Tạp chí khoa học số 2006-12-01

Image: Christopher Bickel NEWS OF THE WEEK Defenders Rally RoundFraud Investigation Clouds Paper on Early Cell Fate 1367 Breast Cancer >> Report p.. SCIENCE CAREERS www.sciencecareers.or

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See also related STKE material on page 1347 or at www.sciencemag.org/sciext/cellsignaling06/

Brassinosteroid Signaling: A Paradigm for Steroid Hormone 1410

Signaling from the Cell Surface

Y Belkhadir and J Chory

New Connections, New Compartments

J E Slessareva and H G Dohlman

M Ehebauer, P Hayward, A Martinez-Arias

Science and Science’s STKE highlights

new insights into signaling mechanismsthat control development and reproduction(see page 1409)

Image: Christopher Bickel

NEWS OF THE WEEK

Defenders Rally RoundFraud Investigation Clouds Paper on Early Cell Fate 1367

Breast Cancer

>> Report p 1467

Genetically Engineer Fruit Flies

>> Science Express Report by K J T Venken et al.

NEWS FOCUS

Brassinosteroid Signaling Pathway

Y Belkhadir, X Wang, J Chory

Sci STKE, http://stke.sciencemag org/cgi/cm/ stkecm;CMP_19131

Arabidopsis Brassinosteroid Signaling Pathway

Y Belkhadir, X Wang, J Chory

Sci STKE, http://stke.sciencemag.org/cgi/cm/stkecm;CMP_19349

Pheromone Signaling Pathways in Yeast

H G Dohlman and J E Slessareva

Sci STKE, http://stke.sciencemag.org/cgi/cm/stkecm;CMP_13999

Notch Signaling Pathway

M Ehebauer, P Hayward, A Martinez-Arias

Sci STKE, http://stke.sciencemag.org/cgi/cm/stkecm;CMP_19043

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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 slipepisodes 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.

J T Costa, reviewed by R Gadagkar

E O Wilson, reviewed by S Bouma-Prediger

POLICY FORUM

L Andrews, J Paradise, T Holbrook, D Bochneak

PERSPECTIVES

P K Maini, R E Baker, C.-M Chuong

S McLaughlin >> Reports pp 1454 and 1458

L R Cardon >> Report p 1461

F M M Morel and J T Groves

TECHNICAL COMMENT ABSTRACTSEVOLUTION

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

BREVIACLIMATE CHANGE

Old-Growth Forests Can Accumulate Carbon in Soils 1417

G Zhou et al.

Old-growth forests in Southern China accumulated atmosphericcarbon at a rate considerably greater than expected for broadleaved evergreen forests

RESEARCH ARTICLEATMOSPHERIC SCIENCE

Southern Ocean

N Meskhidze and A Nenes

Oxidation of aerosols released from a phytoplankton bloom doubled the number of droplets in overlying clouds and reflectedsolar 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

Good Vibrations Great Sections!

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in a horizontal axis, with minimal vibrations in the vertical axis.“ *(According to Prof P Jonas, Institute of Physiology, University of Freiburg, Germany).

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*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

CONTENTS continued >>

SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005 Periodicals Mail postage (publication No.

484460) paid at Washington, DC, and additional mailing offices Copyright © 2006 by the American Association for the Advancement

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paid directly to CCC, 222 Rosewood Drive, Danvers, MA 01923 The identification code for Science is 0036-8075 Science is indexed in the Reader’s Guide to Periodical Literature and in several specialized indexes.

BIOCHEMISTRY

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

PtdIns(4,5)P2Gate 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)P3and PI(4,5)P2Lipids Target Proteins with 1458

Polybasic Clusters to the Plasma Membrane

A Genome-Wide Association Study Identifies IL23R 1461

as an Inflammatory Bowel Disease Gene

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 organismscollected in the wild is used to identify a gut symbiont of the termite

MEDICINE

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

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 Molecule1437

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

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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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

SCIENCE NOW

www.sciencenow.org DAILY NEWS COVERAGE

Taking the Toxin out of CottonEngineered plants have edible seeds, providing a possiblenew source of cheap protein

Clocking Cosmic EyewallsScientists measure the speed of a spinning black hole

Chimps Go Ape Over Older FemalesFindings 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

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

Fit for consumption

rs.info@thomson.com

© Copyright 2006 Thomson EndNote is a registered trademark of Thomson.

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values by an order of magnitude Such ities facilitate high-precision unit standardiza-tion and enhanced measures of fundamentalphysical constants.

capabil-Monsoon Violence

Most climate models have predicted thatextreme 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 centralIndia to show that there was an increase inthe frequency and intensity of heavy rainevents, and a decrease in the frequency oflight to moderate rain events, for the mon-soon seasons from 1951 to 2000 Themean rainfall did not show a significanttrend because the increasing contributionfrom heavy events was offset by a decreas-ing one from light ones These findingssuggest that severe rain events over Indiawill become more common if global warm-ing continues as expected

pre-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 ~1014hertz 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 ing-flux qubits coupled through their mutualinductance With both qubits also coupled to anearby superconducting quantum interferencedevice (SQUID), their mutual inductance andthe extent of the coupling strength could becontrolled by varying the working parameters

superconduct-of the SQUID

Lining Up at the Front

Self-assembly of molecules cancreate nanoscale features on flatsurfaces, but the maximum extent

of a single domain is usually onthe order of tens of micrometers

Van Hameren et al (p 1433)

show that disk-like molecules, inwhich three porphyrin groups bear-ing long alkyl groups assemblearound a central core, form verylong aligned chains over areas

of several square millimetersthrough a dewetting process Onmica, single-column stacks form lines parallel tothe evaporation front of smaller droplets, whereasfor larger droplets, longer evaporation timescause larger lines of aggregates to grow normal

to the evaporation front Patterns formed onrougher glass surfaces were less regular but couldstill be used to align liquid crystal molecules

Among the very few known extragalactic emitters of very high

galaxies with relativistic particle jets that point toward

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

brightness varies daily Such fast variations imply the source of

black hole that lies at the heart of the M87 galaxy Although this

alternative mechanism of proton curvature radiation near to the blackhole is proposed

Continued on page 1351

Open to

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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 inherithigh fertility rates Sperm collected during the rut from males living in natural populations wasused 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 interestbetween 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 mation through a hypothesis of reaction-diffusion, whereby patterns, such as that for hair follicles

for-or feather distribution, can ffor-orm as a result of positive and negative feedback regulation of aninhibitor 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 tive by Maini et al.) have now examined hair follicle arrangements in mice that arise through the

Perspec-WNT activator protein and its inhibitor DKK and show through computation modeling that tion-diffusion can account for the patterning observed

reac-Not Lost in Translation

The canonical mechanism for initiation of protein synthesis ineukaryotes involves a nucleotide cap on messenger RNA(mRNA) that is recognized by an initiation protein factor.However, a variety of pathogenic viruses and cellular mRNAsbypass the canonical mechanism by using structured RNAsequences, 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 anIRES at 3.1 angstrom resolution The RNA prefolds to create aspecific ribosome-binding structure By docking the structureonto 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 becaused 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 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)

associ-significantly lowers an individual’s risk of developing IBDs Interleukin-23 is a cytokine that hasattracted 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 defectivedegradation by the proteasome, and developed aberrant proliferation of the MECs Treatment withthe progesterone antagonist mifepristone (RU 486) prevented or delayed mammary tumor develop-ment in the mice

Science is a way of thinking

much more than it is a body of knowledge.

