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Article Released Sun-1st-November-2009 18:45 GMT
Contact: Ruth Institution: Nature Publishing Group
 Genetics: Cucumber genome sequenced

Summaries of newsworthy papers include Predicting new protein targets for known drugs, Heartbeat awareness, Gamma-rays from a starburst galaxy, Genome of strains of leprosy sequenced and How air can move the earth

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 01 November 2009

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

This press release contains:

· Summaries of newsworthy papers:

Nature: Predicting new protein targets for known drugs

Neuroscience: Heartbeat awareness

Nature: Gamma-rays from a starburst galaxy

Genetics: Genome of strains of leprosy sequenced

Geoscience: How air can move the earth

And finally…Genetics: Cucumber genome sequenced

· 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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[1] Nature: Predicting new protein targets for known drugs
DOI: 10.1038/nature08506

A strategy to identify potential ‘off-target’ effects for known drugs is reported online this week in Nature. Although most drugs are intended to be selective for a single protein target, side-effects can occur if the drug interacts with other proteins in the body. It is hoped that the identification of these ‘off-target’ effects could be used to predict the side-effects of a drug candidate before the molecule is advanced into clinical trials. It might also be possible to use this approach to identify new indications for drugs that have already been approved for use in humans.

Brian Shoichet and colleagues compared 3,665 FDA-approved and investigational drugs against a panel of ligands that were organized into groups according to the protein targets that the ligands modulate. Chemical similarities between the drug and ligand sets were used to predict thousands of potential off-target effects, and several of these interactions were confirmed in the laboratory. The authors also verified the physiological relevance of one of their predictions, involving the effects of the hallucinogenic drug DMT on serotonin receptors, in a mouse model.

This approach may be able to explain and predict the side-effects of new drug candidates, and the authors hope that this could lead to the identification of new indications for drugs that are already approved for human use.

Author contact:
Brian Shoichet (University of California, San Francisco, CA, USA)
Tel: +1 415 514 4126; E-mail: shoichet@cgl.ucsf.edu


[2] Neuroscience: Heartbeat awareness
DOI: 10.1038/nn.2411

The neural pathway by which we feel stimuli originating inside our bodies – such as our heartbeat – is illuminated by studying an unusual patient with unique patterns of brain damage, according to a study published online this week in Nature Neuroscience.

Previous brain imaging studies reported that a network of brain regions were critical for sensing internal stimulus, such as heartbeat. Two such regions of interest are the insular cortex – an area deep in the brain which plays a role in the body’s homeostasis – and the anterior cingulate cortex – a region that regulates automatic functions, such as blood pressure and heart rate. These brain regions are also involved in emotion processing and other cognitive functions.

Sahib Khalsa and colleagues report that a patient who had suffered damage to his insular cortex and anterior cingulate cortex is surprisingly still able to sense an increase in his heartbeat, when given a drug that increased his heart rate. However, when a topical anesthetic was applied to his chest, this patient was no longer able to sense the change in his heart rate.

This study suggests that the neural structures innervating the skin are able to independently monitor self-awareness of one’s own heartbeat and that moreover the insular cortex and anterior cingulate cortex are not necessary for this type of self-awareness.

Author contact:
Sahib Khalsa (University of California, Los Angeles, CA, USA)
Tel: +1 631 804 1614; E-mail: skhalsa@mednet.ucla.edu


[3] Nature: Gamma-rays from a starburst galaxy
DOI: 10.1038/nature08557

Very-high-energy gamma-rays have been detected from the galaxy M82 — a ‘starburst’ galaxy, characterized by extremely high rates of star formation. The detection implies the presence of abundant cosmic rays in the galaxy’s star-forming core, supporting a connection between cosmic-ray acceleration and the formation, life and death of massive stars.

Cosmic rays — energetic particles — originating in our own Galaxy are thought to be accelerated by shock waves surrounding supernova remnants and massive stars, but definitive evidence for this origin remains elusive. The active star-forming regions of starburst galaxies such as M82 should be prolific sources of cosmic rays, which in turn should interact with interstellar gas and radiation to produce diffuse gamma-ray emission. M82 has been predicted to be the brightest starburst galaxy in gamma-rays, but previous searches have not been sensitive enough to detect a signal.

