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Article Released Sun-24th-August-2008 18:02 GMT
Contact: Ruth Institution: Nature Publishing Group
 Predisposition gene for childhood cancer

Summaries of newsworthy papers include Quantifying the Arctic carbon pool, Exploitative tricks of antibiotic-resistant bacteria, Domino drug action, Stem cells classified, Glaciers and river nutrients and A jolt to plume models?

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 24 August 2008

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This press release contains:

· Summaries of newsworthy papers:

Nature: Predisposition gene for childhood cancer

Geoscience: Quantifying the Arctic carbon pool

Nature: Exploitative tricks of antibiotic-resistant bacteria

Chemical Biology: Domino drug action

Nature: Stem cells classified

Geoscience: Glaciers and river nutrients

Geoscience: A jolt to plume models?

· 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: Predisposition gene for childhood cancer
DOI: 10.1038/nature07261

A gene responsible for the majority of inherited cases of a common childhood cancer is reported online this week in Nature. The finding promises to provide a springboard for developing new therapeutic strategies.

Neuroblastoma — a cancer of the nervous system — accounts for 15% of childhood cancer deaths and has bleak survival probabilities of less than 40%. There is a strong familial association and it was predicted over 30 years ago that there was a genetic element to the disease. John Maris and colleagues screened the genomes of 20 affected families, looking for single letter changes in the DNA code or SNPs. They identified inherited mutations in the gene encoding ALK, a tyrosine kinase receptor, as being responsible for causing the disease in the majority of families. Point mutations in this gene were also found in sporadic cases of neuroblastoma. The mutations mapped to a part of the receptor that cause it to be constantly active in promoting cell proliferation, explaining its ability to drive cancer.

The research opens the door for a long-sought-after molecular diagnostic test for predisposition to neuroblastoma, as well as identifying ALK as a promising drug target.

Author contact:
John Maris (The University of Pennsylvania School of Medicine, Philadelphia, PA, USA)
Tel: +1 215 590 5242; E-mail: maris@chop.edu


[2] Geoscience: Quantifying the Arctic carbon pool
DOI: 10.1038/ngeo284

The soils of the North American Arctic contain substantially more organic carbon than previously thought, according to a study published online this week in Nature Geoscience. Carbon stored in high-latitude soils could potentially be released to the atmosphere as CO2 or methane in response to climate change.

Chien-Lu Ping and colleagues used measurements of soil organic carbon to estimate the size of the entire North American Arctic soil organic carbon store. They sampled a wide range of landscapes, to at least 1 metre in depth, to provide a comprehensive assessment of the carbon pool in the region. Previous estimates of the Arctic carbon pool relied heavily on measurements conducted outside of the Arctic in the very top layers of the soil.

In his accompanying News and Views, Christian Beer says “Ping and colleagues calculate a total carbon content...equivalent to approximately one sixth of the current carbon content in the atmosphere. Releasing even a portion of this carbon…would have a significant impact on Earth’s climate”.

Author contact:
Chien-Lu Ping (University of Alaska, Fairbanks, AK, USA)
Tel: +1 907 746 9462; E-mail: pfclp@uaa.alaska.edu

News and Views contact:
Christian Beer (Max Planck Institute, Jena, Germany)
Tel: +49 3641 576281; E-mail: christian.beer@bgc-jena.mpg.de


[3] Nature: Exploitative tricks of antibiotic-resistant bacteria
DOI: 10.1038/nature07250

Antibiotic treatment may compromise the innate immunity of the intestine, a Nature study suggests. The finding may help explain why treating people with antibiotics can lead to increased infection with antibiotic-resistant bacteria, and points to potential therapies that may solve the problem.

Eric Pamer and colleagues found that antibiotic-treated mice had lower amounts of an intestinal antimicrobial protein, RegIII gamma, which can kill antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus (VRE). So therapies that increase levels of this protein may fend off infection with antibiotic-resistant bacteria, they suggest.

Infections caused by highly antibiotic-resistant bacteria, such as VRE, are an increasing menace in hospitalized patients. It’s been assumed that antibiotics kill off many different types of intestinal bacteria, opening up a nutrient-rich niche in which resistant bacteria can thrive. This study, however, suggests an alternative explanation whereby resistant bacteria exploit antibiotic-induced innate immune deficits.

Author contact:
Eric Pamer (Memorial Sloan-Kettering Cancer Center, New York, NY, USA)
Tel: +1 646 888 2679; E-mail: pamere@mskcc.org


[4] Chemical Biology: Domino drug action
DOI: 10.1038/nchembio.108

The antibiotic trimethoprim, used primarily for the treatment of urinary tract infections, works by an unexpected ‘domino effect’ in which two enzymes in a pathway are both inhibited by a single drug, according to a paper online this week in Nature Chemical Biology. The work reveals new insights into the mechanism of a clinically used drug and highlights the potential of looking at metabolic pathways to understand drug action.