Responding to Fraud

Our journal—as well as science with a small “s”—went through a disappointing and troublingexperience with the two stem cell papers from the South Korean research group led by Dr WooSuk 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 amongeditors, our Board of Reviewing Editors, peer reviewers, authors, and agencies responsible forregulatory oversight in South Korea; and notes on telephone conversations This material wasreviewed 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 ourexternal 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 JohnGearhart) 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 fromfurther 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 editand 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 toensure 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 presentsincreased incentives for the production of work that is intentionally misleading or distorted byself-interest It urges us to give special attention to a relatively small number of papers that arelikely 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 andwith committee members to develop criteria for deciding which papers deserve particularlycareful editorial scrutiny Papers that are of substantial public interest, present results that areunexpected and/or counterintuitive, or touch on areas of high political controversy may fallinto this category We are also considering the kinds of special attention that might be given tothese 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 ofthe treatment of digital images The report makes no bones about the fact that for some papersthat meet the higher risk standard, the experience will be time-consuming and expensive for thejournal and “may lead to conflict with authors.”

This is not the first time that scientific journals have had to adapt their procedures to new 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

real-of our authors and the speed real-of our publication process We invite your comments and plan tokeep 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 diseasesmight be similarly amenable to equivalent inter-ventions — SMH

col-lakes that form behind them Garzanti et al

exam-ined the mineralogy and amount of sand dumped

by the Nile into theselakes and found that

~200 million metrictons of sediment aretransported per year,several times the quanti-ties estimated previ-ously The sand is mainlycomposed of basalticrock or feldspar andmetamorphic minerals,indicative of theEthiopian highlands, anarea of abundant deforestation and farming thatreceives monsoon rainfall during summer Thus, arelatively small area of the Nile drainage, greatlyaffected 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)

E C O L O G Y / E V O L U T I O NGoing to the Dingoes

In the past 200 years, since the arrival of Europeans in Australia, 18 of thecontinent’s mammal species have become extinct These extinctions havebeen 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 ofpersecution 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 aregreater Thus, top predators can maintain biodiversity

at middle trophic levels and may help ecosystems toresist invasion by alien species By allowing dingo populations to recover in regions where they have beenpersecuted, it might be possible to insure remaining smallmarsupials against further decline and extinction — AMS

Proc R Soc London Ser B 10.1098/rspb.2006.3711 (2006).

C E L L B I O L O G Y

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

C H E M I S T R Y

Catalyst Compatibility

The isolation and purification procedures that follow synthetic chemical reactions often producesubstantial quantities of waste material Researchhas thus increasingly focused on methods for carrying out multiple reaction steps in a single vessel However, the mutual incompatibility ofmany 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 lyst with a nickel-centered Lewis acid while avoid-

cata-ing the complexation reaction thatwould deactivate both Thepoly(ethyleneimine) base istreated with a cross-linking agent

in a methanol/cyclohexane sion, yielding a microcapsulemorphology that conserves cat-alytic activity in the condensationreaction of benzaldehyde andnitromethane Addition of abis(diamino)nickel catalyst to thereaction mixture promotes aMichael addition of dimethyl mal-onate to the dehydrated product in ~80% yield

emul-Moreover, the compatibility of the two catalysts is aboon to selectivity as well as efficiency; the nickelcomplex 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).

I M M U N O L O G Y

Trekking Lymph Node Tracks

Lymph nodes are crucial staging posts from which

immune responses are launched throughout the

body To achieve this, nạve 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

Immunity 25 10.1016/j.immuni.2006.10.011

(2006)

P H Y S I C S

Fast Track for Fusion

The search for controlled nuclear fusion forenergy production has been hindered by sub-stantial engineering and fundamental physicalchallenges One approach has been to confine

a hot plasma with magnetic fields in a devicecalled a Tokamak and then to heat the plasmauntil nuclear reactions become self-sustaining

As the plasma is heated, however, the velocity ions can drive wave motions and insta-bilities that disrupt its integrity Worse yet, thefast ions can escape with their energy ratherthan contributing to the heating process

highest-Bindslev et al report a diagnostic technique in

which beams of electromagnetic waves at quencies of ~110 GHz are scattered off the ions

fre-in the TEXTOR (Tokamak Experiment for ogy-Oriented Research) reactor in Germany

Technol-The energy spectrum of the scattered photonsfrom this collective Thomson scattering processreveals the velocity distribution of the fast ions

By acquiring spectra at different times duringthe heating of the plasma, the authors canuncover the evolution of the fast ion dynamics

Diagnostic tools such as this are expected to beespecially important when ITER (the Interna-tional Thermonuclear Experimental Reactor)commences operation in 2016 — DV

Phys Rev Lett 97, 205005 (2006).

<< Shedding Light on Immunosuppression

Ultraviolet (UV) radiation from sunlight has been implicated in skincancer and—perhaps not coincidentally—suppresses the immuneresponse UV-dependent immune suppression depends on its absorp-

tion by an epidermal photoreceptor Trans-urocanic acid (UCA) 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-

iso-UCA affects the immune response, however, has been unclear Cis-iso-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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E D I T E D B Y C O N S T A N C E H O L D E N

Reading University last week became the 21st British university to announce the

closure of its physics department since 1997 Despite protests from staff and

stu-dents and a petition from more than 2000 researchers around the world, the

uni-versity council voted on 20 November to accept no more physics students The

department will close in 2010

U.K universities are largely government-funded, with the amounts

deter-mined by numbers of students and quality of research Reading Vice-Chancellor

Gordon Marshall said in an open letter that the physics department is losing

about $1 million a year because it is not getting enough new students—28 this

year against a target of 50—or enough research income

The closure of science and math departments (Science, 4 February 2005,

p 668) prompted the U.K government last month to announce $140 million to

help key departments over the next 3 years But it won’t be enough to help

Reading, Marshall says Philip Diamond of the Institute of Physics in London says

economics favors big departments these days; a half-dozen now account for half

of all U.K physics students, and “small ones are just vulnerable.”

