This Week in Science

Science  19 Dec 2014:
Vol. 346, Issue 6216, pp. 1476
  1. Conservation

    Success for Europe's large carnivores?

    1. Andrew M. Sugden

    Education efforts lead to an increase in European brown bear populations.

    CREDIT: © CHRIS SCHMID/AURORA PHOTOS/CORBIS

    Despite pessimistic forecasts, Europe's large carnivores are making a comeback. Chapron et al. report that sustainable populations of brown bear, Eurasian lynx, gray wolf, and wolverine persist in one-third of mainland Europe. Moreover, many individuals and populations are surviving and increasing outside protected areas set aside for wildlife conservation. Coexistence alongside humans has become possible, argue the authors, because of improved public opinion and protective legislation.

    Science, this issue p. 1517

  2. Photochemistry

    Using ozone below may conserve it above

    1. Jake Yeston

    The accumulation of laughing gas in the atmosphere isn't a laughing matter: Nitrous oxide (N2O) is a powerful greenhouse gas and a depleter of ozone. The manufacture of nylon releases substantial N2O as a byproduct during preparation of the precursor adipic acid. Hwang and Sagadevan now demonstrate an alternate route to adipic acid that involves treating cyclohexane with ozone under concurrent ultraviolet irradiation, generating no N2O. Thus, ironically, the application of ozone as a chemical reagent could ultimately help conserve its concentration in the atmosphere.

    Science, this issue p. 1495

  3. Cancer Therapy

    Drug resistance, up close and personal

    1. Paula A. Kiberstis

    Cancer therapies that target specific genetic mutations driving tumor growth have shown promising results in patients; however, the response is often short-lived because the tumors acquire new mutations that render them resistant to these therapies. Complicating matters, the mechanism of resistance can vary from patient to patient. To identify drugs most likely to be effective against resistant tumors, Crystal et al. established cell lines from the tumors of individual patients after resistance occurred and performed a drug screen and genetic analysis on the cultured cells. This strategy successfully identified drug combinations that halted the growth of resistant tumor cells both in culture and in mice. In the future, pharmacological profiling of patient-derived cells could be an efficient way to direct therapeutic choices for individual cancer patients.

    Science, this issue p. 1480

  4. Paleoceanography

    A brief hiccup in deep ocean circulation

    1. H. Jesse Smith

    During the last interglacial period, Antarctic Bottom Water (AABW) formation slowed markedly. This densest ocean water sinks to the bottom of the sea, and its production helps to flush the oceans and eventually to recycle the carbon dioxide (CO2) that forms from sinking organic matter back into the atmosphere. If the AABW production rate decreases, then CO2 accumulates at depth, potentially causing a corresponding drop in atmospheric CO2 concentration. Hayes et al. found evidence, in the form of a uranium spike, in deep sea sediments that such a slowdown in AABW formation occurred ∼127,000 years ago, which may have caused the atmospheric CO2 minimum observed at that time.

    Science, this issue p. 1514

  5. Immune Tolerance

    For the immune system, silence is golden

    1. Kristen L. Mueller

    For the immune system, balance is key. Immune cells must learn to eliminate invading pathogens but tolerate self. A cell type called regulatory T cells (Tregs) help to maintain this balance, but how they do so, particularly in humans, is unclear. Maeda et al. now report that Tregs “silence” T cells with modest reactivity to self. After culture with Tregs, the silenced T cells proliferated very little and produced almost no cytokines in response to antigen. The authors then examined T cells from healthy donors and from people with an autoimmune disease. Only healthy donors harbored silenced T cells, suggesting that if silencing goes awry, autoimmunity may result.

    Science, this issue p. 1536

  6. Earth Magnetosphere

    How trans-polar arcs transpire above

    1. Margaret M. Moerchen

    Aurora displays such as these over Alaska reflect plasma processes in Earth's magnetosphere

    PHOTO: © TED RAYNOR/IMAGEBROKER/CORBIS

    Auroral arcs within the polar cap are a visual marvel, and they may also indicate trapped energetic plasma in Earth's magnetosphere. Fear et al. combined simultaneous observations of both the aurora and signatures of the trapped plasma in Earth's magnetotail to demonstrate one recent instance of this phenomenon. Some researchers have proposed that flux generated by magnetic reconnection might get trapped in the magnetotail lobe, but the standard magnetosphere model does not predict it. This study confirms the idea by taking advantage of a period when the interplanetary magnetic field points northward, a state not yet well understood.

