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This press release is copyright Nature.
VOL.470 NO.7333 DATED 10 FEBRUARY 2011
This press release contains:
Summaries of newsworthy papers:
Neuroscience: Untangling the neuronal web
Genomics: A new era for personal medicine
Cancer: Genomic complexity of prostate cancer
Immunology: Retinoic acid implicated in coeliac disease
Nanotechnology: Programmable nanowire circuits
Genetics: Gene desert awash with enhancers
Comment: Protein researchers must embrace the unknown
Organic chemistry: Metal-free at last
Physics: Frustrated ferroelectrics
And finally… Out on a limb
Mention of papers to be published at the same time with the same embargo
Geographical listing of authors
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[1] Neuroscience: Untangling the neuronal web (pp 221-226; N&V)
A technique that combines optics and genetics has been used to target a specific population of neurons in the mouse brain that drives aggressive behaviour only, reports a paper in Nature. The neurons involved in offensive aggression in mice are localized within a subdivision of the ventromedial hypothalamus and are intermingled with neurons that are important in mating.
Certain areas of the hypothalamus are known to be involved in aggression but stimulating particular types of cell within a mixed cell population has proved difficult. Dayu Lin and colleagues report that activating specific neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl), targeted using optogenetic techniques, can elicit inappropriate attack behaviours in male mice (towards inanimate objects and females). Electrical stimulation, which has previously been shown to evoke a similar response in other mammals, did not induce the same effect in mice.
Additional genetic and electrophysiological analyses reveal that distinct but overlapping neuronal subpopulations in the VMHvl are involved in fighting and mating. Neurons that are activated during aggression are inhibited during mating, suggesting competition between the two behaviours. The work should facilitate further analysis of the circuitry of the hypothalamus, which could enhance our understanding of how neural circuits control mammalian behaviour.
CONTACT
Dayu Lin (New York University, NY, USA)
Tel: +1 212 263 9405; E-mail: [email protected]
Clifford Saper (Beth Israel Deaconess Medical Center, Boston, MA, USA) N&V author
Tel: +1 617 667 2622; E-mail: [email protected]
[2], [3] & [4] Genomics: A new era for personal medicine (pp 187-213)
A new vision for the future of genomics research could herald the start of a new era for genomic medicine and is presented as part of a special genomics issue of Nature this week. Eric Green and colleagues from National Human Genome Research Institute discuss the emerging opportunities in genomic medicine in light of advances in the field, outlining recommendations for the next decade.
The field of genomics has progressed rapidly following the publication of the human genome sequence ten years ago. The authors argue that improving our understanding of the biology of genomes and diseases will improve the effectiveness of healthcare, emphasizing that efforts must be made to achieve this as quickly as possible to realize the full benefits of genomic research.
They recommend genomics-based tests for disease diagnosis and genome sequencing to define genetic variation within disease, and they believe that cancer genomes need to be comprehensively characterized. Practical systems are needed to make genomic information easily available to patients and healthcare providers; moreover, the role of human microflora in health and disease must be a focus in order to understand the biological relevance of human–microbe interactions.
In another Review article, Eric Lander, who was present at the birth of the Human Genome Project, looks back at what has been achieved in the past ten years and speculates on the future. None of these achievements would have been possible without rapid advances in sequencing technologies, which are discussed by Elaine Mardis in a third article.
CONTACT
Eric Green (National Human Genome Research Institute, Bethesda, MD, USA) Author paper [2]
Tel: +1 301 496 0844; E-mail: [email protected]
Eric Lander (Broad Institute of MIT and Harvard, Cambridge, MA, USA) Author paper [3]
Tel: +1 617 252 1906; E-mail: [email protected]
Elaine Mardis (Washington University School of Medicine, St Louis, MO, USA) Author paper [4]
Tel: +1 314 286 1805; E-mail: [email protected]
[5] Cancer: Genomic complexity of prostate cancer (pp 214-220)
Newly discovered genetic abnormalities in human prostate cancer, reported in this week’s Nature, are helping to shed light on the mechanisms that trigger this common male cancer.
