NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 30 October 2005
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
* Summaries of newsworthy papers:
* Antagonizing gene expression - Nature
* Microbicide gel protects monkeys against simian HIV - Nature
* What's shape got to do with it? - Nature Physics
* Taking away the energy from T cell proliferation - Nature Chemical Biology
* Magnetic nanoparticles for imaging human cell transplants - Nature Biotechnology
* Focus on neurobiology of addiction - Nature Neuroscience
* Sniffing for mates and rivals - Nature Neuroscience
* Mention of papers to be published at the same time with the same embargo
* Papers with a different embargo date and time
* 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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PLEASE CITE THE SPECIFIC NATURE JOURNAL AND WEBSITE AS THE SOURCE OF THE
FOLLOWING ITEMS. IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO THE
APPROPRIATE JOURNAL'S WEBSITE.
****************************NATURE******************
(<http://www.nature.com/nature>)
[1] Antagonizing gene expression
DOI: 10.1038/nature
A new tool promises to help scientists better understand and manipulate
genes whose expression is regulated by non-coding pieces of RNA termed
microRNAs (miRNAs). In a study published by Nature, Markus Stoffel and
colleagues show that a class of specially engineered compounds called
'antagomirs' can effectively silence the action of miRNAs in regulating gene
expression. Antagomirs are short RNA molecules that are constructed to be
stable in vivo; their sequences are designed to be complementary to
individual miRNAs. The antagomir binds to its specific target miRNA, and, as
shown in this work, this interaction inhibits the miRNA's activity.
The team designed a version of this compound to specifically target an miRNA
found only in the liver, and administered the antagomir to mice. This
treatment reduced the usually abundant miRNA to undetectable levels, without
any noticeable toxic effects. The group also saw a drop in plasma
cholesterol levels in mice treated with the antagomir, suggesting that this
miRNA normally regulates genes in the pathway that produces cholesterol. In
the future, antagomirs could assist in deciphering the role of miRNAs in the
control of gene expression, and be used to treat diseases that are
associated with dysregulated miRNA function, such as cancer.
Author contact:
Markus Stoffel (Rockefeller University, New York, NY, USA)
Tel: +1 212 327 8797; E-mail: [email protected]
[2] Microbicide gel protects monkeys against simian HIV
DOI: 10.1038/nature
A potential approach to preventing HIV infection in women is reported in an
online publication from Nature. John Moore and his colleagues tested a
vaginal microbicide containing up to three small-molecule inhibitors to see
if they protected macaque monkeys from vaginal infection. They found that
combinations of inhibitors delivered in a topical microbicide gel provided
substantial protection against infection.
The HIV virus enters human T cells via surface molecules, or
receptors. The protein CCR5 is important for the initial infection. By using
small molecules that bind to the CCR5 receptor, the team could inhibit the
different stages of virus attachment and entry.
The team tested different combinations and concentrations of the
inhibitors, alone and together, which were administered in a vaginal gel.
The monkeys were then exposed to simian HIV (SHIV) and their infection rates
monitored. The extent of protection was striking, using both single
inhibitors and combinations of them. In a small-scale, exploratory
experiment, 4 of 6 macaques were protected even when the microbicide was
delivered 2 or 6 hours before exposure to simian HIV. Some protection was
achieved by giving the animals the inhibitors by mouth.
The advantage of using small, conventional molecules as inhibitors
means that production costs for the microbicide would not be prohibitive.
Clinical trials are needed to assess safety and efficacy in HIV infection in
women.
Author contact:
John Moore (Weill Medical College, Cornell University, New York, NY, USA)
Tel: +1 212 746 4462; E-mail: [email protected]
******************NATURE PHYSICS****************************
(http://www.nature.com/naturephysics)
[3] What's shape got to do with it?
DOI: 10.1038/nphys154
Whether or not a material will superconduct depends on its size and shape,
report Michael Hermele and co-workers in the November issue of Nature
Physics.
If you take a superconductor and simply change its shape, surely it would
still carry a current without any resistance? In their theoretical paper,
the authors considered two thin-film superconductors connected at a point,
in a shape reminiscent of a bowtie. Instead of the expected 'supercurrent'
flow, they found that superconductivity could only exist at zero
temperature. This means even at the lowest attainable temperature, such thin
films will have finite resistance.
Their result is surprising, given that for a larger point of connection, the
resulting circuit is at the heart of the most sensitive device for measuring
magnetic fields (superconducting quantum interference devices, or SQUIDs).
Now that devices are shrinking in size, it will be important to bear this
work in mind.
Author contact:
Michael A. Hermele (Massachusetts Institute of Technology, Cambridge, MA,
USA)
Tel: +1 617 253 6831, E-mail: [email protected]
Other papers from Nature Physics to be published online at the same time and
with the same embargo:
[4] Coherent spinor dynamics in a spin-1 Bose condensate
DOI: 10.1038/nphys153
********************NATURE CHEMICAL BIOLOGY************************
(http://www.nature.com/nchembio)
[5] Taking away the energy from T cell proliferation
DOI: 10.1038/nchembio744
A new class of immunosuppressive compounds is shown to block T lymphocyte
proliferation - the process by which white blood cells are activated during
an immune response - by inhibiting lactate transport, as reported in the
December issue of Nature Chemical Biology.