    Science, this issue p. 1506

  7. Protein Design

    Building transmembrane zinc transporters

    1. Valda Vinson

    The ability to design proteins gives insight into the relation between a protein's fold and its function and also provides a path to custom proteins for bioengineering applications. Impressive strides have been made in the design of soluble proteins, but designing membrane proteins remains a challenge. Joh et al. achieve a milestone by designing a transmembrane Zn2+ transporter (see the Perspective by Lupas). The protein comprises four helices: Two tightly interacting pairs form a weaker interface that facilitates the transport of Zn2+ with concomitant reverse transport of protons.

    Science, this issue p. 1520; see also p. 1455

  8. Imaging

    Look, pathologists! No lens!

    1. Megan Frisk

    Imaging entire human tissues with a light microscope requires stitching 500+ images together — a digitization process largely confined to advanced laboratories. Greenbaum et al. developed a lens-free microscope based on low-cost holographic technology, which enables fields of view a hundredfold larger than conventional technology allows. This tool employs a small chip and allows for three-dimensional focusing through thick tissue samples. The team imaged human cancer cells, abnormal cells in Pap smears, and sickle cells in whole-blood smears with sufficient resolution and contrast for clinical diagnosis. With its high resolution and speedy readout, the new platform could benefit pathology labs worldwide.

    Sci. Transl. Med. 6, 267ra175 (2014).

  9. Protein Evolution

    Controlling the state of dynamic proteins

    1. Valda Vinson

    Small molecules that change the oligomeric state of proteins by binding to a site distant from the interface are called allosteric. They often act by taking advantage of intrinsic protein dynamics and stabilizing a particular conformation of the protein. Perica et al. show that mutations can similarly act at a distance to change protein conformation. They identified 11 mutations in an RNA- binding protein that determine whether it is stable as a dimer or a tetramer. Examination of ancestral sequences showed that the allosteric mutations are part of a downhill adaptation to lower environmental temperatures. This mechanism for modulating the oligomeric state is probably common in evolution.

    Science, this issue 10.1126/science.1254346

  10. Cancer Epigenetics

    Modeling brain cancer from stem to stern

    1. Paula A. Kiberstis

    Diffuse intrinsic pontine gliomas (DIPGs) are aggressive brain tumors primarily affecting children. Because the tumors arise in the brainstem, which controls many vital functions, they cannot be surgically excised and are often fatal. To study the pathogenesis of DIPGs—in particular, the role of a histone H3.3 mutation that occurs in 70% of cases—Funato et al. developed a new tumor model (see the Perspective by Becher and Wechsler-Reya). They first directed the differentiation of embryonic stem cells into neural progenitor cells. They then introduced a specific combination of genes, including the mutant histone gene, and found that this caused the progenitor cells to acquire features characteristic of cancer cells. During this oncogenic transformation, the cells reverted to a more primitive differentiation state and displayed altered histone marks at several key regulatory genes.

    Science, this issue p. 1529; see also p. 1458

  11. Humoral Immunity

    Endogenous retroviruses trigger B cells

    1. Kristen L. Mueller

    Scattered across our genome are endogenous retroviruses (ERVs), ancient “footprints” of previous viral infections. Scientists do not fully understand their functions, but Zeng et al. now report a role for ERVs in mobilizing a particular type of B cell–driven immune response in mice (T cell–independent, TID), which is usually mounted in response to viral capids or bacterial polysaccharides (see the Perspective by Grasset and Cerutti). Immunizing mice with a model TID antigen elicited an increase in ERV RNA and DNA in the cytoplasm of B cells. Innate immune receptors that recognize cytoplasmic nucleotides then triggered signaling cascades that resulted in the production of immunoglobulin M.

    Science, this issue p. 1486; see also p. 1454

  12. Electron Transfer

    Big impact from a well-placed shake

    1. Jake Yeston

    Since the advent of ultrashort laser pulses, chemists have sought to steer reaction trajectories in real time by setting particular molecular vibrations in motion. Using this approach, Delor et al. have demonstrated a markedly clear-cut influence on electron transfer probabilities along the axis of a platinum complex. The complex comprised donor and acceptor fragments—which respectively give and take electrons upon ultraviolet excitation—bridged together by triply bonded carbon chains linked to the metal center. By selectively stimulating the carbon triple-bond stretch vibration with an infrared pulse, the authors could induce substantial changes in the observed electron transfer pathways between the fragments.

    Science, this issue p. 1492

  13. Catalysis

    Dispersing catalytic gold as widely as possible

    1. Phil Szuromi

    In order to maximize the activity of precious metals in catalysis, it is important to place the metal on some support with a high surface area (such as a zeolite) and to maintain the metal as small clusters or even atoms to expose as much metal as possible. The latter goal is more readily achieved with oxides of reducible metals such as cerium or titanium than with the aluminum and silicon oxides that make up most zeolites and mesoporous oxides. Yang et al. show that sodium and potassium can stabilize gold along with hydroxyl and oxo groups to create highly active catalysts for the water-gas shift reaction at low temperatures, a reaction that can be useful in applications such as fuel cells.

