New treatment for muscular dystrophy and cystic fibrosis?

Summaries of newsworthy papers that will be published online on 22 April 2007 in Nature and Nature Research Journals, including: Enzyme curtails allergic reaction to chitin, Magnetic imaging enters the nanoworld, Catalysts under the microscope, The immune system and susceptibility to cancer, Engineering diverse sets of drug sensitive proteins.

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 22 April 2007. This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

New treatment for muscular dystrophy and cystic fibrosis? - Nature
Enzyme curtails allergic reaction to chitin - Nature
Magnetic imaging enters the nanoworld - Nature Nanotechnology
Catalysts under the microscope - Nature Nanotechnology
The immune system and susceptibility to cancer - Nature Genetics
Engineering diverse sets of drug sensitive 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] Molecular biology: New treatment for muscular dystrophy and cystic fibrosis?
DOI: 10.1038/nature05756

A drug that allows cells to ignore a particular type of disease-causing mutation may ease the symptoms of Duchenne muscular dystrophy (DMD), a mouse study suggests.

Many inherited diseases, such as DMD, cystic fibrosis and lysosomal storage disorders, result from premature termination during translation of a messenger RNA into a protein; consequently, an abnormally short protein is made. Online in this week's Nature, Stuart W. Peltz and colleagues report that a small molecule, PTC124, enables the translation machinery to bypass sites that cause premature termination, but still terminate normally at the end of the mRNA. In human and mouse cells, the drug restores normal translation of the gene that is mutated in DMD, and restores muscle function in a well-known mouse model of the disease.

The drug is well tolerated, has a well-characterized activity profile and is selective for mutations that cause premature termination. So it's hoped that PTC124 will prove therapeutically useful for the many diseases with similar translation defects that have limited or no therapeutic options.

Author contact:

Stuart W. Peltz (PTC Therapeutics, South Plainfield, NJ, USA)
Tel: +1 908 222 7000 x110; E-mail: [email protected]

Additional media contact:

Jane Baj (PTC Therapeutics, South Plainfield, NJ, USA)
Tel: +1 908 222 7000 x167; E-mail: [email protected]

[2] Immunology: Enzyme curtails allergic reaction to chitin
DOI: 10.1038/nature05746

Chitin, the main component of arthropod exoskeletons, elicits an innate allergic response in mice that can be controlled by a host enzyme, a Nature paper reveals online this week. The discovery may influence the development of novel therapeutics for allergic diseases such as asthma.

Mice treated with the biopolymer chitin develop an allergic response, characterized by a build-up of interleukin-4-expressing innate immune cells. But the symptoms can be abolished by treating the animals with the chitin-degrading mammalian enzyme AMCase, Richard M. Locksley and colleagues report.

Chitin provides structural rigidity to parasitic worms, fungi, crustaceans and insects, and its widespread presence in the natural world may have driven evolutionary pressure among vertebrates to maintain chitin-recognition molecules. Occupations predicted to have high environmental chitin levels, such as shellfish processors, are marked by high incidences of asthma, suggesting that this pathway may play a role in human allergic disease.

Author contact:

Richard M. Locksley (University of California, San Francisco, CA, USA)
Tel: +1 415 476 5859; E-mail: [email protected]

Other papers from Nature to be published online at the same time and with the same embargo:

[3] A type III effector ADP-ribosylates RNA-binding proteins and quells plant immunity
DOI: 10.1038/nature05737

[4] A chromatin link that couples cell division to root epidermis patterning in Arabidopsis
DOI: 10.1038/nature05763

[5] A positive feedback mechanism governs the polarity and motion of motile cilia
DOI: 10.1038/nature05771

[6] OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells
DOI: 10.1038/nature05778

***********************NATURE NANOTECHNOLOGY**********************

(http://www.nature.com/nnano)

[7] Magnetic imaging enters the nanoworld
DOI: 10.1038/nnano.2007.105

Magnetic resonance imaging could be used to see details at a much smaller scale than ever before, reports a paper published online in Nature Nanotechnology this week. More than half the elements in the periodic table have nuclei that are magnetic, which is why so-called magnetic resonance techniques are widely used in scientific research and the MRI scanners found in many hospitals. However, at present these techniques cannot see details that are smaller than a few micrometres (there are a million micrometres in a metre). The new study reports how magnetic resonance can be used to see details that are at least a factor of 10 smaller than this.

The device built by John Mamin and colleagues relies on a silicon cantilever that vibrates back and forth like a pendulum above a very small magnetic tip. The sample to be studied is placed at the bottom of the cantilever, and the magnetic interaction between the sample and the tip changes the natural vibration frequency of the cantilever. This allows the researchers to make an image of a test object with a resolution of 90 nanometres (there are a 1000 million nanometres in a metre). One of the long-term goals of such research is to make a device that could work out the chemical composition of single molecules.

