This Week in Science

Science  02 Jan 2015:
Vol. 347, Issue 6217, pp. 38
  1. Mutagenesis

    Men beware, when smoke gets in your Y's

    1. Paula A. Kiberstis

    Y chromosomes are more susceptible to effects of smoking

    CREDITS: (TOP TO BOTTOM) YANG ET AL.; MIKDAM/ISTOCKPHOTO

    The relationship between tobacco smoking and elevated cancer risk has been recognized for 60 years. Yet what smoking does to our genetic material is still not fully understood. New work suggests that men should be particularly concerned. In a study of over 6000 men, Dumanski et al. find that men who smoke are more than three times as likely as nonsmokers to show loss of the Y chromosome in their blood cells. Whether this is a causal factor in cancer development or simply a marker of more consequential damage on other chromosomes could not be deduced from the study.

    Science, this issue p. 81

  2. Reaction Dynamics

    A few very brief pauses in the action

    1. Jake Yeston

    Chemical reactions proceed by the cumulative effect of trillions upon trillions of collisions between atoms and molecules. Usually, a given collision bounces the participants right back out again, either in their original form or with the atoms shuffled around into distinct products. In certain cases, the reacting partners experience a brief lull, termed a resonance, before they rearrange. Yang et al. report the discovery of particularly short-lived resonances in certain reactive collisions of chlorine atoms with vibrationally excited hydrogen deuteride (HD). Their results suggest that similar, as yet overlooked, resonances may lurk in other reactions of vibrationally excited molecules.

    Science, this issue p. 60

  3. Quantum Optics

    Engineering a shelter for quantum protection

    1. Ian S. Osborne

    In isolation, quantum states of matter can be stable entities. These states are often seen as useful when they can be made to interact in a controlled way. However, those interactions and the unavoidable interactions with their environment often correlate with decoherence and eventual loss of the quantum state. Kienzler et al. show that they can engineer the interactions between a quantum system (a trapped ion) and the environment to prepare stable quantum states. The generality of the technique implies applications for other interacting quantum systems.

    Science, this issue p. 53

  4. Cancer Etiology

    Crunching the numbers to explain cancer

    1. Paula A. Kiberstis

    Why do some tissues give rise to cancer in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by the number of stem cell divisions. By plotting the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, they found a strong correlation extending over five orders of magnitude. This suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development. Remarkably, this “bad luck” component explains a far greater number of cancers than do hereditary and environmental factors.

    Science, this issue p. 78

  5. Innate Immunity

    Skin infection triggers fat responses

    1. Caroline Ash

    Obesity is associated with chronic inflammation, but does fat tissue offer protection during infection? Zhang et al. noticed that the fat layers in the skin of mice thickened after inoculation with the pathogenic bacterium Staphylococcus aureus (see the Perspective by Alcorn and Kolls). Mutant mice incapable of forming new fat cells were more susceptible to infection. The differentiating fat cells secreted a small-molecule peptide called cathelicidin, specifically in response to the infection. By contrast, mature fat cells produce less cathelicidin, and are thus less protective.

    Science, this issue p. 67; see also p. 26

  6. Virus Structure

    Targeting EV-D68, a respiratory virus

    1. Valda Vinson

    A recent outbreak of respiratory illness in U.S. children was caused by entorovirus D68 (EV-D68). Enteroviruses also include human pathogens such as human rhinovirus, which causes the common cold, and poliovirus. Most of these viruses are stabilized by a factor that binds in a hydrophobic pocket of the capsid protein VP1, and antiviral compounds can act by displacing this factor. Liu et al. report the crystal structure of EV-D68 and its complex with the antiviral compound peconaril. In EV-D68, the hydrophobic pocket contained a fatty acid that was displaced by peconaril. Peconaril efficiently inhibited EV-D68 infection of cells, making it a possible drug candidate against EV-D68.

    Science, this issue p. 71

  7. Organic Chemistry

    Breaking through the milligram floor

    1. Jake Yeston

    When chemists synthesize compounds, the threshold for success is at least a milligram of product. This has been true for decades—even though biochemical assays have long since descended into microgram territory—and results in part from the constraints of characterization methods. Buitrago Santanilla et al. present an automated dosing and characterization protocol for optimizing chemical reaction conditions on the microgram scale. This allowed them to screen numerous base and ligand combinations for catalytic C-N bond-forming reactions between complex pairs of compounds, in short supply, that resisted standard coupling conditions.

    PHOTO: PHLOXII/ISTOCKPHOTO

    Science, this issue p. 49

  8. Immunology

    An immunological fountain of youth

    1. Orla M. Smith

    mTOR signaling, a multipurpose pathway, controls all aspects of cell growth and motility and can also delay onset of aging-related diseases in many species. Mannick et al. now show that mTOR inhibition can benefit humans, too. They evaluated whether the mTOR inhibitor RAD001 could reverse the deterioration of immune function seen as people age. By assessing their elderly subjects' reaction to an influenza vaccination, the authors showed that RAD001 boosted their vaccine-induced immune defenses.

    Sci. Transl. Med. 6, 268ra179 (2014)

  9. Cancer

    Overcoming drug resistance in cancer

    1. Leslie K. Ferrarelli

    Cancer patients frequently develop drug resistance. Martz et al. devised a method of identifying pathways causing resistance in cancer cells and found that Notch signaling mediated resistance to drugs used in breast cancer and melanoma. Winter et al. also used this screening method for myeloproliferative neoplasms, which often have an activating mutation in the kinase JAK2 but are resistant to JAK inhibitors. They pinned the cause of this resistance to RAS, a signaling protein. Thus, screening entire signaling pathways instead of individual genes can identify new therapeutic targets that may be important in multiple types of drug-resistant cancers.

