NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 11 February 2007
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
Genetic indicators of type 2 diabetes risk – Nature
In utero protein regulation – Nature
Common genetic variant protects against breast cancer – Nature Genetics
Large-scale survey of mutations in cancer – Nature Genetics
Sleep deprivation impairs subsequent learning – Nature Neuroscience
Human adult stem cells can regenerate muscle – Nature Cell Biology
Viral highways: spreading from cell to cell – Nature Cell Biology
Finding phosphates on proteins – Nature Methods
· 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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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.
***************************************NATURE************************************************
(http://www.nature.com/nature)
[1] Genetic indicators of type 2 diabetes risk (N&V)
DOI: 10.1038/nature05616
Geneticists have identified five different areas of DNA base-pair change that contribute significantly towards the risk of developing type 2 diabetes mellitus. The finding helps tease apart the complex mix of genetic and environmental factors that contribute to the disease, and may guide the direction of future therapeutics.
Constantin Polychronakos and colleagues used high-density arrays to look for the occurrence of over 390,000 single nucleotide polymorphisms (SNPs) - particular regions of DNA containing a single base-pair change - in the genomes of over 2,000 patients with type 2 diabetes and more than 2,000 controls. They identified four different SNP-containing regions that conferred a significant risk to developing the disease, and confirmed an already known association between the TCF7L2 gene and type 2 diabetes. These five genetic regions together might account for 70% of the genetic risk, the authors say.
The important variants occur in genes related to the control of insulin secretion and pancreatic development. One gene encodes a protein that helps move zinc ions around and is found solely in the secretory vesicles of beta-cells, which make and release insulin. The finding, published online by Nature this week, has possible dietary implications and hints that therapies targeting zinc may be worth a shot.
Author contact:
Constantin Polychronakos (McGill University, Montreal, Quebec Canada)
Tel: +1 514 934 4315; E-mail: [email protected]
Nelson B. Freimer (UCLA, Los Angeles, CA, USA)
Tel: +1 310 794 9571; E-mail: [email protected] (N&V author)
[2] In utero protein regulation
DOI: 10.1038/nature05557
A novel strategy for regulating a protein important in development is described online in Nature this week. Michael T. Longaker and colleagues report that, in mice, glycogen synthase kinase-3beta (GSK-3beta) can be artificially controlled from within the mother's uterus, in a reversible and time-controlled manner.
GSK-3beta plays an integral part in a variety of biological processes, although its specific developmental roles remain unclear. In the present study the authors used an existing chemically regulated form of the GSK-3beta gene, whereby expression of the GSK-3beta protein is controlled by the presence or absence of the drug rapamycin. Using this approach combined with conventional mutant analysis they defined a specific requirement for GSK-3beta in midline development: mice that did not express the protein had cleft palate, incomplete fusion of the ribs and a split sternum.
In addition, the authors were able to rescue some of the developmental defects using maternal rapamycin treatment to restore internal GSK-3beta activity during two distinct windows of gestation. They propose that their studies provide an improved method for defining the timing and level of protein expression during development, a detailed knowledge of which is essential for rescuing developmental defects.
Author contact:
Michael T. Longaker (Stanford University Medical Center, CA, USA)
Tel: +1 650 736 1707; E-mail: [email protected]
Other papers from Nature to be published online at the same time and with the same embargo:
[3] A cytosolic trans-activation domain essential for ammonium uptake
DOI: 10.1038/nature05579
[4] Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4
DOI: 10.1038/nature05613
*********************************NATURE GENETICS ****************************
(http://www.nature.com/naturegenetics)
[5] Common genetic variant protects against breast cancer
DOI: 10.1038/ng1981
Scientists have confirmed that a common genetic variant – CASP8 – offers modest protection against breast cancer, according to a study to be published online this week in Nature Genetics. The report provides some of the strongest evidence so far that common variants affect the risk of developing breast cancer, and the size of the collaboration sets an important precedent for future studies.
Rare mutations in the genes BRCA1 and BRCA2 significantly raise an individual’s risk of breast cancer, but account for only a fraction of the overall variation in genetic risk. More common variants that have a smaller effect on individual risk have been difficult to find, largely due to the size of the studies needed to identify variants of small effect in a convincing manner.
