This press release contains:
• Summaries of newsworthy papers:
Nature: Risk factors associated with multiple sclerosis explains drug side effects
Cell Biology: Identifying a melanoma-promoting factor
Genetics: Exome sequencing of extreme phenotypes
Medicine: Signals of solar injury
Physics: A wave of stress facilitates cell migration
Chemical Biology: Eliminating the impossible
• Geographical listing of authors
[1] Nature: Risk factors associated with multiple sclerosis explains drug side effects
DOI: 10.1038/nature11307
A functional role for a genetic variant associated with multiple sclerosis (MS) that could be predictive of treatment outcome is uncovered in Nature this week. The genetic variant mimics the outcome of drugs whose adverse effects can promote or exacerbate this autoimmune disease. This finding demonstrates that genome-wide association studies (GWAS), which identify disease-associated genetic variants, can serve to directly inform therapeutic choice in the treatment of a common disease.
A genetic variant identified by GWAS and known as rs1800693 is associated with MS, but not with other autoimmune conditions. Lars Fugger and colleagues show that this variant, which falls in a region containing the TNF receptor 1 gene, results in the production of a molecule that can block TNF (tumour necrosis factor). Whereas anti-TNF drugs are beneficial in treating several different common autoimmune diseases, this is not the case for MS. This indicates that knowing the functional consequences of rs1800693 could help to predict the adverse effects of anti-TNF therapy in MS patients.
Author contact:
Lars Fugger (University of Oxford, UK)
Tel: +44 1865 222 351 or: +44 7817 601 028; E-mail: [email protected]
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[2] Cell Biology: Identifying a melanoma-promoting factor
DOI: 10.1038/ncb2535
A factor that promotes the formation and maintenance of pigmented birthmarks called giant congenital naevi, and subsequently of melanoma, is reported online this week in Nature Cell Biology. These findings could provide important insights for the development of therapeutic strategies for this condition.
Olga Shakhova, Lukas Sommer and colleagues used a mouse model of melanoma that combined the presence of mutant Nras, a known melanoma-promoting factor, and deficiency of INK4a, which is often inactivated in human melanoma. The authors identified striking similarities between this mouse model and giant congenital naevi and melanoma in humans. They went on to show that Sox10, a factor needed for the formation of skin pigment cells from neural crest stem cells during development, was present at high levels in naevi and melanoma samples obtained from both the mouse model and human patients. The authors further demonstrated that a decrease in Sox10 levels counteracted melanoma formation in mice by suppressing neural crest stem cell properties, and by blocking cell proliferation and survival.
The finding that Sox10 is crucial for the formation and maintenance of giant congenital naevi and melanoma has the potential to be exploited therapeutically against this aggressive skin cancer.
Author contacts:
Olga Shakhova (University of Zurich, Switzerland)
Tel: +41 44 635 54 43; E-mail: [email protected]
Lukas Sommer (University of Zurich, Switzerland)
Tel: +41 44 635 53 50; E-mail: [email protected]
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[3] Genetics: Exome sequencing of extreme phenotypes
DOI: 10.1038/ng.2344
Individuals with cystic fibrosis are at high risk for Pseudomonas aeruginosa infection, which is associated with worse long-term pulmonary disease and survival. A study published online this week in Nature Genetics reports genetic variants associated with susceptibility to P. aeruginosa infection.
In order to identify host genetic factors that influence risk of P. aeruginosa infection, Michael Bamshad, Mary Emond and colleagues used an extreme phenotype study design, selecting individuals who are at the extreme ends of a phenotype distribution, combined with exome sequencing. Exome sequencing of forty-three individuals with early age of onset of chronic P. aeruginosa infection and 48 older individuals who had not reached chronic P. aeruginosa infection was performed as part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP). This analysis identified variants in DCTN4 that are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis. They validated the finding in 696 additional individuals with cystic fibrosis.
