melt. Cashman et al. review the evidence that shallow magma chambers are actually assembled quickly from much larger, crystal-rich transcrustal magmatic systems. This paradigm helps explain many geophysical and geochemical features of volcanic systems. It also presents challenges for understanding the evolution of magma and provides insight into how and why volcanoes erupt.

    Science, this issue p. eaag3055

  11. Neuroscience

    Dendrites are more active than expected

    1. Peter Stern

    Dendrites occupy more than 90% of neuronal tissue. However, it has not been possible to measure distal dendritic membrane potential and spiking in vivo over a long period of time. Moore et al. developed a technique to record the subthreshold membrane potential and spikes from neocortical distal dendrites in freely behaving animals. These recordings were very stable, providing data from a single dendrite for up to 4 days. Unexpectedly, distal dendrites generated action potentials whose firing rate was nearly five times greater than at the cell body.

    Science, this issue p. eaaj1497

  12. Ion Channels

    Added complexity in an asymmetric receptor

    1. Valda Vinson

    N-methyl-d-aspartate receptors (NMDARs) are heterotetrameric ion channels that initiate chemical and electrical signals in postsynaptic cells. They play key roles in brain development and function and are the targets of drugs for treating neurological disorders such as schizophrenia, depression, and epilepsy. For the channel to open, it must bind glutamate and glycine and release a blocking magnesium ion. Most NMDARs have three different subunits that bind glycine and glutamine, but structural studies have focused on tetramers of only two subunits. Lü et al. determined the structure of triheteromeric NMDAR. The structural studies show how having three different subunits modifies receptor symmetry and subunit interactions and increases the complexity of receptor regulation.

    Science, this issue p. eaal3729

  13. DNA Nanotechnology

    Protein-folded DNA nanostructures

    1. Phil Szuromi

    A wide variety of DNA nanostructures have been assembled by folding long DNA single strands with short DNA staples. However, such structures typically need annealing at elevated temperatures in order to form. To accommodate the formation of such structures in living cells, Praetorius and Dietz developed an approach in which custom protein staples based on transcription activator–like effector proteins fold double-stranded DNA templates (see the Perspective by Douglas). The structures folded into user-defined geometric shapes on the scale of tens to hundreds of nanometers. These nanostructures could self-assemble at room temperature in physiological buffers.

    Science, this issue p. eaam5488; see also p. 1261

  14. Active Matter

    Go with the changing flow

    1. Marc S. Lavine

    The transport of ordinary fluids tends to be driven by pressure differentials, whereas for active or biological matter, transport may be isotropic or governed by the presence of specific chemical gradients. Wu et al. analyzed the emergence of spontaneous directional flows in active fluids containing a suspension of microtubules and clusters of the molecular motor kinesin, confined in a variety of microfluidic geometries (see the Perspective by Morozov). When confined in periodic toroidal channels and cylindrical domains, the flow was organized and persisted in a unidirectional motion, either clockwise or counterclockwise. Oddly, this behavior was independent of scale; as long as the aspect ratio of the geometry was chosen appropriately, flows were observed for a wide range of system dimensions.

    Science, this issue p. eaal1979; see also p. 1262

  15. Perovskite Physics

    How perovskites have the edge

    1. Phil Szuromi

    Two-dimensional Ruddlesden-Popper perovskites form quantum wells by sandwiching inorganic-organic perovskite layers used in photovoltaic devices between organic layers. Blancon et al. show that if the perovskite layer is more than two unit cells thick, photogenerated excitons undergo an unusual but highly efficient process for creating free carriers that can be harvested in photovoltaic devices (see the Perspective by Bakr and Mohammed). Lower-energy local states at the edges of the perovskite layer facilitate dissociation into electrons and holes that are well protected from recombination.

    Science, this issue p. 1288; see also p. 1260

  16. Cancer Therapy

    Chromatin state dictates drug response

    1. Paula A. Kiberstis

    Drugs inhibiting the phosphoinositide-(3)-kinase (PI3K) signaling pathway are effective in a subset of breast cancer patients. Tumors become resistant to these drugs, however, and this transition is often accompanied by increased transcription of genes regulated by the estrogen receptor. A better understanding of the mechanism linking PI3K signaling and estrogen receptor activity could potentially suggest strategies to prevent drug resistance. Toska et al. found that PI3K inhibition activates a specific epigenetic regulator, the histone methyltransferase KMT2D. The protein modifications catalyzed by KMT2D create a more open chromatin state, which unleashes estrogen receptor–dependent transcription. Thus, combination therapies consisting of PI3K inhibitors and KMT2D inhibitors may be more effective than PI3K inhibitors alone.

