NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 3 May 2009
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
Biotechnology: Fresh lead for broad-spectrum Huntington’s therapy
Medicine: A primate-specific potassium channel in schizophrenia
Genetics: Sleep disorder associated with autoimmune response
Medicine: Antituberculosis boosters
Nature: Faulty protein linked to B-cell lymphoma
Chemical Biology: Energized by RNA
Geoscience: Amazonian ice
And finally … Nature: Singing without lessons
· Mention of papers to be published at the same time with the same embargo
· Geographical listing of authors
PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.
Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.
PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not).
NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/.
HYPE: We take great care not to hype the papers mentioned on our press releases, but are sometimes accused of doing so. If you ever consider that a story has been hyped, please do not hesitate to contact us at [email protected], citing the specific example.
PLEASE CITE THE SPECIFIC NATURE JOURNAL AND WEBSITE AS THE SOURCE OF THE FOLLOWING ITEMS. IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO THE APPROPRIATE JOURNAL’S WEBSITE.
[1] Biotechnology: Fresh lead for broad-spectrum Huntington’s therapy
DOI: 10.1038/nbt.1539
New findings may catalyze the development of drugs to treat Huntington’s and other similar diseases, reports a study published online this week in Nature Biotechnology.
We all carry two slightly different copies of most of our genes. Huntington’s disease, a severe neurological disorder, results when a sequence of three bases, CAG, in one of the two copies of the huntingtin (HTT) gene is repeated more than 36 times. The challenge in finding a cure is to silence the defective “stuttering” HTT without switching off the normal copy. So far, research into silencing mutant HTT relied on targeting specific mutations outside the repeats. But these strategies would not help patients with rare HTT mutations.
David Corey and colleagues show that an engineered RNA can discriminate between mutant and normal HTT on the basis of the repeated CAG sequence itself. They selectively target the mutant gene even in patient cells without the variants most commonly associated with Huntington’s. Although more remains to be learned about the mechanisms involved and how well the treatment works in animals, the findings provide a new starting point for developing drugs that may eventually benefit all Huntington’s patients.
Author contact:
David Corey (University of Texas, Southwestern Medical Center, Dallas, TX, USA)
Tel: +1 214 645 6155; E-mail: [email protected]
Additional contact for comment:
Neil Aronin (University of Massachusetts, Worcester, MA, USA)
Tel: +1 508 856 3239; E-mail: [email protected]
[2] Medicine: A primate-specific potassium channel in schizophrenia
DOI: 10.1038/nm.1962
A primate-specific variant of a potassium channel affects cerebral cortex function, cognition, neuronal physiology and risk of having schizophrenia, according to an article published this week in Nature Medicine. The identification of this channel variant provides a new therapeutic target to combat schizophrenia.
Organized neuronal firing is crucial for brain function and is disrupted in schizophrenia. Daniel Weinberger and colleagues have identified a primate-specific, brain-enriched form of the potassium channel KCNH2 that modulates neuronal firing. In the hippocampus, a brain region crucial for cognitive function, the expression of this KCNH2 variant is much higher in people with schizophrenia that in control subjects.
The authors also analyzed 367 families, 1,158 unrelated cases and 1,704 controls subjects and found an association of single nucleotide polymorphisms in KCNH2 with schizophrenia. Risk-associated polymorphisms were indicative of lower intelligence scores and speed of cognitive processing, altered memory and increased hippocampal mRNA levels of the KCNH2 variant.
The authors found that overexpression of the KCNH2 channel variant in neurons induced a rapidly deactivating potassium current that led to high-frequency, persistent neuronal firing that could help explain the neurological abnormalities.
Author contact:
Daniel Weinberger (National Institute for Mental Health, Bethesda, MD, USA)
Tel: +1 301 402 7564; E-mail: [email protected]
[3] Genetics: Sleep disorder associated with autoimmune response
DOI: 10.1038/ng.372
An assault of the immune system on sleep centers of the brain may cause narcolepsy, according to a study published online in Nature Genetics.