Author contact:

John Mamin (Almaden Research Centre, San Jose, CA, USA)
Tel: +1 408 927 2502; E-mail: [email protected]

[8] Catalysts under the microscope
DOI: 10.1038/nnano.2007.106

In a paper to be published in the May issue of Nature Nanotechnology, researchers have used a scanning tunnelling microscope to visualize individual catalysts at work at a solid-liquid interface. The method could therefore eliminate the process of measuring the ensemble properties of a large number of molecules.

Johannes Elemans and co-workers formed arrays of large flat organic molecules, known as porphyrins, on a gold surface. The metal atom at the centre of each porphyrin can react with oxygen to form a catalytic site, which can be used to convert one type of organic compound (an alkene) into another (an epoxide). Using a scanning tunnelling microscope, the team were able to ‘watch’ individual porphyrins at each step of the process. This offered a unique insight into how these reactions work at the single-molecule level, revealing information about catalyst activity, stability and distribution across the surface.

An accompanying News & Views article Richard Nichols describes the work as ‘a significant development in the imaging of chemical reactions at the single-molecule level’.

Author contacts:
Johannes Elemans (Radboud University, Nijmegen, The Netherlands)
Tel: +31 24 365 2185; E-mail: [email protected]

Richard Nichols (University of Liverpool, UK) N&V author
Tel: +44 151 794 3533; E-mail: [email protected]

Other papers from Nature Nanotechnology to be published online at the same time and with the same embargo:

[9] Detection and identification of proteins using nanoparticle-fluorescent polymer ‘chemical nose’ sensors
DOI: 10.1038/nnano.2007.99

**************************** NATURE GENETICS ************************

(http://www.nature.com/naturegenetics)

[10] The immune system and susceptibility to cancer
DOI: 10.1038/ng2030

Variation in a genetic element that regulates the expression of the gene encoding caspase-8 (CASP8) is associated with differential susceptibility to several different cancers, according to a study to be published online this week in Nature Genetics.

CASP8 encodes a protein that triggers cell death in response to environmental signals. One of its roles is to regulate the survival of cells of the immune system that are part of the body’s anti-tumour response. It has been proposed that variation in caspase-8 function or expression might make individuals differentially susceptible to cancer by affecting the population of cells involved in tumour surveillance.

Dongxin Lin and colleagues now report that a newly identified CASP8 variant - a six-nucleotide deletion that reduces the gene’s level of expression - is associated with significantly reduced susceptibility to lung, oesophageal, gastric, colorectal, cervical, and breast cancers in Chinese individuals. This work follows up on recent findings that women of European descent with a different CASP8 variant are at modestly elevated risk for breast cancer, and provides strong support for the idea that an individual’s immune status can affect cancer susceptibility.

Author contact:
Dongxin Lin (Chinese Academy of Medical Sciences, Beijing, China)
Tel: +86 10 8778 8491; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[11] Modifiers of epigenetic reprogramming show paternal effects in the mouse
DOI: 10.1038/ng2031

[12] Serotonin and neuropeptide F have opposite modulatory effects on fly aggression
DOI: 10.1038/ng2029

*****************************NATURE METHODS***************************

(http://www.nature.com/nmeth)

[13] Engineering diverse sets of drug sensitive proteins
DOI: 10.1038/nmeth1046

A paper published online this week in Nature Methods describes a general approach to genetically engineer proteins that are regulated by small chemical drugs.

Previous approaches that combined the strengths of genetics and pharmacology targeted specific proteins; the protein of choice was genetically modified in such a way that it became susceptible to small-molecule drugs. However, a general method for the engineering of drug-sensitive proteins has been lacking.

Mordechai Liscovitch and colleagues now introduce such a general method, which they call ligand interaction scan. They serially insert a short amino acid motif, specific for binding to a small-molecule ligand, into a protein of choice. Then, by scanning the activity of these mutant proteins, they are able to identify proteins that are activated or inhibited by the drug. Any protein can be made drug-sensitive by this approach; the only requirements for the scan are a read-out for protein activity and a cell-permeable drug, if the technique is to be carried out in live cells.

This method will aid in the functional analysis of proteins or even in the generation of transgenic organisms that carry proteins that are sensitive to a small-molecule drug.

