NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 6 November 2005
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
* Summaries of newsworthy papers:
* A path to beating cancer - Nature
* Agonizing over CD40 - Nature Chemical Biology
* Can drug side effects be predicted? - Nature Chemical Biology
* Turning a new leaf in probiotic meat preservation - Nature Biotechnology
* Allergy safety pins - Nature Immunology
* Getting lymphocytes going - 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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*****************************NATURE*********************************
(<http://www.nature.com/nature>)
[1] & [2] A path to beating cancer
[1] DOI: 10.1038/nature04296 &
[2] DOI: 10.1038/nature04304
Although medical research has offered up promising drugs against cancer in
recent years, these treatments still prove unsuccessful in many patients.
Better profiling of tumours might help to promote more targeted and
effective treatment regimes in the future, and two studies published online
by Nature this week report promising developments in this direction.
In the first paper, Joseph Nevins and his colleagues studied gene expression
patterns that reflect the activation of various oncogenic (cancer-causing)
signal transduction pathways. Using combinations of these pathway
signatures, they were able to predict which patients with breast, ovarian or
lung cancer had a particularly poor prognosis The authors also describe how
the ability to identify which molecular pathways are deregulated in a cancer
might be used to predict its sensitivity to specific therapeutic drugs. This
approach could one day help doctors choose drugs that match the molecular
features of a specific tumour.
Further insight into how anti-cancer drugs can be tailored to match the
genetic makeup of a cancer comes from a paper by Neal Rosen and colleagues.
Mutated versions of the RAS and BRAF genes are thought to cause cancer at
least in part by activating a common enzyme pathway. But Rosen and his team
found that only tumours with the BRAF mutation are highly sensitive to a
drug that inhibits this pathway. They suggest that testing patients for the
presence of BRAF mutations may allow doctors to identify those patients most
likely to benefit from this drug.
Author contact:
Joseph Nevins (Duke University Medical Center, Durham, NC, USA) paper no:
[1]
Tel: +1 919 684 2746, E-mail: [email protected]
Neal Rosen (Memorial Sloan-Kettering Cancer Center, New York, NY, USA) paper
no: [2]
Tel: +1 212 639 2369, E-mail: [email protected]
Other papers from Nature to be published online at the same time and with
the same embargo:
[3] A quantitative protein interaction network for the ErbB receptors using
protein microarrays
DOI: 10.1038/nature04177
**********************NATURE CHEMICAL BIOLOGY*******************
(http://www.nature.com/nchembio)
[4] Agonizing over CD40
DOI: 10.1038/nchembio746
A new approach to targeting cellular receptors in the immune system using
small molecules is reported in the December issue of Nature Chemical
Biology. Gilles Guichard and colleagues designed a molecular scaffold that
presents short peptide sequences that bind to and activate cellular
receptors. These molecules offer an attractive model for cancer
immunotherapy and boosting immune responses to infections.
Tumor necrosis factor (TNF) proteins are a family of cytokine proteins that
regulate the functions of immune cells. TNF proteins assemble into bundles
of three - or trimeric bundles - and bind to TNF receptors, which 'read'
cytokine signals on the surface of immune cells. The team set out to create
small molecules that could mimic the cytokine properties of trimeric CD40
ligand (CD40L), which exerts its effects by binding to trimeric CD40
receptors. The authors synthesized a circular 'core' peptide with three
appendages, at twelve, four and eight o'clock. To each appendage, they
attached a short peptide derived from CD40L that is known to interact with
CD40. They showed that these trimeric molecules act as mimics of CD40L by
binding to CD40 on cells and activating downstream signaling pathways. In
addition, the molecules targeted only CD40 and did not activate other TNF
receptor proteins. This specificity suggests that these molecular 'cores'
may be a versatile platform for targeting different TNF receptors by
decorating them with different TNF peptide fragments.
These molecules suggest new strategies for cancer immunotherapy and
activation of immune systems during infection.
Author contact:
Gilles Guichard (Institut de Biologie Moléculaire et Cellulaire, Strasbourg,
France)
Tel: +33 3 88 41 70 25; E-mail: [email protected]
Additional contact for comment on paper:
Sarah Hymowitz (Genentech, Inc., South San Francisco, California, USA)
Tel: +1 650 225 7819, E-mail: [email protected]
[5] Can drug side effects be predicted?
