Tạp chí khoa học số 2007-08-24

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than 400 meters since the early 1980s M107 Science Caters

Fossil Teeth From Ethiopia Support Early, African 1016 ‘Another Threat to Borneo’s Rainforests? 1032

Origin for Apes F.0 Brearley

NSF, NIH Emphasize the Importance of Mentoring 1016 Ocean Aiton and Scleatnan Cras

4 3 5 D Stanley J Response M Fine and D Tehernov

‘HRs, Vesa Gesell Raney Evohra 107 Trait or State? j C Crabbe and C L Cunningham

"New York Research Institute Hopes to Go With the Flow 1019 Stepping Down from the CIHR A Bernstein

Out-of-Body Experiences Enter the Laboratory 1020

Epidemiologist Sees Flaws in Papers on 1020 Penicillin Triumph and Tragedy 1037

Genes and Gender 2 Bud, reviewed by N Rasmussen

Fly 1038 NEWS FOCUS 5 Connor, reviewed by M Berenbaum

Racing to Defuse a Bacterial Time Bomb 1022

Who Ranks the University Rankers? 1026 Sacred Barriers to Conflict Resolution 1039

Cancer's Perpetual Source? 1029 S.Atran,R Axelrod, R Davis

PERSPECTIVES

Bacterial Pathogen Sees the Light 1041

J.TLMM Kennis and S, Crosson

>> Report p 1090 Money Illusion and the Market 1042 JeR Tyran

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‘Adomain structure shared by a mammalian defense protein and a bacterial toxic

protein suggests that both proteins disrupt membranes by forming pores

10.1126/science.1144706

‘STRUCTURAL BIOLOGY

Structure of the Zinc Transporter ViiP

AM, Lu and D Fu

The crystal structure ofa bacterial membrane transporter reveals that it uses an

‘unusual tossite,zinc-forproton exchange mechanism,

10.1126/science.1143748

CONTENTS L

PLANETARY SCIENCE The Dark Side of the Rings of Uranus

1 de Pater, H B Hammel, M R Showalter, M A van Dam Images of Uranus rings, which are currently oriented edge-on to Earth, reveal large changes in dust distribution since Voyagers visit 20 years ago

10.1126/science.1148103 BIOCHEMISTRY

Cysteine Redox Sensor in PKGlc: Enables Oxidant-Induced Activation

TECHNICAL COMMENT ABSTRACTS

EVOLUTION

Comment on Papers by Evans et al and

Mekel-Bobrov et al on Evidence for

Positive Selection of MICPH2 and ASP

'N Timpson, J Heron, G D Smith, W Enard

1036

Response to Comments by Timpson et al and Yu et al

IN Mekel-Bobrov and 8 T- Lahn

full text ot w wii

Visual and sensory stimuli that mimic subjects viewing themselves

from a distance produced a center of awareness (or sense of sel)

outside their bodies

APPLIED PHYSICS Electron-Induced Oxygen Desorption from the TiO,(011)-2%1 Surface Leads to Self-Organized

Vacancies

0 Dulub et al

Removal of oxygen trom a TO, surface by electron bombardment hinders desorption of other nearby oxygen atoms, allowing specific patterns of vacances to be formed

CHEMISTRY Dinitrogen Dissociation on an Isolated Surface Tantalum Atom

P.Avenier et al

‘Acomplex containing hydrogen and one tantalum atom can spit the strong triple bond in Ni, in contrast to established catalysts that rely on the cooperation of several metals

CHEMISTRY Breakdown of the Born-Oppenheimer Approximation 1061

in the F + 0-D, > DF + D Reaction

L Che etal

Simulations that account forthe simultaneous rearrangements

of electrons and nucei precisely match the experimental dynamics ofa problematic triatomic chemical reaction

1052

1056

CLIMATE CHANGE Glaciers Dominate Eustatic Sea-Level Rise 1064

ME Meier etal Alone, accelerated melting of glaciers and ice caps other than the Greenland and Antarctic ice sheets may raise sea levels by

‘up t0.0.25 meters during this century

CONTENTS cont

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Science

REPORTS CONTINUED

OCEAN SCIENCE

The Southern Ocean Biological Response to 1067

‘Aeolian tron Deposition

NN Cassar et al

Windblown iron-rich dust across large regions of the Southern Ocean

enhances photosynthesis by phytoplankton and eventually settlement

of carbon to the seafloor,

EVOLUTION

The Evolution of Selfing in Arabidopsis thaliana 1070

G Tang et al

‘An analysis of sex genes shows that at several times throughout is

history—including about 1 milion years ago—Arabidopsis has

developed the ability to sel-erilize

BIOCHEMISTRY

Anatomy and Dynamics of a Supramolecular 1072

Membrane Protein Cluster

The Evolution of Selfing in Arabidopsis thaliana 1070

Tang et al

‘An analysis of sex genes shows that at several times throughout its

history—including about 1 million years ago—Arabidopsis has

developed the ability to sel-lerilze

BIOCHEMISTRY

Anatomy and Dynamics of a Supramolecular 1072

Membrane Protein Cluster

J) Sieber etal

Clusters of about 75 molecules ofthe membrane protein yntaxin

result from weak attraction among the proteins balanced by steric

repulsion induced by crowding

spective p 10

STRUCTURAL BIOLOGY

Domain Architecture of Pyruvate Carboxylase, 1076

a Biotin-Dependent Multifunctional Enzyme

M St Maurice et al

Biotin activation ofthe enzyme pyruvate carborwase decreases

the distance between the two active sites, facilitating the transfer

of a carboxyl group from one to the other

NEUROSCIENCE

When Fear Is Near: Threat Imminence Elicits 1079

Prefrontal-Periaqueductal Gray Shifts in Humans

D Mobbs etal

Brain activity in fearful humans occurs inthe cognitively advanced

prefrontal cortex when the threat is far away but itches to the

midbrain as the threat draws near

Astrocytes Potentiate Transmitter Release at 1083

Single Hippocampal Synapses

G Perea and A Araque

Certain synapses strengthen upon coincident secretion of the

neurotransmitter glutamate from a neighboring astrocyte,

suggesting that astrocytes contribute to learning

MOLECULAR BIOLOGY CHD1 Motor Protein Is Required for Deposition of | 1087 Histone Variant H3.3 into Chromatin in Vivo

A.Y Konev et al

A molor protein known to remodel chromatin is also required for histone assembly on the paternal genome during early development in Drosophila

MICROBIOLOGY Blue-Light-Activated Histidine Kinases: 1090 Two-Component Sensors in Bacteria

TE, Swartz et al

Alightactvated enzyme with a flavin chromophore is found

‘in several bacterial species, and inone ofthese it regulates light-stimulated macrophage infection

EVOLUTION Blue-Light-Activated Histidine Kinases: 1090 Two-Component Sensors in Bacteria

TE Swartz et al

Alight-actvated enzyme witha flavin chromophore i found

‘in several bacterial species, and inone ofthese it regulates light stimulated macrophage infection

>> Perspective p 1041 EVOLUTION Temporal Fragmentation of Speciation in Bacteria 1093 A.C Retchless and J G Lawrence

Unlike eukaryotes, bacteria can be considered to form new species when lineage-specific genes no longer recombine, long before recombination at other genes ceases completely

PSYCHOLOGY Video Ergo Sum: Manipulating Bodily 1096 Self-Consciousness

B Lenggenhager, I Tadi, T Metzinger, 0 Blanke Visual and sensory stim that mimic subjects viewing themselves from a distance produced a center of awareness (or sense of sl outside ther bos

>> Nes story p 1020; Bev

‘has pad tng Bc tr mati oie c0 ees dnb Dene eÐườnlse-enhp riskcreeSiertd © 20) Wye ean econ eboanan

wo.iehoacrehrcodxleekoen to 9t femmyesgkudrvuee CyRbonetes ADVANCING SCIENCE, SERVING SOCIETY mu0$55 enw curt ‘Days 5 ASU 2 Raa dene hon 1A Mle USA ate 55 dan tm tandem ee Cac a

angel adn es gg dena nd igen: Putman lan 2x 9 Mag, 9200-478 Soca si

{dhe prs db py ha puted cto 27 hud Boe Son AGE een ee nD Te Sond tse one erp! enya Geer oer (hoi pat sn peat 0p i Can Parke ator ann

www.sciencemag.org

SCIENCE VOL317 24 AUGUST 2007

CONTENTS q

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Researchers take dad out of the mouse procreation equation

‘Making Water Do the Splits

‘New catalyst may pave way for greener fuel

Think Pink—or at Least a Reddish Blue Researchers link gender color preferences to mechanics of vision

PB1 domains mediate protein interactions

SCIENCESSTKE

vwwwtste.org_ SIGNAL TRANSDUCTION KNOWLED RONMENT

PERSPECTIVE: The Functions of Plant TIR Domains

TM Burch-Smith and SP Dinesh-Kumar

Plants have evolved novel uses forthe TIR domain in pathogen

detection and possibly in controling transcription factors as well

REVIEW: Structure and Function of the PB1 Domain,

a Protein-Interaction Module Conserved in Animals,

Fungi, Amoebas, and Plants

H, Sumimoto, S Kamakura, T Ito

Canonical and noncanonical PB interactions contribute to cell,

organization and function

Getting through the academia/industry wall

SCIENCE CAREERS

sw sciencecareers.org CAREER RESOURCES FOR SCIENTISTS

US: Tooling Up—The Wall

D Jensen Isthe wall between academia and industry becoming more or less porous?

MMISCINET: Profile—Susan Estes

A Sas50

‘Susan Estes's modest demeanor belies her accomplishments and

Promise as a genetics researcher and mentor

US: Mind Matters—The Complex Biochemistry of Laboratory Friendships

1.5 Levine

‘Many laboratory relationships that go beyond te lab can have advantages and perils, both personal and professional

Us: From the Archives—Project Management for Scientists

S Portny and J Austin How can you create lab environment that allows free exploration yet assures solvency and accountability?

\SCIENCEPODCAST

Download the 24 August

‘Science Podcast to hear about

a dangerous pathogen in Southeast Asia, the rings of Uranus, how the brain responds

to threat, and more,

va ciencemag.or/aboupodcast

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A Clean Break at Tantalum

Bacteria have evolved the remarkably efficient

nitrogenase enzyme to metabolize N, to ammo

nia, whereas the fertilizer industry has long

relied on heterogeneous iron catalysts at high

temperature to perform the same reaction Both

systems appear to require the cooperation of

multiple metal centers to cut the strong N, triple

bond Avenier et al (p 1056) have found that

tantalum hydride complexes bound toa silica

surface can cleave Np in the presence of H, at

isolated metal centers, yielding Ta-NH and Ta-NH,

products Infrared spectroscopy reveals that the

reaction mechanism is distinct from those in the

‘enzymatic and iron-catalyzed reactions and in

homogeneous organometallic systems

A Lot from a Little

Sea-level rise from future melting of the Green-

land and Antarctic ice sheets has received much

attention because these harbor most of Earth's

ice, but melting of the other glaciers and ice

aps will also contribute, particularly over the

next century, as they are melting rapidly Meier

et al (p 1064, published online 19 July; see the

cover) survey these glaciers and ice caps and

show that they are likely to contribute as much

85 10 to 25 centimeters to sea-level rise during

the next 100 years, perhaps up to 60% of the

estimated total increase

Capturing a

Surface Crossing

Computer simulations of chemical reaction

‘dynamics tend to rely on the simplifying Born-

Oppenheimer approximation, which assumes

that electron rearrangement is complete before

the nuclei move about However, experiments

EDITED BY STELLA HURTLEY AND PHIL SZUROMI

<< Let's Get Together

Proteins in the eukaryotic plasma membrane mediate

many different functions and are largely partitioned into clusters Using the SNARE protein syntaxin 1.as an example

