Genetic risk factor for stroke found

Astrophysics: Dark matter mapped, Cancer: Enzyme double act evades drug therapy – Nature, A new source of stem cells – Nature Biotechnology, Population-specific differences in gene expression – Nature Genetics

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 07 January 2007. This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

- Astrophysics: Dark matter mapped – Nature

- Cancer: Enzyme double act evades drug therapy – Nature

- A new source of stem cells – Nature Biotechnology

- Genetic risk factor for stroke found – Nature Genetics

- Population-specific differences in gene expression – Nature Genetics

· 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] Astrophysics: Dark matter mapped (N&V)

DOI: 10.1038/nature05497

Researchers have mapped the distribution of dark matter — the mysterious invisible material that makes up over 80% of the matter in our Universe.

Dark matter can't be seen but it can be detected via its interaction with gravity. So Richard Massey and colleagues used gravitational lensing — the bending of light as it passes a massive object in space — to map its distribution.

Online this week in Nature, they present a high-resolution, three-dimensional map of dark matter that is consistent with predictions that a scaffold of dark matter influences the distribution of normal matter.

Author contacts:

Richard Massey (California Institute of Technology, Pasadena, CA, USA)
Tel: +1 626 395 2654; E-mail: [email protected]

Eric V. Linder (University of California and Lawrence Berkeley National Laboratory,
Berkeley, CA, USA)
Tel: +1 510 486 5568; E-mail: [email protected]

[2] Cancer: Enzyme double act evades drug therapy
DOI: 10.1038/nature05474

A new Nature study, which sheds light on the varied clinical success of a particular class of cancer drug, known as tyrosine kinase inhibitors, may aid the design of more effective cancer therapies.

Tyrosine kinases are enzymes that modify other proteins by adding phosphate groups to them. Specific tyrosine kinases are overactive in many cancers, and drugs that inhibit them, such as the chronic myeloid leukaemia treatment imatinib, can be successful. But they don't work for all tyrosine-kinase-driven cancers. Researchers think they know why.

One particular kinase, called HER2, is frequently overactive in breast cancers and signals through another family member, HER3. Mark M. Moasser and colleagues now show that when HER2 is inhibited by kinase inhibitors, a feedback mechanism causes an increase of active HER3 at the plasma membrane where it continues to signal cancer cell proliferation (as long as HER2 activity is not completely blocked).

More effective inhibitors are needed to block HER2 completely and reign in HER3. Tests that assess HER3 transphosphorylation could also help to predict any such treatment's success.

Author contact:

Mark M. Moasser (University of California, San Francisco, CA, USA)
Tel: +1 415 476 0158; E-mail: [email protected]

*********************************NATURE BIOTECHNOLOGY********************
(http://www.nature.com/naturebiotechnology)

[3] A new source of stem cells

DOI: 10.1038/nbt1274

Amniotic fluid contains stem cells that can be coaxed towards becoming various cell types that might be useful in regenerative medicine, according to a report by Anthony Atala and colleagues in January’s Nature Biotechnology. Amniotic fluid–derived stem (AFS) cells may have advantages over embryonic and adult stem cells as they are readily accessible, replicate rapidly in culture and can be directed towards various differentiated cell types.

The authors isolated AFS cells from discarded samples of amniotic fluid that were originally collected by amniocentesis to test for fetal genetic diseases. AFS cells share properties of both embryonic and adult stem cells and may represent a developmental intermediate between these two types of stem cell. When cultured under the right conditions, AFS cells can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells. Once the methods for culturing and differentiating AFS cells have been optimized, the cells may be useful in therapies designed to regenerate damaged organs and tissues.

Author contact:

Anthony Atala (Wake Forest University, Winston-Salem, NC, USA)
Tel: +1 336 716 5701; E-mail: [email protected]

**************************************NATURE GENETICS **************************
(http://www.nature.com/naturegenetics)

[4] Genetic risk factor for stroke found
DOI: 10.1038/ng1945

Individuals with a particular variant of the gene PRKCH have a 40% increased risk of cerebral infarction, the most common type of stroke, according to a study to be published in the February issue of Nature Genetics.

Michiaki Kubo and colleagues examined more than 50,000 variants across the genome in more than 1,000 Japanese individuals with or without cerebral infarction. One variant in the gene PRKCH was found significantly more frequently in the individuals who had had a stroke. This variant alters the sequence of the protein encoded by PRKCH (PKCη), which is an enzyme that modifies other proteins by attaching phosphate groups to them. The authors show that the risk variant makes the enzyme more active, and that it is abundantly expressed in a variety of different cell types in blocked arteries, which can ultimately lead to stroke. Arteries with more severe blockage tended to have higher levels of PKCη.

Although the association was confirmed in another group of Japanese individuals with cerebral infarction, initial surveys suggest that this PRKCH variant is extremely rare in individuals of European or African descent, suggesting that it may not have a significant effect on the genetic susceptibility to stroke in non-Asian populations.

Author contact:

Michiaki Kubo (University of Tokyo, Japan)
Tel: +81 03 5449 5127; E-mail: [email protected]

[5] Population-specific differences in gene expression

DOI: 10.1038/ng1955

A study to be published in the February issue of Nature Genetics reveals a significant ethnic variation in gene expression. The levels of expression of more than 25% of the genes tested in an initial survey differed between populations, and could explain susceptibility to common diseases.

Although gene expression levels are known to differ among individuals owing to genetic variants that influence gene expression, differences between populations have not been systematically assessed. Richard Spielman, Vivian Cheung and colleagues assessed gene expression levels for more than 4,000 genes in cells derived from individuals of European, Japanese, and Chinese ancestry. More than 1,000 showed modest, but nonetheless significant, differences in levels of expression among the groups. The Japanese and Chinese levels of expression were similar enough that they could be grouped together.

