NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 01 March 2009
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
Nature: ‘PiggyBac’ to pluripotency
Nature: Solving the mystery of nicotine addiction
Neuroscience: Where decisions are made
Chemistry: Microtubes made easy
Immunology: First-rate help
Genetics: Managing iron overload
Nature: Clostridium virulence factor identified
· 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.
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[1] & [2] Nature: ‘PiggyBac’ to pluripotency
DOI: 10.1038/nature07864
DOI: 10.1038/nature07863
Researchers have induced pluripotency in human cells for the first time without using viral methods to deliver the reprogramming factors. The work, described online in Nature this week, demonstrates stable induced pluripotent stem (iPS) cells in both human and mouse fibroblasts using a DNA sequence that can move around the cell known as piggyBac, and combining this approach with a single vector to deliver all the factors into one site on the chromosome, and then excise it.
iPS cells have great potential in applications from regenerative medicine to toxicological testing and drug screening, but most current methods involve viral gene delivery that could cause abnormalities in the induced cells. Keisuke Kaji and colleagues demonstrate in mice that it is possible to use a single vector, containing the coding sequences of the four viral factors commonly used in inducing pluripotency, and synthesise four independent reprogramming factor proteins from that. They then show that the four genes can be removed using sequences surrounding the cassette in combination with an excision protein that cuts the intervening DNA out and rejoins the ends. Kaji and the team go on to generate iPS cells by combining their single-vector cassette with the piggyBac transposon.
Andras Nagy and colleagues take the piggyBac work a step further by combining it with the single-vector method to generate stable iPS cells from both human and mouse embryonic fibroblasts before the vector is removed from the chromosome in one piece. This team also show that the piggyBac method can be used to generate lines in which different combinations of the reprogramming factors are removed individually, making lines that are potentially useful for drug screens and research.
Author contacts:
Keisuke Kaji (The University of Edinburgh, UK) Author paper [1]
Tel: +44 131 650 5844; E-mail: [email protected]
Andras Nagy (Mount Sinai Hospital, Toronto, Canada) Author paper [2]
Tel: +1 416 586 3246; E-mail: [email protected]
[3] Nature: Solving the mystery of nicotine addiction
DOI: 10.1038/nature07768
Nicotine’s ability to selectively activate its receptors in the brain, but not muscle, is explained in a study online this week in Nature. The findings solve the chemical mystery of nicotine addiction.
If nicotine activated its receptors in muscles as potently as in the brain, smoking would cause intolerable and perhaps fatal muscle contractions — so how does the chemical discriminate? Dennis Dougherty and colleagues find that it’s all due to a specific interaction that only occurs in the brain, between the positive charge of nicotine and a specific aromatic amino acid on the brain receptor. This ‘cation–p’ interaction doesn’t happen in muscle, even though the binding sites for nicotine have the same overall structure. The difference is probably due to a subtle difference in the binding pockets, which allows nicotine to bind more tightly to the neuronal receptor.
Author contact:
Dennis Dougherty (California Institute of Technology, Pasadena, CA, USA)
Tel: +1 626 395 6089; E-mail: [email protected]
[4] Neuroscience: Where decisions are made
DOI: 10.1038/nn.2277
Scientists have discovered that the process involved in decision making occurs in different areas of the brain’s frontal lobe, depending on whether the decision is abstract or more concrete.
Damage to the frontal lobes of the brain can impair behavioural control, resulting in impulsivity and aggression. The frontal lobes are also important for cognitive control, or the ability to regulate the allocation of mental resources required for decision-making and planning. A study published online in Nature Neuroscience now finds that the tail end of the frontal lobes is more involved in cognitive control of more concrete actions, whereas the front end is more involved in cognitive control of more abstract actions.
David Badre and colleagues studied patients who had sustained damage to various parts of their frontal lobes. They had the patients do tasks which required either more abstract (for example, deciding whether to email a friend) or more concrete actions (such as actually hitting the keys required to type the email). They found that patients with damage to the tail end of the frontal lobes were more likely to be impaired at performing concrete but not abstract actions. Conversely, patients with damage toward the front end of the lobes were more likely to be impaired at performing abstract but not concrete actions.
The frontal lobes are a large structure, and although earlier work had suggested that cognitive control in these lobes is organized hierarchically, with different parts of the frontal lobes regulating different types of decisions, this report represents the first direct evidence for this organization.
Author contact:
David Badre (Brown University, Providence, RI, USA)
Tel: +1 401 863 9563; E-mail: [email protected]
[5] Chemistry: Microtubes made easy
DOI: 10.1038/nchem.113
Small tubes with diameters ranging from one micrometre to just over a tenth of a millimetre can be grown from inorganic crystals immersed in water, reports a study online in Nature Chemistry this week. Controlling the growth process could lead to networks of tubes that may prove useful for making designer microfluidic – so-called lab-on-a-chip – devices.