Narcolepsy is an elusive autoimmune disorder linked to depletion of cells deep in the regulatory regions of the brain and characterized by sudden onset of daytime sleepiness. Scientists have now detected a significant association between narcolepsy and a gene variant found in individuals of European as well as of Asian ancestry. The gene encodes an important receptor used by T-cells of the immune system to recognize foreign proteins in the body.
Emmanuel Mignot and colleagues carried out a genome wide association study to identify novel areas of the genome associated with susceptibility for narcolepsy. They found three distinct DNA variants in the T-cell receptor gene that were associated with an increased risk of the disorder. Their finding is intriguing since the only previous genetic association with narcolepsy among Europeans, Asians, and African Americans has been with another gene variant that encodes a molecule expressed on white blood cells, called human leukocyte antigen, that is responsible for presenting ‘foreign’ proteins to T-cell receptors.
The variants identified by Mignot and colleagues represent a significant advance into unraveling the cause of the autoimmune component of this disorder. This is also the first involvement of T-cell gene variants to be documented for any disease.
Author contact:
Emmanuel Mignot (Stanford University, Palo Alto, CA, USA)
Tel: +1 650 725 6517; E-mail: [email protected]
[4] Medicine: Antituberculosis boosters
DOI: 10.1038/nm.1950
Scientists have developed molecules for boosting the efficiency of an antibiotic used to treat tuberculosis, according to research published online this week in Nature Medicine. These new ‘booster’ drugs enable a small dose of an existing antituberculosis agent to work as well as conventional high dose treatment to fight off the infection.
Current tuberculosis therapy has side effects, which lead to a high risk of noncompliance with the treatment and to the emergence of drug-resistant bacteria.
Several antituberculosis compounds require metabolic activation before they can kill the bacteria. Drugs such as ethionamide, a second-line anti-tuberculosis compound, are activated by a bacterial enzyme known as EthA. The production of EthA is in turn controlled by a transcriptional repressor dubbed EthR.
Alain Baulard and colleagues designed inhibitors of EthR that boost the metabolic activation of ethionamide more than an order of magnitude in culture. In mice infected with tuberculosis, one of these inhibitors enabled a small dose of ethionamide to lessen the infection as efficiently as the conventional high-dose treatment. Owing to their boosting effect, the new inhibitors should prompt reconsideration of the use of ethionamide and related compounds as first-line anti-tuberculosis drugs.
Author contact:
Alain Baulard (Institut Pasteur de Lille, France)
Tel: +33 320 871 153; E-mail: [email protected]
[5] & [6] Nature: Faulty protein linked to B-cell lymphoma
DOI: 10.1038/nature07968
DOI: 10.1038/nature07969
A protein called A20 is frequently inactivated in B-cell lymphoma, according to two Nature papers published this week. The finding has implications for the design of therapeutic agents.
The protein is often inactivated in certain types of B-cell lymphoma when the A20 gene picks up mutations or deletions. Without A20’s calming influence, a signalling pathway called NF-kB becomes overactive and the cancer forms.
Laura Pasqualucci and colleagues show that A20 is inactivated in around 30% of patients with B-cell lymphoma. Seishi Ogawa and colleagues show that A20-deficient cells generate tumours in immunodeficient mice, and that tumour formation is suppressed when the protein is re-expressed. Both teams show that A20 itself suppresses cell growth in vitro and prompts cells to commit suicide.
