I

NI

"

'CO:ViER
A!U.·~kyprojeil1.i.on of l1'ighe$I"ii5i:l'~Y ros!flnk rays, de'~ocl~d by tlm e ilnem;~ Augi£!r Ob:5e'Ntlllliry' (operm drrcl.es'l th:llt :lUt! (()m~t!!lal.ed ioMth the po)itiO:iTII,~ ,of nealrily 'Qllitl,)t!r.:: {tr1l~~~"a Imea~ulre~ Oi~ 'lhe lor.tl:~ 'gi!~i;lXY dljstfi~b'lUtjoll!.. TII~e s1.!perlQa~gdic al~dlMllllry Way ~I:nu~:s are mariiOO,d.The lb:a~kg~o!.m:di sihows ac"O~po:5~te~mage of illl nearby 9a~x.y (NIB,2) observed by NASA'$ Sl>~n~r:, IHubMe, ;'lln,d Chandr,,, spaC)e: olne'wflitoaies:. 5;ee paige' 938.
,CoJl'lpO£it.e itm:Jge: ,R6I,~y.KmusefSdel~u:!e (jiglJte: Auget ((dla~atioo;' ,malt); ,NASN JPJ.-CtJItec-WSfS",Vt'JNJII\(!f.a .hay CemerlilJlfl.iv.

DEIPARTM IENTS
BS 1 B83
SC,f,eii'Ce O!ilU~e

8138

890

893 8,9S 991 996

Thil!ii Weekil'lScil?l'lce ~ditll.rs,'(hoill!! COrltiil(~5ci12m::e RiI.rndlomSilmlOle:s N'ew:§maifiir~ New Products· Sdf!Il'Cf? UlJeer,!'i

!EDIITOR:IIAIL
8S 7 BiillHidliCIen by {)on~ld.K~nl€d¥

,0/ Mzm~;~SA/At)'II'AIJ(jmu H'(l{Jldm UmvJ

N,cWS 'QFTHE WEEK !~ oi~'ef~"S !i!iigihoesHII!t;lllJly Parti,,~es,l~a(:ed !;!adk

~oOl,h~,r ah!I~_'e's G
;..> ReJ~rrhMid:r P. ~;;8 Om!

II-IETIERS
8'96
.Spe:;:llfj:~'gOw :About U.S. $dence OI!JItplut 913 ) •.P, At'oore; IR,.£ Nelfi1~.rl; 5, Di:Fe(w lI~r~ts to IPrhi'aqi IPrlllt~c~Of!I, (; I. fJf)r"sJl Potem Qh~€:Siili(lli1iS A!fuio-m India"sft:lruit), Vil!cd:ll€: .5. C. Af'YO (j,fi/d (¥, AigaJfWG11R,Iil:5lp'onSle: ,N.,. C. Ullac55(Y et al.

.w.

If'ostd:oc: S:I!!I\f'LrY nmd',s GllfId@[ Sp~it

filllfl1l~[y ~s..'SI.I~sB97

:Spying (l,n INew N!NJro1n5in the HUlmilln IBrail'lB99 >:>' li:I!P011 I!., 'JBfJ S>(IIEiI!llCIES(]J:PE 899

caUEICUOrllIS,

AN,I!) CUlIIFIIIC:A!UONS

914

I
·Ge~elraim.re Somal. Stienre Stu dlie-.s ]!iiI Agem1H~a5led (()i1ll1!?,utalion1lil Mode~if1lgJ. M. fpsteio, revie,V/,edby Vi, [)Jermei~r .MaltiIiIemai!;al.Mooels, d Sociiall. EvdwliDlil II! Guiide 'for~jhe P~r ple:lif!-d :R. McftrruJtlJ an.d ft Boyd, . .revie,w,~ by D. l: R(lQifin 91:8:

HiipopoGillmpi!lll. elbl!Help Rah 'flilin~k AfiIIslIIdl. C

Few Milltiliti cm:s Divid e' .SOO!llIE! -iR~i!>t1llI1HB Sffill]IiI"> ,[llfll1g

900
9ln
'9{l~

'I"

MilIx. PLnck':SAsill11n VenlluUl~Rethillibs Ill5Ag,~ndii Fru~)l Fill!' B:litz.Shaw!> the Pnwer o~ (amp:ara'l.1I1Je
GelilOJl1iks:

908

919

'9'27

IPOIUCY fORUM
Mi!I~oriity'iiiJld.e5in i4illld~lng a IPai~hrow llile. Nexi! iM:a 15 Ra,~rr W'i'lo's; the Qu:~elmiAskth,e ~~ [{:~pDr!p. '185 Genes: R@th~l!likii U!'glfi)@sflil'i!i!.a1i~dl 'W@uwQuar~itY"!1[i Al!lfUCI!lHli ~ U. Yffm'iYal'l.u' et al

920

IPERSPIECT~VES
Mm:DlQI<!Ii ~te[~ar(Kkta~l

C (flcmorme.f amI S. 1~lo!l

How Doe's Rilrdi!i.l.tiOin Oalrrnilge ,Material:5? B.ilJ'. Wirth
';>e>

923

R.f!:pCJfllllP. 956 (Inri 959

Erlrnllndng ColloiiJ.silflrolllgll Ute SurfaCE' f . .c:. Ne;{joflrl{ld Po: ~ BffiO'fJn

mllOlR. Un~li!JiiShoo ,(,G •.Pfoud
!>!>

924

Repchl1 Jl. fJ n

Is.1I"hefl(! ,r'rogfle'SS on y: Wilks.

'ti!lkirn 91:S@Jlsibty 00 Machi ~es?

m
928:

An 11'!,~g"a.tiv,~ i~ .~~Olbesi:IJ V ~. f;, rWi'5$e, fil(itrJ;. .M. ~ 5d1rWGrtt'

CONfENflS

o:mlilllu!E!d »

W\I\.i"IN.sci:ernQeIFlflClg.,org

5CIIENOE VOL 3~B

9' NIOViE M BIEIR 200.7

Science,
SCIIE.N'CE, iEXPRIESS
www.sci(¥)ncexpress
O~EM~:SlAY :s,til!!Ij~!i::Magnl!l:siumm

CONTENTS

..or-g
IMMUNOLOGY

,~p; wire",. Jones, CCfinli'd~ed r~mtl!on! of '"' ilrnigiil~~um ClliMPW mil coo;fidilnmi~.ooby bu~~n~uugl!1iil·bared Ib9Jil1lld~ yll!l!ldsih'ill ~~o!a~l~ ~luswl? .,.,:fi. o_~ida'licm ~~i!lt!lIDfJIh!l!lilr.!rn~nl:.

c..

Cgmlpt:)!.!od~ vritlh ,MQ·.~!giBoliidis A. Sto$r:h

iii; .Koyo:gokf ,e!i ,ttl.

DU 8J\~ IO!l:ub~q!;jlit~Vla:seT1hat ReQlllla,t!i::S 'TryPE: I Ai

~1J'lt~fll:ironl

:iProdll.U:ti(l'fI

1.0. :U:2!6Jsdemlce"lnlS:0856
MEDIOI:II.UE

~nt~fr~rnn St'(ittlOiil inllfil5'poose ta,viira] llflr.e(it~Qnlis f~!WCed bvan! '~I11:!:'Jm~lhat remli~S u'biillJ!liililii ohaum rrom pr.!lIMfiS"ii1fi ~lJeGlthat ooutdimiliD'il;inl~:oimlflll!Jfle- di:sea!~~, mO.:n2Msjd:N1Ge.1l14.5 9'me
E.COLOGV

1IIhe Obe~Assllt~!fIIt:ed FlO l[i'ene' 1E'lilloodll5t12·0xog lutafi1lNi-IDepellllGJlemt INm1el(Acid [)emd1ilyt;L~e r. tierkt?n ell :iI ~. !!l! g'~ne'lh!!l~~i~red~~n ~1:!:dind~I"~ri:s&.l1If f)b~jly Ciad~5 fllr ~ prot~i n '!n~t 1!~I11!(I1l~
P1!E!l~,

As~mmeil:ric

,M:a.tilng ~tli1tNiUfiolil~ IDriii~!! W~rl'!.'1\\;pmi3id1n;\I'ilIsijDlillfl.md

Dis:pla~E!m,~n.t 11'10;, WfuJitd~y

SA·.l.iuet,al,
:line ~IICW~ of I~hefl1l1"i!lsi!;'~ hu!elly il"!l{hilll~ <lndIJl!IlI~!ri!!llia !i11!! r,~~It,a:i w b ~~pmdYC:li'I!~ suj!t,pre!~5ijCln of ~!!iU"'E!Pi:ipula~~an~ b~ lJ~li!invOOliM·.

gro!!!ps [rom DNA, 0!1~n~il!9h how 'this (uln!l:lion ~g;!:!!~t'1l'~~be'$~ i;s uru:lIll~r. 1-0.11:2iM;ch!i~Cld 'lt51710

'lO.112MSJdjltrlo~,11-49'S87

T,ECIHN~CAl COM M ENT ABSTRACTS

IBOTANY C,@!lIUliiE!!i!,t (ln
l

"A G ~rotr!~~=((I!JIlp~ed

ASl,RO II'HYSIQ;

R~'Cl1!pb:M1S:,i!!
HOnnQ\iI'8

9114

C(lri~lati~n~m-

~h,£! H!$!Jhl1!$Hfler:gy

C051111iik Ra.vs

938

Absit]sll!!: Aala" c. A. JiJ.lmstDn et ilIlL

F"laslfI'lai Me,tilIil:ilrrane' lReloepmr folt®'lili! PLant.

