Gene transfer protects monkeys against SIV infection

Summaries of newsworthy papers The biology of ice, Gut acid levels determine healthy bones, Identifying problems in proteomics, Dopamine neurons are a mixed bunch, Natural products in reach, Interleukin 17—a Jekyll and Hyde of the immune system? and Gene variants to set your biological clock by


For papers that will be published online on 17 May 2009

This press release is copyrighted to the Nature journals mentioned below. Its use is granted only for journalists and news media receiving it directly from the Nature journals.

This press release contains:

· Summaries of newsworthy papers:

Medicine: Gene transfer protects monkeys against SIV infection
Geoscience: The biology of ice
Medicine: Gut acid levels determine healthy bones
Methods: Identifying problems in proteomics
Nature: Dopamine neurons are a mixed bunch
Chemical Biology: Natural products in reach
Immunology: Interleukin 17—a Jekyll and Hyde of the immune system?
And finally … Genetics: Gene variants to set your biological clock by

· 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 Press contacts for the Nature journals are listed at the end of this release.

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HYPE: We take great care not to hype the papers mentioned on our press releases, but are sometimes accused of doing so. If you ever consider that a story has been hyped, please do not hesitate to contact us at [email protected], citing the specific example.


[1] Medicine: Gene transfer protects monkeys against SIV infection
DOI: 10.1038/nm.1967

Delivering an antibody-coding gene to the muscle of monkeys protects them against the infection simian immunodeficiency virus (SIV), according to research published online this week in Nature Medicine.

Finding a way to elicit persisting antibodies with broad neutralizing activity against HIV would be a major breakthrough for vaccine development, but progress on this front has been very scarce. Using the SIV primate model, Philip Johnson and his colleagues have taken a different approach: delivery of a gene that expresses antibodies with predetermined SIV specificity. With this approach, the muscle that the gene is delivered to produces antibodies that passively travel to the bloodstream and specifically target SIV.

With this strategy, the team elicited long-lasting neutralizing activity in the serum of macaques, leading to complete protection against intravenous challenge with virulent SIV. This approach could hold promise as an alternative approach to an HIV vaccine.

Author Contact:

Philip Johnson (Children’s Hospital of Philadelphia, Philadelphia, PA, USA)
Tel: +1 267 426 0351; E-mail: [email protected]

[2] Geoscience: The biology of ice
DOI: 10.1038/ngeo521

Biological particles, such as bacteria, fungal spores and plant material, trigger ice formation in clouds, suggests a study published online in Nature Geoscience. The finding could prove important because the effect of airborne particles on the formation of cloud ice is one of the largest remaining sources of uncertainty in climate change projections.

Kim Prather and colleagues loaded a newly developed mass spectrometer onto an aircraft and examined the chemical composition of atmospheric ice-forming particles in a cloud over Wyoming. They found that biological particles accounted for 33% of the ice-forming particles, and mineral dust accounted for 50%.

Using a global aerosol model the team suggest that biological particles can enhance the formation of cloud ice that forms in response to desert storms.

Author contact:

Kim Prather (Scripps Institution of Oceanography, San Diego, CA, USA)
Tel: +1 858 822 5312; Email: [email protected]

[3] Medicine: Gut acid levels determine healthy bones
DOI: 10.1038/nm.1963

Gastric acidification plays a key role in regulating the proper calcium levels needed to maintain healthy bones. The study, online this week in Nature Medicine, could have implications in the bone condition osteopetrosis as well as for patients on proton pump inhibitors that are used to treat gastrointestinal diseases such as peptic ulcers.

Osteopetrosis is a condition of pathologically high bone mass. In a subset of these patients there is also evidence of osteopetrorickets - brittle bones due to low calcium levels. Recent evidence has pointed to associations of osteopetrosis with mutations in the TCIRG1 gene, which encodes for a subunit of a proton pump that is required for the proper activity of bone-resorbing cells, called osteoclasts. Michael Amling and colleagues show that Tcirg1 mutant mice have an osteopetrorickets phenotype; whereas, historically, mice mutated in other genes that also control osteoclast activity have only an osteopetrosis phenotype, indicating that these two diseases are distinct.

