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Article Released Sun-24th-May-2009 17:17 GMT
Contact: Ruth Institution: Nature Publishing Group
 Genetics: Malaria gene scan tackles diversity of West African populations

Summaries of newsworthy papers include A mushroom mystery solved, Candida genome sequenced, No role for Snowball Earth in ancient extinction, Initiator of allergic responses, How do inhibitors activate kinases? and Targeting muscle disorders

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 24 March 2009

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

This press release contains:

· Summaries of newsworthy papers:

Genetics: Malaria gene scan tackles diversity of West African populations

Chemical Biology: A mushroom mystery solved

Nature: Genetics: Candida genome sequenced

Geoscience: No role for Snowball Earth in ancient extinction

Immunology: Initiator of allergic responses

Chemical Biology and Structural & Molecular Biology: How do inhibitors activate kinases?

And finally … Cell Biology: Targeting muscle disorders

· 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] Genetics: Malaria gene scan tackles diversity of West African populations
DOI: 10.1038/ng.388

Genome scanning techniques that have been successful in finding genetic variants contributing to common diseases in European and Asian ancestry will have to be modified for studies in Africans because of the sheer genetic diversity of African populations, according to an international study of severe malaria published this week in Nature Genetics.

Dominic Kwiatkowski and colleagues looked for genetic variants associated with malaria affecting the brain, and severe malaria anemia in thousands of children from four major ethnic groups and several other groups living in a small area of The Gambia, in Western Africa. The team found that, in order to find highly significant effects of even the sickle cell hemoglobin variant already known to protect against malaria, they had to sequence that gene in DNA of 62 individuals and then predict missing genetic variants using a computational model.

Author contact:
Dominic Kwiatkowski (Oxford University & Sanger Institute, Oxford, UK)
Tel: +44 1865 287 654; E-mail: dominic@well.ox.ac.uk


[2] Chemical Biology: A mushroom mystery solved
DOI: 10.1038/nchembio.179

The toxic culprit in recent cases of mushroom poisoning – which has lead to several deaths – has been identified as a single small molecule. The specific toxic agent in these poisoning cases was previously unknown and the findings, published online this week in Nature Chemical Biology, will enable biological experiments to determine how the molecule causes fatalities.

To uncover the fatal molecule, Kimiko Hashimoto and colleagues first determined which species of mushroom was causing the negative reactions. They then isolated the active molecule and determined that it was cycloprop-2-ene carboxylic acid, a tiny compound with only 4 carbon atoms. This compound has been used in synthetic chemistry research, but has never been found in a biological system. However, biological testing in mice confirmed that the compound causes severe biological symptoms suggestive of rhabdomyolysis - the rapid breakdown of skeletal muscle tissue.

Author contact:
Kimiko Hashimoto (Kyoto Pharmaceutical University, Japan)
Tel: +81 75 595 4666, E-mail: kimikoh@mb.kyoto-phu.ac.jp

[3] Nature: Candida genome sequenced
DOI: 10.1038/nature08064

The genomes of six different Candida species have been sequenced. The data, revealed in this week’s Nature, offer insights into the yeast’s biology, including the evolution of pathogenicity and sexual reproduction.

Christina Cuomo and colleagues decoded the genomes of six different types of Candida, including sexual and non-sexual, and disease-causing and benign species. Comparisons against two other yeast genomes revealed many new Candida-specific genes, as well as genes linked to the disease-causing process. Surprisingly, key components of mating and cell division pathways are missing from several species, raising questions about how these processes are controlled.

Author contact:
Christina Cuomo (Broad Institute, Cambridge, MA, USA)
Tel: +1 617 452 4735; E-mail: cuomo@broad.mit.edu


[4] Geoscience: No role for Snowball Earth in ancient extinction
DOI: 10.1038/ngeo525

A widespread biotic turnover in a tropical ocean 740 million years ago seems to be linked to an increase in surface nutrients – an idea that rules out Snowball Earth. The study online in Nature Geoscience shows that the biotic turnover ­— in which a diverse assemblage of plankton was replaced by a bacterial bloom — preceded the onset of low-latitude glaciation associated with Snowball Earth by 16 million years.