In this week’s Nature, the VERITAS Collaboration reports the detection of gamma-rays from M82 with energies above 700 billion electron volts. The observed flux of gamma-rays implies a cosmic-ray density in M82’s starburst core that is about 500 times the average in our Galaxy. This demonstration of a connection between cosmic rays and star formation supports the suggested role of massive stars and supernovae in the origin of cosmic rays.

Author contact:
Wystan Benbow (Harvard-Smithsonian Center for Astrophysics, Amado, AZ, USA)
Tel: +1 520 670 5726; E-mail: wbenbow@cfa.harvard.edu


[4] Genetics: Genome of strains of leprosy sequenced
DOI: 10.1038/ng.477

A second complete genome sequence of the pathogen M. leprae, which causes leprosy, has been determined. These findings, as well as the deep re-sequencing of two other M. leprae strains, are reported online in this week’s Nature Genetics.

M. leprae is the bacterial pathogen that causes leprosy, a disease that is characterized by disfiguring lesions on the skin and loss of sensation. Although leprosy is no longer a significant health problem in developed countries, pockets of high-risk areas remain in less-developed countries, such as those in Africa or South-East Asia. Currently, the worldwide burden of leprosy is under 250,000 cases a year.

The genome of an M. leprae strain from India was previously sequenced. Here, Stewart Cole and colleagues have assembled the complete genome of an M. leprae strain from Brazil and have also sequenced two more M. leprae strains from Thailand and the United States. Although the four M. leprae strains come from geographically distant locations, comparison of their four genomes shows that they are 99.995% identical. This surprising result implies that leprosy has arisen from a single clonal strain. Lack of genomic diversity in M. leprae is encouraging for treatment, as it suggests that drug effectiveness should be similar for most strains of M. leprae.

Author contact:
Stewart Cole (Ecole Polytechnique Fédérale de Lausanne, Switzerland)
Tel: +41 216 931 851; E-mail: stewart.cole@epfl.ch


[5] Geoscience: How air can move the earth
DOI: 10.1038/ngeo659

Tides in the atmosphere — working much like ocean tides — can trigger an episode of movement in an ongoing landslide. The study, published online this week in Nature Geoscience, found that episodic sliding of land near Slumgullion pass in Colorado, USA, tends to occur during the daily atmospheric low tide.

William Schulz and colleagues compared hourly measurements of the slip speed of the landslide over nine months with equally frequent observations of local atmospheric pressure. The scientists found a significant correlation between both time series. The effect could be caused by an upward movement of air and water molecules in the soil during periods of low atmospheric pressure, which reduces the friction that usually holds the landslide in place.

The researchers suggest that atmospheric pressure could trigger other geological phenomena that involve sliding surfaces, such as earthquakes, volcanic eruptions and glacier movement.

Author contact:
William H. Schulz (United States Geological Survey, Denver, Colorado, USA)
Tel: +1 303 273 8404; E-mail: wschulz@usgs.gov


[6] And finally…Genetics: Cucumber genome sequenced
DOI: 10.1038/ng.475

The genome of the cucumber, an economically important crop, has been sequenced, according to a report published online this week in Nature Genetics.

The cucumber is part of the cucurbit botanical family, which also includes melon, watermelon, squash and pumpkin. Altogether, cucurbit crops utilize nine million hectares of land and yield 184 million tons of fruit, vegetables and seed each year. The cucumber is the seventh plant to have its genome sequenced, following the well-studied plant model Arabidopsis thaliana, the poplar tree, grapevine, papaya, and the crops rice and sorghum.

Jun Wang and colleagues used both traditional DNA sequencing methods and next-generation sequencing technologies to assemble the cucumber genome. This was the first time next-generation sequencing data was used in the initial assembly of a plant genome. The cucumber genome is 245 million base pairs, similar to the rice genome, which is 389 million base pairs. The sequenced genome will be a resource for plant breeders developing elite varieties of cucurbits and will also be useful for studying different aspects of plant development.

