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See also related STKE material on page 1347 or at
www.sciencemag.org/sciext/cellsignaling06/
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1341
CONTENTS
CONTENTS continued >>
DEPARTMENTS
1347 Science Online
1349 This Week in Science
1355 Editors’ Choice
1360 Contact Science
1363 Random Samples
1365 Newsmakers

1471 New Products
1472 Science Careers
EDITORIAL
1353 Responding to Fraud
by Donald Kennedy
1374
1410
INTRODUCTION
Size, Mates, and Fates 1409
PERSPECTIVES
Brassinosteroid Signaling: A Paradigm for Steroid Hormone 1410
Signaling from the Cell Surface
Y. Belkhadir and J. Chory
G Protein Signaling in Yeast: New Components, 1412
New Connections, New Compartments
J. E. Slessareva and H. G. Dohlman
Notch, a Universal Arbiter of Cell Fate Decisions 1414
M. Ehebauer, P. Hayward, A. Martinez-Arias
SPECIAL SECTION
Cell Signaling
Volume 314, Issue 5804
COVER
Artist’s representation of communication
pathways initiated by cell surface receptors
that influence cell physiology and organelle
function. This joint special issue between
Science and Science’s STKE highlights
new insights into signaling mechanisms
that control development and reproduction
(see page 1409).

Image: Christopher Bickel
NEWS OF THE WEEK
China’s Fraud Buster Hit by Libel Judgments; 1366
Defenders Rally Round
Fraud Investigation Clouds Paper on Early Cell Fate 1367
SCIENCESCOPE 1369
Squelching Progesterone’s Signal May Prevent 1370
Breast Cancer
>> Report p. 1467
Three Methods Add Up to One New Way to 1371
Genetically Engineer Fruit Flies
>> Science Express Report by K. J. T. Venken et al.
WHO Panel Weighs Radical Ideas 1373
NEWS FOCUS
Doing More With Less 1374
Burst-Hunter’s Rich Data Harvest Yields a 1376
Cosmic Enigma
South Africa Bolsters HIV/AIDS Plan, but 1378
Obstacles Remain
The Saola’s Last Stand 1380
CONNECTIONS MAPS
Brassinosteroid Signaling Pathway
Y. Belkhadir, X. Wang, J. Chory
Sci. STKE, encemag. org/cgi/cm/ stkecm;CMP_19131
Arabidopsis Brassinosteroid Signaling Pathway
Y. Belkhadir, X. Wang, J. Chory
Sci. STKE, />Pheromone Signaling Pathways in Yeast
H. G. Dohlman and J. E. Slessareva
Sci. STKE, />Notch Signaling Pathway
M. Ehebauer, P. Hayward, A. Martinez-Arias

Sci. STKE,
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www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1343
CONTENTS continued >>
SCIENCE EXPRESS
www.sciencexpress.org
MOLECULAR BIOLOGY
P[acman]: A BAC Transgenic Platform for Targeted Insertion of Large DNA
Fragments in Drosophila Melanogaster
K. J. T. Venken, Y. He, R. A. Hoskins, H. J. Bellen
A method allows efficient site-specific integration of large DNA sequences and thus
manipulation of proteins in vivo in Drosophila and potentially other organisms.

>> News story p. 1371
10.1126/science.1134426
EVOLUTION
Homoploid Hybrid Speciation in an Extreme Habitat
Z. Gompert, J. A. Fordyce, M. L. Forister, A. M. Shapiro, C. C. Nice
As postulated by theory, a new species of butterfly evolved when a hybrid of two
existing species became adapted to an extreme alpine environment.
10.1126/science.1135875
GEOPHYSICS
Slow Earthquakes Coincident with Episodic Tremors and Slow Slip Events
Y. Ito, K. Obara, K. Shiomi, S. Sekine, H. Hirose
A series of weak low-frequency earthquakes correspond with seismic tremor and slip
episodes on a subduction zone beneath Japan, perhaps increasing overall stress.
10.1126/science.1134454
ASTROPHYSICS
Spectropolarimetric Diagnostics of Thermonuclear Supernova Explosions
L. Wang, D. Baade, F. Patat
A survey of supernovae shows that brighter ones have more spherical explosions,
constraining the physics of burning and improving their use as standard candles.
10.1126/science.1121656
LETTERS
Balancing Communication and Safety S. A. Ehrlich 1387
Glossing Over the Complexity of Water G. Kallis,
M. Kiparsky, A. Milman, I. Ray
Mitochondrial DNA and Population Size O. F. Berry;
J. P. Wares et al. Response E. Bazin et al.
BOOKS ET AL.
The Other Insect Societies 1391
J. T. Costa, reviewed by R. Gadagkar
The Creation An Appeal to Save Life on Earth 1392

