NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 02 December 2007
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
A mechanical test for cancer - Nature Nanotechnology
Restoring bacterial killing in cystic fibrosis - Nature Medicine
Bad to the bone - Nature Medicine
Run away from your depression - Nature Medicine
Genetic risk factor for psoriasis - Nature Genetics
Genetic variants predispose to lupus - Nature Genetics
Fuelling allergic inflammation - Nature Immunology
· 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.
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/.
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 NANOTECHNOLOGY **************************
(http://www.nature.com/nnano)
[1] A mechanical test for cancer
DOI: 10.1038/nnano.2007.388
Cancer cells are softer than healthy cells, according to mechanical measurements published online this week in Nature Nanotechnology. The results suggest that this mechanical signature may be a powerful way to detect cancer in the clinic and could also have applications in personalized medication.
James Gimzewski and colleagues show that cancer cells taken from the body fluid of patients with suspected lung, breast and pancreas cancer are more than 70% softer than benign cells. Even though the patients had very different clinical histories, the different types of cancer cells showed similar values of stiffness, so the healthy and diseased states could be clearly identified. Moreover, normal cells that looked like cancerous cells could be distinguished with this technique.
"This nanomechanical approach provides a potentially powerful means for detecting cancer along with the other ancillary biomarkers currently used for diagnosis," says Subra Suresh in an accompanying News and Views article. However, before the new approach can be used in the clinic, further tests are needed to explore, among other things, the influence of other existing diseases on the mechanical properties of normal and cancerous cells.
Author contact:
James Gimzewski (University of California, Los Angeles, CA, USA)
Tel: +1 310 794 7514; E-mail: [email protected]
Additional contact for comment on paper:
Subra Suresh (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 3320; E-mail: [email protected]
Other papers from Nature Nanotechnology to be published online at the same time and with the same embargo:
[2] Layer-by-layer assembled charge-trap memory devices with adjustable electronic properties
DOI: 10.1038/nnano.2007.380
[3] Recapturing and trapping single molecules with a solid-state nanopore
DOI: 10.1038/nnano.2007.381
[4] Improved broadband and quasi-omnidirectional anti-reflection properties with biomimetic silicon nanostructures
DOI: 10.1038/nnano.2007.389
********************************** Nature MEDICINE ********************************
(http://www.nature.com/naturemedicine)
[5] Restoring bacterial killing in cystic fibrosis
DOI: 10.1038/nm1690
A report online in Nature Medicine this week reveals that high protease levels in the lungs of patients with cystic fibrosis disable immune cells, explaining why CF patients fail to clear lung infections. The findings also offer a therapeutic strategy to boost bacterial killing in these patients.
Individuals with cystic fibrosis have high levels of the protein IL-8 in their lungs. IL-8 normally triggers bacterial killing by immune cells called neutrophils, but the lungs of CF patients are often colonized by bacteria, despite the presence of high numbers of lung neutrophils. Somehow, the neutrophils of CF patients do not function properly.
Dominik Hartl and colleagues report that IL-8 activates neutrophils by binding to a cytokine receptor termed CXCR1. CF patients have abnormally high levels of lung proteases, as well as high levels of the neutrophil-activating cytokine IL-8. This high protease activity explains both the defective neutrophil function and the high levels of IL-8 in the lungs of CF patients. The proteases cleave the CXCR1 receptor, effectively disabling the neutrophils’ bacterial killing activity by making the cells unresponsive to IL-8. Meanwhile, the cleaved receptor fragment stimulates further secretion of IL-8 from lung epithelial cells by interacting with the protein toll-like receptor 2.
The authors also found that CF patients receiving four weeks of inhalation therapy with alpha1-antitrypsin - a protease inhibitor - have reduced numbers of the bacteria Pseudomonas aeruginosa in their sputum, which correlates with improvements in the bacterial killing ability of neutrophils, restoration of CXCR1 on the surface of the neutrophils and reduced amounts of the soluble receptor fragment in the lungs of the CF patients.