Sieber et al (p 1072; see the Perspective by White) inves-

tigate the mechanism of clustering using high-resolution

optical imaging, quantitative biochemistry, and molecular dynamics simulations Weak protein-protein interactions are balanced by steric repulsion to give densely crowded clusters containing about 75 syntaxins Proteins within the

duster are immobile, but can exchange with freely diffus-

ing molecules This conceptual framework likely applies to many other membrane proteins

hhave shown that certain triatomic reactions subset of genes in prokaryotes encodes for pro- violate the approximation; for example, inthe | teins that function as light-activated LOV- hist abstraction of one deuterium atom from Dạ, an | dine kinases Light activation of the LOV domain electronically excited fluorine atom can forma | leads to the formation of a flavin-cysteinyl

ground-state OF product Che et al (p 1061) | adduct, which is the photoreceptor-signaling undertook a more exact theoretical treatment of | state that activates the kinase domain Light- this reaction, encompassing multiple electronic | activated LOV-histiine kinases were found in potential eneray surfaces, and also measured | two important plant and animal pathogens and product distributions experimentally at different | in a marine photosynthetic bacterium and indi collision energies They found strong agreement | cate that the LOV-histidine kinases are an impor- between theory and experiment in capturing the | tant family of bacterial photosensory receptors

precise quantum-mechanical factors underlying

cher \ tivity x

‘When a magnet behaves classically, the spins on

Fertilizing the adjacent atoms ae fixed and ordered and are typ-

ically correlated over distances of about

Southern Ocean 3 nanometers (nm) Con

Experiments have shown that adding iron to sur- | fining the spins to

primary production and net community produc- | and the spins become

increases export production and that windblown | present inelastic neutron scattering measure-

dust enhances gross primary production across | ments on the spin chain material Y,BaNiO, Their

despite the quantum effects, extends to more

Bacteria Seeing Blue than the classical coherence length,

Phototropins, blue-light receptors in plants, are light-activated serine/threonine kinases with a

flavoprotein LOV domain as their ight-sensing | Threat, Distance,

module In addition to the phototropins found in

eukaryotes, gene sequence analysis predicts that | AN Dread

LOV domains should be present in prokaryotes, | Behavioral experiments suggest that the dis

and archaea Swartz et al (p 1090; see the Per- | tance froma threat affects the state of fear in

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This Week in Science

Continued from page 1005

rodents Mobbs et al (p 1079; see the Perspective by Maren) developed a computer program in which

human subjects were chased by a virtual predator that could inflict real pain As the virtual predator

closed in, brain activity switched from the prefrontal cortex tothe periaqueductal gray part of the mid

brain, Higher-cortical systems thus control behavior when the degree of threat is perceived as low, while

extreme levels of threat evoke phylogenetically older regions that control fast reflexive behaviors

Astrocytes at Single Synapses

Astrocytes respond to synaptic activity and can release different gliotransmiters, which modulate

neuronal activity and neurotransmission, Perea and Araque (p 1083) examined the role of astro

cytes on synaptic transmission at single hippocampal excitatory synapses Ca? elevation in astrocytes

led toa transient release of the neurotransmitter glutamate from astrocytes, which was mediated by

‘metabotropic glutamate receptors Potentiation became long-lasting when glial activation was paired

with postsynaptic depolarization

Metabolic Enzyme Nailed é

Carboxylases transfer carboxyl groups in a number of essential

‘metabolic reactions The enzymes have distinct active sites to

catalyze different steps of the overall reaction, and the cova

lently bound biotin cofactor is used to transfer activated car

boxyl intermediates between the sites, but how this transfer is

achieved has not been clear Now St Maurice et al (p 1076)

report the complete structure of pyruvate carboxylase Pyruvate

carboxylase is active as a tetramer, and transfer of an activated car

boxyl group occurs between active sites on separate polypeptide chains

Motoring Chromatin Assembly

Molecular motor proteins, such as the chromodomain-containing factor CHD1, function in remodel-

ing nucleosomes In vitro analyses suagest that CHD1 acts as an ATP-utilizing chromatin assembly

factor Konev et al (p 1087) now examine the role of CHO1 in vivo in the fruit fly Drosophila

‘melanogaster Elimination of this factor results in infertile females because mutant embryos are

tunable to incorporate a histone variant into the paternal genome after protamine removal from the

sperm The Chd1 null eggs cannot decondense sperm chromatin, resulting in the exclusion of

paternal chromatin from the zygote and the generation of nonviable haploid embryos

From Clone to Species

Because of widespread exchange of genes, bacteria do not ft easily into the conventional paradigm

of species Retchless and Lawrence (p 1093) have devised a method to extract the time of diver

gence for different genes in different bacterial species Using these data, they show genes that

encode lineage-specific traits became genetically isolated long before recombination ceased at other

loci Thus, as bacterial lineages begin to separate, they can be considered different species at some

genes, but the same species at other genes This is quite different from any speciation process

described for eukaryotes Thus, ecologically distinc species must exist within traditionally named

bacterial species, which may impact the use of microbial taxonomy to inform human decisions, such

as medical diagnosis, epidemiology, or bioterrorism

In Two Places at Once

The sense of being outside of one’s physical body (an out-of-body experience) has generally fallen

within the realms of neurological dysfunction, either organic or pharmacologically aided, or of para

‘normal phenomena, The advent of virtual realty has offered a noninvasive and reproducible

approach to inducing out-of-body experiences in normal subjects, as shown by Ehrsson (p 1048)

and by Lenggenhager et al (p 1096; see the news story by Miller) Head-mounted displays were

Used to demonstrate that subjects would reliably report the sensation of inhabiting a virtual body,

from which vantage point they would be looking at themselves In addition, they reacted autonom

cally in response to harm directed at their virtual body and displaced their bodily sense of self toward

their doppelganger and away from their physical body

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in 2001, Presid Executive Order banning any use of federal funds

to support research on stem cells (save, of course, for those 78 preexisting cell lines, only 21 of hich are available) That position is reiterated most recently in another

Bush’s veto of the 2007 Senate bill (S.5) th The convergence is with the pre ing of the precisely on that anniversary For those who collect Fane act is (gasp) America Creating Opportunities to Meanin Education, and Science Its content embodies many of the provisions and the spirit of the president's American Competitiveness Initiative (ACD), and thus both bills are responses to

‘unusually influential report from the National Academies Called Rising Above the Gathering Storm and produced by a high-level

‘committee chaired by Norman Augustine, former chairman and CEO of Lockheed Martin, its recommendations ineluded programs for the education of students in technology, engineering, and mathematics: STEM, in th

The irony is unmistakable The prospects of a basic research effort that might have extraordinary clinical applications, one approved by a substantial majority of Americans, are still dim So,

no stem, But STEM is all over the Ameriea COMPETES Act, signedon the anniversary of Bush turning the lightsouton stem cell = research, Sul jddent cannot subliminal

in the convergence Or could he’

merica COMPETES implements number of initiatives derived from the Augustine report and ACI It provides substantial increases to three physical science gencies for the period 2008 to 2010: a total of $22 billion for the National Science Foundation F), $17 billion forthe Department of ') Office of Scienc billion for the National Institute of Standards and Technology (NIST) Much sma amounts £0 to the Department of Education for two new middle-school math programs, advanced courses in high school, and inducements for college science majors to become K-12 teacher

Itis difficult to find fault with these proposals, There is consensus that the physical science 's were about due for their turn at having research funding doubled, The STEM education programs are little harder for the White House to swallow: The president's science adviser, John Marburger, has called them an unwarranted expansion of efforts not yet proven effe and this month Bush declared that he will support only those pieces of the new law that mirror his own ACI Still, the research direction appears to be right, and scientists supported by NSF or DOE ought to be looking happier than their colleagues in biomedicine They should be warned, though, that doubling is a blessing only until it ends in a real-dollar dropoff, at which point they'll start to feel dumped on

So here we are On the one hand, the scientific community ought to thank the Augustine

‘committee for a report that somehow avoided the usual fate of dying on a government shelf, and

be appreciative of a president who says he cares about science Yet that same chief executive is prepared to apply his own set of “moral values” to prevent some promising research And we are still grappling with the effects of the 2002 No Child Left Behind Act, Bush's contribution to his legacy in which billions of dollars in unfunded mandates have been left to the 50 states to pay

merica COMPETES in fact, is an authorization and not an appropriation, full though it ood intentions Perhaps the president is attracted to its business-triendly lan,

welcomes the fact focus is on STEM rather than lowercase stem With that empha

‘could be the other bookend for his legacy Maybe “No Grownup Left Behind.”

1010

Replenishing the Power Stations

Mitochondria—the microscopic powerhouses of the cell—contain their

‘own vestigial genome (mtDNA), and each cell needs a collection of healthy organelles to survive Mitochondria are highly dynamic and undergo both fission and fusion They produce adenosine 5“-triphos- phate by transferring electrons from organic substrates through a series

of respiratory enzyme complexes to molecular oxygen Chen et al examined the function of the mitochondrial fusion protein mitofusin 2;

mutations in the gene /fƒn2 have been linked to the peripheral neu- ropathy Charcot-Marie-Tooth type 2A, in which the very long motor and sensory neurons of the lower leg die They generated mice that lacked [Mfn2 specifically inthe cerebellum and found that the mutant mice suf-

fered cerebellar degeneration Mitochondrial distribution,

morphology, and function were all compromised

in Min2-deficient cells, and many mito-

MOLECULAR BIOLOGY

The Sign of Four

Nucleosomes constitute the principal structural

mot of eukaryotic chromosomes and contain

octomers of highly conserved histones with the

almost invariant stoichiometry of two copies

each of H2A, H2B, H3, and H4 Centromeres are

specialized regions within chromosomes that

play a critical role in the accurate segregation of

duplicated chromosomes during cell division

Centromere nucleosomes contain an alternative

histone, CenH3, nhỉch is thought to define cen:

tromere identity and participate in mitotic

mechanics

Dalal et al have explored these issues

through a biochemical and biophysical analysis

‘of centromere nucleosomes in Drosophila Cross

linking of bulk chromatin from crude extracts

and within purified nuclei revealed that CenH3

appears in a heterotypic tetrameric half-sized

nucleosome, with one copy each of CenH3, H2A,

H2B, and H4 This composition was confirmed by

mass spectrometry, and atomic force microscopy

showed tetramers to be half the height of

octomers The tetramers protect less DNA [~120

base pairs bp] than the canonical octomers

(~150 bp) and do not seem to form as regular

higher-order structures as the octomer, yielding

longer and more variable DNA linker lengths

This looser chromatin conformation, embedded within heterochromatin, may be critical for teth ering the kinetochore to the centromere — GR

PLoS Biol 5, €218 (2007)

CHEMISTRY Three in a Column

Numerous compounds comprising two bonded metal centers stabilized by bulky organic igands have been cha

acterized However, zinc, cad:

rium, and mercury, which straddle the boundary between d-block and p block metals, have only very recently been observed in this motif, ơy Zhu etal previously prepared zinc and cadmium dimers bearing bis(diiso propylphenyl)phenyl tig:

ands, and have now synthesized a mercury dimer with the same ligand set to complete a homolo:

ous series The compounds were accessed by reduction of metal halide precursors, and their solid-state structures characterized by x-ray crys tallography As predicted by theoretical calcula

changes in the distribution and respiratory activity of their mitochondria, perhaps as a consequence

of their extensive ra

Cell 130, 548 (2007)

tions, the mercury-mercury bond i longer (and thus likely weaker) than the analogous zinc link age, but shorter than the cadmium bond The cal: culations implicate relativistic effects inthis bond shortening, in keeping with a higher proportion of srorbital character (as well as a measure of dz? overlap) in the mercury dimers highest occupied molecular orbital (HOMO) All three compounds have effectively linear C-M-M-C geometries, with the terminal phenyl rings canted at

an approximate right angle relative

to one another The authors also prepared zinc and cadmium dimers incorporating bridging hydride ligands for structural com- parison; the mercury hydride proved