E. O. Wilson, reviewed by S. Bouma-Prediger
Nota Bene: Game On Science Museum, London 1393
POLICY FORUM
When Patents Threaten Science 1395
L. Andrews, J. Paradise, T. Holbrook, D. Bochneak
PERSPECTIVES
The Turing Model Comes of Molecular Age 1397
P. K. Maini, R. E. Baker, C M. Chuong
>> Report p. 1447
Variable High-Energy γ Rays from the Elliptical 1398
Galaxy M87
A. C. Fabian
>> Report p. 1424
When Dry Air Is Too Humid 1399
T. Peter et al.
Tools to Tamper with Phosphoinositides 1402
S. McLaughlin
>> Reports pp. 1454 and 1458
Delivering New Disease Genes 1403
L. R. Cardon
>> Report p. 1461
Edward I. Stiefel (1942–2006) 1406
F. M. M. Morel and J. T. Groves
TECHNICAL COMMENT ABSTRACTS
EVOLUTION
Comment on “Population Size Does Not Influence 1390
Mitochondrial Genetic Diversity in Animals”
C. J. Mulligan, A. Kitchen, M. M. Miyamoto
full text at www.sciencemag.org/cgi/content/full/314/5804/1390a
BREVIA

CLIMATE CHANGE
Old-Growth Forests Can Accumulate Carbon in Soils 1417
G. Zhou et al.
Old-growth forests in Southern China accumulated atmospheric
carbon at a rate considerably greater than expected for
broadleaved evergreen forests.
RESEARCH ARTICLE
ATMOSPHERIC SCIENCE
Phytoplankton and Cloudiness in the 1419
Southern Ocean
N. Meskhidze and A. Nenes
Oxidation of aerosols released from a phytoplankton bloom
doubled the number of droplets in overlying clouds and reflected
solar radiation as much as severe air pollution.
REPORTS
ASTRONOMY
Fast Variability of Tera–Electron Volt γ Rays from 1424
the Radio Galaxy M87
F. Aharonian et al.
Very-high-energy gamma rays from the radio galaxy M87
vary daily, implying that they originate close to the central
supermassive black hole. >> Perspective p. 1398
PHYSICS
Solid-State Qubits with Current-Controlled Coupling 1427
T. Hime et al.
Manipulation of the mutual inductance between two qubits can be
used to switch their coupling on and off.
CONTENTS
Good Vibrations Great Sections!
”Ideally, a tissue slicer should generate large-amplitude and high-frequency movements of the cutting blade

in a horizontal axis, with minimal vibrations in the vertical axis.“ *(According to Prof. P. Jonas, Institute of
Physiology, University of Freiburg, Germany).
Leica translated this into the Leica VT1200 and the Leica VT1200 S Vibrating Blade Microtome for cutting
fresh and fixed tissues.
Designed with You in Mind!
* Ref: Pflügers Arch - Eur. J. Physiol. (2002) 443:491-501
Patch-clamp recording in brain slices with improved slicer technology
*J.R.P. Geiger - J. Bischofberger - I. Vida - U. Fröbe
S. Pfitzinger - H.J. Weber - K. Haverkampf - P. Jonas
www.leica-microsystems.com/VT1200 S
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1345
CONTENTS continued >>
SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last week in December, by the American Association
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BIOCHEMISTRY
Structural Basis for Ribosome Recruitment and 1450
Manipulation by a Viral IRES RNA
J. S. Pfingsten, D. A. Costantino, J. S. Kieft
The structure of a viral RNA containing an internal ribosomal
entry site suggests how translation can begin in the middle

