Viewing receptor clusters in a heartbeat, Diagnostic methods promise smallpox detection, Avoiding regret in the brain, Taking complements away, Helping smokers quit.

Nature research journals - For papers that will be published online on 7 August 2005


For papers that will be published online on 7 August 2005

* Viewing receptor clusters in a heartbeat - Nature Chemical Biology
* Diagnostic methods promise smallpox detection - Nature Medicine
* Avoiding regret in the brain - Nature Neuroscience
* Taking complements away - Nature Immunology
* Helping smokers quit - Nature Structural & Molecular Biology

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

[1] Viewing receptor clusters in a heartbeat

DOI: 10.1038/nchembio726

An article in the September issue of Nature Chemical Biology reports the use
of a high-resolution imaging technique to visualize heart cell receptor
clusters for the first time. The receptors that control heart rate are known
to cluster into distinct signalling zones. The density of receptors in these
signalling zones defines the basis of the stimulatory signal.
The heart rate is controlled by beta-adrenergic receptors located on the
surface of heart cells. Adrenergic receptors belong to a class of receptor
called G protein-coupled receptors, which are common in many cell types and
participate in many important biological functions. Although much is known
about the structures and properties of this class of receptor, little is
known about the receptors' actual cellular location and distribution during
cell-signalling events.

Now, Pezacki and coworkers have used a state-of-the-art microscopy technique
called near-field scanning optical microscopy (NSOM) to visualize
cell-surface beta-adrenergic receptors of heart cells. Because NSOM has
higher resolution than conventional light microscopy, it is possible to
visualize individual molecules located on the cell surface. The authors
showed that between 15% and 20% of the receptors located on the cell surface
were clustered into distinct groups or signalling islands. Using a
combination of NSOM and fluorescence microscopy, the authors were able to
estimate the density of receptors clustered in the signalling zones.
Receptor stimulation produced no change in receptor density, which suggests
that the receptors are prearranged into signalling islands.
This work clearly demonstrates the power of NSOM as an imaging technique.
Its application to other signalling receptors could provide valuable
insights into the signalling events that occur in both healthy and diseased

Author contact:
John Paul Pezacki (Steacie Institute for Molecular Sciences and Chemical
Biology, National Research Council Canada, Ottawa, Canada)
Tel: +1 613 993 7253, E-mail: [email protected]

Additional contact for comment on paper:
Krzysztof Palczewski (University of Washington, Seattle, WA, USA)
Tel: +1 206 543 9074, E-mail: [email protected]

****************NATURE MEDICINE*************************

[2] Diagnostic methods promise smallpox detection

DOI: 10.1038/nm1273

Smallpox is a significant bioterror threat, but there are no rapid, accurate
methods to detect it. In the September issue of Nature Medicine, researchers
report on a diagnostic method that could be used to accurately detect
smallpox. The report also shows that smallpox vaccination confers protection
for decades.

Routine smallpox vaccination in the US stopped in 1972, more than 20 years
after the last case of smallpox in the country. Erika Hammarlund and
colleagues used data from a 2003 outbreak of monkeypox in the US to develop
diagnostic methods. Monkeypox, less dangerous than its deadly cousin
smallpox, is caused by a virus of the same family.

The researchers' analysis showed that the monkeypox outbreak was of a larger
scale than previously thought, at least in part because of protection
conferred by smallpox vaccination. The data suggest that smallpox
vaccination can protect against similar diseases, such as monkeypox, for up
to 75 years after inoculation, the researchers say.

Author contact:
Mark Kenneth Slifka (Oregon Health & Sciences University, Beaverton, OR,
Tel: +1 503 418-2751; E-mail: [email protected]

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

[3] Hyaluronan accumulates in demyelinated lesions and inhibits
oligodendrocyte progenitor maturation
DOI: 10.1038/nm1279

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

[4] Avoiding regret in the brain

DOI: 10.1038/nn1514

A brain region called the medial orbitofrontal cortex mediates the influence
of emotions like regret on decision-making, shows a functional imaging study
in the September issue of Nature Neuroscience.

People offered a certain $50 or a 1 in 100 chance of winning $5000 will
usually choose the sure thing. But people are more likely to take the risky
alternative if they know they'll find out later whether they would have won
the gamble. Economists attribute this behavior to a desire to avoid the
regret that would result from knowing that one has passed up a big prize.

Subjects in the study were offered a choice of two gambles, one riskier than
the other, and the authors induced regret on some trials by providing
outcome information for both gambles. As the experiment proceeded, subjects
modified their choices to reduce the potential for regret, and activity in
the medial orbitofrontal cortex and amygdala increased. This pattern of
brain activity was seen after a choice that inspired regret (when the
riskier gamble that was not chosen paid off), and when the subjects were
deciding which gamble to choose. This pattern of activity was absent when
subjects' 'choices' were determined by a computer - indicating that personal
responsibility was important for activating these areas.