‘monomeric and was characterized spectroscopically — JS¥

c } Am Chem Sọc 129,

10.1021/a072682 (2007)

MATERIALS SCIENCE

An Inside View of Weaving

Fiber-reinforced composites (FRCS) are finding increasing use as structural materials because they offer good performance at low weights The mechanical properties of any given FRC depend

on many variables, including the distribution and

orientation ofthe fibers within the matrix mate-

rial However, for most composites, nondestructive

visualization ofthe fibers’ response to stresses is

precluded either by the opacity of the matrix

material or by insufficient contrast between the

fibers and the matrix

Davies et al surmount this challenge by prob

ing an FRC through diffraction of a high-flux,

microfocused x-ray beam from a synchrotron

source The sample comprised woven polyp:

phenylene phthalamide) (PTA) fiber mats

embedded in an epoxy matrix hole drilled into

the center ofthe specimens modeled the rivet

holes typically used to attach composite panels in

aeronautical applications The diffraction data

clearly resolved the interleaved pattern of the

woven fibers Damage tothe fibers was localized

near the hole, and the tit angle increased for

fibers parallel to the strain direction asthe

stresses were transferred to neighboring fibers

away from the hole, Because PPTA forms oriented

fibers, the authors were able to determine

changes in orientation of the yarn and could thus

observe reorientation of the horizontal fibers

caused by stress transfer — MSL

‘op Phys Lett 91, 044102 (2007)

MATERIALS SCIENCE

Sublimed Clusters

Inorganic thin films can be formed under vac:

‘uum conditions by transferring material from

cone surface as a vapor and depositing it on a

nearby substrate However, forming the vapor

phase often involves harsh conditions—such as

heating to very high temperature or bombard:

‘ment with high-energy ions or photons—to des

orb atomic species ora distribution of clusters

Asa result, preserving intricate synthetic struc:

tures during the transfer is often difficult Chao

etal, show that silicon nanocrystals (with mean

‘were examined with a range of microscopy tech- niques The nanocrystals initially grew as two- dimensional istands but could also form three- dimensional clusters — PDS

‘Nat Nanotechnol 2, 486 (2007)

ECOLOGY/EVOLUTION

The Whole Is the Sum of the Parts

The fragmentation of natural ecosystems as a by:

product of human activity is generally held to have adverse consequences for biodiversity, because it reduces the area of each habitat as well as the opportunities for dispersal and

gene flow Yaacobi etal tease apart the effects of areal loss from those of degree of fragmen- tation in a Mediterranean scrub

‘ecosystem in Israel The total num ber of species of beetles and plants remained unaffected by the degree

of subdivision of the landscape: a patch of area A having a similar numberof species to n smaller patches

of total area A Despite this absence of

an effect, the authors caution that the absolute

‘number of species is not the only goal of conser vation Fragmentation also affects the abundance

of individual species, some of which may be charismatic, and the composition of ecological communities in patches, features that are key determinants of ecosystem health, — AMS

Proc R Soc london 8274, 10.1098/sp0.2007.0674 (2007)

cathelicidin precursor involves cleavage ofthe proprotein by the kallikrein family protease stratum

comeum tryptic enzyme (SCTE); rosacea samples had elevated levels of SCTE and protease activity

The abundant cathelicidin fragment LL-37 stimulated interleukin-8 (IL-8) production in cultured

hhuman keratinocytes and caused erythema, vascular dilation, neutrophil infiltration, thrombosis,

and hemorrhage when injected subcutaneously into mice; injection of SCTE caused similar symp-

toms In mice deficient for the gene Camp, which encodes cathelicidin, inflammation was substan

tially less than normal after application of a contact skin irritant or physical abrasion — NRG

Discovery of Antibody Biomarkers for Cancer

and Autoimmune Disease

Participating Experts:

Eng M.Tan, M.D

SarppsResearch nstiute Michael Snyder, Ph.D

Yale University Paul Predki, Ph.D

Invtogen Corporation Moderator:

» Obtain insight into how to advance Sener semen your biomarker

proteomics approaches

> Hear about successful application of protein arrays, tobiomarker discovery in ovatian cancer

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Things That Drip

(One grows in caves over thousands of years;

the other appears in the back of your fridge in

a matter of hours But new research suggests

that forall their differences, the mathematics

describing stalactites and icicles is the same

According to work presented last week at a

‘meeting on natural complesity at the British

Antarctic Survey in Cambridge, U.K., the rate

of growth of either a stalactte or an icicle can

be modeled by a simple power law based on

the radius and the inclination of the surface

at any given point Raymond Goldstein,

a theoretical physicist at the University of

Cambridge, U.K., developed the model to

describe the growth of stalactites, based on the

rate at which calcium carbonate precipitates

from water Icicles grow by an entirely different

‘mechanism: heat transfer from water to the

surrounding air, which causes the water to

freeze “Despite the time scales and dimensions

of molecules being very different in the two

«cases, out pops the same mathematical formula,”

says Goldstein “It’s a big mystery why nature

would select the same power law.”

“Nobody had a good model for the global

shape of either stalactites or icicles before this,

0 0 find a solution for both is impressive,”

says Stephen Morris, a physicist at the University

of Toronto, Canada

Polar Ice Watch

Atelting sign of climate change is the declining

amount of Arctic sea ice that remains at the

end of summer And it's not just

an indicator Arctic ice also influences climate by cooling the planet

You can follow changes

in sea-ice status atthe Web site

of the National Snow and Ice Data Center in

Boulder, Colorado, which posts regular updates

‘on ice conditions and analyses of trends By

‘mid-August, this year’s melt had already broken

wwwsciencemag.org

| BANDOMSAMPLES

EDITED BY CONSTANCE HOLDEN

the record set in 2005, when only 5.3 million square kilometers of ice were left at the end of the season, 31% below average The site wil provide fresh information until the melting halts, usually in September

Johannesburg, South Africa, describes his design as an “equilibrium” combination

12 panels of a pentagonal dodecahedron and

30 of a rhombic triacontahedron That makes for 42 panels—10 more than the popular

‘Buckminster design and 28 more than the newer 14-panel Adidas Teamgeist “The more panels you have, the more spherical the ball

becomes,” he says

“A etter design would be wel:

come, considering that the balls used in 2006 moved at times unpredictably, like knuckle balls in baseball,” says Ken Bray, a theoretical physicist at the University of Bath, U.K Lurie has sent his design to Adidas, hop ing the company will test the ball for the next World Cup, which will be held in South Africa in 2010 Adidas has so far failed to express interest and has defended its Teamgeist as “a perfectly round ball allowing great accuracy and control.”

‘Much of the north remains “intact,” the authors say “Great flocks of birds still move over the land 15 stil flow naturally Floods come and go.”

But northern Australia is also being threatened by climate change, poor fire management, weeds, and feral animals (including the fast-moving cane toad scourge), according to the Pew Environment Group and The Nature Conservancy This summer, the two groups launched the Wild Australia Program, a $14 million, 3-year conservation effort

Open savanna with

termite mounds in Queensland

‘Comparative Genomic Hybridization (CGH): Unique AutoPMT function in Axon GenePix Pro ensures

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now part of MDS Analytical Technologies Expect more We'll do our very best to exceed your expectations,

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EDITED BY YUDHI)IT BHATTACHARJEE

WAR OVER WORDS Pediatrics researcher Frederick Zimmerman (left) is finding out that baby talk can be dangerous, Last week, the Walt Disney Co attacked a study he published this month in the Jounal of Pediatrics suggesting that baby videos might do more harm than good to infants” language development Robert Iyer CEO of Disney, which owns the popular Baby Einstein series of educational videos, said that Zimmerman’s work was flawed and that a press release from his institution, the University of Washington (UW), Seattle, misrepresented the study’s findings UW President Mark Emmert has defended the

‘work and rejected Disney’s call fora retraction of the rek The study, based on parental interviews, found that infants who watched a lot of

“baby DVDs" understood fewer words than those who viewed fewer videos under- stood Disney says Zimmerman and colleagues shouldn't have lumped together all

baby videos and that other studies have shown that “the specific nature of content and

(@) n Campus Zinman sy wa welcome on Dison thee [the video] is consumed are vitally important.” and thi

paper “is not the definitive study in the area

INSIDE GOVERNMENT

WHO'S THE BOSS? Since its creation in 1950,

the National Science Foundation (NSF) has pro-

vided staff and support to the National Science

Board (NSB), the body that oversees the $6 bil-

lion agency The arrangement has grown some-

what contentious in recent years, however, as

NSB has sought to assert its independence This

‘month, the tension reached a new high when

Lawrence Rudolph (below), NSF's longtime and

influential general counsel, suggested at the board's most recent meeting that the 24-member presi- dentially appointed panel might want to ask Congress for per- mission to hire its own general counsel and other key stafers if the board felt its interests and those of NSF were no longer compatible

Rudolph’s blunt words come in the wake of

recent congressional unhappiness with the

board's behavior (Science, 3 August, p 579)

And they appear to have caught NSB chair

Steven Beering and NSF Director Arden Bement

off-guard, “I can’t take seriously the idea that

we separate the two bodies,” says Beering "This

relationship has worked for 57 years, and | think

it should be strengthened, not weakened.”

Bement says the board and the agency have

MOVERS

OFF THE RAILS? Three research policy leaders within the U.S Department of Health and Human Services are leaving, and their posts may remain vacant until the next Administration John Agwunobi, a pediatrician who has been assistant secretary for health since 2005, is joining Wal-Mart as a senior Vice president overseeing its health division

Congress doesn’t seem to be in any big hurry

to approve President George W Bush’s nomi- nee for surgeon general, James Holsinger Jr., especially after the previous incumbent, Richard Carmona, recently denounced his former bosses for stifling science And next month, career fed Bernard Schwetz steps down as head of the Office for Human Research Protections Fortunately, says bio- medical lobbyist Anthony Mazzaschi, such Pioneers >>

Positions are often held on an acting basis by

“pretty competent federal employees who keep the train on the track.”