of a messenger RNA.
NEUROSCIENCE
Rapid Chemically Induced Changes of 1454
PtdIns(4,5)P
2
Gate KCNQ Ion Channels
B C. Suh, T. Inoue, T. Meyer, B. Hille
Neurotransmitters close a potassium channel by changing
the lipid content of the surrounding plasma membrane.
>> Perspective p. 1402
CELL BIOLOGY
PI(3,4,5)P
3
and PI(4,5)P
2
Lipids Target Proteins with 1458
Polybasic Clusters to the Plasma Membrane
W. D. Heo et al.
Two phospholipid signaling molecules are also essential to anchor
proteins that have clusters of basic amino acids to the cell membrane.
>> Perspective p. 1402
GENETICS
A Genome-Wide Association Study Identifies IL23R 1461
as an Inflammatory Bowel Disease Gene
R. H. Duerr et al.
People with a rare sequence variant of the gene encoding the
receptor for an immunological cytokine have a reduced risk
of inflammatory bowel disease. >> Perspective p. 1403
MICROBIOLOGY
Microfluidic Digital PCR Enables Multigene Analysis 1464

of Individual Environmental Bacteria
E. A. Ottesen, J. W. Hong, S. R. Quake, J. R. Leadbetter
A DNA analysis method that can link genes to individual organisms
collected in the wild is used to identify a gut symbiont of the termite.
MEDICINE
Prevention of Brca1-Mediated Mammary 1467
Tumorigenesis in Mice by a Progesterone Antagonist
A. J. Poole et al.
Experiments in mice suggest that a mutation leading to
breast cancer acts in part by altering signaling by the steroid
hormone progesterone. >> News story p. 1370
CONTENTS
1439
REPORTS
CONTINUED
APPLIED PHYSICS
Optical Atomic Coherence at the 1-Second Time Scale 1430
M. M. Boyd et al.
A highly stable laser and the ability to trap a large number of atoms
coherently provide a tenfold increase in measuring spectral lines
needed for precision applications.
MATERIALS SCIENCE
Macroscopic Hierarchical Surface Patterning of 1433
Porphyrin Trimers via Self-Assembly and Dewetting
R. van Hameren et al.
Upon dewetting, a molecule containing porphyrin and long alkyl
groups can self-assemble in long chains and patterns over areas
as large as several square millimeters.
CHEMISTRY
Probing the Chiroptical Response of a Single Molecule 1437

R. Hassey et al.
Circular dichroism spectra at high resolution reveal that weak
aggregate signals arise because the effects of distinct conformations
in a chiral ensemble cancel each other.
GEOCHEMISTRY
Organic Globules in the Tagish Lake Meteorite: 1439
Remnants of the Protosolar Disk
K. Nakamura-Messenger et al.
Carbon-rich nanospheres in a primitive meteorite are relatively
enriched in the heavy nitrogen isotopes and deuterium, suggesting
that these grains have a pre-solar origin.
ATMOSPHERIC SCIENCES
Increasing Trend of Extreme Rain Events Over India 1442
in a Warming Environment
B. N. Goswami et al.
The frequency and intensity of heavy rainfall events during monsoon
storms in Central India have increased during the past 50 years as the
climate there has warmed.
EVOLUTION
Male Fertility and Sex Ratio at Birth in Red Deer 1445
M. Gomendio et al.
Like females, males can affect offspring sex ratio; more-fertile male
red deer sire more sons and less-fertile males sire more daughters.
DEVELOPMENTAL BIOLOGY
WNT and DKK Determine Hair Follicle Spacing 1447
Through a Reaction-Diffusion Mechanism
S. Sick, S. Reinker, J. Timmer, T. Schlake
Modeling and experimental tests explain how a growth factor
and its inhibitor determine the density and pattern of hair follicles
in the developing mouse. >> Perspective p. 1397

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www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1347
ONLINE
SCIENCE’S STKE
www.stke.org

SIGNAL TRANSDUCTION KNOWLEDGE ENVIRONMENT
EDITORIAL GUIDE: Signal Reception and Transmission
N. R. Gough
New pathways and updates to the Database of Cell Signaling
highlight how signals received at the surface are transmitted
into the cell to mediate complex cellular responses.
SCIENCENOW
www.sciencenow.org DAILY NEWS COVERAGE
Taking the Toxin out of Cotton
Engineered plants have edible seeds, providing a possible
new source of cheap protein.
Clocking Cosmic Eyewalls
Scientists measure the speed of a spinning black hole.
Chimps Go Ape Over Older Females
Findings give clues to evolution of human mate preference.
SCIENCE CAREERS
www.sciencecareers.org
CAREER RESOURCES FOR SCIENTISTS
EUROPE: Navigating the Stem Cell Research Maze
S. Webb and E. Pain
Building a stem cell research career in Europe means navigating
the policy maze in each country.
US: It Ain’t Over Till It’s Over
B. Benderly
A bureaucratic snag has stalled California’s postdoc unionization
drive.
CANADA: Winning the HHMI International Research Award
A. Fazekas
A young biomedical researcher explains how career choices
translated into professional success.