The team also investigate why osteoclast function is affected in both diseases yet rickets occur in only one and not in the other. They show that Tcirg1 is also expressed in gut cells that control gastric pH levels and that mutant Tcirg1 mice have abnormally high gastric pH. The results suggest that a combination of defects in bone resorption and in gastric pH, likely affecting calcium absorption from the diet, explains the osteopetrorickets phenotype.

This study shows that defects in proton pump activity lead to distinct bone diseases, depending on which cell type is affected. These results could have important clinical implications for patients on proton-pump inhibitors that are used to treat various gastrointestinal conditions, as alterations in gastric pH by these drugs could reduce calcium absorption, weakening their bones.

Author Contact:

Michael Amling (University Medical Center Hamburg-Eppendorf, Germany)
Tel: +49 40 42803 6083; E-mail: [email protected]

[4] Methods: Identifying problems in proteomics
DOI: 10.1038/nmeth.1333

Common problems encountered during proteomics workflows - the analysis of all proteins in a biological sample – are identified in a paper online in Nature Methods this week. Proteomics is most often carried out using mass spectrometry technology, which has gained a reputation of being poorly reproducible. This work could therefore be used as a basis for looking into how to overcome these issues.

John Bergeron and colleagues from several other laboratories created test samples consisting of 20 highly purified proteins present at equal concentrations. They sent these samples to 27 different labs, asking the members of these labs to identify the 20 proteins by the mass spectrometry instrumentation and workflows they routinely use. Initially, only 7 of the 27 labs correctly reported all 20 proteins. However, when the study designers reanalyzed the labs’ data, they found that almost all of the labs had generated sufficient data to identify the proteins but for various reasons were unable to report the correct protein identities. Although some of the labs made simple mistakes in sample handling, most of the problems stemmed from difficulties in applying proteomic database search tools to interpret the data rather than from the mass spectrometry technology itself. In the end, with coaching from the study designers, members of all 27 labs were able to identify all 20 proteins.

Though 20 proteins is, of course, not representative of a complex biological proteome, the study demonstrates that high-quality, reproducible data can be generated by different labs using different mass spectrometry–based proteomics workflows. However, in an accompanying News & Views, Ruedi Aebersold emphasizes that proper training is very important for correctly applying this technology.

Author contact:

John Bergeron (McGill University, Montreal, Canada)
Tel: +1 514 398 1259; E-mail: [email protected]

Ruedi Aebersold (ETH Zurich, Switzerland) N&V author
Tel: +41 44 633 31 70; E-mail: [email protected]

[5] Nature: Dopamine neurons are a mixed bunch
DOI: 10.1038/nature08028

Dopamine neurons are more heterogeneous than was previously thought, a Nature paper suggests. The finding challenges widely held conceptions about this cell type, which are known to be involved in motor control and reward processing.

Masayuki Matsumoto and Okihide Hikosaka report that in monkeys, two types of dopamine neuron distinctly convey positive and negative motivational signals. The different cell types, located in slightly different brain regions, have specific responses to pleasant and unpleasant stimuli, as well as to the trigger stimuli that have become linked with these events.

The findings contradict the view that dopamine neurons act as a functionally homogeneous group, guiding motor learning by reward-related signals. Here, separate groups of dopamine neurons transmit signals related to ‘salience’ and ‘value.’

Author contact:
Masayuki Matsumoto (National Eye Institute, Bethesda, MD, USA)
Tel: +1 301 451 9905; E-Mail: [email protected]

[6] & [7] Chemical Biology: Natural products in reach

DOI: 10.1038/nchembio.176
DOI: 10.1038/nchembio.177

New ways to obtain elusive natural products are reported in two studies published online this week in Nature Chemical Biology. These small molecules are particularly important as they often play a central role in drug discovery efforts, either by serving directly as drugs or lead compounds, or by providing new chemical scaffolds.

