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Article Released Sun-21st-December-2008 18:36 GMT
Contact: Ruth Institution: Nature Publishing Group
 Stem cells and disease modelling

Summaries of newsworthy papers include Breaking through the barrier, Clearing plaques in blood vessels in Alzheimer’s disease, Agriculture could increase the release of carbon dioxide from rivers, Prions and smell, Rotoviruses stick to sugars, Tropical volcanic eruptions drive cooling in the tropics, The twisted history of snail shells

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 21 December 2008

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

This press release contains:

· Summaries of newsworthy papers:

Nature: Stem cells and disease modelling

Biotechnology: Breaking through the barrier

Cell Biology: Clearing plaques in blood vessels in Alzheimer’s disease

Geoscience: Agriculture could increase the release of carbon dioxide from rivers

Neuroscience: Prions and smell

Chemical Biology: Rotoviruses stick to sugars

Geoscience: Tropical volcanic eruptions drive cooling in the tropics

And finally… Nature: The twisted history of snail shells

· 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.

Warning: This document, and the Nature journal papers to which it refers, may contain information that is price sensitive (as legally defined, for example, in the UK Criminal Justice Act 1993 Part V) with respect to publicly quoted companies. Anyone dealing in securities using information contained in this document, or in advance copies of a Nature journal’s content, may be guilty of insider trading under the US Securities Exchange Act of 1934.

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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] Nature: Stem cells and disease modelling
DOI: 10.1038/nature07677

Scientists have generated pluripotent stem cells from the skin cells of a patient with spinal muscular atrophy (SMA), and show that these cells can be used to model the specific pathology for inherited diseases. The research, published online in Nature this week, represents a promising tool for understanding disease at a cellular level and also for drug screening.

SMA is a genetic disorder, and one of the most common inherited forms of neurological disease in children. Allison Ebert and colleagues use skin cells from a child with SMA and his unaffected mother. They show, for the first time, that human induced pluripotent stem cells can be used to model the disease mechanisms, as the differentiated neural tissue and motor neurons derived from these cells maintain the disease phenotype. The cultures also responded to drugs known to increase the levels of the protein associated with the disease. This creates a tool for studying disease pathology at the cellular level, and for developing and screening new drugs and therapies.

Author contact:
Allison Ebert (University of Wisconsin-Madison, WI, USA)
Tel: +1 608 262 7331; E-mail: ebert@waisman.wisc.edu


[2] Biotechnology: Breaking through the barrier
DOI: 10.1038/nbt.1515

A non-invasive method to deliver genes to the central nervous system in mice is reported online this week in Nature Biotechnology. The research could one day lead to new therapies for neurodegenerative disorders such as Lou Gehrig’s disease.

Getting drugs or genes into the brain and spinal cord to treat neurodegenerative diseases is problematic because of the blood–brain barrier (BBB)—a tight wall of cells that restricts the movement of molecules between the blood and neural tissue. Until now, no viruses or viral vectors have been found that cross through the BBB after intravascular injection. Brian Kaspar and colleagues show that a particular strain of virus – AAV9 – can be used to carry genes across the BBB in mice and into the brain cells beyond. The team also find that the virus targets cells of the spinal cord and so can be used to deliver genes to widespread regions of the central nervous system.

It is hoped that the technology could one day be used to introduce working copies of the genes that are damaged in diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease.

Author contact:
Brian Kaspar (Nationwide Children’s Hospital, Columbus, OH, USA)
Tel: +1 614 722 5085; E-mail: Brian.Kaspar@NationwideChildrens.org

Additional contact for comment on paper:
Pedro Lowenstein (University of California Los Angeles, CA, USA)
Tel: +1 310 423 7330; E-mail: Pedro.Lowenstein@cshs.org


[3] Cell Biology: Clearing plaques in blood vessels in Alzheimer’s disease
DOI: 10.1038/ncb1819

Scientists have uncovered the role of two critical proteins that negatively affect the clearance of amyloid beta in the brain, the accumulation of which is thought to lead to the development of Alzheimer’s disease. The research, published online in Nature Cell Biology this week, identifies potential therapeutic targets for treating defects associated with cognitive decline and faulty clearance of amyloid beta in brain blood vessels.