Author contacts:
Laura Pasqualucci (Columbia University, New York, NY, USA) Author paper [5]
Tel: +1 212 851 5256; E-mail: [email protected]
Seishi Ogawa (University of Tokyo, Japan) Author paper [6]
Tel: +81 3 3815 5411; E-mail: [email protected]
[7] Chemical Biology: Energized by RNA
DOI: 10.1038/nchembio.175
Scientists have discovered a new class of enzymes that use a type of RNA to make natural products, according to a study published online this week in Nature Chemical Biology. Transfer RNA, called tRNA, add amino acids to a growing chain of amino acids that becomes a protein. However, in this study Jean-Luc Pernodet and colleagues report on tRNA assisting in secondary metabolism, widening the function of this central biomolecule.
There are many natural products that include certain amino acids joined into a small ring, but it has not been known how these rings are made. The scientists now identify a group of enzymes that make these molecules. The enzymes are unusual in that they do not have a way to harness ATP, the biological currency of energy, to generate the energy needed to perform the reaction. However, the authors solve this mystery by demonstrating that the enzymes use activated tRNAs—those with an amino acid already ‘energized’ by being attached to the RNA—to complete the reaction. This result expands our understanding of tRNA function and establishes a completely new biosynthetic pathway.
Author contacts:
Jean-Luc Pernodet (Centre National de la Recherche Scientifique, Orsay, France)
Tel: +33 1 69 15 46 41; E-mail: [email protected]
Muriel Gondry (Commissariat à l’Energie Atomique, Gif-sur-Yvette, France)
Tel: +33 16 90 87 647; E-mail: [email protected]
[8] Geoscience: Amazonian ice
DOI: 10.1038/ngeo517
Biological particles and mineral dust are responsible for ice formation in clouds in the Amazon, according to a study published online in Nature Geoscience. Microscopic particles initiate ice formation in the atmosphere, but the identity of these particles has been a matter of debate.
Anthony Prenni and colleagues examined the chemical composition of ice-forming particles in the Amazon basin during the wet season. They show that locally produced biological particles and mineral dust account for the majority of these ice-forming particles. Using a simple model, they suggest that the contribution of local bio-particles to ice formation is increased at higher atmospheric temperatures.
Author contact
Anthony Prenni (Colorado State University, Boulder, CO, USA)
Tel: +1 970 491 8414; E-mail: [email protected]
[9] Nature: Singing without lessons
DOI: 10.1038/nature07994
The singing style of zebra finches is, in part, genetically determined and can develop without singing ‘lessons’, reports a study published online in Nature this week.
Bird song is a crucial form of communication for zebra finches, and variations in songs are commonly found in different geographical locations. In the wild, young male zebra finches develop their individual singing styles by imitating adult males.
Olga Fehér and colleagues find that these lessons may not be necessary for song culture to develop. The scientists isolated a group of developing zebra finches before they were exposed to the adults’ songs. They found that the isolated finches’ song culture differed markedly from that of finches in the natural colony. The next generation imitated the isolated adults, but they had distinct differences in their songs. In three to four generations, the isolated colony’s songs evolved towards that of wild-type finches.
This model of the evolution of song culture evolution may be revealing of the importance of genetics in social learning in other animals, including humans.
