Highlights from this week's Nature and August issues of Nature Research Journals

Biology: A structure of antidepressants' binding sites; Botany: A twist on corn-on-the-cob; Fast diodes speed up organic electronics; Small doses go a long way; Interfering with HIV.

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 24 July 2005

This press release contains:
* Biology: A structure of antidepressants' binding sites - Nature
* Botany: A twist on corn-on-the-cob - Nature
* Fast diodes speed up organic electronics - Nature Materials
* Small doses go a long way - Nature Biotechnology
* Interfering with HIV - Nature Structural and Molecular Biology

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

[1] Biology: A structure of antidepressants' binding sites

DOI: 10.1038/nature03978

Some of the body's most important signalling molecules - such as serotonin
and dopamine - rely on transporters to successfully clear them out of the
extracellular space in the brain. Transporters move these neurotransmitters
across the cell membrane by capitalizing on differences in ionic gradients.
Eric Gouaux and his colleagues have now captured the crystal structure of a
bacterial sodium/chloride-dependent transporter, which moves leucine across
membranes. The structure, detailed in a paper published online by Nature, is
the first glimpse of this large class of neurotransmitter sodium symporters.
The newly described structure has revealed the binding sites for ions and
leucine, together with the 'gates' that must be opened to allow access to
these sites. Gouaux and his team note that dysfunction of
sodium/chloride-dependent transporters in humans contributes to multiple
disorders, including Parkinson's disease and epilepsy. One member of this
family of transporters, which moves serotonin, is currently targeted by
fluoxetine (Prozac). Knowing the binding sites of these synaptic players
will probably help experts to design better drug treatments for depression
and neurodegenerative disorders.

Author contact
Eric J.E. Gouaux (Columbia University, New York, NY, USA)
Tel: +1 212 305 4062; E-mail: [email protected]

[2] Botany: A twist on corn-on-the-cob

DOI: 10.1038/nature03892

Corn-on-the-cob, a staple food of summer barbeques, has a hidden twist:
scientists have produced a gnarly mutant cob by disrupting the action of a
transcription factor that normally promotes gene expression. These findings,
published as an advance online publication by Nature, reveal secrets about
the plant's evolution.
Normally, structures of the maize plant branch out of a single point, giving
rise to the well-organized arrangement of kernels on the cob. Robert
Martienssen and his colleagues show that the transcription factor ramosa1 is
responsible for this organization. Disrupting the action of the ramosa1 gene
leads to branching in steps, which in turn gives rise to strangely formed
corn-on-the-cob.
The spaced branching caused by removing ramosa1 in maize resembles that of
other plants in the grass family, such as wheat. Interestingly, Martienssen
and his team found that rice, which has long branches, lacks this
transcription factor. Their findings provide insights into the evolutionary
development of the maize plant.

Author contact
Robert Martienssen (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY,
USA)
Tel: +1 516 367 8322; E-mail: [email protected] <mailto:[email protected]>

********************NATURE MATERIALS*********************
(<http://www.nature.com/naturematerials>)

[3] Fast diodes speed up organic electronics

DOI: 10.1038/nmat1434

A diode that can convert radio-frequency signals of up to 50MHz into
electric power is reported in the August issue of Nature Materials. This
all-organic electronic circuit, developed by Soeren Steudel and colleagues
could have widespread implications for the radio-frequency identification
(RFID) tags that are commonly used for tracking items such as commercial
goods for stocktaking purposes, airline luggage or for anti-theft devices in
shops.
Previous organic rectifier diodes were not able to work with the necessary
speed required for these tags to function, resulting in the use of
more-expensive silicon-based alternatives. By using all-organic circuits,
the production costs should be reduced. This could open the way for new
types of applications, such as replacing supermarket barcodes with RFID
tags. These tags would not require the scanning of individual items at the
checkout, but instead would allow the customer simply to walk through the
counter while a wireless scanner registers all the items in the basket at
once.

Author contact:
Soeren Steudel (IMEC, Polymer & Molecular Electronics, Leuven, Belgium)
Tel: +32 16 28 1751; E-mail: [email protected] <mailto:[email protected]>

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

[4] Coherent spin transport through dynamic quantum dots
DOI: 10.1038/nmat1430

[5] Low-temperature fabrication of dye-sensitized solar cells by transfer of
composite porous layers
DOI: 10.1038/nmat1433

[6] Multipurpose microfluidic probe
DOI: 10.1038/nmat1435

[7] Heterogeneity in polymer melts from melting of polymer crystals
DOI: 10.1038/nmat1437

******************NATURE BIOTECHNOLOGY******************
(http://www.nature.com/naturebiotechnolgy)

[8] Small doses go a long way

DOI: 10.1038/nbt1122

Researchers have found a way of delivering small RNA molecules
targeted against the hepatitis B virus at doses that are low enough to allow
this new therapeutic approach to be used in people. In the August issue of
Nature Biotechnology, David Morrissey and his colleagues incorporate
so-called small interfering RNAs (siRNAs) into lipid (fat-like) particles
that protect them against digestive enzymes in the blood, thereby increasing
their stability when injected into mice and reducing the dose needed for
therapeutic effect. These enzymes normally degrade RNA molecules in cells or
the circulation.
Previous studies suggested that the amounts of siRNA needed to achieve a
therapeutic effect in people far exceed safe levels of exposure to nucleic
acids. The work by Morrissey and his colleagues should enable siRNA to be
dosed at clinically relevant levels. In their experiments, mice carrying
replicating hepatitis B virus were given daily doses of encapsulated siRNAs
that specifically targeted the virus. Compared with the plain siRNAs used in
previous studies, the encapsulated siRNAs were much more effective at
inhibiting viral replication in mice-for up to 7 days after the last dose
was given-and worked at much lower doses. What's more, the encapsulated
siRNAs showed persistent activity against hepatitis B virus for up to 6
weeks when given only once a week. These results represent an important step
toward the practical implementation of siRNA-based therapeutic strategies.