The exact causes of Alzheimer’s disease are still unclear. Previous studies have shown that the disease is associated with plaques or tangles of protein fragments in the brain. These fragments, known as amyloid beta, accumulate in small arteries of the brain and contribute to the defects that occur during Alzheimer’s disease.

Berislav Zlokovic and colleagues examined the effect of two interacting proteins, SRF and MYOCD, which bind to DNA and control gene expression. They show that these proteins are highly expressed in blood vessel cells in Alzheimer’s patients and in mouse models of the disease, and that high levels of these proteins prevent the clearance of amyloid beta from vessel walls. These proteins act by activating a third protein that regulates gene expression and is known to prevent the expression of the lipoprotein receptor protein 1, a factor that promotes clearance of amyloid beta in blood vessel cells.

Author contact:
Berislav Zlokovic (University of Rochester, NY, USA)
Tel: +1 585 273 3131; E-mail: berislav_zlokovic@urmc.rochester.edu

Additional media contact:
Tom Rickey (University of Rochester, NY, USA)
Tel: +1 585 275 7954; E-mail: Tom_Rickey@URMC.Rochester.edu


[4] Geoscience: Agriculture could increase the release of carbon dioxide from rivers
DOI: 10.1038/ngeo391

Intensive agriculture decreases the chemical complexity of dissolved organic matter in nearby rivers, suggests a paper online in Nature Geoscience. Simplification of organic material could affect the release of carbon dioxide from river systems.

Henry Wilson and colleagues examined the quality of organic matter dissolved in 34 rivers in Ontario, Canada, along a gradient of minimal-to-intensive agriculture. The researchers found that higher levels of cropland cultivation and usage resulted in a decrease in the structural complexity of the dissolved organic matter in the river. They suggest that the reduced complexity of organic matter could lead to elevated rates of microbial carbon-processing. As a result organic matter may be more readily removed from rivers — either through storage in sediments or through release into the atmosphere as carbon dioxide.

Author contact:
Henry Wilson (Trent University, Peterborough, Ontario, Canada)
Tel: +1 705 748 101; E-mail: henrywilson@trentu.ca


[5] Neuroscience: Prions and smell
DOI: 10.1038/nn.2238

Prions help us to distinguish odours, finds a study published online this week in Nature Neuroscience. The research provides tantalizing clues as to the normal function of these mysterious proteins.

Prions are proteins involved in devastating diseases such as Creutzfeld-Jacob Disease (CJD) and Bovine Spongiform Encephalopathy (BSE) but little is known about how they normally function. Stuart Firestein and colleagues studied transgenic mice that lacked the prion protein in neurons of the olfactory system – the part of the brain that controls our sense of smell. They find that these mice could still detect odours, but were deficient in some odour-guided behaviours such as finding buried food or an odour discrimination task. Replacing the protein in olfactory bulb neurons alone rescued this odour discrimination defect. The authors also find specific changes in the communication among neurons in the olfactory bulb of these transgenic mice.

It is not clear how these changes in odour discrimination relate to the pathology of prion diseases, but the research provides greater understanding of these enigmatic proteins.

Author contact:
Stuart Firestein (Columbia University, New York, NY, USA)
Tel: +1 212 854 4531; Email: sjf24@columbia.edu


[6] Chemical Biology: Rotoviruses stick to sugars
DOI: 10.1038/nchembio.134

Sugar molecules on the surface of host cells are linked to all rotovirus infections, according to research published online in Nature Chemical Biology this week. The unexpected finding promises to aid efforts to develop treatments for this dangerous virus.

Rotoviruses attack cells of the gut and are the leading cause of severe diarrhea in young children. Many animals can be treated for the virus with a protein called sialidase, which cuts sialic acids – a specific group of sugar molecules – from the cell surface. Unsuccessful attempts to treat other rotoviruses with this protein resulted in the rotoviruses being grouped into two classes of ‘sialidase-sensitive’ and ‘sialidase-insensitive’ strains.

Mark von Itzstein and colleagues use nuclear magnetic resonance and cellular assays to demonstrate that a ‘sialidase-insensitive’ virus strain, Wa, does recognize sialic acids and in fact this interaction increases its ability to infect the host cell. The research demands a rethinking of how rotoviruses work and may point to new treatments for the infection.