Some natural products have evolved as a response to a particular ecological cue, such as the presence of an enemy or adverse weather conditions. As a result, the compounds are not typically produced in laboratory environments. Two papers describe methods to find these compounds by manipulating or reading the genes that encode them.

Joern Piel and colleagues tackled the complicated system of interacting symbionts in sea sponges. Because the bacteria often depend on the sponge for growth, and many kinds of bacteria can be housed in a single sponge, characterizing a single bacterium is significantly challenging, if not impossible. The authors used their understanding of the chemical reactions that are required to make the molecules to search for the DNA sequence of a particular type of biosynthetic enzyme - the ketosynthases. With the DNA in hand, the authors were able to quickly identify all of the genes needed for compound synthesis.

In a different approach, Nancy Keller and colleagues were inspired by the discovery that natural products might be regulated by histone modifications, or epigenetic signals. By removing a critical component of a protein complex involved in histone modifications, the authors observed the appearance of several small molecules.

Both strategies should provide general approaches for natural product discovery.

Author contacts:

Joern Piel (University of Bonn, Germany) Author paper [6]
Tel: + 49 228 732 652, E-mail: [email protected]

Nancy P. Keller (University of Wisconsin-Madison, WI, USA) Author paper [7]
Tel: +1 608 262 9795, E-mail: [email protected]

[8] Immunology: Interleukin 17—a Jekyll and Hyde of the immune system?
DOI: 10.1038/ni.1736

Interleukin 17 (IL-17)—a soluble factor thought to promote inflammation and autoimmunity—can actually suppress the onset of inflammatory bowel disease, shows a paper published online in this week’s Nature Immunology.

Previous work documented high concentrations of IL-17 and interferon-gamma, another cytokine implicated in inflammation and autoimmunity, in colon tissue of humans with Crohn’s disease and mice with colitis.

Using a mouse model of colitis in which immune cells called T cells initiate disease, Richard Flavell and colleagues note that T cells lacking IL-17 or the IL-17 receptor induced more severe colitis than T cells able to produce and respond to IL-17. IL-17-deficient T cells also released more interferon-gamma.

These findings suggest net effects of IL-17 may be pro- or anti-inflammatory, and likely depend on the tissue and environment being examined.

Author contact:

Richard Flavell (Yale University, New Haven, CT, USA)
Tel: + 1 203 737 2216; E-mail: [email protected]

[9], [10], [11], [12] & [13] Genetics: Gene variants to set your biological clock by

DOI: 10.1038/ng.382
DOI: 10.1038/ng.383
DOI: 10.1038/ng.385
DOI: 10.1038/ng.386
DOI: 10.1038/ng.387

Genes may provide some clues to the variation in the age at which a woman gets her first and last menstrual period according to five independent studies published online this week in Nature Genetics.

Reproductive lifespan is a fundamental mystery of the aging body and these two landmark events of the biological clock are powerful predictors of health outcomes such as personal lifetime risks of breast cancer and osteoporosis.

These studies find that the timing contribution of each gene variant identified was small relative to the range naturally found among women, but some of the same variants are also found associated with height and body weight.

The onset of puberty in particular is also strongly influenced by environmental factors such as nutrition and athletic training and this research provides new ways to investigate how these characteristics influence one another.

Author contacts:

Ken Ong (University of Cambridge, UK) Author paper [9]
Tel: +44 1223 769 207; E-mail: [email protected]

Ruth Loos (University of Cambridge, UK) Co-author paper [9]
Tel: +44 1223 769139; E-mail: [email protected]

Patrick Sulem (deCODE Genetics, Reykjavik, Iceland) Author paper [10]
Phone +354 570 2371; E-mail: [email protected]

Chunyan He (Harvard School of Public Health, Boston, MA, USA) Author paper [11]
Tel: +1 617 432 7092; E-mail: [email protected]