‘After 4 years on the job, physicist Robert Dynes has announced that he wil step down as president of the University of California system

in June 2008 and retum to full-time research at UCSan Diego Dynes's tenure has been marked

by controversy, including what critics said were extravagant salaries and perks awarded to dozens of senior university administrators

William Jeffrey, a physicist by training,

is resigning after 2 years as director of the National Institute of Standards and Technology to head the science and tech- nology effort at the Institute for Defense Analysis in Alexandria, Virginia

QUICKENING THE PACE One of Japan’s hottest stem cell scientists is

‘moving to California, in part because of a more favorable research envi-

ronment Shinya Yamanaka, who last year conferred the transformative Z

powers of embryonic stem cells upon skin cells taken from adult mice, will be joining the Gladstone Institute of Cardiovascular Disease in San y Francisco, where his work will be partly funded by the state's stem cell

initiative He'l initially spit his time between Gladstone and his current

institution, Kyoto University, and within a few years leave his Kyoto post

and move to San Francisco

Yamanaka’s accomplishment with mouse cells has raised hopes of

developing therapies that avoid ethical concerns about using human

endured some rocky times but are now in sync

“The board chairman and | pledged upon his

election to do our utmost to improve communi-

cations, and as a result they have improved

considerably,” he notes Rudolph declined to

Š elaborate on his comments,

eggs or embryos (Science, 8 June, p 1404) He is now racing with other researchers to repro- {gram adult human cells, and he says that work will proceed faster in California than it would in Japan, where lengthy applications and prolonged reviews slow down research Yamanaka plans first to bring his human cell research to Gladstone, where he did a postdoc in the 1990s, and leave his mice in Japan for now

wwwsciencemag.org

1016

PALEOANTHROPOLOGY

Fossil Teeth From Ethiopia Support

Early, African Origin for Apes

Fossils of a new species of lange-bodied ape are

giving a rare glimpse of the origins of the

African apes This week in Natwe, a team of

Ethiopian and Japane:

discovery of nine teeth that resemble those of

ụ but that belonged to an ape that lived about 10 million yearsago in the Afar

Rift of Ethiopia, The team st

newly discovered ape, called Chororapithecus

gorilla or a close relative Ifso, it pushes back

the origin of gorillas fromabout 8 million yea

» to more than 10.5 million years

paleoanthropologist Gen Suwa of The Univer-

sity Museum of the University of Tokyo

Gorilla or not, several experts agree that an

ape of this antiquity in Africa strikes a blow ata

hypothesis that the common ancestor of

African apes arose in Eurasia and migrated to

Afiica “These are very important fossils.” says

Alan Walker.a paleoanthropol

vania State University in State Colleg

NSF, NIH Emphasize the Importance of Mentoring

Like apprentices in other fields, U.S postdocs

work for peanuts and are discouraged from

pursuing their own ideas in return for the

chance to learn the profession, But supervi-

sors must also hold up their end of the bargain

ood mentors That's what two key cies hi

by being gì

fe reminded invest this month in policy directives that emphasize

their role in helping postdocs grow into inde-

pendent researchers,

The messag

enacted Amer

is tucked into the newly

‘OMPETES Act (Science,

10 August, p 736) It requires researchers to

include a mentoring plan in every grant appli-

cation to the National Science Foundation

¢NSF) 'Salso contained in a statement issued

by the National Institutes of Health (NIH) clar-

ifying that its grantees may use some of their

time to mentor postdocs and students, Both

Ai apes from where researchers have found diverse million to But despite many searches, almost no ape fos- sils have been found in Africa between 12 mil- lion and 7 million years ago, with the notable exception of a 9.5-million-year-old upper jaw

tors of modem A rican apes

When the researchers discovered the first

Returning o the site last March, they found

ht molars The teeth, from at least three individuals, were “indistinguishable” in size and proportions from those of gorillas

Micro-computed tomography scans showed

hing skills, and training in Although many applicants

ly do this, says James Li adviser in the NSF director's office, maki

The detailed analysis of the teeth is

“one of the best I've seen,” says paleo- anthropologist Jay Kelley of the University

of Illinois, Chicago Still, he and others say the teeth may have belonged to apes

that had independently adapted to a>

training/q&a.hum#mentor) says that grantees

t time spent training students and

elated activities provided the training is related to the research being funded, That would enable postdocs to attend workshops and seminars relevant to their proj- says Walter Schafer, senior scientific adviser for extramural research at NIH But Schaffer says it would not allow Pls to dispatch their postdocs to teach te students

The policy is a small step forward, says

h Micoli, an NPA board member and

i the University of Alabama, B ingham, But more steps are needed

Kei researcher

If post- does can’t do work on a project that’s not

gorillalike diet Suwa acknowledges in

Nature that the dental evidence for a close

relationship with gorillas is “inconclusive”

but adds that no other living or fossil apes

this big have molars as specialized for

shredding fibrous vegetation

If Chororapithecus is indeed an early form

of gorilla, it would falsify the Eurasian-or

hypothesis, says Walker It would also push

back the origin of gorillas to between

10.5 million and 12 million years

so force resea

archers to recalibrate when the human and chimp lineages split to between

7 million and 10 million years ago (up from

5 million to 7 million), and when ora

Regandless of whether Chororapithecus is

China, Vietnam Grapple With ‘Rapidly Evolving’ Pig Virus

A pig disease ravaging China now appears

to have spilled into Vietnam, Scientists fear

that a deadlier strain of a longtime foe,

porcine reproductive

drome (PRRS), or blu;

on the loose

“We're fairly confident tha

an outbreak of PRRS here,” says Andrew

Speedy, who represents the U.N Food and

iculture Organization (FAO) in Vi

An FAO mission that completed a weeklong

visit to Vietnam on 20 August also uncovered

many secondary infections that increase the

disease’s death toll, Speedy says The team

concluded that PRRS can likely be controlled

through vaccination and antibiotic treatment

of secondary infections

PRRS was first identified

in the United States in the

mid-1980s; the causative

ind respiratory syn-

attacks macrophages, whi

bacteria With a crippled

imm

susceptible to secondary

infections, Adults usually

recover and develop immu-

nity, but the virus and second-

st and remove invadin;

ne response, pigs are

ary infections can kill piglets,

whose ears often turn blue

from the secondary infections

“The evolution of the virus

is really quite startlin

probably one of the most rap-

www.sciencemag.o

idly evolving viruses that I know of.” says Trevor Drew, head of virology at the Veteri- nary Laboratories Agency in Weybridgs

UK He explains that, typically, a vius circu lating ina new host initially causes severe di ease and becomes less pathogenic over time, With PRRS the

hhas occurred: A nonpathogenic strain was cir- culating among pigs in North America before itevolve

is evidence that the opposite

\d started causing disease

An even nastier strain seems to be on the

rampage in China, sows as well as piglets This strain first appeared in the summer of 2006 China has reported losing 400,000 pigs to the disease through death or culling in 2006 and another 243,000 this,

In an analysis of viral samples from pigs

in China published online in PLoS ONE on

nizations, Drew says that's not so, point-

ing to Gao’s paper and to China’s reporting on the out- break to the Paris-based World

organization has not yet asked China’s Ministry of Agricul- ture for samples or to allow an

outside team to investigate

although it expects to make formal request shortly Vietnam didn’t wait to be

first reported there in March, Last

month, the government asked FAO for assistance after the outbreaks increased in June and July

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RIVER MONITORING

New York Research Institute

Hopes to Go With the Flow

An ambitious plan to monitor the entire Hud-

son River in real time is one step closer to

reality, thanks to a new collaboration with

IBM announced last week The ultimate goal

isa system that could track the movement of

PCB-contaminated sediment, for example,

warn a commercial power plant to shut its

intake valve temporarily because of an

approaching school of fish, “It will be the first

real-time, distributed river network in the

world” says John Cronin, director of he non

profit Beacon Institute for Rivers and Estuar-

ies in New York

The River and Estuary

Observatory Network (REON)

grated Ocean Observing Sys-

tem, a federally funded pro-

gram to expand and link

scientists is hoping to interest

the National Science Founds

tion in funding a network of

eight to 10 research stations

around the country that would

study threats to water supplies

ce 2003, the Beacon

Institute has been coordinating

a prototype, called Riverscope Re

from Lamont-Doherty Earth Observatory

and Rensselaer Polytechnic Institute have

measured temperature, salinity, and other

variables in a few spots along the Hudson

River Although REON is still early in the

design phase, heavyweights have already

signed on The state of New York has commit-

ted $50 million, most of which will support a

new research building Groundbreaking is

expected in 2009at Denning’s Point

con, New York, but scientists hope to begin

deploying new sensors this sprir

On 16 August, the Beacon Institute

announced a major partnership: IBM will

pick up the tab for a new computer system

designed to analyze streams of data in real

time—a contribution worth perhaps tens of

millions of dollars “It is very, very excitin,

‘secologist Margaret Palmer of the Univer-

yy of Maryland Center for Environmental

Science in Cambridge, Maryland

‘would include permanent sensor haps even robotic submersibles that can beam back data This full system will require another $150 million of fundraising Cronin estimates Philip Bodgen, who directs the Gulf of Maine Ocean Observing System, says he thinks the institute good chance of

for ongoing mai and op

because the Hudson River is less challen ing logistically than the ocean and the proj- ect is more visible to potential donors

‘Once running, REON could be used for everything from studying the impact of tilizers to monitoring the quality of drink- water

Thais Say Aye to GM?

BANGKOK—Thailand may lift a 6-year-old ban on field trials of genetically modified (GM) crops Concerned that the country’s agriculture efforts are lagging behind those of China and other neighbors, Thailand's agriculture min istry was expected this week to petition the country’s Cabinet, installed after a coup last year, to rescind a moratorium on open-air experiments, Critics of GM crops say the coun:

try lacks adequate biosafety laws and are urg ing the Cabinet to stand firm, The ministry's top priority isa GM papaya strain resistant to a ringspot virus that has decimated orchards in Thailand and elsewhere -RICHARD STONE

German Physics Facilities Achieve Fusion

BERLIN—Materials scientists will have anew

‘one-stop shop in Berlin when BESSY, an accelerator-driven x-ray source, and the Hahn Meitner institute (HAND, which boasts a reactor based neutron source, merge into asingle inst tute in 2009, Both facilites allow scientists to probe the atomic structure of materials, from protein crystals to high-tech ceramics The

‘merger, announced last week, will produce an institute with 1000 employees and a yearly budget of $136 milton, almost entirely from the German federal government Thats a sig nificant funding boost for BESSY, which will no longer have to charge users for beam time The fusion will produce one of the ew places in the world with expertise with both types of probes, says HMI Director Michael Steiner

~GRETCHEN VOGEL

Mmmm, Beer

Farmers, biofuel enthusiasts, and, yes, brew

‘masters could soon get little enlightenment from German plant geneticists Last week, the German government put up 8 million to

‘more fully map and partially sequence the genome of barley, a key crop used worldwide

in animal feed, human food, and beer

Funding agencies have been stow to tackle crops such as wheat and barley because ofthe daunting size of their genomes At billion bases, barley's genome is nearly double the size

of the human genome, But itis only one-third wheat’ size and lacks that genome’s multiple copies, so it should be easier to sequence, says plant geneticist Nis Stein ofthe Institute of Plant Genetics and Crop Plant Research in Gatersleben, Germany, whose team will create a draft sequence of 10% of the genome Stein hopes the work, along with a British-ted barley sequencing pilot, will set the table for a large scale sequencing project ELIZABETH PENNISI

SCIENCE VOL317 24 AUGUST 2007

1020

Out-of-Body Experiences Enter the Laboratory

associated more with tabloid

newspapers, New Age Web

ntific discussion Yet

re often reported by rep-

utable people who suffer from

migraine headaches,

and other neurologic:

ditions, Intrigued by such

accounts, some researchers

are trying to figure out how

the brain creates an aspect of

human consciousness so fun-

damental that we take it for

granted: the perception that

the “self” conforms to the

borders of the physical body

Now, two teams of cogni

tive neuroscientists inde-

pendently report on pages

1048 and 1096 methods for inducing ele-

ments of an out-of-body experience in

healthy volunteers Both groups used

head-mounted video displays to give peo-

plea different perspective on their own

bodies Each team also drew upon the

sense of touch to enhance the illusio

Although details of the experience dif-

fered, the people in both experimen

reported feelings of dissociation from

as ifthey are really there

“Iv’s striking because when you hear about out-of: speriences, it sounds so deeply weird,” says Chris Frith, a cognitive

neurose Coll not parti research

show you can actually manip- ulate it experimentally.” The illusions add to evidence that the brain’s representation of

the physical body is mal-

leable and can be modified by information from the senses,

Frith says

For one of the studies, a team led by Bigna Lenggen-

of the Swiss Federal Institute

be caused by the highlighter on their vir- tual back hem feelas ifthe virtual body was in fact their own body

