This Week in Science

Science  26 Aug 2016:
Vol. 353, Issue 6302, pp. 882
  1. Cancer Metastasis

    Myeloma enzyme makes way for metastasis

    1. Megan Frisk

    X-ray revealing bone cancer of the skull

    PHOTO: ZEPHYR/SCIENCE SOURCE

    Bone tissue is built up by osteoblasts and broken down by osteoclasts in a balanced remodeling process. In metastatic cancer, however, the balance is tipped, leading to the formation of cancerous growths in the bone. Attempts to prevent metastasis have not been successful in the clinic, so Liu et al. set out in search of a new pathway to target. The authors found that an enzyme called thymidine phosphorylase (TP), which is produced by myeloma cells, suppressed osteoblast activity (new bone formation) and enhanced osteoclast activity (bone resorption). Inhibiting this enzyme reduced the incidence of myeloma-induced osteolytic bone lesions, suggesting a new target for translation to the clinic—especially given that certain TP inhibitors are already approved for human use.

    Sci. Transl. Med. 8, 353ra113 (2016).

  2. Structural Biology

    How spliceosomes make the first cut

    1. Valda Vinson

    In eukaryotes, transcribed precursor mRNA includes noncoding sequences that must be spliced out. This is done by the spliceosome, a dynamic complex in which five small nuclear RNAs and several proteins go through a series of ordered interactions and conformational rearrangements to achieve splicing. Two protein structures provide a look at the first catalytic step in the pathway. Yan et al. report the structure of the activated spliceosome (the Bact complex) at 3.5 Å resolution, revealing how latency is maintained even though the complex is mostly primed for catalysis. Wan et al. report the structure of the catalytic step 1 spliceosome (the C complex) at 3.4 Å resolution; this complex forms after the first step of the splicing reaction.

    Science, this issue pp. 904 and 895

  3. Ultrafast Dynamics

    Shining a fast light on diamonds

    1. Jake Yeston

    Conceptually, the electronic structure of matter is a fixed scaffold of energy levels, which electrons climb with the help of light absorption. In reality, the light's electromagnetic field distorts the scaffold, a phenomenon that becomes increasingly evident with rising field intensity. Lucchini et al. studied a manifestation of this phenomenon, termed the dynamical Franz Keldysh effect, in diamond substrates exposed to sudden, moderately intense infrared fields. Using attosecond probe pulses and accompanying theoretical simulations, they resolved and accounted for the extremely rapid ensuing electron dynamics.

    Microcrystalline diamonds are used to measure electron dynamics.

    PHOTO: DAVID SCHARF/SCIENCE SOURCE

    Science, this issue p. 916

  4. Time Series Analysis

    Harnessing complexity in ecology

    1. Andrew M. Sugden

    Ecology concerns the behavior of complex, dynamic, interconnected systems of populations, communities, and ecosystems over time. Yet ecological time series can be relatively short, owing to practical limits on study duration. Ye and Sugihara introduce an analytical approach called multiview embedding, which harnesses the complexity of short, noisy time series that are common in ecology and other disciplines such as economics. Using examples from published data sets, they show how this approach enhances the tractability of complex data from multiple interacting components and offers a way forward in ecological forecasting.

    Science, this issue p. 922

  5. Single-Cell Genomics

    Visualizing gene expression in nuclei

    1. Laura M. Zahn

    Gene expression can vary greatly within a single cell. Using techniques that they developed for sequencing single nuclei and labeling proliferating cells in vivo, Habib et al. performed RNA sequencing of 1402 single nuclei from the adult mouse hippocampus. Combining this approach with a clustering algorithm for single-cell and -nucleus RNA sequencing data delineated specific cell types during cell differentiation and development. By providing polyadenylated RNA from nuclei alone, as opposed to cytoplasmic RNA, these methods open the application of single-cell transcriptomics to tissues in which individual cells are difficult to isolate.