Author contact:
Dominik Hartl (Children’s Hospital, Munich, Germany)
Tel. +49 895 160 7716; E-mail: [email protected]
[6] Bad to the bone
DOI: 10.1038/nm1672
A drug commonly prescribed to diabetes patients may have negative effects on the bone, suggests a paper online this week in Nature Medicine.
Proper bone strength is maintained by a balance between the activities of the cells that degrade bone - osteoclasts - and the cells that build it - osteoblasts. Rosiglitazone, which is prescribed to people with diabetes to increase their response to insulin, has been associated with increased fracture risk, owing to an inhibitory action on osteoblasts. Ron Evans and colleagues show that, in mice, rosiglitazone also results in the inappropriate maturation of osteoclasts, providing an additional explanation for why thiazolidinediones (the group of drugs including rosiglitazone) can increase fracture risk.
The team found that deletion of the gene encoding the protein PPAR-gamma, the molecular target of rosiglitazone, specifically in the cells that give rise to mature osteoclasts impaired their differentiation, leading to higher bone mass. By contrast, when they used rosiglitazone to activate PPAR-gamma, they saw more osteoclast activity and thinner bones - osteoporosis.
These results raise the concern that long-term use of rosiglitazone to treat diabetes could lead to osteoporosis.
Author contact:
Ron Evans (The Salk Institute for Biological Studies, La Jolla, CA, USA)
Tel: +1 858 453 4100, Ext.1302; E-mail: [email protected]
[7] Run away from your depression
DOI: 10.1038/nm1669
Scientists have discovered a molecule with antidepressant actions, which is produced by the brain as a result of physical exercise.
Exercise has many health benefits, including antidepressant actions in humans, but the mechanisms underlying these effects are not fully clear. In a study online in Nature Medicine this week, Ronald Duman and colleagues used microarrays to identify genes whose expression changed in the mouse brain in response to exercise. One of the genes they identified was the gene encoding a growth factor known as VGF, a molecule known to influence neural activity. The authors went on to show that administration of VGF produced a robust antidepressant response in mice and, conversely, that mutation of VGF in mice had the opposite effects. The results imply VGF as a potential therapeutic target for antidepressant drug development.
Author contact:
Ronald Duman (Yale University School of Medicine, New Haven, CT, USA)
Tel: +1 203 974 7726; E-mail: [email protected]
Other papers from Nature Medicine to be published online at the same time and with the same embargo:
[8] In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for bacterial persistence in mice
DOI: 10.1038/nm1683
[9] Therapeutic differentiation and maturation of lymphatic vessels after lymph node dissection and transplantation
DOI: 10.1038/nm1689
************************************ NATURE GENETICS *******************************
(http://www.nature.com/naturegenetics)
[10] Genetic risk factor for psoriasis
DOI: 10.1038/ng.2007.48
Individuals carrying extra copies of a cluster of genes encoding a family of small antimicrobial proteins are at increased risk of developing psoriasis, reports a study online this week in Nature Genetics. Psoriasis is a common inflammatory skin disease affecting up to 2% of the population in developed countries.
Recently, scientists have recognized that some individuals carry more than two copies of certain genes, while others carry less, and have speculated that these so-called ‘copy number variants’ might influence an individual’s risk of developing common diseases. One such region, present at a range of 2-12 copies per individual in the population, contains a cluster of genes encoding a family of secreted proteins known as beta-defensins. Since beta-defensins are expressed in skin and can induce inflammation in response to infections or other environmental triggers, John Armour and colleagues speculated that variation in beta-defensin copy number might influence the risk of developing psoriasis. In two independent studies involving individuals from the Netherlands and Germany, the authors found that individuals with psoriasis had, on average, more copies of the beta-defensin genes compared to individuals without the disease.
Beta-defensins are components of the innate immune system that serve to protect against a wide range of infectious agents. They are rapidly induced in response to infection or injury and can trigger the release of other proteins, such as the interleukins IL-8, IL-18 and IL-20, that promote inflammation and which have a known role in psoriasis.
