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Article Released Sun-11th-May-2008 17:33 GMT
Contact: Ruth Institution: Nature Publishing Group
 Frogs on call

Nocturnal tree frogs living in China have been found to possess extraordinary vocal skills comparable to dolphins, elephants and humans. Summaries of other newsworthy papers include The origins of the modern tomato, Insight into devastating pregnancy condition, Targeting dormant leukaemia cells, Tracking plates in the subsurface & more


For papers that will be published online on 11 May 2008

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

This press release contains:

· Summaries of newsworthy papers:

Nature Genetics: The origins of the modern tomato

Nature Cell Biology: Stem-cell regeneration of the breast relies on adhesion

Nature: Strengthen your synapses for better reward-directed learning

Nature: Insight into devastating pregnancy condition

Nature Genetics: Modeling psychiatric disorders in mice

Nature Chemical biology: Stopping DNA synthesis before it starts

Nature: Targeting dormant leukaemia cells

Nature Geoscience: When glaciers cut deep

Nature Medicine: Fighting glioma-associated edema

Nature Geoscience: Tracking plates in the subsurface

Nature Immunology: Strength in numbers

And finally… Nature: Frogs on call

· 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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NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: (For example, For more information about DOIs and Advance Online Publication, see


[1] Nature Genetics: The origins of the modern tomato
DOI: 10.1038/ng.144

Scientists have identified a genetic mutation that acts as a major contributor to the extreme fruit size associated with the modern tomato, according to a study published online this week in Nature Genetics.

Modern cultivated tomatoes produce fruit as much as 1,000 times larger than their wild progenitors. One clear reason for the increase in tomato size during its domestication is the increased number of carpels – organs – which determines the final number of compartments in the fruit.

Steven Tanksley and colleagues crossed lines of tomatoes with either high or low compartment number, and carried out genetic mapping studies to identify the gene or genes responsible for the variation in carpel number. They identified an insertion of 6–8 kilobases in a gene they call fas only in the tomatoes with high compartment number. Expression of the gene is reduced in the developing flower buds in tomatoes carrying the insertion. A survey of 30 different lines of cerasiforme, the wild form of tomato thought to be related to the smaller progenitors, showed that none carried the insertion.

As the insertion is found exclusively in modern cultivated tomatoes, the authors suggest that the mutation occurred recently in tomato domestication, and then spread rapidly as a result of selection for larger fruit.

Author contact:
Steven Tanksley (Cornell University, Ithaca, NY, USA)
Tel: +1 607 255 1673; E-mail:

[2] Nature Cell Biology: Stem-cell regeneration of the breast relies on adhesion
DOI: 10.1038/ncb1734

Interaction of basal stem cells in the breast with their cellular environment is crucial for their function, and helps towards the regeneration of the mammary glands during pregnancy, reports a paper online this week in Nature Cell Biology.

The basal stem cells of the breast are enriched in proteins called integrins that mediate contact with the extracellular matrix surrounding the cells. Marina Glukhova and colleagues show that expression of beta 1 integrin in the basal cells is essential for the regenerative potential of these stem cells and for proper development of the mammary gland during pregnancy.

Deletion of the beta 1 integrin gene from the basal layer of mouse mammary tissue led to an abnormal ductal branching pattern in the mammary gland during pregnancy, which results in the regenerative potential of the mammary tissue stem cells being abolished, leading to a dysfunctional gland. In basal stem cells lacking beta 1 integrin, cells divide abnormally and this results in the altered branching pattern.

The environment that surrounds most stem cells, the stem cell niche, is known to be important for a number of stem cells. However, our understanding of stem cell niches remains patchy. These findings establish a central role of direct interaction between basal stem cells and their extracellular matrix in the maintenance of the mammary stem-cell population.

Author contact:
Marina Glukhova (CNRS-Institut Curie Research, Paris, France)
Tel: +33 1 42 34 63 33; E-mail:

[3] Nature: Strengthen your synapses for better reward-directed learning
DOI: 10.1038/nature06963

No one quite understands the neuronal changes that govern reward-directed learning. A paper in this week’s Nature helps to clarify the synaptic mechanisms involved.

