Metabolite levels go awry in brain tumours

Bacterial skin care, Mismatch associated with graft-versus-host-disease, East Antarctic ice loss, High levels of HLA-C associated with slower HIV/AIDS progression, A stroke against stroke, Balancing European emissions, Assessing natural memory and An amplifier for terahertz waves


For papers that will be published online on 22 November 2009

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

This press release contains:

· Summaries of newsworthy papers:

Nature: Metabolite levels go awry in brain tumours

Medicine: Bacterial skin care

Genetics: Mismatch associated with graft-versus-host-disease

Geoscience: East Antarctic ice loss

Genetics: High levels of HLA-C associated with slower HIV/AIDS progression

Medicine: A stroke against stroke

Geoscience: Balancing European emissions

Medicine: Inhibition present in absences

Cell Biology: Feeding back on tumour initiation

Immunology: Assessing natural memory

And finally…Photonics: An amplifier for terahertz waves

· 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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[1] Nature: Metabolite levels go awry in brain tumours
DOI: 10.1038/nature08617

Mutations in an enzyme that result in unusually high brain levels of the metabolite 2-hydroxyglutarate (2HG) may contribute to the formation of certain malignant brain tumours, a Nature paper suggests. Strategies that block 2HG production may prove useful therapeutically.

People with particular brain tumours, such as lower grade gliomas, often carry a mutated version of the gene that encodes the enzyme IDH1. Here, Shinsan Su and colleagues show that these mutations cause the enzyme to catalyse a different reaction, resulting in the production and build-up of 2HG.

Malignant glioma samples with IDH1 mutations had over a 100-fold more 2HG than similar samples from patients lacking the mutation, the team show. So measuring 2HG levels could be used to help identify patients with IDH1 mutant brain tumours, which is useful prognostically as they tend to outlive patients with certain other gliomas.

Author contact:
Shinsan Su (Agios Pharmaceuticals, Cambridge, MA, USA)
Tel: +1 617 649 8601; E-mail: [email protected]

[2] Medicine: Bacterial skin care
DOI: 10.1038/nm.2062

A bacterium normally present in the skin can control cutaneous inflammation, a study in this week’s Nature Medicine reports.

The normal bacterial flora of the skin includes staphylococcal species which are certain bacteria that induce inflammation when present below one of the layers of skin but are harmless on the surface layer. Richard Gallo and his coworkers found a mechanism by which staphylococci bacteria inhibit skin inflammation. This inhibition depends on the amount of LTA, a molecule produced by the staphylococci that acts on skin cells.

The authors discovered that skin cells require activation of a pathogen-sensing receptor called TLR3 to release proinflammatory molecules. Staphylococcal LTA inhibits this release acting through a second pathogen-sensing receptor: TLR2. This work is the first time that the skin flora is documented to regulate specific inflammatory responses in the skin.

Author contact:
Richard Gallo (University of California, San Diego, CA, USA)
Tel: +1 858 642 3504; E-mail: [email protected]

[3] Genetics: Mismatch associated with graft-versus-host-disease
DOI: 10.1038/ng.490

A genetic mismatch involving the gene UGT2B17 is associated with risk of acute graft-versus-host-disease, according to a study published online in this week’s Nature Genetics.

Graft-versus-host-disease (GVHD) is a common complication after bone marrow transplant and is caused by an immune response mounted by the donor-derived cells against the host’s body. GVHD occurs in 30-40% of transplants between related donors and recipients and up to 60-80% of transplants between unrelated donors and recipients.

Steven McCarroll and colleagues analyzed gene deletions in over 1000 sibling donor-recipient pairs and found a greater risk of acute GVHD in pairs where the donor had deletions in both copies of the gene UGT2B17 and the recipient did not have these deletions. The risk effect of UGT2B17 mismatch is comparable to the established risk effect of gender mismatch – such as female donor and male recipient.

