Lung cancer characterization

Summaries of newsworthy papers include In vivo folding lights up, RNA interference insecticides, Genetic variants associated with rheumatoid arthritis and Genes for Transplants

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 04 November 2007

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Genetics: Lung cancer characterization – Nature

In vivo folding lights up – Nature Chemical Biology

RNA interference insecticides – Nature Biotechnology

Genetic variants associated with rheumatoid arthritis – Nature Genetics

Genes for Transplants – 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.

Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.

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************************************************

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

[1] Genetics: Lung cancer characterization

DOI: 10.1038/nature06358

A huge overview of genetic alterations in lung cancer is presented online in Nature this week. The study takes a new approach to analysing copy number changes in lung adenocarcinoma, identifying a gene that has a significant role in many of these tumours.

Matthew Meyerson and colleagues analyse a large collection of tumours and identify 31 recurrent focal events, including 24 amplifications and 7 deletions occurring on both alleles. A new candidate oncogene, NKX2-1, is shown to be significant in a large number of lung cancers.

The results, when added to other such recent studies, illustrate the power of systematic copy-number analysis.

Author contact:

Matthew Meyerson (Dana-Farber Cancer Institute, Boston, MA, USA)
Tel: +1 617 632 4768; E-mail: [email protected]

*************************************NATURE CHEMICAL BIOLOGY ***********************************

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

[2] In vivo folding lights up

DOI: 10.1038/nchembio.2007.49

A method to determine how proteins fold inside cells could provide important insights into the different behaviors of proteins within the cell versus those in a test tube, as reported online this week in Nature Chemical Biology.

Proteins are created in a linear polymer chain and ‘fold’ from this two-dimensional chain into a final, unique three-dimensional structure. Understanding this folding process is important because the protein structure determines the behavior of the protein. Although folding has been studied extensively in artificial laboratory conditions, the complex cellular environment is likely to cause big differences in how a protein creates its three-dimensional shape.

Schepartz and colleagues have now broken the amino acid tag needed to bind a known fluorescent molecule, or fluorophore, into two pieces, with each piece placed far apart in the protein chain. When the protein folds correctly, these pieces come together and the fluorophore lights up; this fluorescent signal doesn’t occur if the protein cannot fold normally.

Author contact:

Alanna Schepartz, (Yale University, New Haven, CT, USA)

Tel: +1 203 432 5094; E-mail: [email protected]

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

[3] Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin

DOI: 10.1038/nchembio.2007.46

*******************************************NATURE BIOTECHNOLOGY*********************************

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

[4] & [5] RNA interference insecticides

DOI: 10.1038/nbt1352

DOI: 10.1038/nbt1359

Plants expressing a specific type of RNA molecule that kills infesting caterpillars could open the way to more targeted pesticides, suggest two independent papers published online this week in Nature Biotechnology.

RNA molecules are messengers that carry out the instructions encoded in DNA. When certain types of RNA are expressed in plant tissues, they kill specific insects that eat the plants but should not harm other organisms. The most effective current approach to protect plants from insects is to modify them to express a crystalline protein called Bt toxin, which disrupts the insect’s intestinal lining. However, Bt does not work on all insects pests, may inadvertently kill beneficial insects and may become redundant if harmful bugs develop resistance to it.

The two groups, led by Xiao-Ya Chen and James Roberts, show that when destructive insects—including the cotton bollworm, western corn rootworm, southern corn rootworm and Colorado potato beetle—ingest leaves engineered to express an RNA molecule that interferes with essential insect RNA molecules, the pest dies. Previous studies showed that this strategy worked when the interfering RNA was injected into insects, but these are the first reports showing success when plants are modified to express the interfering RNA.

An important advantage of this approach over the current alternatives is that the interfering RNA could probably be made to target pests very selectively. This could satisfy concerns about insecticides indiscriminately killing key links in the food chain.