Levi Garraway and colleagues sequenced the complete genome of seven primary prostate cancers and identified complex patterns of balanced rearrangements — chromosomal regions where chunks of DNA have ‘swapped over’. The anomalies, which lie physically close to known cancer genes, are thought to arise through errors in transcription (the creation of RNA from DNA) or chromosome structure. And their occurrence is likely to be a critical event in the development of primary prostate cancer.
CONTACT
Levi Garraway (Dana-Farber Cancer Institute, Boston, MA, USA)
Tel: +1 617 632 6689; E-mail: [email protected]
[6] Immunology: Retinoic acid implicated in coeliac disease (AOP)
DOI: 10.1038/nature09849
***This paper will be published electronically on Nature's website on 09 February at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 10 February, but at a later date. ***
Retinoic acid, a metabolite of vitamin A, may have a role in the immune response that causes gluten intolerance in coeliac disease, according to a study published this week in Nature. The research may help to provide more clues about the pathogenesis of inflammatory and autoimmune disorders, such as intolerance to dietary antigens.
Bana Jabri and colleagues report that retinoic acid acts synergistically with interleukin-15 (IL-15), a cytokine that is upregulated in the gut of patients with coeliac disease. Together, IL-15 and retinoic acid seem to induce a proinflammatory response in the intestine, encouraging an inflammatory immune response to gluten.
The findings reveal an unexpected role for retinoic acid, which may inform our understanding of how best to treat autoimmune and inflammatory intestinal disorders.
CONTACT
Bana Jabri (University of Chicago, IL, USA)
Tel: +1 773 834 8670; E-mail: [email protected]
[7] Nanotechnology: Programmable nanowire circuits (pp 240-244)
A significant advance in the complexity and functionality of nanoelectronic circuits built ‘from the bottom up’ is reported in Nature this week. Charles Lieber and colleagues show how transistors made from semiconductor nanowires can be combined into scalable, programmable ‘logic tiles’, which could form the basis of fully integrated nanoprocessors.
The construction of a nanoprocessor from instrinsically nanometre-scale building blocks has been a long-standing goal of nanotechnology. Although simple logic gates have been built from nanoscale components, these circuits have fallen short of what is required for integration into a scalable, multifunctional nanoprocessor.
Lieber and colleagues build their circuits from transistors made from single germanium/silicon nanowires. These transistors have programmable threshold voltages, allowing individual transistors in an array to be switched between inactive and active states. A logic tile, with an area of only ~960 square micrometres, comprises 496 of these configurable transistors in two interconnected arrays. The tile can be programmed to perform a range of digital logic operations, with sufficient gain to drive other tiles in a cascading sequence. This should allow the creation of nanoprocessors, with computing, memory and addressing capabilities. An early application could be application-specific ‘nanocontrollers’, which might make possible tiny embedded electronic systems, including therapeutic devices.
CONTACT
Charles Lieber (Harvard University, Cambridge, MA, USA)
Tel: +1 617 496 3169; E-mail: [email protected]
[8] Genetics: Gene desert awash with enhancers (pp 264-268)
A Nature paper that helps unravel the previously identified link between a specific region of non-coding DNA and coronary artery disease (CAD) may help explain why some people are more genetically susceptible to CAD than others.
Dissecting associations that lie in non-coding DNA and that have been identified by genome-wide association study approaches is particularly challenging; only a few attempts have been successful. The region, found on chromosome 9, is known to contain various single base-pair changes (single nucleotide polymorphisms or SNPs) associated with CAD and type 2 diabetes. Kelly Frazer and colleagues studied this so-called ‘gene desert’ and identified 33 enhancers, snippets of DNA that increase the expression of other genes.
CAD-associated SNPs are found in one of the enhancers, where they affect binding of the regulatory protein STAT1 — an important find because STAT1 is known to influence the inflammatory response, which is in turn associated with the CAD hallmark of atherosclerosis. The authors show that the region is also influenced by the inflammatory molecule interferon-gamma, which can affect how local chromatin is organized in three dimensions, thereby affecting STAT1-binding and the expression of nearby genes.
CONTACT
Kelly Frazer (University of California, San Diego, CA, USA)
Tel: +1 858 246 0208; E-mail: [email protected]
Comment: Protein researchers must embrace the unknown (pp 163-165)
More than 75% of current research activity on human proteins still focuses on the 10% of proteins that were known before the genome was mapped — even though many more have been genetically linked to disease in the decade since.
