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Article Released Wed-13th-August-2008 17:37 GMT
Contact: Ruth Institution: Nature Publishing Group
  'Hidden' cholera much more widespread than thought

Summaries of newsworthy papers include Practical cloaking devices, Biofuels: A genomic approach, Key receptor identified for HCMV infection, A two-faced drug, A trick to conjure with, Solid at the core, Changing cycles and Spooky speed limit

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This press release is copyright Nature.

VOL.454 NO.7206 DATED 14 AUGUST 2008

This press release contains:

· Summaries of newsworthy papers:

Materials: Practical cloaking devices

Public health: 'Hidden' cholera much more widespread than thought

Biofuels: A genomic approach

Immunology: Key receptor identified for HCMV infection

Immunology: A two-faced drug

Bucky balls: A trick to conjure with

Earth sciences: Solid at the core

Palaeoclimate: Changing cycles

And finally… Spooky speed limit

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

Editorial contacts: While the best contacts for stories will always be the authors themselves, in some cases the Nature editor who handled the paper will be available for comment if an author is unobtainable. Editors are contactable via Ruth Francis on +44 20 7843 4562. Feel free to get in touch with Nature's press contacts in London, Washington and Tokyo (as listed at the end of this release) with any general editorial inquiry.

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[1] Materials: Practical cloaking devices (AOP)
DOI: 10.1038/nature07247

***This paper will be published electronically on Nature's website on 13 August at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 14 August, but at a later date. ***

Invisibility cloaks get a step closer to realization, with the demonstration of a new material that can bend (visible) light the wrong way for the first time in three dimensions. In Nature this week, researchers report a metamaterial that produces negative refraction of visible light, and show that it can be can be easily probed from free space, paving the way for practical optical device applications.

Metamaterials are artificially engineered structures that have properties, such as negative refractive index, not attainable with naturally occurring materials. Only thin, effectively two-dimensional materials have been demonstrated until now, limiting practical applications. Jason Valentine, Xiang Zhang and colleagues create a multilayered, ‘fishnet’ structure which unambiguously exhibits negative refractive index. This straightforward and elegant demonstration enhances our ability to mould and harness light at will.

CONTACT
Jason Valentine (University of California, Berkeley, CA, USA)
Tel: +1 510 643 4972; E-mail: valentij@newton.berkeley.edu

Xiang Zhang (University of California, Berkeley, CA, USA)
Tel: +1 510 643 4978; E-mail: xiang@berkeley.edu


[2] Public health: 'Hidden' cholera much more widespread than thought (pp 877-880)

Symptomless cholera may be much more prevalent than experts had previously reckoned, according to a new analysis of public health data from Bengal spanning 50 years. The data suggest that the ratio of asymptomatic to disease-causing infections may be much higher than thought, and that immunity to the disease may wane much more quickly.

Researchers led by Aaron King examined records of cholera mortality collected from 1891 to 1940 in what was then the British East Indian province of Bengal — the endemic home of cholera. According to their mathematical analysis of the data, published in this week's Nature, patterns of cholera prevalence are best explained by assuming that only 0.4% of infections are fatal, and that immunity disappears just months or even weeks after exposure to the pathogen.

This is in stark contrast to previous estimates, which suggested that more infections resulted in disease, and that immunity waned more slowly. The new discovery therefore means that many people may have been spreading cholera without realizing it. King and colleagues suggest that the size of this symptomless carrier population has traditionally been underestimated by epidemiologists and public health officials, because only the most serious cases receive medical attention — among those hospitalized with cholera in Bengal, death rates have historically been over 50%.

CONTACT
Aaron King (University of Michigan, Ann Arbor, MI, USA)
Tel: +1 734 936 7861; E-mail: kingaa@umich.edu


[3] Biofuels: A genomic approach (pp 841-845)

If the potential for ‘greener’ biofuels is to be realised, new technologies for their large-scale production will be required. A review in Nature this week assesses the field of genomics for these fuels and looks to the future prospects of this cellulosic biofuel production.

The first wave of biofuels has had a significant impact on world energy markets. However, there are major concerns about the knock-on effects on food prices. Hence, there is a growing interest in ‘cellulosic’ feedstocks, such as microbes, grasses, wood and crop residues, as a source of biomass for ‘greener’ biofuels that do not remove land from food production.

Edward Rubin considers biomass, biomass degradation and biofuel production with genomics in mind and concludes that the strategies pioneered in sequencing and interpreting the human genome for the improvement of human health are now poised to be an important contributing technology in the challenge to develop environmentally and socially acceptable alternatives to fossil fuels.

CONTACT
Edward Rubin (Joint Genome Institute, Walnut Creek, CA, USA)
Tel: +1 510 486 5072; E-mail: emrubin@lbl.gov


[4] Immunology: Key receptor identified for HCMV infection (AOP)
DOI: 10.1038/nature07209

***This paper will be published electronically on Nature's website on 13 August at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 14 August, but at a later date. ***

Researchers have identified a critical receptor required for human cytomegalovirus (HCMV) infection. The protein, platelet-derived growth factor-a receptor (PDGFR-a), may prove a useful target for new anti-viral therapies.

