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Article Released Sun-28th-June-2009 19:57 GMT
Contact: Ruth Institution: Nature Publishing Group
 Immunology: Uncovering allergy bias

Summaries of newsworthy papers include Stopping the pumps in chemotherapy-resistant tumours, Mississippi drowning, Genetic variants associated with kidney stones, Solid-state quantum circuits, Mystery solved for immunoglobulin D role, Future forest changes, Efficiently moving through chemical space, Tropical rain shift 600 years ago

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 28 June 2009

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

This press release contains:

· Summaries of newsworthy papers:

Biotechnology: Stopping the pumps in chemotherapy-resistant tumours

Geoscience: Mississippi drowning

Genetics: Genetic variants associated with kidney stones

Chemical Biology: Metabolism in motion

Nature: Solid-state quantum circuits

Immunology: Mystery solved for immunoglobulin D role

Geoscience: Future forest changes

Chemical Biology: Efficiently moving through chemical space

Geoscience: Tropical rain shift 600 years ago

And finally…Immunology: Uncovering allergy bias

· 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.

[1] Biotechnology: Stopping the pumps in chemotherapy-resistant tumours
DOI: 10.1038/nbt.1547

A novel type of artificial drug delivery system that blocks cancer cells’ ability to expel chemotherapy and thereby acquire drug resistance is published online this week in Nature Biotechnology. In mice, this approach successfully inhibits the growth of drug-resistant colon, breast and uterine tumours and substantially extends life expectancy.

Himanshu Brahmbhatt and colleagues’ technique relies on minicells – empty, lifeless bacteria without genetic material – which can be filled with different types of drug. Mice were sequentially given two sets of minicells – the first filled with small RNA molecules to block production of the pumps that confer drug-resistance, and the second one loaded with toxic chemotherapy drugs to kill the tumour cells with disabled pumps.

Since the drugs are not released into general circulation, they can kill cancer cells at much lower dosage than normally required, thus avoiding undesirable side effects.

Author contacts:
Himanshu Brahmbhatt (EnGeneIC, Sydney, Australia)
Tel: +61 94 205 833; E-mail: hbrahmbhatt@engeneic.com

Daniel Anderson (Massachusetts Institute of Technology, Cambridge, MA, USA) N&V author
Tel: +1 617 258 6843; E-mail: dgander@mit.edu


[2] Geoscience: Mississippi drowning
DOI: 10.1038/ngeo553

Sediments deposited in the Mississippi delta cannot keep up with regional sea-level rise, suggests a study published online in Nature Geoscience. The researchers propose that the imbalance makes the submergence of the delta inevitable.

Michael Blum and Harry Roberts examined rates of sediment deposition in the Mississippi delta over the past 12,000 years and found that the Mississippi carried substantially more sediments before dam building started. They estimated that 18–24 billion tons of sediment would be required by 2100 to sustain the existing surface area of the Mississippi delta as sea levels rise. This exceeds current supply in the Mississippi river.

The researchers suggest that without an increase in sediment load, 10,000 to 13,500 square kilometres of deltaic land will be lost by 2100.

Author contacts:
Michael Blum (Louisiana State University, Baton Rouge, LA, USA)
Tel: +1 713 431 7554; E-mail: mblum@lsu.edu

Harry Roberts (Louisiana State University, Baton Rouge, LA, USA)
Tel: +1 225 578 2964; E-mail: hrober3@lsu.edu


[3] Genetics: Genetic variants associated with kidney stones
DOI: 10.1038/ng.404

Common genetic variants are associated with an increased risk of kidney stone disease, according to a study published online in this week’s Nature Genetics.

Kidney stone disease is a common disorder in the West and although it has a clear heritable component, common genetic risk factors had not yet been discovered.

Gudmar Thorleifsson and colleagues examined the genomes of 46,283 individuals and found that common variants within the CLDN14 gene are significantly associated with kidney stone disease. Individuals with certain CLDN14 variants can have a slightly increased risk of developing kidney stone disease compared to individuals who do not have the risk-associated variants.

The CLDN14 gene encodes a protein that likely regulates important cellular functions in the kidney, although further research is needed to determine how this protein might affect kidney stone formation.

Author contact:
Gudmar Thorleifsson (DeCODE, Reykjavik, Iceland)

Please contact this author through the following press officer:
Edward Farmer (DeCODE, Reykjavik, Iceland)
Tel: +44 779 601 0107; E-mail: edward.farmer@decode.is


[4] Chemical Biology: Metabolism in motion
DOI: 10.1038/nchembio.186

A quantitative and comprehensive investigation of enzyme reactions within cells is published online in this week’s Nature Chemical Biology. The findings provide the groundwork to ask more specific questions about how cells interact with their natural environment and how they control their own metabolism.