Moreover, when the researchers turned >

Epidemiologist Sees Flaws in Papers on Genes and Gender

An epidemiologist who for years has eri-

tiqued the veracity of published papers has

now tackled hot area in genomics, sex-based

genetic differences He argues that most

reported findings are poorly documented and

that about sixth may actually be wrong

As researchers move beyond uncovering

new disease genes and into the realm of

gene-environment interactions, John Toannids,

a clinical and molecular epidemiologist at

the University of loannina School of Medi-

cine in Greece, decided to follow them He

wondered especially about genetic associa

tions with diseases that seem to vary by gen-

der—for example, a particular gene

that confers increased risk in women but not

two colleagues analyzed data from

77 papers covering everything from multi- ple sclerosis to lung ¢: they found that!9 had at least aim they judged to be “spurious,” or apparently correct Only four papers cont

ther spurious nor insufficiently documented claims, says loannidi

He and his colleagues searched online for papers whose titles touted

gene effects, then exam (a total of 432 sex-difference

77 papers) To determine whether claims were spurious, they considered the groups being compared—for example, older men and older women, which would be appropri ate, orolder men and younger women, which would not They looked for evidence in the paper that claims reached statistic:

cance Those without were judged not sufti- ciently documented The analysis was pub- lished in the 22/29 August issue of the Jour nal of the American Medical Association

Of the; nder Findings, says oamidis,

“there isa problem with just accepting them and believing that they're true.” Proper documentation was found in only 55 claims,

or 13% of the total

The Ioannidis paper reinforces con- cerns about the quality of published genet- ies results, says Neil Risch, a genetic demiologist at the University of Califor- San Francisco Still, he defends some findings in the field, such as a greater

risk for women with an Alzheimer’s gene and a greater risk for males who carry a

‘ne variant linked to rheumatoid arthri-

The loannidis analysis did not pick up

off the video display, guided the subjects

back a few steps, and then asked them to

blindly return to their former position, sub-

jects overshot the spot where they'd actu-

ally been standing and walked to a point

closer to the apparent location of their vir~

tual body

Adopting a similar strategy to attempt to

induce out-of-body experiences, Henrik

Ehrsson of the Karolinska Institute in

Stockholm, Sweden, asked men and women

tossit ina chair and don a video headset con-

nected to two cameras that provided

stereoscopic view of their backs As a sub-

ject viewed his or her own back from

behind, Ehrsson used two plastic rods to

simultaneously stroke the subject's chest

and a location behind the subject’s back

Although people felt the rubbing on their

chest, in the headset they could only see

Ehrsson’s arm moving behind their back,

reinforcing the sense that they were sitting

ia location behind their actual body The

experience often elicited surprised gi

says Ehrsson, who has tried it out h

‘You really feel that you are sitli

ferent place in the room and you're looking

yourself and you know i

doesn’t feel like yourself” he say:

most like you're looking at a dummy

Nearly all subjects reported similar impr

sions on a questionnaire

Ehrsson also repeated the illusion with

electrodes.attached to each person's

to measure skin conductance, a physiologi-

Both experiments show that visual per- spective and coordination between the senses of vision and touch are important for the sensation of being within the body, says Peter Brugger a neuroscientist at University Hospital Ziirich in Switzerland Yet neither study replicated the full-blown out-of-body experiences in which people report “an enormously compelling sensation of separi- tion from the body.” he notes Even so, Brugger says, these illusions may be as close ast is possible to get in the lab

Previous research has pointed to several

Which of these brain regions contribute to

which aspects of these strange experiences,

and that in turn, says Blanke, could lead to

better understanding of how the brain gen-

~GREG MILLER

erates a concept of self

these papers in its literature search because

it netted only those with “polymorphism”

and either “sex” or “gender” in the title,

Some scientists whose papers Toannidis

has critiqued agree that it’s difficult to know

here is a problem with

just accepting [the claims]

and believing that they're true.”

—Jdohn loannidis,

University of loannina

whether a finding will hold until it’s been

observation such as ours lies not only with

the experimental design, but with the ability

of other investigators to reproduce the obser-

# vation,” wrote Judith Miller, a kidney disease

& specialist at the University of Toronto,

Š Canada, in an e-mail David Christiani,

Toannials, however, thinks that researchers need to doa much better job of stating the lim- its of their findings “The papers should have been published” he says, noting that “nothing

is perfect.” But “better transparency” is sorely needed

ims from their data that just are not there,” agrees Kathleen Merikangas of the National Institute of Mental Health in Bethesda, Maryland Con- tributing to the problem, she says, is that many studies that fail to replicate a genetic inding are never published because they're not new

themselv advance their career.”

ing to

“JENNIFER COUZIN

Time Out for Institute Leader

Alarge number of scientists at the National Institute of Environmental Health Sciences (NIEHS) have turned against their embattled director Of 146 staff scientists who responded

to a survey by NIEHS's Assembly of Scientists,

107 said they did not have confidence in David Schwartz's leadership This week, Schwartz (below) stepped down temporarily asthe National Institutes of Health (NIH) launched a sweeping management review of the $642-million-a-year institute in Research Triangle Park, North Carolina, NIH Director Elias Zerhouni said

thatthe review is in response to congres- sional inquiries, which have included Schwartz's manage- iment of his personal lab, his consulting for law firms, and his handling of NIEHS's journal (Science,

6 uly, p26)

Senator Charles Grassley (R-1A) wrote Zethouni this week to ask why some NIEHS employees had recently been given a form for logging calls received from congressional investigators The form could intimidate potential whistleblowers, which would be “not only wrong but also illegal,” Grassley says

“JOCELYN KAISER

U.S Targets Add-On Patents

Inan effort to streamline its operations, the U.S, Patent and Trademark office is clamping down on how often applicants can tweak their inventions Last year, 30% of all patent filings were continuations, in which inventors add details toa pending application So this week, after 18 months of wrangling with the com:

munity, the office decided to limit such filings

to two per patent, with petitions required for further continuations

Biotech companies oppose the new limits, which they believe will deprive the patent office of information that could strengthen applications, including results from ongoing work, But Lawyer Peter Zura of Bell, Boyd &

Uloyd LLP in Chicago, illinois, thinks the changes are not an “end-of-the-world thing”

because firms that write biotech patent applications, including his own, will devise ways to protect their proposed inventions, such as more rigorously constructing original applications But “it's definitely going to make life more difficult,” he says

“ELI KINTISCH

(/

1021

1022

CUT ignored as an obscure

disease, melioidosis and the

frighteningly versat

that causes ït are draWÏg

UBON RATCHATHANI, THAILAND——A Thai

man with lank black hair and grizzled stub-

ble lolls on a cot parked in a hallway outside

a crowded ward The 61-year-old farmer

answers tersely as a senior physician,

Wipada Chaowagul, quizzes him When the

‘man was admitted on 9 May with sepsis and

an abscess in his chest wall, Wipada fin-

gered an old nemesis: melioidosis But

although nearly nine out of 10 melioidosis

patients in Thailand with septic shock die

somehow the farmer beat the odds After

spending 2 months in Sappasithiprasong

Hospital here in northeastern Thailand, the

taciturn man with watery eyes is almost well

enough to go hom

Wipada can’t explain how the farmer, who

suffers from kidney disease, managed to fend

off'a bacterium, Burkholderia pseudomallei,

that in its fiercest incarnation kills

mostof its vietims Indeed, there is

no shortage of scientific puzzles

surrounding melioidosis Over

the 2 decades that Wipada has

studied the once-obscure malady,

more and more experts have

become intrigued by the ability of

B pseudomallei to alter its form

and survive in environments as

disparate as soil, distilled wat

and the human body

“There's something incredibly

interesting and important go

on with pseudomallei, and

nobody knows what that is” says

Colin Manoil, a geneticist at the

University of Washington, Seattle

24 AUGUST 2007

Melioidosis is largely confined to Southeast Asia and northern Australia

and, fortunately for the rest of the world,

researchers don’t anticipate the shape-

bug breaking out of its ecological anytime soon, But

on the trail of melioidosis “But it still has

a significant terror factor Once soil is con- taminated, B pseudomalle’ is very hard to get rid of

Scientists know they are up against a worthy foe “Viruses are very smart, Bac ria are normally not so smart pseudomallei acts like a virus” in its deviousness, says Surasakdi Wongratanacheewin, director of the Melioidosis Research Center at Thai- land’s Khon Kaen University Hoping to strengthen their defenses, researchers launched a drug trial this month at Sappa- sithiprasong And a pilot experiment is under way in Ubon Ratchathani to take the battle to B pseudomalle’’s home turf: Th land's ubiquitous rice paddies

‘The Great Mimicker Melioidosis was first described

MỐI trom opium addicts in Burma

in 1911, and in 1947, two cases involving POWs held in Siam

were reported in the British Medical Journal It wasn’t until the Viel however, when soldiers came home with the ase, that melioidosis attracted ignificant attention in the West,

‘The first Thai case was reported in

No one had ever seen this says tropical medicine specialist Sompone Punyagupta, former president of V

Hospital in Bangkok In the 1960s,

Grim prognosis Burkholderia pseudomallei

colonies in a blood agar dish

scientists isolated B pseudomallei from soil

throughout Thailand and determined that

about a third of Thai soldiers sampled had

antibodies to it But with no further confirmed

cases among the Thai population, Sompone

says, researchers

clinically important disease.”

That assessment chai

‘Sompone took overa tropi

we unitat Ramathibodi Hospital in Bangkok and real-

ized that untold numbers of melioidosis cas

were being overlooked or misdiagnosed as

TB or other ailments He dubbed the disease

“the Great Mimicker” The bacterium eluded

detection in part because it grows slowly in

culture Back then, dishes were typically dis-

carded after 3 days, says Sompone, because

other pathogens of interest form colonies

within hours of inoculation After giving

B pscudomalleicolonies moretimeto form, he

says, "we began to see more and more:

Since then, scientists have sketched

picture of a malady most perplexing It’s

unknown whether B pseudomallei lives

freely in soil, in association with rhizomes

that stud roots, or ina host like an amoeba

infects humans by accident,

northeast Thailand, nearly ev

the population shows no antibody response,

Peacock says Researchers suspect that

B pseudomallei enters the body through cuts

or abrasions, or through the lungs In Ubon

Ratchathani province, the incidence fell

3 years ago when boots were handed out to

curb leptospirosis, a waterborne disease,

says Direk Limmathurotsakul, who runs

MORUS Lab Melioid at Sappasithiprasong

Hospital But the farmers didn’t like weati

boots and case numbers shot back up (see

graph, p 1024) “The incidence looks quite

bad this year” says Surasakdi

‘Once the bacterium enters its human host,

illness can set in within hours

patients deteriorate very fast

Sirirurg Songsivila

Thailand’

Development Agency In other people, the

bác lays low for years Two years azo,

resi reported the curious case of an

2004, he developed an infected ulcer on his

right hand Lab tests confirmed melioido-

sis—a whopping 62 years after his presumed

exposure to B pseudomallei (Journal of

Clinical Microbiology February 2008, p.970)

Although no one knows for sure where the

microbe lurks in asymptomatic people, ike!

hideouts include the lymph nodes, reticular epithelial cells, the spleen, and bone marrow

“We don't understand how the body tolerates

it so long,” says Peacock Antibodies don’t seem to confer protection,

In more than half the known cases, a chronic illness such as diabetes or kidney dis- ease is the spark that ignites a latent infection

or allows infection from a fresh exposure In Thailand, about 75% of cases occur during the

nủ log barefoot in

erson trans mission is rare, and relapses are common

“Patients need to be followed up forthe rest of their lives,” says Sirirurg

Although melioidosis cases pop up spo- radically around the world (see map), only

Environmental isolates [S Unconfirmed reports

Scientists are striving to unravel the machinery that underlies B pseudo-

"s exceptional hardiness and viru- lence Its penchant for morphing—a phe- nomenon called phenotype switching

appears to be central to its versatility “There

is unbelievable variability in how it presents itself It like a population of several differ- ent organisms,” says Manoil MORU researchers have identified seven morpho- types, each with a distinct gene-expression pattern Type | is most often cultivated from people and soil “If you cause it to switch to another morphotype by starving it, for

1 is someone exposed regularly to soil

patients, who are treated in int fe wards, are much more likely to survive than Thai patients, who are usually treated in ordinary wards

At MORUSS main lab at Mahidol Univer- sity in Bangkok, Lek is running a simple experiment with chilling implications In

1993, she put some B, pseudomallei cells in double-distilled water to see how long the

47 colleagues published B pseudomallei’s nome (Proceedings of the National Academy of Sciences, 28 September 2004,

p 14240) It weighs in ata hefty 7.25 million base pairs on two chromosome:

ria have one), and its chromosomes are dotted with “genomic islands” harbor

acquired from other ong

jons that equip it to

survive and thrive in the environment.” says Holden, That includes “a well-stocked arsenal

of virulence factors,” he says Like salmonella and shigella, the bacterium appears to use a molecular syringe to invade host cells Other elements of its repertory remain shadowy “The virulence mechanisms

of this bug are Virgin territory.” says Manoil,

‘who is working with Sirirung at Siriraj Hospital

in Bangkok to probe the relation between

B pscudomallei’s morphotypes and virulence

Genetic differences between strains will shed

1024

light on variations in virulence and on the bac-

terium’s enigmatic origins, predicts Bart

Currie, head of the melioidosis research pro-

sgramat the Menzies School of Health Research

in Darwin, Australia Also intriguing are the

mutational hot spots, called short sequence

repeats thatare found in two-thirds ots genes

‘When I first heard about this, I was stunned?

says Manoil The bottom line, Holden says, is

that B, pseudomalle’is “adept at adapting.”