/lJllrm ill ~~ >l~JI(f'ImlY.~fJ!lt[g;i((.tm'fn~IVjH,lj8

SlI914c

I1i;l!:spoJilsew (ommemt o:n ";A 61 P,~ote:~!1~oup~e:dl l1lJe()~~lter 1115 P1~i3J5IiFh~1 a Me:mb!ralile Re(eptJ):Jjr,~rthe Plant HOIll'l'uJrle A!lb~(~s.k Add" X. Hu., it, ¥U(i iW' it L M'a
taU

'I/Iliith N'~riby E:drag~la,(,ttc Ob·j~CltS Th,f/ ,Pi'e'f.I,~.AlJgf!( Coltubr:J'fl1Uol'J TIi'II! rolllrce dimd:iofli:~ or U1e mOSi!:,en,erg;etllc'Cio~ic 'rays oorreialeVjm. 10 ra'liOFi s of ill 9ii1JiJ'I' at:.~i~!i19i11.aclij)(lilIuc[e.:i,implyiln~ till affi.l.ifJ!3VrQ.nm [rom :~~perri:'flla!.S'lllil!IbIM~. niJOO5~
J>;!>

I!Jem lle!}, p. HWI

f~xr Dr IMI'~~5('i!,,~mog_rJfgk9;i(L(JnI~rlfIJUI3.18J5S

5mHd

c:rlLBIOliOrGY ~RIEl SigllaUtlilg AJiiec'ls CelU fate' Dutlliin[i~he: U nfok~e,d IPrateim H~5pOi1ll5e }. H. U/l et o;~.
When lfIfIi5Jll~di!d pr:o~~iIM;JI;OJIITIl!lnall! l.!Ifii!htin ·~heel1ido~:~SI1Ili~[

944

R EVil lEW
IMEDICI:NE A General Madel of Pt~iirm Stran:1II5anti]hieir 930

~e'~itull;lm; r;I~O~~Live re:5p:olli~e~ ane ]li1ii:~i~led IIIllil1ilaite'lif ll'Hmiers e.e:lldeil~h pa~tw~afs.

ool P'rQlO.!1!11tOOS!)r'l!5-S

r'_'ilIglenrkity I; C~'lfif:ilg~tlr1d A, fl. Clotk€

BRIEVIIA
IPALEONTOlOGY

PI9IVS~CS

.A. Cremc:eol!llllHoofed M[lmmilll ~m.ml 1IIIIId~[I 937 (J, v: .R.• P«1fO,(j,. (). Verma, it Salil'n.p, v: .P:armaf,;.1t Khos$a A flJ~Sil.~()O~'h fT11l!ies!,h~t e<I~lYI.!ngl!lg~e5. wn ich a'tbie:ru,lilse·aPJil~r ~ ,dl:!!!f the tOO ·(i~e~~(eo;u:> e.~li!l!c:lh!~!i), eiflG:led~1iI Inod'" Ii'Ih~'1eit WillS adlril't :Ir,orn ,ath e~ roi'lU_l:Ien~~.

liIIe 5iimpb:!!~tDelJol,e'Slit,; Interh~welil~E! ,and 949 ~1ii'!t!1!!1:gl.em,El'!1t iiil DOil;! bk!~ PIiI,~tl)i(lnilatiol!il 'om-&1;2 . D. Akou,ry et Qil Ti'le ooguta,r paUer!'! f~SU:ltil'!g whel'l boI!JhIlleclfOn:s arr:~,ej,ede'lli rrorn
s

"~ rmpli:e~ ~hatauh!l!~r elfl!ergies bl:lcom.e oomparable., ~lneTrbenra'\!'1or c:n:anglil;5,JiI~mwave~ike~ palrH.de-~ike. G~:OPHV:S I:CS

A.ci(let€!ratel!i Uplift ,Hi~1Magmalitlhc ~fitrl~si'@n cnlii~ 952 Veno\M~tD'!iJt! GaJLa'efiili, 2004· to 2'006, WA. ebony, R'.. 8'.5mtih,C W{c\li5,. ,M, Fatftl~ C. M P.uskas J.
5alll1Rile radar amdlGP.S meas~reJfI1nl:ii'l'ts ifld1(are ~hl'lllih e ell n~ral

,,!(,cllo'i'll'!ilClne boei11f1 rising 1Iy '7 rem~ime~Brser year~~(1f ha/~ p

imp~yin9'thi'kllllil<l~.nfI<i~sinhdini:! OOktll!. MATmiAIi.S, SCIENOC

2nCW"

944

ObSe[loIiltio'ni ofthle: One:--Oilfli'lims.t<lnIiiil D~IIl.iSionof IN,i!lflom'e:t:er''$i zed Dilllmillfion loops; ,K" A~a.lnl,w£i et ill.

956

Ell@1II!Indm' I'lo. ~;(~~IIiI"~. s~r,~$, aleop ofdl!!fr2!::1L5 ilf! ~10m c<J11fII dmlll~ ium
~~!~C!l:

~rll

one- di~,rUon.in<l1Foil,~ dl~p~nrdilllg,on tl;S'.~~Q; 15 < do:ubllek~rnbirnr'!oo

~rm ~~f)ch~!.iQlny ~~ l'e!$pect&e p. .•

"i!~

CONTENTS

o:mlilllu!E!d »

Science.
CEILL SIGNA.UNG Rheb Am1iillt~, llililirORby Aliltil:Q em,zllII,gl Its 977' II:I!lldll<g,enoll~, ,rnlil]l:iitor, I4KBP~8 s: :8€lJ,; ,il :M'a. ,Ai. Uu, x.. SJ1€'1l', .0: J. WDJJ:g.Y., Hu,. Y}inng N l!I~ri!!Ii1i~~ mil ~ n!9!wlill.Qr of edt g;m~~h ~m,ol[ilffiliiriMiltiion, bY' tun:) di5p1acil'!g~1'I ]~hibilor ~;!I'Ll'ie'reg1.l!<I!or'~ k!1~'~~ <Kli:v:i'~It~m!l ,~ s!'!'!l~ll !J~Ol!Q,oi!<;rn@ lirtpho~hirt~e·.

CONTENTS
M~CRDBIOL{){iV A Bliflilnmolllil'l. Si'l(terial PrOeliri Lilflk:s GI[1.11 914 lO'hjpla;~e:mil!m tID IR.abl Activ.atiion M'. ,~ Machnef ,(J',n'li ,R. it 15b,~[g T~l! jja,i:'t~riuiTlllli,ifI ,ea'u5tls L~iLDiliooin~' dis~B:S!E I~E()jIUJlsa,nD~tprorein toot ~9~~resW!Sidili ~ftiUid:iIli9Ilif niilnfridir.9! ~,@sl"'<'id:w~mg ~rD~ll!ifi,S.

~=- f'e~pmi¥f

p.. ')16

N EUFiOSC!l EN!CE

~'EPOIRTS CONTINUEO"SCIIENC E on:!1!!·mlimm5~:omd fa!;. Miglra,tiolfl

MlATEIRIALS ~I!IWI.e!ltab

,e,fVilttltm!l:y (ih~!iterrs '959

,L. ,N.. Mang~n~s,~t. il!. o A rainy i3Jdl1l fOi.ilnd olil~Y~FIne!urai, PI'Og~fJ:@r (t~is'calil be Fr'IrOnilOllool biy
NlMllspe!l:1Ii05,OOlP1ill1lMllIgl j;umoo~to 5howlh~t neumgem~·.si5;linllthl'l llil!lpoc"~IJ~ dI]U,~<IS~ Wi1h agQ.
~~ ~"'., ltozy p. 8'!!9

,MaJ!:[lli'!etTIlCII!I~ona!me ,S,pe:ctrciSc'e,pyll[dentine$; iProgtl!riW~ IGe'~I~s tJIil,e: ,Lijl!.r'i!: ~ U l1rt~nIB:raiff;l inl

t'IJ·(!:!:wal. 980

K i\f6,rwkow.,(l (lj1d $, J. Zill'k1e: OM,er.u<!bolils @r r.!dn!!!ti(med~T11O!£IE'!!.i !J,(Jldll(l'ii~ sI~,cw lh~~ clY~5~els"I

lao or mt!r<la !I.a(a!i'!oes

p. fJ]3

mlgral:e fOlsmr ~n'lOn,e dlmmsiO'n thaillasingltl!

'O'<),c.anqtclioes vI.!! iii r.mel om wa~k.