Keeping Book on Baby

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Diseases on the Move

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Some whales have a

specialized brain cell

that hitherto has been

seen only in humans

and great

apes—lead-ing some scientists to

suggest that cetaceans

evolved their relatively

advanced brains before

primates did

Humans, chimps, and gorillas share a type of cortical nerve cell—called a

spindle neuron—that is lacking in all other primates The cells appear to

con-nect regions implicated in higher cognitive functions to other parts of the brain

Neuroscientist Patrick Hof and neuroendocrinologist Estel Van der Gucht of

Mount Sinai School of Medicine in New York City have now discovered spindle

neurons, in areas homologous to their location in human brains, in several

large-brained cetaceans including humpback and fin whales The researchers estimate

that bigger-brained whales evolved spindle neurons 22 million to 30 million

years ago Because the common ancestor of great apes only dates to about 15

mil-lion years ago, the pair concludes that these cells must have evolved

independ-ently in apes and whales Reporting online this week in The Anatomical Record,

they speculate that whale talents such as the formation of social groups as well as

singing and other communicative skills are linked to the enhanced connectivity

provided by spindle neurons

Clever but smaller-brained dolphins don’t have spindle neurons John Allman,

a neurobiologist at the California Institute of Technology in Pasadena, says the

neurons are probably “adaptations that support fast communication … in very

large brains.” Allman says his group is looking to see whether elephants also

have the cells

Baby books, those little pamphlets that record baby’s first stepsand first words, now interest more than doting relatives Scholarsare finding the books a new source of close-up information onthe early lives of infants from different times

Last month, the University of California, Los Angeles (UCLA),Louise M Darling Biomedical Library held a reception to intro-duce its collection of

more than 500 babybooks dating back to

1884 It’s a historicaltreasure trove thatcharts shifting atti-tudes about publichealth and parent-hood, says archivistRussell Johnson “Aspace for the father

t o m a k e e n t r i e s

d o e s n ’ t s h o w u puntil around WorldWar II,” he notes

The books mayhave emerged as part

of a late–19th tury public healthcampaign to “Save the Babies,” according to Jacqueline H Wolf,

cen-a mediccen-al historicen-an cen-at Ohio University in Athens “Bcen-aby booksrepresented a change in cultural thinking,” she says “Infantswere not weak and susceptible, as people had long argued.Rather, infant death was preventable.”

Russell says UCLA welcomes donations from all eras, cially because the library often battles collectors of famouschildren’s book illustrators when copies come up on eBay

espe-1930babybook

Humpbackwhale

WELL-WIRED WHALES >>

ANOTHER PHYSICS DEPARTMENT DOWN

EDITED BY YUDHIJIT BHATTACHARJEE

THE FIRST PODSTER There you are, standing byyour poster at the big annual meeting, when theBig Kahuna in your field walks up If only you had some multime-dia to make a quick impression Next time, try attaching some videoiPods to your poster, says graduate student Pascal Wallisch of theUniversity of Chicago in Illinois, who unveiled what may be theworld’s first “Podster” at October’s meeting of the Society forNeuroscience in Atlanta, Georgia

Wallisch got the idea after a poster session at the 2005 science meeting in which he used his laptop to show videos of hisresearch on the primate visual system Reaching around to point atthe screen was awkward, however, and the batteries ran out So thisyear, he replaced the laptop with two iPods, each loaded withvideos to explain different features of his experiment It gave visi-tors a more interactive experience, he says, and left his hands free

neuro-Passers-by loved the concept, says Wallisch, as did two AppleComputer reps from a nearby booth—until they found out he’d used

a Microsoft product to create the poster’s text and graphics “Thenthey just left,” Wallisch says

Up Next

O N C A M P U S

CLEVERNESS CONTROVERSY A Danish

IQ researcher who was suspended after his

research suggested that men have slightly

higher IQs than women has been found

guilty of “official misconduct” but reinstated

in his job

Psychologist Helmuth Nyborg, 69, of the

University of Aarhus was suspended last

spring following criticism of a report from a

longitudinal study called the Skanderborg

project Nyborg reported in a June 2005 paper

in the Journal of Personality and Individual

Differences that when IQ test scores of

62 Danes he has beenfollowing since the1970s are properlyanalyzed, they reveal

a roughly four-pointadvantage for males

Although Nyborg isnot alone in reportingsuch a sex difference,some scholars criti-cized the research onmethodologicalgrounds University officials set up a committee

to investigate, and in July, it reported that there

was no evidence of fraud In September, the

university declared that Nyborg had

demon-strated “grossly negligent behavior” and issued

him a “severe reprimand” before revoking his

suspension Colleagues from around the world

have rallied to his defense, accusing the

univer-IN TANDEM Sometimes a little sibling rivalrycan be a good thing Last week, KevinShenderov, a 19-year-old senior at New YorkUniversity, followed the footsteps of his brotherEugene by winning a Rhodes Scholarship

Kevin (left) intends to pursue a doctorate inimmunology at Oxford University—just asEugene (center) is now doing

The brothers credit their parents, Peter, amedical physicist, and Faina, who is complet-ing a doctorate in pharmacy, for inculcating a love of science Both worked at MemorialSloan-Kettering Cancer Center in New York City when the boys were growing up, and “thedinner conversation pretty much always centered around what was going on at the hospital,”

says Eugene, 23, who won a Rhodes 2 years ago “Science was the family’s bread and butter.”

Peter says the brothers have pushed each other but remain close “This kind of competition ispulling them together,” he says “The accomplishment is the icing on the cake.”