Author contact:
Olga Feher (City College of New York, NY, USA)
Tel: +1 212 650 8608; E-mail: [email protected]
******************************************************
Items from other Nature journals to be published online at the same time and with the same embargo:
Nature (http://www.nature.com/nature)
[10] F-Box Protein FBXO31 Mediates Cyclin D1 Degradation to Induce G1 Arrest Following DNA Damage
DOI: 10.1038/nature08011
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[11] In vivo effects of a GPR30 antagonist
DOI: 10.1038/nchembio.168
NATURE CHEMISTRY (http://www.nature.com/nchem)
[12] Chlorotrinitromethane and its exceptionally short carbon–chlorine bond
DOI: 10.1038/nchem.179
NATURE GENETICS (http://www.nature.com/naturegenetics)
[13] Common variations in BARD1 influence susceptibility to high-risk neuroblastoma
DOI: 10.1038/ng.374
[14] Epigenetic control of retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine 5 methyltransferase DNMT2
DOI: 10.1038/ng.360
[15] Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates
DOI: 10.1038/ng.343
[16] Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia
DOI: 10.1038/ng.359
NATURE GEOSCIENCE (http://www.nature.com/ngeo)
[17] The spatial and temporal complexity of the Holocene thermal maximum
DOI: 10.1038/ngeo513
[18] Observed sources and variability of Nordic seas overflow
DOI: 10.1038/ngeo518
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[19] TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88–independent TLR4 pathway
DOI: 10.1038/ni.1727
[20] Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance
DOI: 10.1038/ni.1728
[21] Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2
DOI: 10.1038/ni.1730
[22] Transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation
DOI: 10.1038/ni.1731
[23] Development of immunoglobulin lambda-chain–positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappa B signals
DOI: 10.1038/ni.1732
NATURE MATERIALS (http://www.nature.com/naturematerials)
[24] Similarities between structural distortions under pressure and chemical doping in superconducting BaFe2As2
DOI: 10.1038/nmat2443
[25] Controlling interpenetration in metal–organic frameworks by liquid-phase epitaxy
DOI: 10.1038/nmat2445
[26] Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA
DOI: 10.1038/nmat2444
[27] Free-standing nanoparticle superlattice sheets controlled by DNA
DOI: 10.1038/nmat2440
Nature MEDICINE (http://www.nature.com/naturemedicine)
[28] Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C–dependent buffering mechanism
DOI: 10.1038/nm.1960
NATURE METHODS (http://www.nature.com/nmeth)
[29] Automated Unrestricted Multigene Recombineering for Multiprotein Complex Production
DOI: 10.1038/nmeth.1326
[30] Tissue tectonics: morphogenetic strain rates, cell shape change and intercalation
DOI: 10.1038/nmeth.1327
[31] High-throughput Ethomics in Large Groups of Drosophila
DOI: 10.1038/nmeth.1328
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
[32] Multifunctional nanoarchitectures from DNA-based ABC monomers
DOI:10.1038/nnano.2009.93
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[33] Adult neurogenesis promotes synaptic plasticity in the olfactory bulb
DOI: 10.1038/nn.2298
[34] Na+-activated K+ channels express a large delayed outward current in neurons during normal physiology
DOI: 10.1038/nn.2313
[35] Long-term plasticity of excitatory inputs to granule cells in the rat olfactory bulb
DOI: 10.1038/nn.2319
[36] Synaptotagmin-1 functions as the Ca2+ sensor for spontaneous release
DOI: 10.1038/nn.2320
Nature PHYSICS (http://www.nature.com/naturephysics)
[37] High-fidelity transmission of entanglement over a high-loss free-space channel
DOI: 10.1038/nphys1255
[38] Physical forces during collective cell migration
DOI: 10.1038/nphys1269
[39] The distribution of spatially averaged critical properties
DOI: 10.1038/nphys1268
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[40] Active nuclear import and cytoplasmic retention of activation-induced deaminase
DOI: 10.1038/nsmb.1598
******************************************************
[41] Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche
DOI: 10.1038/nm.1951
******************************************************
GEOGRAPHICAL LISTING OF AUTHORS
The following list of places refers to the whereabouts of authors on the papers numbered in this release. 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.
