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Article Released Sun-30th-November-2008 18:07 GMT
Contact: Ruth Institution: Nature Publishing Group
 Medicine: Bringing Galatea to life?

Summaries of newsworthy papers include Return of North Atlantic deep convection, Family ‘friendly’ bacteria, Lessons from New Orleans, Reviving exhausted immune cells, Unbreak my heart, Molecular arms race, Snowball Earth or open oceans? and Sexual cycle of a fungus

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 30 November 2008

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

This press release contains:

· Summaries of newsworthy papers:

Medicine: Bringing Galatea to life?

Geoscience: Return of North Atlantic deep convection

Nature: Family ‘friendly’ bacteria

Geoscience: Lessons from New Orleans

Immunology: Reviving exhausted immune cells

Nature: Unbreak my heart

Nature and Structural and Molecular Biology: Molecular arms race

Geoscience: Snowball Earth or open oceans?

And finally…Nature: Sexual cycle of a fungus

· 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] Medicine: Bringing Galatea to life?
DOI: 10.1038/nm.1888

Inflammation is a key step in the progression of heterotopic ossification – where soft tissue turns into bone – according to research in Nature Medicine this week. The study shows that an inhibitor of the disease gene’s protein product is partially therapeutic, and therefore offers hope for this devastating condition.

In a reverse of the ancient myth of Pygmalion, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue ‘ossified’ — in effect, turning the patients into statues. A major form of heterotopic ossification is fibrodysplasia ossificans progressiva (FOP), which in about 98% of cases results from a mutation in a specific bone morphogenetic protein receptor.

A mouse model of FOP involving the same mutation found in people has yet to be made, but Paul Yu and colleagues have now developed a mouse model of the general phenomenon by expressing a related version of the mutated receptor. They found that just expressing the mutant version of the protein receptor was not sufficient to cause the disease – an inflammatory stimulus was also needed. Yu’s team also show that inhibiting inflammation with glucocorticoids—a treatment commonly used in the clinic—helps reduce the incidence of heterotopic ossification in their model.

Importantly, the authors also show that a small molecule inhibitor of the protein receptor likewise reduced the incidence of disease progression. This form of treatment represents a potential breakthrough, as long-term use of glucocorticoids causes severe side-effects. The authors caution, however, that much more research is needed before the drug could be considered for human trials.

Author contact:
Paul Yu (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
Tel: +1 617 643 3493; E-mail: pbyu@partners.org


[2] Geoscience: Return of North Atlantic deep convection
DOI: 10.1038/ngeo382

The mixing of surface waters to depths greater than 1,000 metres in the northern North Atlantic Ocean has returned during the winter of 2007/2008, scientists report online this week in Nature Geoscience. This deep mixing, an essential part of the Atlantic Ocean circulation, has been absent for almost a decade, and is an important regulator of both carbon dioxide uptake by the oceans and heat transfer between the ocean and atmosphere. The lack of recent deep mixing in the Labrador Sea had been linked with climate warming, leading to concerns about possible future changes in ocean circulation.

Kjetil Våge, Robert Pickart and colleagues use data from a network of measuring floats to detect the deep mixing of surface waters. They also evaluate local observations, computer reconstructions of past climate and satellite data to understand the mechanisms that lead to deep convection. They find that a combination of air temperatures in the northern hemisphere, storm pathways, flow of freshwater to the Labrador Sea and the distribution of pack ice cooled the ocean surface, allowing convection to mix surface waters to greater depths.

The authors conclude that the convective system in the North Atlantic Ocean is too complex to allow straightforward predictions of future deep mixing events.

Author contacts:
Kjetil Våge (Woods Hole Oceanographic Institution, Woods Hole, MA, USA)
Tel. +1 508 289 2847; E-mail: kjetil@whoi.edu

Robert Pickart (Woods Hole Oceanographic Institution, Woods Hole, MA, USA)
Tel: +1 508 289 2858; E-mail: rpickart@whoi.edu

[3] Nature: Family ‘friendly’ bacteria
DOI: 10.1038/nature07540

Genetic elements of our gut bacteria are shared between individuals, finds a study published online this week in Nature.