Susannah Porter and colleagues reconstructed the timing of the plankton shift using samples from rocks exposed in the Grand Canyon of the United States. The researchers sampled a particular unit of rocks with uniquely high sedimentation rates for their age, which allowed them to create an unprecedented temporal reconstruction of the events leading up to the local extinction.

Their analyses show that the evidence for a rise in surface nutrients and the extinction appears millions of years before the first evidence of glaciers appeared in the rocks, ruling out Snowball Earth as the cause of this particular event.

Author contact:
Susannah Porter (University of California at Santa Barbara, CA, USA)
Tel: +1 310 613 3694; E-mail: porter@geol.ucsb.edu

[5], [6], & [7] Immunology: Initiator of allergic responses

DOI: 10.1038/ni.1737
DOI: 10.1038/ni.1738
DOI: 10.1038/ni.1740

A new ‘antigen-presenting’ function for specialized immune cells that allows them to initiate allergy or mount immune responses against parasites is reported online in three papers in Nature Immunology. The research highlights the cells, known as basophils, as therapeutic targets for short-circuiting allergic responses.

Basophils are an immune cell that releases chemical mediators that can trigger the wheezing, itching and other symptoms that accompany allergic reactions. Groups led by David Artis, Kenji Nakanishi and Ruslan Medzhitov show basophils act as the first responders that present antigen to naïve T cells. These ‘primed’ T cells instruct the immune system to secrete interleukin 4 and immunoglobulin E, which help to repel worms and other parasites, but also underlie allergic responses.

Previously, basophils were thought to act after individuals had become ‘sensitized’ through previous contact with allergen or worm exposure. The new work reveals how these cells both initiate and amplify allergic reactions, such that once initiated by contact with allergen they become difficult to control, as any allergy sufferer can attest.

This research rules out earlier assumptions that dendritic cells, an important antigen-presenting cell for viral and bacterial infections, initiate the allergic response.

Author contacts:
Kenji Nakanishi (Hyogo College of Medicine, Japan) Author paper [5]
Tel: +81 798 45 6572; E-mail: nakaken@hyo-med.ac.jp

Ruslan Medzhitov (Yale University School of Medicine, New Haven, CT, USA) Author paper [6]
Tel: +1 203 785 7541; E-mail: ruslan.medzhitov@yale.edu

David Artis (University of Pennsylvania, Philadelphia, PA, USA) Author paper [7]
Tel: +1 215 898 7920; E-mail: dartis@vet.upenn.edu


[8] & [9] Chemical Biology and Structural & Molecular Biology: How do inhibitors activate kinases?
DOI: 10.1038/nchembio.183
DOI: 10.1038/nsmb.1606

Inhibitor binding leads to pre-activation of two kinases according to papers published online this week at Nature Chemical Biology and Nature Structural & Molecular Biology. The surprising finding may have important implications for drug discovery.

Kinases, which are a type of enzyme, are often ‘primed’ for full activity by the addition of small chemical groups called phosphates. Kinase inhibitors, used clinically to treat cancer, function by blocking kinase activity. As a result, it was unexpected when an inhibitor of the cancer-associated kinase Akt was found to cause the ‘priming’ phosphates to be added.

Using chemical tools to look closely at this phenomenon, Kevan Shokat and colleagues find that binding of the Akt inhibitor is directly responsible for this increased phosphorylation. Peter Parker and colleagues find a similar effect with the related kinase PKCε – inhibitor binding directly triggers priming phosphorylation.

Since, as discussed in an accompanying commentary by Stephen Frye and Gary Johnson, it may not be desirable to have drugs that increase the activity ‘readiness’ of the kinases they are designed to inhibit, these results have important implications for drug discovery.

Author contact:
Kevan Shokat, (University of California, San Francisco, CA, USA) Author paper [8]
Tel: +1 415 514 0472; E-mail: shokat@cmp.ucsf.edu

Peter Parker (Cancer Research UK, London, UK) Author paper [9]
Tel: +44 20 7269 3513; E-mail: peter.parker@cancer.org.uk

Stephen Frye (University of North Carolina, Chapel Hill, NC, USA) Commentary author
Tel: +1 919 843 5486; E-mail: sfrye@email.unc.edu


[10] Cell Biology: Targeting muscle disorders
DOI: 10.1038/ncb1884

A molecular link between the loss of function of the enzyme MIP/MTMR14 and the muscle defects in mice is reported online this week in Nature Cell Biology. The finding points towards new potential therapeutic targets for certain types of hereditary muscle disorders.