Author contact:
Mark von Itzstein (Griffith University, Brisbane, Australia)
Tel: +61 7 5552 7025, E-mail: m.vonitzstein@griffith.edu.au


[7] Geoscience: Tropical volcanic eruptions drive cooling in the tropics
DOI: 10.1038/ngeo393

Over the past 450 years, the aerosols and gases emitted from volcanic eruptions in the tropics have caused tropical sea-surface temperatures to cool for years after the eruption, according to a study online in Nature Geoscience. Although a similar relationship has been observed in the high northern-latitudes, this is the first time a consistent pattern has been observed in the tropics.

Rosanne D’Arrigo and colleagues compiled temperature records from corals and tree rings throughout the Indian and Pacific oceans. Like the well-known cooling that followed the 1815 Tambora eruption in Indonesia, a clear correlation was found between the most explosive volcanic eruptions at low latitudes and decreased sea-surface temperatures in the following years. The team concludes that the relationship between eruptions and sea-surface cooling highlights the sensitivity of tropical temperatures to the amount of sunlight reaching the Earth’s surface.

Author contact:
Rosanne D’Arrigo (Columbia University, New York, NY, USA)
Tel: +1 845 365 8617; E-mail: rdd@ldeo.columbia.edu


[8] And finally… Nature: The twisted history of snail shells
DOI: 10.1038/nature07603

The direction of snail shell coiling is regulated by nodal, a gene well known for its role in vertebrate body patterning. The find, reported online in this week’s Nature, sheds light on the evolutionary history of this signalling pathway.

Cristina Grande and Nipam Patel show that evolutionary equivalents of the nodal gene are present in two species of snail. The gene is expressed asymmetrically during embryonic development in a manner correlating with the direction of shell coiling, and blocking the pathway produces animals with non-coiled shells.

Until now, nodal was generally regarded as an invention of the deuterostomes — the group of animals that includes vertebrates, starfish and some worms — where it influences left–right asymmetry. The new data indicate that the role of the gene in left–right asymmetry is not deuterostome-specific and may be an ancestral feature of bilaterally symmetrical animals.

Author contact:
Nipam Patel (University of California at Berkeley, CA, USA)
Tel: +1 510 643 4605; E-mail: nipam@uclink.berkeley.edu

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

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

[9] Artificial nanopores that mimic the transport selectivity of the nuclear pore complex
DOI: 10.1038/nature07600

[10] A stress-responsive RNA switch regulates VEGFA expression
DOI: 10.1038/nature07598

[11] Direct observation of the nanoscale dynamics of membrane lipids in a living cell
DOI: 10.1038/nature07596

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

[12] Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a potential target for glioblastoma therapy
DOI: 10.1038/nbt.1513

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

[13] UNC‑6 (netrin) orients the invasive membrane of the anchor cell in C. elegans
DOI: 10.1038/ncb1825

[14] Mouse differentiating spermatogonia can generate germinal stem cells in vivo
DOI: 10.1038/ncb1826

[15] Topoisomerase IIa controls the decatenation checkpoint
DOI: 10.1038/ncb1828

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

[16] Cytochrome bd confers nitric oxide resistance to Escherichia coli
DOI: 10.1038/nchembio.135

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

[17] Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs
DOI: 10.1038/ng.266

[18] The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation
DOI: 10.1038/ng.268

[19] Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3’ exons of TACSTD1
DOI: 10.1038/ng.283

[20] Common variants in the NLRP3 region contribute to Crohn’s disease susceptibility
DOI: 10.1038/ng.285

[21] Accelerated genetic drift on chromosome X during the human dispersal out of Africa
DOI: 10.1038/ng.303

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

[22] Unprecedented recent warming of surface temperatures in the eastern tropical Pacific Ocean
DOI: 10.1038/ngeo390

[23] Upper mantle seismic anisotropy resulting from pressure-induced slip transition in olivine
DOI: 10.1038/ngeo389

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

[24] Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils
DOI: 10.1038/ni.1686

[25] The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells
DOI: 10.1038/ni.1690

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

[26] MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis
DOI: 10.1038/nm.1889

[27] Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder
DOI: 10.1038/nm.1897

[28] Gamma-secretase inhibitors reverse glucocorticoid resistance in T cell acute lymphoblastic leukemia
DOI: 10.1038/nm.1900

[29] Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production
DOI: 10.1038/nm.1905

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

[30] An in vitro microfluidic approach to generating protein interaction networks
DOI: 10.1038/nmeth.1289