HCMV is a ubiquitous human herpesvirus that can cause life-threatening disease in the fetus and immunocompromised patients. In this week’s Nature, Charles Cobbs and colleagues show that HCMV requires PDGFR-a binding and activation for internalization, expression of essential viral genes, production of infectious virus, and activation of key downstream signaling.

If the receptor is knocked out or inactivated, HCMV cannot enter the cell and viral genes are not expressed. The team highlights two compounds — the anti-cancer drug Gleevec and the PDGFR-a-blocking antibody IMC-3G3 — that yield this effect, suggesting that these currently available pharmaceutical agents could prove useful in the treatment of HCMV infection.

CONTACT
Charles Cobbs (University of California San Francisco Medical Center, CA, USA)
Tel: +1 415 317 7606; E-mail: charles.cobbs@gmail.com


[5] Immunology: A two-faced drug (pp 894-898; N&V)

Low doses of an immunosuppressive drug can eliminate chronic virus infection in mice, according to research published in Nature this week. The surprising finding could translate into treatment for chronic human infections.

The mouse virus lymphocytic choriomeningitis establishes long-term chronic infections by escaping immune responses. John Altman and colleagues found that treatment of infected mice with low doses of the drug FTY720 boosted anti-viral immune responses and enabled the mice to resolve infection.

FTY720 has already been tested in human clinical trials for treating autoimmune diseases and preventing tissue transplant rejection. It is regarded as a new type of immunosuppressive agent that works by trapping white blood cells in lymph nodes and keeping them away from the sites of disease. However, during viral infection the lymph nodes are an important site of immune induction and even viral replication. Further work is required to understand how FTY720 works to enhance the immune response in this setting, helping mice to clear the virus. In a related News and Views article, Michael Bevan and Pamela Fink say the research gives “an unexpected twist to the potential side effects of this immunosuppressive drug.”

CONTACT
John Altman (Emory University, Atlanta, GA, USA)
Tel: +1 404 727 5981; E-mail: jaltman@rmy.emory.edu

Michael Bevan (Department of Immunology, University of Washington, Seattle, WA, USA) N&V Author
Tel: +1 206 685 3610; E-mail: mbevan@u.washington.edu

Pamela Fink (Department of Immunology, University of Washington, Seattle, WA, USA) N&V Author
Tel: +1 206 685 3608; E-mail: pfink@u.washington.edu


[6] Bucky balls: A trick to conjure with (pp 865-868)

Fullerenes — football look-alike molecules assembled from 60 carbon atoms — are normally made by vaporizing graphite. But a paper in this week’s Nature has found a more controlled way to make them, opening up an opportunity to juggle with the process and conjure up some unusual fullerene variants.

José Martín-Gago and colleagues build on pioneering but laborious experiments to produce fullerenes. They concentrate on the final dehydrogenation step in the synthesis and are able vastly to improve its efficiency — obtaining the sought-after fullerenes with almost 100 per cent yield.

Their method is to deposit the final precursors on to a platinum surface and then heat it to nearly 500 degrees Celsius, which transforms all the precursors into fullerenes. Interesting modifications to standard fullerenes might be produced by using different precursor molecule structures.

CONTACT
José Martín-Gago (Instituto Ciencia de Materiales de Madrid-CSIC, Spain)
Tel: +34 9 13 34 90 87; E-mail: gago@icmm.csic.es


[7] Earth sciences: Solid at the core (pp 873-876; N&V)

Using more than 700 borehole seismometers, researchers have detected very subtle waves from the Earth's inner core. The work, published in Nature this week, presents observations of inner-core shear-wave phases and gives insights into the physical properties of the inner core.

In the centre of the Earth's liquid outer core is the inner core, a ball about 2,400 kilometres in diameter, made up mostly of iron, which is thought to be solid. At tremendous pressure and a temperature of over 5,000 kelvin, it was formed by slow freezing of liquid iron from the outer core.

An array of over 700 borehole seismometers across Japan has allowed James Wookey and George Helffrich to detect the very subtle inner-core shear-wave phase 'PKJKP', which has long been sought by seismologists. This enables them to draw conclusions about the structure and properties of the inner core.

CONTACT
James Wookey (University of Bristol, UK)
Tel: +44 117 954 5496; E-mail: j.wookey@bristol.ac.uk

Kenneth Creager (University of Washington, Seattle, WA, USA) N&V author
Tel: +1 206 685 2803; E-mail: kcc@ess.washington.edu


[8] Palaeoclimate: Changing cycles (pp 869-872)

Around 2.7 million years ago the Earth’s glacial cycles changed in period from about 41,000 to 100,000 years. The reasons behind this shift have been a mystery, but research in Nature this week suggests that the increased ability of the merged North American ice sheets to survive periods where the sun is in position to provide maximum warmth may be the answer.