Author contacts:

Xiao-Ya Chen (Shanghai Institute for Biological Sciences, Shanghai, China)

Tel: +86 21 54924033; E-mail: [email protected] Author paper [4]

James Roberts (Monsanto Company, Chesterfield, Missouri, USA)

Tel: +1 636 7375169; E-mail: [email protected] Author paper [5]

Additional contact for comment:

Peter Waterhouse (CSIRO Plant Industry, Canberra, Australia)

Tel: +61 6 246 4911; E-mail: [email protected]

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

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

[6] & [7] Genetic variants associated with rheumatoid arthritis

DOI: 10.1038/ng.2007.27

DOI: 10.1038/ng.2007.32

Genetic variants in a region on chromosome 6 are associated with risk of rheumatoid arthritis, report two studies online this week in Nature Genetics. Rheumatoid arthritis is the most common inflammatory arthritis, affecting up to 1% of the adult population, and these variants join a very short list of confirmed genetic factors that affect susceptibility to the disease.

Robert Plenge and colleagues carried out a genome-wide association study of individuals with rheumatoid arthritis, identifying a variant on chromosome 6, which was very close to a different variant on chromosome 6 identified in previous studies. They show that these variants probably independently contribute to risk of the disease.

In a separate study, Jane Worthington and colleagues attempted to replicate all variants identified in a recent comprehensive report, and found that the one on chromosome 6 was unequivocally replicated. Although these variants are not located in a gene, the authors suggest that a gene some distance from them (TNFAIP3) is a plausible candidate to explain the effects of these markers, given its involvement in inflammatory processes.

Author contacts:

Robert Plenge (Broad Institute of Harvard and MIT, Cambridge, MA, USA)

Tel: +1 617 324 1763; E-mail: [email protected] Author paper [6]

Jane Worthington (University of Manchester, UK)

Tel: +44 161 275 5037; E-mail: [email protected] Author paper [7]

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

[8] A survey of genetic human cortical gene expression

DOI: 10.1038/ng.2007.16

[9] Genome-wide in situ exon capture for selective resequencing

DOI: 10.1038/ng.2007.42

*******************************************NATURE IMMUNOLOGY ************************************

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

[10] Genes for transplants

DOI: 10.1038/ni1527

A gene that allows mice to accept human bone marrow cells more efficiently is presented online in Nature Immunology this week. The gene, called Sirpa, limits graft failure of transplanted blood stem cells and was found by studying different strains of immunodeficient mice that varied in their ability to accept human blood stem cell transplants.

Such mice serve as valuable tools to study human blood cell deficiencies or diseases. That closely related inbred mouse strains showed differences in engraftment frequencies quickly narrowed the search for the gene. The mouse Sirpa genes are polymorphic, meaning that stable inherited differences are found in these genes that can alter their function.

The protein encoded by Sirpa, SIRP-alpha, interacts with another protein called CD47 expressed on the surface of the human blood cells. This interaction is thought to prevent a class of immune scavenging cells called phagocytes from attacking and eating cells that lack CD47 or have CD47 molecules that cannot be recognized by SIRP-alpha. This latter possibility is why some mouse strains rejected their human blood transplant while other strains did not.

These differences, however, are not restricted to mice. Humans likewise display polymorphisms in the human SIRPA gene. The authors speculate such differences might explain why some bone marrow transplants are rejected despite being ‘tissue matched’ by other criteria for donor-recipient compatibility. If correct, SIRPA can be added to this list of markers used to screen for suitable donors to make bone marrow transplant safer and more successful.

Author contact:

Jayne S Danska (Hospital for Sick Children, Toronto, ON, Canada)
Tel: +1 416 813 8810; E-mail: [email protected]

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

[11] CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation–mediated apoptosis of effector CD4+ T cells

DOI: 10.1038/ni1536

***************************************************************************************************************

Items from other Nature journals to be published online at the same time and with the same embargo:

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

[12] Unexpected features of branched flow through high-mobility two-dimensional electron gases

DOI: 10.1038/nphys756

[13] How pre-melting on surrounding interfaces broadens solid–liquid phase transitions

DOI: 10.1038/nphys754

[14] Impact of long- and short-range disorder on the metallic behaviour of two-dimensional systems

DOI: 10.1038/nphys757

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

[15] Lattice dynamics of the Zn–Mg–Sc icosahedral quasicrystal and its Zn–Sc periodic 1/1 approximant