,,~ P~llp~e

IPLA.NETARY SCIENCE

W'id~Sipr~gdl M~!iiTIlh"g Dri~t~ (I!illiitai1l M. A'ddmlii'!:w.fcs, M'.~, ~ng. C. l.a~ltr~ I. dlt

'962
~r1tft

Illrrare~ lfI1iipp~liIgoi the< MrnrlO!ijigere or Sahl nn'smooiii i1'lita'i'l1 ~ugge$tsUnil't SiTIfliillllmelliarne drop~~lS, ~lfIail.f01i'1fIl 00,(111mm1l'l1if1'!i 1111:1llp m,~lIIimni~ qrd@ inM'I''''eJ~ilIlh~',al~IfIfI:DiSp,h!!:re ~udElm, aiild
EVOLUTmN

GEN'ETICS Sex·ll.ij'I!l~.d Gemetll: Il1Jnlil'~ibe Ollil CaJ,fie 985 lDe~,erJiJ1irnaillii:ol1J <I. Termite 1m y: ,Naya~hi, .N. J!.(l,. 1:1.. Mijl'Jta" ,0, K{l:oae A~igJii mil\nl or ~Qrlrrui~,~ '!os,!f!'rill! Iiffil:r!k:l!ror rcprod I!dilY~ '~Stl1Si p!ie'liiolij~ly thougilt ~o'boede~,anm~ n!!dsolely ~y efi!flro",me~tal, CiO.ndiliD~$, hM a CrUM::~l !1I~iielic oompollei'it.
;,.> Ne'ft. jrc,l)' p.. SIlO

PSYCH OlOGY

IFfli!:::li~lati1,V!l!Mii.t~ (il!u),i~' ri\i1ii5.Adaptive D

965

IHybrildiz.M:io.m K. 5. ~{'M'flig F~m!ii!1!~p~;d@rDot lo~ds 111~ nl!;lrt! ~ib~' lQ chooO~e' mll~f!~ilf ,~no!lii!!f sp~d~~wI'leili ~uehl:It!·h ....",iorm~')I'jnClri~oi!~ Qlhl?r~!ilg su~l MOl..EC1JLAFiIB~moG.Y 1f!,yp<!l'r1~ '(l~';lrJfI!J·A, L,,!>ioll!l!>ijeflleratedl i]illril"lg .Anticalnl(elrr 1iIreatmE'!fI'i: with (:ispka.til'l Iby DNA.IPolymer<lse 'Wi! 967

Mntli1lil~:iili( Fl!!!nctio:n .~~~~~ D!or~~lat:il:fal Pti1@frontaJl 987 (oHf!:ll.iin (C:ilftkt-llildl!!!(@idl Bli!iilaviofai AdJliIsm1@rr~ .f.. AI. M'(jI~5o.Uil~ M. t. B,lJrklq. K Tonaka D®~.li()<ti!J~Blai.prclrofitill r;t~iI:.IJlH rHJt a,nterior (fiJli9i!J1,IIl'l! (o~rn; .il; m
!:!'S'S~rnli.!lif;DJ [lJJllIm[~·i'nduo~d Bh~1l,1(ii]ral~diju b slmil!int

A\.,tlJr etat
A spediil!ii1,ec!. polllmE'lase slIa:essfl! ~f I!!! ptic,l!.es· d.armaged DMA :bI~ pa'~tial~y COli'l'lpo!1il~l1Img rOf disllmlon Oihllie Itoo!U;(IiJ!rodluc!oo b;r Ihe f

S H,C IiA L FE,A TlH~.1E

Managing a Productive Lalboliaito1lry

.~~rnii!g,ing Sd;e.rntM,u.
TOWill rrd a Phill®5Il\P,h'Y!ll~ I!1.ie!lO!I!n;ce alliloCig;e:m~mt M

las-ion.
BI~OC IHEM IISlFI.Y Glt'tAH:ik!!l: 'Stf,M:e~:1iY P(1~lrkJe'llid!l: O'ai!1! ~liritil'lti'(!r! fi!JliI t. (ill! ~'lal~, #m ,em::y,m.e In ,c.vanob:iM:~eria.~ll:at unexpe(l!oo Lit ",Is ,n·am 5~cleI~IIf:alnde:t:[Ji~~ aiild ,c:ala~es. de(ovboocrlalioUi Gillinbe ('Orsyn~lile!.:ls,of an a n~i(<JI'Wi!r poi\ykl'lide.

ill~~

l~AAAS
~'.J'~,",,,,,,,,,,~, ..~,g",~ooId,,,,d

~~'iHU'Il!o'!iIl,~~(!rJ..~1 ~ ,....[;Ioi!ilft""J;tiii~~, .. ;,q;l1l;;, 1ij!~'_illil~ijjjloir.1o:i 1r..lliiotl<lii ,l!.Dio<lii~iin, '~"~I<d'\o_~IOt~~CI!'1i!i :~~ N' .. ~ _ _, fl!1W;"",,~ngl~DI:,~IXi!I5"'~IciJ~EI;IiliII~ ~~If'lIi~b""I~, ~~6~' ~iiiI ~.W.tltHiIOli, I!t...,U/IUI;,wJ 'IN~"~ Ofl_ ~!II'O 2QO.t~I'ilI'~A.IWi!l!:.iltl'" rill IhMtnti"""'" ~~itrn'.I~f~!'iI!.i;;!~!,"1 ~I!i~ i~!M~i!I;~!I!!i~ Q;!.~. ~41i'ii:!!!!~i'!l! ~!;!,~d:!~~!~~,~~~~!'!<!!t!~ m~ en1!!••• H~,~ b ...h'l,n,~""'b&"'OiIk ~1iI~u~ ... l,~u!I.. '_'I!mn{!a.~J .. r."!l",p"'\l~"'I;O:.M..!o~, .i.~,rj",rN. f l~g~~ 1~~tL(ji'lii~"till"!r~u~!'dtL~ ~~!I. r.!.l,t ~~aJmil lliibl::i~ .ail~I~ib!lfiii,!HI.i~~ ~~r;:I.'~~~'I"~~rliii.ll"lt~ WJlIl:iI. '~m ""111111'. Q!;.~ .',12~0I~n~.l" !ilItl!I!!!i! cI.YIl t.. oI;lO~i!iiji!!l' Numb la~~ri:l4. .. !iIl[l,jC~ 'k, ~m~ ~uo· fO-'"p".!I.'"1I"""~"":!",,_I'Il~ Ioi!io-IRU,

:"i'iA

3·1)~/~post.,wnsum@r

Wlflnted on

n"",oddo""""","d,M~ ••• troJr1""ltiI"', 1\Jmo.,1i<I! ~s."d,...... ",oII,Orl<i!""I"nI5" '~',.ElJJ Mll'~'~"~b", DC.Z<m!iD-l5ill!l.:51¥,"'!':I' ..... ~ ~I~.o!! ~fit.f~ ~.., Ul'.«!Ii!~ !liiit ~ !iiil:o;ii'!I ...~t~~;'..!!!l'!tl!O! ~;;;!. il!y!foloi·iu,'I!it!!'1i I~~ !!O!!I!<Ii!!I!", Iii!;,'Oif~r.!iO!!~"~ "fiIJ!!r'~O.i"'~iK ~.~[I;~";.~I~. fill .... ~,,';';;'n;,d f~.~I¢'I.iiOI.' .. ,Ii".,,1od ""MASiJ fibr"1o!, .~o]"" ...... ''1ii''I''''d·.. ~li:ii.,efOjroOjllI CiIo.or •• ~ GftTllfl'ifttt;lfr."",IIlJuj, R"".utl) _:o:.p.,..m)Oj illllJ UUlJ'II'ff,l<'Iloloil f'!'i~II!"'Ii~'~w;..~~~R~_~I(Ii1Ot.~"" .. t!'..I,I,'t~~,u.;:.!!lt,IliiI01!NiQ!il;>1t~'~,br,Jfi!'!lo!i!lM'QI~1! ... ,.~~"o!i!!i~t;li~· ...t~~'frN4l,!;!~~·~!!'il!!;i.iI,~~WIi!!lIIi!ljI!ii!&rJ·~ .... !I'!.

r,ecycted p,aJp,er.

CONfENflS

o:m1illlu!E!d»

W\I\J"IN.sci:ernQetnflCIJg ..org

5CIIENOE

VOL 3~ B

9' NIOViE M BIEIR200.7

879'

-_lcience

NL NE
www.sdenQ€magl.org

SCIEINCE. NOW
wW;\I,.:sdence,flow.arg DAiLYNEWS CO\l'ER~G'E

Str~5,Painl .• anid Pllri!> tiI~tt:O:1iI .tt (.lm~i1ilrd (.l!iI~J;)lJit(If tj~ ~~'lity ~.(MiS~~ ~~al$ !I

c:ufi:oo s gencf.cr cilififcJ!oce if'! J!i!k~.

Robot Dleal[~5i:il
Ci!)~(i'rt!il ~!fl0\'!i

i!lfliinitv

~{Ir~~f~~

!Dg(~'!l~

Plilllil.tiilllg IRN'Aon tine: Fa rm

Moo~Yt1il1g(~1Op~ willI! ~maJIl RiM1i\5esn bea ~!lImcdrm' pests,

SCI E NCiE CAR:E !ERS

N!fl1l.scielm(&;;m~e[5,Or9 CARIEERRESOUI':.C5 fOR SClElfn5TS
%'.3

se- tMJi~mg ," Prn4iJctl~l.abo!!l'loqt~IllII'~~,.~~ IGWIBJl,l;

}. Aus;un

:S:P~iil!~ Fe~w~~l.ib

MilIllil"g,em,~(!t

s"[ieJ'i!L~tC;[l.~1r£r5olilers p,nme;rr", i~a llaiborr,at.ory.

