Immunity: Holding dormant cancers in check

Summaries of newsworthy papers include More single photons, Neural networks organise themselves, Gene prevents sudden death in mice after infection, Optimistic neurons, How the visual system grows up, Suppressing allergy and Getting attached to measles

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 18 November 2007

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

This press release contains:

· Summaries of newsworthy papers:

Immunity: Holding dormant cancers in check – Nature

More single photons – Nature Photonics

Neural networks organise themselves – Nature Physics

Gene prevents sudden death in mice after infection – Nature Genetics

Optimistic neurons – Nature Neuroscience

How the visual system grows up – Nature Neuroscience

Suppressing allergy – Nature Immunology

Getting attached to measles – Nature Structural & Molecular Biology

· 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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****************************************************NATURE************************************************

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

[1] Immunity: Holding dormant cancers in check (N&V)

DOI: 10.1038/nature06309

Dormant cancer cells are actively kept in check by the host’s immune system — those that escape go on to develop into clinically detectable tumours. A paper online in this week’s Nature identifies a crucial stage in the battle, at which point defences stall the expansion of cancer cells that may have managed to dodge past early immunosurveillance.

Robert Schreiber and co-workers use a mouse model to show that the animal’s immune system can keep tumour growth in check over an extended period. Clinicians have suspected the existence of such an ‘equilibrium’ state, because dormant cancers sometimes take off when inadvertently transferred from a donor to an immunosuppressed recipient during organ transplantation.

This newly discovered staging post could also explain the presence of occult tumour cells — in the prostate, for example — in individuals with no symptoms of disease. Eventually it could be used to devise immunotherapies for tightening control of tumour growth, suggest the authors.

In an accompanying News & Views article, Cornelis Melief comments on the ‘startling results’ and says: ‘they demonstrate that considering cancer as a fatal disease is not always appropriate’.

Author contact:

Robert Schreiber (Washington University School of Medicine, St Louis, MO, USA)

Tel: +1 314 362 8747; E-mail: [email protected]

Cornelis Melief (Leiden University Medical Center, Netherlands) N&V author

Tel: +31 71 526 3800; E-mail: [email protected]

Other papers from Nature to be published online at the same time and with the same embargo:

[2] A hierarchy of timescales in protein dynamics is linked to enzyme catalysis

DOI: 10.1038/nature06407

[3] Intrinsic motions along an enzymatic reaction trajectory

DOI: 10.1038/nature06410

******************************************NATURE PHOTONICS******************************************

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

[4] More single photons

DOI: 10.1038/nphoton.2007.227

Single packets of light can be generated at a record rate from a compact device, suggests a paper online this week in Nature Photonics. The ’brighter’ source is an important step towards processing information in a unique way that is made possible by the fundamental laws of physics.

Stefan Strauf and colleagues made a light source that emits isolated photons — indivisible light packets — at a rate of approximately 30 million per second, five times better than previously possible. Importantly, the photons can be created on-demand, not randomly as in alternative approaches, and their orientation, or polarization, can be controlled.

An efficient single-photon source could be crucial in offering benefits to information processing by quantum physics.

Author contact:

Stefan Strauf (Stevens Institute of Technology, Hoboken, New Jersey, USA)

Tel: +1 201 216 5639; E-mail: [email protected]

Addition contact for comment on paper:

Charles Santori (Hewlett-Packard Laboratories, Palo Alto, California, USA)

Tel: +1 650 857 2154; E-mail: [email protected]

Other papers from Nature Photonics to be published online at the same time and with the same embargo:

[5] Bright, multicoloured light-emitting diodes based on quantum dots

DOI: 10.1038/nphoton.2007.226

***********************************************NATURE PHYSICS*****************************************

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

[6] Neural networks organise themselves

DOI: 10.1038/nphys758

Neural networks dynamically organize themselves to operate in a range that is optimal for information processing, according to a theoretical model reported online in Nature Physics this week. The results provide an understanding of how neurons interact with each other and how they can build efficient networks.