Author contacts:
Michael Bamshad (University of Washington, Seattle, WA, USA)
Tel: +1 206 221 4131; E-mail: [email protected]
Mary Emond (University of Washington, Seattle, WA, USA)
Tel: +1 206 543 3406; E-mail: [email protected]
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[4] Medicine: Signals of solar injury
DOI: 10.1038/nm.2861
RNAs damaged by ultraviolet B radiation (UVB) causes inflammation and injury of the skin, reports a new study published online this week in Nature Medicine. Recognition of these RNAs by the immune system and skin cells could be blocked to treat photosensitive disorders.
Inflammation and injury result from sunburn caused upon exposure to UVB. Richard Gallo and colleagues show that damage of skin cells by UVB leads to the release of a specific form of damaged RNA from these cells. This RNA is then sensed by unirradiated skin cells and immune cells in the blood, causing secretion of proinflammatory factors. Mice lacking the receptor toll-like receptor 3 (TLR3), which mediates innate immune responses, failed to secrete the inflammatory molecules and showed less redness, indicating that the inflammatory response caused by UVB damage is dependent on this receptor.
Although other products formed after UVB exposure can contribute to inflammation and further testing in humans is needed, the findings suggest that RNAs from damaged skin cells can serve as signals of solar injury.
Author contact:
Richard Gallo (University of California, San Diego, CA, USA)
Tel: +1 858 822 4608; E-mail: [email protected]
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[5] Physics: A wave of stress facilitates cell migration
DOI: 10.1038/nphys2355
The massive cellular migration that occurs in our bodies during early development works on the same principle as the healing of wounds in adulthood: cells move in large monolayer sheets, responding to chemical cues that guide migration. A paper published online this week in Nature Physics suggests that there is an additional feedback mechanism at work in cell migration, beyond chemical-gradient sensing, involving physical forces.
Cells, as they move, apply traction forces to their surroundings, and transmit forces to one another via intercellular junctions. In doing so, they build up gradients of tension across the group, which then migrates in the direction of maximum stress. Xavier Trepat, Jeffrey Fredberg and colleagues now report that these stress gradients are established via a slow mechanical wave that propagates through the cell population from the leading edge of migration.
Their observation challenges the long-held assumption that viscous stress dominates elastic stress on the timescales of migration. The reinforced patterns of stress and strain that emerge in the study provide direct evidence of a physical process enabling cell migration, which may play a role in wound healing, morphogenesis and the early stages of metastasis.
Author contacts:
Xavier Trepat (Institute for Bioengineering of Catalonia, Barcelona, Spain)
Tel: +34 934020265; E-mail: [email protected]
Jeffrey Fredberg (Harvard University, Boston, MA, USA)
Tel: +1 617 432 0198; E-mail: [email protected]
Manuel Théry (Institut de Recherches en Technologies et Sciences pour le Vivant, Grenoble, France) N&V author
Tel: +33 438 789 126; E-mail: [email protected]
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[6] Chemical Biology: Eliminating the impossible
DOI: 10.1038/nchembio.1042
Insights into the pathways that regulate how genes are turned on or off are published online this week in Nature Chemical Biology.
Epigenetic pathways can regulate gene expression by controlling the levels and types of molecular marks on genes and the proteins associated with these genes. DNA methylation—in which small ‘methyl’ groups are attached at or near genes is an important epigenetic pathway in stem cells and cancer. The pathways for how methyl groups are installed on DNA are fairly well characterized, but it remains unclear how these groups are removed from DNA, called DNA demethylation. One model proposes that deaminase enzymes, which are known to convert cytosine bases into uracil bases in DNA, have a central role in DNA demethylation.
Rahul Kohli and colleagues use a biochemical approach to evaluate whether deaminase enzymes can operate on DNA segments containing these epigenetic marks. They found that the marked segments are poor substrates for these enzymes both in the test tube and within cells, which leads them to conclude that DNA demethylation pathways involving deaminases are less probable that other proposed alternatives. This discovery should refocus research efforts for understanding this important regulatory pathway for controlling gene expression.