Andre Uitterlinden (Erasmus MC, Rotterdam, The Netherlands) Author paper [12] & [13]
Tel: + 31 10 704 3573; E-mail: [email protected]


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

Nature (

[14] Hippocampal theta oscillations are travelling waves
DOI: 10.1038/nature08010

[15] dUTP incorporation into genomic DNA is linked to transcription in yeast
DOI: 10.1038/nature08033

[16] The Listeria transcriptional landscape from saprophytism to virulence
DOI: 10.1038/nature08080


[17] Efficient siRNA delivery into primary cells by a peptide transduction domain–dsRNA binding domain fusion protein
DOI: 10.1038/nbt.1541


[18] p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug
DOI: 10.1038/ncb1875

[19] Local auxin biosynthesis modulates gradient-directed planar polarity in Arabidopsis
DOI: 10.1038/ncb1879

[20] The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C– Cdh1
DOI: 10.1038/ncb1881

[21] TGF‑b signalling is regulated by Schnurri‑2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3
DOI: 10.1038/ncb1885


[22] Room-temperature molecular-resolution characterization of self-assembled organic monolayers on epitaxial grapheme
DOI: 10.1038/nchem.212

[23] Spongy chalcogels of non-platinum metals act as effective hydrodesulfurization catalysts
DOI: 10.1038/nchem.208

[24] Manipulating single-wall carbon nanotubes by chemical doping and charge transfer with perylene dyes
DOI: 10.1038/nchem.214


[25] Tectonic history of the Earth’s inner core preserved in its seismic structure
DOI: 10.1038/ngeo522

[26] Mid-Pliocene climate change amplified by a switch in Indonesian subsurface throughflow
DOI: 10.1038/ngeo520

[27] Volcanism in the Solar System
DOI: 10.1038/ngeo529


[28] RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci
DOI: 10.1038/ni.1735


[29] Size-controlled stabilization of the superionic phase to room temperature in polymer-coated AgI nanoparticles
DOI: 10.1038/nmat2449

[30] Templated formation of giant polymer vesicles with controlled size distributions
DOI: 10.1038/nmat2446

[31] A highly ordered nanostructured carbon–sulphur cathode for lithium–sulphur batteries
DOI: 10.1038/nmat2460


[32] Inhibition of osteoblastic bone formation by nuclear factor-kB
DOI: 10.1038/nm.1954

[33] Prophylactic treatment with sialic acid metabolites precludes the development of myopathic phenotype in the DMRV-hIBM mouse model
DOI: 10.1038/nm.1956

[34] Netting neutrophils in autoimmune small-vessel vasculitis
DOI: 10.1038/nm.1959


[35] Rapid creation and quantitative monitoring of high coverage shRNA libraries
DOI: 10.1038/nmeth.1330


[36] Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release
DOI: 10.1038/nn.2315

[37] Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells
DOI: 10.1038/nn.2339


[38] Near-infrared imaging with quantum-dot-sensitized organic photodiodes
DOI: 10.1038/nphoton.2009.72

[39] Observing angular deviations in the specular reflection of a light beam
DOI: 10.1038/nphoton.2009.75

Nature PHYSICS (

[40] Wave–particle duality of single surface plasmon polaritons
DOI: 10.1038/nphys1278

[41] Photon burst detection of single atoms in an optical cavity
DOI: 10.1038/nphys1282

[42] Individual topological tunnelling events of a quantum field probed through their macroscopic consequences
DOI: 10.1038/nphys1276


[43] Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes
DOI: 10.1038/nsmb.1597

[44] Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases
DOI: 10.1038/nsmb.1604

[45] Cancer-associated regulation of alternative splicing
DOI: 10.1038/nsmb.1608



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.