Neurons signal to each other through junctions known as synapses. Using these connections they can build extended networks. Computer simulations of neural networks indicate that for specific connection patterns, properties such as computational power or memory capacity are maximized. This picture is supported by experimental findings in cell cultures. However, how neural networks can be tuned to the optimal setting is still an open question.

Michael Herrmann and colleagues argue that there is no need for fine-tuning. They factor in that synapses are not static — that is, the efficiency of transmission through synapses depends on the frequency of their use — and show in their model that neural networks dynamically organize themselves to operate in a favourable range.

Author contact:

Michael Herrmann (Universität Göttingen, Germany)

Tel: +49 551 517 6424; E-mail: [email protected]

Additional contact for comment on paper:

John Beggs (Indiana University, Bloomington, IN, USA)

Tel: +1 812 855 7359; E-mail: [email protected]

Other papers from Nature Physics to be published online at the same time and with the same embargo:

[7] Quantum non-demolition detection of strongly correlated systems

DOI: 10.1038/nphys776

[8] Optical antennas based on coupled nanoholes in thin metal films

DOI: 10.1038/nphys785

***********************************************NATURE GENETICS **************************************

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

[9] Gene prevents sudden death in mice after infection

DOI: 10.1038/ng.2007.25

Mice that lack a particular gene die suddenly and without overt signs of illness in response to an infection that is usually harmless, according to a study to be published online this week in Nature Genetics. This work may lead to new insights into the origins of sudden death in humans, although such a link has not yet been made.

Bruce Beutler and colleagues treated mice with a chemical mutagen – an agent that changes genetic information; and examined the third-generation offspring of the mutant mice for susceptibility to cytomegalovirus (CMV). This virus, at the dose delivered, is normally harmless. The progeny of four of the original mutants, however, died suddenly between 36 hours and 3 days after inoculation. One of these lines has a large deletion in Kcnj8, a gene encoding a component of a potassium channel expressed in smooth muscle and endothelial cells of the coronary artery (two of the other lines carry different mutations in Kcnj8).

The protein that interacts with Kcnj8 has a counterpart in the fruit fly, and the authors show that it similarly protects flies against sudden death after challenge with flock house virus (FHV). The authors propose that this potassium channel is required for the coronary arteries to survive the systemic metabolic stress and arterial constriction that accompanies the innate immune response to viruses such as CMV and FHV.

Author contact:

Bruce Beutler (Scripps Research Institute, La Jolla, CA, USA)

Tel: +1 858 784 8610; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[10] The maize tasselseed4 microRNA controls sex determination and meristem cell fate by targeting Tasselseed6/indeterminate spikelet 1

DOI: 10.1038/ng.2007.20

[11] Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha

DOI: 10.1038/ng.2007.15

[12] Cystatin C modulates cerebral beta-amyloidosis

DOI: 10.1038/ng.2007.23

[13] Cystatin C inhibits amyloid-beta deposition in Alzheimer’s disease mouse models

DOI: 10.1038/ng.2007.29

*******************************************NATURE NEUROSCIENCE ***********************************

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

[14] Optimistic neurons

DOI: 10.1038/nn2013

In rats given a choice between two rewards, neurons that predict the value of expected rewards responded as though the animal had chosen the best available reward, no matter what the rat actually did. These results, reported online this week in Nature Neuroscience, suggest that the opportunity to make a choice may be as valuable as the best available option on the menu.

The authors trained rats to learn to associate each of three odours with an action. Two of the odours signalled that the rat was required to move either left or right to receive a reward, with one location containing a better reward than the other. The third odour indicated that the animal could choose to go to either location. Dopaminergic neurons in the ventral tegmental area, part of the brain’s “reward processing system,” responded more for the odour that cued the rat to move to the location associated with the better reward, as expected from previous studies.

The rewards varied either in the amount of juice or in how long the rat had to wait for its delivery, and responses to the odour cues were correlated with both reward size and delay. The dopaminergic neurons responded just as strongly to the odour indicating that the rat could choose which reward to collect as to the better reward, even though the rat eventually chose the worse reward nearly 30% of the time on the free choice trials.

