Taste: Receptor switch explains water's taste; Cancer: Stem cells and leukaemia; The physics behind our sensitive senses; A PEG between two sulphurs; Neural effects of cocaine withdrawal; Teaching transplant tolerance

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE - For papers that will be published online on 23 April 2006


For papers that will be published online on 23 April 2006

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

This press release contains:

* Summaries of newsworthy papers:
Taste: Receptor switch explains water's taste - Nature
Cancer: Stem cells and leukaemia - Nature
The physics behind our sensitive senses - Nature Physics
A PEG between two sulfurs - Nature Chemical Biology
Neural effects of cocaine withdrawal - Nature Neuroscience
Teaching transplant tolerance - Nature Immunology
* 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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[1] Taste: Receptor switch explains water's taste

DOI: 10.1038/nature04765

Scientists explain online this week in Nature why water sometimes tastes strangely sweet. Using a 14-member tasting panel, Paul Breslin and his colleagues show that certain low-calorie sweeteners such as saccharin and acesulfame-K begin to taste bitter at high concentrations - and that at these same concentrations, water rinses begin to taste sweet.

The researchers show that this effect is mirrored in cultured cells that express the human receptor for sweet molecules. This receptor is inhibited by high concentrations of sweeteners, and becomes activated when the sweetener is washed away by water.

The authors propose that at low concentrations, the sweetener attaches to a high-affinity binding site that activates the receptor, and that at high concentrations it may also attach to a second, low-affinity binding site that inhibits the receptor and is washed away by water.

Author contact

Paul Breslin (Monell Chemical Senses Center, Philadelphia, PA USA)
Tel: +1 215 898 5021; E-mail: [email protected]

[2] Cancer: Stem cells and leukaemia

DOI: 10.1038/nature04747

One of the many jobs of haematopoietic stem cells is to keep in balance the normal expansion of cell numbers in the bone marrow without creating an overabundance of cells that may lead to leukaemia. A tipping point of this fine balance may have been found in a signalling molecule known as phosphatase and tensin homologue, or PTEN.

In a study to be published online this week by Nature, Linheng Li and colleagues show that this molecule, which normally keeps in check the phosphatidylinositol-3-OH kinase (PI(3)K) proliferation pathway, is crucial in this process. The researchers placed bone marrow stem cells containing an inactive form of PTEN into recipient mice and found that these mutant cells generated more myeloid and T-lymphoid cells, mimicking the onset of myeloid and lymphoid leukaemia.

Pinpointing the difference between leukaemic stem cells and haematopoietic stem cells with molecules such as PTEN may one day lead to more targeted therapies that can better distinguish between cancer and normal stem cells.

Author contact
Linheng Li (Stowers Inst for Medical Research, Kansas City, MO USA)
Tel: +1 816 926 4081; E-mail: [email protected]

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

[3] Neurons in the orbitofrontal cortex encode economic value
DOI: 10.1038/nature04676

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

(http://www.nature.com/naturephysics <http://www.nature.com/naturematerials>)

[4] The physics behind our sensitive senses

DOI: 10.1038/nphys289

An explanation of how our senses can process physical stimuli that vary over extremely wide ranges is reported by Osame Kinouchi and Mauro Copelli in the May issue of Nature Physics. The study could advance our understanding of how sensory systems can handle environmental signals whose intensities vary, for example, from the sound of a pin drop to that of a bomb blast, or from the subtle smell of the skin to the intense scent of a heavy perfume.

Surprisingly, the unit cells making up our sensory systems can only cope with inputs from a rather small range. This raises the question of how a network of identical elements can be sensitive to a much larger span of signals than its constituent units. Kinouchi and Copelli propose that the answer lies in the dynamics emerging from the interaction of the coupled elements. Using network theory - a branch of statistical physics - the authors show that an appropriately setup network of ‘excitable elements’ can be both extremely sensitive to small perturbations, and still able to detect large inputs without saturation.

