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Volume 465 Issue 7294, 6 May 2010

Alternative splicing allows a single gene to produce more than one protein, and shapes how genetic information controls cellular processes. The Frey and Blencowe labs at the University of Toronto have combined forces to develop a 'splicing code' that predicts how hundreds of RNA features work together to regulate tissue-dependent alternative splicing for thousands of exons (see News page 16). The code has been used to predict how alternative splicing acts in various developmental and neurological processes, and the code has been incorporated into a web tool that allows researchers to scan uncharacterized exon and intron sequences to predict tissue-dependent splicing patterns. Cover graphic by Brendan Frey.

Editorial

  • Governments have typically regulated their coastal waters as if fishing, shipping and the like were separate entities. A new, integrated approach could change all that — while greatly boosting marine science.

    Editorial

    Advertisement

  • Ways to obtain more accurate data can and should be put in place to police greenhouse-gas emissions.

    Editorial
  • A new approach to technology assessment would supplement expert opinion with input from society.

    Editorial
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Research Highlights

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Journal Club

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News

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News Feature

  • Fifty years ago this month, a massive earthquake in Chile broke new ground in seismic science. Roff Smith looks back at the largest quake ever recorded.

    • Roff Smith
    News Feature
  • Systems neuroscientists are pushing aside their electrophysiology rigs to make room for the tools of 'optogenetics'. Lizzie Buchen reports from a field in the process of reinvention.

    • Lizzie Buchen
    News Feature
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Column

  • A small non-profit organization shows how to reduce the vulnerability of poor countries to earthquakes, says Daniel Sarewitz.

    • Daniel Sarewitz
    Column
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Correspondence

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Opinion

  • The tightening of the US science budgets could improve both teaching and research, argues Diane Auer Jones — by forcing academics and their institutions to play to their strengths.

    • Diane Auer Jones
    Opinion
  • Jonathan Shanklin, one of the team who discovered the thinning ozone layer over the Antarctic 25 years ago, reflects on lessons learned from a tale of luck, public perception and fast environmental change.

    • Jonathan Shanklin
    Opinion
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Books & Arts

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News & Views

  • Earth's spin rate varies with time. A six-year periodic signal in the planet's core is partly responsible, and increases the interior magnetic-field strength to much higher levels than previously thought.

    • Andy Jackson
    News & Views
  • Controversy has raged over the identity of the metal cofactor of membrane-bound methane monooxygenase, a methane-oxidizing enzyme. A study suggests that the answer is a cluster of two copper ions.

    • J. Martin Bollinger Jr
    News & Views
  • Optoelectronic circuits with delayed feedback provide a convenient bench-top platform to study a wide range of nonlinear dynamic systems, from ultrastable clocks to complex chaotic devices.

    • Laurent Larger
    • John M. Dudley
    News & Views
  • Infection with hepatitis C is one of the main causes of liver disease, yet there are no broadly effective treatments. Discovery of a potent inhibitor of this virus shows that researchers must think outside the box.

    • Catherine L. Murray
    • Charles M. Rice
    News & Views
  • An elastic polymer has been made whose molecular structure mimics that of titin, a protein found in muscle. The resulting material is tough, stretchy and dissipates energy — just like muscle itself.

    • Elliot L. Chaikof
    News & Views
  • Diverse messenger RNAs, and thus proteins, can be generated from a single piece of DNA. A computational approach is helping to uncover complex combinatorial rules by which specific gene instructions are selected.

    • J. Ramón Tejedor
    • Juan Valcárcel
    News & Views
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Addendum

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Article

  • The brain is apt to sort sensory stimuli into discrete perceptual categories, but the neuronal activity behind this capability has been unclear. Here, the problem has been investigated by presenting zebrafish with different concentrations or types of odours. The results show that the activity of neuronal populations in the olfactory bulb is largely insensitive to changes in odour concentration, but that morphing one odour into another produces abrupt transitions between odour representations.

    • Jörn Niessing
    • Rainer W. Friedrich
    Article
  • The coding capacity of the genome is greatly expanded by the process of alternative splicing, which enables a single gene to produce more than one distinct protein. Can the expression of these different proteins be predicted from sequence data? Here, modelling based on information theory has been used to develop a 'splicing code', which can predict, with good accuracy, tissue-dependent changes in alternative splicing.

    • Yoseph Barash
    • John A. Calarco
    • Brendan J. Frey
    Article
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Letter

  • Ultraluminous infrared galaxies are among the most luminous objects in the local Universe and are thought to be powered by intense star formation. In these objects, the rotational lines of molecular hydrogen (H2) observed at mid-infrared wavelengths are not affected by dust obscuration, but the source of excitation has been unknown. Here it is found that H2 emission originates outside the obscured regions; it is proposed that H2 emission traces shocks in the surrounding material that are excited by interactions with nearby galaxies.

    • Nadia L. Zakamska
    Letter
  • Recent progress in solid-state quantum information processing has stimulated the search for amplifiers and frequency converters with quantum-limited performance in the microwave range. Here, a phase-preserving, superconducting parametric amplifier with ultra-low-noise properties has been experimentally realized.

    • N. Bergeal
    • F. Schackert
    • M. H. Devoret
    Letter
  • Here, artificial proteins are described that mimic the molecular architecture of titin — a protein that helps to govern the passive elastic properties of muscle. The new artificial proteins combine structured and unstructured domains, and can be photochemically crosslinked into a solid biomaterial that is resilient at low strains and extensible and tough at high strains. This provides an example of tailoring the macroscopic properties of a material through engineering at the single-molecule level.