Autosomal centronuclear myopathy belongs to a class of genetic muscle disorders characterized by severe alteration of skeletal muscle structure and metabolism. Inactivating mutations in the gene that encodes the enzyme MIP/MTMR14 have previously been associated with autosomal centronuclear myopathy. Cheng-Kui Qu and colleagues now show that mice that lack MIP/MTMR14, which is essential for the modification of the signalling molecule phosphatidylinositol phosphate (PIP), displayed muscle weakness and fatigue and their muscles produced less contractile force. Rapid changes in levels of intracellular calcium are essential for muscle contraction, and the team showed that, in the absence of MIP/MTMR14, intracellular calcium was abnormally elevated due to accumulation of unmodified PIPs and their ability to bind and activate the calcium release channel RyR1 on intracellular calcium stores.

By providing evidence that fine regulation of the MIP substrates in muscle cells is crucial for maintenance of proper calcium levels and therefore for muscle performance, this study sheds light onto potential new therapy targets of myopathies associated with loss of MIP/MTMR14 function.

Author contact:
Cheng-Kui Qu (Case Western Reserve University, Cleveland, OH, USA)
Tel: +1 216 368 3361; E-mail: cxq6@case.edu or cheng-kui.qu@case.edu

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

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

[11] Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs
DOI: 10.1038/nbt.1543

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

[12] A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis
DOI: 10.1038/ncb1876

[13] The Patched dependence receptor triggers apoptosis through a DRAL–caspase-9 complex
DOI: 10.1038/ncb1880

[14] Replication stress induces sister-chromatid bridging at fragile site loci in mitosis
DOI: 10.1038/ncb1882

[15] The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities
DOI: 10.1038/ncb1883

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

[16] Mechanistic and structural insights into the proteolytic activation of Vibrio cholerae MARTX toxin
DOI: 10.1038/nchembio.178

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

[17] Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests
DOI: 10.1038/ng.344

[18] SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy
DOI: 10.1038/ng.378

[19] Mutations in the b-tubulin gene TUBB2B result in asymmetrical polymicrogyria
DOI: 10.1038/ng.380

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

[20] Structural reactivation in plate tectonics controlled by olivine crystal anisotropy
DOI: 10.1038/ngeo528

[21] Vertical mantle flow associated with a lithospheric drip beneath the Great Basin
DOI: 10.1038/ngeo526

[22] Oceanic forcing of the Marine Isotope Stage 11 interglacial
DOI: 10.1038/ngeo527

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

[23] Local ordering and electronic signatures of submonolayer water on anatase TiO2(101)
DOI: 10.1038/nmat2466

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

[24] Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome
DOI: 10.1038/nm.1965

[25] A shear gradient–dependent platelet aggregation mechanism drives thrombus formation
DOI: 10.1038/nm.1955

[26] Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion
DOI: 10.1038/nm.1968

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

[27] Versatile P(acman) BAC Libraries for Transgenesis Studies in Drosophila melanogaster
DOI: 10.1038/nmeth.1331

[28] A toolkit for high-throughput, cross-species gene engineering in Drosophila
DOI: 10.1038/nmeth.1334

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

[29] New aspects of the metal–insulator transition in single-domain vanadium dioxide nanobeams
DOI:10.1038/nnano.2009.141

NATURE PHOTONICS (http://www.nature.com/nphoton)

[30] High-performance crosslinked colloidal quantum-dot light-emitting diodes
DOI:10.1038/nphoton.2009.92

[31] Manipulation of multiphoton entanglement in waveguide quantum circuits
DOI:10.1038/nphoton.2009.93

[32] Rapid and precise absolute distance measurements at long range
DOI:10.1038/nphoton.2009.94

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

[33] Vortex nucleation as a case study of symmetry breaking in quantum systems
DOI: 10.1038/nphys1277

[34] Near-field electrical detection of optical plasmons and single-plasmon sources
DOI: 10.1038/nphys1284

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

[35] E2 interaction and dimerization in the crystal structure of TRAF6
DOI: 10.1038/nsmb.1605

[36] The N-terminal domain of GluR6-subtype glutamate receptor ion channels
DOI: 10.1038/nsmb.1613

[37] Loss of the Mili-interacting Tudor domain–containing protein-1 activates transposons and alters the Mili-associated small RNA profile
DOI: 10.1038/nsmb.1615

***************************************************************************************************************
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.