These findings suggest a clear physical basis for the laws of psychophysics, the field concerned with how our perceptions relate to physical stimuli.

Author contact:

Osame Kinouchi (Universidade de São Paulo, Brazil)
Tel: +55 16 3602 3779, E-mail: [email protected]

Additional contact for comment on paper:
Dante Chialvo (Northwestern University, Chicago, IL, USA)

Tel: +1 312 503 4198, E-mail: [email protected]

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

[5] Controlling attosecond electron dynamics by phase-stabilized polarization gating

DOI: 10.1038/nphys281

[6] Determination of the carrier-envelope phase of few-cycle laser pulses with terahertz-emission spectroscopy

DOI: 10.1038/nphys286

[7] Correlation-induced inhomogeneity in circular quantum dots

DOI: 10.1038/nphys293

***********************NATURE CHEMICAL BIOLOGY*******************

(http://www.nature.com/nchembio <http://www.nature.com/natureneuroscience>)

[8] A PEG between two sulfurs

DOI: 10.1038/nchembio786

Scientists have demonstrated that the ubiquitous disulfide bonds found in proteins are not as resistant to chemical modification as was once thought. A study reported in the May issue of Nature Chemical Biology utilized the chemical reactivity of the sulfur atoms of the disulfide bonds to introduce a modification that helps to stabilize proteins for therapeutic use, such as in treating Hepatitis C.

Current therapies against Hepatitis C include treatment with the immune system modulator, interferon alpha2b. Chemical modification with a long extension of polyethylene glycol (PEG) helps to improve the amount of time the interferon remains within the body. Sunil Shaunak and colleagues describe a new chemical modification method to introduce a 3-carbon bridge between sulfur atoms within interferon alpha2b. The carbon bridge serves as a scaffold for introducing PEG.

Using this strategy, the authors also tagged another protein, an antibody against CD4, a protein on the surface of immune cells, demonstrating the general utility of their disulfide chemistry.

Author contact:

Sunil Shaunak (Imperial College London, UK)

Tel: +44 208 383 2301; E-mail: [email protected]

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


[9] Neural effects of cocaine withdrawal

DOI: 10.1038/nn1687

Vulnerability to relapse after drug withdrawal is a central problem in treating drug addiction. Exposure to drugs, or even to cues that remind addicts of drug use, can trigger relapse. Mu-ming Poo and colleagues now describe a mechanism in the brain that may contribute to the cue-triggered drug seeking during abstinence in the May issue of Nature Neuroscience.

The authors studied a brain area called the ventral tegmental area (VTA) known to be involved in reward and reinforcement associated with drug addiction. During a period of cocaine withdrawal in rats previously given daily cocaine injections for 5-7 days, they found that synapses onto dopamine-releasing neurons showed a heightened susceptibility to increase in strength, so that even weak stimulation could cause long-lasting increases in the neurons’ responses. This enhanced plasticity required a growth factor called BDNF, which has previously been linked to drug-seeking behavior after withdrawal.

Drug craving and relapse may involve a specific enhancement of reward signals in response to drug-associated cues. The results described by Poo and colleagues suggest a mechanism that might allow for such enhancement.

Author contact:

Mu-ming Poo (University of California, Berkeley, CA, USA)
Tel: +1 510 642 2514; E-mail: [email protected]

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

[10] Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex

DOI: 10.1038/nn1689

[11] End stopping in V1 is sensitive to contrast

DOI: 10.1038/nn1693

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

[12] Teaching transplant tolerance

DOI: 10.1038/ni1333

A study explaining how specific immune cells help to make transplanted donor tissue ‘tolerable’ is reported in the June issue of Nature Immunology. Much is known about how transplanted tissues are rejected, but exactly how the immune system learns to ‘tolerate’ transplants remained unclear.

Jordi Ochando and colleagues show that special immune cells called plasmacytoid dendritic cells acquire bits of transplanted heart tissue that are transported to the nearby lymph nodes. Once inside the lymph node, the plasmacytoid dendritic cells deliver signals to different resident immune cells that develop into cells that ‘suppress’ the possible activation of immune responses that can attack the transplanted tissue.