Author contact:
Steven McCarroll (Broad Institute of Harvard and MIT, Cambridge, MA, USA)
Tel: +1 415 215 7545; E-mail: [email protected]

[4] Geoscience: East Antarctic ice loss
DOI: 10.1038/ngeo694

East Antarctica seems to have started losing ice in 2006, according to a study published online this week in Nature Geoscience. Gravity measurements of ice mass in Antarctica confirm earlier estimates of ice loss in West Antarctica, and suggest that East Antarctica has dropped out of balance in the past few years.

Jianli Chen and colleagues used data obtained with the Gravity Recovery and Climate Experiment (GRACE) to estimate Antarctica’s ice mass between April 2002 and January 2009. Their estimate of a loss of 132 gigatonnes of ice per year from West Antarctica provides an independent confirmation of earlier results. However, the researchers also found that the East Antarctic ice sheet, which had been in balance within error margins, started to lose mass from about 2006.

The estimated loss comes from East Antarctica’s coastal regions and lies at 57 gigatonnes per year, albeit with a large uncertainty range of +/-52 gigatonnes per year.

Author contact:
Jianli Chen (University of Texas, Austin, TX, USA)
Tel: +1 512 232 6218; Email: [email protected]

[5] Genetics: High levels of HLA-C associated with slower HIV/AIDS progression
DOI: 10.1038/ng.486

High levels of the protein HLA-C – a crucial part of the immune system – are associated with slower progression of HIV/AIDS, according to a study published online this week in Nature Genetics.

About 40 million people worldwide are living with HIV/AIDS, a serious disease of the immune system. Although many anti-retroviral medications have been developed that can extend the lives of HIV-positive individuals, none of these medications can cure the disease.

Previously, a genetic variant found near the HLA-C gene had been associated with expression levels of HLA-C mRNA as well as levels of HIV RNA. Mary Carrington and colleagues now extend these findings, showing that this genetic variant is also associated with HLA-C protein levels. Furthermore, the authors show that HIV-positive individuals with high levels of HLA-C progress more slowly to AIDS and that their HIV levels are significantly better controlled.

Author contact:
Mary Carrington (National Cancer Institute, Frederick, MD, USA)
Tel: +1 301 846 1390; E-mail: [email protected]

[6] Medicine: A stroke against stroke
DOI: 10.1038/nm.2064

A new cellular mechanism linked to neuronal damage during stroke is reported this week in Nature Medicine. Targeting this mechanism may have therapeutic potential in people.

Damage caused by overactivation of excitatory receptors in the brain is a principal cause of neuronal loss after stroke. Among these receptors, the so-called NMDA subtype of glutamate receptors is a key player. Yu Tian Wang and his team found that activation of a molecule called SREBP-1 in affected neurons is an essential step in NMDA receptor–mediated neuronal death in stroke in mice.

According to the authors, the activation of SREBP-1 is linked to the loss of a known SREBP-1 binding partner known as Insig-1. Using a compound capable of inhibiting the loss of Insig-1, the team could interfere with SREBP-1 activation, and therefore reduce neuronal damage and prevent neurological deficits after stroke in mice. This highlights the potential of agents that reduce SREBP-1 activation in cases of stroke.

Author contact:
Yu Tian Wang (University of British Columbia, Vancouver, Canada)
Tel: +1 604 822 0398; E-mail: [email protected]

[7] Geoscience: Balancing European emissions
DOI: 10.1038/ngeo686

Emissions of methane and nitrous oxide from feedstock and agriculture negate the uptake of carbon dioxide by forests and grasslands in Europe, according to a study published online this week in Nature Geoscience.

Detlef Schulze and colleagues compiled estimates of European carbon dioxide, methane and nitrous oxide fluxes between 2000 and 2005, and developed a greenhouse-gas balance for Europe. Forests and grasslands seem to function as a carbon dioxide sink. However, agricultural methane and nitrous oxide emissions fully compensate for this sink, resulting in a near neutral greenhouse-gas balance across the continent.