Richard Bintanja and his colleague use a comprehensive ice-sheet model and a simple ocean-temperature model to extract three-million-year mutually consistent records of surface air temperature, ice volume and sea level from marine benthic oxygen isotopes. Their findings suggest that the switch to 100,000 year cycles was due to increased cooling in conjunction with the merging, expansion and ultimate collapse of the North American ice sheets once it had reached a certain threshold size.

CONTACT
Richard Bintanja (Koninklijk Nederlands Meteorologisch Instituut, De Bilt, Netherlands)
Tel: +31 30 220 6499; E-mail: bintanja@gmail.com


[9] And finally… Spooky speed limit (pp 861-864; N&V)

Einstein famously used the phrase 'spooky action at a distance' to describe the continuing interaction between distant photons that possess the quantum mechanical property of entanglement. A paper in this week's Nature gives the lower speed limit of any such 'spooky action' as 10,000 times the speed of light.

Experimental tests known as Bell inequalities have all but ruled out a classical explanation for these correlations between entangled photons, but the possibility remains that a first event could influence a second one, if the influence occurs faster than the speed of light. The test performed by Daniel Salart and colleagues lasted more than 24 hours, and ran between two Swiss villages 18 kilometres apart with the source precisely in the middle. Taking advantage of the Earth's rotation, the experiment allowed the determination of a lower bound for the speed of any such influence.

The team conclude that the minimal speed of hypothetical spooky action at a distance for this experiment is at least 10,000 times the speed of light. The existence in nature of a real spooky action at a distance is therefore deemed implausible. In a related News & Views article, Terence Rudolph says “any theory that tries to explain quantum entanglement… will need to be very spooky – spookier, perhaps, than quantum mechanics itself”.

CONTACT
Daniel Salart (University of Geneva, Switzerland)
Tel: +41 22 379 6936; E-mail: daniel.salart@physics.unige.ch

Terence Rudolph (Imperial College, London, UK) N&V author
Tel: +44 20 7594 7863; E-mail: t.rudolph@imperial.ac.uk


ALSO IN THIS ISSUE…

[10] Compositional differences between meteorites and near-Earth asteroids (pp 858-860)

[11] On the spontaneous emergence of cell polarity (pp 886-889)

[12] Dynamic thiolation–thioesterase structure of a non-ribosomal peptide synthetase (pp 903-906; N&V)

[13] Structural basis for the selectivity of the external thioesterase of the surfactin synthetase (pp 907-911; N&V)


ADVANCE ONLINE PUBLICATION

***These papers will be published electronically on Nature's website on 13 August at 1800 London time / 1300 US Eastern time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included them on this release to avoid multiple mailings they will not appear in print on 14 August, but at a later date. ***

[14] Type IV collagens regulate BMP signaling in Drosophila
DOI: 10.1038/nature07214

[15] T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance
DOI: 10.1038/nature07210

[16] Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance
DOI: 10.1038/nature07208

GEOGRAPHICAL LISTING OF AUTHORS…

The following list of places refers to the whereabouts of authors on the papers numbered in this release. For example, London: 4 - this means that on paper number four, there will be at least one author affiliated to an institute or company in London. 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.

AUSTRIA
Vienna: 16

BELGIUM
Leuven: 16

GERMANY
Frankfurt am Main: 13
Marburg: 13
Munich: 16

JAPAN
Tokyo: 16

NETHERLANDS
Noordwijk: 10
Utrecht: 6

RUSSIA
Pushchino: 13

SPAIN
Madrid: 6
Tarragona: 6

SWITZERLAND
Geneva: 9

UNITED KINGDOM
Bristol: 7
Claremont: 12
London: 2
Manchester: 14

UNITED STATES OF AMERICA

California
Berkeley: 1, 3
Claremont: 12
Palo Alto: 16
San Francisco: 4
Walnut Creek: 3

Georgia
Atlanta: 5

Hawaii
Hilo: 10
Honolulu: 10

Maryland
Bethesda: 15
Laurel: 10

Massachusetts
Boston: 12, 13
Cambridge: 10

Michigan
Ann Arbor: 2

New Mexico
Santa Fe: 2

Texas
Dallas: 11

Wisconsin
Madison: 11

PRESS CONTACTS…

From North America and Canada
Katherine Anderson, Nature New York
Tel: +1 212 726 9231; E-mail: k.anderson@natureny.com

Katie McGoldrick, Nature Washington
Tel: +1 202 737 2355; E-mail: k.mcgoldrick@naturedc.com
From Japan, Korea, China, Singapore and Taiwan

Mika Nakano, Nature Tokyo
Tel: +81 3 3267 8751; E-mail: m.nakano@natureasia.com

From the UK/Europe/other countries not listed above
Jen Middleton, Nature London
Tel: +44 20 7843 4502; E-mail j.middleton@nature.com

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Keywords associated to this article: Materials, Public health, Biofuels, Immunology, Bucky balls, Earth sciences, Palaeoclimate, spooky action
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