Author contact:
Jun Wang (Beijing Genomics Institute -Shenzhen, China)
Tel: +86 755 25 27 3796; E-mail: wangj@genomics.org.cn


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

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

[7] Observation of the fractional quantum Hall effect in graphene
DOI: 10.1038/nature08582

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

[8] The transcription unit architecture of the Escherichia coli genome
DOI: 10.1038/nbt.1582

[9] Microdroplet-based PCR enrichment for large-scale targeted sequencing
DOI: 10.1038/nbt.1583

[10] An integrative approach to reveal driver gene fusions from paired-end sequencing data in cancer
DOI: 10.1038/nbt.1584

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

[11] Phosphorylation of STIM1 underlies suppression of store-operated calcium entry during mitosis
DOI: 10.1038/ncb1995

NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)

[12] Moonlighting proteins Hal3 and Vhs3 form a heteromeric PPCDC with Ykl088w in yeast CoA biosynthesis
DOI: 10.1038/nchembio.243

[13] Spatiotemporal modulation of biodiversity in a synthetic chemical-mediated ecosystem
DOI: 10.1038/nchembio.244

[14] A synergistic small-molecule combination directly eradicates diverse prion strain structures
DOI: 10.1038/nchembio.246

NATURE CHEMISTRY (http://www.nature.com/nchem)

[15] Type-zero copper proteins
DOI: 10.1038/nchem.412

[16] Complete chiral symmetry breaking of an amino acid derivative directed by circularly polarized light
DOI: 10.1038/nchem.416

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

[17] Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells, and fibroblasts
DOI: 10.1038/ng.471

NATURE GEOSCIENCE (http://www.nature.com/ngeo)

[18] Large-scale distribution of Atlantic nitrogen fixation controlled by iron availability
DOI: 10.1038/ngeo667

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

[19] PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4
DOI: 10.1038/ni.1815

[20] T cell–intrinsic role of Nod2 in promoting type 1 immunity to Toxoplasma gondii
DOI: 10.1038/ni.1816

[21] Requirement for the basic helix-loop-helix transcription factor Dec2 in initial TH2 lineage commitment
DOI: 10.1038/ni.1821

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

[22] Nanostructured arrays of semiconducting octahedral molecular sieves by pulsed-laser deposition
DOI: 10.1038/nmat2567

[23] Gold nanocages covered by smart polymers for controlled release with near-infrared light
DOI: 10.1038/nmat2564

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

[24] Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy
DOI: 10.1038/nm.2037

[25] Activation of PKC-delta and SHP1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy
DOI: 10.1038/nm.2052

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

[26] High-speed nanoscopic tracking of the position and orientation of a single virus
DOI: 10.1038/nmeth.1395

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

[27] Design considerations for tumour-targeted nanoparticles
DOI: 10.1038/nnano.2009.314

[28] True solutions of single-walled carbon nanotubes for assembly into macroscopic materials
DOI: 10.1038/nnano.2009.302

[29] Nanomechanical motion measured with an imprecision below that at the standard quantum limit
DOI: 10.1038/nnano.2009.343

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

[30] A novel pathway comprised of Sox14 and Mical governs severing of dendrites during pruning
DOI: 10.1038/nn.2415

[31] Adult generation of glutamatergic olfactory bulb interneurons
DOI: 10.1038/nn.2416

[32] Input normalization by global feed-forward inhibition expands cortical dynamic range
DOI: 10.1038/nn.2441

[33] Self-generated theta oscillations in the hippocampus
DOI: 10.1038/nn.2440

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

[34] A universal origin for secondary relaxations in supercooled liquids and structural glasses
DOI: 10.1038/nphys1432

[35] Quantum oscillations from Fermi arcs
DOI: 10.1038/nphys1431

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

[36] Single-molecule analysis of protein-free U2-U6 snRNAs
DOI: 10.1038/nsmb.1672

[37] Regulation of a muralytic enzyme by dynamic membrane topology
DOI: 10.1038/nsmb.1681

*** The following paper was published electronically on Nature Immunology’s website on 22 October at 2000 London time / 1500 US Eastern time. The paper is no longer under embargo, though the rest of the above articles on this release remain under embargo until 01 November at 1800 London time / 1300 US Eastern time ***

[38] Enteric defensins are essential regulators of intestinal microbial ecology
DOI: 10.1038/ni.1825