A gnawing fear is that terrorists may

exploit this resourceful bug Unsetlingly, one

of the few biowarfare agents ever deploy

a cousin of B pseudomalle’s,B mallei, which

causes glanders, a disease that primari

affects horses but ean also cause an illness in

people thats similar to melioidosis The bac

terium, unleashed on Allied forces in World

War I, evolved from B pseudomallei

Melioidosis is more sinister than glanders

1's different from most other potential

bioweapons in that melioidosis is actually an

important human disease,” Manoil says

There is no vaccine And because it takes

months on antibiotics to eradicate the bac-

terium from the body, treating many patients

in an emergency “would be extremely expen-

sive, difficult to manage, and pose an enor-

mous burden,” says Herbert Schweizer, a

microbiologist at Colorado State University in

Fort Collins who will speak at a biothreat

symposium at the Sth World Melioidosis

Congress in November in Khon Kaen

Preparedness against melioidosis is sorely

lacking in countries where the disease is not

endemic, Schweizer says, Butts ability to taint

food or water has led the US Department of

Homeland Security and two other agencies to

designate “determining the growth and sur-

vival characteristics” of B pseudomallei in

foods as a research priority

At ground zero

Every Tuesday in Ubon Ratchathani, Wipada,

vice director of Sappasithiprasong Hospital,

runs a melioidosis clinic for survivors

Relapses can occur years after an initial bout Suwan Baoyai, a 36-year-old diabetic, came

in last December with a feverand abscesses in her spleen and right armpit “I feel enough to work in the rice field now

joties, however, the mass in her armpit has not disappeared

A short walk away, a technician at MORU’ Lab Melioid is busy inoculating plates undera safety hood The lab has documented more than 3000 cases since

1986, with northeast Thailand having the highest incidence in the world Thanks to its location at the disease’s epicenter, the laboratory a has been at the fore- front of drug testin

is Gram-negative, it has a sugar on its cell wall that interacts with TLR-2 The TLR-4 knockouts were as likely as normal mice to succumb to meli whereas TLR-2 knockouts, surpri

advantage, the res

to test whether com- pounds that muzzle TLR-2 reduce the severity of melioido-

that heanibiede eaten Masedscxsnresiminte Ses

halved the death rate, bringing overall mor tality down from 90% to 50% (In Thailand, the death rate of septic shock patients remains stubbornly around 90%.)

Earlier this month, Lab Melioid launched a trial pitting ceftazidime against the antibiotic

of choice for treating septic melioidosis in Australia, meropenem, Scientists expect to enroll more than 500 patients over 3 yea Another team is testing whether granulocyte colony-stimulating factor, a cytokine that boosts neutrophil counts, can help save patients with sepsis

One counterintuitive treatment strategy might be to block a Toll-like receptor (TLR),

an immune system protein, that recognizes

B pseudomallei but appears to interfere with other components of the immune response A team led by Joost Wiersinga of

B pseudomalle’s virulence factors for vaccine candidates, But “the

Surasaikdi cautions

A different strategy is to unleash competing microbes that knock down B pseudomallei soil concentrations to levels that cause few or no infections (A high density is correlated with a

zh infection rate.) At MORU, Lek added

a commercially ible biofertilizer loaded with beneficial bacteria—to soil that had been sterilized and seeded with B pseudomallei The biofenilizer suppressed B pseudomallei

Now Lek istrying this out on arice fieldon the outskirts of Ubon Ratchathani A 10-year- old boy, under the watchful eyes of his proud father, is using a motorized plow to prepare a paddy for transplantation while his younger brother also barefoot, stands idly in the mid- dle of the paddy The boys are up to their ankles in mud that is almost certainly teeming with B pseudomallei

ilier this summer, Lek added Effective Microorganisms to a nearby paddy and left another paddy untouched Over the coming

‘months, she will compare how B pseudomallei fares in the two plots “I's too early to say any- thing” Lek says But for millions of people at risk of falling prey to the Great Mimicker, even along shot is one worth taki

fected two strains of

As the ranks of excavated artifacts grow, museums are running out of space—and

money—to care for them all

the MeClung Museum

Knoxville row upon row of boxes are stuffed with

brown paper bags, which are in turn filled

with hundreds of thousands of artifaets rang

ing from 10,000 to 200 years old The arti-

facts, includin;

arrowheads, were excavated during the

1960s and 1970s when the Tennessee Valley

Authority (TVA) dammed the Tennessee

River and its tributaries, flood

and stone tools, pottery,

al sites along the banks

Researchers visit the collections about

10 times a year, but museum curator Lynne

ullivan, like many of her counterparts

elsewhere, faces a tough job cari

them, Some of the bags have split, spilli

their contents into the boxes And the arti-

nce inform:

they came from, which is vital to their

research value—is written on the bags

TVA is required by law to care for the arti-

facts, which belong to the federal govern-

but the strapped agency doesn’t have

the money So the University of Tennessee

has stepped up to provide space and

staffing, but it can’t afford to rehabilitate

the collections

The result: a curatorial crisis “We don’t

even know at some level what

those bags.” Sullivan says, adding ing on in hat some

www.sciencemag.org

of the metal artifacts parts, and hoes—are rust Sullivan isn’t alone in her plight Many collections in other repositories are in

axes, knives,

“much worse shape.” she says, Indeed, says Dean Snow, president of the Society for Amer

problem is at crisis proportions.” The effects are being felt not only by

can Archaeology “the curation

researchers using museum collections but also by archaeologists in the field, who

worry about where to store the artifacts

and whether they should

“I think its the end of the days of endless archaeology.” says archae- ologist Teresita Majewski of Statistic Research Ine

ment firm in Tueson, Arizona, The curatorial problem has bi for decades In 2000, a report on the U.S Army Corps of E

tions—millions of artifacts occupying nearly $0,000 cubic feet of space that could fill adozen tractor-trailers—concluded that

in about 75% of cases, artifacts had been stored in improper conditions and were quietly disintegrating; about 10% ni immediate attention “If not properly for soon,” the report concluded, [artifacts] will lose th

research value.”

they recover recover any atall

mer curator Julia lege of Maryland explains

because it is not the objects alone but “the relationships between the artifacts that

the critical contribution of archaeology”

Curating the corps” collection, which includes projectile points and stone tools from some of the New World’s earliest inhabitants, would cost an estimated

$20 million, officials estima

In December 2005, Heritage Preservation, a nonprofit on, tion in Washington, D.C., made the first comprehensive survey of U.S

collections held in the public trust They found that roughly 20% of archaeological collections need better and that more than 40% of bulk cataloged archaeological collections

Lack of space is a critical problem

Federal and state laws often require archaeo- logical surveys before construction work, so collections swell wherever development is rapid, A repository at the University of Cali- fornia, Los Angeles’ Fowler Museum is almost full, says curator Wendy

Teeter In Arizona, the fastest

in the country, archaeologists are doing more than twice as much work as they did several years ago, says Majewski The governor recently appointed a commission to study the curation problem, and the resulting report predicted that Arizona’s principal repositories will be full in 5 to 10 years; the

Arizona State Museum in Tueson, is now storing some

state's main repository

items offsite

sts are thinking lect "For decades

As a result, archaeolo;

harder about what they c‹

and decades, people were colleetin and keeping it all,” says S Terry

gist with the National Park Service in Washington, D.C Now archaeologists try to choose a representative

a dig in Maryland in which one of her col- eagues, working pro bono, left the artifacts

in the ground instead of cleaning and analyz- ing them, He identified them—and the house he was tryin, as 20th cen-

tury; later, more detailed excavation showed

that it was 19th century

One extreme solution is the use of no- collection surveys, says Childs, in which

24 AUGUST 2007

1026

researchers simply record artifaets" loca-

tion on the surface and leave them there

This is just horrible.” she says, adding that

anecdotal reports suggest such surveys are

on the rise, Omitting actual artifacts risks

the: “8 ees Christopher

Pulliam of the Army Corps of Engineers

Archaeology professes to be a science,”

he says, “If one can’t replicate research

results or reanalyze the materials from a

site, then [archaeology] can’t proclaim to

bea science.”

Another solution is to remove redundant

ms or those with little research value,

called deaccessioning For example, until a

ago, the San Diego Archacologi- ter in California housed 30 boxes of ear-old, decomposing soil samples

owned by the Department of Defense

Given their minimal research value, center

director Cindy Stankowski kept representa-

tive samples of various soil types and threw

But artifacts uninteresting to some are

valuable to others Back in the 1990s, King

co-directed the excavation of the 17th cen-

tury home of Charles Calvert, governor of

Maryland, and found many brick frag-

ments Bricks were considered expendable

and most were discarded, but King says

some revealed the earliest evidence ofa de, orative technique used in the Chesapeake

The federal government is drafting new rules to guide deaccessioning some of their hundreds of milli the Department of the Interior

sible for 90 million artifacts The govern ment tried to implement deaccessioning regulations in 1991 but backed off after ferocious opposition from archaeolo

Everyone would like to score well in an academic beauty contest But is it really

possible to assess an institution's worth?