Got a tip for this page? E-mail people@aaas.org

sity of having political motives and claimingthat the errors in his research were trivial

P O L I T I C S

U.K SCIENCE MINISTER An educator turnedpolitician is the new U.K minister for scienceand innovation Malcolm Wicks, 59, succeedsDavid Sainsbury, who stepped down last monthafter 8 years marked by a doubling of U.K

spending on research

The son of a Labour Member of Parliamentand a Labour MP himself since 1992, Wicksmost recently guided a strategic plan for a dra-

as energy minister in the Blair government

Slowing the buildup ofgreenhouse gases, hesaid, is the “world’smost pressing chal-lenge.” Wicks hascalled the UnitedKingdom’s and theworld’s failure toaddress nuclear waste

“an absolute disgrace,”

although he has alsosaid that nuclear power could be a clean alternative to fossil fuels Wicks attended theLondon School of Economics but has no formaltraining in science

NEWS >>

THIS WEEK Progesterone and

breast cancer A new way to engineer flies

cop, Fang Shi-min, was dealt a pair of

set-backs last week in his high-profile crusade

against academic misconduct Two Chinese

cour ts handed down libel judgments

against Fang, known by his nom de guerre

Fang Zhouzi, and the newspapers and

Inter-net sites that have featured his writings on

pseudoscience and fraud Fang’s

revela-tions have cost several scientists their jobs

and reputations

With Fang now on the defensive, his

backers are setting up two funds to help foot

the costs of litigation “If you strike false

science, false science [makers] will strike

you,” says Guo Zhengyi, a science writer

and a co-organizer of one foundation Guo

and others say they hope that, by drawing

attention to what they call “absurd” court

rulings, they may force the government to

crack down on corruption

Fang received a Ph.D in biochemistry

and did a postdoc in the United States

before becoming a science essayist He got

fired up about fraud in 2001, after reading

dubious claims in the Chinese media about

“nucleotide supplements.” Fang then

started using his Web site, Xin Yu Si (“New

Threads”), to debunk pseudoscience

a n d expose alleged misconduct, from

10 August 2001, p 1039)

By Fang’s tally, New Threads has aired

allegations against more than 500 als Fang uncovered some cases himself, butmost were e-mailed to him by others Fewexposures have led to off icial investiga-tions, and fewer still have resulted in pun-ishment—the most notable being the dis-missals earlier this year of an assistant dean

individu-of Qinghua University’s medical school inBeijing and a dean at Tongji University inShanghai, both for having falsif ied theirrésumés and exaggerated achievements

The anonymous allegations published

on New Threads trouble some people,

who liken them to dazibao, or posters,

used during the Cultural Revolution todenounce “class enemies.” Fang and hissupporters contend there’s a big differ-

ence: The Web postings are individualactions not directed by the state The Chi-nese gover nment takes an ambiguousstance: It blocks access in China to NewThreads’ U.S.–based site, www.xys.org,but allows access to mirror sites

Fang’s recent setbacks came on tive days On 21 November, a Beijing inter-mediate court ruled that an article Fangwrote in 2005 defamed the late Liu Zihua, aSichuan provincial government employee

consecu-In a dissertation written in France in the1930s, Liu presented calculations based onthe eight trigrams of an ancient divination

text, I Ching (Book of Changes), predicting

the existence of a 10th major planet in thesolar system Liu’s prognostication was res-urrected after last year’s announced discov-ery of 2003UB313 (now officially a dwarfplanet named Eris) A Sichuan newspaperran a story extolling Liu’s prophecy

In an essay, Fang labeled Liu’s prediction

“pseudoscience” and noted that a Chineseastronomer discredited it in the 1940s Liu’swidow and son sued Fang and several news-papers and Internet content providers forlibel The court judged Fang’s words “insult-ing” to Liu and ordered him to apologizepublicly and pay Liu’s family $2500 pluslegal fees The family did not respond to aninterview request

Then on 22 November, a court in Xi’anslapped another libel judgment on Fang,

ordering him and Beijing Keji Bao (Beijing

Sci-Tech Report) to pay Xi’an Fanyi

Univer-sity $18,750 and its president Ding Zuyi

$1250 in damages plus legal fees In 2004,Chinese newspapers ran stories citing a

“report” in the Los Angeles Times lauding

Ding as one of China’s most respected sity presidents and his private college fortraining translators as the 10th-ranked univer-

univer-sity in China In a 2005 article in Beijing

Sci-Tech Report, Fang quoted an education

ministry spokesperson, who stated that tigations showed the report to be “a self-paidadvertisement.” Ding sued Fang for libel.Ding could not be reached for comment Fang is appealing another libel verdict

inves-by a Wuhan court last July In this case,Xiao Chuan-guo, a urology professor atHuazhong University of Science and Tech-nology in Wuhan and a clinical associateprofessor at New York University School ofMedicine, sued after Fang accused him in an

China’s Fraud Buster Hit by Libel

Judgments; Defenders Rally Round

essay last year of counting conference

abstracts as publications in international

journals to inflate his achievements Fang

also challenged Xiao’s claim that a surgical

procedure he invented is recognized

inter-nationally and has won neurourology’s

“highest award.” The presiding judge ruled

that Fang’s criticisms “seriously lacked

facts” and ordered him to apologize publicly

and pay Xiao $3750 in compensation A

final ruling is expected in early December

Xiao told Science that the accusations are

groundless and that Fang “intentionally

con-fused” Xiao’s urology awards Xiao says he

supported Fang until 2002, after which he

concluded that Fang had begun to “misguidethe public” with less-than-solid accusations

In response to the Wuhan ruling, ZhangFeng, a Florida-based financial analyst andcollege classmate of Fang’s, along with eightother expatriates, last month established theOrganization for Scientific and AcademicIntegrity in China to raise money for Fangand other anticorruption campaigners Sofar, the nonprofit has received more than

$10,000 in donations And in China, Guoand others are creating a separate sciencefraud-f ighting fund Fang’s lawyer, PengJian, hopes the foundations will raise money

to “implement systematic investigations into

some individual cases or organize seminars

to discuss legal punishments against provedmisconduct makers.”

Fang vows to continue “using tongued criticism” to expose misconductand folly But he doubts that his freelancefraud busting can play a “decisive role” incleaning up Chinese academia To be moreeffective, he says, he intends to report futureallegations, when appropriate, to a new dis-ciplinary office at China’s Ministry of Sci-ence and Technology and wait for a responsebefore posting them online