Leroy Cronin and colleagues take crystals of inorganic compounds known as polyoxometallates — large clusters made up of metal and oxygen atoms — and drop them into water containing positively charged organic molecules. In a matter of seconds, a tubular structure begins to grow from each crystal, and the direction of a given tube can be controlled by either placing a physical object in its path or applying a voltage to the solution. In this way, tubes can be grown into each other and merged to form branched junctions. By flowing a fluorescent dye through the tubes, Cronin and co-workers demonstrate that the structures are hollow and robust enough not to leak.
The diameter of the growing tubes can be controlled by varying the quantity or type of the charged molecules dissolved in the water. Moreover, the recipe for growing the microtubes is a fairly general one and a range of different polyoxometallates can be used. This enables the chemical properties of the tubes to be tuned, and offers the possibility of making microfluidic channels that not only direct the flow of solutions, but can chemically interact with them for applications such as catalysis or sensing.
Author contact:
Leroy Cronin (University of Glasgow, UK)
Tel: +44 141 330 6650; E-mail: [email protected]
[6] & [7] Immunology: First-rate help
DOI: 10.1038/ni.1704
DOI: 10.1038/ni.1715
Scientists reveal new details on how immune cells communicate upon vaccination in two papers online this week in Nature Immunology. The process enables the body to generate long-term highly effective antibody protection and understanding it better could lead to improved vaccination formulation.
Both papers focus on the interactions of specialized immune cells called follicular helper T cells (TFH) and their interaction with antibody-producing B cells. Michael McHeyzer-Williams and colleagues show only those T cells with highest affinity for the immunizing protein develop into TFH cells in lymph nodes and the spleen. TFH cells then form intimate contacts with B cells in lymphoid follicles, much like dance partners.
Richard Locksley and colleagues show these TFH cells give chemical instructions, known as cytokines, directly to their partner B cells. This interaction directs the B cell to refine its antibody-encoding genes to generate high-affinity antibodies tailored to give the most efficient immune response.
Author contacts:
Michael McHeyzer-Williams (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 8259; E-mail: [email protected] Author paper [6]
Richard Locksley (University of California, San Francisco, CA, USA)
Tel: +1 415 476 5859; E-mail: [email protected] Author paper [7]
[8] & [9] Genetics: Managing iron overload
DOI: 10.1038/ng.320
DOI: 10.1038/ng.335
A growth factor involved in inducing bone formation has an unsuspected role in iron metabolism, according to two studies published online this week in Nature Genetics.
Genetic hemochromatosis is a disorder caused by mutations in genes that encode the major iron regulatory hormone hepcidin and a cell surface receptor called hemojuvelin. Independent studies carried out by Marie-Paule Roth and by Jodie Babitt now show that in response to sensing iron levels, BMP6, a protein known previously to induce the formation of bone and cartilage, binds the hemojuvelin receptor to stimulate the release of the liver hormone hepcidin in order to prevent iron overload in mice.
The sustained deficiency of hepcidin causes excessive iron absorption from the diet and leads to the deposition of iron in the liver and other tissues, which in turn results in organ damage functional failure. These characteristics were similarly observed in mice with targeted disruption of the Bmp6 gene which resulted in massive iron overload in the liver, heart and pancreas.
It remains to be seen how iron regulates Bmp6 expression, which in turn will augment our understanding of how iron affects hepcidin expression. However, while patients with BMP6 mutations have yet to be described, drugs that act in a similar manner to BMP6 may be a useful alternative treatment strategy for managing iron-overload disorders.
Author contacts:
Marie-Paule Roth (INSERM, Toulouse, France)
Tel: +33 5 62 74 45 08; E-mail: [email protected] Author paper [8]
Jodie Babitt (Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA)
Tel: +1 617 643 3181; Email: [email protected] Author paper [9]
[10] Nature: Clostridium virulence factor identified
DOI: 10.1038/nature07822
Toxin B is essential for the virulence of Clostridium difficile, a Nature paper suggests. The find represents a paradigm shift in our understanding of this pathogen, which is the leading cause of infectious diarrhoea in hospitals worldwide.
C. difficile possesses two toxins, A and B, and researchers had thought that toxin A was the major virulence factor. Julian Rood and colleagues use an animal model and C. difficile mutants to show that toxin B, and not toxin A, is essential for the bacterial infection.