Patricia Janak and colleagues trained rats to self-administer a sugar reward. They showed that reward learning depends on increased activity and synaptic strength in the amygdala, a brain region important for emotional-based learning.

The level of learning attained by individual animals correlated well with the degree of synaptic strength enhancement — enabling the team to identify a key mechanism that could underlie goal-directed behaviour.

Author contact:

Patricia Janak (University of California at San Francisco, Emeryville, CA, USA)
Tel: +1 510 985 3880; E-mail:

[4] Nature: Insight into devastating pregnancy condition
DOI: 10.1038/nature06951

Pre-eclampsia is a devastating condition that can erupt towards the end of pregnancy, with life-threatening consequences for mother and baby. A paper published online in Nature has identified two culprits likely to trigger pre-eclampsia if they are in short supply, opening up the possibilities of early diagnosis and even treatment of the disorder.

Raghu Kalluri and colleagues genetically engineered a pre-eclampsia-like condition in mice by preventing them from producing an enzyme called catechol-O-methyltransferase (COMT), which normally inactivates a class of neurotransmitters known as catecholamines. They found that the mice also failed to produce 2-methoxyoestradiol, a natural metabolite produced by COMT that normally increases during the last three months of human pregnancy.

This correlates with women with severe pre-eclampsia, whose levels of COMT and 2-methoxyoestradiol tend to be low. The authors hope that their discovery may assist diagnosis of the condition with a simple blood or urine test. They suggest that supplementation with 2-methoxyoestradiol might improve or possibly prevent pre-eclampsia.

Author contact:
Raghu Kalluri (Harvard Medical School, Boston, MA, USA)
Tel: +1 617 667 0445; E-mail:

[5] Nature Genetics: Modeling psychiatric disorders in mice
DOI: 10.1038/ng.138

One of the molecular causes of the behavioral and cognitive deficits observed in mice with a small chromosomal deletion has been identified, according to a study published online this week in Nature Genetics. The corresponding deletion in the human genome gives rise to a range of psychiatric disorders, and accounts for approximately 1–2% of cases of schizophrenia in the general population.

Deletion of a small region on chromosome 22 is associated with anxiety, depression, attention-deficit hyperactivity disorder, autism, and deficits in working memory. Approximately 30% of the individuals carrying such a deletion eventually develop schizophrenia.

Maria Karayiorgou, Joseph Gogos and colleagues generated a model in which the corresponding region was deleted in the mouse genome. Mice carrying a single deletion show a range of behavioral and cognitive deficits that mimic some aspects of the human syndrome. Of particular interest is the increased expression of precursors of the small regulatory RNAs known as microRNAs in the brains of the mutant mice. The authors went on to show that loss of one of genes in the deleted region, Dgcr8, is responsible for this increased abundance of precursors, as the normal role of Dgcr8 is to process them into mature microRNAs. By generating mice that have only one copy of Dgcr8, the authors showed that this mutation by itself results in at least some of the deficits observed in mice with the deletion of the surrounding region.

Although the specific downstream targets of altered microRNA expression in the brain are not yet known, the authors suggest these findings could have general implications for understanding the genetic basis of psychiatric disorders.

Author contacts:
Maria Karayiorgou (Columbia University Medical Center, New York, NY, USA)
Tel: +1 212 568 4189; E-mail:

Joseph Gogos (Columbia University Medical Center, New York, NY, USA)
Tel: +1 212 305 0744; E-mail:

[6] Nature Chemical Biology: Stopping DNA synthesis before it starts
DOI: 10.1038/nchembio.90

A small-molecule inhibitor of Cdc7 kinase prevents DNA synthesis and has antitumour activity, suggests a paper online this week in Nature Chemical Biology. The finding could help scientists develop methods of treating tumours with less toxicity than is associated with related anticancer drugs currently in clinical use.

One characteristic of cancer cells is uncontrolled cell division, and many widely used—and quite toxic—anticancer drugs work by interfering with later stages of DNA replication. Cdc7 works at the very early stages of DNA replication by activating a group of proteins clustered at ‘origins of replication’, thus initiating DNA synthesis.