Cellular metabolism includes the creation and consumption of small molecules, or metabolites, that are used in creating proteins, the cell membrane, and in many other biological processes. The reactions for these biological processes are facilitated by enzymes.

Metabolites are often studied by determining relative concentrations of various molecules – the amount of one compound in comparison to another. Joshua Rabinowitz and colleagues used several metabolomic analysis tools to determine the absolute concentration, or the specific amount of compounds in cells independent of any other molecules. By comparing these concentrations to a database of known enzyme parameters, the scientists were able to tell which of the cell’s molecules are constantly being used in reactions, and which are likely being used to respond to other factors such as whether the cell is actively growing, or under attack.

Author contact:
Joshua Rabinowitz (Princeton University, NJ, USA)
Tel: +1 609 258 8985; E-mail: joshr@princeton.edu


[5] Nature: Solid-state quantum circuits
DOI: 10.1038/nature08121

An electrically controlled, solid-state quantum processor has been put through its paces by executing two quantum algorithms. The results are revealed in this week's Nature.

The superconducting processor, reported by Leonardo DiCarlo and colleagues, represents an important step in quantum computing with integrated circuits. Quantum processors based on a few quantum bits have been demonstrated before using nuclear magnetic resonance, cold ion traps and optical systems, but making a solid-state processor proved difficult.

The current prototype contains just two quantum bits, but holds promise for a fully scalable technology.

Author contact:
Leonardo DiCarlo (Yale University, New Haven, CT, USA)
Tel: +1 617 620 4343; E-mail: leonardo.dicarlo@yale.edu


[6] Immunology: Mystery solved for immunoglobulin D role
DOI: 10.1038/ni.1748

The function of the antibody called immunoglobulin D has puzzled immunologists for years. A study in Nature Immunology reports that immunoglobulin D helps combat upper respiratory infections.

Andrea Cerutti and colleagues show antibody-producing cells located in tonsils and upper airway tissues release immunoglobulin D (IgD). IgD then recognizes bacteria and other disease-causing microbes. IgD-bound bacteria trigger immune cells known as basophils to release fever-inducing agents and a variety of antimicrobial substances to rid the infectious agent.

This work therefore places IgD antibodies as a foot soldier in the immune arsenal against respiratory infections.

Author contact:
Andrea Cerutti (Weill Medical College of Cornell University, New York, NY, USA)
Tel: +1 212 746 6396; E-mail: acerutti@med.cornell.edu


[7] Geoscience: Future forest changes
DOI: 10.1038/ngeo555

Even if climate change is halted, ecosystems will probably continue to change for a long time, according to a study published online this week in Nature Geoscience. The work suggests that our commitment to future changes in ecosystems through past changes in climate needs to be taken into account when determining levels of ‘dangerous climate change’.

Chris Jones and colleagues analysed simulations with a coupled climate–vegetation model to investigate long-term effects of climatic changes on terrestrial ecosystems. They ran a number of climate-change simulations but stabilized the climate in each run at a different level of atmospheric greenhouse gases. In their simulations, forest coverage continues to change significantly for decades after the climatic boundary conditions have been held constant.

The authors conclude that substantial reduction in tropical forest coverage and spreading of high-latitude forests could be inevitable before the ecosystem changes are observed.

Author contact:
Chris Jones (Met Office Hadley Centre, Exeter, UK)
Tel: +44 1392 884514; E-mail: chris.d.jones@metoffice.gov.uk


[8] & [9] Chemical Biology: Efficiently moving through chemical space
DOI: 10.1038/nchembio.187
DOI: 10.1038/nchembio.188

A new user-friendly software tool for navigating chemical space and an application of this tool in identifying drug leads more efficiently are reported in two papers online this week in Nature Chemical Biology.

Chemical space – all possible chemical molecules – is enormous and it can be difficult to easily understand how different chemicals relate to one another. Better understanding the connection between related chemical structures and their associated biological activity would help in efficiently identifying new drug leads.

Herbert Waldmann and colleagues developed a computer software program that creates trees in which a ‘branch’ starts from a complicated chemical structure and is gradually broken down to its simpler chemical components. By using biological activity data – for instance which chemicals in a large chemical library inhibit a particular enzyme – to guide the creation of these chemical trees, the authors are able to identify new inhibitors, which have significantly different chemical structures from the known inhibitors for particular drug targets.