GRANTSNET: December 2006 Funding News
J. Fernandez
Read about the latest in research funding, scholarships,
fellowships, and internships for postdocs and students.
Adapting to stem cell
research policies.
Separate individual or institutional subscriptions to these products may be required for full-text access.
www.sciencemag.org
Fit for consumption.
SPECIAL SECTION
Cell Signaling
CREDIT (SCIENCE CAREERS): NIH
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values by an order of magnitude. Such capabil-
ities facilitate high-precision unit standardiza-
tion and enhanced measures of fundamental
physical constants.
Monsoon Violence
Most climate models have predicted that

extreme rainfall events will become more
common as air temperature rises, but obser-
vational evidence of this trend has been
hard to find. Goswami et al. (p. 1442)
used a daily rainfall data set for central
India to show that there was an increase in
the frequency and intensity of heavy rain
events, and a decrease in the frequency of
light to moderate rain events, for the mon-
soon seasons from 1951 to 2000. The
mean rainfall did not show a significant
trend because the increasing contribution
from heavy events was offset by a decreas-
ing one from light ones. These findings
suggest that severe rain events over India
will become more common if global warm-
ing continues as expected.
Controlled Coupling
of Qubits
Performing logical operations on quantum com-
puters will require the coupling and decoupling
of qubits so that individual qubits can be pre-
pared in a given quantum state, allowed to
interact, and be read out once the final state is
Phytoplankton Clouds
Phytoplankton produce compounds that can
become aerosols, which suggests that biologi-
cal productivity might exert an important con-
trol on cloudiness over the ocean if these
aerosols act as cloud condensation nuclei.

Meskhidze and Nenes (p. 1419, published
online 2 November) combine satellite observa-
tions of surface ocean chlorophyll a content
and cloud cover to show that biological produc-
tivity can have a significant effect on shallow
marine clouds. Cloud droplet number concen-
trations over a phytoplankton bloom in the
Southern Ocean doubled, and cloud effective
radius was reduced by 30%, which led to a
large change in the short-wave radiative flux at
the top of the atmosphere.
In Tune for a Second
High-resolution spectroscopy generally
requires a trade-off between the size of the
ensemble being probed and the coherence of
that sample during the course of the measure-
ment, so that increasing the sample size to
raise signal strength often broadens the signal
of interest. Boyd et al. (p. 1430) have used an
optical trap to inhibit the random motion of
strontium atoms in order to maintain coher-
ence of the photoexcited sample for ~1 second.
By careful frequency stabilization of the probe
laser, an absorption line at ~10
14
hertz could
be measured with a corresponding width of
~1 hertz. The attained ratio of frequency to
linewidth, or quality factor, exceeds previous
achieved. Hime et al. (p. 1427) demonstrate

on-and-off control on a pair of superconduct-
ing-flux qubits coupled through their mutual
inductance. With both qubits also coupled to a
nearby superconducting quantum interference
device (SQUID), their mutual inductance and
the extent of the coupling strength could be
controlled by varying the working parameters
of the SQUID.
Lining Up at
the Front
Self-assembly of molecules can
create nanoscale features on flat
surfaces, but the maximum extent
of a single domain is usually on
the order of tens of micrometers.
Van Hameren et al. (p. 1433)
show that disk-like molecules, in
which three porphyrin groups bear-
ing long alkyl groups assemble
around a central core, form very
long aligned chains over areas
of several square millimeters
through a dewetting process. On
mica, single-column stacks form lines parallel to
the evaporation front of smaller droplets, whereas
for larger droplets, longer evaporation times
cause larger lines of aggregates to grow normal
to the evaporation front. Patterns formed on
rougher glass surfaces were less regular but could
still be used to align liquid crystal molecules.