To see if preventing the initiation of DNA synthesis would be an effective and less toxic approach to chemotherapeutics, Corrado Santocanale and colleagues identified a potent inhibitor of Cdc7. In mouse studies, the inhibitor reduced tumor size with relatively low levels of toxicity, thus validating Cdc7 as an anticancer target. This new inhibitor will also be important in investigating the role of Cdc7 in cell division and cancer.

Author contact:
Corrado Santocanale (National University of Ireland Galway, Ireland)
Tel: +353 91 495 174; Email:

[7] Nature: Targeting dormant leukaemia cells
DOI: 10.1038/nature07016

A new role for a protein involved in leukaemia is described in Nature this week; the research demonstrates its potential as a therapeutic target to eradicate dormant leukaemia-initiating cells.

The promyelocytic leukaemia protein (PML) tumour suppressor is known to be involved in the development of some forms of leukaemia. Pier Paolo Pandolfi and colleagues identify a new and unexpected role for PML in the maintenance of both haematopoietic stem cells and leukaemia-initiating cells. They demonstrate, in mice, that targeting the protein with arsenic trioxide eliminates the cancer-initiating cells, thought to be resistant to chemotherapy and other therapies.

The team believes that their results present a new pharmacological approach to target cells that are missed by other therapies and therefore lead to disease relapse.

Author contact:
Pier Paolo Pandolfi (Harvard Medical School, Boston, MA, USA)
Tel: +1 617 667 3289; E-mail:

[8] Nature Geoscience: When glaciers cut deep
DOI: 10.1038/ngeo201

Scientists have found that preferential ice flow and erosion explain why fjords often extend to depths below sea level, according to research published online in Nature Geoscience this week.

Mark Kessler and colleagues use a two–dimensional numerical model to examine the conditions that lead to the intense glacial erosion that is associated with fjord formation. Starting from a landscape with four shallow valleys, the team found that the ice preferentially flows through the lowest valley. The amount of erosion increases proportionally with increasing ice discharge through each channel, and therefore quickly exaggerates the relief of the landscape. Over a few million years, these small valleys are eroded into the dramatic features we see throughout the Arctic region today, with fjords plunging kilometres below sea level.

In an accompanying News and Views, Johan Kleman says ‘The model clearly shows that the glacial system is extremely relief-enhancing and capable of greatly magnifying subtle height differences in the initial relief. This […] has not previously been shown numerically.’

Author contact:
Mark Kessler (University of Colorado, Boulder, CO, USA)
Tel: +1 914 874 2190; E-mail:

Additional contact for comment on paper:
Johan Kleman (Stockholm University, Sweden)
Tel: +46 70 796 8203; E-mail:

[9] Nature Medicine: Fighting glioma-associated edema
DOI: 10.1038/nm1772

Excessive accumulation of fluid in the brain can be prevented by inhibiting glutamate transport to prolong survival. Online this week in Nature Medicine, scientists describe a mouse model of glioma, and point to a potential new way of reducing the mortality associated with these types of tumours.

Neuronal death and brain edema are hallmarks of human malignant brain tumours. Ilker Eyüpoglu and his colleagues now show that inhibiting the glutamate transporter xCT by pharmacological or genetic means in vivo blocks neurodegeneration, reduces edema and prolongs survival in mice.

Author contact:
Ilker Eyüpoglu (University of Erlangen-Nuremberg, Germany)
Tel: +49 9131 85 44756; E-mail:

[10] Nature Geoscience: Tracking plates in the subsurface
DOI: 10.1038/ngeo200

In the complex tectonic setting of central Japan, two oceanic plates overlap with each other as they sink into the mantle, resulting in fluid release, mantle melting and volcanism. A study published online this week in Nature Geoscience quantifies the relative contribution of each plate to the overall fluid budget and helps clarify the subsurface configuration of the plates.

Hitomi Nakamura and colleagues analysed young volcanic rocks from central Japan to determine the chemical signature of fluids released by the Philippine Sea and Pacific plates as they dip down. They found that the fluid contributed by each plate is chemically distinct and that even though the plates overlap, the Philippine Sea plate appears not to block fluid released from the underlying Pacific plate.