Author contact:
Herbert Waldmann (Max-Planck Institute, Dortmund, Germany) Author paper [8] & [9]
Tel: +49 231 133 2400; Email: herbert.waldmann@mpi-dortmund.mpg.de


[10] Geoscience: Tropical rain shift 600 years ago
DOI: 10.1038/ngeo554

During the Little Ice Age, the Pacific section of the circumglobal tropical rainbelt was up to 500 km south of its present position. Published online in this week’s Nature Geoscience, these results indicate a very sensitive response of tropical rainfall patterns — which many people in Africa, Asia and South America rely on for subsistence agriculture — to small changes in Earth’s radiation budget.

Julian Sachs and colleagues use microbiological, molecular and isotopic analyses of lake sediments from three islands in the eastern, central and western equatorial Pacific Ocean, respectively, to determine wet and dry periods on each island. The periods of humidity they identify in the three locations suggest that the intertropical convergence zone — which marks the position of the most vigorous rainfall events — were substantially further south than today between about ad 1400 and 1850. At this time, European temperatures were relatively cool, possibly owing to low solar radiation.

Author contact:
Julian Sachs (University of Washington, Seattle, WA, USA)
Tel: +1 206 221 5630; E-mail: jsachs@u.washington.edu


[11] And finally…Immunology: Uncovering allergy bias
DOI: 10.1038/ni.1747

A gene that helps explain why some individuals are more likely to develop allergies is reported online in this week’s Nature Immunology. These findings increase our understanding of how immune cells that impact infectious, autoimmune, and allergic disease susceptibility are regulated.

‘Type 2’ immunity is necessary for resistance to parasites but can also lead to allergic reactions. A team led by Mark Bix and Masato Kubo trace the genetic bias underlying development of ‘type 2’ immunity to expression of the gene Mina.

Mina encodes a protein that blocks early expression of interleukin 4 (IL-4), a key molecule responsible for inducing allergic-like immune responses. Immune cells from allergic-prone mice express less Mina protein and consequently express IL-4 more readily than those from strains lacking this bias.

Author contacts:
Mark Bix (St. Jude Children’s Research Hospital, Memphis, TN, USA)
Tel: +1 901 595 5459; E-mail: mark.bix@stjude.org

Masato Kubo (RIKEN Yokohama Institute, Kanagawa, Japan)
Tel: +81 45 503 7047; E-mail: Raysolfc@rcai.riken.jp

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

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

[12] Regulation of the innate immune response by threonine phosphatase of Eyes absent
DOI: 10.1038/nature08138

[13] MicroRNA-Mediated Switching of Chromatin Remodeling Complexes in Neural Development
DOI: 10.1038/nature08139

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

[14] Multi-site assessment of precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma
DOI: 10.1038/nbt.1546

[15] Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins
DOI: 10.1038/nbt.1550

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

[16] Molecular printing
DOI: 10.1038/nchem.258

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

[17] The 8q24 cancer risk variant rs6983267 demonstrates long-range interaction with MYC in colorectal cancer
DOI: 10.1038/ng.403

[18] The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling
DOI: 10.1038/ng.406

[19] Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II
DOI: 10.1038/ng.405

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

[20] Essential function for the GTPase TC21 in homeostatic antigen receptor signaling
DOI: 10.1038/ni.1749

[21] Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair
DOI: 10.1038/ni.1758

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

[22] An omnidirectional retroreflector based on the transmutation of dielectric singularities
DOI: 10.1038/nmat2489

[23] Periodic rotation of magnetization in a non-centrosymmetric soft magnet induced by an electric field
DOI: 10.1038/nmat2492

[24] Selective positioning of organic dyes in a mesoporous inorganic oxide film
DOI: 10.1038/nmat2475

[25] Printed artificial cilia from liquid-crystal network actuators modularly driven by light
DOI: 10.1038/nmat2487

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

[26] Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system
DOI: 10.1038/nm.1980

[27] Targeted depletion of lymphotoxin-alpha–expressing TH1 and TH17 cells inhibits autoimmune disease
DOI: 10.1038/nm.1984

[28] Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease
DOI: 10.1038/nm.1987

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

[29] Self-assembled cationic peptide nanoparticles as an efficient antimicrobial agent
DOI:10.1038/nnano.2009.153

[30] Determination of protein structural flexibility by microsecond force spectroscopy
DOI:10.1038/nnano.2009.156

[31] Evaluation of nanoparticle immunotoxicity
DOI:10.1038/nnano.2009.175

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

[32] Resolving single cone inputs to visual receptive fields
DOI: 10.1038/nn.2352