Author contact:
Rahul Kohli (University of Pennsylvania School of Medicine, Philadelphia, PA, USA)
Tel: +1 215 573 7523; 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
[7] The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming
DOI: 10.1038/nature11272
[8] Novel role of PKR in inflammasome activation and HMGB1 release
DOI: 10.1038/nature11290
[9] SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors
DOI: 10.1038/nature11207
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NATURE CHEMICAL BIOLOGY
[10] The siderophore yersiniabactin binds copper to protect pathogens during infection
DOI: 10.1038/nchembio.1020
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NATURE CHEMISTRY
[11] Guided desaturation of unactivated aliphatics
DOI: 10.1038/nchem.1385
[12] Key stabilizing elements of protein structure identified through pressure and temperature perturbation of its hydrogen bond network
DOI: 10.1038/nchem.1396
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NATURE CLIMATE CHANGE
[13] Decline of forereef corals in response to recent warming linked to history of thermal exposure
DOI: 10.1038/nclimate1577
[14] Harmful filamentous cyanobacteria favoured by reduced water turnover with lake warming
DOI: 10.1038/nclimate1581
[15] Impact of intensified Indian Ocean winds on mesoscale variability in the Agulhas system
DOI: 10.1038/nclimate1587
[16] Orbital forcing of tree-ring data
DOI: 10.1038/nclimate1589
[17] Reconciling disparate twentieth-century Indo-Pacific ocean temperature trends in the instrumental record
DOI: 10.1038/nclimate1591
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NATURE GENETICS
[18] TGFB2 loss-of-function mutations cause familial thoracic aortic aneurysms and acute aortic dissections associated with mild systemic features of Marfan syndrome
DOI: 10.1038/ng.2348
[19] Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm
DOI: 10.1038/ng.2349
[20] FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair
DOI: 10.1038/ng.2347
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NATURE GEOSCIENCE
[21] Global rates of water-column denitrification derived from nitrogen gas measurements
DOI: 10.1038/ngeo1515
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NATURE IMMUNOLOGY
[22] The transcription factor Lyl-1 regulates lymphoid specification and the maintenance of early T lineage progenitors
DOI: 10.1038/ni.2365
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NATURE MATERIALS
[23] Label-free identification of single dielectric nanoparticles and viruses with ultraweak polarization forces
DOI: 10.1038/nmat3369
[24] Ferroelectric order in individual nanometer-scale crystals
DOI: 10.1038/nmat3371
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Nature MEDICINE
[25] Robust tumor immunity to melanoma mediated by Interleukin 9 producing T cells
DOI: 10.1038/nm.2856
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NATURE METHODS
[26] Multicolor two-photon tissue imaging by wavelength mixing
DOI: 10.1038/nmeth.2098
[27] False discovery rate estimation for cross-linked peptides identified by mass spectrometry
DOI: 10.1038/nmeth.2103
[28] Identification of cross-linked peptides from complex samples
DOI: 10.1038/nmeth.2099
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NATURE NANOTECHNOLOGY
[29] Characterization of the motion of membrane proteins using high-speed atomic force microscopy
DOI: 10.1038/nnano.2012.109
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Nature NEUROSCIENCE
[30] Protein kinase C acts as a molecular detector of firing patterns to mediate sensory gating in aplysia
DOI: 10.1038/nn.3158
[31] Spontaneous activity mediates a developmental switch in thalamocortical axon growth by regulating Robo1 transcription
DOI:10.1038/nn.3160
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NATURE PHOTONICS (http://www.nature.com/nphoton)