The data suggest that chemical signatures of plate-derived fluids can be used to understand the geometry of subducting plates and hence the seismicity such settings.

Author contact:
Hitomi Nakamura (Institute of Geoscience and Geoinformation, Ibaraki, Japan)
Tel: +81 3 5841 4515; E-mail:

[11] Nature Immunology: Strength in numbers
DOI: 10.1038/ni.1611

A large number of signalling motifs in the receptor complex expressed on the surface of T lymphocytes helps prevent autoimmunity, according to a study published online this week in Nature Immunology. As auto-aggressive T lymphocytes can attack healthy tissues and thereby exacerbate many autoimmune diseases, understanding the mechanisms regulating the activity of this cell type is important.

Compared to other immune cells, T lymphocytes contain the highest number—10—of these signalling motifs, called ITAMs, which are required for transmission of intracellular signals. Using a complex genetic manipulation strategy, Dario Vignali and co-workers generated a panel of mice expressing various numbers of functional ITAMs on T lymphocytes. Mice with less than seven functional ITAMs suffered from lethal autoimmune disease precipitated by impaired deletion of self-reactive auto-aggressive T lymphocytes. In general, T lymphocyte development required high numbers of ITAMs, whereas mature T lymphocyte function required lower numbers of ITAMs.

The molecular basis for these different ITAM ‘thresholds’ remains to be understood.

Author contact:
Dario Vignali (St. Jude Children’s Research Hospital, Memphis, TN, USA)
Tel: +1 901 495 2332; E-mail:

[12] And finally… Nature: Frogs on call
DOI: 10.1038/nature06719

Nocturnal tree frogs living in China have been found to possess extraordinary vocal and localization skills, comparable to dolphins, elephants and humans. A paper online in Nature this week analyses the ultrasonic mating calls of the female torrent frog Odorrana tormota to reveal a surprisingly well-developed acoustic communication system, which is an adaptation to the noisy environment of rushing streams.

Vocalized mating calls play a key role in frog reproduction — male frogs are typically dominant, advertising their virility, with the females tending to be more passive, occasionally producing a weak reciprocal call or rapping sounds during courtship. Although the females have an unusually well-developed vocal production system, whether or not they produce calls in a communication system dominated by males has so far been unclear.

Jun-Xian Shen and colleagues recorded the vocalizations of female frogs in a quiet, darkened room using an ultrasonic microphone linked up to a computer. They found that, just before ovulating, female frogs emit short, high-frequency ultrasonic signals distinct from the males’ advertisement calls. They then played back the female calls to examine the response of the male frogs, and found that they both increased their calling activity and approached the source of the noise. On hearing the female call, a male usually oriented his body and made a long-distance hop towards the loudspeaker with remarkable precision.

The authors suggest that the torrent frogs may have developed this high-frequency ultrasonic system as a method of unambiguous communication in the presence of their noisy habitat.

Author contact:
Jun-Xian Shen (Chinese Academy of Sciences, Beijing, China)
Tel: +86 10 6488 8542; E-mail:

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

Nature (

[13] IL-21 and TGF-b are required for differentiation of human TH17 cells
DOI: 10.1038/nature07021


[14] The type I TGF-beta receptor is covalently modified and regulated by sumoylation
DOI: 10.1038/ncb1728

[15] Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B
DOI: 10.1038/ncb1732

[16] Extra centrosomes and/or chromosomes prolong mitosis in human cells
DOI: 10.1038/ncb1738


[17] X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment
DOI: 10.1038/ng.149

[18] De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy
DOI: 10.1038/ng.150


[19] Foxo1 directly regulates the transcription of recombination-activating genes during B cell development
DOI: 10.1038/ni.1612

[20] The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues
DOI: 10.1038/ni.1615


[21] Direct in situ determination of the polarization dependence of physisorption on ferroelectric surfaces
DOI: 10.1038/nmat2198

[22] Photonic metamaterials by direct laser writing and silver chemical vapour deposition
DOI: 10.1038/nmat2197

