NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 7 May 2006
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
- HIV: Nuclear protein controls virus invasion – Nature
- Keeping drugs on target - Nature Chemical Biology
- Ion channels served up quickly - Nature Chemical Biology
- Common genetic variant associated with prostate cancer – 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] HIV: Nuclear protein controls virus invasion (AOP)
DOI: 10.1038/nature04682
A protein in the cell’s nuclear membrane regulates the ability of the HIV virus to invade human cells, reveal Jean-Marc Jacque and Mario Stevenson in a study to be published online in this week’s Nature.
The researchers show that HIV has difficulty infecting the immune system’s macrophages if they lack emerin, a component of the inner nuclear envelope. This is because copies of the viral genetic material — complementary DNA (cDNA) — cannot integrate into the knot of nuclear DNA and protein called chromatin.
The researchers propose that emerin is necessary for the viral cDNA to localize with chromatin before inserting into the host’s cellular DNA — and suggest that small molecules that inhibit the interaction between emerin and viral cDNA might help block HIV infection.
Author contact
Mario Stevenson (Massachusetts University Medical Center, Worcester, MA, USA)
Tel: +1 508 856 4582; E-mail: [email protected]
Other papers from Nature to be published online at the same time and with the same embargo:
[2] Identification of a tumour suppressor network opposing nuclear Akt function
DOI: 10.1038/nature04809
*******************NATURE CHEMICAL BIOLOGY ************************
(http://www.nature.com/nchembio)
[3] Keeping drugs on target
DOI: 10.1038/nchembio790
A method for identifying unintended effects of drugs is reported in the June issue of Nature Chemical Biology. During research and development, drugs are typically tested for their inhibition of a desired therapeutic target. However, when a drug is used clinically, side effects can be caused by unexpected interactions inside cells. These unintended effects may often be responsible for drug failure during clinical trials.
Stephen Michnick, John Westwick and colleagues have developed a high-throughput screen that monitors the effects of a drug on a wide range of cellular signaling pathways. They analyzed the effects of over 100 known drugs on these pathways and found that drugs with similar chemical structures or protein targets often had similar intended—and also unintended—effects on cellular signaling. Using this approach, they also showed that four known drugs also displayed previously unknown abilities to block the growth of cancer cells
This new assay may now allow researchers to optimize the desired effects of drugs while simultaneously minimizing the undesired effects during the drug discovery process. Additionally, the ability to uncover unexpected but potentially useful drug actions, including inhibiting cell proliferation, could increase the efficiency of the drug discovery process.
Author contact:
Stephen Michnick, John Westwick (Université de Montréal, Canada)
Tel: +1 514 343 5849, E-mail: [email protected]
[4] Ion channels served up quickly
DOI: 10.1038/nchembio793
A new method for the rapid screening of membrane proteins, including ion channels, is reported in the June issue of Nature Chemical Biology. Despite the fact that only a small proportion of drugs target ion channels, these drugs yield multiple billions of dollars in sales each year. The search for new drugs targeting ion channels could lead to therapeutics in areas such as heart disease and cancer. However, identifying small-molecule inhibitors of ion channels has been slowed by the laborious process necessary to assay ion channel activity.
Holden and colleagues have now developed a rapid assay for screening membrane protein function. They first touch a glass probe to a colony of E. coli that is producing a membrane protein. They then touch this same glass probe to an artificial lipid bilayer that mimics the environment of a cellular membrane. By this simple transfer, which takes only minutes, a functional single channel can be tested for activity. As an example of the speed possible with this approach, the authors screened 100 pore-forming proteins, each with a different amino acid altered, and found a mutant of the pore protein with a new function in just a few hours.
In addition to its important potential to speed ion channel–targeted drug discovery, this method will likely also be useful for membrane protein proteomics and for developing new sensor technology.
Author contact:
Matthew Holden (University of Oxford, UK)
Tel: +44 1865 285108, E-mail: [email protected]
Other papers from Nature Chemical Biology to be published online at the same time and with the same embargo:
[5] The catalytic cycle of a thiamin diphosphate enzyme examined by cryocrystallography
DOI: 10.1038/nchembio788
*************************NATURE GENETICS ****************************
(http://www.nature.com/naturegenetics)
[6] Common genetic variant associated with prostate cancer
DOI: 10.1038/ng1808
A common genetic marker that is found more frequently in men with prostate cancer than those without is reported in a study to be published in the June issue of Nature Genetics. This the first identification of a major genetic risk factor for prostate cancer in the general population.
Kari Stefansson and colleagues show that a particular marker on chromosome 8 is significantly more frequent in men with prostate cancer in populations studied in Iceland, Sweden, and the United States, including both European and African Americans. About 8% of prostate cancers in Europeans might be attributed to this variant. The genetic marker is significantly associated with high-grade prostate cancer in the four populations studied, and not with the benign precursor to prostate cancer, suggesting that it specifically increases the risk of malignant prostate tumors. The risk variant has not yet been definitively linked to a particular gene, although nearby regions on chromosome 8 harbor several candidates.