EDITED BY STELLA HURTLEY AND PHIL SZUROMI
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1349
CREDITS (TOP TO BOTTOM): AHARONIAN ET AL.; GOSWAMI ET AL.
<< Fast Flickering
Among the very few known extragalactic emitters of very high
energy tera–electron volt (TeV) γ rays are blazars, which are
galaxies with relativistic particle jets that point toward
Earth. It has been suggested that the TeV γ rays originate in
those jets. By monitoring the nearby radio galaxy M87,
whose twin jets are oriented in the plane of the sky rather
than pointed at us, Aharonian et al. (p. 1424, published
online 26 October; see the Perspective by Fabian) show that
γ rays in active galaxies are actually produced near the cen-
tral black hole. M87 is bright in γ rays up to 10 TeV, and its
brightness varies daily. Such fast variations imply the source of
the γ rays lies near the Schwarzschild radius of the supermassive
black hole that lies at the heart of the M87 galaxy. Although this
behavior may fit some leptonic models for γ-ray production, an
alternative mechanism of proton curvature radiation near to the black
hole is proposed.
Continued on page 1351
EDITED BY STELLA HURTLEY AND PHIL SZUROMI
Open to
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www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
CREDIT: PFINGSTEN ET AL.
This Week in Science
More Boys Preferred
Biases in sex ratio at birth have led to the suggestion that females may manipulate the sex of their
offspring. Gomendio et al. (p. 1445) now show that males may also influence offspring sex ratio.
In red deer, more fertile males tend to produce proportionally more sons who are likely to inherit
high fertility rates. Sperm collected during the rut from males living in natural populations was
used for artificial insemination to minimize known female effects on sex ratio. Such male contribu-
tions to biases in offspring sex ratio suggest an evolutionary scenario in which conflicts of interest
between males and females in relation to the sex of their offspring may play an important role.
Turing Patterning in the Mouse Hairs
More than 50 years ago, Alan Turing provided a theoretical explanation of biological pattern for-
mation through a hypothesis of reaction-diffusion, whereby patterns, such as that for hair follicles
or feather distribution, can form as a result of positive and negative feedback regulation of an
inhibitor and activator. Turing models have since been used to account for patterns in many chemi-
cal systems, but have not been successful in explaining biological pattering in developmental
model systems such as the fly. Sick et al. (p. 1447, published online 2 November; see the Perspec-
tive by Maini et al.) have now examined hair follicle arrangements in mice that arise through the
WNT activator protein and its inhibitor DKK and show through computation modeling that reac-
tion-diffusion can account for the patterning observed.
Not Lost in Translation
The canonical mechanism for initiation of protein synthesis in
eukaryotes involves a nucleotide cap on messenger RNA
(mRNA) that is recognized by an initiation protein factor.

However, a variety of pathogenic viruses and cellular mRNAs
bypass the canonical mechanism by using structured RNA
sequences, called internal ribosomal entry sites (IRESs), to
initiate translation. Pfingsten et al. (p. 1450) have deter-
mined the structure of the ribosome-binding domain of an
IRES at 3.1 angstrom resolution. The RNA prefolds to create a
specific ribosome-binding structure. By docking the structure
onto cryoelectron microscopic reconstructions of an IRES-
ribosome complex, contacts were identified that drive bind-
ing and induce conformational change in the ribosome.
Of Genes and Gut Reactions
Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis are thought to be
caused by an inappropriate immune response to commensal intestinal bacteria. There is strong evi-
dence that these disorders have a genetic component; for example, individuals carrying specific
sequence variants of the NOD2/CARD15 gene are at increased risk. Now, in a genome-wide associ-
ation study, Duerr et al. (p. 1461, published online 26 October; see the Perspective by Cardon)
find that a rare sequence variant of the gene encoding the receptor for interleukin-23 (IL23R)
significantly lowers an individual’s risk of developing IBDs. Interleukin-23 is a cytokine that has
attracted increasing attention because of its role in a wide range of chronic inflammatory diseases
in mouse models, including IBDs, multiple sclerosis, and arthritis.
Progesterone and Breast Cancer
Mutations in the breast cancer susceptibility gene BRCA1 greatly increase a woman’s risk of develop-
ing breast and ovarian cancers. Why do these mutations predominantly affect hormone-responsive
tissues when the mutant gene is widely expressed throughout the body? Poole et al. (p. 1467; see
the news story by Marx) suggest that this tissue specificity is caused in part by BRCA1-mediated
effects on signaling by the hormone progesterone. Mammary epithelial cells (MECs) of Brca1/p53-
deficient mice accumulated high levels of progesterone receptors, probably through defective
degradation by the proteasome, and developed aberrant proliferation of the MECs. Treatment with
the progesterone antagonist mifepristone (RU 486) prevented or delayed mammary tumor develop-
ment in the mice.