***************************************************************************************************************
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
Canberra: 6

BANGLADESH
Dhaka: 4

BRAZIL
Goias: 4

CANADA:
Montreal: 3, 33
Quebec: 25
Vancouver: 35

CHINA
Beijing: 6, 19
Hubei: 21
Guangzhou: 6
Jinan: 6
Nanjing: 4
Shanghai: 21
Shenzhen: 6

DENMARK
Aarhus: 6
Copenhagen: 6
Odense: 6

FRANCE
Palaiseau: 3
Paris: 4, 31

GERMANY
Berlin: 24
Cologne: 24
Freiburg: 31
Heidelberg: 24
Kiel: 18
Koln: 35
Lubeck: 24
Munich: 31
Munster: 24
Neuherberg: 31
Wurzburg: 24

HUNGARY
Budapest: 31

ICELAND
Reykjavik: 8

INDIA
New Delhi: 37

IRAN
Tehran: 4

IRELAND
Cork: 3
Dublin: 3
Galway: 3

ISRAEL
Haifa: 28

JAPAN
Kyoto: 5
Tokyo: 4

KOREA
Jinju: 6

MEXICO
Nuevo Leon: 4

NEPAL
Kathmandu: 4

NETHERLANDS
Geleen: 16
Groningen: 16, 38
Nijmegen: 16

NORWAY
Oslo: 25

SINGAPORE
Singapore: 30

SPAIN
Barcelona: 12
Madrid: 20

SOUTH AFRICA
Rondebosch: 18
Stellenbosch: 12

SWITZERLAND
Lausanne: 4
Zurich: 26, 31

THAILAND
Pathum-than: 21

UNITED KINGDOM
Cambridge: 31
Colchester: 18
Leeds: 3
London: 4, 31
Manchester: 4
Plymouth: 18
Portsmouth: 4
Scotland: 12
Southampton: 18

UNITED STATES OF AMERICA

Alabama
Auburn: 28

California
Davis: 6, 38
La Jolla: 8, 9, 32, 34
Los Angeles: 3, 4, 37
Menlo Park: 15
Pasadena: 15, 35
San Francisco: 1
Santa Cruz: 3
Stanford: 12, 18
Storrs: 22

Colorado
Boulder: 29
Denver: 5
Fort Collins: 4

Connecticut
Branford: 9

Delaware
Newark: 3

Illinois
Argonne: 3
Chicago: 3

Indiana
Anderson: 3
Greencastle: 3
West Lafayette: 3

Iowa
Grinnell: 3
Iowa City: 2, 3

Kansas
Pittsburg: 3

Maryland
Baltimore: 17, 30
Bethesda: 21

Massachusetts
Boston: 17, 25, 27
Cambridge: 27
Lexington: 9
Watertown: 14

Michigan
Ann Arbor: 1, 10, 20
Detroit: 36

Missouri
St Louis: 3, 23, 38

New Hampshire
Durham: 13

New York
Ithaca: 6, 15
New York: 3, 7, 12

North Carolina
Chapel Hill: 1
Research Triangle Park: 11

Ohio
Cleveland: 1, 25

Pennsylvania
Philadelphia: 14, 28

Tennessee
Nashville: 7

Texas
College Station: 37
Houston: 21, 28
Lubbock: 28

Utah
Salt Lake City: 3

Virginia
Richmond: 1, 8

Washington
Seattle: 31

Wisconsin
Madison: 6, 30
Milwaukee: 38

VENEZUELA
Caracas: 4

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: r.twinn@nature.com

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: n.afsarmanesh@us.nature.com

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail: r.francis@nature.com

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

Nature Biotechnology (New York)
Craig Mak
Tel: +1 212 726 9284; E-mail: biotech@us.nature.com

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: cellbio@nature.com

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: chembio@us.nature.com

Nature Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: s.cantrill@nature.com

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9324; E-mail: natgen@us.nature.com

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: h.langenberg@nature.com

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: immunology@us.nature.com

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: materials@nature.com

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: medicine@us.nature.com

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: methods@us.nature.com

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: p.rodgers@nature.com

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail: neurosci@us.nature.com

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: a.wright@nature.com

Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: nsmb@us.nature.com

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