    • Shanshan Lv
    • Daniel M. Dudek
    • Hongbin Li
    Letter
  • The magnetic field inside the Earth's outer core cannot be directly probed. The intensity of the magnetic field at the core–mantle boundary is estimated to be 0.3 mT, and geodynamo models predict a value about ten times larger (3 mT) for the core's interior. Other data, however, indicate an internal field of only around 0.2 mT. This discrepancy has now been resolved: an ensemble inversion of core flow models finds a torsional wave recurring every 6 years, leading to an estimated field strength of around 4 mT inside the core.

    • Nicolas Gillet
    • Dominique Jault
    • Alexandre Fournier
    Letter
  • Slip on a subduction megathrust can occur during an earthquake or aseismically. The size, location and frequency of earthquakes that a megathrust can generate depend on where and when aseismic creep is taking place, and what fraction of the long-term slip it accounts for. Here this issue is addressed by looking at the central Peru megathrust, and specifically at the Pisco earthquake of 2007. The findings show that aseismic creep accounts for 50–70% of the slip budget on the seismogenic portion of the megathrust.

    • Hugo Perfettini
    • Jean-Philippe Avouac
    • Pierre Soler
    Letter
  • Mutations in mitochondrial DNA (mtDNA) are a common cause of human genetic disease. It has been shown in non-human primates that nuclear transfer techniques might be an approach to prevent the transmission of mtDNA mutations. The proof of principle has now been extended to human embryos. Pronuclei were transferred between human zygotes, which developed onwards to the blastocyst stage in vitro. Carry-over of mtDNA from the donor zygotes to the recipients was minimal.

    • Lyndsey Craven
    • Helen A. Tuppen
    • Douglass M. Turnbull
    Letter
  • Notch and Delta are transmembrane proteins that allow neighbouring cells to communicate during development. Here, quantitative time-lapse microscopy has been used to show that the response of Notch to Delta on a neighbouring cell is graded, whereas its response to Delta on the same cell is sharp and occurs at a fixed threshold. A mathematical model explores how this new design principle enhances the sharpness of developmental boundaries set by classical lateral inhibition.

    • David Sprinzak
    • Amit Lakhanpal
    • Michael B. Elowitz
    Letter
  • Animals must detect water in their environment to stay alive, but the molecular basis for water detection has been unclear. Here the essential mediators of water-sensing and drinking in fruitflies have been identified: an ion channel of the degenerin/epithelial sodium channel family, and the sensory neurons that make it.

    • Peter Cameron
    • Makoto Hiroi
    • Kristin Scott
    Letter
  • Almost 200 million people worldwide are chronically infected with hepatitis C virus. Current treatments are poorly tolerated and not wholly effective, so new drugs are needed. Here, a potent new inhibitor of hepatitis C virus is described. This inhibitor targets the viral protein NS5A, and shows potential as part of a therapeutic regimen based on a combination of viral inhibitors.

    • Min Gao
    • Richard E. Nettles
    • Lawrence G. Hamann
    Letter
  • Before mating, a yeast cell must detect a partner cell that is close enough and expresses sufficiently large amounts of a sex pheromone. The mating decision is an all-or-none, switch-like response to pheromone concentration. It is now shown that this decision involves the competition of one kinase and one phosphatase enzyme for multiple phosphorylation sites on a 'scaffold' protein. The results should prompt a re-evaluation of the role of related signalling molecules that have been implicated in cancer.

    • Mohan K. Malleshaiah
    • Vahid Shahrezaei
    • Stephen W. Michnick
    Letter
  • DNA methylation is an important epigenetic mark in many eukaryotes. In Arabidopsis plants, small interfering RNAs bound to the Argonaute 4 (AGO4) protein can direct de novo DNA methylation and consequent gene silencing. Here, a new regulator of RNA-directed DNA methylation has been discovered. This protein, RDM1, is proposed to bind to methylated DNA and to function in the AGO4 effector complex.

    • Zhihuan Gao
    • Hai-Liang Liu
    • Jian-Kang Zhu
    Letter
  • The ability of plants to 'green' in the dark is attributed to the activity of the dark-operative protochlorophyllide oxidoreductase (DPOR). This enzyme catalyses the stereospecific reduction of the C17≡C18 double bond of protochlorophyllide to form chlorophyllide a, the direct precursor of chlorophyll a. The X-ray crystal structure of the catalytic component of DPOR has now been solved. A chemical mechanism is proposed by which the reduction of the double bond may occur.

    • Norifumi Muraki
    • Jiro Nomata
    • Yuichi Fujita
    Letter
  • Particulate methane monooxygenase (pMMO) is an integral membrane protein, found in methanotropic bacteria, that can selectively oxidize methane to produce methanol. This metalloenzyme contains three subunits, and the metal composition and exact location of its active site has been the subject of much speculation. Here it is found that the enzyme's activity is dependent on copper, and that the active site is located in the soluble domains of the pmoB subunit.

    • Ramakrishnan Balasubramanian
    • Stephen M. Smith
    • Amy C. Rosenzweig
    Letter
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Corrigendum

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Regions

  • With targeted recruiting efforts under way, Kentucky is attempting to build a life-sciences hub.

    Regions
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Careers Q&A

  • Ben Keeton, executive director of the Kentucky BioAlliance, discusses the challenges of transforming a state historically dependent on agriculture, mining and manufacturing into a biotech presence.

    • Paul Smaglik
    Careers Q&A
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Prospects

  • Augmenting your full-time job with additional work can bring many rewards, says Peter Fiske.

    • Peter Fiske
    Prospects
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Futures

  • Virtual success.

    • Giulio Zambon
    Futures
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