The community of bacteria that live in our gut help us to digest our food, ward off infections and can even have an impact on our risk of obesity and diabetes. Jeffrey Gordon and colleagues looked at the different types and the genetic make-up of bacteria living in the guts of pairs of identical and non-identical twins, and their mothers. By sequencing the DNA of the bacteria, collected from faecal samples, the team were able to compare the bacterial communities within and across families and correlated these results with obesity.

Bacterial communities were more similar within families, but each individual carried a unique set of bacterial species. However, the core functions encoded by the bacterial communities appear to be conserved, identifying a ‘core microbiome’ at a genetic rather than a species level. The team show that deviations from this core are associated with obesity.

Author contact:
Jeffrey Gordon (Washington University School of Medicine, St Louis, MO, USA)
Tel: +1 314 362 7243; E-mail: jgordon@wustl.edu


[4] Geoscience: Lessons from New Orleans
DOI: 10.1038/ngeo365

Densely populated coastal areas will become more vulnerable to the damaging effects of tropical cyclones, regardless of whether hurricane activity increases, suggests a Commentary online in Nature Geoscience this week. As sea levels rise, cities around the world could learn useful lessons from New Orleans following hurricane Katrina.

Torbjörn Törnqvist and Douglas Meffert suggest that preserving protective shorelines and wetlands, limiting the growth of urban centres on low-elevation coasts, concentrating the inhabitants of seaside cities in the least threatened areas and rebuilding destroyed housing in a more resilient fashion could all contribute to enhanced safety at the oceans’ shores.

Author contact:
Torbjörn Törnqvist (Tulane University, New Orleans, LA, USA)
Tel: +1 504 314 2221; E-mail: tor@tulane.edu


[5] Immunology: Reviving exhausted immune cells
DOI: 10.1038/ni.1679

The way in which immune system exhaustion occurs and what steps can be taken to revitalize anti-viral immune responses is reported online in Nature Immunology.

Viral infections, such as the common cold or influenza, trigger the immune system. Specific ‘killer’ cells known as CD8+ T cells attack virally infected cells, thereby destroying the offending viruses and the patients usually recover within a matter of days. However, some persistent infections, such as hepatitis viruses and HIV, create infections that the immune system fails to cure.

John Wherry and colleagues explored the basis for this immune non-response. They find chronic infection in mice disarms their killer cells by causing them to express multiple ‘inhibitory receptors’. Expression of these receptors is not random, but occurs in a specific order such that more severe infections prompt the expression of a more diverse array of inhibitory receptors. By blocking multiple ‘inhibitory’ receptors, the team could restore the ‘killing’ activity of the CD8+ T cells.

The authors plan on future studies to determine whether inhibitory receptor blockade might ‘rejuvenate’ exhausted T cells during chronic infections in humans.

Author contact:
John Wherry (The Wistar Institute, Philadelphia, PA, USA)
Tel: +1 215 495 6825; E-mail: jwherry@wistar.org


[6] Nature: Unbreak my heart
DOI: 10.1038/nature07511

A new target for the treatment of heart disease has been uncovered in mice, reports a study published online this week in Nature.

MicroRNAs are short pieces of nucleic acid that regulate gene expression. They have also been implicated in the development of many different diseases. Stefan Engelhardt and colleagues find that one such microRNA — miR-21 — activates a signalling pathway in heart cells that leads to the tissue damage associated with heart disease. They show, in mice and in human tissue samples, that diseased hearts contain more miR-21 than healthy hearts.

Using a drug that inhibits miR-21, the team were able to reverse its damaging effects in a mouse model of heart disease. The findings demonstrate that a similar therapy targeting mi-R21 could be useful to treat human disease.

Author contact:
Stefan Engelhardt (University of Wuerzburg, Germany)
Tel: +49 931 201 48710; E-mail: stefan.engelhardt@virchow.uni-wuerzburg.de


[7] & [8] Nature and Structural & Molecular Biology: Molecular arms race
DOI: 10.1038/nature07529
DOI: 10.1038/nsmb.1529

A key immunity-related protein evolved quickly in a molecular ‘arms race’ with poxviruses, a Nature paper suggests this week. It is thought that the strategy helps host stay ahead of pathogen.