Precisely how the plasmacytoid dendritic cells induce the development of the suppressor cells is not known. However, these results might help us understand how the immune system is ‘taught’ to tolerate the presence of unfamiliar tissues.

Author contact:
Jordi Ochando (Mount Sinai School of Medicine, New York, NY, USA)
Tel: +1 212 659 8244; E-mail: [email protected]

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

[13] ABIN-2 is required for optimal activation of Erk MAP kinase in innate immune responses
DOI: 10.1038/ni1334


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

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

[14] Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer

DOI: 10.1038/nm1398

[15] Coexpression of virulence and fosfomycin susceptibility in Listeria: molecular basis of an antimicrobial in vitro-in vivo paradox

DOI: 10.1038/nm1396

[16] Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE
DOI: 10.1038/nm1402

Nature BIOTECHNOLOGY (<http://www.nature.com/naturebiotechnolgy>)

[17] Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins
DOI: 10.1038/nbt1204

NATURE GENETICS (<http://www.nature.com/naturegenetics>)

[18] Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band

DOI: 10.1038/ng1781

[19] A distant upstream enhancer at the maize domestication gene tb1 has pleiotropic effects on plant and inflorescent architecture

DOI: 10.1038/ng1784

[20] A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

DOI: 10.1038/ng1783

[21] Total insulin and IGF-I resistance in pancreatic Beta cells causes overt diabetes
DOI: 10.1038/ng1787

[22] Ablation of PDK1 in pancreatic Beta cells induces diabetes as a result of loss of Beta cell mass

DOI: 10.1038/ng1774

Nature STRUCTURAL & MOLECULAR BIOLOGY (<http://www.nature.com/natstructmolbiol>)

[23] EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3’ UTR length
DOI: 10.1038/nsmb1081

[24] Reconstruction of the chemotaxis receptor-kinase assembly
DOI: 10.1038/nsmb1085

[25] APOBEC3G DNA deaminase acts processively 3’à5’ on single-stranded DNA
DOI: 10.1038/nsmb1086

[26] WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing
DOI: 10.1038/nsmb1088

[27] Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex
DOI: 10.1038/nsmb1090



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: 18
Woolloongabba: 20

Vienna: 15

Recife: 4
Soa Paulo: 4

Toronto: 17

Orsay: 7
Paris: 21
Talence: 5

Dresden: 12
Frankfurt: 6
Hannover: 6
Heidelberg: 6
Nuthetal: 1
Tubingen: 19

Milan: 5, 14
Padova: 5

Kobe: 22
Tokyo: 21, 22

Moscow: 5

Barcelona: 18
Leon: 15
Madrid: 15

Lund: 16
Malmo: 16

Basel: 23
Bern: 23
Geneva: 22

Bristol: 15
London: 8, 13

Berkeley: 9, 26
La Jolla: 22, 26
Los Angles: 2, 7, 25
Groton: 26
Kansas City: 2
Bethesda: 12
Boston: 3, 11, 21, 23
Brighton: 10
Cambridge: 10
Ann Arbor: 21
Kansas City: 2
North Carolina
Durham: 7, 10
New York
Ithaca: 7, 24
New York: 12, 27
Troy: 17
Philadelphia: 1, 20
Nashville: 21
Richmond: 21
Dallas: 26
Madison: 19


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

Victoria Picknell (Nature London)
Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, 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)
Kathy Aschheim
Tel: +1 212 726 9346; E-mail: [email protected]

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

Nature Chemical Biology (Boston)
Beatrice Chrystall
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)
Maria Bellantone
Tel: +44 20 7843 4556; E-mail: [email protected]

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

Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)

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

Nature Structural & Molecular Biology (New York)
Ed Feng
Tel: +1 212 726 9351; E-mail: [email protected]

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Published: 23 Apr 2006

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