Conservative funding and peer-review systems, and especially the availability of the research tools needed to study proteins, such as antibodies and chemical inhibitors, are to blame, argue Aled Edwards and his colleagues in a Comment piece in this week’s Nature.
The authors assessed how research activity has changed over time for three protein families that are central in disease and drug discovery. The group searched for mentions of every human kinase, ion channel and nuclear receptor in almost 20 million of papers published between 1950 and 2009. They discovered that for all three classes of protein, “the same small fraction of family members have remained the ‘favourites’ for nearly 20 years.”
What’s more, write the authors, “the availability of chemical probes for a given receptor dictates the level of research interest in it” — not the importance of the protein. This is suggested by the publication patterns for nuclear hormone receptors.
“Ensuring high-quality tools are developed for all the proteins discovered may be all that is needed to drive research into the unstudied parts of the human genome — even within funding and peer review systems that are inherently conservative,” say Edwards and his colleagues.
CONTACT
Aled Edwards (University of Toronto, Canada)
Tel: +1 416 946 3795; E-mail: [email protected]
[9] Organic chemistry: Metal-free at last (pp 245-249; N&V)
A solution to a tricky problem in the field of asymmetric catalysis is reported in Nature this week. Dean Toste and colleagues show that a metal-free organic acid can catalyse asymmetric reactions that previously required the use of metal catalysts.
Many chemical reactions can be catalysed by complexes that contain transition metals, such as copper or palladium. But there is a growing interest in finding chemical transformations that rely on simpler, metal-free catalysts. Chemists are also interested in asymmetric synthesis reactions, because the two mirror-image versions of a molecule can have very different biological activities. Chiral organic Brønsted acids — proton-donating molecules that are themselves asymmetric — are known to catalyse a wide range of asymmetric chemical transformations without requiring the addition of metals. But until now it has not seemed possible to use these organic acids to catalyse the highly asymmetric (‘enantioselective’) addition of functional groups to simple, ‘unactivated’ carbon–carbon multiple bonds.
Toste and colleagues now show that appropriately designed dithiophosphoric acids can catalyse the addition of amine and aryl groups to carbon–carbon double bonds, with excellent yield and enantioselectivity. The authors present analytical data that support their proposed ‘covalent catalysis’ mechanism, and argue that it should prove applicable to other asymmetric addition reactions.
CONTACT
Dean Toste (University of California, Berkeley, CA, USA)
Tel: +1 510 642 2850; E-mail: [email protected]
Matthew Gaunt (University of Cambridge, UK) N&V author
Tel: +44 1223 336318; E-mail: [email protected]
[10] Physics: Frustrated ferroelectrics (AOP)
DOI: 10.1038/nature09752
***This paper will be published electronically on Nature's website on 09 February at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 10 February, but at a later date. ***
Geometric frustration — a phenomenon well known in magnetic systems — has now been observed in simulations of a ferroelectric material: compositionally graded barium–strontium titanate, (Ba,Sr)TiO3. The findings, published online this week in Nature, add this technologically important class to the list of materials that can exhibit frustration, and may offer a new route to the experimental study of this widespread phenomenon.
Geometric frustration occurs when a system is unable to satisfy the demands of competing interactions, so that it cannot reach a single, lowest-energy state. Frustration has been observed for a wide range of magnetic materials, in which it gives rise to exotic states such as spin glasses and spin liquids. But in ferroelectric materials, where electrical polarization has the role that spin has in ferromagnets, there has not been any evidence of frustration.
Narayani Choudhury and colleagues have now changed this picture, by finding manifestations of geometrical frustration in their computational simulations of compositionally graded (Ba,Sr)TiO3. The simulations show the formation of exotic ordered phases, which shed light on the microscopic origin of frustration in this system. The authors note that, because compositionally graded ferroelectrics can be synthesized to order by standard techniques, these materials could provide a new experimental testbed for the study of frustration.