Author Contact:

Matthew Roesch (University of Maryland School of Medicine, Baltimore, MD, USA)

Tel: +1 410 706 8910; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[15] Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity

DOI: 10.1038/nn2008

[16] Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
DOI: 10.1038/nn2014

[17] Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
DOI: 10.1038/nn2015

*******************************************NATURE IMMUNOLOGY ************************************

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

[18] Suppressing allergy

DOI: 10.1038/ni1533

Researchers have identified a protein that blocks the release of chemical mediators that produce the symptoms of allergic reactions. The work appears in an article online this week in Nature Immunology.

Mast cells are specialized immune cells that are capable of secreting large amounts of inflammatory compounds when triggered by an allergen or certain parasites. The regulatory protein, called RGS13, inhibits mast cell release of histamine and other inflammatory compounds that can occur when an allergen is encountered by sensitized individuals. RGS13 short-circuits the signaling pathway triggered when the allergen binds specialized receptors found on the mast cells. Mice lacking RGS13 exhibit heightened allergic responses as compared to littermates that express RGS13.

Identifying RGS13 as a negative regulator of mast cell degranulation – the term used to describe release of their inflammatory products – may lead to new ways of blunting allergic responses.

Author contact:

Kirk M Druey (National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA)
Tel: +1 301 435 8875; E-mail: [email protected]

**********************NATURE STRUCTURAL AND MOLECULAR BIOLOGY************************

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

[19] Getting attached to measles

DOI: 10.1038/nsmb1342

A new structure described online this week in Nature Structural & Molecular Biology may lead to therapies to prevent measles virus infection, which currently affects about 20 million people each year.

Chris Garcia and colleagues have determined the crystal structure of measles virus hemagglutinin (MVH), a protein found on the surface of the virus. MVH recognizes and binds to specific protein receptors on host cell surfaces, an interaction required for virus entry into the host cell. Knowledge of MVH’s structure will facilitate structure-based drug design efforts targeted to prevent measles infection.

Author contact:

Chris Garcia (Stanford University Medical School, CA, USA)

Tel: +1 650 498 7332; E-mail: [email protected]

Other papers from Nature Structural & Molecular Biology to be published online at the same time and with the same embargo:

[20] p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation

DOI: 10.1038/nsmb1316

[21] PYM binds the cytoplasmic exon-junction complex and ribosomes to enhance translation of spliced mRNAs

DOI: 10.1038/nsmb1321

[22] A YY1-INO80 complex regulates genomic stability though homologous recombination-based repair

DOI: 10.1038/nsmb1332

[23] Stability of the proteasome can be regulated allosterically through engagement of its proteolytic active sites

DOI: 10.1038/nsmb1335

[24] L3MBTL1 recognition of mono- and dimethylated histones

DOI: 10.1038/nsmb1340

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

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

[25] Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism

DOI: 10.1038/nchembio.2007.54

[26] Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY

DOI: 10.1038/nchembio.2007.40

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

[27] Surface effects on the orbital order in the single-layered manganite La0.5Sr1.5MnO4

DOI: 10.1038/nmat2061

[28] Electronic functionalization of the surface of organic semiconductors with self-assembled monolayers

DOI: 10.1038/nmat2059

[29] Liquid-crystal materials find a new order in biomedical applications

DOI: 10.1038/nmat2010

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

[30] Downscaling of self-aligned, all-printed polymer thin-film transistors

DOI: 10.1038/nnano.2007.365

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

[31] T cell–encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection

DOI: 10.1038/nm1676

[32] Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection

DOI: 10.1038/nm1679

[33] A pivotal role for galectin-1 in fetomaternal tolerance

DOI: 10.1038/nm1680

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

[34] Microscale culture of human liver cells for drug development

DOI: 10.1038/nbt1361

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

[35] Filopodia are required for cortical neurite initiation

DOI: 10.1038/ncb1654

[36] Filopodial actin bundles are not necessary for microtubule advance into the peripheral domain of Aplysia neuronal growth cones

DOI: 10.1038/ncb1655

[37] Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts

DOI: 10.1038/ncb1657

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

[38] Quantized Plasmon quenching dips nanospectroscopy via plasmon resonance

energy transfer

DOI: 10.1038/nmeth1133

[39] Npro fusion technology to produce proteins with authentic N termini in E. coli

DOI: 10.1038/nmeth1116

[40] Using expression profiling data to identify human microRNA targets

DOI: 10.1038/nmeth1130

[41] Prion strain discrimination using luminescent conjugated polymers

DOI: 10.1038/nmeth1131

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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.