Proliferating T cells rely on energy from aerobic glycolysis, a process
which generates ATP through the conversion of glucose to pyruvate or
lactate. Clare Murray and colleagues have found that the immunosuppressive
molecules function by inhibiting monocarboxylate transporter 1 (MCT1), a
membrane protein involved in pumping lactate out of cells. Forcing
intracellular lactate accumulation reduces the levels of glycolysis
sufficiently to sap the energy required for rapid cellular growth, say the
team.
Starting with compounds that showed potent inhibition of T cell
proliferation in vitro and effective immunosuppression in vivo, Murray used
proteomic methods to identify the target protein as MCT1. Consistent with
MCT1 being the functional target, proliferating T cells had higher levels of
MCT1 than resting cells did. These increased protein levels corresponded
with increased lactate transport, which could be blocked by the inhibitory
compounds, resulting in intracellular lactate accumulation and reduced
glycolysis.
In addition to identifying a promising new target for developing
immunosuppressants, these compounds will now provide a new tool for
understanding MCT1 biology and the role of glycolysis in cell proliferation.
Author contact:
Clare Murray (AstraZeneca R&D Charnwood, UK)
Tel: + 44 1509 644230, e-mail: [email protected]
**********************NATURE BIOTECHNOLOGY***********************
(http://www.nature.com/naturebiotechnolgy)
[6] Magnetic nanoparticles for imaging human cell transplants
DOI: 10.1038/nbt1154
Scientists have succeeded in using magnetic resonance imaging (MRI) to
visualize therapeutic cells transplanted into patients. The technique,
described in November's Nature Biotechnology, should be useful for improving
numerous experimental therapies based on transplanting various types of
cells, such as immune cells and stem cells.
'Dendritic cells' are specialized immune cells that are being investigated
as a means of fighting cancer. To understand why clinical trials using
dendritic cells have been less successful than scientists had hoped, Figdor
and colleagues wished to determine what happens to the cells after they are
transplanted. Adapting an approach that has been demonstrated in animals,
they coaxed cultured dendritic cells to take up tiny magnetic particles made
of iron oxide. The iron-containing cells were then injected into the lymph
nodes of melanoma patients. Imaging with MRI gave a clearer picture of the
cells compared with an X-ray method and revealed that, in half the patients,
the injection had missed the lymph node altogether, explaining the lack of
clinical efficacy. Because the success of any cell therapy depends on
getting the cells to the correct site in the body and assuring their
survival, the ability to image transplanted cells with MRI will likely
facilitate the optimization of many such therapies.
Author contact:
Carl Figdor (Radboud University Nijmegen Medical Centre, The Netherlands)
Tel: +31 243617600, E-mail: [email protected]
Additional contact for comment on paper:
Laurence Zitvogel (Institut Gustave Roussy (IGR), Villejuif, France)
Tel: +33 1 42 11 50 41, E-mail: [email protected]
Other papers from Nature Biotechnology to be published online at the same
time and with the same embargo:
[7] Design of siRNAs producing unstructured guide-RNAs results in improved
RNA interference efficiency
DOI: 10.1038/nbt1151
***********************NATURE NEUROSCIENCE*********************
(<http://www.nature.com/natureneuroscience>)
Focus on neurobiology of addiction
The neurobiology of addiction is examined in a collection of articles in the
November issue of Nature Neuroscience. Drug abuse and addiction are
pervasive worldwide, taking an enormous toll not just on the health and
welfare of addicts, but also on society. The answer to the problem may seem
simple - just say no to drugs - but addiction is a biological condition.
Taking drugs causes changes in the brain that interact with the user's
genetic make-up and environmental stressors. Many addicts are unable to
resist the urge to take drugs and even those who quit may suddenly relapse
into drug use after years of abstinence. To develop effect treatment and
prevention strategies, we must understand addiction from all angles - from
the biological basis of drugs, to the genetics that predispose certain
people to addiction, to the meaning of addictive behavior itself.
Subjects under the spotlight include what genetic or behavioral
characteristics make certain individuals more vulnerable to drug addiction
and whether common brain targets for all addictive substances could be
exploited to provide a 'magic bullet' for addiction treatment. The focus
issue also looks at the user's evolving relationship with a drug during the
transitions from voluntary drug use, to habitual use, to addiction. Exposure
to drugs causes changes in brain circuits related to reward and motivation,
and three commentaries consider which changes in the brain are likely to be
critical to addiction. Alcohol and nicotine are the most highly abused legal
drugs. With most people having imbibed at some point, this special issue
examines the links between nicotine addiction and alcoholism and discusses
the neurobiology of alcohol abuse.