'OJlIlJll\!li!l1l9~i!l9

p~opLe,md

~OUliCe!l

IGllQtBAL: I.aIU:g:~ltEM]11thE! [Lab W'I'IelFlliIsoom~e~~~ hmlona iii d'erIH mlifilolllt5ill!JilIlioiil!> al1!d 1l'1crea~e1pt'~rlUC.'Ii'Ol'i~.

I. s.. w1.mr. k

if! N'e,y[Clllla'~.Mi'9rMi'ol'l
C::, H. ,FtlW: and')., G. Poma'l.etfJs

Do cakwm rl.91lla15~oord'i1I:aile WleiUrolilail migWiillklll?

l1:

i!j

'" Nlmard ~
f: ill]

P,ER:S,PEC'l'~VE: rl!I[IlJb~il'llg~lin IlilitEir-.a:(,t]'Ii\ei ay to Mav@ W

.

~ H. Sa,no,.5. R:IC(},,;do,iii. ,lelilml!1nn ~ Border o~11suse Irm!JI~iple lifIerniulijs,!i1'6 ,t.o

~8'];al

(,ORelitWiI'! ,ufilit

Download

thl2

,[} ~IO>lj'EIlii

~ REVIEW~ IDli!!alRI~i.!latl~n ,~~IErndoth@llal~ ]un"olii~l ~ Penn@abiUty "" Y. A Komlllm~a,Cl.1.M'ehtQ; A. 8. M1JiI~k i IIllUlImmalmy Ill~di<lil'm: bolh diliflllpl: snd hellp ~e~ir't1lIe
~ E!iM'lllillE!!lii!ll.m,~IiiE!~.

~(itJ!l(~ Ipoo'"a~'tl.iil' tle.Ellf

ber .about.

...
IiJ

E!'ldd"a£la~<lC11C Iliign".ener:gy t:!Ml'I1(ic fa,y~!, Ih~ ~ 'illliV~~:ww!rn~~ Ciit WMM!IH~~ d'i:iXI,Slng, ~e i'J~)!.t t .MiliW$ illi~r L~ jIIdifil9 ~i~" afild! ii'ii:i!:ril!,
Th1!'!fW,$di!Iil"~.fNJ.GW<iIxiU!1po&.a!it.,m1il

6
~

e I!lI
Q

!li

-,

'

c 'e -_c
III

« :5p,e'edierV,eUow5t'one Up'lift
The niW~.o'W:s~olleul~.d:E!r,a h ti~,E! remllafl~ ,o~ '~:hrl@el giafl~
'E!!fUlptiOiU 641-0,000 ~a rsa go'. as WIllU as nl.lmeoo l!I ssma,IUIE!!f 'E!!rlJlp~~O:mlISplr~ol~ to 70,IOOOYE!!;u!I ,ago .e The: rlE!9'~ol1is s:till vs ~y,ac:tivean!l'il if!~pElil'ffie,mI,c:e:5rthql~,a ~e5, htlilt 'fIiollW, allmld ea >glrCH!If!d d'E!'for.m(!.t~:olill\l as WiI1!U as hydmtl~enn!i!l adhdty. (;,hi!I!f!:!:ii ef Qt, (p,. 95a~ I~r'esfn~ sate'i,lit'e rad!arandl 'gllobil!l

,(gjtc:lewi.ll lI!'!dlerwel1ta pe.ri~d orfact'eleluaJt'ed IWI pllii between 2011'4 aJnd 2006. ]'tIe' Iffillig"est Irall!e of !)ilbollDt , '~entffim'eb;!;rrs; per year ils mioH~~han~hlree~m!es·f.ast!erthdll'l upl~.ift:I'tlltes me<1s'ur'E!d!l;]ml(lE!~he 192,Qs. TI'l@ u~Uft may lleUect Olml,[,!ollmJl[lj
:maglmEl reci'lEl rgealrllolfluidl r,ediSJIJriib:lIlti,on,

,posiHonilml;91 saterme

l1Ile<aS!JIr emlenb
l

whkb sl~,OiliVth-~t the

IEnerg'izl,ng Cosmic Rays

CQSflJl"~ r,aJy;~areClll1le,rgdc p.:llftid~:s 'lFlQll ,iilf1i: aOCf1~~wClU!d by magll~tii(, fg~ldsill :tlpa,(;~" ,Ao 1;'Elry

1!10,fil!llli!lili:! ,ii!L~ ~m'I

I~r~r,eni!n~~'"O(1fl the- llin ominlg ~ly

$mtd~ frillct~omof the- ((;15m lc rays l!n iilt p~m~l'rat~

1~'~lnh'~ 1!~m~!Sphelre hal'!!'!: ueme,fldoi!!:i emn;,U'gies;. eix(eediiAg)~e!'l~o:~ {l. Be\( ls ]lOJIB ,el!eCU(l!f! EeV

\rohs). 11~ei~ ilJ'esenceis p~u~if!!J beceuse OOSW!i!ic

r~s shouitd lose 'energy veii'ij qlll~ck~,VQ!5.~hey

\!,!}lrigjt~Ofl ~,nmetih,al1€' ['elalilol\e Ihl!Jlifliid~ S Uy, 11:5,lIel~ ~sl!(l! wimldls,i3lrtd t.(I~O'g r,g:p~y. ThiJ~, \ .III1IQlrrm! driZ1!~e ~I~!Nid'esp~18d1i3ind may' ~!! time ing d!i)!iIllnlllani mechalilism ro~ r etl,llrlllin,g irormlliile
1

uibulero

that

s~cleof the

Le;a.d]m!QIhe~~~IP:herr,e. Whkhs!liJgg:ests dijYm",~ tempe'J'at~re glfad~'ef!ii;s !iiliii!Yi:QIiI~

if!! stilI!! ~f~ IlIsmis:s,iofl~IKb'l)ifl mflofosr:QIlo/ ObS~f~ vatiQJi!s Qfgoldltolll slPediilile!llsth~t co~tghi!ed ill 1!i:!I~gerl!..liflilb~r of l,I"alcalF!d~ end olils:e"l'ved \!'1a;'l!IfIq{ 10 (Ips. sholNiillg 10 Oisd~lat~1Y nt1otio:n, A prls1iI1~:tk~~igilli~ mobiil!€: vacan,cy.!lYlPe d'isl.occa(iof' IQ>Op ,cal'! s(pontlln.E!(IlliJsiy ua~5JiOI'l1!lIin~o a stark-

in:g falld,t!etraheOrO:I1.

,[lilmosplhern.L ,me;[llla,lIIe to~he !l;l!lrface.

tfal;l'el tlhrOlJgh :5:i!I:3Ic.e, alilld so these ffiI~gll1lest·

elille,rgy p-articies woumd no~.'lile~xpt&lioo to survi'Li'~ the jamlilley., Ui@ ''i'E!rre AllIIgelr ,c~m'aJboll'a;· tiol1l (p. 93:8,; see the (over ndi the lilIelN!> !>lolry by Clmlo) detected SO of hlil e futn :liIesl,·enlE!'rgy msmk g rays an d iocaledthlO'ir diredhmll lll1l 1111,~ by :'Sky comh':liIing two d:eiectlion ~e(hll1iqllles.The most ~mle,r'!leti( msm]( r<I,Y50 naie5ti:lU~tll(il ~Iy~mm miigi "Hei~ofnil·e ~kythat an~ po:pulaJt~d by lfilecuby a(lwe Qlaladic Iilui(lei. wWh th ern s:e1~'ie5 ~1'ilI.'OO !.iI,]laxy~nch Ir~ian~, liil alim~Lla@' th~ $u;l]~r~ glalaClic: ptilfl @. nus:~the cO!!l!'lltic fililj$' Ilflll!g;e en@r·· ~ gil~ migllht be expl~ine(j Ulh~y \!It,meiilt:c@I@'r.atf!'(i i.· d~,(ll!f!d gialflt ~ala,~,ic blad:. hol.e5; MllIg' With]n ~ 75 m,eg!alpgr~ecs o:f the· .!Milky 'Way,

Thrown for a

Strairtilng to llnderstand

Dislocation Loop
Elilild

Prien Diseases
~eI5·,
,Mi:lmlllldn pf~Qn dh>ea.Si~ iHI~ 11l1f.&tnou I.elliiiil'~. lle'lIJIrodegellieralwe d']!>oH~~n.5,,, ille pa~hoglenI1;( T agellilo~ Ipriolfl di;56ase5, i~tholugl1t to l~aid,

The Ifnn Qlncitlon l~e,hCi\!'im o~ llIlC<lmJie!> il'l~er5:litia~. d101lll~ fire or hmpQrt~n(~in I!i!nd~r~ 5taJllding radlsfinn

1~i:1llili1a,g(il ~~f;e-cUilli iitli!te',rralts a IlIdi meldhal'lic;a[

.~e~Qns€s, 'te ,alp,plij~d stJ'es5Ies

nlu.Jldeic "dds~bUilinsteadl r,e:li:l'!'S OJ! the p,Wp,. Ii'Q!lition ,of a, pa.tilo~ogi(al aJ'nfollfll,aJ~ii,Qn of lh@' p,r~Qfl [pJomin, alfl '~Ilidoglefllo~s gllyoo"
IP'r(lt~'in. 'C!1l~li!i!g:ill gllll:d CllilrkE! (p. 930) 1~e'view5Iel,!\eral~spect~ of ~ri~!'!dij:sf'" "

f!'a~eis\<irldudinlJ hocw prl:clflI

lbe 'geJ:le,f'ated

S~fa iriS ,Yill!