Trimethoprim is known to inhibit a bacterial enzyme called dihydrofolate reductase (DHFR). By using a method for simultaneously measuring all of the folate-related chemicals in a bacterial cell, Joshua Rabinowitz and colleagues found that trimethoprim was blocking not just the activity of DHFR, but also another enzyme in folate metabolism. The second enzyme was not directly inhibited by trimethoprim. Instead, inhibiting DHFR caused accumulation of the substrate, dihydrofolate, which was an inhibitor of the second enzyme. Therefore, trimethoprim created a cascade of enzyme inhibition.

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


[5] Nature: Stem cells classified
DOI: 10.1038/nature07213

A new method for classifying stem cells should help researchers distinguish one stem cell type from the next.

There are many types of ‘stem cell’ all bound under the same umbrella term by their ability to self renew and differentiate into other more specialized cell types. However, they occur in different parts of the body at different times of life, and various methods are used to isolate them; alongside a paucity of reliable markers, this makes their classification difficult.

The new technique, devised by Jeanne Loring and colleagues, is based on a database of transcriptional profiles. In this week's Nature, they show how it can be used to classify reliably a variety of human stem cell types including embryonic, neural and induced pluripotent stem cells.

The technique is timely given the anticipated value of human stem cells to regenerative medicine, and the team hopes that their method will serve as a useful tool for characterization and classification.

Author contact:
Jeanne Loring (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 7191; E-mail: jloring@scripps.edu


[6] Geoscience: Glaciers and river nutrients
DOI: 10.1038/ngeo280

The concentration of nutrients entering coastal watersheds in southeast Alaska is in part controlled by the extent of glacial coverage in the river catchment area, according to research published online this week in Nature Geoscience. These rivers supply coastal ecosystems with nutrients and fresh water. Changing levels of glacial coverage in southeast Alaska could therefore potentially affect nutrient concentrations in nearby rivers and alter the nutrient dynamics of coastal ecosystems along the Gulf of Alaska.

Eran Hood and Durelle Scott sampled three adjacent watersheds along the Gulf of Alaska with differing levels of glacial coverage. They found that higher levels of glacial coverage were associated with increased phosphorous input to the rivers, whereas smaller glacial extent led to more organic matter entering the watershed. Areas of recent glacial retreat had temporarily increased levels of nitrogen, owing to the colonization of plants on the newly exposed terrain.

Author contact:
Eran Hood (University of Alaska Southeast, Juneau, AK, USA)
Tel: +1 907 796 6244; E-mail: eran.hood@uas.alaska.edu

[7] Geoscience: A jolt to plume models?
DOI: 10.1038/ngeo281

Extensive rock deposits at the base of the Emeishan large igneous province in China — previously interpreted as sediments shed from a rapidly uplifting dome — formed as a result of interaction between lava and sea water, suggests a paper online this week in Nature Geoscience. These findings challenge a major assumption of models that implicate a mantle plume in triggering the Emeishan flood basalt eruptions ~260 million years ago.

Ingrid Ukstins Peate and Scott Bryan conducted detailed geological fieldwork and documented the physical characteristics of rocks at the base of the Emeishan province. They found that the earliest eruptions occurred at or near sea level. They found no evidence of extensive doming and uplift of the land surface prior to the eruptions — a hallmark of plume models.

The team concludes that the Emeishan province did not undergo plume-induced uplift before the onset of volcanism.

Author contacts:
Ingrid Ukstins Peate (University of Iowa, Iowa City, IA, USA)
Tel: +1 319 335 1824; E-mail: ingrid-peate@uiowa.edu

Scott Bryan (Kingston University, Kingston Upon Thames, UK)
Tel: +44 020 8547 7497; E-mail: s.bryan@kingston.ac.uk

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

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

[8] STING is an endoplasmic reticulum adaptor that facilitates innate immune signaling
DOI: 10.1038/nature07313

[9] TMEM16A confers receptor-activated calcium-dependent chloride conductance
DOI: 10.1038/nature07317

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

[10] Photoswitchable fluorescent proteins enable monochromatic multilabel imaging and dual color fluorescence nanoscopy
DOI: 10.1038/nbt.1493

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

[11] Identification of a copper-binding metallothionein in pathogenic mycobacteria
DOI: 10.1038/nchembio.109

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

[12] Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease
DOI: 10.1038/ng.215

[13] A common sequence motif associated with recombination hot spots and genome instability in humans
DOI: 10.1038/ng.213

[14] MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity
DOI: 10.1038/ng.225

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

[15] Notch integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity
DOI: 10.1038/ni.1649

[16] Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin
DOI: 10.1038/ni.1646

[17] Sensing of ‘danger signals’ and pathogen-associated molecular patterns defines binary signaling pathways ‘upstream’ of Toll
DOI: 10.1038/ni.1643