The authors go on to show that variation in levels of gene expression can be associated with particular genetic variants. The differences in gene expression, they note, can be explained by the differing frequencies of these genetic variants in the populations. Susceptibility to common diseases is likely to be influenced by levels of gene expression. As such, the authors conclude that the varying incidence of certain diseases among populations may be due in part to the population-specific differences in gene expression identified here.

Author contacts:

Richard Spielman (University of Pennsylvania School of Medicine, Philadelphia, PA, USA)
Tel: +1 215 898 5763; E-mail: [email protected]

Vivian Cheung (University of Pennsylvania School of Medicine, Philadelphia, PA, USA)
Tel: +1 215 590 4950; E-mail: [email protected]

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

[6] Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution
DOI: 10.1038/ng1960

[7] Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions
DOI: 10.1038/ng1948

*****************************************************************************
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)

[8] Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites
DOI: 10.1038/nchembio853

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

[9] Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein
DOI: 10.1038/nm1488

[10] Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract
DOI: 10.1038/nm1529

[11] Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection
DOI: 10.1038/nm1530

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

[12] Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study
DOI: 10.1038/nn1826

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

[13] B and T lymphocyte attenuator regulates CD8+ T cell–intrinsic homeostasis and memory cell generation
DOI: 10.1038/ni1418

[14] CNS myeloid dendritic cells presenting endogenous myelin peptides ‘preferentially’ polarize CD4+ TH-17 cells in relapsing experimental autoimmune encephalomyelitis
DOI: 10.1038/ni1430

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

[15] Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate cullin-based E3 ligase activity
DOI: 10.1038/nsmb1191

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

[16] Rapid identification of functionally critical amino acids in a G protein-coupled receptor
DOI: 10.1038/nmeth990

[17] Mining a yeast library for brain endothelial cell-binding antibodies
DOI: 10.1038/nmeth993

[18] Detection of minor drug-resistant populations by parallel allele-specific sequencing
DOI: 10.1038/nmeth995

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

***These papers will be published electronically on Nature Nanotechnology’s website on 03 January at 1700 London time (GMT) / 1200 US Eastern time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. We have included them on this release to avoid multiple mailings. All other papers on this release are embargoed for 1800 GMT Sunday 07 January.***

[19] Towards an in vivo biologically inspired nanofactory
DOI: 10.1038/nnano.2006.180

[20] Electrically driven thermal light emission from individual single-walled carbon nanotubes
DOI: 10.1038/nnano.2006.169

[21] Rare-earth solid-state qubits
DOI: 10.1038/nnano.2006.174

[22] Self-assembly of an organic–inorganic block copolymer for nano-ordered ceramics
DOI: 10.1038/nnano.2006.168

[23] Size-dependent structure of MoS2 nanocrystals
DOI: 10.1038/nnano.2006.171

[24] Effect of supramolecular structure on polymer nanofiber elasticity
DOI: 10.1038/nnano.2006.172

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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.

ARGETINA
Buenos Aires: 9

CANADA:

Montreal: 9

Ottawa: 9

Toronto: 7, 9

Vancouver:

Waterloo: 1

CHINA
Hong Kong: 10, 11

DENMARK

Aarhus: 6, 23

Ballerup: 6

Gentofte: 6

Glostrup: 6

FRANCE

Gif-sur-Yvette: 1

Grenoble: 21

Marseilles: 1, 21

Paris: 1

GERMANY

Essen: 6

Garching: 1

Goettingen: 9

Heidelberg: 12

Marburg: 6

ICELAND

Reykjavik: 6

ISRAEL
Haifa: 12, 24

JAPAN

Aichi: 15

Fukuoka: 4

Ibaraki: 15

Iwate: 9

Matuyama: 1

Nagoya: 15

Osaka: 15

Sapporo: 9

Tokyo: 4, 15

Yokohama: 4

KAZAKHSTAN

Almaty: 9

RUSSIA

Kazan: 21

St Petersburg: 21

SPAIN

Barcelona: 8

Colmenar Viejo: 8

Madrid: 8

SWITZERLAND

Berne: 12

Lausanne: 13

UNITED KINGDOM

Edinburgh: 1

London: 9, 11

UNITED STATES OF AMERICA

California

Irvine: 8

La Jolla: 13, 19

Pasadena: 1

San Francisco: 2

Santa Barbara: 14

Santa Clara: 20

Stanford: 7, 9, 20

District of Columbia

Washington: 6

Florida

Gainesville: 20

Georgia:

Atlanta: 19

Illinois

Chicago: 13, 14

Urbana: 19

Maryland

Baltimore: 1

Bethesda: 16

College Park: 19

Frederick: 8

Massachusetts

Amherst: 19

Boston: 3, 7, 9, 11, 19

Cambridge: 9, 19

New Jersey:

Hoboken: 19

Princeton: 8

New York

Albany: 9, 19

Cold Spring Harbor: 19

Niskayuna: 22

North Carolina

Durham: 18

Raleigh: 19

Winston-Salem: 3

Pennsylvania

Philadelphia: 5, 6

Pittsburgh: 8, 19

South Carolina:

Clemson: 19

Texas

Houston: 19

Wisconsin

Madison: 17

PRESS CONTACTS…

For media inquiries relating to embargo policy for all the Nature Research Journals:

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For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

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Nature Genetics (New York)

Orli Bahcall

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Nature Immunology (New York)

Laurie Dempsey

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Nature Medicine (New York)

Juan Carlos Lopez

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Nature Methods (New York)

Allison Doerr

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Nature Nanotechnology (London)

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Published: 07 Jan 2007

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