(5J~lhe~~e~
H~ I:ny :W'i~h), Arakawil ef ,(l!~, (p,9'56)sihow'that fou

!Morni ng ,Methane M,ist i m~lIl.

I

and m~iil1t~il!i1ed :lli'id $lJgges,~,p1 i!1iiodelriOf haw plrio~ ~rolP~g~~i(m iilill~olVE;S ,t~ gener;:aliol1 nf ta~k e in~~'rGTlediat~s.

Wfutellit the Ii1LI:i'f,ielll5:pJ"ob~ lami d\eCllonl it ~ dlf'Sc!Emdedthroug ~ dmu:ls of metlmi:lllleand ~ I.a.m:l,~ ena dalr:rnpsJl!lriace'INeUed hy fIlIe:ll~allle ~ mi!>1. li1llrgerr,~uvi<ll~ c~lIlrnn~ls "lugge.!>lth.a!t Titillil "s "!;\Iea~iIle:r IllIiIi!I.y ibeoollll@'.s:tormieri3llild lila!!!prompM d ~ the need 1m uililder!iti:lllidi ng {JIri~ alnn05phE!nic ~ m~thaJlliE!!vdes. A_ltal!!l1lkmriCi, etat. (p. 962, ( ~ pllJlbQi~~ ~ Illlijn~ O[tolllJen} u s;&i teu9'1itI11a,1 ~ 11 ~U!~~smp,l\'.s, to m11,P iljir5'!'S Mlliligfh"in~iI'arm ~ m~1i1laJl1i~ padllyin TitallJ'!lI~G~ertropo!5pilll!,n,~. o .

m·hol'l"derect loeps c[ln lIfl~gr,[lle el!flfn IiJmleif a. z.e,no·"lre:siS mn dlitio:FI. Motion ,ar'i5eslhiool:JgJh ~In,e Jmm'1l!tiolfl lof dOllbh~1 kil!ilks. i!lll'Id HlJduatiolfls. ~JlI their m.lm· be:rr dI11v@%l1h@ motioln O'r 1.0(1) '~@f~ru; ~h~ii[ d~f~u· ~~](mratE' d'epen.d~ol1 .he loop :;i2lei'.• Tlhe~~'olb~IN·' \,i'itk!'n~ h@lp dl rcc:~y c'onlfirll11i1 malifl}! .Q~ t~e~H~1S :aJSSoditli!dm~lhUl:e- mig ratio~ of raliJiatiaif'l" ililduce:dldefeirns an d1dlis~ocfltliol'l~ ~MiPS. IPrior
Si]iifiij~iailiioiil 's,t~d'i~$ha,v~ lilldiicatl!l!d itih,at smalll vac.af1iCY loops, wo~,dd 110~,i!f1defglo o!il€"d~!me;f'!~ l s·]on'a:l tam miglfatiQua fn l~ce"cefliL:ered(ubk mel!ll!ls. Mabulkgj'lmla,!ild :z!i!i!tt!1! (p.. 9~'9]!l)Jse

life and Death D,edsions

Hlow d 0 I(e~is; cletelrmi l'If'whie<li:J er to IlWe o:r die
alf~~nllli!p[ls;!lire 10 s:tre:5S[llrs ~h,i:lt calli

~e:rni s;folld· illig af ]~tr'flOl!~llJ[;ar I)ro~@!~ns;? et at. (I!: lLiln 94:~.) find that the ~RH siglll1lflllillllg Ibri1li1l:ch o~ ~he ul1Iol,dllffil :p'rotein IfI!liSpOIlS~ pltaJy~ tillk~ W~lj: llifl pra!IilIIO~,]mJ Icell !:.l:llfviv,al ,anew Ipr~U!'in mi ~fo~(!" g ingi n U:h~.~n{j.()plasmit H~tn bJilTlll{lEA}. IthJlm iimi (lJ

g il'he.S!~ sW(i~f!~rev~i3ilecllilii el~!,Hl~~loiJ:ds iillild = d~p~~ts be-low 15 knOilll!~te-f$ a,llt~~)L!d@alf!d

r.:dls shul oM IRE! 's,igna,Ung ,IlIUl!l!f pro[ong:e-d rnis;fold~,f!tgi!l ol'1dfliW~Q eoha!f!ce (Iell s!,l~viYaJl.
!;i~pfO~eiJil

~ m~hiJ!n;e- dnu~~ rD~~O!j\i .5 kl~orm~te;r$.Th~~ phe-

88:3

Donald Kenllied1~ lS~h~ ~flit{]r-]rJFCiIlt?r of ~iI'lOO,

THE .5Ci1lENlIFIIC COMMIlJIN ITY LOn A RIENIAIRIKABU:R:ESOU ReE WlnN WILLIAM 1T.G.Ol:[}IEN. for~J;;arn U~~ t['!..~Iil!~'~]" oflh~ Am~riCli!~ A~ooeeaJ;ioll fw U:\CAdlv;lJ'loome:nt ofSole:l'l_ce (AAAS) aJii'iiO!lg man:y o:ther t'lMn~'lj,I~S.~OOaway Ori 1 Ootob~r ohhi8: y~!: fulbc ~g.e 'Qf 9'1. BUl had a ~ujJ!mi:ng c[®~r. '1ii~1l Ol'iiitio:fLCdi alt O:!(;ljum:;:lw(j fth~ soi~:woo:~ ~.ovOO. and th('j pi;i'blie iiwt~rust p Q h1' ""htch he was S(J' ded!ica:~oo.U:e will be: missed f'Qr!n'!!Il)"rca~miJs. rlQl Ilea;!;'~bccalu:~e was a he rn:a.stn:yofkno~~ed.~ alndre>c@I.lecU.o.ll~bo1ijt S!c:t~IlCC aJlld p.lbl.ilC PQU~. 111e list ofld!$ {)Olil1Ill1Ulilni!]u:s is nOI men'!ly :~OI1ig;ifs '&111 o~h:igh spo.ts, :r:brl~;SJrf'<I Oenillll'j!" ~.C\"I~d.S a majoo- aJm]n.or1ItYOlm. the ~ds~!lry and pl:!lclticeofgi.ving SciiCllOC a(!,v[oc to ~1JiH~ gm'Clnmi0J1;t'. Hli.s US, book Scierloe .AcMat tD ,~h(t J'llsidem ''WaSrlIrrS't ~tublis~led by AM'S in~9.80! is mrw inits second P edilltioIru, and. is l',eql[ui1r~ .1:e:adi~lgform1f!yO:blI;eserioWilY~ntere'S.wdiJm,i!l;le emlfLt[On ef'seieece pollicy. Bi~~fIDrst dilPped :into personai. ~:lvo]ve.enl in scieaee rig~u9'ter his release ti'O!lfiiIll~lCdi'!,i\e wa:rllime N;fJ;'iIYseiIVijce, and he dki:JlIll ~o,p fer III nroment Imti,] his dem:h. rn.tseeill:lS~mfbto say tm.t the scientUfnic oomm~m~ty the mliteo Sm.~ in has: mLeVCT had ~ strang:;er or mOI:e resQ,lut.e snpporter. Bllitth,n~w()~]d1 IJJrnirn~rilyexdtl.de hisi~m,1pommce tCii]m,!:eil'll.lmiol,1<I~~ielil;ce, whicih he SCT\>etdl ~i'i *l][tip.~e\cVOiWs" iiIDIIlllongwhich two ilre especially S'ign~tl}c<illilt. ln the

ca[~y :~99 Os" 00 (';lltdb:iiished <!too, !:!efVOO'-ISthe o!;gan~i!'lCr ~t1d le~&J Qf~le C;'!n~gfuGv(J;~p. an :I1isoo<:iatioH O'fsc.i(;!f!O: OO;visenl,O'!!'!d mb:li8i:f;;rs·l:fro\m the G1 miwiOJ1is,.The-8¢ cnmJid sessieus ~,lrlda po~;iri,ve etfc(.;.1on sckll1tific coordit~tio:n a_m,~:mg toosccol,J!_mrles. <lllldi ~ooordingli() the hue Il A~~"HlI nifOlll~~:, f:OrIner :Sdc:l'IICt; A.dv~~ to P~Wcnt George, H. W. BMSi~. '~l(; Cm:me~(; Grol1jJ'1.&"Ould not h<):VJ;) istoo \'I.~U10l!!l6 (lIiOOn. ~