Author contact:
Julian Rood (Monash University, Clayton, Australia)
Tel: +61 3 9902 9157; E-mail: [email protected]
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Items from other Nature journals to be published online at the same time and with the same embargo:
Nature (http://www.nature.com/nature)
[11] The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex
DOI: 10.1038/nature07830
[12] A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range
DOI: 10.1038/nature07862
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[13] The anti-apoptotic gene survivin contributes to teratoma formation by human embryonic stem cells
DOI: 10.1038/nbt.1527
[14] Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
DOI: 10.1038/nbt.1529
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[15] Inhibition of Wnt signaling by Disheveled PDZ peptides
DOI: 10.1038/nchembio.152
NATURE GENETICS (http://www.nature.com/naturegenetics)
[16] Gene expression divergence in yeast is coupled to evolution of DNA-encoded nucleosome organization
DOI: 10.1038/ng.324
[17] Intrinsic variability of gene expression encoded in nucleosome positioning sequences
DOI: 10.1038/ng.319
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
[18] Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses
DOI: 10.1038/ni.1707
[19] Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids
DOI: 10.1038/ni.1710
Nature MEDICINE (http://www.nature.com/naturemedicine)
[20] Regulation of endocytosis via the oxygen-sensing pathway
DOI: 10.1038/nm.1922
[21] Coordination of PGC-1beta and iron uptake in mitochondrial biogenesis and osteoclast activation
DOI: 10.1038/nm.1910
[22] Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells
DOI: 10.1038/nm.1928
[23] Toll-like receptor 2–dependent induction of vitamin A–metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits T helper type 17–mediated autoimmunity
DOI: 10.1038/nm.1925
NATURE METHODS (http://www.nature.com/nmeth)
[24] Nanoscale live cell imaging using hopping probe ion conductance microscopy
DOI: 10.1038/nmeth.1306
[25] Quantification of rare allelic variants from pooled genomic DNA
DOI: 10.1038/nmeth.1307
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
[26] Mechanically controlled binary conductance switching of a single-molecule junction
DOI:10.1038/nnano.2009.10
[27] Phonon populations and electrical power dissipation in carbon nanotube transistors
DOI:10.1038/nnano.2009.22
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[28] Trans-synaptic adhesion between NGL-3 and LAR regulates the formation of excitatory synapses
DOI: 10.1038/nn.2279
[29] Altered chloride homeostasis removes synaptic inhibitory constraint of the stress axis
DOI: 10.1038/nn.2274
[30] Interval-time coding by neurons in the presupplementary and supplementary motor areas
DOI: 10.1038/nn.2272
[31] Thalamic activity that drives visual cortical plasticity
DOI: 10.1038/nn.2284
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[32] The mechanism of folding of im7 reveals competition between functional and kinetic evolutionary constraints
DOI: 10.1038/nsmb.1562
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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.
AUSTRALIA
Melbourne: 10
CANADA:
Calgary: 29
Montreal: 20
Toronto: 1, 2, 15, 20
CHINA
Hong Kong: 12
Shanghai: 12
CROATIA
Zagreb: 9
FRANCE
Gif-sur-Yvette: 8
Toulouse: 8
GERMANY
Berlin: 12
Dresden: 32
ISRAEL
Jerusalem: 13
Rehovot: 16
ITALY
Modena: 9
JAPAN
Aichi: 21
Ibaraki: 21
Kyoto: 21
Nagasaki: 21
Osaka: 18, 21
Saitama: 21
Sendai: 30
Tokyo: 18, 21, 30
SOUTH KOREA
Daejeon: 11, 28
Seoul: 17, 26
SWEDEN
Molndal: 21
UNITED KINGDOM
Cambridge: 21, 24, 32
Edinburgh: 1, 2
Glasgow: 5
Hinxton: 2
Leeds: 32
London: 12, 24
York: 32
UNITED STATES OF AMERICA
California
Berkeley: 4, 26
Emeryville: 15
La Jolla: 6
Pasadena: 3
San Francisco: 7, 15, 19
Florida
Gainesville: 9
Georgia
Atlanta: 23
Illinois
Evanston: 16
Hines: 10
Maywood: 10
Kentucky
Lexington: 24
Massachusetts
Boston: 9
Cambridge: 28, 31
Charlestown: 28, 31
Michigan
Grand Rapids: 20
Missouri
St Louis: 25
New York
New York: 14, 26
Upton: 26
Yorktown Heights: 27
North Carolina
Chapel Hill: 16, 20
Durham: 18, 27
Research Triangle: 18
Rhode Island
Providence: 4
Texas
Edinburg: 22
Houston: 22
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]
Katherine Anderson (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)
Peter Hare
Tel: +1 212 726 9284; 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 Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; 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 Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]
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