    Sci. Signal. 7, ra121 and ra122 (2014).

  10. 2D Materials

    Layered materials power the cause

    1. Marc S. Lavine

    Methods for storing and converting energy, including fuel cells, solar cells, and water splitting, often benefit from having materials with a large surface area. When combined with a high surface reactivity, high conductivity, or useful optical properties, two-dimensional layered materials become of notable interest for a range of applications. Bonaccorso et al. review the progress that has been made using graphene and other layered or two-dimensional materials at laboratory scales and the challenges in producing these materials in industrially relevant quantities.

    Science, this issue p. 10.1126/science.1246501

  11. Structural Biology

    Energy conversion in complex 1

    1. Valda Vinson

    ATP, the energy source of the cell, is synthesized by a protein residing in the mitochondrial inner membrane. The synthesis is driven by a proton gradient generated by redox reactions that transfer electrons between a series of enzymes in the membrane. The largest complex in this electron transfer chain is the 1-MD complex 1. It couples electron transfer from NADH to ubiquinone to the translocation of four protons. Zickermann et al. report the crystal structure of a complex comprising the 14 central subunits and the largest accessory subunit of mitochondrial complex 1 from a yeast-genetic model at 3.6 Å resolution. The structure identifies four potential proton translocation pathways and gives insight into how energy from the redox reactions is transmitted to drive proton pumping.

    Science, this issue p. 44

  12. Organic Chemistry

    Shifting hydroformylation into reverse

    1. Jake Yeston

    The hydroformylation reaction is applied on large scale in the chemical industry to make aldehydes by adding hydrogen and carbon monoxide to olefins. The reverse process could also prove useful in modifying complex molecules for pharmaceutical research, but methods directed toward that end often strip off the CO without the hydrogen. Murphy et al. now show that a rhodium catalyst can achieve selective dehydroformylation of a diverse range of compounds under mild conditions (see the Perspective by Landis). The protocol relies on effective transfer of the CO and H2 equivalents to a sacrificial strained olefin added to the mix.

    Science, this issue p. 56; see also p. 29

  13. Protein Synthesis

    Tagging truncated proteins with CAT tails

    1. Guy Riddihough

    During the translation of a messenger RNA (mRNA) into protein, ribosomes can sometimes stall. Truncated proteins thus formed can be toxic to the cell and must be destroyed. Shen et al. show that the proteins Ltn1p and Rqc2p, subunits of the ribosome quality control complex, bind to the stalled and partially disassembled ribosome. Ltn1p, a ubiquitin ligase, binds near the nascent polypeptide exit tunnel on the ribosome, well placed to tag the truncated protein for destruction. The Rqc2p protein interacts with the transfer RNA binding sites on the partial ribosome and recruits alanine- and threonine-bearing tRNAs. Rqc2p then catalyzes the addition of these amino acids onto the unfinished protein, in the absence of both the fully assembled ribosome and mRNA. These so-called CAT tails may promote the heat shock response, which helps buffer against malformed proteins.

    Science, this issue p. 75

  14. Lateral Gene Transfer

    Killing, sex, and gene swaps in bacteria

    1. Caroline Ash

    The bacterial type VI secretion system (T6SS) is used by bacteria to inject toxins into neighboring cells to eliminate competition. This molecular machine is thus considered to be a mechanism by which bacteria can exert social control in complex microbial communities. Borgeaud et al. have discovered that in Vibrio cholerae, T6SS genes are co-regulated with genes involved in DNA uptake. Hence, T6SS-dependent killing of other bacteria is directed at neighboring cells, which release their DNA to be taken up by the killer, which can then integrate valuable genes and rapidly evolve, leading to antibiotic resistance or virulence.

    Science, this issue p. 63

  15. Aging

    Lysosomes signal the nucleus to control aging

    1. L. Bryan Ray

    Folick et al. propose a mechanism by which a lysosomal enzyme influences nuclear events that control longevity in the worm (see the Perspective by Shuo and Brunet). Increased expression of the lysosomal acid lipase LIPL-4 increased longevity, and this effect depended on the presence of the lysosomal lipid-binding protein LBP-8. LBP-8 acts as a chaperone that helps carry lipds to the nucleus. The authors identified the fatty acid oleoylethanolamide (OEA) as a potential signaling molecule whose transport to the nucleus could activate nuclear hormone receptors and transcription factors NHR-49 and NHR-80. The transcriptional targets of NHR-49 and NHR-80 in turn regulate longevity.

    Science, this issue p. 83

  16. Microbiology

    How bacterial populations get ready for stress

    1. Julia Fahrenkamp-Uppenbrink

    Populations of bacterial cells must be able to react to stressful situations, such as exposure to antibiotics, in order to survive. Holden explains that persisters, a very small subpopulation of bacterial cells that stop dividing, are key to this stress response. These cells are not genetically antibiotic-resistant but can nevertheless survive exposure to antibiotics before beginning to grow again. Single-cell analyses have provided insight into the molecular pathways through which bacterial cells enter the persister state. The results may help to develop successful treatments for recurrent infections.

    Science, this issue p. 30

  17. Mosquito Genomics

    Mosquito adaptability across genomes

    1. Caroline Ash

    Virtually everyone has first-hand experience with mosquitoes. Few recognize the subtle biological distinctions among these bloodsucking flies that render some bites mere nuisances and others the initiation of a potentially life-threatening infection. By sequencing the genomes of several mosquitoes in depth, Neafsey et al. and Fontaine et al. reveal clues that explain the mystery of why only some species of one genus of mosquitoes are capable of transmitting human malaria (see the Perspective by Clark and Messer).

    Science, this issue p. 10.1126/science.1258524 and 10.1126/science.1258522; see also p. 27