DOI: 10.1038/nchembio747
A paper in the December issue of Nature Chemical Biology reports a method
for correlating a drug's biochemical activity with its clinical side
effects. During clinical trials, drug candidates have a high failure rate,
which results in part from unexpected toxicities. A method for predicting
these unwanted side effects could prove important for choosing the right
drug candidates to enter into clinical trials.
Robert Volkmann and Anton Fliri and colleagues hypothesized that the
biochemical activities of chemical compounds could be used to predict side
effects. To test this idea, the authors looked at the biochemical activity
of a drug in inhibiting a large panel of proteins. This resulted in a
'fingerprint' of the compound's biochemical activity. They then looked at
the side effects induced by the same drug during clinical trials, which led
to a fingerprint of the compound's side effects. By comparing the
biochemical and side effect fingerprints for 1,045 drugs, the authors found
that there was a significant correlation between a drug's biochemical
activity in vitro and the clinical side effects it induced.
This result suggests that it will eventually be possible to predict
the expected side effects of a new drug candidate by analyzing its
biochemical activity fingerprint, which would significantly improve the
success rate of drug development.
Author contact:
Robert Volkmann or Anton Fliri (Pfizer Global Research and Development,
Groton, CT, USA)
Tel: +1 860 441 4662, E-mail: [email protected]
Anton Fliri (Pfizer Global Research and Development, Groton, CT, USA)
Tel: +1 860 441 4475, E-mail: [email protected]
*************************NATURE BIOTECHNOLOGY*******************
(http://www.nature.com/naturebiotechnolgy)
[6] Turning a new leaf in probiotic meat preservation
DOI: 10.1038/nbt1160
French scientists have sequenced a lactic acid bacterium, Lactobacillus
sakei 23K, which helps suppress the bacteria that cause meat to spoil. The
availability of the complete sequence of L. sakei, reported by Zagorec and
colleagues in December's Nature Biotechnology, should permit further
development and exploitation of the biopreservative potential of this
bacterium.
Lactic acid bacteria are widely used in the meat industry as starter
cultures for sausage fermentation. They contribute to flavor development and
also inhibit the growth of competing bacteria that are found on meat,
including spoilage bacteria and, occasionally, pathogens such as
enterobacteria and Listeria species. Lactic acid bacteria achieve this
probiotic effect by acidifying the environment, producing chemicals that
kill microbes and competing for nutrients on the meat surface.
The 1,885-kilobase genome of L. sakei is thought to encode 1,883 proteins, a
portion of which clearly sets it apart, metabolically speaking, from other
known lactobacilli. Most of these proteins are presumed to help L. sakei
outcompete other bacteria, for example, by forming a biofilm or by enduring
harsh conditions during food processing.
Author contact:
Monique Zagorec (Unité Flore Lactique et Environnement Carné, Jouy en Josas,
France)
Tel: + 33 1 34 65 22 89, E-mail: [email protected]
Additional contact for comment on paper:
Vincent G.H. Eijsink (Norwegian University of Life Sciences, Aas, Norway)
Phone: +47 6496 5892, E-mail: [email protected]
************************NATURE IMMUNOLOGY***********************
(<http://www.nature.com/natureimmunology>)
[7] Allergy safety pins
DOI: 10.1038/ni1266
Sneezing, wheezing and other unpleasant symptoms of asthma and
allergic responses result from factors released by activated eosinophils -
very short-lived blood cells that are rapidly recruited to body sites, such
as the lung and skin, upon contact with allergens. Coincident with this
tissue infiltration, eosinophils become activated and release multiple
inflammatory mediators, including GM-CSF, a survival factor that increases
the lifespan of eosinophils. In the December issue of Nature Immunology,
researchers identify the enzyme Pin1 that increases the stability of mRNAs
encoding GM-CSF. Targeting Pin1 activity may therefore reduce or alleviate
many allergic reactions.