hilithe early ye.1M:~,oithe C~~~'t'O:n~Ml!n~ni!itnUU(HiIi .l3.iU(i~W the lmoCCI(ill for lUO:rc !il(l~e:nitifl(.':~n'llI!t~n the ncp~rl],l"Iellll!t af SUIte., snd with others, suceeeded in ma:mJ<I!glug iii :rent ~;hat: :~Ol on~y ~.'eq:lill.i:red his: p,erlH)li1IJilll ]ngentdty bu,t:cost h~m .so!mcthi.~g a:s \VeH. He pcrsuacl:ed 8ccret~I'Y oii; SUI'~eA[br~gl11te request: <Ii N.i1IltiQlI1IlI] ACfldem~es s~udy 0:1]1he r{i~C of science •.tf!!c~mo!ogy"<lind t heail:hilll,fQ:re[g~l <lJflfarnrs.. State <lind tfu,eAC3Jde:Nli1ies\NO~ed Hlgefi]llcr on Hli,c st.lItdy,. Bin p8ilid l'or ]it. Sel::rela!iY A~bl:ig]Dilace epicd, [t-s fi]Thd[ngs. <lind. erman Neureiter WJS alPPo]~.n:ed.<'liS: herr N sc,]e(llcc~<Idvi.ser. Tile pOiS~t~mll was <Ihisim.icfint B:I1Ild deserves to be nl:<ldep~n1:1iIJll~'nl. m\lfOu~:d. guess ~b:1I1Ihc'de-cpe-s.timpact o:fBi,M ~ vi.skm (;;Ulliile f100ut nlimu,gh his c:ha:irmlffl1sInip, with Jo~h.1!nJ1iI.lederOO:i!" ofl:oo C1Jimegie CmnliiW15!!lWIlI 01111 SdeIDlce,. Tecbnology, ;and GOlf-cmIJlent. ltwasthe brainditi[d QiflDaV]d~I'lmbll:~. preskruentof the Ci'lrne~e Cor~mtkm of New York 11:artllIJutgI~d <1! wiltegy :i'lOOiWI! cD~nl.issioo~ thllit llolll.go'.,-eum.e,11I:t gm-llpS. ihppmpriiiJ,t.e]yro]1J.ned <:Illd !il11IPPOO~d, eould lrn f~'iC a nali(lJi1:a.rn v,o;ic<;and <'Ll1infil!CflOe ~l ~e;'I:i1' <IS g~,t1l8 ~liOSie of b'KlUp8 fonned by S~'!femMe~n. his one had 3! m(':ffll1e~hipdU'n h'!C~u(licdfur!T!,C;!'Pr,estd~m: T OSirlC:lf and ,11 rester ef s,cicflt:hlt~.W1!iver8ity proflidellililS, lIlmdfOlflIUelf govermnent OffiCllds. ~1lit Most of !he ~I \vo~~a~, do_~e by 't~k for:ee(i~:;iigJili.idlO OFt! pW1:ie1!ll~r pr,ob!emg" We'U ever aJ dO;.o~l :fiI;"po;r~ \;,;,i:!'e prodUced; tI:w;y sit Oi~ ~y shelf arid ai'L:: u~fijl etl()ug1~ th~tt 1 gtiliil,gc~:siO!!Wllly ~b." to U~I'i1. Bi!l~~f~\I()\ril~. 1,w:g ~ilJiC~y fln::lt of ~l~se:l Sc£eiJce (INil Trx:Jl'floJog;)l ij~V.s. !;iJet7i,a!1fJiw.IAjJiti:NI, 'd'iC I"]C \ii{Ilot~roll~lbre"l\'(irdw.11l LoocribllIg ,find! cl~~rl.y b~t~ghittile re[pQrtilmll) pl~a,t(he begil'l1iiiing ofhfs eltbr~:'to,illiect:!icieW!cep:olicy ~ltO irI.c .Dep.lIrim~ll!t'QfSmte, :1Llo YOlllsee a ,ce~mhlilipsneru he:re? Go! dell y,;oul(1 di'5QO¥er ill pl.'OffiJ.iel1il, and i.1 it \wsi]iffilmrlam e:rloagh.he goun carlystart~ cIK·aiDng.1UJS~1ices mlcl'er'l1!!1rich l!iis p~n for OO!cfu.·es.<>ingt oouldgalnl i some CI\ooibl11itiy.later •.tJrn:atp]a:n eould 11m1!ererred to aSffii1Iel1f1lbl.fngdllCu..el!nt inthe Iflliht~o.gra])}hy Of.lIll offl,C;~1l sru,d(y 0]11tffiIle problem. llffurther sh:ldtes:we~.e needed,.iI!l.1.ey~ru~d gel done, perl1liiilips tboong%a,Bi.lrsf:i,lmnci,ru. as "",\e~1m ~mdlect!!tR:1 giJls~ Tlme afte:'r 'lime, wI.lell he saw a real lneed,. he t'mrruJ ill \V''''Y to fill lit. V!.'ha,t mm,e;poJa,ph!

'''''Q~

W\J\Mi'.sci:ernQeIFlflClg ..org

5CIIENOE

VOL 3~B

9' NIOViE M BIEIR 200.7

IEIDITH) BV GILBE.RT G-IIIN' A NIl) JAKE YEST(H',JI

BWCIHIIUHn

Threefimes Two ls Six

PhotClsl(!ilimeti'!l: ol~ga!'l~smstalke a~ivaJnlta!J'~ I)~ ;QJ!i!1 !lltl'~mdg!i!()e o~ !i!'II~~,gen, by it1ori!'!!:i it' as 3!r911I'!ill!l~ <1!'iIh~~eS'i,~ ctiffi!l! (lO!lIta'lll!ls a I! !li.itrog ~n"lu~ch 'glllaJii id~,~i urn '9rfHiJp), :iii fI~gld'i~i!Uiilthat h: !:aJtal~Yl~d bey th,!)!,dim.ewic plil;lte;illl N'~(I~IS~lI)fta!lll~te kiin,as,!)! (~Jl\GI()~,aJ!II 'M~m~ th'a~ is:" !1!(I~ 'S1!Irprisi!:lgIV. s'~b~!)!ct tCl f~~db!'!(k i!i!hffibiti'E).!il by'a~gi!i!llf!e, Pil proteins ar~ orne 'Ilfthe: I;len~rraillill~lbo@lk coo,~di'l'la~ors·cHffca uilb~li'l' and nitmglf'liI i~~a.u:'e5; prl)~ifll is ,a Ihalm a:trimelrr .md has beensin,oll'lln this pre 1iiiou '!ily ta, lIIeglu'late' am mOlilii.. in'~ll.u:intm~etls, by [1lI.5'ertiingits 11"' temp ililito lliI'e cyto,iJlll:5mk ve:stlilllllile of the~riimeriic ,ammonia d'ilailll,nlel; 'too mimi'! Oif 81 gaod thiiilllg: tillil be h8izanloulsro o:me':s addIJba!H~ eqfllilfib~iilllm.,. Uliu!'!' et 01: c:le.s()~~ib!1!! !ltfllctllllfil~fll1d blm:l~ellTlkal swdi es or the ililtel~lc:tilOl'I be1wOO'IiIIPandl NIA.GK in 'tilfJe! qIIal'lobtld':ell1iiu.n1f1 5ynem!Dwc,U'}". ilt~y s!fJ,o,wthat alt@lral1lfl'· II ,erl1:t:I~II~. '{.allJrinrirullr,eil' dim!lll1i) of NA,GK B sfillilaiWidi:edl bya IP~ r o~ Pllb;ilmelllll~ ~(lthtllt QBm oil' tliie :si.~P!l :subulilits m.tL'Iiles.fl re'll\~rsill~e mma m~.erin;9 aoom &010 P.~witha ~ingl~e N'AGK. ,SLlib~iIIi,l EiiiC:!liNM!K mmeriiSorieillt:e(iiii"t!fi1ii .!llillgl:!!: to, ~liie pli'iill,e of the' rilfig, iil~ilfi th~ bla:d,e:sofili I PfOjpe~,~EM. i)lliIdlth,e billl din 91'oil'Pl~ilil('r'~ii.sles~1ii'1! .aJlt9le ~Iiglhtly. lihe! aJ~lilllin;~·billildiiliig ~ites ~re IDcarted Mith~ hllllen~llmer slJ!lffCi~e$. !fiilld til~ti IIIg th,!!:! !dhfIflersallildl iIIlteilf IiIgtlleilrrterdimtf CQnIai'~.I[·ed1Y!cesth ebJlrrdlllig aIi!lltity fQf liugi 1iI]1l!! Iby lSr~oI"dllhilt~k€:it:; dffir«t;io~ibitil;):fi! ,of ~he amlifnQ~i~(bif'lml!l. the: effe:a of P!l ibirldil'll!jl en NAGK, th.c:Jl!gh a1sOr!n~d'iated il'l lali'ge: pgn by th~ 'i I~ClOjli'f Ie:n;tirely ~!IIdii~,taliil~ dbt!liilt ~roJlilllb~thtbe' (:~lyth:aliildl gJLl,(lS1~ricS]te5, ~. G]C iis iPfiOC. No<~l,A{al1'. Sa U.SA.lO~I176!l.$ (200n