sharp-–JIA HEPENG AND HAO XIN

Jia Hepeng is a writer in Beijing

Fraud Investigation Clouds Paper on Early Cell Fate

A surprising report in a contentious area of

developmental biology has sparked a

scien-tific misconduct investigation at the

Univer-sity of Missouri, Columbia Until that

inquiry is complete, the results of the

impli-cated paper, published in Science earlier this

year, remain in limbo

Contrary to prevailing dogma, the report

claimed that mouse embryo cells have

dis-tinct fates from the time of the very first

cell division If true, those findings would

dramatically change the current

under-standing of mammalian embryo

develop-ment—and could also play a role in

on-going political and ethical debates over

cloning and stem cells

But the senior author of the paper now

says the results are not trustworthy and

pre-dicts that the paper will be retracted as soon

as the university completes its

investiga-tion The paper, which was accepted as

Science editors were embroiled in the

scan-dal surrounding Woo Suk Hwang’s human

cloning papers in early 2006 (see Editorial

on p 1353), again raises questions about

the limitations of the peer-review process in

detecting fraud

Published in the 17 February issue of

Science (p 992), the paper caused an

immediate stir It is well known that

embry-onic cells of insects and amphibians have

distinct fates from the first cell divisions,

but the picture for mammalian embryos has

been far murkier (Science, 6 May 2005,

p 782) Experiments in which mouse

embryos are teased apart and cells planted from one embryo to another havesuggested that until about a week after fer-tilization, mammalian embryo cells arequite interchangeable There is an ongoingdebate, however, over whether very earlyembryo cells—when the embryo is at thefour- or eight-cell stage—might have a ten-dency toward one fate or another, althoughthey are not yet committed The resultspublished in February indicated a muchearlier differentiation than anyone else in

trans-the field had suggested

The corresponding author, R MichaelRoberts, is an expert in bovine embryologyand until this year had not been involved inthe debate In the paper, Roberts, with post-doctoral fellows Kaushik Deb and Hwan YulYong and microscope technician MayandiSivaguru, claimed that in most mouseembryos there was a distinct differencebetween cells from the first cell division on

One cell had strong expression of a gene

called Cdx2, the paper claimed, and

eventu-ally went on to give rise to the placental

tis-sues The other, which had less Cdx2

expres-sion, went on to form the eventual fetus Thescientists argued that their observations mighthelp explain why cloning in mammals is so

inefficient If Cdx2 expression is disrupted by

cloning, they speculated, then embryos mighthave a hard time developing further

Proponents of so-called alternativenuclear transfer were also excited by theresults This technique has gained some sup-port among people otherwise opposed to

stem cell research and human nuclear fer because it hypothetically offers a way toderive stem cells without destroying anembryo If scientists use egg cells or somatic

trans-cells lacking Cdx2 for their nuclear transfer,

the reasoning goes, the resulting cells would

be unable to form a true embryo

The Roberts results seemed to help thesupporters’ case: If the gene is so crucialfrom the very beginning, then that wouldstrengthen the argument that cells lacking itcould not be called an embryo

DEVELOPMENTAL BIOLOGY

Surprisingly clear The paper reported finding the Cdx2 protein (green) concentrated in just one of the cells

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of animal experimentation, appears to bethe first political party devoted to animalwelfare Its platform includes a ban on trans-genic animals, better oversight of animalexperiments, including better housing anddaily checks by independent vets, and moreresearch on alternatives.

–MARTIN ENSERINK

Dawkins Versus the Gods

After scanning the titles in a local bookshop,Oxford University geneticist Richard Dawkinsdiscovered that “real science” was “out-numbered three to one by pseudoscience.”

Concerned that “the enlightenment is under

threat,” the author of The God Delusion has

created and will help fund the Richard DawkinsFoundation for Science and Reason The newcharity, with U.S and U.K branches, will sup-port research on “the psychological basis ofunreason,” produce videos and books, and run

a Web site (richarddawkins.net/foundation)

Another goal, “to oppose … well-financedefforts to teach creationism in science classes,”will put it up against the U.K.–based Truth inScience, which recently sent “intelligentdesign” promotional packs to 5700 British sec-ondary schools Truth in Science claims itreceived 59 positive responses

–ELIOT MARSHALL

Hope for German GM crops

BERLIN—In a move to support plantresearchers, the German agriculture ministerhas apparently agreed to ease rules controllingthe planting of genetically modified (GM)crops German media reported last week thatthe minister, Horst Seehofer, will proposeallowing the government to pay for damagesresulting from any gene-altered pollen thatescapes from government-funded researchplots Under current rules, the farmers orresearchers who plant GM seeds are liable forany pollen that might contaminate a neigh-bor’s field, preventing it from being sold asGM-free The proposal, contained in a measurethat could be presented to legislators earlynext year, would also restrict public access toinformation about where GM crops areplanted Despite overwhelming public opposi-tion to GM foods, research minister AnnetteSchavan has been pushing for such rules

–GRETCHEN VOGEL

The results, however, “were so drastically

different from any of the results obtained by

any other group” that most people viewed them

skeptically from the start, says Magdalena

Zernicka-Goetz of the University of

Cam-bridge, U.K However, it wasn’t immediately

clear why the results were so different, she

says A different strain of mice or a different

labeling technique might have been the

cause, she says

Others in the field were less willing to

suspend their disbelief Within weeks of the

paper’s publication, Roberts says, several

scientists wrote to Science, to Roberts, and

to the University of Missouri, pointing out

problems with the data Some of the images

seemed suspiciously similar to each other,

they said In others, the staining didn’t seem

to line up exactly with the cells By late

April, Roberts says, the university had

started an investigation

It was soon clear that there

was reason to worry about the

data’s veracity, Roberts says “In

my view, there are a number of

questionable images,” he says

But until the university

investi-gation is complete, he says, the

team will not be able to explain

the details of what is wrong or

retract the paper Roberts says

the university is being very

cau-tious about assigning any blame

before the investigation is

com-plete All the co-authors have

since left the university Two

have found other jobs, and a third

has apparently dropped out of

contact In the meantime, Science

issued an “Editorial Expression

of Concern” to alert the

commu-nity that it should not trust the

p u bl i s h e d r e s u l t s ( S c i ence,

27 October, p 592)

Some critics question why the

paper was published in the first place or why

image-analysis techniques—which Science

editors said they put in place at the beginning

of the year—didn’t spot the apparent

problems Davor Solter of the Max Planck

Institute for Immunobiology in Freiburg,

Germany, one of the scientists who wrote to

Science, contends that the review process

was flawed Science editors declined to

dis-cuss the specif ics of the review process,

which is confidential, but Katrina Kelner,

deputy editor for biology, says, “Science

published the paper based on feedback we

got from the field.”