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

[18] Highly compressed ammonia forms an ionic crystal
DOI: 10.1038/nmat2261

[19] Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells
DOI: 10.1038/nmat2269

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

[20] The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A
DOI: 10.1038/nm.1857

[21] Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption
DOI: 10.1038/nm.1860

[22] An efficient and versatile system for acute and chronic modulation of renal tubular function in transgenic mice
DOI: 10.1038/nm.1865

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

[23] Patterning of light-emitting conjugated polymer nanofibres
DOI: 10.1038/nnano.2008.232

[24] A microcavity-controlled, current-driven, on-chip nanotube emitter at infrared wavelengths
DOI: 10.1038/nnano.2008.241

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

[25] Requirement for COUP-TFI and II in the temporal specification of neural stem cells in central nervous system development
DOI: 10.1038/nn.2168

[26] Age-dependent epigenetic control of differentiation inhibitors is a critical determinant of remyelination efficiency
DOI: 10.1038/nn.2172

[27] Divergence of fMRI and neural signals in V1 during perceptual suppression in the awake monkey
DOI: 10.1038/nn.2173

[28] Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex
DOI: 10.1038/nn.2177

[29] GABAergic synapses are formed without the involvement of dendritic protrusions
DOI: 10.1038/nn.2180

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

[30] How to make a bilayer exciton condensate flow
DOI: 10.1038/nphys1055

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

[31] A proposed OB-fold with a protein-interaction surface in Candida albicans telomerase protein Est3
DOI: 10.1038/nsmb.1471

[32] The Est3 protein associates with yeast telomerase through an OB-fold domain
DOI: 10.1038/nsmb.1472

[33] Structure of the DBL3x domain of pregnancy-associated malaria protein VAR2CSA complexed with chondroitin sulfate A
DOI: 10.1038/nsmb.1479

***************************************************************************************************************
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
St Lucia: 7

AUSTRIA
Hall: 14
Innsbruck: 14

BELGIUM
Ghent: 1

CANADA:
Montreal: 12
Toronto: 4, 12

FRANCE
Paris: 14
Strasbourg: 17

GERMANY
Aachen: 20
Berlin: 5
Datteln: 14
Erlangen: 14
Esslingen: 14
Goettingen: 10
Hamburg: 5, 14
Heidelberg: 22
Kiel: 5
Mannheim: 22
Martinsried: 29
Munich: 22

ISRAEL
Rehovot: 28
Tel Aviv: 5, 28

ITALY
Genoa: 1
Lecce: 23
Rome: 1

JAPAN
Saitama: 25
Tochigi: 15
Tokyo: 15, 21, 25
Tokushima: 15
Tsukuba: 15
Yokohama: 15

NETHERLANDS
Nijmegen: 21
Utrecht: 14

SOUTH KOREA
Busan: 21
Daejeon: 21
Jeollanamdo: 21
Seoul: 9, 21

SWEDEN
Uppsala: 12

SWITZERLAND
Reinach: 20
Zurich: 22

TAIWAN
Kaohsiung: 20

UNITED KINGDOM
Cambridge: 14, 18, 26
London: 9
Oxford: 13
Sheffield: 14
St Andrews: 18
Surrey: 7

UNITED STATES OF AMERICA

Alaska
Fairbanks: 2
Juneau: 6
Palmer: 2

California
Berkeley: 16
Davis: 5, 16
Irvine: 5
La Jolla: 1, 3, 5, 32
Los Angeles: 12, 28
Novato: 5
Orange: 5
San Diego: 5
Stanford: 16, 22

Colorado
Boulder: 19

Connecticut
New Haven: 12, 20

Florida
Miami: 8, 20

Iowa
Iowa City: 7

Maryland
Baltimore: 12
Bethesda: 27
Frederick: 5
Rockville: 33

Massachusetts
Boston: 5, 12, 20, 22
Cambridge: 12, 13, 16

Michigan
Ann Arbor: 31

Minnesota
Minneapolis: 12

New Jersey
Newark: 11
Piscataway: 26
Princeton: 4

New York
Addison: 2
Ithaca: 13
New York: 3, 11, 20, 26, 28, 31
Yorktown Heights: 24

Pennsylvania
Hershey: 33
Philadelphia: 1
Pittsburgh: 12
University Park: 22

Texas
Austin: 30
Houston: 3, 32

Virginia
Blacksburg: 6
Charlottesville: 2
Richmond: 26

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Tel: +1 212 726 9311; E-mail: natgen@natureny.com

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Tel: +1 212 726 9372; E-mail: immunology@natureny.com

Nature Materials (London)
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Tel: +44 20 7843 4593; E-mail: materials@nature.com

Nature Medicine (New York)
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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

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

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

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