Nedlands: 12
Parkville: 4
Victoria: 4

Linz: 38
Vienna: 6, 28

London: 4
Montreal: 4
Saint Laurent: 4
Sherbrooke: 45
Toronto: 4, 37
Vancouver: 4
Waterloo: 31, 42

Concepcion: 41

Beijing: 4
Shanghai: 41

Copenhagen: 10
Herlev: 10
Odense: 9

Gif-sur-Yvette: 44
Grenoble: 25
Orsay: 28
Paris: 16

Berlin: 3, 34
Bochum: 4
Bonn: 6
Bremen: 26
Bremerhaven: 26
Erlangen: 24, 38, 39
Freiburg: 24
Goettingen: 19
Hamburg: 3
Heidelberg: 34
Jena: 6
Karlsruhe: 38
Kiel: 26
Lubeck: 34
Mannheim: 34
Martinsried: 34
Munich: 34
Stuttgart: 40
Ulm: 3
Wurzburg: 6

Kopavogur: 12
Reykjavik: 10, 12

Kharagpur: 26

Dublin: 4

Florence: 12
L’Aquila: 3
Rozzano: 3
Segrate: 3
Trieste: 24

Fukuoka: 29
Hyogo: 29
Kyoto: 29, 33
Sapporo: 29
Tokyo: 8, 17, 29, 33
Yamaguchi: 4

Amsterdam: 13
Eindhoven: 13
Leiden: 39
Nijmegen: 10
Rotterdam: 12, 13
Tilburg: 13
Utrecht: 13

Wellington: 6

Seoul: 4

Pamplona: 16
Salamanca: 20

Orebro: 9
Umea: 16, 19

Lausanne: 9
Zurich: 43

Tainan: 6
Taipei: 18

Bristol: 9
Cambridge: 9, 12, 13
Didcot: 44
Exeter: 12
Lancaster: 27
London: 9, 12, 13, 20, 28, 44
Sheffield: 30

Aliso Viejo: 4
Carlsbad: 4
Foster City: 4
Irvine: 4
La Jolla: 2, 4, 17
Los Angeles: 4, 6, 8, 32
Milford: 4
Monterey: 2
Pasadena: 14
San Diego: 32
San Francisco: 34, 35
Santa Clara: 4, 35
Santa Cruz: 6
Boulder: 2
Fort Collins: 2
New Haven: 8, 28
District of Columbia
Washington: 4, 41
Atlanta: 9, 10
Evanston: 22, 23
Urbana: 42
Lawrence: 6
Baltimore: 12
Bethesda: 4, 5, 11, 12, 21
College Park: 41
Boston: 4, 11, 12
Cambridge: 4, 11, 42
Framingham: 12
Southborough: 1
Ann Arbor: 32
Minneapolis: 12, 28
St Louis: 28
New Hampshire
Durham: 30
New Jersey
Hackensack: 21
New York
New York: 28
North Carolina
Chapel Hill: 12
Durham: 15
Raleigh: 19
Columbus: 1, 6
Corvallis: 2
King of Prussia: 9
Philadelphia: 1, 28
Pittsburgh: 4, 8
Austin: 17
College Station: 40
Houston: 12
Salt Lake City: 42
Bellingham: 23
Seattle: 4
Madison: 6, 36
Laramie: 2


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

Rachel Twinn (Nature London)
Tel: +44 20 7843 4658; E-mail: [email protected]

Neda Afsarmanesh (Nature New York)
Tel: +1 212 726 9231; E-mail: [email protected]

Ruth Francis (Head of Press, Nature, London)
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)
Craig Mak
Tel: +1 212 726 9284; E-mail: [email protected]

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 Chemistry (London)
Stuart Cantrill
Tel: +44 20 7014 4018; E-mail: [email protected]

Nature Genetics (New York)
Myles Axton
Tel: +1 212 726 9315; E-mail: [email protected]

Nature Geoscience (London)
Heike Langenberg
Tel: +44 20 7843 4042; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Vincent Dusastre
Tel: +44 20 7843 4531; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Hugh Ash
Tel: +1 212 726 9627; E-mail: [email protected]

Nature Nanotechnology (London)
Peter Rodgers
Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; 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)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]

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Published: 18 May 2009

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