[32] Detection of photons emitted from single erbium atoms in energy-dispersive X-ray spectroscopy
DOI: 10.1038/nphoton.2012.148
[33] Conversion of broadband to narrowband thermal emission through energy recycling
DOI: 10.1038/nphoton.2012.146
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Nature PHYSICS
[34] A wideband, low-noise superconducting amplifier with high dynamic range
DOI: 10.1038/nphys2356
[35] Commensurability and chaos in magnetic vortex oscillations
DOI: 10.1038/nphys2362
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Nature STRUCTURAL & MOLECULAR BIOLOGY
[36] The translin–TRAX complex (C3PO) is a ribonuclease in tRNA processing
DOI: 10.1038/nsmb.2337
[37] Functional characterization of an active Rag-like transposase
DOI: 10.1038/nsmb.2338
[38] LEDGF (p75) promotes DNA-end resection and homologous recombination
DOI: 10.1038/nsmb.2314
[39] Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis
DOI: 10.1038/nsmb.2318
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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
Sydney: 20
BELGIUM
Antwerp: 19
Ghent: 19, 35
CANADA:
Vancouver: 38
CHINA
Beijing: 28
Hong Kong: 35
CZECH REPUBLIC
Olomouc: 38
DENMARK
Aarhus: 1
Copenhagen: 1, 38
FINLAND
Rovaniemi: 16
FRANCE
Boulogne: 18
Guyancourt: 18
Marseille: 29
Maubeuge: 20
Orsay: 35
Palaiseau: 16, 35
Paris: 5, 18, 20, 26, 29, 31
Plouzané: 15
Rouen: 20
GERMANY
Bochum: 1
Düsseldorf: 1, 22
Erlangen: 2, 20
Freiburg: 20
Geesthacht: 16
Giessen: 16
Hamburg: 16, 20
Heidelberg: 27
Mainz: 16
Martinsried: 1
Tubingen: 20
ISRAEL
Rehovot: 7
ITALY
Bassano del Grappa: 9
Modena: 9
Naples: 22
Novara: 20
Padova: 9
Padua: 9
Turin: 20
JAPAN
Akishima: 32
Fukuoka: 32
Kyoto: 33
Tsukuba: 32
NETHERLANDS
Nijmegen: 19
Utrecht: 20
NEW ZEALAND
Wellington: 20
PORTUGAL
Vairão: 13
SOUTH AFRICA
Cape Town: 15
SPAIN
Barcelona: 5, 23
Madrid: 23
San’t Joan d’Alacant: 31
SWEDEN
Stockholm: 8, 19
SWITZERLAND
Basel: 12, 20, 29
Bern: 16
Kilchberg: 14
Lausanne: 2
Liestal: 20
Zurich: 2, 14, 20, 27
UNITED KINGDOM
Cambridge: 22
Harrow: 19
Liverpool: 8
Oxford: 1
St Andrews: 16
UNITED STATES OF AMERICA
Arizona
Huntsville 20
California
Berkeley: 24, 39
Irvine: 21
La Jolla: 11
Los Angeles: 21
Pasadena: 34
San Diego: 4
San Francisco: 31
San Jose: 28
Stanford: 27
Colorado
Boulder: 17
Florida
Miami: 4
Hawaii
Laie: 22
Louisiana
New Orleans: 24
Maryland
Baltimore: 3, 6, 19, 30, 37
Bethesda: 1
Chevy Chase: 20
Massachusetts
Boston: 5, 8, 25, 37, 39
Worcester: 36, 39
Michigan
Ann Arbor: 20
Mount Pleasant: 24
Missouri
St Louis: 10, 18, 19
New Jersey
Piscataway: 4
Princeton: 21
New York
Manhasset: 8
New York: 8, 20, 24, 31
North Carolina
Chapel Hill: 3, 6, 8, 13
Research Triangle: 25
Pennsylvania
Philadelphia: 6
South Carolina
Columbia: 13
Texas
Dallas: 36
Houston: 18, 22
Washington
Seattle: 3, 10, 18, 19, 21
Wisconsin
Madison: 20
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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]
Eiji Matsuda (Nature Tokyo)
Tel: +81 3 3267 8751; E-mail: [email protected]
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For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:
Nature Biotechnology (New York)
Michael Francisco
Tel: +1 212 726 9288; E-mail: [email protected]
Nature Cell Biology (London)
Sowmya Swaminathan
Tel: +44 20 7843 4656; E-mail: [email protected]
Nature Chemical Biology (Boston)
Elissa Bolt
Tel: +1 617 475 9241, E-mail: [email protected]
Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]
Nature Climate Change (London)
Rory Howlett
Tel: +44 20 7014 4009; E-mail: [email protected]
Nature Genetics (New York)
Myles Axton
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)
Ray Parker
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 9331; E-mail: [email protected]
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