[23] Phase instability induced by polar nanoregions in a relaxor ferroelectric system
DOI: 10.1038/nmat2196


[24] The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination
DOI: 10.1038/nm1769


[25] Next generation high density self assembling functional protein arrays
DOI: 10.1038/nmeth.1210

[26] Three-dimensional sub-100 nm resolution fluorescence microscopy of thick samples
DOI: 10.1038/nmeth.1211

[27] Real-time imaging of the intracellular glutathione redox potential
DOI: 10.1038/nmeth.1212


[28] Functionalized graphene sheets for polymer nanocomposites
DOI: 10.1038/nnano.2008.96

[29] Impact of carbon nanotubes on the ingestion and digestion of bacteria by ciliated protozoa
DOI: 10.1038/nnano.2008.109


[30] Drosophila TRPA channel PAINLESS modulates sugar-stimulated neuronal excitation, avoidance and social interaction
DOI: 10.1038/nn.2119

[31] Activity-dependent site-specific changes of glutamate receptor composition in vivo
DOI: 10.1038/nn.2122


[32] Nanometric optical tweezers based on nanostructured substrates
DOI: 10.1038/nphoton.2008.78

[33] Grating formation by metal-nanoparticle-mediated coupling of light into waveguided modes
DOI: 10.1038/nphoton.2008.80

Nature PHYSICS (
[34] Breakdown of the adiabatic limit in low-dimensional gapless systems
DOI: 10.1038/nphys963


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.

Adelaide: 17
Heidelberg West: 17
Parkville: 17
Sydney: 11

Vancouver: 5
Waterloo: 29

Beijing: 12
Shanghai: 12

Bogota: 1

Lyon: 15
Paris: 2, 6

Cologne: 9
Erlangen: 9
Goettingen: 31
Heidelberg: 4, 27
Karlsruhe: 22
Leipzig: 31
Martinsried: 2
Stuttgart: 26
Wurzburg: 31

Galway: 6

Holon: 17
Petaq Tikvah: 17
Tel Aviv: 17

Nerviano: 6
Torino: 24
Turin: 7
Vicomoscano: 6

Fuchu: 18
Hamamatsu: 18
Ibaraki: 10
Matsue City: 10
Niigata: 18
Tokyo: 7, 10
Yamagata: 18
Yokohama: 18
Yokosuka: 10

Amsterdam: 9

Singapore: 2

Gothenburg: 33

Zurich: 9

Abu Dhabi: 28

Belfast: 17
Birmingham: 4
Cambridge: 17
Manchester: 32


Berkeley: 19
Carlsbad: 26
Emeryville: 3
Los Angeles: 12, 17
San Francisco: 3, 14
Stanford: 11

Boulder: 8

Wilmington: 17

Athens: 30
Atlanta: 15
Augusta: 15

Evanston: 28
Urbana: 12

Indianapolis: 4

Bar Harbor: 26
Orono: 26

Baltimore: 23
Gaithersburg: 23

Boston: 4, 7, 13, 17, 34
Cambridge: 25, 34
Woods Hole: 16

New Jersey
Princeton: 28

New York
Albany: 16
Buffalo: 8
Cold Spring Harbor: 5
Ithaca: 1
New York: 5, 7, 20, 24
Stony Brook: 23
Upton: 23

Philadelphia: 4, 21

Memphis: 11

Austin: 28
Dallas: 11
Houston: 2

Richmond: 4


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

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

Katherine Anderson (Nature New York)
Tel: +1 212 726 9231; E-mail:

Ruth Francis (Head of Press, Nature, London)
Tel: +44 20 7843 4562; E-mail:

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

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail:

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail:

Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail:

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

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

Nature Materials (London)
Alison Stoddart
Tel: +44 20 7843 4593; E-mail:

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

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

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

Nature Neuroscience (New York)
Kalyani Narasimhan
Tel: +1 212 726 9319; E-mail:

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail:

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Keywords associated to this article: Genetics, Cell Biology, learning, pregnancy, psychiatric disorders, DNA, leukaemia cells, glaciers, edema, Geoscience, Immunology, Frogs
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