Pain: Treatment with feeling

Summaries of newsworthy papers include Containing uranium, Tethering HIV, Regenerating hair in waves, Listeria dodges host’s immune response, Identifying skin cancer starter cells, Encoding biopolymers with instructions, RNA and tumour suppression and Sing-a-long-a-neuron


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VOL.451 NO.7176 DATED 17 JANUARY 2008

This press release contains:

· Summaries of newsworthy papers:

Pain: Treatment with feeling

Chemistry: Containing uranium

Immunology: Tethering HIV

Cell signalling: Regenerating hair in waves

Bacterial infection: Listeria dodges host’s immune response

Cancer: Identifying skin cancer starter cells

Self-assembling molecules: Encoding biopolymers with instructions

Cancer biology: RNA and tumour suppression

And finally… Sing-a-long-a-neuron

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

· Geographical listing of authors

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[1] Pain: Treatment with feeling (pp 330-334)

Treatment of chronic pain without unwelcome side effects could be possible in the future, thanks to research published in Nature this week. The research identifies a potential pharmaceutical target that could help reduce problems involved in current pain therapeutics.

Hanns Zeilhofer and colleagues demonstrate in mice that targeting two specific subunits of a spinal receptor, GABAA, effectively treats the pain without unwanted sedation and impaired motor function. The mice did not build up a tolerance to treatment, unlike with many drugs. The team go on to show that brain activity in rats in areas related to associative-emotional components of pain is much reduced when they received the same targeted treatment.


Hanns Zeilhofer (University of Zurich, Switzerland)
Tel: +41 446 355 912; E-mail: [email protected]

[2] Chemistry: Containing uranium (pp 315-317; N&V)

A charged oxide is one of uranium’s most prevalent forms, and is a problematic contaminant because of its radioactivity, ready solubility in water and chemical inertness. But a demonstration in this week’s Nature shows that when this species is placed in the iron grip of a specially designed ligand, it can be changed into different forms that are potentially more easily trapped and manipulated.

The chemical inertness of the charged uranium oxide results from the strong bonding between the uranium and its two oxygen atoms. Polly Arnold and colleagues’ trick was to place the molecule in a ligand framework that perturbs the strong bonding and allows one of the two oxygen atoms to react with other compounds. They suggest that this approach might be developed into a useful strategy for manipulating uranium in its most common form in solution, and also for dealing with related, highly radioactive derivatives of plutonium and neptunium.


Polly Arnold (University of Edinburgh, UK)
Tel: +44 131 650 5429; E-mail: [email protected]

James M Boncella (Los Alamos National Laboratory, NM, USA) N&V author

Tel: +1 505 665 0795; E-mail: [email protected]

[3] Immunology: Tethering HIV (AOP)

DOI: 10.1038/nature06553

***This paper will be published electronically on Nature's website on 16 January 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 17 January, but at a later date. ***

An antiviral molecule called a ‘tetherin’ that acts to inhibit HIV-1 particle release from cells is identified in a paper published online in Nature this week. The protein CD317 is involved in tethering HIV particles to the cell surface, and stopping the release of the virus.

The HIV protein Vpu is required for the release of viral particles, and evidence for a tetherin molecule has accumulated over the last few years. Paul Bieniasz and colleagues show that Vpu works to neutralize the host cell protein CD317, which they rename tetherin. In this way it allows efficient discharge of HIV-1 particles from infected cells. The team argue that inhibition of virus release by tetherin is a previously unknown mechanism by which organisms protect themselves against certain viruses.


Paul Bieniasz (Rockefeller University, New York, NY, USA)

Tel: +1 212 448 5070; E-mail: [email protected]

[4] Cell signalling: Regenerating hair in waves (pp 340-344)

The thousands of hair follicles on the skin of furry animals are each going through a cycle of hair growth and rest, but how do they all coordinate their activity with one another? A paper in this week’s Nature identifies a molecular factor that helps to control the mechanism underlying this process.

Cheng-Ming Chuong and colleagues analysed the cyclic activation of hair-follicle stem cells that regenerate hair on mice. They discovered that skin proteins known as bone morphogenetic proteins (BMPs) act as ‘switches’ to regulate hair growth in individual follicles as well as to coordinate it with neighbouring follicles.

Hair growth cycles are complicated, so outwardly similar skin of mice of different ages may not be the same at all. This could have implications for carcinogenesis and stem-cell engineering studies, which assume mouse skin stays homogeneous during lengthy experiments.


Cheng-Ming Chuong (University of Southern California, Los Angeles, CA, USA)
Tel: +1 323 442 1296; [email protected]

[5] Bacterial infection: Listeria dodges host’s immune response (pp 350-354)

Pregnant women are advised not to eat delicious unpasteurized cheeses because of the risk of infection by the bacterium Listeria monocytogenes. A paper published in this week’s Nature investigates the life cycle of this organism to discover how it manages to establish a state of persistent infection in the host.

Listeria is swallowed up by cell components known as phagosomes once it has gained entry into its host, but drills its way out using a specially made molecule called listeriolysin O. Free again in the clear medium (‘cytosol’) surrounding the cell nucleus, the bug multiplies rapidly to bring down its host. However, sometimes Listeria sets up colonies inside ‘bubbles’, or vacuoles, in macrophage phagosomes instead. John Brumell and colleagues show that the bacteria can continue to replicate inside these vacuoles, but much more slowly than they do in the cytosol.

The team suggest that this strategy of hiding inside vacuoles may help the bacteria to survive the host’s defensive immune response and establish persistent infection.