D e'(I'~.hby

(0 nsu

m p t~ a,n

IR~,1!JlatolY T n,~g) rel~S:('jrDnllilill,lre kl c:omm!i3!nd alte:tnliOliliinrhe mind~ ,o~ ]liI1mUll'lIOl(lgi:~t.s,l!ilot l.e-'as~IIbBCilUseltJ eomerna ni!sm s by wlhklill ~ey eil:lffl ~he:~,~ ~li!lpprle-ssi"e ,effu,cts, rr;e;malilila:Ib~(I!n·e. Am] Ol!lglh (l,liIe pO!!1snbmuy 1illlli OIl T ~oelh Iparr aly.z·e llalllliUlillar [111 ~(itij(lll1l$ ~,n eniOOOlr 'i' cells •.Pi!llliidily<l lI1I et ,rill: prr,eslml evlld BIiICJe l~ frj' Gil 1m :star'lfethe~ r tlfmt ~argets 10 deaflh. WiHl!mJ ~lh~ :Mel types o'r T 'ooll~ w@r~ p:l~c::edlill
ClIUilJr~ t09l~11'1!efj

imlpo!il>il ntf,acttnr. (@Il d'lNlll1 Iby 'qlt.o~:n~ with" d fillllllalw~s (Olfltro[~ed by ~iiluace'~Il.!i~~r l~e,(niil~orS.• S!I[l(:ln al' the' p.f(I':3popl1otk I]r,@te!in Bim.. ~'!IId(lim" d erir;iefllt re5!pr:)nde~ T celis wer~: aiMe ,to ~e1:ist 5!uppmes5iOiil by li~qjceU$, (l(Wkii~ ecol'1:su ifl"!pliol'l b'yT'~[I aefui. MiS abm ri(lu~d '1.:0 Mod: pathogeffiik T cells iili! 11 mouse c!Qliili5 1TfI:od'el,mggle!>ting tilalt l~~s mernaniislill rnig!~l be Inoildly nlrl:ro!;'I,IIooil"l r~glLllating pro.;inlaimlillil"tory1r eells, - SJS Mat J.mm.ul'llJ!l 18, 13'5] {2007}.
OI[.Mi.5TRV

al~p~ndoo~U!o'i!'!itia1U!r$ ~liIIdl(lf1l!E!-'tv!\!) 1I"'lidr.Pi1 o~ ~efhraJt,jve~ to .ea,dh chain 'iUi! a sampie of C!,oryti!!::: addlaO'YI~.!i!ilijd'e oopotY!iiIil err.1fheyU:! e~ e~lPo5~cl a & $U n'ace ~'umJcticula~lizl~ with bi,otin 'In i~;trlis seim 5i fig ~ pO~Yfillier' <lind d ~~e<too :l!vidil1,·biol]1il bin diilil!')1 by ~
<if

Fro III !Pa~hoge,rmto PoLy 11Iler?

Diagl'!io~iJ1g dt5e~s~s: \IK!'l!l ~d 'ideaUy 'efiltQl~l

add ilng aqllJefiu ~ a.crylate ll1o.lilIQ rnler"!],and ijlrlrad~!il,t· ~ ing ~he sa n1lple.swith 1m lilirllV'iirDl.elll:g h~!.o 11il dLlce ~ ~ po~.ymeriz!i3&ill:m w~er,e ~~e lnmaJtm:s wer,e beu IiId, :z .A.10-minrirr8Jdiiat:ioo '1i1Tfl:~ W'<JS suHiidienrt to pro~ dU(I~vJ 51 lJ~ewtm~~ppolylfrller spots en sam pll~ ~ . ~ (i(Dnitallrring fI:5 IeI(!' ill) 1000 'biotin ~iil't'5: ill II ft'JlIlQm;e ~everalomer5 olr magnitude: .lfIlme sen ~ ~ !litiv!!! tniiuiIalill!lmYlfll.J8r"bla~ied lIISStI!j illliP~jl'lrdtothe: ~ !lame: 'S!I'ljt@~Jt ~ ll5Y ~ N~'!',Mafef. lO.1033r!i'lmai~2(1!i'12 ~2,Q01. •

)s

s
!
~. G
~
~

the ~ffe(l~r'(a.~SiCl (a~~edlhe

rt:5~'oli1cle'r)! C[)~~' 11' c~l~ pOPIll ~ailion elfreiil,tlUally I,IIffiidlennellil! dI~.i!lt~i'll iii 1Iil![iin" Iller rem]li!~s(eirll ofltJli!lt ssen !i'III"IBrI T cell~s,iiIlre' lep:rilled of cyI.okililie!S,. It. d !!!rI'Ilerge-d ~hat IiiI e Trl1>!l o~~:s WeIf\e mn5l11mill1lQllile' glrilJli'lith r~'[mr intJefle~kin 2 (1Il-·2).and pos:siblly' (JllfuJer q(~(lI!Ji'liIes ilIS!M!'~l. This; depte;tlioPii ilwe,ned to a,p e\I'.at~ onW:,rwn em! ~Ih,~ 'twa tyPlB OIrCde4:~'5 W~ffi ~In dose p.J;'Q:.;iiiriilly, S:~~lg~.s,tlllilg ail the biili'imli;:)~ 111 bf!'Meeli!th~ :SYpipty of 5~oreted o;Wkilllll'.s ,ilFi·(i~he \!'orad(n.!!sllle:sS ofth:~ Tf~ c~~Is;mig hil ile illl'I

~im·lP~e,a:~kl,ine~pe~sive tests Witlit! r b~th leiigl'l se'J1'5Hi'lri'ty :3i'i1dhigh 5:lPecfrricity,

o ~e 'lIi'idicly a.pp~ieda

[ELL

arut o

G'I'

pproaWail. the m~le·oul~r leve~ hi;!:;";beeWIthe ~n:zym~·

Frem IFat to flJs~(,u~

Inldiiabet'eS, tilpiid dro,~~et.s (iilfti Qiflien be 5leeDll to i!I(CU mu late: 'i lilI m Imsde8Jl'ld Uverr !(lens. The e.:dellilt to winkhilill dilvnidlmi!ll. iipid d rrQpl:Btsilnl:e'J"il(~ withilll ~he: is not ve,ry lWe~llJlIiidler!>~ood. 130'5tlliiml etol. des(.niJ.e h IJrW.5~dlllililtri31£Enutalr Upi,d dr'Op~ilItst1l1"1 gmwmthin il, ceUL by UI~ fusion Ijrinrdi'll'idu8ll d rop~elts; ~hi:~ mE!rg ~lng ni5 promoted b:l!' wlililpla.n~nt~o:f ~h'f1 ]lIUrilU~~lJ'lar '!I~i(lJ!' r~sialn m.adfJ~,nery,li\ihi'~1ii au 1:!lIll·,tltilIT biOWli'i as ~Ih~mc'I'~i:!Lar mf!'d'nat.o~:s· ofU'aii1s~on veside f~si Oililwitlh tn@irta~g~~limlt!'ilrlbl[aiH~S.

ce~~.

Unl~ed ]lllllJlll,llrllO$or1berul i3iSS'ay{~LlSA.'l, in '

whfdh an i!llliJti~e:nJa:s..,odated !i\ln~tr.th:e di!;e:iil~ei5inldlm(edt(l bind with an <JfilliiJ,ooy lI;ttcc:hed ~n a lilI elll!ZY,rnle.Am bstrateis the'n added th ill ~h e enl!:y.lfIl~ t1l1l1 m:Gldilry toO lllnd~ il \:'i,;ib~e 1[~POIlS@, such illi n!Jolres(em.~. rm qu ali1ti~kiilli(],fI.lln sOllie cases, :liIowE':.I'elr, EILISAscalni be'()Olilflplk:amd toim~I@IilI(!lTtaind lifI~na1 ,of'l"er ttl@' mquisite ~ll'n:5ltiy:jlly. Sf~€li eJ' at p'f~S!E!ntal ilrornis!!'ilg p'~Um~il1~ry ~tp~Cl!'alio:Fi ,f o alnl .i3iltlffn!;jUi\i~,alp,~rOill::fuJ, iII1whidlii ~Ifi~ lenl~~ iiS

(en

~.
o;i
Iij

~
~

I
1il
~

rr'~p~aJc:ed by " sVmJth~~c j;!hotQgniUator ~rfr!E!'~ r,aJdlkalIPOl\ylilfu;ri'zatig:l'I, SpedfkaU~,. t~e aut~ors

VOL 3.18 SCliErNICE,

lipId drop.I~,ts,

we ~'e'~iSQ~a~~d ·cdril1 actiof!a:tio'~ iii m! d Shlrlfllfl to ~ by

r~lJfIII fibFQbl>as-t

cdts·]~(uhur'f!'