Solter speculates that leading scientists

in the field did not review the paper, noting

that if they had, they likely would havecaught the problems But Richard Behringer

of M D Anderson Cancer Center in ton, Texas, is not sure the problems couldhave been spotted ahead of time AlthoughBehringer now says he can see the evidence

Hous-of duplicated images, he says at first ing the paper seemed solid, if surprising

read-“I can understand why referees wouldsay OK,” he says

Kelner and Science Editor-in-Chief

Donald Kennedy add that even if the data arefound to have been manipulated, the newimage-analysis techniques would not havepicked it up Those techniques can flagunmatched pixels that are signs of deletions

or cut-and-paste manipulations But cated images—like those in the Hwangpaper—are harder to spot, Kelner says

dupli-In retrospect, Roberts says he wishes hehad been more cautious with the results his

lab members presented to him “I didn’t gointo this with preconceived ideas I got into it

by happenstance,” he says The research was

aimed at determining whether Cdx2 was

involved in turning on another gene inbovine embryos, he explains, and the mouseembryos were used as controls to analyze

Cdx2 expression “But the results looked so

beautiful, you couldn’t come to any otherconclusion.” Since questions about the paperwere raised, he says, “I’ve obviously ques-tioned myself and my judgment I haven’thad a good night’s sleep since February.”

The University of Missouri is expected tofinish its investigation later this month

–GRETCHEN VOGEL

Senior author R Michael Roberts says the paper will likely beretracted as soon as the University of Missouri finishes its investigation

NEWS OF THE WEEK

A woman who carries a mutated BRCA1

gene faces a daunting decision: She can opt

for constant monitoring hoping to catch

any cancer early, while it’s still curable, or

she can elect to have her breasts or ovaries

removed to prevent cancer from

develop-ing in the first place Results described on

page 1467 now suggest that one day there

may be a third option: using drugs rather

than surgery to prevent BRCA1-mediated

breast cancers

BRCA1 is a so-called tumor suppressor,

a gene that in its normal form protects

against cancer One way it does this is by

helping cells repair DNA damage that

might otherwise result in cancer-causing

mutations The new work, which comes

from Eva Lee and her colleagues at the

Uni-versity of California, Irvine, points to

another cancer-preventing role for BRCA1.

By aiding in the degradation of the receptor

through which progesterone exerts its

effects, the gene’s protein product

appar-ently checks the hormone’s

growth-pro-moting action on breast tissue

Lee’s team also showed that

mifepris-tone, a drug that induces abortions by

inhibiting the progesterone receptor, blocks

the development of mammary tumors in

mice that have had the rodent version of

BRCA1 inactivated in their mammar y

glands “The paper has a mechanism [of

BRCA1 activity] and has clinical

implica-tions It’s potentially important,” says Eliot

Rosen of Georgetown University School of

Medicine in Washington, D.C., who is also

studying the interaction between BRCA1

and progesterone

Previous work had raised suspicions

that progesterone fosters breast cancer

development For example, women

tak-ing both estrogen and progesterone to

treat menopausal symptoms have a higher

risk of developing breast cancer than

wo m e n wh o t a ke e s t r og e n o n ly A n d

working with human breast cancer cells

in lab cultures, Rosen’s team found that

normal BRCA1 inhibits the action of the

progesterone receptor, although how has

been unclear

In the current work, Lee and her

col-leagues created mice that lacked

function-ing copies of the rodent versions of both

BRCA1 and p53, another tumor suppressor

that is frequently mutated in breast cancers

Although the female mice had never been

mated, their mammar y tissue showed

increased cell proliferation—much as thebreasts of pregnant woman do when highprogesterone levels prepare the mammaryglands for lactation What’s more, all therodents developed mammary cancers bythe age of 8 months Mice treated with

mifepristone, however, were still free at 12 months of age

tumor-Lee and her colleagues then took a closerlook at the epithelial cells that give rise tobreast cancer “A lot more cells” from thedouble-mutant mice had progesteronereceptors, she says, than did cells from nor-mal animals or from animals in which only

the p53 gene had been knocked out.

Further work on cultured mouse andhuman cells revealed that the progesteronereceptor is broken down less readily whenBRCA1 activity is missing As a result,

“the [hormone’s] signal goes on muchlonger,” Lee says The excessive cell

g rowth this produces provides extrachances for cancer-promoting DNA muta-

tions to occur, especially because BRCA1

loss also handicaps the cell’s DNA repairmachinery The participation of the proges-

terone receptor in BRCA1-mediated breast

cancer could help explain why tumorsoccur specifically in the breast and ovarieseven though the gene is mutated in cellsthroughout the body Those other cellsdon’t carry progesterone receptors

Lee points out that mifepristone itselfmay not be suitable for long-term use incancer prevention because it acts on steroidreceptors besides the one for progesterone

It might therefore cause unacceptable sideeffects such as immune suppression Othermore specif ic progesterone blockers areunder development, Lee notes

There is uncertainty about how rately the new mouse model reflectshuman breast cancer Lee cites findings byJeff Boyd’s team at Memorial Sloan-Kettering Cancer Center in New York Citythat tissue adjacent to human breast tumors

accu-with BRCA1 mutations shows elevated

progesterone expression compared to

t i s sue from nor mal breast However,Christine Clarke and her colleagues at theUniversity of Sydney at Westmead Millen-nium Institute in Westmead, Australia,actually saw a decrease in progesteronereceptors in tissue removed by mastectomy

from BRCA1 carriers

The two situations aren’t quite rable “The status of tissue around tumors

compa-is different from that of tcompa-issue taken fromnor mal breast,” Clarke says But thatissue, and likely many others, needs to beresolved before cancer prevention trials ofprogesterone inhibitors can begin

–JEAN MARX

Squelching Progesterone’s Signal May Prevent Breast Cancer

MEDICINE

Releasing the brakes The ducts from mouse

mammary tissue in which both the p53 and BRCA1 genes have been inactivated (bottom) show

increased growth and branching compared to ducts

from either normal mice (top) or animals in which only p53 is inactive (middle).

EPA, Berkeley Think Small

The U.S Environmental Protection Agency(EPA) has decided to regulate silver ions, thebacteria-killing nanoparticles used in prod-ucts as diverse as shoe liners and food storagecontainers The agency will require Samsung,which sells an ion-emitting device in a wash-ing machine, to spell out possible environ-mental impacts under rules that apply to pes-ticides, even though the agency does not yetknow whether the device involves nanomateri-als “The fact that EPA seems to be addressingthis is a good thing,” says physicist AndrewMaynard of the Woodrow Wilson InternationalCenter for Scholars in Washington, D.C Theupcoming federal notice could clarify whetherthe decision heralds broader federal limits onnanotechnology

Meanwhile, scientists in Berkeley, fornia, say their work will not be affected by aproposed city rule, the first of its kind in theUnited States, that would require the registra-tion of nanoparticles The council is expected

Cali-to discuss the measure next week

–ELI KINTISCH

South Korean Flu Mystery

An outbreak of the H5N1 strain of bird flu inSouth Korea may reignite debate over how thedisease is spread Researchers had longargued about whether the H5N1 strain, whichhas killed 258 humans since it started sweep-ing through Asia in 2003, is spread by wildbirds or the movement of infected poultry andcontaminated crates and vehicles