    Science, this issue p. 925

  6. Virology

    New insights into norovirus entry

    1. Kristen L. Mueller

    There's no escaping norovirus when you have it—the symptoms from this gastroenteritis-causing virus, though brief, are often debilitating. Preventing infections will rely on improving our understanding of how norovirus enters host cells. Orchard et al. show that the entry of murine norovirus (MNoV) into host cells requires a protein called CD300lf. In cell culture, mouse cells needed to express CD300lf in order for MNoV binding, entry, and replication to occur. Deleting the gene encoding CD300lf in mice protected them against MNoV infection. Human cells expressing CD300lf allowed MNoV to break the species barrier, a finding that may lead to new insights into the infectivity of this virus.

    Science, this issue p. 933

  7. Innate Immunity

    A new trick for IL-1β

    1. Anand Balasubramani

    One strategy to tame the symptoms of autoimmune diseases is to block the pain-causing inflammation. For rheumatoid arthritis, one such therapy is the interleukin-1β (IL-1β) receptor antagonist anakinra; however, patients who receive anakinra have increased susceptibility to group A Streptococcus (GAS) infections. LaRock et al. examined the mechanisms governing this effect and found that a microbial protease, SpeB, activates IL-1β by directly cleaving the prodomain that prevents IL-1β signaling. Blocking this inflammatory response with anakinra may account for the more frequent GAS infections in patients with rheumatoid arthritis, an effect that may also hold true for their increased susceptibility to infection by other microorganisms.

    Sci. Immunol. 1, aah3539 (2016).

  8. Geophysics

    A seismic “weather bomb” detector

    1. Brent Grocholski

    Seismic tomography is like an x-ray of Earth's interior, except that it uses earthquakes for the illumination. Earthquakes are imperfect illuminators because they are clustered on plate boundaries, leaving much of the interior in the shadows. Using a seismic array in Japan, Nishida and Takagi detected seismic waves that they attribute to a severe and distant North Atlantic storm called a “weather bomb” (see the Perspective by Gerstoft and Bromirski). The seismic energy traveling from weather bombs through the Earth appears to be capable of illuminating the many dark patches of Earth's interior.

    Science, this issue p. 919; see also p. 869

  9. Materials Science

    From quantum dot to quantum dot

    1. Marc S. Lavine

    A wide range of materials can now be synthesized into semiconducting quantum dots. Because these materials grow from solutions, there is scope to combine quantum dots into devices by using simple, low-cost manufacturing processes. Kagan et al. review recent progress in tailoring and combining quantum dots to build electronic and optoelectronic devices. Because it is possible to tune the size, shape, and connectivity of each of the quantum dots, there is potential for fabricating electronic materials with properties that are not available in traditional bulk semiconductors.

    Science, this issue p. 885

  10. Structural Biology

    A window into the cell for vitamin A

    1. Valda Vinson

    Vitamin A is an essential nutrient for mammals, and its metabolites affect diverse biological processes. It is carried in the bloodstream as retinol by retinol binding protein (RBP); a protein called STRA6 is implicated in facilitating retinol translocation across the cell membrane. Chen et al. determined the structure of zebrafish STRA6 to a resolution of 3.9 Å by electron microscopy. A lipophilic cleft is a likely binding site for RBP, and an opening in the cleft may allow retinol to diffuse into the membrane. Unexpectedly, the structure also includes bound calcium-modulated protein, but its function remains unclear.

    Science, this issue p. 887

  11. Actinide Chemistry

    Bonding to berkelium

    1. Jake Yeston

    A geographical theme prevailed in the recent naming of the heaviest chemical elements. The choices brought to mind berkelium (Bk) and californium (Cf), the names chosen for elements 97 and 98 over half a century ago. Silver et al. now revisit the chemistry of Bk, which has proven fiercely challenging to study over the years on account of its vigorous radioactive decay. Synthetic crystallized Bk borate and dipicolinate compounds structurally resembled Cf analogs in the solid state but manifested distinct electronic and magnetic characteristics stemming from spin-orbit coupling effects.