Key to controlling allergic reactions is to understand how eosinophil
longevity is increased upon their recruitment to allergen-sensitized
tissues. James Malter and colleagues show Pin1 regulates GM-CSF mRNA
abundance by altering its binding to one of two factors, AUF1 or hnRNP C,
leading to rapid GM-CSF mRNA destruction or increased stability,
respectively. Pin1 alters AUF1 to prevent its binding to GM-CSF mRNA, which
then bind to hnRNP C instead. This step leads to increased GM-CSF protein
synthesis, in turn leading to increased eosinophil survival. Importantly,
Pin1 is activated by signals the eosinophil receives after exiting the
bloodstream, ensuring eosinophil survival in the affected tissue sites.
To show the potential clinical relevance of these findings, the authors
collected eosinophils from the lungs of human volunteers who had been
challenged with aerosolized allergens. Eosinophils isolated after such
challenge show increased Pin1 activity (and longer survival times) as
compared to blood-borne eosinophils isolated from these same individuals.
Culturing the lung eosinophils with Pin1 inhibitors reduces eosinophil
survival. These results show Pin1 plays a crucial role in determining how
long eosinophils will live. These findings point to potential therapeutic
strategies to target Pin1 activity in allergy patients, lessening their
unpleasant immune response to allergen exposure.
Author contact:
James S. Malter (University of Wisconsin School of Medicine, Madison, WI,
USA)
Tel: +1 608 263 6043, E-mail: [email protected]
[8] Getting lymphocytes going
DOI: 10.1038/ni1272
Immune cells, called lymphocytes, form physical structures or synapses with
specialized cells to trigger an immune response during pathogen attack. How
synapses initiate immune responses during infection is not known, however.
In the December issue of Nature Immunology scientists report that
'microclusters' of molecules are the discrete physical structures required
for triggering and, importantly, sustaining immune signals.
Previously, studies of synapses focused on large structures at the center of
the synapses called central supramolecular clusters (cSMACs). Most studies
have implicated cSMACs as the physical structures where lymphocyte signaling
begins. But work by Takashi Saito and colleagues demonstrate instead that
microclusters of tens of molecules form in the physical space around cSMACs
- and importantly precede cSMAC formation - to initiate and sustain
signaling. Their work also implies the contrary view that cSMACs actually
stop signaling instead of starting it, an interpretation that decreases the
importance of cSMACs while emphasizing microcluster formation as the
critical event of lymphocyte activation - a necessity for robust immune
responses against pathogens.
Author contact:
Takashi Saito (RIKEN Research Center for Allergy and Immunology, Yokohama,
Japan)
Tel: +81 45 503 7037, E-mail: [email protected]
Other papers from Nature Immunology to be published online at the same time
and with the same embargo:
[9] Interleukin 15 controls generation of the restricted T cell receptor
repertoire of gamma delta intestinal intraepithelial lymphocytes
DOI: 10.1038/ni1267
[10] Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin
DOI: 10.1038/ni1268
[11] Sphingosine 1-phosphate type 1 receptor agonism inhibits
transendothelial migration of medullary T cells to lymphatic sinuses
DOI: 10.1038/ni1269
******************************************************************
Items from other Nature journals to be published online at the same time and
with the same embargo:
Nature PHYSICS (http://www.nature.com/naturephysics)
[12] Emergence of soliton chirality in a quantum antiferromagnet
DOI: 10.1038/nphys152
NATURE MATERIALS (<http://www.nature.com/naturematerials>)
[13] Anharmonic motions of Kr in the clathrate hydrate
DOI: 10.1038/nmat1525
[14] Identifying and counting point defects in carbon nanotubes
DOI: 10.1038/nmat1516
Nature MEDICINE (<http://www.nature.com/naturemedicine>)
[15] Protection of macaques from vaginal SHIV challenge by an orally
delivered CCR5 inhibitor
DOI: 10.1038/nm1321
NATURE GENETICS (<http://www.nature.com/naturegenetics>)
[16] Autoimmune-associated lymphoid tyrosine phosphatase is a
gain-of-function variant
DOI: 10.1038/ng1673
[17] Quantitative trait loci mapped to single-nucleotide resolution in yeast
DOI: 10.1038/ng1674
[18] DICER-LIKE 4 is required for RNA interference and produces the
21-nucleotide small interfering RNA component of the plant cell-to-cell
silencing signal
DOI: 10.1038/ng1675
[19] Genomic buffering mitigates the effects of deleterious mutations in
bacteria
DOI: 10.1038/ng1676
Nature NEUROSCIENCE (<http://www.nature.com/natureneuroscience>)
[20] Neural population coding of sound level adapts to stimulus statistics
DOI: 10.1038/nn1541
[21] Uncertainty-based competition between prefrontal and dorsolateral
striatal systems for behavioral control
DOI: 10.1038/nn1560
[22] Neuronal correlates of subjective sensory experience
DOI: 10.1038/nn1587
[23] Regulation of neuronal morphology and function by the tumor suppressors
Tsc1 and Tsc2
DOI: 10.1038/nn1566
[24] Cognitive control mechanisms resolve conflict through cortical
amplification of task-relevant information
DOI: 10.1038/nn1594
NATURE CELL BIOLOGY (<http://www.nature.com/naturecellbiology>)
[25] Differential role of CENP-A in the segregation of holocentric C.