    Science, this issue p. 1324

  17. Cholesterol Sensing

    Lysosomal cholesterol activates mTORC1

    1. L. Bryan Ray

    The mTORC1 kinase is a master nutrient sensor that governs cellular metabolism. When dysregulated, this kinase drives several human diseases, including cancer and diabetes. Recent work has delineated a pathway through which amino acids regulate mTORC1. In contrast, little is known about how sterols may affect mTORC1 signaling. Castellano et al. provide detailed mechanistic evidence for how cholesterol, derived from the processing of low-density lipoprotein in the lysosomal lumen, drives mTORC1 signaling. They identify the key players that couple lysosomal cholesterol levels to mTORC1 activation. Unexpectedly, the putative amino acid transporter SLC38A9, which is implicated in mTORC1 regulation by arginine, is essential for mTORC1 activation by cholesterol. Furthermore, the authors uncover a physical and functional interaction between SLC38A9 and the major lysosomal cholesterol transporter, Niemann-Pick C1 (NPC1) protein. The SLC38A9-NPC1 complex is key to the ability of mTORC1 to respond to variations in dietary lipid supply.

    Science, this issue p. 1306

  18. Aging

    NAD+ binding modulates protein interactions

    1. L. Bryan Ray

    An unexpected function of the oxidized form of nicotinamide adenine dinucleotide (NAD+) could underlie some effects of aging and propensity to age-related diseases. Li et al. found that the protein DBC1 (deleted in breast cancer 1) contains a domain that specifically binds NAD+. Binding of NAD+ inhibited the interaction of DBC1 with PARP1 [poly(adenosine diphosphate–ribose) polymerase 1], an enzyme important in DNA repair. Activity of PARP1 is inhibited by interaction with DBC1. Thus, the reduced abundance of NAD+ associated with aging may decrease PARP1 activity by promoting the interaction of PARP1 with DBC1. This mechanism could help explain the reported rejuvenating actions of NAD+ supplementation in older animals.

    Science, this issue p. 1312

  19. Signal Transduction

    Tugging on Notch receptor tunes signaling

    1. L. Bryan Ray

    Notch proteins are transmembrane receptors that are important in the regulation of cell fate. They are unusual in that their ligands are membrane-bound on adjacent cells. Luca et al. provide insights into the signaling interactions between Notch and its various ligands. The crystal structure of Notch complexed with a variant of its ligand Jagged1 revealed the interaction of Notch domains containing O-linked glycans with particular domains in Jagged1. Measurements of the effects of various forces on the interaction showed that application of force increases the lifetime of bonds between receptor and ligand. The studies help explain how low-affinity interactions of Notch with its ligands can lead to signaling and indicate that forces may differentially affect Notch-ligand interactions.

    Science, this issue p. 1320

  20. Ecology

    Fire management, made to measure

    1. Julia Fahrenkamp-Uppenbrink

    Ecosystems, and the species within them, respond to fire in a variety of ways that can affect how they recover. In a Perspective, Kelly and Brotons highlight recent studies of the relationship between fire and biodiversity in fire-prone ecosystems in North America and Australia. The results show that the occurrence of fires and their spatial and temporal characteristics shape a region's biodiversity. These findings can help to tailor fire management efforts, such as planned burning and fire suppression, to support conservation efforts.

    Science, this issue p. 1264

  21. Vaccines

    Influenz-ing IFN responses in dendritic cells

    1. Lindsey Pujanandez

    Seasonal influenza vaccines have been produced and marketed for decades, but they are not always protective. Athale et al. tested a trivalent vaccine against the monovalent vaccine made by the same manufacturer. They looked at the ability to activate human dendritic cell subsets, which are crucial for launching adaptive immune responses. Both vaccines could activate plasmacytoid dendritic cells, but only the trivalent vaccine could induce antiviral interferon (IFN) responses in other types of dendritic cells. Moreover, people immunized with the monovalent vaccine did not show early IFN responses in the blood, but those immunized by trivalent vaccination did. These intriguing results may help to explain vaccine underperformance that cannot be attributed to antigenic mismatch.

    Sci. Transl. Med. 9, eaaf9194 (2017).

  22. Remote Sensing

    It's easier to see green

    1. Shahid Naeem

    Green pixels in remote sensing data that estimate plant production can tell us much about Earth's ecosystems. However, one needs to know what proportion of the surface captured by the pixel is actually vegetated. Badgley et al. developed a method based on near-infrared reflectance of terrestrial vegetation (NIRV) to assess the proportion of a pixel that is vegetated. NIRV's ease of calculation and its applicability to decades of moderate-resolution remote sensing data will help to quantify agricultural and natural ecosystem responses to climate and land-use change.

    Sci. Adv. 10.1126/sciadv.1602244 (2017).