Nobel Prize? The question seems

it’s important for the reputations of two

Berlin universities The reason: Even Nobels

bagged 90 years ago are counted in the

“Shanghai ranking,” an influential list of the

World 500 best universities Both Free Uni-

versity (FU), founded in West Berlin in

1948, and Humboldt University (HU), on

the other side of the former Wall, claim to be

the heirs of the University of Berlin, the erst-

while home of Albert

other Nobelists

The resulting tug of war has had bizarre

results, When the team at Shanghai Jiao Tong,

University produced its first ranking in 2003,

it assigned the prewar Nobels to FU, helping

it earn a respectable 95th place Swayed by

protests from the otherside of town, the team

assigned them to HU in 2004, prope

to 95th rank and dropping FU by more than

100 places After FU in turn cried foul—and

24 AUGUST 2007 VOL317 SCIENCE

many e-mails between Germany and China later —the team simply took both universities out of the race Both are still missing in the

2007 edition, published 3 weeks ago

The controversy is just one among many

in the booming business of university rank- ings Invented by the magazine U.S News &

World Report in 1983 asa way to boost sales, these academic beauty contests—called

‘league tables” in the UK.—now exist at the national level in a dozen countries: there are

a handful of European and global lists as well Almost all have come under fire from universities, scientist

fellow rankers

This year, for instance, presidents of more than 60 liberal arts colleges refused

to participate in a key component of the

US News & World Report rankings, pub- lished last week The rankings, they wrote, imply a false precision and authority” and

“say nothing or very little about whether

and, in some cases,

who said that even artifacts of no research value now might yield important informa- tion when examined with future technolo- gies But Childs, who chairs the working group drafting the guidelines, says the cur- rent effort is likely to be more successful The guidelines are expected to be made available for public comment in the next 6 months or so

Despite the gloomy outlook, ma archaeologists see signs of progress, as insti- tutions such as the National Endowment for the Humanities and Save Ame

sures, both in Washington, D.C., the value of certain archaeological collec tions and pay to restore them, But there’s mutch to do, “The problem with coll

is that they're not considered sexy Childs She and others note that many more Ph.D.s are awarded for field-based than collections-based research, and that few uni-

es offer classes in collections manage- She and her collections-minded col- ues hope to change that The future of chaeology” says Childs, “is in excavating the collections

~MICHAEL BAWAYA Michael Bawaya is the editor of American Archaeology

ning at particu

* Last year, 26 Cana- dian universities revolted against a simi exercise by Maclean's magazine,

The critics take aim not only at the rank- ings’ methodology but also at their undue influence For instance, some U.K employers use them in hiring decisions, says Ellen Hazelkorn of the Dublin Institute of Technol- ogy, adding that funding organizations, phi- lanthropists, and governments are paying increasing attention as well France’s poor showing in the Shanghai rankings—it had only two universities in the first top 100 helped trigger a national debate about higher education that resulted in a new law, passed last month, wiving universities more freedom

-ges or universitie

to be indicators of quality After giving each

a different, predetermined “weight.” the

indicators are added up to a total score that determines a university's rank But there are vast differences in the number and the nature of the indicators, as well as the way

ional university rankings cater prima- rily to aspiring students about to choose

where to study, which is why they focus on

education, In the U.S News & World Report

ranking of “national universit

instance (there are separate |

other types of institutions and programs),

student retention rates count for 20%, the

average amount spent on each student for

10%, and alumni donations, believed to

reflect student satisfaction, for 5% (see

graph) The University Guide published by

the Guardian newspaper in the U.K has a

formula with some of the same indicators, but

soa 17% weight on graduates’ job prospects

Most international rankings, meanwh

put a heavy emphasis on research output

That's in part because they are aimed more at

policymakers but also because education sys-

temsand cultural contextsare so vastly differ-

ent from country to country that solid and

sf data are hard to come by Average

spending per student, for instance, doesn’t

tell you much if you compare China with

Germany Nonetheless, the Times Higher

Education Supplement (THES) tries to cap-

ture education with a few very simple indica-

tors that it believes to be universally valid: the

stafl’student ratio and the percentages of stu-

dents and staff from overseas, regarded as a

measure ofa schoo!’ intemational cachet

Ranking education poses another prob-

Jem: Many rankings rely on universities

themselves to provide key data, “which is

always a deal with the devil.” says Alex

Usher of the Educational Poliey Institute

Canada in Toronto, who studies rank

There are documented cases of universi

cheating in the U.S News rankin

instance, and although U.S News

checks the data with other sources, there are

always ways to manipulate them For exam-

ple, colleges are known to encourage appli-

cations just so they ean rejeet more students,

thus boosting their score on the “student

selectivity” indicator

Even more controversial are peer-review

surveys in which academic experts judge

institutions, THES, for instance, assigns a

whopping 40% to the opinions of more than

3700 academics from around the globe

Whereas the judgment of recruiters at inter-

national companies is worth another 10% But

= when researchers from the Centre for S

ind Technology Studies (CWTS) at Leiden

University in the Netherlands compared the

reviewers’ judgments with their own a

sis—based on counting citations, an accepted

measure of scientific impact—they found

no correlation whatsoever “The result is suf

ficient to seriously doubt the value of the

THES ranking study.” CWTS Director

Anthony van Raan wrote in a 2005 paper

newspapers—siv universities from Aust

‘ended up in the THES top 50 in 2004, wrote Van Raa eographi cal bia a con- tributing editor who manages the THES rank- ing, says that the survey has gotten better since 2004 and has a good geographical bal- ance He believes Australia’s strong showing may have been the result of aggressive mar- keting of its universities in Asia But he co cedes that reputation surveys ma

and old universiti Peer review is also a major bone of con- intion in the U.S News ranking “We

st of several hundred institutions,

‘Academic performance with respect to the size

of an institution 10%

‘Alumni Nobet Prizes and Fields

US News editor Brian Kelly dismisses the boycott’s significance The ranking has always had its detractors, he says, but more than half of university officials stil fill out the questionnaire And the magazine could always find other people to review schools

Shanghai surprise The Shanghai ranking avoid:

problems by eschewing univers data and expert reviews Instead,

y available dat ions in Nature and Science, the num- ber of Nobel Prizes and Fields Medals won by alumni and staff, and the number of highly cited researchers The result is a list based almost excl Nian Cai Liu,

all of these -provided uses only

Percentage of I percentage of overseas staff overseas students

U.S News & World Report*

Spending per student 10%

Graduation rate performance 5%

‘Alumni giving rate 5%

SCIENCE VOL317 24 AUGUST 2007

such as the number of

1028

who heads the Institute of Higher Education

10 Tong University, started the ears ago because he wanted to

ies were placed

in the global pecking order When colleagues

started asking for the data, Liu put them ona

te, which now gets thousands

ing has its own problems For example,

Shanghai credits the institu-

US News of changing its method preci

to shake up the tables and thus boost sales, charge the magazine rejects

In part to boost their credibility, the rankers have founded the International Rank- ings Expert Group (IREG), which in 2006 came up with a set of ranking guidelines, Called the Berlin Principles, they stress fac tors such as the importance of transparency picking relevant indicators, and using veri-

they do provide a more com-

tion where the Nobe County shanghai iag, ais her ny plete picture

worked at the time of the —————_ et Others are going further, award And that can make a DUUUUDDUUUUUWU | UUUUUUUUUUUUU ‘The Centre for Higher Educa-

difference Andrew Fire’s 5 UUUUUUUUUUUUUU |_ V7 ”{/1/(/(/00/U70U tion Development (CHE) in

medicine helped his current UUUUUUUUUUU 00:7 university departments with-

institution, Stanford Univer- _ Netherlands 1 ‘out trying to aggregate them, sity in Palo Alto, California, Australia 0U UUUUUUU and the departments are sim- move up from third to second Japan UUU000 uuu ply slotted into top, middle, place, even though Fire did Germany UUUUU UUU and lower tiers It also allows his groundbreaking work on Sacer UU 0u00U the user to sort universities RNA interference while atthe —— france uuu j ‘uuu ir own favorite Carnegie Institution i Balt TT TA | aoaue

more, Maryland TT

Universities that fous on ——C2naé@_UUU0 _) =

also tend to suffer under the Singapore _ - Universe contest without a

Shanghai system Recogniz- ‘New Zealand vu winner But a spokesperson

ing that scientists in those India uu for Die Zeit, the German ciplines gravitate to different uU sper that publishes the journals, Liu doesn’t count Italy U (CHE rankings, says its annual Nature and Science papersand israel ử bestseller redistributes that 20% share Peork 5 7 anyway, and the interactive across other indicators Still, Tay a sign lures many readers to the effect is noticeable: In nha 7 its Web site,

2006, the well-respected Lon- an P 5 With all the complaints, it don School of Economies and easy to forget that rankings

the list, Liu no longer gives — Š9whKeres U versities to actually perform individual ranks), whereas the ‘Austria U better, he Says,and the rankings

THES awarded the school y =nenivestyn the top 100 * ines HongKong (3 universes) provide students and policy-

17th place

Well aware of their influ-

ence, and the criticisms, the

rankers themselves acknowl-

edge that their charts aren’t the last word,

US News & World Report, for instan

advises students to take many factors into

account when choosing a college A

window on Liu’s Web site warns that

are still many methodological

problems” and urges “cautions” when using

the result

In response to the critics, some rankers

are also continuously tinkering with their

formulas But that opens them up to another

criticism, namely, that a university can

appear to become significantly better or

worse in a single year Many have accused

Who's right? Although both agreed that the U.S led the list and the U.K came second, the 2006 Shanghai and THES rankings differed markedly on where Earth’s 100 best universities were located,

denominators” among groups of rankers with very different views Many rankings a fully compliant with the rules yet

CWTS researcher Henk Moed

The group in Leiden, for instance, produces rankings of European universities based purely on publication and citation data and

makers with answers—even if they re imperfect—to legiti- mate questions about quality Other rankers point out that universities tout the results ifthey do well, and they don’t like being excluded, Perhaps that's why the presidents of the competing Berlin universities announced shortly after the 2007 Shanghai ranking appeared that they would sit down a:

“MARTIN ENSERINK wun sciencemag.org

Cancer's Perpetual Source?

The discovery of tumor cells that behave like stem cells suggests why cancer may be

so hard to eradicate—and how new therapies might be targeted

Beginning about 15 ye „ John Dick’

team at the University of Toronto in Canada

provided a new clue as to what makes cancer

such a formidable foe They found that only a

tiny population of leukemia cells could trans-

mit the cancer from one experimental animal

to another More remarkably, the cells had a

property previously seen only in stem cells: the

ability to produce an exact copy of themselves

each time they divide, thereby maintaining the

ability to reproduce in perpetuity Th

called cancer stem cells, Dick sugges

might be what makes the disease so hard to

eradicate with radiation or chemotherapy

ince then, such cells have been found in

many other cancers, including those of the

breast, brain, colo

‘Cancerstem cells

tually every cancer,”

University of Michigan Comprehensive Can-

goo Centr in Ann Arbor

§ Not everyone is convinced that the stem-

& keels found in cancers play sucha key role

in tumor growth and maintenance But if that,

idea is correct, “the ramifications could be

# huge,” says Craig Jordan of the University of |

§ Rochester School of Medicine and Dentistry

3 in New York state In that event, therapies that

cancer stem cells may prove more

rent cancer treatments

in Bethesda, Maryland, which held a work- shop in mid-May on stem cells as targets for cancer prevention

Cancer researchers are beginning to understand what makes cancer stem cells dangerous Among other things, they foster the formation of new blood vessels needed to feed tumor growth, Recent work is al uncovering the cellular signaling pathways that control cancer stem cell proliferation,

ng hopes of new treatments that selec- tively kill these cancer seeds Indeed, some existing cancer drugs and others that may soon be tested in people appear to tanget the cells, new studies indicate “By gainin sophisticated understanding of how norm and cancer stem cells differ, we'll be able to design a new cl

Blood vessel stimulator When transplanted into

‘mouse brains, glioma stem cells form larger and

‘more vascular tumors (middle row) than do nonstem cells (top) As shown by the mouse at right, an anti body to the angiogenesis-promoting protein VEGF greatly inhibits the growth of glioma stem cell tumors; the mouse at left isan untreated control

and Peter Dirks of the Hospital for Sick Children in Toronto and his colleagues identified them in

a variety of brain cancers (Science 5 Septem- ber 2003, p 1308)

In the past several months, that early trickle of results has tuned into a flood In the

4 January issue of Nature, for example, two independent teams, one led by Dick and the other by Ruggero De Maria of the Istituto Superiore di Sanita in Rome, reported the dis- covery of cancer stem cells in colon cancer, and others have reported finding them in can- cers of the prostate, lung, panereas, head and and the deadly skin cancer melanoma,

‘ancer stem cell research has gone from an interesting sidelight to ma

short time,” Jordan says, What's more, cancer stem cells display an array of traits that aid in their proposed role of driving and maintaining cancer growth For example, Jeremy Rich’s team at Duke Univer- sity in Durham, North Carolina, looked at their ability to resist radiation

In one key set of experiments, these researchers transplanted cells obtained from human glioblastomas, which are highly

‘malignant brain tumors, into mice and then subjected the animals to radiation doses sim- ilar to those used to treat human patients, Other than surgery, Rich says, “radiation ther- apy is the most effective [treatment] for brain tumors, but itis rarely curative.”