Previous work has shown that patients with lesions to the orbitofrontal
cortex have difficulty making appropriate choices in such gambling tasks,
lending support to the authors' conclusions.

Author contact:
Angela Sirigu (CNRS, Institut des Sciences Cognitives, Bron, France)
Tel: +33 04 37 91 12 12; E-mail: [email protected]

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

[5] Extensive piano practicing has regionally specific effects on white
matter development
DOI: 10.1038/nn1516

[6] Sleep-disordered breathing after targeted ablation of preBötzinger
complex neurons
DOI: 10.1038/nn1517

[7] Filling-in of visual phantoms in the human brain
DOI: 10.1038/nn1518

[8] 'Breaking' position-invariant object recognition
DOI: 10.1038/nn1519

[9] Selective inhibition of 2-AG hydrolysis enhances endocannabinoid
signaling in hippocampus
DOI: 10.1038/nn1521

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

[10] Taking complements away

DOI: 10.1038/ni1235

Staphylococcus aureus is an important human pathogen that can hide from the
immune system. In the September issue of Nature Immunology, scientists have
identified a staphylococcal protein that can block the complement cascade -
an important arm of the early immune response - aiding the bacteria to
escape detection by the immune system.

Rooijakkers and colleagues show that SCIN, a protein secreted by S. aureus,
inhibits a key molecule in the complement pathway called C3 convertase. By
binding to C3 convertase, SCIN effectively switches off the complement
cascade, reducing the ability of immune cells to engulf and kill S. aureus.
This molecule could prove useful for the treatment of complement-related
diseases in the future.

Author contact:
Suzan Rooijakkers (University Medical Center Utrecht, Netherlands)
Tel: +31 30 250 6525, E-mail: [email protected]

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

[11] Function of NKG2D in natural killer cell-mediated rejection of mouse
bone marrow grafts
DOI: 10.1038/ni1236

[12] The Jak-STAT signaling pathway is required but not sufficient for the
antiviral response of drosophila
DOI: 10.1038/ni1237


[13] Helping smokers quit

DOI: 10.1038/nsmb971

Methoxsalen is a drug that has been clinically proven to decrease smoking. A
study in the September issue of Nature Structural & Molecular Biology
reveals how methoxsalen interacts with and blocks the action of a protein
that breaks down nicotine. This information could aid in the development of
more potent drugs to help people reduce their craving for nicotine and stop

People who have nicotine addiction continue to smoke to maintain high
nicotine levels in the brain. Methoxsalen specifically prevents the protein
cytochrome P450 2A6 from degrading nicotine. Cytochrome P450 2A6 also breaks
down carcinogens found in tobacco to more harmful chemicals that can cause
cancer. Eric Johnson and C. David Stout and colleagues show how methoxsalen
binds to this protein and blocks its action.
Understanding this drug interaction will help guide future studies aimed at
improving inhibitor design. Ultimately, this may lead to better drugs aimed
at decreasing nicotine dependence that at the same time could also reduce
the risk of tobacco-related cancers.

Author contact:
Eric F. Johnson (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 7918, E-mail: [email protected]

C. David Stout (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 8738, E-mail: [email protected]

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

[14] Regulated degradation of replication-dependent histone mRNAs requires
both ATR and Upf1
DOI: 10.1038/nsmb972

[15] Chromatin remodeling through directional DNA translocation from an
internal nucleosomal site
DOI: 10.1038/nsmb973

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


[16] Quantitative equivalence between polymer nanocomposites and thin
polymer films
DOI: 10.1038/nmat1447

[17] Polymer hollow particles with controllable holes in their surfaces
DOI: 10.1038/nmat1448

[18] On-demand release of corrosion-inhibiting ions from amorphous Al-Co-Ce
DOI: 10.1038/nmat1451


[19] Epimutation of the telomeric imprinting center region on chromosome
11p15 in Silver-Russell syndrome
DOI: 10.1038/ng1629

[20] Intragenic tandem repeats generate functional variability
DOI: 10.1038/ng1618

[21] Contributions of low molecule number and chromosomal positioning to
stochastic gene expression
DOI: 10.1038/ng1616


[22] A GTPase-activating protein controls Rab5 function in endocytic
DOI: 10.1038/ncb1290



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.

Leuven: 20

Ottawa: 1

Besançon: 19
Bron: 4
Paris: 12, 19
Strasbourg: 12

Martinsried: 22

Budapest: 9

Parma: 9
Urbino: 9

Tokyo: 11

Pohang: 16

Leiden: 10
Utrecht: 10

Stockholm: 5

London: 4
Oxford: 10

Irvine: 9
La Jolla: 13
Los Angeles: 6
Palo Alto: 11
San Francisco: 11
Baltimore: 3
Cambridge: 8, 20, 21
New Jersey
Princeton: 7
New York
Niskayuna: 16
Troy: 16
North Carolina
Chapel Hill: 14
Cleveland: 3
Beaverton: 2, 3
Portland: 3
Nashville: 7
Salt Lake City: 15
Charlottesville: 18
Seattle: 17


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