Continued from page 1349
Science is a way of thinking
much more than it is a body of
knowledge.
Scientist
(
1934-1996
)
Our core strengths include not only technologies that support superior products and services, but also the spark of ideas that
lights the way to a brighter future. Shimadzu believes in the value of science to transform society for the better. For more than
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problems. The solutions we develop find applications in areas ranging from life sciences and medicine to flat-panel displays.
We have learned much in the past hundred years. Expect a lot more.
Carl Sagan
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1353
EDITORIAL
Responding to Fraud
Our journal—as well as science with a small “s”—went through a disappointing and troubling
experience with the two stem cell papers from the South Korean research group led by Dr. Woo
Suk Hwang. As a result of an investigation by a committee from Seoul National University,
the first paper from this group, Science 303, 1669 (2004), was found to be fraudulent and was
subsequently retracted by Science. A second paper, Science 308, 1777 (2005), published a year
later, was retracted for the same reasons.
What Science did then entailed two steps. First, we compiled a chronological anthology of
the editorial review process for both papers; it included all submissions; correspondence among
editors, our Board of Reviewing Editors, peer reviewers, authors, and agencies responsible for
regulatory oversight in South Korea; and notes on telephone conversations. This material was
reviewed by an internal review committee of six in-house
editors. This archive and their comments were then sent to

an outside committee consisting of three members of our
external Senior Editorial Board (John Brauman, George
Whitesides, and Linda Partridge), a former Science senior
editor who is now the U.S. Executive Editor at Nature
(Linda Miller), and two distinguished biologists who work
in the stem cell community (Doug Melton and John
Gearhart). The committee was asked to make a thorough
and unsparing analysis of Science’s handling of both papers and to make recommendations
for changes in procedure that might protect both the journal and the scientific community from
further unfortunate outcomes of this kind.
The report, and a short response from Science, are available at www.sciencemag.org/cgi/
content/full/314/5804/1353/DC1. The report is notable for its thoroughness, insight, and candor.
It reaches several conclusions; some of these apply to our journal and to those of us who edit
and publish it, and others are relevant for the larger community of scientists. The good news for
Science is that its editors and peer reviewers not only followed the procedures in place here
and at other top-tier journals, but made a substantially greater effort than for most papers to
ensure that the science was sound. The not-so-good news is that the report sends us some tough
messages about what Science should do to confront a present reality and prepare for a more
challenging future. It points out forcefully that the environment for science now presents
increased incentives for the production of work that is intentionally misleading or distorted by
self-interest. It urges us to give special attention to a relatively small number of papers that are
likely to be especially visible or influential.
We are now formulating ways to respond to this advice. The report recommends developing
a risk assessment template. We have been conducting discussions among ourselves and
with committee members to develop criteria for deciding which papers deserve particularly
careful editorial scrutiny. Papers that are of substantial public interest, present results that are
unexpected and/or counterintuitive, or touch on areas of high political controversy may fall
into this category. We are also considering the kinds of special attention that might be given to
these high-risk papers. These might include higher standards for including primary data,
demands for clearer specification of the roles of all authors, and more intensive evaluation of

the treatment of digital images. The report makes no bones about the fact that for some papers
that meet the higher risk standard, the experience will be time-consuming and expensive for the
journal and “may lead to conflict with authors.”
This is not the first time that scientific journals have had to adapt their procedures to new real-
ities in the world they live in. After 9/11 and the subsequent anthrax releases in the United States,
journals developed guidelines for recognizing and dealing with papers that might present inter-
national security problems. As we did then, we will be looking for ways to meet a new challenge,
while maintaining the integrity of the review process and minimizing damage to the expectations
of our authors and the speed of our publication process. We invite your comments and plan to
keep you informed as we develop particular policies in response to these recommendations.
– Donald Kennedy
10.1126/science.1137840
Donald Kennedy is the
Editor-in-Chief of Science.
“The report sends us some tough
messages about what Science
should do to confront a present
reality and prepare for a more
challenging future.”
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disease, and other protein misfolding diseases
might be similarly amenable to equivalent inter-
ventions. — SMH
Cell 127, 803 (2006).
GEOLOGY
Sediment Sources
The Nile River drains much of northeast Africa, and
its sediments reflect erosion across the continent.
Dams such as the Aswan have caused efficient col-
lection of these sediments in the human-made
lakes that form behind them. Garzanti et al. exam-
ined the mineralogy and amount of sand dumped
by the Nile into these
lakes and found that
~200 million metric
tons of sediment are
transported per year,
several times the quanti-
ties estimated previ-
ously. The sand is mainly
composed of basaltic
rock or feldspar and
metamorphic minerals,