The researchers warn that the trend towards more intensive agriculture and logging is likely to make Europe a significant source of greenhouse gases in the future.

Author contact:
Detlef Schulze (Max-Planck Institute for Biogeochemistry, Jena, Germany)
Tel: +49 3641 576100; Email: [email protected]

[8] Medicine: Inhibition present in absences
DOI: 10.1038/nm.2058

An unexpected role of inhibitory activity in promoting epilepsy is reported in a study in this week’s Nature Medicine. The work points to new potential targets for the treatment of certain types of seizures.

Epileptic activity in the brain is commonly believed to be the result of reduced inhibitory activity and increased neuronal excitation. David Cope and his colleagues show that inhibitory activity is actually increased in mouse and rat forms of epilepsy known as absence seizures – usually characterized by a lack of movement and sufferers ‘staring into space’.

The team found that the increased inhibition is due to a reduction in the uptake of GABA—the main inhibitory neurotransmitter in the nervous system. The team also found that the selective activation of GABA receptors was sufficient to elicit absence seizures in mice and rats.

These results disclose an unexpected mechanism that may have importance in human epilepsy and point to novel potential targets for the treatment of absence seizures.

Author contact:
David Cope (Cardiff University, UK)
Tel: +44 2920 879113; E-mail: [email protected]

[9] Cell Biology: Feeding back on tumour initiation
DOI: 10.1038/ncb1998

The protein ZEB1 – which is known to promote invasiveness of epithelial tumours– also influences the tumour initiating capacity of pancreatic and colorectal cancer cells, and could possibly promote cancerous cells proliferation once they have reached a new organ. The finding, published online this week in Nature Cell Biology, suggests that targeting a feedback loop in which ZEB1 is involved in might represent a promising avenue for the treatment of certain cancers.

The small RNAs of the miR200 family were previously reported to inhibit cell invasion and movement of certain cancerous tissues via direct inhibition of ZEB1. ZEB1 in turn suppresses the expression of miR200. Thomas Brabletz and colleagues now show that miR200 also inhibits various factors required for the maintenance of stem cells characteristics, including factors that promote self-renewal, proliferation and inhibit differentiation. They also demonstrate that loss of ZEB1 in human pancreatic cancer cell lines reduces their tumour initiation potential by suppressing miR200-dependent inhibition of stem cells factors. By examining primary pancreatic cancer tissues of mouse and human origins, they show that less differentiated tumours express high levels of ZEB1 and stem cell factors, while tumours isolated from patients that are long term survivors of pancreatic cancers have low ZEB1.

This study suggests that ZEB1 promotes both tumour spread and initiation by enhancing the stem cells characteristics of the cells that migrate away from the primary tumour to form metastases.

Author contact:
Thomas Brabletz (University of Freiburg, Germany)
Tel: +49 761 270 2577; E-mail: [email protected]

[10] Immunology: Assessing natural memory
DOI: 10.1038/ni.1826

How immune cells remember a natural pathogen varies depending on the route of infection, according to a report published this week online in Nature Immunology. The finding could affect vaccination strategies for achieving long-term immunologic protection in humans.

Marc Jenkins and colleagues assessed the generation and function of memory CD4+ T cells – also called T helper cells – in mice infected with bacteria that expressed a unique marker. This allowed the authors to count the number of those specific memory CD4+ T cells, thereby giving a more accurate measure of memory cell formation and longevity of these cells during a natural infection.

Infections occurring directly through the blood steam trigger more T cells that express the inflammatory molecule interferon-gamma (IFN-gamma), which helps to destroy host cells infected by the pathogen. Intranasal vaccination led to higher numbers of immune cells producing interleukin 17 (IL-17), which recruits more immune cells and triggers antimicrobial responses. Surprisingly, the IL-17-expressing immune cells are short-lived and wane several weeks after infection, whereas memory cells capable of producing IFN-gamma survived months longer.