The Breast Cancer Association Consortium, which comprises more than 20 collaborating research groups, examined 9 previously reported breast cancer susceptibility variants in at least 10,000 affected women and 10,000 disease-free women in a study led by Angela Cox. For 8 of the 9 genes, the Consortium reported either no association with breast cancer risk, or marginal evidence for an association. For a variant in the gene CASP8, however, they found a significant association. The particular variant assessed in the study is found in approximately 13% of women of European descent, and is protective, lowering the risk of breast cancer by approximately 10%.
Author contact:
Angela Cox (Sheffield University Medical School, UK)
Tel: +44 1142712373; E-mail: [email protected]
[6] Large-scale survey of mutations in cancer
DOI: 10.1038/ng1975
One of the largest surveys of mutations in human cancers is reported online this week in Nature Genetics. The study provides a preview of results that may be generated by even larger projects such as The Cancer Genome Atlas, set to begin soon.
Previous attempts at cataloguing mutations in different types of cancer have relied on DNA sequencing, which can be too expensive when applied to a large number of tumors. Levi Garraway and colleagues applied a previously developed technique called mass spectrometric genotyping to identify the frequency and distribution of 238 known mutations in 17 oncogenes in 1,000 tumors. The genotyping approach is more sensitive than the sequencing approach, identifying more mutations, and simultaneously detects mutations in multiple oncogenes in a cost-effective manner.
The authors report that mutations in three of the oncogenes were not found in any of the tumors, while mutations in the other genes were observed in only 30% of the tumors, indicating that many cancer-causing events remain to be discovered. There were relatively few examples where a specific mutation was found more than once, suggesting that mutations occurring at high frequency will be uncommon.
Author contact:
Levi Garraway (Dana-Farber Cancer Institute, Boston, MA, USA)
Tel: +1 617 632 6689; E-mail: [email protected]
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[7] The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells
DOI: 10.1038/ng1970
[8] X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation
DOI: 10.1038/ng1983
****************************NATURE NEUROSCIENCE ***********************************
(http://www.nature.com/natureneuroscience)
[9] Sleep deprivation impairs subsequent learning
DOI: 10.1038/nn1851
Sleep deprivation may impair memory for subsequent experiences by altering the function of the hippocampus, reports a paper in the March issue of Nature Neuroscience. Previous research has shown that sleep occurring after an experience can be critical to learning and memory but this new study shows why sleep before an experience is also critical, and that memory systems do not function normally without it.
Matthew Walker and colleagues deprived people of a night’s sleep and then asked them to observe and remember a large set of picture slides for a subsequent recognition test. Brain activity was monitored with fMRI – functional magnetic resonance imaging – while subjects viewed the slides. Following a full night of sleep, the subjects were then queried about the slides on the next day. The researchers found that sleep-deprived subjects showed decreased activity in the hippocampus – a brain region important for memory – relative to control subjects who were not sleep-deprived while viewing the pictures; sleep-deprived people also had poorer subsequent recall abilities. The relationship of activation in other brain areas to activation in the hippocampus was also altered, suggesting that sleep deprivation alters memory-encoding strategies.
Author contact:
Matthew Walker (Harvard Medical School, Boston, MA, USA)
Tel: +1 617 731 6378; E-mail: [email protected]
Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:
[10] Experience-dependent binocular competition in the visual cortex begins at eye opening
DOI: 10.1038/nn1844
[11] Alternative splicing controls G protein–dependent inhibition of N-type calcium channels in nociceptors
DOI: 10.1038/nn1848
[12] Intrinsic electrical properties of spinal motoneurons vary with joint angle
DOI: 10.1038/nn1852
[13] Vesicular glutamate release from axons in white matter
DOI: 10.1038/nn1850
[14] Vesicular release of glutamate from unmyelinated axons in white matter
DOI: 10.1038/nn1854
**************************NATURE CELL BIOLOGY ************************************
(http://www.nature.com/naturecellbiology)
[15] Human adult stem cells can regenerate muscle
DOI: 10.1038/ncb1542
Human adult stem cells isolated from human adult blood vessels are able to regenerate muscle in a mouse model of muscular dystrophy, according to a study published online this week in Nature Cell Biology.
The lure of a cure for muscle-wasting diseases has lead researchers to explore the regeneration potential of stem cells isolated from the walls of blood vessels. In a recent Nature paper Giulio Cossu and colleagues showed that such cells isolated from young golden retrievers regenerated the muscles of dystrophic dogs when injected into their circulation. A new study by the same team demonstrates that cells with similar properties can be isolated from human juvenile and adult blood vessels.