    Science, this issue p. 1498

  14. Nanomaterials

    Nanoparticle growth starts at the edges

    1. Phil Szuromi

    The high activity of precious metals such as platinum for reactions that occur in fuel cells can be enhanced by alloying with metals such as nickel and cobalt to form shaped nanoparticles, where platinum is concentrated at the corner and edge sites. Gan et al. used a combination of high-resolution imaging and modeling to follow the formation of octadedral nanoparticles of these alloys with increasing growth times. A platinum-rich phase with an extended morphology forms initially and becomes the edges and corners for the particles, and the alloying metals deposit to fill in the facets.

    Science, this issue p. 1502

  15. Biophysics

    Stark influence on reaction rates

    1. Jake Yeston

    Enzymes accelerate chemical processes by coaxing molecules into just the right reactive states. Fried et al. now elucidate the way the enzyme ketosteroid isomerase pushes its substrate toward product through exertion of a local electric field (see the Perspective by Hildebrandt). First the authors calibrated the shifts in molecular vibrational frequencies, known as Stark shifts, that fields of varying strength impose on a substrate analog; then they measured the vibrational spectrum of that compound in the enzyme's active site. The experiment uncovered an unusually strong field that the local enzyme structure directed to the precise spot where the substrate would react.

    Science, this issue p. 1510; see also p. 1456

  16. Gene Expression

    Promoters tune gene expression noise

    1. Beverly A. Purnell

    Although cells in a tissue are genetically identical and appear the same, they often exhibit variability in their patterns of gene expression. Organisms may need this to prepare for exposure to varying environmental stresses. Using the tools of synthetic biology, Jones et al. construct a wide range of E. coli promoters in which the key molecular parameters (such as protein binding and unbinding rates) are systematically varied and compare the resulting expression noise to parameter -free model predictions. This work demonstrates that expression noise is a tunable parameter, with different generegulatory architectures giving rise to different, but predictable, patterns of expression noise.

    Science, this issue p. 1533

  17. Protein Design

    Designing activity at an interface

    1. Valda Vinson

    Enzymes are proteins that are the workhorses of the cell. Designing enzymes with new functions that are also manifested in living systems could be extremely valuable in bioengineering and synthetic biology applications. However, enzyme design is a challenging task and so far has mainly been restricted to repurposing natural enzymes and to in vitro systems. Song and Tezcan started with a monomeric redox protein and introduced mutations that cause it to assemble into a tetramer with catalytic zinc ions in its interfaces. This protein assembly displayed β-lactamase activity, the primary mechanism of antibiotic resistance, and enabled E. coli cells to survive ampicillin treatment.

    Science, this issue p. 1525

  18. Climate Change

    Can regional climate change be predicted?

    1. Julia Fahrenkamp-Uppenbrink

    Global climate models (GCMs) provide broad-brushstroke projections of future climate. These projections lack the resolution required to understand and respond to regional changes. “Downscaling” methods use GCM results as the starting point to model regional climate change. Hall explains that researchers and planners interested in regional adaptation planning should interpret results from such downscaling with care: Climate warming patterns can often be downscaled with confidence, but changes in atmospheric circulation are much harder to capture.

    Science, this issue p. 1461

  19. Cancer

    Menacing exosomes spread cancer

    1. Lisa D. Chong

    Exosomes are tiny vesicles released from cells that carry proteins, lipids, and nucleic acids: cargo that can affect the biology of recipient cells. In a Perspective, Anastasiadou and Slack highlight recent studies that reveal how these vesicles act as vehicles to spread cancer. Exosomes that are released by cancer cells harbor oncogenic microRNAs (miRNAs), proteins involved in miRNA biogenesis, and miRNAs that induce inflammatory conditions that support tumor growth and metastasis. Such cancer exosomes cause normal cells to form tumors in animal studies. The findings could guide the development of exosome-based diagnostics and therapies for cancer.

    Science, this issue p. 1459

  20. Immunology

    Stopping inflammation after infection

    1. John F. Foley

    In response to microbes, innate immune cells activate the transcription factor NF-κB, resulting in pro-inflammatory cytokine release. Once an infection has been resolved, NF-κB signaling must be inhibited to prevent excessive inflammation and tissue damage. Tanaka et al. found that this feedback inhibition requires the chaperone protein HSP70, which enabled the breakdown of the NF-κB subunit p65 in dendritic cells. HSP70-deficient dendritic cells produced more pro-inflammatory cytokines than did wild-type cells, and HSP70-deficient mice had more sustained inflammatory responses to bacterial infection than did wild-type mice.

    Sci. Signal. 7, ra119 (2014).

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