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

[31] One-step DNA-programmed growth of luminescent and biofunctionalized nanocrystals
DOI: 10.1038/nnano.2008.373

[32] Carbon nanotubes might improve neuronal performance by favouring electrical shortcuts
DOI: 10.1038/nnano.2008.374

[33] Enzyme-assisted self-assembly under thermodynamic control
DOI: 10.1038/nnano.2008.378

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

[34] Task-specific signal transmission from prefrontal cortex in visual selective attention
DOI: 10.1038/nn.2237

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

[35] Sub-ångström-resolution diffractive imaging of single nanocrystals
DOI: 10 1038/nphys1161

[36] Energy gaps in the failed high-Tc superconductor La1:875Ba0:125CuO4
DOI: 10 1038/nphys1159

[37] A key role for unusual spin dynamics in ferropnictides
DOI: 10 1038/nphys1160

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

[38] Inverse coupling in leak and voltage-activated K+ channel gates underlies distinct roles in electrical signaling
DOI: 10.1038/nsmb.1525

[39] High resolution structure of the open NaK channel
DOI: 10.1038/nsmb.1531

[40] Structural analysis of ion selectivity in the NaK channel
DOI: 10.1038/nsmb.1537

[41] ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8
DOI: 10.1038/nsmb.1535

*************************************************************************************************************
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
Parkville: 6
Southport: 6

BELGIUM
Brussels: 20
Leuven: 20
Liege: 20
Wilrijk: 32

CANADA:
Chicoutimi: 20
Montreal: 20
Peterborough: 4
Sherbrooke: 20
Toronto: 20, 31

CHINA
Hong Kong: 19
Shanghai: 18

FRANCE
Fontenay aux Roses: 14
Orleans: 14

GERMANY
Berlin: 26
Bonn: 11
Goettingen: 11
Muenster: 9

INDIA
Kolkata: 10

IRELAND
Dublin: 32

ISRAEL
Beer-Sheva: 38

ITALY
Milan: 32
Padua: 28
Trieste: 32

JAPAN
Kanagawa: 36
Matsumoto: 24
Sendai: 24, 36
Tokyo: 24, 34
Yokohama: 24

NETHERLANDS
Nijmegen: 19
Rotterdam: 28

SOUTH KOREA
Seoul: 23

SPAIN
Granada: 28

SWITZERLAND
Lausanne: 30, 32
Zurich: 5

UNITED KINGDOM
Colchester: 16
Edinburgh: 7
Glasgow: 33
Manchester: 33
Sheffield: 16
St Andrews: 7

UNITED STATES OF AMERICA

Arizona
Tucson: 22

California
Berkeley: 8, 36
La Jolla: 5
Los Angeles: 12
Palo Alto: 41
Riverside: 23
San Francisco: 17, 41
Stanford: 30, 36

Connecticut
New Haven: 15, 38
Storrs: 27

District of Columbia
Washington: 37

Florida
Melbourne: 22

Illinois
Urbana: 35

Kentucky
Highland Heights: 22

Maryland
Bethesda: 17, 21, 29
Chevy Chase: 12

Massachusetts
Boston: 12, 21, 25
Cambridge: 12, 18, 21
Woods Hole: 22
Worcester:

Minnesota
Rochester: 15

Missouri
Columbia: 1

Nevada
Reno: 2

New Mexico
Los Alamos: 9

New York
New York: 5, 9, 12, 28
Palisades: 7
Rochester: 3
Stony Brook: 3
White Plains: 5

North Carolina
Chapel Hill: 29
Durham: 13
Greenville: 29

Ohio
Cleveland: 10
Columbus: 2

South Carolina
Columbia: 28

Tennessee
Knoxville: 36

Texas
Austin: 17
Dallas: 39, 40

Wisconsin
Madison: 1, 13

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

Katherine Anderson (Nature New York)
Tel: +1 212 726 9231; E-mail: k.anderson@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)
Peter Hare
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)
Orli Bahcall
Tel: +1 212 726 9311; 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 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

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Keywords associated to this article: Stem cells, disease modelling, biotechnology, Cell Biology, Alzheimer’s disease, Geoscience, Agriculture, carbon dioxide, Neuroscience, Chemical Biology, Rotoviruses, Tropical volcanic eruptions, snail shells
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