Author contact:
John Armour (University of Nottingham, UK)
Tel: +44 115 823 0308; E-mail: [email protected]
[11] Genetic variants predispose to lupus
DOI: 10.1038/ng.2007.47
Individuals with a particular combination of genetic variants near the gene TNFSF4 are at higher risk of developing lupus, according to a study to be published online this week in Nature Genetics. Lupus is a complex autoimmune disorder, more common in women than men, that causes inflammation and damage to a wide range of tissues.
It had previously been shown that a region on chromosome 1 was likely to harbour variants that affect the risk of developing lupus. Timothy Vyse and colleagues focused on TNFSF4 as a candidate gene in this region because its product is known to affect cells of the immune system that distinguish the body’s own tissues from foreign pathogens.
In a collection of affected families from the UK, and one from Minnesota, the authors found a series of variants flanking TNFSF4 to be associated with the disease when inherited in combination. These risk variants seem to promote elevated expression of TNFSF4 in blood lymphocytes isolated from individuals with lupus.
Author contact:
Timothy Vyse (Imperial College, London, UK)
Tel: +44 20 8383 2337; E-mail: [email protected]
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[12] Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis
DOI: 10.1038/ng.2007.44
[13] Germline rates of de novo meiotic deletions and duplications causing several genomic disorders
DOI: 10.1038/ng.2007.40
********************************* NATURE IMMUNOLOGY ***************************
(http://www.nature.com/natureimmunology)
[14] & [15] Fuelling allergic inflammation
DOI: 10.1038/ni1546
DOI: 10.1038/ni1550
Two studies online this week in Nature Immunology pinpoint the cellular machinery required to drive allergic reactions. When faced with allergens, immune cells known as mast cells release compounds that elicit wheezing, itching and swelling - the hallmarks of allergic inflammation. Although prior work established that calcium plays a key role in mounting allergic responses, the channel through which calcium flows into mast cells was unknown.
The groups of Monika Vig and Tomohiro Kurosaki generated mice lacking CRACM1 and STIM1 - components implicated in channeling calcium into other cell types. Mast cells from these mutant mice failed to take in calcium and send out allergic mediators upon allergen challenge. As such, these mutant mice were resistant to stimuli normally capable of provoking severe allergic reactions.
This research adds to our body of knowledge about allergic disorders and, along with future work, could be useful in the design of therapies.
Author contacts:
Tomohiro Kurosaki (RIKEN Yokohama Institute, Yokohama, Japan) Author Paper [14]
Tel: +81 45 503 7019; E-mail: [email protected]
Monika Vig (Harvard Medical School, Boston, Massachusetts) Author Paper [15]
Tel: +1 617 667 0677; E-mail: [email protected]
Other papers from Nature Immunology to be published online at the same time and with the same embargo:
[16] CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
DOI: 10.1038/ni1547
[17] The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells
DOI: 10.1038/ni1538
**********************************************************************************
Items from other Nature journals to be published online at the same time and with the same embargo:
Nature (http://www.nature.com/nature)
[18] Coevolution with viruses drives the evolution of bacterial mutation rates
DOI: 10.1038/nature06350
[19] Reconstitution of a microtubule plus-end tracking system in vitro
DOI: 10.1038/nature06386
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
[20] An allosteric potentiator of M4 mAChR modulates hippocampal synaptic transmission
DOI: 10.1038/nchembio.2007.55
[21] Discovery and characterization of a marine bacterial SAM-dependent chlorinase
DOI: 10.1038/nchembio.2007.56
Nature PHYSICS (http://www.nature.com/naturephysics)
[22] Algebraic charge liquids
DOI: 10.1038/nphys790