indicative of the
Ethiopian highlands, an
area of abundant deforestation and farming that
receives monsoon rainfall during summer. Thus, a
relatively small area of the Nile drainage, greatly
affected by humans, supplies most of the sedi-
ments carried by the river to artificial lakes. — BH
Earth Planet. Sci. Lett. 10.1016/j.epsl.2006.10.001
(2006).
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
1355
CREDITS (TOP TO BOTTOM): MARTIN HARVEY/PETER ARNOLD, INC.; KARL VERNES; CORBIS
EDITORS’CHOICE
ECOLOGY/EVOLUTION
Going to the Dingoes
In the past 200 years, since the arrival of Europeans in Australia, 18 of the
continent’s mammal species have become extinct. These extinctions have
been chiefly attributed to introduced, non-native predators, especially
foxes and cats. Johnson et al. present evidence that the success of these
medium-sized introduced predators has been the direct result of
persecution by humans of Australia’s native large predator,
the dingo. In areas where dingoes have been left alone,
foxes and cat populations are kept at bay, and the
diversity and abundance of native marsupials are
greater. Thus, top predators can maintain biodiversity
at middle trophic levels and may help ecosystems to
resist invasion by alien species. By allowing dingo
populations to recover in regions where they have been
persecuted, it might be possible to insure remaining small
marsupials against further decline and extinction. — AMS

Proc. R. Soc. London Ser. B 10.1098/rspb.2006.3711 (2006).
CELL BIOLOGY
Toward the Chaperome
The expression of misfolded or aberrant proteins
on the cell surface could wreak havoc with the
immune system. Cells have therefore developed
an efficient quality-control system, which diverts
misfolded membrane and secretory proteins
from the secretory pathway by retaining and
degrading them at the entry portal to the secre-
tory pathway, the endoplasmic reticulum (ER).
One well-studied example of quality control
involves the cystic fibrosis transmembrane con-
ductance regulator (CFTR), misfolding of which is
responsible for disease in a large proportion of
sufferers. However, sometimes quality control is
too stringent, and functional, though mutant,
proteins are retained. Wang et al. used a system-
atic approach to examine the folding pathway
and protein interaction partners of CFTR and the
common disease variant CFTR ΔF508, which,
even though functional, is retained in the ER.
A variety of chaperone proteins, which help to
promote protein folding, are present in the ER,
and a chaperome of over 30 proteins involved in
CFTR folding and transport was identified from
among more than 200 interacting proteins.
In particular, Aha1, a Hsp90 co-chaperone
ATPase regulator, was found to be important in
retaining mutant CFTR. When levels of Aha1

were reduced, mutant CFTR managed to escape
from the ER and reached the plasma membrane.
Interfering with CFTR-specific chaperone mecha-
nisms may thus be a useful strategy to correct
CHEMISTRY
Catalyst Compatibility
The isolation and purification procedures that
follow synthetic chemical reactions often produce
substantial quantities of waste material. Research
has thus increasingly focused on methods for
carrying out multiple reaction steps in a single
vessel. However, the mutual incompatibility of
many catalysts, in particular Lewis acids and bases,
presents a major challenge to this approach.
Poe et al. present an encapsulation technique
that allows the mixing of a polymeric amine cata-
lyst with a nickel-centered Lewis acid while avoid-
ing the complexation reaction that
would deactivate both. The
poly(ethyleneimine) base is
treated with a cross-linking agent
in a methanol/cyclohexane emul-
sion, yielding a microcapsule
morphology that conserves cat-
alytic activity in the condensation
reaction of benzaldehyde and
nitromethane. Addition of a
bis(diamino)nickel catalyst to the
reaction mixture promotes a
Michael addition of dimethyl mal-

onate to the dehydrated product in ~80% yield.
Moreover, the compatibility of the two catalysts is a
boon to selectivity as well as efficiency; the nickel
complex staves off a side pathway that would lead
to a double nitromethane adduct. — JSY
J. Am. Chem. Soc. 128, 10.1021/ja066476l (2006).
EDITED BY STELLA HURTLEY AND JAKE YESTON
Continued on page 1357
The Aswan Dam.
Dingo (top), rat-kangaroo (right).