CONTACT
Narayani Choudhury (University of Arkansas, Fayetteville, AR, USA)
Tel: +1 425 516 8956; E-mail: [email protected]
[11] And finally… Out on a limb (pp 250-254; N&V)
Scientists have reconstructed sea-surface temperatures from near the tip of the Antarctic Peninsula for the past twelve thousand years. The record, reported in Nature this week, could help understanding of climate feedbacks and improve models of how the Antarctic ice sheet responds to climate change.
The Antarctic Peninsula is one of the fastest-warming places on Earth, experiencing dramatic regional climate change in recent decades, especially during La Niña years. But the long-term variability of the peninsula’s climate has remained unclear, and this has limited our ability to evaluate ongoing changes in a historical context and to understand what part underlying forcing mechanisms might play.
Amelia Shevenell and colleagues present data from a marine sediment core, which they use to reconstruct sea surface temperatures for the past twelve thousand years. The data show that long-term cooling of 3 to 4 degrees Celsius occurred in waters near the tip of the peninsula and was related to changes in local insolation, but short-term variability was strongly influenced by westerly winds. They propose that the present influence of the El Niño/Southern Oscillation (ENSO) system on the Antarctic Peninsula may have developed only over the past two thousand years. The authors suggest that if ENSO increases in strength and frequency and the westerly winds move south and intensify, as expected from future climatic warming, this connection may strengthen, with implications for Antarctic ice-sheet stability and sea-level rise.
CONTACT
Amelia Shevenell (University College London, UK)
Tel: +44 20 7679 0671; E-mail: [email protected]
James Bendle (University of Glasgow, UK) N&V author
Tel: +44 141 330 6864; E-mail: [email protected]
ALSO IN THIS ISSUE…
[12] Structural basis for the subunit assembly of the anaphase-promoting complex (pp 227-232; N&V)
[13] Acoelomorph flatworms are deuterostomes related to Xenoturbella (pp 255-258)
[14] lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3’ UTRs via Alu elements (pp 284-288)
ADVANCE ONLINE PUBLICATION
***These papers will be published electronically on Nature's website on 09 February at 1800 London time / 1300 US Eastern Time as part of our AOP (ahead of print) programme. Although we have included them on this release to avoid multiple mailings they will not appear in print on 10 February, but at a later date. ***
[15] Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome
DOI: 10.1038/nature09855
[16] Telomere dysfunction induces metabolic and mitochondrial compromise
DOI: 10.1038/nature09787
GEOGRAPHICAL LISTING OF AUTHORS…
The following list of places refers to the whereabouts of authors on the papers numbered in this release. For example, London: 4 - this means that on paper number four, there will be at least one author affiliated to an institute or company in London. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.
AUSTRALIA
Melbourne: 16
CANADA
Montreal: 13
GERMANY
Berlin: 13
ISRAEL
Rehovot: 5
JAPAN
Shimoda: 13
SWEDEN
Fiskebäckskil: 13
Uppsala: 13
UNITED KINGDOM
London: 11, 12, 13
Oxford: 12, 13
UNITED STATES OF AMERICA
Arkansas
Fayetteville: 10
California
Albany: 6
Berkeley: 9
La Jolla: 8
Palo Alto: 15
Pasadena: 1
Santa Monica: 5
Stanford: 15
Connecticut
New Haven: 5
Florida
Gainesville: 13
Tampa: 10
Illinois
Chicago: 6
Maryland
Bethesda: 2, 6
Chevy Chase: 5
Massachusetts
Boston: 5, 16
Cambridge: 3, 5, 7, 16
Worcester: 16
Minnesota
Rochester: 6
Mississippi
Vicksburg: 10
Missouri
St Louis: 4
New Hampshire
Hanover: 13
New Jersey
Princeton: 15
New York
Clinton: 11
New York: 5
Rochester: 14
Pennsylvania
Philadelphia: 6
Texas
Houston: 15
Virginia
McLean: 7
Washington
Seattle: 1, 11
PRESS CONTACTS…
From North America and Canada
Neda Afsarmanesh, Nature New York
Tel: +1 212 726 9231; E-mail: [email protected]
From Japan, Korea, China, Singapore and Taiwan
Mika Nakano, Nature Tokyo
Tel: +81 3 3267 8751; E-mail: [email protected]
From the UK
Rebecca Walton, Nature, London
Tel: +44 20 7843 4502; E-mail: [email protected]
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