The incidence of prostate cancer is increasing and, after skin cancer, is now the most common form of cancer diagnosed in men. African Americans have a particularly high incidence, and are more likely to die from the disease than European Americans. The fact that the identified risk variant is four times more frequent in African Americans than European Americans suggests that it might explain at least a fraction of the elevated risk borne by Americans of African ancestry.
Author contact:
Kari Stefansson (deCODE Genetics, Reykjavik, Iceland)
Tel: +354 570 1900, E-mail: [email protected]
Edward Farmer (Director of Corporate Communication, deCODE genetics Inc.)
Tel: +1 646 417 4555; E-mail; [email protected]
Other papers from Nature Genetics to be published online at the same time and with the same embargo:
[7] The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4
DOI: 10.1038/ng1786
[8] Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome
DOI: 10.1038/ng1805
[9] Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus
DOI: 10.1038/ng1796
[10] Epigenetic maintenance of the vernalized state in Arabidopsis thaliana requires LIKE HETEROCHROMATIN PROTEIN 1
DOI: 10.1038/ng1795
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Items from other Nature journals to be published online at the same time and with the same embargo:
NATURE MATERIALS (http://www.nature.com/naturematerials)
[11] Atomic spin structure of antiferromagnetic domain walls
DOI: 10.1038/nmat1646
[12] Multifunctional composites using reinforced laminae with carbon-nanotube forests
DOI: 10.1038/nmat1650
Nature MEDICINE (http://www.nature.com/naturemedicine)
[13] Eradication of established tumors in mice by a combination antibody-based therapy
DOI: 10.1038/nm1405
[14] Gamma secretase–mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke
DOI: 10.1038/nm1403
[15] Carminerin contributes to chondrocyte calcification during endochondral ossification
DOI: 10.1038/nm1409
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
[16] The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells
DOI: 10.1038/nn1694
[17] Eph receptors are negatively controlled by protein tyrosine phosphatase receptor type O
DOI: 10.1038/nn1697
[18] Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells
DOI: 10.1038/nn1698
[19] BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex
DOI: 10.1038/nn1699
Nature IMMUNOLOGY (http://www.nature.com/natureimmunology)
[20] Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes
DOI: 10.1038/ni1340
[21] Transcription factor Pax5 (BSAP) transactivates the RAG-mediated VH-to-DJH rearrangement of immunoglobulin genes
DOI: 10.1038/ni1339
[22] Activation of the integrated stress response during T helper cell differentiation
DOI: 10.1038/ni1338
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
[23] RNA helicase A is necessary for translation of selected messenger RNAs
DOI: 10.1038/nsmb1092
[24] Exon ligation is proofread by the DExD/H-box ATPase Prp22p
DOI: 10.1038/nsmb1093
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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
Victoria: 13, 20
CHINA
Beijing: 7
Shanghai: 7
GERMANY
Berlin: 7
Cologne: 7
Freiburg: 7
Halle: 5
Hamburg: 10
Hannover: 7
Matinsreid: 7
Munich: 20
ICELAND
Regkjavik: 6
ITALY
Cagliari: 8
Chieti: 8
Pavia: 8
Rome: 8
JAPAN
Hyogo: 7
Niigata: 13
Okayama: 10
Okazaki: 17
Sapporo: 24
Tokyo: 13, 15
Yamagata: 10
SINGAPORE
Science Drive: 10
SWEDEN
Orebro: 6
Stockholm: 6
SWITZERLAND
Zurich: 7, 8
TAIWAN
Taiwan: 14
UNITED ARAB EMIRATES
Al Ain: 8
UNITED KINGDOM
Newcastle Upon Tyne: 7
Oxford: 4
UNITED STATES OF AMERICA
Alabama
Birmingham: 21
California
Irvine: 19
La Jolla: 7, 8, 21
Los Angeles, 10
Orange: 19
San Francisco: 22
San Ramon: 3
Canada
British Columbia: 7
Quebec: 3, 16
Colorado
Denver: 21
Florida
Gainesville: 19
Georgia
Atlanta: 13
Hawaii
Honolulu: 12
Illinois
Chicago: 6, 14, 24
Louisiana
Shreveport: 14
Massachusetts
Boston: 18
Charlestown: 7
Worcester: 1
Michigan
Ann Arbor: 6, 7
Missouri
St Louis: 6
New Jersey
Princeton: 16
New York
Albany: 16
New York: 2
Saranac Lake: 22
Troy: 12
Ohio
Columbus: 23
Pennsylvania
Philadelphia: 16, 23
Washington
Seattle: 7
PRESS CONTACTS…
For media inquiries relating to embargo policy for all the Nature Research Journals:
Victoria Picknell (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)
Kathy Aschheim
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Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]
Nature Chemical Biology (Boston)
Beatrice Chrystall
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 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)
Ed Feng
Tel: +1 212 726 9351; E-mail: [email protected]
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