IMMUNOLOGY
Trekking Lymph Node Tracks
Lymph nodes are crucial staging posts from which
immune responses are launched throughout the
body. To achieve this, naïve lymphocytes must
locate and respond to their specific antigens,
which are relatively scarce. The active migratory
tendency of lymphocytes helps to achieve this,
and the structural organization of the lymph node
itself also improves the chances of antigen
encounter. Bajenoff et al. now find that organized
networks of stromal cells provide trackways for
lymphocytes to travel around lymph nodes. With a
combination of microscopy and real-time intravi-
tal imaging, T cells were seen to enter the lymph
node paracortex by interacting with fibroblastic
reticular cells (FRCs). Inside the lymph node, the
FRC formed a three-dimensional network along
which a large proportion of T cells could crawl.

Antigen-presenting dendritic cells also associated
with the FRC network, which is consistent with
the idea that this would optimize the rate of en-
counter between the two types of cell. B cells were
also seen to move along the FRC tracks within the
www.sciencemag.org SCIENCE VOL 314 1 DECEMBER 2006
EDITORS’CHOICE
CREDITS: BAJENOFF ET AL., IMMUNITY 25 10.1016/J.IMMUNI.2006.10.011 (2006)
paracortex, transferring to a similar network of
dendritic cells once they had entered the lymph
node follicle. It will now be interesting to elucidate
the molecular cues that govern migration along
these cellular highways and byways. — SJS
Immunity 25 10.1016/j.immuni.2006.10.011
(2006).
PHYSICS
Fast Track for Fusion
The search for controlled nuclear fusion for
energy production has been hindered by sub-
stantial engineering and fundamental physical
challenges. One approach has been to confine
a hot plasma with magnetic fields in a device
called a Tokamak and then to heat the plasma
until nuclear reactions become self-sustaining.
As the plasma is heated, however, the highest-
velocity ions can drive wave motions and insta-
bilities that disrupt its integrity. Worse yet, the
fast ions can escape with their energy rather
than contributing to the heating process.
Bindslev et al. report a diagnostic technique in

which beams of electromagnetic waves at fre-
quencies of ~110 GHz are scattered off the ions
in the TEXTOR (Tokamak Experiment for Technol-
ogy-Oriented Research) reactor in Germany.
The energy spectrum of the scattered photons
from this collective Thomson scattering process
reveals the velocity distribution of the fast ions.
By acquiring spectra at different times during
the heating of the plasma, the authors can
uncover the evolution of the fast ion dynamics.
Diagnostic tools such as this are expected to be
especially important when ITER (the Interna-
tional Thermonuclear Experimental Reactor)
commences operation in 2016. — DV
Phys. Rev. Lett. 97, 205005 (2006).
Continued from page 1355
1357
<< Shedding Light on Immunosuppression
Ultraviolet (UV) radiation from sunlight has been implicated in skin
cancer and—perhaps not coincidentally—suppresses the immune
response. UV-dependent immune suppression depends on its absorp-
tion by an epidermal photoreceptor. Trans-urocanic acid (UCA) iso-
merizes to cis-UCA in response to UV exposure, and epidermal UCA
acts as a UV photoreceptor that can mediate immune suppression. The mechanism whereby cis-
UCA affects the immune response, however, has been unclear. Cis-UCA forms a ring-like struc-
ture in solution, and Walterscheid et al., who serendipitously observed that the serotonin recep-
tor antagonist ketanserin blocked UV- and cis-UCA–mediated immune suppression, now find
that cis-UCA can bind to human serotonin receptors. Cis-UCA stimulated calcium mobilization
in cells that express the serotonin receptor, and this calcium mobilization was blocked by
ketanserin. UV- or cis-UCA–induced immune suppression in mice was blocked by antibodies

directed against serotonin (as well as by antibodies directed against cis-UCA) and by serotonin
receptor antagonists. Thus, the ability of cis-UCA to suppress the immune response—and that
of UV radiation—are mediated through the serotonin receptor. — EMA
Proc. Natl. Acad. Sci. U.S.A. 103, 17420 (2006).
www.stke.org
T cell (blue) on the FRC network (red and green).
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