Author contact:
Mordechai Liscovitch (Weizmann Institute of Science, Rehovot, Israel)
Tel: +972 8 934 2773; E-mail: [email protected]

Other papers from Nature Methods to be published online at the same time and with the same embargo:

[14] A yeast two-hybrid smart pool array system for protein interaction mapping
DOI: 10.1038/nmeth1042

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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)

[15] Introducing genetically encoded aldehydes into proteins
DOI: 10.1038/nchembio878

Nature PHYSICS (http://www.nature.com/naturephysics)

[16] Ultrafast two-dimensional nuclear magnetic resonance spectroscopy of hyperpolarized solutions
DOI: 10.1038/nphys597

[17] Universal thermodynamics of strongly interacting Fermi gases
DOI: 10.1038/nphys598

[18] Breaking the delay-bandwidth limit in a photonic structure
DOI: 10.1038/nphys600

NATURE MATERIALS (http://www.nature.com/naturematerials)

[19] Strong isotropic flux pinning in solution-derived YBa2Cu3O7-x nanocomposite superconductor films
DOI: 10.1038/nmat1893

[20] Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors
DOI: 10.1038/nmat1891

Nature MEDICINE (http://www.nature.com/naturemedicine)

[21] The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress
DOI: 10.1038/nm1574

[22] Antielastin autoimmunity in tobacco smoking–induced emphysema
DOI: 10.1038/nm1583

Nature BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)

[23] A high-quality catalog of the Drosophila melanogaster proteome
DOI: 10.1038/nbt1300

[24] Quantitative proteomic assessment of very early cellular signaling events
DOI: 10.1038/nbt1301

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[25] Caenorhabditis elegans TRPA-1 in mechanosensation
DOI: 10.1038/nn1886

[26] Detection and prediction of periodic patterns by the retina
DOI: 10.1038/nn1887

[27] Medial prefrontal cell activity signaling prediction errors of action values
DOI: 10.1038/nn1890

[28] Sniffing controls an adaptive filter of sensory input to the olfactory bulb
DOI: 10.1038/nn1892

[29] Serotonin modulates the response of embryonic thalamocortical axons to netrin-1
DOI: 10.1038/nn1896

Nature IMMUNOLOGY (http://www.nature.com/natureimmunology)

[30] Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
DOI:10.1038/ni1460

[31] Origin of dendritic cells in peripheral lymphoid organs of mice
DOI:10.1038/ni1462

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[32] Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
DOI: 10.1038/ncb1567

[33] pVHL and GSK3beta are components of a primary cilium-maintenance signalling network
DOI: 10.1038/ncb1579

[34] Loss of Drosophila Myb interrupts the progression of chromosome condensation
DOI: 10.1038/ncb1580

Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)

[35] Structural basis for Rab GTPase activation by VPS9 domain exchange factors
DOI: 10.1038/nsmb1232

[36] The structure of a polyQ­­–anti-polyQ complex reveals binding according to a linear lattice model
DOI: 10.1038/nsmb1234

[37] Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection
DOI: 10.1038/nsmb1239

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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: 11, 17
Clayton: 11
Parkville: 11
Sydney: 8

CANADA:
Hamilton: 30
Vancouver: 22

CHINA
Beijing: 10, 17

DENMARK
Ballerup: 23
Lyngby: 23
Odense: 24

GERMANY
Bielefeld: 3
Martinsried: 24
Munich: 30

ISRAEL
Rehovot: 13, 16

JAPAN
Aichi: 27
Osaka: 21
Saitama: 21, 27, 37
Tokyo: 21, 27

NETHERLANDS

Amsterdam: 2
Nijmegen: 8
Utrecht: 23

NORWAY
Oslo: 6

SOUTH AFRICA
Cape Town: 30

SPAIN
Barcelona:19
Madrid: 4

SWITZERLAND
Zurich: 23, 33

UNITED KINGDOM
Brighton: 26
Cambridge: 25
London: 30
Oxford: 16

UNITED STATES OF AMERICA
California
Berkeley: 15
Irvine: 25
La Jolla: 5, 25
Los Angeles: 14
Pasadena: 20, 36
San Diego: 12, 25
San Francisco: 2
San Jose: 7
Stanford: 7, 34
Connecticut
New Haven: 28, 29, 31
Georgia
Atlanta: 9
Indiana
West Lafayette: 14
Maryland
Bethesda: 37
Massachusetts
Amherst: 9
Boston: 28
Charlestown: 2
Worcester: 1, 35
Minnesota
Minneapolis: 28
Rochester: 6
Nebraska
Lincoln: 3
New Jersey
Princeton: 26
South Plainfield: 1
New York
Bronx: 11
Ithaca: 18
New York: 31
Stony Brook: 15
North Carolina
Triangle Park: 6
Pennsylvania
Philadelphia: 1, 32
Tennessee
Nashville: 29
Texas
College Station: 36
Houston: 22, 37
Washington
Seattle: 23

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 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 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]

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Published: 22 Apr 2007

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