    Science, this issue p. 888

  12. Health Economics

    Delivering chlorine to those who use it

    1. Gilbert Chin

    In developed countries, a consumer's valuation of a health product can be measured by his or her willingness to pay for it. But poorer individuals, especially those in developing countries, might want and need a product yet be unable to pay for it with money. Dupas et al. demonstrate that a nonprice voucher mechanism can be used to deliver chlorine for water treatment to people in Kenya who are too poor to pay for it, but who use it when they get it (see the Perspective by Olken). Having to redeem the vouchers screens out people who would accept the free chlorine solution but not use it.

    Science, this issue p. 889; see also p. 864

  13. Organic Synthesis

    Rapid ryanodol route

    1. Jake Yeston

    The plant-derived compound ryanodine and its hydrolyzed cousin ryanodol are biochemically interesting for their calcium-regulating capacity and chemically interesting for their dense tangle of carbon rings brimming with oxygen appendages. Chuang et al. report an efficient 15-step asymmetric synthesis of ryanodol from the structurally much simpler terpene pulegone (see the Perspective by Verdaguer). Key steps include a Pauson-Khand cyclization of a tethered alkene and alkyne with carbon monoxide to set the ring motifs, followed by an oxidation using selenium dioxide that delivers three different oxygen substituents in tandem.

    Science, this issue p. 912; see also p. 866

  14. Signal Transduction

    How hypoxia controls the kinase Akt

    1. L. Bryan Ray

    The protein kinase Akt controls cell survival and proliferation. In human cells in culture, Guo et al. found that Akt was modified by the prolyl hydroxylase EglN1 (see the Perspective by Voulgarelis and Tsichlis). Such prolyl hydroxylation suppressed enzymatic activity of Akt. EglN1 is sensitive to oxygen concentrations, and in cells experiencing hypoxia, EglN1 activity decreased and Akt became activated. This activation was associated with decreased binding of Akt to the pVHL tumor suppressor protein, which bound preferentially to prolyl-hydroxylated Akt and inhibited its activity. These effects could promote growth and survival of tumor cells exposed to hypoxia.

    Science, this issue p. 929; see also p. 870

  15. Conservation

    Harnessing expert knowledge

    1. Julia Fahrenkamp-Uppenbrink

    Complex conservation efforts can fail without effective communication between experts, policy-makers, and local people. For example, an attempt to use electric fences to prevent crop raiding by elephants in Kenya failed because the design did not fully account for the interests of different local groups. In a Perspective, Adams describes how experts' views of ecosystems may evolve under different scenarios, irrespective of their backgrounds. Transdisciplinarity, diversity, and transparency are crucial for groups of scientific experts to best contribute to effective conservation efforts.

    Science, this issue p. 867

  16. Neuronal Plasticity

    More responsive with epigenetics

    1. Nancy R. Gough

    Various neuropsychiatric and neurological diseases can change intrinsic membrane excitability, which affects how responsive neurons are to stimuli. Meadows et al. found that inhibiting the methylation of cytosines in DNA made cultured cortical neurons more responsive to stimuli. The increase in responsiveness was due to a decrease in the activity of a specific family of potassium channels, and inhibiting these channels enhanced intrinsic membrane excitability to a similar extent as inhibiting DNA cytosine methylation. Thus, epigenetic remodeling of DNA can control neuronal activity by altering the electrophysiological properties of the entire neuron.

    Sci. Signal. 9, ra83 (2016).

  17. Photosynthesis

    Sometimes, red light means grow

    1. Nicholas S. Wigginton

    Some cyanobacteria are able to use the far-red end of the light spectrum by synthesizing chlorophyll f pigments. Introducing the protein responsible for chlorophyll f synthesis into crop plants could potentially expand the range of wavelengths that such plants use during photosynthesis and thereby increase their growth efficiency. Ho et al. identified chlorophyll f synthase (ChlF) in two cyanobacteria that are acclimatized to grow using far-red light. Introducing the ChlF-encoding gene into a model cyanobacterium allowed the organism to synthesize chlorophyll f. Similarities between ChlF and a core protein of photosystem II suggest that they have a close evolutionary relationship, and ChlF may even represent a more primitive photochemical reaction center.

    Science, this issue p. 886