The transplantation results, which appeared in the 7 December 2006 issue of Nature, suggest an explanation In irradiated tumors, the proportion of cancer stem cells

‘went up from about 2% to about 8%, as indi- cated by the number bearing the protein CD133, a marker for brain cancer stem cells This shows that those cells survived the radi- ation whereas other tumor cells succumbed

The stem cells overcame the radiation, further analysis suggested, because they

thought that was a great papet

who's now at Stanford University Alto, California, “It provided experimental evidence for what we've all been predi

A second way that cancer stem

may pose a threat is by 12

genesis, the formation of new blood ve

cells or in the more developmentally advanced progenitor cells can produce cancer stem cell When these

cells divide, one daughter is an exact copy of the original and retains the ability to divide—and to initiate

additional tumors—whereas the other target differentiates to produce nontumorigenic cells

that support tumor growth, For example,

the Duke team recently found that glioma

stem cells in culture produce much more of

the angiogenesis-promoting protein VEGF

than do other glioma cells

The VEGF discovery suggests that one

current drug may be a prototype of thera-

to block VEGF action that is already used

for cancer therapy And when the Duke team

transplanted human glioma stem cells

and treated the animals with the anti:

body, “the tumors from cancer stem cells

shrank dramatically.” Rich says “It looks

like bevacizumab is a kind of anticancer

stem cell therapy.”

‘And cancer stem cells may have yet

another dangerous property: the ability to

drive metastasis, the spread of tumors in the

body The presence of tumor cells in the bone

marrow of breast cancer patients is a bad

prognostic sign, indicating that such patients

have a high risk of cancer spread Last fall,

Marija Balic, Richard Cote, and their col-

leagues at the University of Southem Califor-

nia in Los Angeles reported that roughly

70% of the tumor cells in bone marrow carry

the surface markers of breast cancer stem

cells Although it hasn’t been proven that

those cells seed metastatic tumors, such

possibility isin line with the idea that cancer

stem cellsare the tumor-initiating cells, Other

24 AUGUST 2007 VOL317 SCIENCE wwwsciencema:

research has shown that genes involved in cell migration and tissue invasion are highly active in breast cancer stem cells

Searching for vulnerability

In their search for ways to disrupt cancer stem cell activities, researchers are focusing heavily on the signaling pathways needed for their maintenance and development, And several intriguing connections between genes already linked to cancer development have emened

Atthis year'sannual meeting of the Amer ican Association for Cancer Research in April, Hasan Korkaya, a member of WiehaX group at Michigan, reported that reducing expression of PTEN, a known tumor suppres- sor gene, in cultured human breast cancer cells increased cancer stem cell populations

by as much as fivefold Boosting expression ofthe HER2 oncogene at the same time do bled that increase In addition, such cells migrate more in culture, an indication that they may seed metastases This might help explain why women whose breast cancers have both loss of PTEN and extra HER2 copies usually have a poor prognosis

Other work also points to PTEN loss as a trigger for cancer stem cells Early last year, Owen Witte’s team at the David Geffen School of Medicine in Los Angeles found that when PTEN is deleted in the prostate cells of mice, the number of cells bearing a

has found that deleting PTEN

i the intestines leads to the pro- duction of stem cells that form polyps that can develop into full-blown cancers Finally, Morrison's team has found in mice that PTEN deficiency promotes the formation of leukemia stem cells while depleting normal hematopoietic stem cells

This suggests, he notes, that it may be pos- sible to selectively strike cancer stem cells Indeed, Morrison and his colleagues have evi dence that the dr

help make up for PTEN loss, can prevent leukemia development in their mouse model while at the same time restoring normal hematopoietic stem cell

citing.” Morrison say:

the possibility of developing therapies that

IIs but are less toxi ue.” Rapamycin is already used clini- cally as an immunosuppressant and is bei studied in cancer therapy, and the group hopes to begin a clinical trial to test it in patients with acute myeloid leukemia (AML) Researchers seeking to target cancer stem cells are also looking at several more path-

‘ways previously implicated in stem cell main- tenance Among these are the Wnt pathway, which is implicated in intestinal and other cancers, and also the Polycomb and sonic hedgehog pathways

Some surprising aspeets of cancer stem cells may also provide unexpected new targets for therapies In a recent screen of 1267 com- pounds ina library of pharmacologically active agents, Dirks and his colleagues ident fied 160 agents that decreased the prolife tion of brain cancer stem cells in lab cultures Many of these drugsaffected unexpected neu- ronal functions, such as neurotransmission, which were supposed to be properties of mature neurons rather than unspecialized stem cells The mechanisms that control can- cer stem cell growth “may be more diverse than what we see right now.” Dirks says

Even a folk remedy promise against cancer stem cells Rochester's

‘working with Dianna Howards tam

at the University of Kentucky Medical Center

in Lexington, has evidence from both cells in culture and a mouse model that the dru: parthenolide—the active ingredient in a herbal remedy called feverfew— specifically kills AML stem cells

In addition to simply screening for com- pounds that kill eancer stem cells, Dick and his colleagues are going after leukemia stem

cells with an antibody that binds to a protein

called CD44 that is highly expressed on the

surface of AML cells, When the researchers

transplanted human AML stem cells into

mice and then administered the antibody, the

treatment apparently abolished the tumor

stem cells driving the leukemia Closer exam-

ination showed that the antibody prevents

AML stem cells from migrating to the spleen

\d bone marrow, where they would other-

wise reside “The [leukemia] stem cells still

need to interact with their niche,

re with their trafficking,

maintain themselves,” Dick says

Even if cancer stem cells can't be killed or

their spread blocked, they might be restrained

in another way: by inducing them to lose their

ss” and differentiate into nonrenewing

stem cells in this Fash-

ion “It’s an interest

ing paper.”

Dirks “It opens up

the field to consider-

Despite the outpour-

ing of results in the

past few years, finda

mental questions

remain about cancer

stem cells One big

issue concerns the

ature of the original

cell that gives rise to them “That's a harder

question than people appreciate.” Jordan says

“It doesn’t have to start with a normal stem

ell.” In work done a few years ago, Irving

Weissman team at Stanford University

examined the genetic mutations in human

AML cells and concluded that the ori

cancer-causing mutations can strike more

developmentally advanced, although still

immature, progenitor cells

About a year ago, Scott Armstrong and

colleagues at Children’s Hospital Boston pro-

vided further support for that idea Many

leukemia cells feature gene translocations in

macrophage progenitor cells to produce MLL-AF9 and transplanted the cells into mice, they gave rise to a leukemia similar to AML Subsequent isolation of leukemia ste cells from the mice showed that they resem- bled the original granulocyte-macrophage progenitors but had activated genes needed for sel

Indeed, work published by the Clarke team in the 12 June issue of the Proceedings

of the National Academy of Sciences sug- gests that stem cells of a given type of ancer may arise from different cells For these

experiments, the researchers looked at colon cancer stem cells obtained from four differ- ent patients, There were “subtle differences”

in cancer stem cell characteristies from patient to patient, says Clarke “This sug- gests that the cell of origin varies from patient to patient’

Despite the huge growth in the cancer stem cell field, skepties remain, One potential problem is that virtually all the work has involved transplanting human cancer cells into immunodeficient mice This has raised concerns that the experiments do not accu- rately reflect what happens during cancer development in humans Indeed, Andreas

Is into genetically compatible healthy all the recipients developed leukemia,

n those injected with as few as 10 cell

Strasser's team reported in the 20 July issue of

Science (p 337) That could not have hap- pened if only a tiny minority of tumor cells had the ability to initiate tumor formation, a the stem cell hypothesis holds, Strasser says

He suggests that the mouse doesn’t provide the right environm

human cancer cells,

0 that only afew mar

to survive and multiply, thus creating a false impression that tumor-initiating cells are rare “Those data have been ma overinterpreted” Strasser maintains

Dick disagrees He notes that the cancer stem cell hypothesis rests on the prospective isolation of distinct populations of tumor- initiating and noninitiating cells rather than just on the rarity of cancer stem cells Dick points out that his team has re-created human leukemias in mice by injecting the animals

\with normal human blood-forming cells that had been engineered to carry a fusion gene known to make cells leukemic (Science,

27 April, p.600)

These animals, which are more compara- ble to Strasser’s genetically engineered mice, developed leukemias similar to those seen in humans, and the frequency of tumor- initiating cells was relatively high—one to two in 100—rather than the one in a million seen in the early experiments Other researchers have reported similar results

Dick suggests that different cancers will vary in cancer stem cell frequency, depend- ing on the particular oncogenic pathways operating in the cells

Although others share Strasser’

ismaboute tainties remai the possible

mportance of can

as therape 4s, the field will continu

to grow And at least one skeptic has already been convinced Duke University’s Rich says that he came into the research hoping to dis- prove the importance of cancer stem cells

Now, he says, “we are very early in studying cancer stem cells, but understanding them may impact the way we diagnose and treat patients in the near future

t for the growth of

1031

edited by Etta Kavanagh

Another Threat to Borneo's Rainforests?

- I WELCOME THE RECENT Indonesia, and Mai:

forests on the island of B (Last

est and associated loss o

sp effort to save Borneo’s tropical rainforests

13 July p 192) This is timely and hopefully will lead toward improved conservation efforts and more sustainable land use in this be

INITIATIVE BY THE GOVERNMENTS OF BRUNEI, sia to commit to €

Borneo through the Jeart of Borneo” initiative nserve the highly diverse

FRANCIS Q BREARLEY Department of Environmental and Geographical Sciences, Manchester Metropolitan University, Chester Street, Manchester

M1560, UK E-maf: Lạ beealer@mmaac.uk

References

1 C Rewcastle} Ungoed-Thomas, “ining giant to raze apes

2 WF Laurance, Biotropica 39,20 (2007) forest home,” Sunday Times, 5 July 2007, p 20

Ocean Acidification and

Scleractinian Corals

IN THEIR BREVIA “SCLERACTINIAN CORAL

species survive and recover from decalcifica-

tion” (30 March, p 1811), M Fine and

creased atmospheric CO,, a subject currently

at the height of public concem (1.2) The fact

that these authors demonstrated that five

species of living scleractinian corals could

lose their aragonitic skeletons, in response to

elevated CO,, and then continue to exist

An important implication of this work is the arbitrary and artificial nature of the curre phy!

corals Sel calcified skeleton when essentially identical

Jenetic classification of scleractin

id some anemones, Why should Order

Fine and Tchemov’s decalcification exper-

iments may not be representative of all va

ties of orals I suspect that zooxanthellate reef-building species would have responded very differently to the experiment because of

the complex nature of their photosymbiosis (6) Readers should not misconstrue this paper

as tacit validation that we need not be as con- cemed about the growin

acidification with regard to corals and reefs

‘GEORGE D STANLEYJR

‘University of Montana Paleontology Center, Department of Geosciences, University of Montana, Missoula, MT 59812, USA

6 Stanley Jc, orth Sci Re 60,195 (2003)

0 H Ewin, Extinction: How Life on Earth Neorly Ended

250 Mon YeorsAgo(riceton Uni Pes, Princeton,

iy, 2006)

6 6.0 Stanly, Science 312,857 (2006)

Response STANLEY HIGHLIGHTS THE DUAL SIGNIFICANCE

of our findings: a confirmation of his naked hypothesis (/) and a plausible explana- tion forthe enigma of discontinuity in the geo-

ley uses our findins sest that

The evolution and basic physiology of the studied species are indistt Je from that

of the colonies of the studied species are

teduced growth, lower competitive abilities, and reduced physiolog

cal state when losing their endosymbiotic Wwww.sciencemag.org,