Despite the enormous social and economic cost of addiction, few long-term
treatments or pharmaceutical treatments are available. This issue discusses
the social issues that may be hampering development and access to treatment
and how we might move the process of drug development forward.
***A full listing of the contents and contacts will be available from the
relevant section of the Nature press site, alongside full text pdfs of the
articles***
[8] Sniffing for mates and rivals
DOI: 10.1038/nn1589
In many species, the urge to mate is driven by the smell of sexual hormones
called pheromones. Traditionally researchers have thought that these scents
are detected in rodents by a specialized organ called the vomeronasal organ,
which is separate from the main olfactory system where other odors are
detected. Now it appears that normal sexual behavior requires intact
functioning of the main olfactory system, according to a paper in the
December issue of Nature Neuroscience.
Nirao Shah and colleagues examined the behavior of male mice with a
genetic modification that disrupted function of the primary smell organ
(called the main olfactory epithelium), but did not affect function in the
vomeronasal organ. Normal male mice eagerly sniff out females by following
their urine trails, and when males and females are left to their own devices
for a week, pregnancy inevitably ensues. In contrast, the mutant mice failed
to show any sexual behavior toward females and were uninterested in the
scent of female urine, which fascinates normal male mice. When other male
mice were placed in their cage - a situation that arouses aggression in
normal males - the mutant mice did not check out the intruders, and were
reluctant to fight. These findings show the importance of the main olfactory
system for smelling odors of other members of the same species - a behavior
that is a necessary prelude to sexual and aggressive behavior.
Author contact:
Nirao Shah (University of California, San Francisco, CA, USA)
Tel: +1 415 514 4381; E-mail: [email protected]
Other papers from Nature Neuroscience to be published online at the same
time and with the same embargo:
[9] Matching storage and recall: hippocampal spike timing-dependent
plasticity and phase response curves
DOI: 10.1038/nn1561
[10] Dissociation between physical and mental number line bisection in right
hemisphere brain damage
DOI: 10.1038/nn1563
[11] BK channel beta4 subunit reduces dentate gyrus excitability and
protects against temporal lobe seizures
DOI: 10.1038/nn1573
[12] Synaptic background activity controls spike transfer from thalamus to
cortex
DOI: 10.1038/nn1591
****************************************************************************
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>)
[13] Platelets mediate cytotoxic T lymphocyte-induced liver damage
DOI: 10.1038/nm1317
[14] Signal amplification in molecular imaging by pretargeting a
multivalent, bispecific antibody
DOI: 10.1038/nm1322
NATURE GENETICS (<http://www.nature.com/naturegenetics>)
[15] An evaluation of HapMap sample size and tagging SNP performance in
large-scale empirical and simulated data sets
DOI: 10.1038/ng1670
[16] Inherited susceptibility to lung cancer may be associated with the
T790M drug resistance mutation in EGFR
DOI: 10.1038/ng1671
[17] SMC1beta-deficient female mice provide evidence that cohesins are a
missing link in age-related nondisjunction
DOI: 10.1038/ng1672
[18] Sex-specific role of Drosophila melanogaster HP1 in regulating
chromatin structure and gene transcription
DOI: 10.1038/ng1662
NATURE CELL BIOLOGY (<http://www.nature.com/naturecellbiology>)
[19] Endocytic control of epithelial polarity and proliferation in
Drosophila
DOI: 10.1038/ncb1324
****************************************************************************
Nature STRUCTURAL & MOLECULAR BIOLOGY
(<http://www.nature.com/natstructmolbiol>)
[20] The structures of exocyst subunit Exo70p and the Exo84p C-terminal
domains reveal a common motif
DOI: 10.1038/nsmb1017
****************************************************************************
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.
FRANCE
Bordeaux: 12
Gif sur Yvette: 12
GERMANY
Berlin: 7
Dresden: 17
Freiburg: 12
ITALY
Pisa: 10
Rome: 10
THE NETHERLANDS
Nijmegen: 6
SWITZERLAND
Basel: 18
Zurich: 18
UNITED KINGDOM
Alderley Park, Macclesfield: 5
Exeter: 15
Hinxton: 15
London: 2, 5, 9, 15
Loughborough: 5
Newcastle: 15
Nottingham: 5
Oxford: 9, 15
UNITED STATES OF AMERICA
Alabama
Birmingham: 16
California
Berkeley: 19
La Jolla: 13
Los Angeles: 13
Pasadena: 3
San Francisco: 8
Santa Barbara: 3
Stanford: 11
Connecticut
Wallingford: 2
New Haven: 20
Georgia
Atlanta: 4
Illinois
Urbana: 3
Louisiana
Covington: 2
Maryland
Baltimore: 6
New Jersey
Belleville: 14
Morris Plains: 14
Rahway: 2
New York
New York: 1, 2, 17
Ohio
Cleveland: 17
Texas
Houston: 11
San Antonio: 11
Virginia
Norfolk: 5
Washington
Pullman: 17
PRESS CONTACTS...
For media inquiries relating to embargo policy for all the Nature Research
Journals:
Katharine Mansell (Nature London)
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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