The same researchers isolated this type of stem cell from juvenile dystrophic patients and grew them in cell culture. Muscular dystrophy is linked to a mutation in dystrophin, a gene required for muscle formation, and the authors genetically modified the stem cells to make them express the corrected version of the gene. After injection into the blood vessels of dystrophic mice, these cells found their way to skeletal muscle, which they were able to partly regenerate. Importantly, the cells were shown to reconstitute the muscle’s own stem cell population. The authors suggest that the isolation of these stem cells raises hope for treating muscular dystrophy using the patient’s own cells.
Author contact:
Giulio Cossu (Stem Cell Research Institute, Rome, Italy)
Tel: +39 02 2643 4954; E-mail: [email protected]
[16] Viral highways: spreading from cell to cell
DOI: 10.1038/ncb1544
A number of retroviruses, including HIV, induce cells to form long bridges along which the virus particles move from infected cells to uninfected cells, according to a paper in the March issue of Nature Cell Biology.
Viral transmission has long been recognized to be more efficient between infected and target cells that are in direct contact with each other. Exactly how viruses move from one cell to another is unclear, although structures called virological synapses, which contain the virus particle and form between areas of cell–cell contact, are thought to be important in this process.
In the present study Walther Mothes and colleagues describe a novel mode of cell–cell transmission for three retroviruses – murine leukaemic virus, human immunodeficiency virus and avian leucosis virus – along the outside of long, thin intercellular bridges. These bridges seem to be stabilized by an association between a viral protein expressed by the infected cell and a viral-receptor protein in the target cell. Mutants of these proteins that cannot interact destabilize the bridges and markedly reduce viral spreading from cell to cell. This mode of transmission is observed in a variety of different cells, suggesting that it may be a general mechanism of viral spreading.
Whether these intercellular viral highways represent a predominant mode of viral transmission, their relative importance for different viruses, and their relationship to virological synapses are open questions. However, interference with the bridge structures described by Mothes and colleagues may provide a new avenue to limit the infectivity of a number of key viral diseases.
Author contact:
Walter Mothes (Yale School of Medicine, New Haven, CT, USA)
Tel: +1 203 737 2203; E-mail: [email protected]
Other papers from Nature Cell Biology to be published online at the same time and with the same embargo:
[17] Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2
DOI: 10.1038/ncb1545
[18] Caspase-11 regulates cell migration by promoting Aip1–Cofilin-mediated actin depolymerisation
DOI: 10.1038/ncb1541
*************************NATURE METHODS******************************************
(http://www.nature.com/nmeth)
[19] Finding phosphates on proteins
DOI: 10.1038/nmeth1005
A comparative analysis of the three most common strategies for isolating peptides with attached phosphates is presented online this week in Nature Methods.
The enzymatic addition and removal of phosphate groups on proteins is a crucial part of many biological processes, and it is therefore important to identify the sites where this occurs. Several strategies have been described for isolating phosphorylated peptides for subsequent analysis, but so far there has been no consensus on which method is ‘best’. Ruedi Aebersold and colleagues found that three popular methods isolated partially overlapping, yet somewhat different, sets of phosphorylated peptides from cells. They concluded that no single isolation method is currently sufficient for a comprehensive analysis of the ‘phosphoproteome’ – the total population of phosphorylated proteins in a given sample.
This warning should help the research community not to overestimate the predictive capabilities of a certain method to analyze phosphorylated proteins in biological samples.