Author contact:
Marc Jenkins (University of Minnesota, Minneapolis, MN, USA)
Tel: +1 612 626 2715; E-mail: [email protected]

[11] Photonics: An amplifier for terahertz waves
DOI: 10.1038/nphoton.2009.213

A powerful amplifier for boosting Terahertz waves — radiation that lies between the microwave and infrared regions of the spectrum — is reported this week online in Nature Photonics. This study could be the key to unlocking the potential of terahertz waves (THz) for applications in pharmaceuticals research, security screening for explosives or drugs, and biological imaging.

Terahertz waves are often very weak, which has so far limited their use. Nathan Jukam and colleagues have shown that a powerful amplifier for boosting THz waves can be made by integrating a special switch with a semiconductor laser. This can override the usual limit of the signal strength in the short time period before the laser settles into normal operation mode. The researchers show that the signal can be amplified by a factor of 400, which could greatly enhance the performance of THz equipment.

Author contact:
Nathan Jukam (Université Paris 6, France)
Tel: +33 1 44 32 34 44; E-mail: [email protected]

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

Nature (

[12] Extreme particle acceleration in the microquasar Cygnus X-3
DOI: 10.1038/nature08578


[13] DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity
DOI: 10.1038/nbt.1587


[14] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex
DOI: 10.1038/ncb1990

[15] YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway
DOI: 10.1038/ncb1993

[16] Cell fate decisions are specified by the dynamic ERK interactome
DOI: 10.1038/ncb1994


[17] Confinement-induced quorum sensing of individual Staphylococcus aureus bacteria
DOI: 10.1038/nchembio.264

[18] Ureide catabolism in Arabidopsis thaliana and Escherichia coli
DOI: 10.1038/nchembio.265

[19] Automatic policing of biochemical annotations using genomic correlations
DOI: 10.1038/nchembio.266

[20] HIV-1 Nef membrane association depends on charge, curvature, composition and sequence
DOI: 10.1038/nchembio.268


[21] Pressure-induced bonding and compound formation in xenon–hydrogen solids
DOI: 10.1038/nchem.445

[22] Template synthesis of precisely monodisperse silica nanoparticles within self-assembled organometallic spheres
DOI: 10.1038/nchem.446


[23] Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans
DOI: 10.1038/ng.484


[24] Migration of early aftershocks following the 2004 Parkfield earthquake
DOI: 10.1038/ngeo697

[25] Prolonged mantle residence of zircon xenocrysts from the western Eger rift
DOI: 10.1038/ngeo695


[26] Exceptionally large positive and negative anisotropic thermal expansion of an organic crystalline material
DOI: 10.1038/nmat2583

[27] Liquid-gated interface superconductivity on an atomically flat film
DOI: 10.1038/nmat2587


[28] Comprehensive genomic access to vector integration in clinical gene therapy
DOI: 10.1038/nm.2057

[29] A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6–dependent B cell lymphomas
DOI: 10.1038/nm.2059

[30] A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q– syndrome
DOI: 10.1038/nm.2063


[31] A novel intracellular protein delivery platform based on single-protein nanocapsules
DOI: 10.1038/nnano.2009.341

[32] Nanoscale chemical mapping using three-dimensional adiabatic compression of surface plasmon polaritons
DOI: 10.1038/nnano.2009.348


[33] Nardilysin regulates axonal maturation and myelination in the central and peripheral nervous system
DOI: 10.1038/nn.2438

[34] Endogenous amyloid-b regulates temporal code at single hippocampal synapses
DOI: 10.1038/nn.2433

[35] Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides
DOI: 10.1038/nn.2452


[36] Optimal quantum cloning of orbital angular momentum photon qubits through Hong–Ou–Mandel coalescence
DOI: 10.1038/nphoton.2009.214

[37] Non-resonant dot–cavity coupling and its potential for resonant single-quantum-dot spectroscopy
DOI: 10.1038/nphoton.2009.215