ARMENIA
Yerevan: 2
AUSTRALIA
Victoria: 19
AUSTRIA
Innsbruck: 3
Vienna: 37
BELGIUM
Brussels: 4
Ghent: 23
Leuven: 15
Louvain-la-Neuve: 17
BRAZIL
Sao Paulo: 8
CANADA:
Halifax: 16
Montreal: 3, 16, 40
CHILE
La Serena: 34
CZECH REPUBLIC
Prague: 3
DENMARK
Copenhagen: 20
FINLAND
Helsinki: 17, 28
FRANCE
Antony: 7
Evry: 1, 7
Gif-sur-Yvette: 7, 17
Grenoble: 24, 29
Illkirch: 29
Lille: 4
Orsay: 7
Paris: 20, 33, 40
Strasbourg: 3
GERMANY
Berlin: 15, 24, 28
Bochum: 25
Cologne: 23
Erlangen: 28
Frankfurt: 24
Hanover: 28
Halle: 14
Kulmback: 28
Mainz: 8, 20
Mannheim: 2
Marburg: 3, 25
Martinsried: 23
Munich: 2, 3, 12, 28
Nuremberg: 28
Regensburg: 28
Schwalmstadt-Treysa: 3
HUNGARY
Szeged: 15
IRELAND
Dublin: 19
ITALY
Bari: 2
Bologna: 3
Milan: 5
Naples: 13
Palermo: 13
Rome: 13
JAPAN
Kanagawa: 6
Kyoto: 6
Nagoya: 6
Okayama: 6
Saga: 41
Saitama: 6
Setagaya: 3
Shibukawa: 6
Tokyo: 3, 6, 7
Yamaguchi: 7
NETHERLANDS
Amsterdam: 17, 28
Utrecht: 17
NORWAY
Bergen: 18
Oslo: 3
Trondheim: 19, 40
SOUTH KOREA
Suwon: 3
SPAIN
Barcelona: 38
Bellaterra: 25
SWEDEN
Gothenburg: 18
Stockholm: 29
SWITZERLAND
Bellinzona: 5
Villigen: 29
Zurich: 29
UNITED KINGDOM
Birmingham: 13
Bristol: 29
Cambridge: 7, 30
London: 39
Oxford: 20
Surrey: 13
UNITED STATES OF AMERICA
California
Berkeley: 23
La Jolla: 3
Los Angeles: 13
Oakland: 3
Palo Alto: 3, 36
Pasadena: 31
San Francisco: 3
Stanford: 3, 41
Colorado
Fort Collins: 8
Connecticut
New Haven: 26
Florida
Gainesville: 13, 15
Illinois
Evanston: 3
Iowa
Ames: 24
Louisiana
New Orleans: 12
Maine
Bar Harbor: 23
Maryland
Bethesda: 2
College Park: 12
Massachusetts
Boston: 16, 23, 30, 38
Cambridge: 8, 30, 32, 38
Worcester: 10, 19
Missouri
St Louis: 34
New Mexico
Albuquerque: 11
Las Cruces: 11
New York
Ithaca: 27, 32
New York: 5, 9
Ohio
Cleveland: 12, 31, 35
Oklahoma
Oklahoma City: 16
Pennsylvania
Philadelphia: 11, 13
Texas
Dallas: 1, 36
Galveston: 36
Houston: 21
Utah
Salt Lake City: 41
Washington
Seattle: 3, 22, 34
Wisconsin
Madison: 3
URUGUAY
Montevideo: 40
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]
Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]
Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]
For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Biotechnology (New York)
Craig Mak
Tel: +1 212 726 9384; E-mail: [email protected]
Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]
Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]
Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]
Nature Genetics (New York)
Lily Khidr
Tel: +1 212 726 9324; E-mail: [email protected]
Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]
Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]
Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]
Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]
Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]
Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: [email protected]
Nature Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: [email protected]
Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]
Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]
About Nature Publishing Group (NPG):
Nature Publishing Group is a division of Macmillan Publishers Ltd, dedicated to serving the academic and professional scientific and medical communities. NPG’s flagship title, Nature, was first published in 1869. Other publications include Nature research journals, Nature Reviews, Nature Clinical Practice and a range of prestigious academic journals including society-owned publications. NPG also provides news content through Nature News. Scientific career information and free job postings are offered on Naturejobs.
NPG is a global company with principal offices in London, New York and Tokyo and offices in Basingstoke, Boston, Buenos Aires, Delhi, Hong Kong, Madrid, Melbourne, Munich, Paris, San Francisco, Seoul and Washington DC. For more information, please go to www.nature.com