Author contact:
Ruedi Aebersold (Swiss Federal Institute of Technology, Zurich, Switzerland)
Tel: +41 44 633 31 70; E-mail: [email protected]
Other papers from Nature Methods to be published online at the same time and with the same embargo:
[20] Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC
DOI: 10.1038/nmeth1010
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Items from other Nature journals to be published online at the same time and with the same embargo:
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[21] TRPM8 voltage sensor mutants reveal a mechanism for integrating thermal and chemical stimuli
DOI: 10.1038/nchembio862
Nature PHYSICS (http://www.nature.com/naturephysics)
[22] Two-dimensional vortices in superconductors
DOI: 10.1038/nphys540
[23] Effects of disorder on electron spin dynamics in a semiconductor quantum well
DOI: 10.1038/nphys537
NATURE MATERIALS (http://www.nature.com/naturematerials)
[24] Breakdown of the adiabatic Born–Oppenheimer approximation in graphene
DOI: 10.1038/nmat1846
[25] Self-assembly route for photonic crystals with a bandgap in the visible region
DOI: 10.1038/nmat1841
[26] Peak effect versus skating in high-temperature nanofriction
DOI: 10.1038/nmat1836
[27] Remotely powered self-propelling particles and micropumps based on miniature diodes
DOI: 10.1038/nmat1843
Nature MEDICINE (http://www.nature.com/naturemedicine)
[28] Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1
DOI: 10.1038/nm1542
Nature IMMUNOLOGY (http://www.nature.com/natureimmunology)
[29] Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4
DOI: 10.1038/ni1441
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[30] Structures of the Cd44-hyaluronan complex provide insight into a fundamental carbohydrate-protein interaction
DOI: 10.1038/nsmb1201
[31] Structure of a VEGF-VEGF receptor complex determined by electron microscopy
DOI: 10.1038/nsmb1202
[32] RPA-like proteins mediate yeast telomere function
DOI: 10.1038/nsmb1205
[33] Dynamics of the unbound head during myosin V processive translocation
DOI: 10.1038/nsmb1206
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[34] Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions
DOI: 10.1038/nm1557
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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
Brisbane: 5
Melbourne: 5
AUSTRIA
Innsbruck: 28
Salzburg: 28
Vienna: 6
BELGIUM
Leuven: 21, 29
CANADA:
Montreal: 1
Toronto: 1
DENMARK
Copenhagen: 5
FINLAND
Kuopio: 5
Helsinki: 5
FRANCE
Corbeil-Essonnes: 1
Lille: 1
Lyon: 5
Montpellier: 17
Paris: 24
Villjuif: 1
GERMANY
Bonn: 13
Cologne: 6, 29
Hannover: 5
Heidelberg: 5, 16, 28
Homburg: 29
Konstanz: 23
Munich: 16
Stuttgart: 3, 5
Tubingen: 5
Ulm: 5
ITALY
Milan: 15, 28
Modena: 15
Pavia: 15
Rome: 15
Trieste: 26
JAPAN
Ibaraki: 4, 7
Kyoto: 7
Nagoya: 6
Sapporo: 14
Shimotsuga: 34
Tokyo: 4, 7, 34
Tsukuba: 34
KOREA
Goyang: 5
Seoul: 5, 18
Ulsan: 5
NETHERLANDS
Utrecht: 25
NEW ZEALAND
Dunedin: 5
POLAND
Lodz: 5
Warsaw: 5
SINGAPORE
Singapore: 5
SPAIN
Madrid: 5
SWEDEN
Stockholm: 5
SWITZERLAND
Lugano: 26
Villigen: 31
Zurich: 6, 19
THAILAND
Bangkok: 5
UNITED KINGDOM
Cambridge: 5, 24
Hull: 27
London: 1, 2, 5, 16, 34
Manchester: 23, 24, 30
Oxford: 30
Sheffield: 5
Surrey: 5
UNITED STATES OF AMERICA
California
La Jolla: 32
Los Angeles: 6, 10
Palo Alto: 2
San Francisco: 2
Stanford: 3, 33
Colorado
Boulder: 23
Connecticut
New Haven: 16
Storrs: 14
Florida
Tallahassee : 22
Illinois
Argonne: 22
Chicago: 6, 11, 12
Evanston: 22
Maryland
Baltimore: 14
Bethesda: 5, 6
Gaithersburg: 5
Rockville: 5
Massachusetts
Boston: 6, 9, 18, 20, 31
Cambridge: 6
Minnesota
Minneapolis: 5
Rochester: 5
New Jersey
Princeton: 25
New Mexico
Albuquerque: 27
North Carolina
Chapel Hill: 8
Raleigh: 27
Pennsylvania
Philadelphia: 6
Rhode Island
Providence: 22
Texas
Dallas: 6, 18
Houston: 32
Washington
Seattle: 15, 19
Wisconsin
Madison: 8
Milwaukee: 22
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Katherine Anderson (Nature London)
Tel: +44 20 7843 4502; E-mail: [email protected]
Ruth Francis (Senior Press Officer, 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 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 Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected]
Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]
Nature Materials (London)
Maria Bellantone
Tel: +44 20 7843 4556; E-mail: [email protected]
Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]
Nature Methods (New York)
Allison Doerr
Tel: +1 212 726 9393; E-mail: [email protected]
Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; 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]
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