Poxviruses, such as smallpox, produce a protein called K3L, which closely mimics the substrate of protein kinase R (PKR), an important component of vertebrate immunity. Nels Elde and colleagues show that PKR evolved under dramatic episodes of positive selection in primates, substituting amino acids at sites where K3L and PKR meet. The changes increase the probability of the host defeating the mimic and see the two protagonists locked in a molecular ‘arms race’, each trying to gain the upper hand.

In a related paper published online this week in Nature Structural & Molecular Biology, Stefan Rothenburg and colleagues provide evidence for poxvirus-driven evolution of PKR in vertebrates. They show that substituting a single amino acid in mouse PKR with the amino acid found at the same position in human PKR renders mouse PKR more resistant to K3L. The research demonstrates how an antiviral protein has evolved to avoid being deactivated by the virus, while maintaining its primary function.

Author contacts:
Nels Elde (Fred Hutchinson Cancer Research Center, Seattle, WA, USA)
Tel: +1 206 667 4512; E-mail: nelde@fhcrc.org Author paper [7]

Stefan Rothenburg (National Institute of Child Health and Human Development, Bethesda, MD, USA)
Tel: +1 301 594 7256; E-mail: rothenst@mail.nih.gov Author paper [8]


[9] Geoscience: Snowball Earth or open oceans?
DOI: 10.1038/ngeo355

According to the ’Snowball Earth’ concept, the entire globe was frozen for extended intervals more than 600 million years ago. Not so, concludes a review article online in Nature Geoscience that examines earlier work on the topic.

Philip Allen and James Etienne evaluate earlier studies that investigated the Cryogenian period, approximately 840 to 635 millions of years ago, which was characterized by exceptionally severe periods of icehouse climate when low-altitude glaciers reached the low latitudes. The researchers conclude that, contrary to the Snowball Earth concept, the sedimentary evidence from this time points to a continuously active water cycle on Earth, which is inconsistent with the idea of oceans that were completely sealed by ice.

Determining whether substantial parts of the oceans remained ice-free has important consequences for our understanding of the survival and diversification of life and Earth’s carbon cycle.

Author contact:
Philip Allen (Imperial College, London, UK)
Tel. +44 20 7594 7363; E-mail: philip.allen@imperial.ac.uk


[10] And finally…Nature: Sexual cycle of a fungus
DOI: 10.1038/nature07528

A fungus with associations to human asthma and sinusitis is shown to have a sexual cycle, contrary to assumed knowledge about this and other fungal species. The finding, reported in this week’s Nature, has wider implications because almost one in five of all fungi have no known sexual stage and may need to be revisited.

Aspergillus fumigatus is an opportunistic human pathogen in immunocompromised individuals that until now has been thought to reproduce asexually. 145 years after the first discovery of this fungus, Paul Dyer and colleagues show that it can reproduce sexually, for which isolates of complementary mating type are required. Implications of this demonstration include a possibility of classical genetic analyses that in turn will facilitate research into the genetic basis of pathogenicity and fungicide resistance.

Author contact:
Paul Dyer (University of Nottingham, UK)
Tel: +44 115 951 3203; E-mail: Paul.Dyer@Nottingham.ac.uk

Please note that this author is travelling with limited access to email, therefore his co-authors below can be contacted.

Dr. Hubert Fuller (University College Dublin, Ireland)
Tel: +353 1 716 2341; E-mail: hubert.fuller@ucd.ie

Ms Céline O'Gorman (University College Dublin, Ireland)
Tel: +353 1 716 2350; E-mail: ogorman@ucd.ie

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

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

[11] The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear
DOI: 10.1038/nature07520

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

[12] MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification
DOI: 10.1038/nbt1511

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

[13] Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility
DOI: 10.1038/ncb1808

[14] MG53 nucleates assembly of cell membrane repair machinery
DOI: 10.1038/ncb1812

[15] An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response
DOI: 10.1038/ncb1816

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

[16] Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2
DOI: 10.1038/ng.265

[17] Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness
DOI: 10.1038/ng.278