[33] A trophic role for Wnt-Ror kinase signaling during developmental pruning in Caenorhabditis elegans
DOI: 10.1038/nn.2347

[34] A discrete alcohol pocket involved in GIRK channel activation
DOI: 10.1038/nn.2358

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

[35] Engineering the quantum transport of atomic wavefunctions over macroscopic distances
DOI: 10.1038/nphys1310

[36] Quantum error correction beyond qubits
DOI: 10.1038/nphys1309

[37] Stylus ion trap for enhanced access and sensing
DOI: 10.1038/nphys1311

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

[38] Structural determinants of gating in the TRPV1 channel
DOI: 10.1038/nsmb.1633

[39] The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo-active site in signaling
DOI: 10.1038/nsmb.1632

[40] Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP
DOI: 10.1038/nsmb.1607

[41] H3K64 trimethylation marks heterochromatin and is dynamically remodeled during developmental reprogramming
DOI: 10.1038/nsmb.1629

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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
Darlinghurst: 1
Kensington: 1
Sydney: 1

AUSTRIA
Vienna: 5

CANADA:
Calgary: 17
Montreal: 26
Sherbrooke: 5
Toronto: 15
Victoria: 14
Waterloo: 5

CHINA
Hangzhou: 29
Nanjing: 10

CZECH REPUBLIC
Brno: 6, 22

DENMARK
Ballerup: 3
Herlev: 3

FINLAND
Helsinki: 18
Jyvaskyla: 18
Oulu: 18

FRANCE
Kremlin Bicetre: 19
Strasbourg: 28, 41

GERMANY
Berlin: 26, 41
Dortmund: 8, 9
Düsseldorf: 26
Erlangen: 36, 37
Frankfurt am Main: 9
Freiburg: 41
Heidelberg: 19
Munich: 19
Potsdam: 10
Rostock: 19
Ulm: 19

ICELAND
Reykjavik: 3

ITALY
Brescia: 6
Naples: 19
Sesto Fiorentino: 35

JAPAN
Fukuoka: 33
Kyoto: 12, 36
Saitama: 33
Sendai: 23
Tokyo: 33, 36
Yokohama: 11

MEXICO
Mexico City: 38

NETHERLANDS
Amsterdam: 26
Eindhoven: 9, 25
Nijmegen: 3

SINGAPORE
Singapore: 22, 29

SOUTH AFRICA
Johannesburg: 9

SOUTH KOREA
Seoul: 24

SPAIN
Catalonia: 17
Madrid: 20
Salamanca: 20

SWEDEN
Malmo: 6

SWITZERLAND
Allschwil: 28
Basel: 8, 9, 41
Epalinges: 28
Zurich: 10

UNITED KINGDOM
Cambridge: 18
Exeter: 7
London: 25, 28
Oxford: 18, 40
St Andrews: 22
Sutton: 18
York: 36

UNITED STATES OF AMERICA

Alabama
Birmingham: 32

California
Berkeley: 32
La Jolla: 34
Los Angeles: 17
Novato: 14
San Diego: 4
San Francisco: 14, 27, 32, 39
Stanford: 13, 26

Colorado
Boulder: 37

Connecticut
New Haven: 5, 12

District of Columbia
Washington: 14

Georgia
Atlanta: 3

Illinois
Evanston: 16

Indiana
Indianapolis: 14
West Lafayette: 14

Iowa
Iowa City: 17

Louisiana
Baton Rouge: 2

Maryland
Bethesda: 14
Frederick: 31
Gaithersburg: 14
Silver Spring: 31

Massachusetts
Boston: 10, 14, 17, 19, 21
Cambridge: 14, 17, 30
Lexington: 14

Mississippi:
Jackson: 6

New Jersey
Princeton: 4

New Mexico
Albuquerque: 8, 9

New York
Cold Spring Harbor: 1
New York: 6, 14, 18

North Carolina
Chapel Hill: 14
Research Triangle: 31

South Carolina
Charleston: 29

Tennessee
Memphis: 11
Nashville: 14

Texas
College Station: 14
Houston: 2

Utah
Salt Lake City: 19

Washington
Seattle: 10, 11

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

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: chembio@boston.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@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)
Hugh Ash
Tel: +1 212 726 9627; E-mail: methods@natureny.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@natureny.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@natureny.com

About Nature Publishing Group (NPG):

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Keywords associated to this article: Biotechnology, Geoscience, Genetics, Chemical Biology, Nature, Immunology, Geoscience, Chemical Biology
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