elegans chromosomes during meiosis and mitosis
DOI: 10.1038/ncb1331
[26] RNA-dependent integrin alpha3 protein localization regulated by the
Muscleblind-like protein MLP1
DOI: 10.1038/ncb1335
[27] Centering of a radial microtubule array by translocation along
microtubules spontaneously nucleated in the cytoplasm
DOI: 10.1038/ncb1332
Nature STRUCTURAL & MOLECULAR BIOLOGY
(<http://www.nature.com/natstructmolbiol>)
[28] Structure of the heterodimeric core primase
DOI: 10.1038/nsmb1014
[29] Compact and ordered collapse of randomly generated RNA sequences
DOI: 10.1038/nsmb1013
[30] Structural basis for transcription inhibition by tagetitoxin
DOI: 10.1038/nsmb1015
****************************************************************
GEOGRAPHICAL LISTING OF AUTHORS
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.
BELGIUM
Brussels: 4
CANADA
Ottawa: 13
Saskatoon: 13
Vancouver: 27
CHINA
Beijing: 4
FRANCE
Grenoble: 12
Jouy-en-Josas: 6
Strasbourg: 4, 18
GERMANY
Dortmund: 13
Garching bei Munich: 12
Kiel: 13
IRELAND
Dublin: 12
ISRAEL
Jerusalem: 21
ITALY
Cagliari: 16
Sassari: 16
JAPAN
Hyogo: 30
Kanagawa: 8
Mishima: 8
Tsukuba: 30
MEXICO
Mexico City: 22
THE NETHERLANDS
Leiden: 4
NORWAY
Oslo: 16
SWEDEN
Goteborg: 19
Stockholm: 19
SWITZERLAND
Bern: 12
Epalinges: 4
Villigen: 12
Zurich: 12
UNITED KINGDOM
Cambridge: 28
Chilton: 12
London: 20, 21
Oxford: 10, 28
UNITED STATES OF AMERICA
Alabama
Birmingham: 30
California
Davis: 19, 27
Irvine: 11, 14
La Jolla: 10, 11, 16, 25
Los Angeles: 16
Palo Alto: 17
Stanford: 17
Colorado
Denver: 10
Connecticut
Farmington: 27
Groton: 5
New Haven: 10
Florida
Tampa: 1
Georgia
Atlanta: 10
Illinois
Argonne: 13
Louisiana
Covington: 15
Massachusetts
Boston: 2, 10, 23
Cambridge: 2, 3, 29
Chestnut Hill: 29
Worcester: 9
Michigan
Ann Arbor: 2
New Jersey
Kenilworth: 2
Rahway: 15
New York
New York: 2, 8, 15, 23, 24
North Carolina
Durham: 1
Ohio
Columbus: 30
Pennsylvania
Philadelphia: 10, 27
South Carolina
Charlestown: 26
Wisconsin
Madison: 7
PRESS CONTACTS...
For media inquiries relating to embargo policy for all the Nature Research
Journals:
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Tel: +44 20 7843 4658; 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 Structural & Molecular Biology (New York)
Ed Feng
Tel: +1 212 726 9351; E-mail: [email protected]
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