[38] A passively mode-locked external-cavity semiconductor laser emitting 60-fs pulses
DOI: 10.1038/nphoton.2009.216

[39] Tuning a terahertz wire laser
DOI: 10.1038/nphoton.2009.218

Nature PHYSICS (

[40] Observation of a d-wave nodal liquid in highly underdoped Bi2Sr2CaCu2O8+delta
DOI: 10.1038/nphys1456

[41] Breaking the 10nm barrier in hard-X-ray focusing
DOI: 10.1038/nphys1457


[42] Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions
DOI: 10.1038/nsmb.1725

[43] Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II
DOI: 10.1038/nsmb.1689

[44] Reconstitution of both steps of Saccharomyces cerevisiae splicing with purified spliceosomal components
DOI: 10.1038/nsmb.1729

[45] Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain
DOI: 10.1038/nsmb.1731


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.

Sydney: 13
Parkville: 34
Perth: 25
Westmead: 42

Vienna: 20

Braunschweig: 7
Brussels: 23
Wilrijk: 7

London: 23
Vancouver: 6

Beijing: 31
Hefei: 25
Shanghai: 2

Helsinki: 3
Joensuu: 7
Kylmala: 12

Cachan: 28
Gif-sur-Yvette: 7
Orsay: 40
Paris: 11, 28

Bergisch-Gladbach: 45
Berlin: 18
Dortmund: 20
Frankfurt: 35
Freiburg: 9, 35
Garching: 20
Goettingen: 44
Heidelberg: 7, 28
Homburg: 35
Jena: 7
Konstanz: 2
Marktredwitz: 25
Munich: 25
Stuttgart: 7, 37, 40
Tuebingen: 25
Wurzburg: 37

Dublin: 16

Haifa: 40
Tel-Aviv: 34

Bologna: 12, 16
Catanzaro: 32
Como: 12
Frascati: 12
Genova: 32
Milan: 28
Milano: 12
Modena: 28
Napoli: 36
Palermo: 8, 12
Pavia: 12, 32
Rome: 7, 12, 28, 36
Trieste: 12, 32
Torino: 12
Viterbo: 7

Aichi: 33
Hyogo: 41
Ibaraki: 40
Kanagawa: 14
Kobe: 33
Kyoto: 33
Osaka: 41
Saitama: 27, 33
Sendai: 27
Tokyo: 22, 35
Tsu: 33

Msida: 8

Amsterdam: 7, 23
Groningen: 23
Utrecht: 23
Wageningen: 7
Zwolle: 23

Oslo: 23

Nizhnij Arkhyz: 12

Stellenbosch: 26

Lausanne: 5
Villigen: 40
Zurich: 19

Taichung: 6

Al Ain: 23

Aberdeen: 7
Cardiff: 8
Cambridge: 3, 5, 12, 30, 38, 45
Edinburgh: 7, 9
Glasgow: 9, 16
Leeds: 11
London: 28
Middlesex: 16
Oxford: 30
Scotland: 16
Southampton: 38


Birmingham: 43

La Jolla: 2
Los Angeles: 1, 25, 31, 39
San Diego: 2
San Francisco: 5

District of Columbia
Washington: 21

Augusta: 29
Atlanta: 24

Argonne: 21, 40
Chicago: 21, 40

Iowa City: 14

Louisville: 9

Baltimore: 5
Bethesda: 29
Frederick: 5
Rockville: 5

Boston: 1, 3, 5, 15
Cambridge: 1, 3, 12, 39
Charlestown: 15

Ann Arbor: 3

Minneapolis: 10

New Hampshire
Durham: 5
Hanover: 17

New Jersey
Piscataway: 43
Princeton: 1

New Mexico
Albuquerque: 17, 39

New York
New York: 19, 29, 35, 40

Cincinnati: 28
Columbus: 40, 43

Philadelphia: 1

Austin: 4
College Station: 15
Dallas: 2

Seattle: 3


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 9324; 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 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: 22 Nov 2009

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