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

[18] Delivery of marine-derived nutrients to streambeds by Pacific salmon
DOI: 10.1038/ngeo364

[19] Highly unradiogenic lead isotope ratios from the Horoman peridotite in Japan
DOI: 10.1038/ngeo363

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

[20] Probing interfacial equilibration in microsphere crystals formed by DNA-directed assembly
DOI: 10.1038/nmat2338

[21] Surface-chemistry-driven actuation in nanoporous gold
DOI: 10.1038/nmat2335

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

[22] Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
DOI: 10.1038/nm.1890

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

[23] High-resolution mapping of copy-number alterations with massively parallel sequencing
DOI: 10.1038/nmeth.1276

[24] Stable knockdown of microRNA in vivo by lentiviral vectors
DOI: 10.1038/nmeth.1277

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

[25] Controlled polytypic and twin-plane superlattices in III–V nanowires
DOI: 10.1038/nnano.2008.359

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

[26] The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning
DOI: 10.1038/nn.2235

[27] Representation of negative motivational value in the primate lateral habenula
DOI: 10.1038/nn.2233

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

[28] Vertically emitting microdisk lasers
DOI: 10.1038/nphoton.2008.248

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

[29] Superconducting nanocircuits for topologically protected qubits
DOI: 10.1038/nphys1151

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

[30] Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1
DOI: 10.1038/nsmb.1519

[31] Molecular basis of Pirh2-mediated p53 ubiquitylation
DOI: 10.1038/nsmb.1521

***************************************************************************************************************
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
Melbourne: 15
Parkville: 15

BELGIUM
Brussels: 17

CANADA:
Dartmouth: 2
Downsview: 2
Prince George: 18
Toronto: 13, 31

DENMARK
Copenhagen: 2

FRANCE
Evry: 17
Marseille: 3
Paris: 2, 17, 29
Plouzane: 2

GERMANY
Bremen: 21
Freiburg: 16
Giessen: 15
Heidelberg: 6
Karlsruhe: 21
Martinsried: 12
Munich: 6
Ulm: 16
Wurzburg: 6

IRELAND
Dublin: 10

ITALY
Milan: 24
Pisa: 28

JAPAN
Kyoto: 13, 14
Miyagi-ken: 19
Saitama: 1, 14
Tohoku: 14
Tokyo: 14
Tottori-ken: 19

NETHERLANDS
Utrecht: 17

PORTUGAL
Lisbon: 17

SWEDEN
Linkoping: 31
Lund: 25

SWITZERLAND
Basel: 22
Zurich: 28

UNITED KINGDOM
Abingdon: 9
Cambridge: 28
London: 6, 9
Nottingham: 10

UNITED STATES OF AMERICA

California
Carlsbad: 6
Livermore: 21
Los Angeles: 11
Pasadena: 11
San Francisco: 6, 13

Colorado
Boulder: 3

Connecticut
Branford: 3

Illinois
Chicago: 6

Louisiana
New Orleans: 4

Maryland
Bethesda: 8, 17, 27

Massachusetts
Boston: 1, 5, 22, 23
Cambridge: 1, 6, 23, 26
Charlestown: 22
Danvers: 22
Woods Hole: 2, 3

Michigan
Ann Arbor: 1

Missouri
St Louis: 3

New Jersey
Piscataway: 14, 29

New York
Buffalo: 8
New York: 6, 24, 30

North Carolina
Research Triangle: 1

Oklahoma
Norman: 3

Pennsylvania
Philadelphia: 5, 20

South Carolina
Columbia: 3

Tennessee
Memphis: 5
Nashville: 1

Texas
Houston: 17, 26

Washington
Seattle: 2, 7

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 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 Materials (London)
Alison Stoddart
Tel: +44 20 7843 4593; 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 Photonics (Tokyo)
Oliver Graydon
Tel: +81 3 3267 8776; E-mail: o.graydon@natureasia.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

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Keywords associated to this article: Medicine, Galatea, North Atlantic deep convection, Family ‘friendly’ bacteria, New Orleans, Immunology, heart, Molecular arms race, Snowball Earth, open oceans, fungus
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