Last week, the South Korean governmentconfirmed H5N1 as the culprit behind thedeaths of 6000 chickens on a farm in Iksan,south of Seoul, the first known H5N1 outbreak

in Korea since 2003 The route of infection inthat incident has never been proven, althoughSouth Korea’s Ministry of Agriculture & Forestryhas since warned on its Web site about thepotential for H5N1 transmission from migratorybirds to domestic chickens to people

Casting the blame on migratory fowl

“could lead to the vilification of wild birds”

and attempts to slaughter them or disturbtheir habitat, warns ornithologist Nial Moores

of Birds Korea, a conservation group “The realdanger comes from poultry infecting wild birdsand not the other way around,” Moores says

He’s particularly worried about major ing grounds at the mouth of the Geum River,

winter-5 kilometers from Iksan, currently home to theworld’s largest concentration of Baikal teal “Ifavian influenza gets transmitted into this flock,

it could be devastating,” Moores says

–DENNIS NORMILE

When Koen Venken began a Ph.D project on

fruit fly genetics at Baylor College of

Medi-cine in Houston, Texas, 4 years ago, he quickly

became frustrated by limitations of the

stan-dard techniques for genetically engineering

the insects So he turned his attention to

devel-oping a novel procedure The result, described

in a paper published online by Science this

week (www.sciencemag.org/cgi/content/

abstract/1134426), appears to be a powerful

new way of making transgenic flies, one that

will likely make it easier to study fruit fly

genes that were previously too large to work

with and to compare the behavior of similar

genes belonging to different fly species

The work eases two roadblocks that have

long troubled the fly community: inserting

genes longer than about 20,000 DNA

bases—which make up more than 5% of the

insect’s genes—and controlling where in the

genome those genes land, which impacts how

they get expressed “The real advantage here

is that it’s a way of putting in really big bits of

DNA” into the fly, says Michael Ashburner, a

fly geneticist at the University of Cambridge,

United Kingdom

Traditionally, geneticists create

trans-genic flies with help from a piece of fly DNA

called the P element Roughly 2 decades ago

Gerald Rubin, now director of the Howard

Hughes Medical Institute’s (HHMI’s) Janelia

Farm in Loudoun County, Virginia, and his

colleagues spliced a stretch of DNA into aportion of a P element and found that the newDNA was easily incorporated into the fly’sgenome The P element, however, can’t inte-grate long stretches of DNA like the onesVenken wanted to work with when he joinedthe Baylor lab of geneticist and HHMI inves-tigator Hugo Bellen

So Venken took components of the

P element, including ones that allow it tointegrate DNA into the fly genome, andadded them to loops of bacterial DNAcalled plasmids These bacterial artificialchromosomes (BACs) can more stablyretain larger amounts of foreign DNA than

a P element alone To add into those BACsthe DNA he wanted to insert into the flies,Venken next turned to a technique calledrecombineering, which was developedabout 8 years ago Recombineeringinvolves allowing a BAC to recombine with

an intended transgene within bacteria, lating that BAC, and then using other bacte-ria to make multiple copies of it

iso-Finally, Venken used a third existingtechnique to control where in the flygenome the BAC-ferried gene would land

When he injected the BACs into fruit flyembryos, Venken also injected messengerRNA that encodes an enyzme made by abacterial virus called a phage This enzymenormally inserts a phage’s DNA into spe-cif ic sites on a bacterial genome, but inthese circumstances, it integrates the BAC-carried gene at similar DNA sequencesengineered into the fly genome

Using this combination of methods,Venken, Bellen, and their colleagues haveinserted DNA stretches as long as 133,000bases into the fly genome “It’s now not clearwhat the upper limit is,” says Daniel Barbash,

a geneticist at Cornell University Bellen’slab is now assembling a library of fly DNA inthe novel BACs for interested researchers

The new approach “is a significant nical advance,” says Rubin It “allows us to

tech-do certain things we couldn’t tech-do before,”

such as study the effects of whole gene plexes, like the homeotic genes that affectearly development And several scientistsnote that this blended approach might work

com-to genetically modify other organisms “Thepotential to export this system to … otheranimals is quite high,” says Barbash

–JENNIFER COUZIN

BAC-ed up A new method allows researchers to

insert lots of DNA into fruit flies

Three Methods Add Up to One New

Way to Genetically Engineer Fruit Flies

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Lifesaving antiretroviral drugs have been

available for a decade in wealthy countries,

yet millions of HIV-infected people south of

the equator still can’t get them The medicine

cupboard is equally bare for people afflicted

by tropical illnesses such as visceral

leishma-niasis, sleeping sickness, and Chagas

disease, for which there are no truly good

therapies Western medical

sci-ence has not done well by the

world’s poor, and some critics

blame this on its reverence for

intellectual property (IP) Is it

time to overhaul the IP

protec-tion system? A new working

group hosted by the World Health

Organization (WHO) will

con-sider that question in a series of

meetings beginning next week in

Geneva, Switzerland

Critics of the current IP

pro-tection system hope that WHO’s

Intergover nmental Working

Group (IGWG) on Public

Health, Innovation and

Intellec-tual Property will reform—or

even hack down—the

still-expanding worldwide patent

system They say it puts

life-saving new drugs beyond the reach of poor

patients and hampers development of new

medicines for tropical diseases But others,

including the pharmaceutical industry,

argue that the IP protection system isn’t the

real problem and that the talks in Geneva

risk distracting people from practical

solu-tions The IGWG—whose members will

include representatives of governments as

well as nongovernmental organizations—

appears “motivated by anticapitalism rather

than logical thinking about how to get drugs

to patients,” says Trevor Jones, a former

director of research and development at the

Wellcome Foundation

Patents are designed to spur the

inven-tion of new products But they also allow

companies to charge high prices, putting

people without purchasing power at a

dis-advantage Many critics say it is not enough

to help the poor get access to drugs; the

sys-tem’s incentives must be changed To

pro-duce new drugs for neglected diseases, they

say, the world needs a new R&D system that

rewards not market sales but the potential to

save lives and improve health

One such framework, which the IGWG

may consider, is a hotly debated proposalfor an international treaty to open up drugdiscovery, championed since 2002 by JamesLove, director of the Consumer Project onTechnology in Washington, D.C UnderLove’s “R&D Treaty,” countries wouldagree to spend a minimum percentage of

g ross domestic product on medical

research, including

a portion for lected diseases Inaddition, the treatywould promote openaccess to researchfindings and possiblyadd R&D incentives For instance, govern-ments could award big monetary prizes forthose who invent important new medicines

neg-Manufacturers would then be free to duce and market them cheaply

pro-The treaty, recommended in a letter tothe World Health Assembly by 162 scien-tists, health experts, and others last year, “iswidely seen as the end of the pharmaceuti-cal industry as we know it,” says Anne-Laure Ropars, a researcher at the GeorgeInstitute for International Health in London