DOI: 10.1038/nmat2044

[16] Asymmetric superstructure formed in a block copolymer via phase separation

DOI: 10.1038/nmat2038

[17] Bicontinuous emulsions stabilized solely by colloidal particles

DOI: 10.1038/nmat2055

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

[18] Injectable nanocarriers for biodetoxification

DOI: 10.1038/nnano.2007.339

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

[19] Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1

DOI: 10.1038/nm1677

[20] Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis

DOI: 10.1038/nm1667

[21] Extralymphatic virus sanctuaries as a consequence of potent T-cell activation

DOI: 10.1038/nm1670

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

[22] Lamina-specific axonal projections in the zebrafish tectum require the type IV collagen Dragnet
DOI: 10.1038/nn2002

[23] Masking epilepsy by combining two epilepsy genes
DOI: 10.1038/nn1999

[24] The neural correlates of subjective value during intertemporal choice
DOI: 10.1038/nn2007

[25] Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body
DOI: 10.1038/nn2005

[26] GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI
DOI: 10.1038/nn2001

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

[27] Integrin-dependent anchoring of a stem-cell niche

DOI: 10.1038/ncb1660

[28] Telomere lengthening early in development

DOI: 10.1038/ncb1664

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

[29] In situ proteolysis for protein crystallization and structure determination

DOI: 10.1038/nmeth1118

[30] Quantifying small numbers of antibodies with a ‘near-universal’ protein-DNA chimera

DOI: 10.1038/nmeth1127

***************************************************************************************************************

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: 14, 19

BELGIUM
Ghent: 5

CANADA:

Montreal: 18

Toronto: 1, 10, 27, 29

Vancouver: 27

CHINA
Guangzhou: 28
Shanghai: 4

FRANCE

Gif-sur-Yvette: 15

Grenoble: 15

St Martin d’Heres: 15

GERMANY

Berlin: 21

Cologne: 1

Geesthacht: 16

Goettingen: 21

Heidelberg: 20

Magdeburg: 26

Potsdam: 13

Stuttgart: 15

Ulm: 1

ISRAEL

Rehovot: 12

JAPAN

Hyogo : 15

Ibaraki: 15

Kanagawa: 14

Nagoya: 1

Sapporo: 15

Sendai: 15

Tsukuba: 15

NORWAY

Tromsø: 1

SLOVAKIA

Bratislava: 15

SOUTH AFRICA

Bloemfontein: 3

SPAIN

Madrid: 28

SWEDEN

Stockholm: 6

SWITZERLAND

Basel: 21

Zurich: 2, 21, 26

TAIWAN

Hsinchu: 25

UNITED KINGDOM

Aberdeen: 7

Cambridge: 14, 27

Cardiff: 8

Edinburgh: 17

Leeds: 7

London: 7, 8

Manchester: 7

Oxford: 7

Sheffield: 7

UNITED STATES OF AMERICA

Alabama

Birmingham: 3

Arizona

Phoenix: 8

California

Berkeley: 30

Davis: 6

San Francisco: 22

Stanford: 12

Colorado

Fort Collins: 28

Connecticut

New Haven: 2

Florida

Miami: 8

Tampa: 28

Indiana

Indianapolis: 20

Iowa

Ames: 15

Maryland

Bethesda: 1, 3, 6, 8, 11, 20

Massachusetts

Boston: 1, 6

Cambridge: 1, 6

Michigan

Ann Arbor: 1

Minnesota

Minneapolis: 19

Missouri

Chesterfield: 5

St Louis: 1

New Jersey

Murray Hill: 12

Princeton: 12

New Mexico

Los Alamos: 15

New York

Cold Spring Harbor: 9, 25

Manhasset: 6

New York: 1, 6, 24, 25, 27

North Carolina

Winston-Salem: 3

Ohio

Columbus: 19

Oklahoma

Oklahoma City: 20

Texas

Dallas: 1

Galveston: 1, 23

Washington

Seattle: 19

Wisconsin

Madison: 9

Milwaukee: 1, 20

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)

Fabio Pulizzi

Tel: +44 20 7014 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]

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.

NPG is a global company with headquarters in London and offices in New York, San Francisco, Washington DC, Boston, Tokyo, Paris, Munich, Hong Kong, Melbourne, Delhi, Mexico City and Basingstoke. For more information, please go to www.nature.com.