Author Contact:

David V. Morrissey (Sirna Therapeutics, Inc. Boulder, CO, USA)
Tel: +1 303 546 8188, E-mail: [email protected]
<mailto:[email protected]>

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

[9] High-throughput generation of small antibacterial peptides with improved
activityQ1
DOI: 10.1038/nbt1113

[10] A bacterial one-hybrid system for determining the DNA-binding
specificity of transcription factors
DOI: 10.1038/nbt1120

[11] In vivo imaging platform for tracking immunotherapeutic cellsQ1
DOI: 10.1038/nbt1121

**************NATURE STRUCTURAL AND MOLECULAR BIOLOGY********************
(<http://www.nature.com/natstructmolbiol>)

[12] & [13] Interfering with HIV

DOI: 10.1038/nsmb967 &
DOI: 10.1038/nsmb964

Scientists have found a molecule that interferes with the formation of
infectious Human immunodeficiency virus (HIV) particles. The findings,
reported in two papers in the August issue of Nature Structural & Molecular
Biology could lead to the development of a new class of HIV drugs that slow
or prevent the progression of HIV in individuals.
More than 40 million people globally are currently infected with HIV, the
causative agent of AIDS, and approximately 5 million people become infected
each year. The current treatment for HIV infection involves a combination of
drugs that interfere with the activity of proteins crucial for the
production of new HIV particles and those that block the entry of the virus
into the cell. While the combination therapy has been highly successful, the
emergence of HIV strains resistant to more than one of these drugs has made
the identification of alternative targets a high priority.
HIV-1 is released from the infected cell as an immature, noninfectious
particle with a protein shell composed of Gag proteins. Formation of the
infectious particle requires the cleavage of Gag into smaller proteins. One
of these smaller proteins, called capsid, must interact with other capsid
proteins to form the mature, infectious virus. Now, Hans-Georg Kräusslich
and colleagues identify a 12 amino acid peptide that binds to capsid and
prevents its interactions with other capsid proteins. In an accompanying
paper, Felix Rey and colleagues show in three-dimensional detail how the
peptide interferes with capsid-capsid interactions. These studies identify
the first inhibitor directed against the transformation of immature HIV-1
into infectious particles, which can be developed for antiviral treatment.
Furthermore, these studies identify the immature virus particle as a new
target for drug design.

Author contacts:
Hans-Georg Kräusslich (Hygiene-Institut, Heidelberg, Germany)
Tel: +49 6221 565001; E-mail: [email protected]
<mailto:[email protected]>

Felix Rey (CNRS, Gif-sur-Yvette, France)
Tel: +33 1 45 68 85 63; E-mail: [email protected]
<mailto:[email protected]>

Additional contact for comment on papers:
Volker M. Vogt (Cornell University, Ithaca, NY, USA)
Tel: +1 607 255 2443, E-mail: [email protected] <mailto:[email protected]>

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

[14] Target RNA motif and mRNAs of the Quaking STAR protein
DOI: 10.1038/nsmb963

[15] Molecular architecture of a eukaryotic DNA transposase
DOI: 10.1038/nsmb970

***********************************
Items from other Nature journals to be published online at the same time:

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

[16] Killed but metabolically active microbes: a new vaccine paradigm for
eliciting effector T-cell responses and protective immunity
DOI: 10.1038/nm1276

[17] NFAT and Osterix cooperatively regulate bone
DOI: 10.1038/nm1270

[18] Hyperactivation of Stat3 in gp130 mutant mice promotes gastric
hyperproliferation and desensitizes TGF-beta signaling
DOI: 10.1038/nm1282

[19] Angiotensin II and EGF receptor cross-talk in chronic kidney diseases:
a new therapeutic approach
DOI: 10.1038/1275

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

[20] Demonstrating stratification in a European American population
DOI: 10.1038/ng1607

[21] A stress-sensitive reporter predicts longevity in isogenic populations
of Caenorhabditis elegans
DOI: 10.1038/ng1608

[22] Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in
frontotemporal dementia
DOI: 10.1038/ng1609

[23] Nova regulates brain-specific splicing to shape the synapse
DOI: 10.1038/ng1610

[24] Karyotypic abnormalities create discordance of germline genotype and
cancer cell phenotypes
DOI: 10.1038/ng1612

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

[25] Multiple origins of Cajal-Retzius cells at the borders of the
developing pallium
DOI: 10.1038/nn1511

[26] Motility-associated hair bundle motion in mammalian outer hair cells
DOI: 10.1038/nn1509

[27] Activation of p75NTR by proBDNF facilitates hippocampal long-term
depression
DOI: 10.1038/nn1510

NATURE IMMUNOLOGY (<http://www.nature.com/natureimmunology>)

[28] An essential function for the calcium-promoted Ras inactivator in
Fcgamma receptor-mediated phagocytosis
DOI: 10.1038/ni1232

NATURE CELL BIOLOGY (<http://www.nature.com/naturecellbiology>)

[29] Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex
in centrosome duplication
DOI: 10.1038/ncb1282

[30] Prohibitin is required for Ras-induced Raf-MEK-ERK activation and
epithelial cell migration
DOI: 10.1038/ncb1283

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]
<mailto:[email protected]>

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

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]
<mailto:[email protected]>

Nature Materials (London)
Ed Gerstner
Tel: +44 20 7843 4826; E-mail: [email protected]
<mailto:[email protected]>

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

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

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

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Published: 24 Jul 2005

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