ARGENTINA
Rosario: 20

AUSTRALIA
Clayton: 25
Melbourne: 25

AUSTRIA
Vienna: 12, 19, 37

BURKINA FASO
Ouagadougou: 1

CAMEROON
Buea: 1

CANADA:
Calgary: 24
London: 24
Montreal: 4
Vancouver: 7

CHINA
Wuhan: 23

DENMARK
Copenhagen: 11, 12
Hoersholm: 12

FRANCE
Caen: 19
Grenoble: 37
Lyon: 13
Marseille: 19
Montpellier: 20
Paris: 1, 19, 33
Rennes: 19
Sophia Antipolis: 20
Villejuif: 15

GAMBIA
Banjul: 1

GERMANY
Bielefeld: 12
Dortmund: 12
Dresden: 28
Hamburg: 1
Heidelberg: 12, 37
Jena: 3
Munich: 18
Wurzburg: 12

GHANA
Accra: 1
Kumasi: 1

IRELAND
Dublin: 3

ITALY
Milan: 18
Parma: 18
Rome: 1
Trieste: 18

JAPAN
Guangzhou: 26
Hyogo: 5
Kumamoto: 26
Kyoto: 25, 37
Nagoya: 17
Saitama: 5
Shiga: 2
Tokyo: 2, 17
Tsukuba: 17
Yokohama: 2

KENYA
Kilifi: 1

MALAWI
Blantyre: 1

MALI
Bamako: 1

NETHERLANDS
Amsterdam: 3, 7
Den Haag: 19

NIGERIA
Ibadan: 1

PAPUA NEW GUINEA
Madang: 1

PORTUGAL
Aveiro: 3

SENEGAL
Dakar: 1

SOUTH KOREA
Gyeonggi-Do: 30
Gyungbuk: 34

SPAIN
Barcelona: 33
Madrid: 9

SRI LANKA
Colombo: 1

SUDAN
Khartoum: 1

SWEDEN
Stockholm: 1

SWITZERLAND
Bern: 31

TANZANIA
Moshi: 1
Dar es Salaam: 1

THAILAND
Bangkok: 1

UNITED KINGDOM
Aberdeen: 3
Bristol: 22, 31
Cambridge: 1
Exeter: 3
Glasgow: 22
Hertfordshire: 1
Hinxton: 3
London: 1, 3, 9, 22, 23
Newcastle: 3, 18, 22
Oxford: 1, 14, 19
Sheffield: 3
Southampton: 22

UNITED STATES OF AMERICA

Arizona
Tempe: 21

California
Berkeley: 8, 27, 35
La Jolla: 13, 36
Oakland: 27
San Francisco: 8
Santa Barbara: 4
Stanford: 3, 16

Colorado
Boulder: 32

Connecticut
Branford: 3
Farmington: 10
New Haven: 6

Georgia
Atlanta: 16

Illinois
Chicago: 24, 27
Urbana: 3

Iowa
Iowa City: 3

Louisiana
New Orleans: 23

Maryland
Baltimore: 1
Bethesda: 35, 36

Massachusetts
Boston: 3, 11
Cambridge: 3, 21, 33

Michigan
East Lansing: 1

Minnesota
Minneapolis: 3

Montana
Kansas City: 10

New Jersey
Princeton: 23

New York
New York: 11, 19, 35
Stony Brook: 3

North Carolina
Durham: 3

Ohio
Cleveland: 10

Pennsylvania
Philadelphia: 6, 7

Texas
Houston: 3, 21, 27, 35

Utah
Logan: 4
Salt Lake City: 35

Washington
Seattle: 7, 29

Wisconsin
Madison: 8, 10

VIETNAM
Ho Chi Minh City: 1

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@natureny.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)
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Tel: +1 212 726 9284; E-mail: biotech@natureny.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@boston.nature.com

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

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

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

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

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

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