No wonder the industry is vehementlyopposed The treaty would create an

“extremely complicated inter nationalbureaucracy,” says Eric Noehrenberg of theInternational Federation of PharmaceuticalManuf acturers and Associations inGeneva, adding that the award systemwould never work Instead, Noehrenberg

offers a different idea: The world shouldcreate markets where they currently don’texist For instance, companies could beenticed with research g rants from a

“Global Tropical Disease Fund” or thepromise of guaranteed sales should theydevelop an effective new drug

The industry also contributes through amodel called the public-private partnership(PPP) Over the past 10 years, more thantwo dozen PPPs have sprung up to tacklediseases of the poor Enlisting industry,academia, governments, and foundations,these partnerships, such as the TB Allianceand the Medicines for Malaria Venture(MMV), have produced many new candi-

date drugs (Science, 13 January, p 167).

And the IP protection regime has not been

an obstacle, says MMV president ChrisHentschel: “If people spent less time think-ing about IP and more about other things,

we would make more progress.”

But others point out that health PPPs have

a narrow base: 60% of their funding comesfrom a single source, the Bill and MelindaGates Foundation; governments con-tribute very little Moreover, industrytends to help PPPs that work on dis-eases that affect both the poor andpeople from rich countries, such asmalaria and TB, says Els Torreele,project manager at the Drugs forNeglected Diseases Initiative Giventhe scope of the problem, somethingmore radical is needed, she says

Whether the IGWG can deliver asolution remains to be seen Thegroup’s predecessor at WHO, theCommission on Public Health, Inno-vation, and Intellectual PropertyRights, issued a raft of recommenda-tions in April—such as increasing contribu-tions to PPPs and building clinical trial capac-ity—but could not agree on some key patentissues Some predict that when the IGWGissues its final report to the World HealthAssembly in May 2008, it may propose ways

to implement the less controversial parts fromthe April review rather than a radical reform.But Love thinks the world may be readyfor a change He notes that, although theU.S government has generally aligneditself with the pharmaceutical industry, itstrongly supported increased access toHIV drugs in Africa It also unexpectedlyvoted for the resolution introduced byKenya and Brazil that called the IGWG intoexistence (The drug companies and theEuropean Commission opposed the plan.)Love is hoping for another surprise

–MARTIN ENSERINK

WHO Panel Weighs Radical Ideas

DRUG RESEARCH

N America (268.8) Europe (180.4) Japan (69.3) Oceania (7.7) Former USSR (5.0) Southeast Asia (28.8) Latin America (26.6) India (6.7) Africa (6.7) Middle East (4.9)

World Pharmaceutical Market by Region

$ billions (2005)

No profit? A minuscule cal market in developing countrieslimits R&D on drugs against try-panosomes, which cause Africansleeping sickness and Chagas disease

pharmaceuti-NEWS FOCUS

Doing More With Less

Many U.S educators think that a streamlined

science curriculum with fewer topics per grade

is a necessary first step toward boosting

student achievement

WHAT DO SCHOOLCHILDREN NEED TO

know to be scientifically literate? Scientists

and educators keep coming up with new

answers to that deceptively simple question

As states gear up for two nationwide

assess-ments of student achievement in science,

many educators think that the time is ripe to

take another hard look at what children

should be taught But others worry that

reviving debate on that contentious topic

may divert attention and resources from the

bigger challenge of actually improving

stu-dent performance in science

Everybody agrees that current practices

aren’t good enough “It is the height of

national folly to think that America can

main-tain any competitive edge in science the way

we are now teaching and testing it,” asserts

Michael Casserly, executive director of the

Council of the Great City Schools in

Wash-ington, D.C., after urban schools last month

reported low performance in science There’s

also consensus that the curriculum is a big

part of the problem A September report by a

panel of experts assembled by the National

Academies’ National Research Council

(NRC) deplores curricula that “contain too

many disconnected topics that are given equal

priority, with too little attention to how …

[knowledge] is enhanced from grade to

grade.” The result, says the panel in Taking

Science to School (nap.edu), is that students

receive a “fragile foundation” in science Thatfragile foundation is exposed in both nationalassessments of what students know and ininternational comparisons with their peers

Those poor performances are fueling acampaign by the National Science TeachersAssociation (NSTA) to develop a nationalconsensus around what NSTA ExecutiveDirector Gerald Wheeler calls “scienceanchors”: a small number of concepts thateducators agree are essential for students tounderstand at any particular grade level

“There are way too many things in the dards,” Wheeler says, “and too much diver-gence in what’s being taught across the coun-try.” He sees the anchors as a de facto core cur-riculum drawn from topics that most schoolsare already teaching, “like Newton’s law ofgravity, or evolution and natural selection.”

stan-Wheeler hopes to influence two testingregimens that dominate U.S elementary andsecondary school education The first, the

2001 federal No Child Left Behind Act(NCLB), requires states to test students ingrades 3 through 8 each year in reading andmathematics Its importance derives from thesanctions facing schools whose students donot make sufficient progress each year Nextyear, science will be added to that lineup,although the law doesn’t hold schools

accountable for student achievement in thatsubject The second is the National Assess-ment of Educational Progress (NAEP), a non-binding, quadrennial federal assessment

of student achievement in grades 4, 8, and

12 across several subjects Although calledthe nation’s report card, its results are notbroken out by schools and districts, and thereare no penalties for poor performance

One big sticking point is that, thanks to thecountry’s 200-year history of local controlover education, there isn’t a national curricu-lum Casserly and many educators would like

to see voluntary national standards that wouldreduce variations among the 50 states and15,000 local school districts Two Senate billsintroduced earlier this year would move thecountry in that direction by asking expert pan-els to identify common ground among statecurricula and standards One bill (S 3790),from Senator Hillary Clinton (D–NY), wouldeven develop a model math and science cur-riculum and sample assessment questions.The other (S 2357), by Senator Edward

“Ted” Kennedy (D–MA), would help statesalign their curricula and standards to nationalbenchmarks Neither bill attracted muchattention this year, but that’s likely to changenext year, when Kennedy takes over as chair

of the Senate panel with jurisdiction over eral education efforts