[23] Universal scaling between structural relaxation and vibrational dynamics in glass-forming liquids and polymers
DOI: 10.1038/nphys788
[24] Spectral weight transfer in the integer quantum Hall effect and its consequences
DOI: 10.1038/nphys786
[25] Electrohydrodynamic tip streaming and emission of charged drops from liquid cones
DOI: 10.1038/nphys807
NATURE MATERIALS (http://www.nature.com/naturematerials)
[26] Sliding charge-density wave in manganites
DOI: 10.1038/nmat2071
[27] Three-dimensional photonic metamaterials at optical frequencies
DOI: 10.1038/nmat2072
[28] Thermochromism in an organic crystal based on the coexistence of sigma- and pi-dimers
DOI: 10.1038/nmat2067
[29] Gate-induced insulating state in bilayer graphene devices
DOI: 10.1038/nmat2082
Nature BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
[30] Redirecting lipoic acid ligase for cell surface protein labeling with small-molecule probes
DOI: 10.1038/nbt1355
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[31] Semaphorin-3A guides radial migration of cortical neurons during development
DOI: 10.1038/nn2018
[32] Neuromuscular consequences of reflexive covert orienting
DOI: 10.1038/nn2023
[33] GTP-independent rapid and slow endocytosis at a central synapse
DOI: 10.1038/nn2021
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[34] Structure of phage P22 cell envelope-penetrating needle
DOI: 10.1038/nsmb1317
[35] Substrate RNA positioning in the archaeal H/ACA ribonucleoprotein complex
DOI: 10.1038/nsmb1336
[36] A regulator of Dscam mutually exclusive splicing fidelity
DOI: 10.1038/nsmb1339
[37] Evidence of fibril-like beta-sheet structures in a neurotoxic amyloid intermediate of Alzheimer’s beta-amyloid
DOI: 10.1038/nsmb1345
NATURE METHODS (http://www.nature.com/nmeth)
[38] Resolution of de novo HIV production and trafficking in immature dendritic cells
DOI: 10.1038/nmeth1137
***************************************************************************************
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: 2
CANADA:
London: 32
Montreal: 11
Toronto: 22, 32
Vancouver: 24
CHINA
Shanghai: 31
CZECH REPUBLIC
Prague: 12
FINLAND
Helsinki: 9
Kuopio: 9
Turku: 9
GERMANY
Berlin: 12
Erlangen: 8, 10
Heidelberg: 19
Leipzig: 12
Magdeburg: 12
Manheim: 12
Marburg: 12
Munich: 5
Munster: 10, 12
Nuremberg: 10
Stuttgart: 27
HUNGARY
Szeged: 12, 18
INDIA
Lucknow: 12
ITALY
Rome: 23
Pisa: 23
JAPAN
Chiba: 28
Fukuoka: 28
Osaka: 28
Saitama: 28
Tokyo: 17, 28
Yokohama: 14, 17, 28
KOREA
Seoul: 2
NETHERLANDS
Amsterdam: 5, 19
Delft: 29
Nijmegen: 10
SPAIN
Palma de Mallorca: 18
SWEDEN
Stockholm: 12
SWITZERLAND
Bern: 5, 12
TAIWAN
Hsinchu: 4
Taichung: 4
Taipei: 4
UNITED KINGDOM
Cambridge: 11, 13, 26
Leicester: 10
London: 11, 13, 16
Newcastle: 16
Nottingham: 10
Oxford: 18
UNITED STATES OF AMERICA
California
Berkeley: 30, 36
La Jolla: 6, 21, 36
Los Angeles: 1
San Diego: 36
San Francisco: 11
Connecticut
Farmington: 36
New Haven: 5, 7
Florida
Tallahassee: 35
Georgia
Athens: 35
Illinois
Chicago: 37
Indiana
West Lafayette: 25
Maryland
Bethesda: 20, 33
Massachusetts
Boston: 3, 12, 15
Cambridge: 22, 30
Lexington: 15
Michigan
Ann Arbor: 17
Minnesota
Minneapolis: 11
Missouri
Kansas City: 36
New Mexico
Los Alamos: 26
New York
New York: 7, 8, 38
Syracuse: 34
North Carolina
Research Triangle Park: 15
Oklahoma
Oklahoma City: 11
Rhode Island
Providence: 36
Tennessee
Nashville: 20
Oak Ridge: 24
Utah
Salt Lake City: 23, 34
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 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 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)
Fabio Pulizzi
Tel: +44 207 014 4024; 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 Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [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]
About Nature Publishing Group
Nature Publishing Group (NPG) is a division of Macmillan Publishers Ltd, dedicated to serving the academic, 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 [email protected]. Scientific career information and free job postings are offered on Naturejobs.
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