John Brumell (Hospital for Sick Children, Toronto, ON, Canada)
Tel: +1 416 813 7654; E-mail: [email protected]

[6] Cancer: Identifying skin cancer starter cells (pp 345-349)

Cells that initiate human skin cancer are identified in Nature this week, and researchers demonstrate how targeting these cells with antibodies can slow the growth of melanomas.

Cancer stem cells have been isolated from a number of human tumours. Here Markus H. Frank and colleagues identify tumour-initiating cells in clinical human malignant melanomas. Tumours with ABCB5+ cells grow faster and spread quicker than those without. Preliminary evidence also suggests that these melanoma stem cells can be specifically targeted with antibodies targeted against ABCB5, which offers a potential therapeutic strategy against melanomas.


Markus H. Frank (Children's Hospital Boston and Brigham & Women's Hospital, Boston, MA, USA)
Tel: +1 617 919 2993; E-mail: [email protected]

[7] Self-assembling molecules: Encoding biopolymers with instructions (pp 318-322)

The replication and regulation of biological systems such as DNA depend on the dynamic assembly and disassembly of participating molecules — also a goal of nanotechnology engineering. A paper in this week’s Nature brings that goal a step closer by programming the dynamic self-assembly of a range of artificially produced DNA structures.

Niles Pierce and colleagues use specially designed DNA ‘hairpins’ as building blocks, which self-assemble into assorted structures when triggered by an initiator single DNA strand. The particular structure formed is determined by sequences encoded in the DNA system itself.

To simplify the overall design process, the team developed a general ‘reaction graph’ abstraction to represent the hairpins and to rewire their interactions. The molecular programs can execute a variety of dynamic functions, including a self-propelled DNA ‘walker’ — a loop of DNA that cartwheels along a DNA track.


Niles Pierce (California Institute of Technology, Pasadena, CA, USA)

Tel: +1 626 395 8086; E-mail: [email protected]

[8] Cancer biology: RNA and tumour suppression (pp 335-339)

Deletions on chromosome 5q are associated with certain blood-cell-production diseases and in Nature this week researchers identify a candidate tumour suppressor gene for these.

Using an RNA-interference-based approach to identify haploinsufficient tumour suppressor genes, Todd R. Golub and colleagues identify a molecule called RPS14. It usually acts as a regulator of ribosomal RNA processing and the research adds to the growing list of ribosomal factors that are linked to tumour suppression when they are not expressed properly. Forced expression of RPS14 in patient-derived bone marrow cells rescued the disease phenotype. The research demonstrates that RNAi screening is an effective strategy for identifying genes for haploinsufficient disorders — which occur when only a single copy of a gene is functional.


Todd R. Golub (Broad Institute of Harvard and MIT, Cambridge, MA, USA)
Tel: +1 617 252 1927; E-mail: [email protected]

[9] And finally… Sing-a-long-a-neuron (pp 305-310; N&V)

Neurons in the songbird brain that monitor matches between sung and heard songs are reported in an article in Nature this week. So-called ‘mirror neurons’ are active in primates when performing or observing specific hand gestures and are thought to be an important basis for brain mechanisms of communication, but, until now, they have not been reported for vocal communication.

Richard Mooney and colleagues identify a certain class of neuron in the swamp sparrow forebrain that has similar responses when the bird sings a series of notes, and when it hears a similar sequence sung by another bird. These neurons are connected to structures important for learning, and the authors believe that singing-related activity in these cells could help guide vocal learning. They conclude that similar mirror neurons could be involved in rapid decoding and encoding of speech in humans.


Richard Mooney (Duke University Medical Center, Durham, NC, USA)

Tel: +1 919 684 5025; E-mail: [email protected]

Ofer Tchernichovski (City College of New York, NY, USA) N&V author

Tel: +1 212 650 8540; E-mail: [email protected]


[10] The nonlinear Fano effect (pp 311-314; N&V)

[11] Net production of oxygen in the subtropical ocean (pp 323-325)

[12] Dry mantle transition zone inferred from the conductivity of wadsleyite and ringwoodite (pp 326-329)

[13] The bacterial enzyme RppH triggers messenger RNA degradation by 59 pyrophosphate removal (pp 355-358)

[14] Translational control of intron splicing in eukaryotes (pp 359-362)

[15] Structural basis of microtubule severing by the hereditary spastic paraplegia protein spastin (pp 363-367)


***These papers will be published electronically on Nature's website on 16 January 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 17 January, but at a later date. ***

[16] Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells

DOI: 10.1038/nature06498

[17] NLRX1 is a regulator of mitochondrial antiviral immunity

DOI: 10.1038/nature06501


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.


Montreal: 16

Toronto: 5


Evry: 14

Gif-sur-Yvette: 14

Orsay: 14

Paris: 14

Villeuerbanne: 14


Munich: 10

Munster: 1

Nuremburg: 1

Wurzburg: 6


Hyogo: 16

Tottori: 12


Zurich: 1


Edinburgh: 2, 10

Oxford: 4

Sevenoaks: 2



Birmingham: 16


Los Angeles: 4

Moss Landing: 11

Pasadena: 7

San Francisco: 15

Santa Barbara: 10


Louisville: 8


Chevy Chase: 8


Belmont: 1

Boston: 5, 6, 8

Cambridge: 8

Worcester: 8

New York

New York: 3, 13

North Carolina

Chapel Hill: 16

Durham: 9


Athens: 10


Dallas: 16


Seattle: 11


For North America and Canada

Katie McGoldrick, Nature Washington

Tel: +1 202 737 2355; E-mail: [email protected]

For Japan, Korea, China, Singapore and Taiwan

Mika Nakano, Nature Tokyo

Tel: +81 3 3267 8751; E-mail: [email protected]

For the UK/Europe/other countries not listed above

Katherine Anderson, Nature London

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

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Published: 16 Jan 2008

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