ARGENTINA
Buenos Aires: 33

AUSTRALIA
Melbourne: 1

Victoria: 1, 9

AUSTRIA
Kundl: 39
Innsbruck: 39
Vienna: 39

CANADA:

Burnaby: 16

Montreal: 11, 15

Ottawa: 20

Quebec City: 41

Toronto: 24, 40

Vancouver: 16

CHINA
Beijing: 5

Wuhan: 24

DENMARK

Copenhagen: 7

FRANCE

Castanet Tolosan: 32

Grenoble: 27

Illkirch: 11

Paris: 11, 33

Strasbourg: 2, 3, 9, 11

GERMANY

Berlin: 17, 33

Goettingen: 6, 17

Halle: 3

Jena: 33

Lubeck: 3

Regensburg: 17

Tubingen: 12

HUNGARY
Pecs: 33

ISRAEL
Haifa: 23

ITALY
Brescia: 1
Pisa: 15
Rome: 32

JAPAN

Tsukuba: 27

NETHERLANDS

Leiden: 4

NEW ZEALAND

Wellington: 32

SPAIN

Barcelona: 7

Bellaterra: 7

Castelldefels: 7

Granada: 33

SWEDEN

Gothenburg: 8

Linkoping: 41

Lund: 12

SWITZERLAND

Basel: 12, 15

Zurich: 17, 41

UNITED KINGDOM

Cambridge: 30

UNITED STATES OF AMERICA

Arkansas

Fayetville: 5

California

Albany: 10

Berkeley: 38

Davis: 26

La Jolla: 9, 36, 41

San Diego: 32

San Francisco: 38

Santa Barbara: 4

Stanford: 3, 19, 26, 35

Connecticut

New Haven: 36, 40

Delaware

Wilmington: 10

Illinois

Argonne: 27

Iowa

Ames: 27

Iowa City: 10

Johnston: 10

Maryland

Baltimore: 3, 14, 35

Bethesda: 18, 20, 22

Massachusetts

Boston: 1, 18, 22, 23, 25, 34

Cambridge: 2, 3, 18, 22, 34, 35

Charlestown: 25

Waltham: 2, 3

Michigan

Grand Rapids: 35

Missouri

St Louis: 1

Nebraska

Lincoln: 3

New Jersey

Hoboken: 4

Piscataway: 28

New Mexico

Albuquerque: 22

New York

Cold Spring Harbor: 15

New York: 1, 12, 13, 15, 31

Orangeburg: 13

Stony Brook: 15

Upton: 27

Pennsylvania

Philadelphia: 21

Radnor: 13

University Park: 5

Rhode Island

Providence: 29

Tennessee

Nashville: 25

Utah

Salt Lake City: 26

Virginia

Charlottesville: 37

Washington

Seattle: 20

Wisconsin

Madison: 35

PRESS CONTACTS…

For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)

Tel: +44 20 7843 4502; E-mail: [email protected]

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Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)

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Nature Cell Biology (London)

Bernd Pulverer

Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)

Andrea Garvey

Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)

Orli Bahcall

Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)

Laurie Dempsey

Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)

Fabio Pulizzi

Tel: +44 20 7014 4024; E-mail: [email protected]

Nature Medicine (New York)

Juan Carlos Lopez

Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)

Allison Doerr

Tel: +1 212 726 9393; E-mail: [email protected]

Nature Nanotechnology (London)

Peter Rodgers

Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)

Sandra Aamodt (based in California)

Tel: +1 530 795 3256; E-mail: [email protected]

Nature Photonics (Tokyo))

Oliver Graydon

Tel: +81 3 3267 8776; E-mail: [email protected]

Nature Physics (London)

Alison Wright

Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)

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Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 18 Nov 2007

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