g
~

"} NOVcMBE.R :~007

'WYIfIN"sol)enoomOlg,org

EDITORS1CHIO~CE

[Q,l1Iiaffin $e\!'e~<1.1. pmleilll

s, ilnclll!ld~ I1"Igm·erJll bers o~

o~ lifielillttHi3Jn~ fm;]on

01 U'lISTR'I'

the "l(N:::d.e,g SNAAIE.r8Jmily

fmnt.eili1 s, Illni!lln1l!,slIY or lipid dr:op~et ]II:1siOl1Ji I] lMl1g (ell~.r the kirllockdow,1iI cd lipid-dmpMaS5oci1l!te,a SNIlIR:h ['edili (jed th·!! n ulII1I!J;e,r (lir fUi~ilOrlI~VlmlS ,(lb.sI.'l'II1,I~ctllbyl!IIp to 15~~.tlirlh~r·· f more, 'in I1nlusd~ ce[rs;, ti1~ C:i(HJi~tin 9 o~ Oil tl of th~ S!NA[RE), Sf1IlAP23.,tcl ~ipi;(i d'ropl@!l1i{fo!' ex;a,mp!~,by' g,t! a~iilg ~1Iicfea~sjlflg iil,mOUilrUS of the f',aU'!fadd 'oleic il!icid~1 may Ipla~ ,3, r-olle iiillthe dleV~D iJm~fil o,fi il!sll l]ifiI f~:slist:.1i Illydhl'ert]1Ii1::i iii(~ th~ :S!NA~~ from it'S !,!(jflir'iailfll!iiidio'li! ~f!ddl,!!,ler~ ~ll'Ig gh.i (~lsetrgl'l:$J,~olrter's; b;l tih,ecell 51,1~'a~e ~'I!'I r re'5l,pOlllse toinSlIlUI:l. - :SMJII Not Cr:liBwl. 91.1286 Cl.OO1i,
II'H'f!iIC.iIi

IP~(kwngl artners P
lh~ 1~'I!1ctliticm[F~str.1IitE!g~:~s for
!liyll1lhE!~,]lil!ilgl cempLe); Ofglalnrit: IfIiIO~(\\CUi~eos irE:llle-d ][[a ~a,fg~ pari!: on a 1~€epEtf!]rra g 1~!idel'Stall d]~glof ~Ih~ I~.ati~·~~cticfl

~,aJte~~~:~ne~:sul~UydbUeriili gr~ fl(l!J10n a~.gi~OOpS;. Ra1:iO!l!gll ass~mlJ[:y'of larger, sl!,~ramoltll'cl!t~r $;~~i(lcti!!res" hiCh are held 'log elihel'bv a:~~~~)J or w a .Iii!!o!iI'~ov,!lter'!t i~~.er~OliQns. is Iii!!)Wp,'l'Qc~din:~ ,aJb)!Iii!!:lI.Qj s;i~~ll~r(Oillr~S!e,wi~hpredicti'\!'e iP,rind;j#le:s
le;Jlle;!'ging from ca~dl,llt ~ys~unatJi( :swdies:. ln tfuJis vein, .Aakero;y efal: hlllw~ ,~.:>:plmed thif' (omIK'Lijtion bEtwe'enl i1ydmfJelill <lndl ~i!I~ogen oolilldiilllgin the eacrY:S~iil.~t':zalio!il Qf5evel'al !maW i!llrOITl'Citic buiM~lI1g ltD 1000. One (ryj!taUili!~ 119,parlll1ell' mn -, tallned tWOI n ~tIrogen s~tes (pyr1iidinl1' and be Iillilililidam~.e)!, Ba.dil ofw,hidn ml!lld pOltimliaJ~[li"act as all al(cJep'tor ~oW1llm eUh er iii pG]!~i3i1ii"11N'j 1i'I:;drogem or tI, hal~og;lm" 'Tille:do~orr ,palrlirrl~'MS@\lim bore an oxime' (CIH""NOH)groul~, w~idi Wiljldin1!er~c~: tilirOiJgl1 1~1tl1J~rliie (.J,H orth:~ I[)·ilfl :5iJ1.~,.1'JIS~U as iii UUIIr

Atom Gyroscopes
We~~rreis,11riall~ ~I!ffid to
(DIfiII p;aS~

r~ad~i'i,gs,~Ji'ic:~~ng l!~:i:t:a us, or IIiIII Cliff< U nmffiltly ]1IiI a di:9itili~forli1ll!1l1 hom g:looallPositliol1 ~
f!ng ~y~t~rns. IFor~h~ U~S

get Olll~' ooalrill1l~S

fmlflll

of '~tl!il~i~.E::S..owibiting

~e~,esc:O'IJ'iB,. probes; na¥iig'ilIi'i~g t~rough deep ,~n:d $p.cl~e, t~~ 'Sty-$t~lifIsof ,ho,]ce tD pO'ln t th!i! way {H,e:

lfin~,b!romli~e.oriodintl' $u1DstiliJ!£:fit,p,ois,e-d (iCilf hltog)en: ~oli1d rJii!g., C!y,st:aL~oglrii!phy oov·~ ~~dih,a!t

in aU t~n;le (Ocry~tats, the' ben,zJimklg~o~e ~ r!ormedan HIben d whlhl\he o,dme OH, I~ ~ihe~~
,llIfid IBlr~;su'bstihJ'ledl sy-stems. t~e p'Y'ridl~file N ,~[lra(~ed: the (~H!1l rollJp;.'(mj~yil1lhe lodo C-ase did a .hallogieflb~iild 'r!orfil'li nstel1!d. ~. ]is,'~:' JAlm. Chm;r, SilJC. 129. lQ 102 ]Ij:1!0732(1k
(20(7). OIIHI'iISllR'I(

Slagle!; of IGrowth
,Ma ny ]rrIlport'il~~ (ilt11~11.i'W .are ~ompiO.~oo Or5~p.po:li1:ed n1rl!l~lQ~aJIopariffides. AJthougn )(~,]y n ,alJoofptiiD!iISP@CIJiO$(iopy ~a:s be100 u:sedIOpr1l~IJl~ l~eimpac:t o:~IJliirdcl.esii!eand $!1ape 001 'chemica~ ~'~Cli~ty, ~~:isdlif~Cl![ltcl ~l(~a cl~!'IfCIrma!lio:n beyo~dllhe n~s,t few ~o(l~diflatioflls~ e~1s.and there 'is: 11 r is.': ~~lh 'th]5,too1:miql;l~ IJif r~dialioil1i d~ma-ge to 'I~e .s;i1!lilI1p1'~.Cl:1ypa:s.,~t,(fI. show i[I1,~t~~ m:(lI'1:i" I t~in~g theL':ha~!:le f~ paIr ,di·skiblJ'l1ol'1 fUillctions: ham the "l(aUe,r1l11gl of we.ak~~ lIbs«hed (all1d "I,lS
1IfI~liIirnCiU1fdamag~rag) ~igh-e'lillerr9Y x-rays, fl1l~'

b~I$OO01nl! ,yroSCg!p~s a\UI~~e,~ ~~'ll~ g di~Mim~ re(i. g

S~1IIrr.T@ sitlildy P!'ledldl(1I1!S of g~ne~a:L mel.a· SYU'l ,~<'S ,rll"a Ill'te d!~a.g:gil'!g/~he dfec~s Off

~ e~eflce

~ tivity
:whkh

!i'I\CIulci e' seen '~I:;:;tUig$ o:nthie rotaJt~OI1l a:d~ h ~ olr~he glyr(]i5, 1lI~gill s.e'IiI~itnvily or the gyrosmpes ~ 'k! rot:atio.lI1I is a pl~Efequ ~i5~:Ii~,. ~hi~O!Jnt.e\!:t IIIi1 ~ atom illlt!:~ffe~Qmeters:c.m ~mpast5 ,liIilechllfllicCil iE g(yrOSiwpes 'Dr o.piticail. in1l8rferrmlflte1t.err:5, y Otrdlet~ b ~ or IiIiItI;gll1itutd~" Wu ,e\t .r:Jl. r'li'porit (llI1Itlhl~ deve'l!op· ment o'~<II I[(JM·\i!~oll!lli nterfe rrlom~te~in wmkh ,til

'ca,n 'bad: th~ groMh oJ f[il IDlaI1l0p'llUlic.~e5wiih lilTll.~"Iley :'lru!1i~I~IIIDIereQur!I!.i:on ,0'1" F\lC~t, 5aJPPI1l:li1iedi OJ) mcln]!JIm diloxidie, ,at ~NIIpermJ!!Ire5 hom 100f'tu 2(1'1]11'(.Hm PiIi·( I. mm~la,tiolil$ diemJ:tIsea ' linBfl~~,ywilh time withool ailil~!!'IdlJdion period,
SllJgg~Jjtlilmgliliil!lth~ ftffiI'Ud:h.'l1li!!j Ino~~lllt0t:at~l~~~i)[;, t ;a!S·I1~ Il~!ffil Si~11 'r<Df IP1~-t:s:p6.dies 1If! so~tJiI!i:oo.Data!

~ mll~Jte>rW!iiW

or Rbfl:tOIlfl!i

l!lj, ~51PUtmJh\'{)rWl~h ]

~ bo-th iii al.'te~ ~ll\nt i'llrou n:d op'p;Os;it~ p'1'I1~ r(\\p ~t· ~ ~ edly and: iJr'Ci'i!i~hl t(jg~the:f €igaiiii 'to p~ijdijce alii '" ~!l'it~rflflfi!liiic~ jja.tlhmlil. The lilli~se 51i tti ~ S:!iims;itN:~

loollm&! d:!!nlru~the :~~fII~liIgp@r]oo nw@a['lliIt'I :s!lilm.lli1 tliie dom]m!lIllf1t Ipro'e,~shom reQuellan o'f 'lliii~ "".iO;i;iS (!to !lJi'iaike 'i~(jta!too rmeLa[.a~Qm:s· :siiIlI ai~l. or Idt~s~e~s~,ralPid! growlh '~r sij~t~ri!1 91, iil ~dfi!,!g:lly ·t~!
riP(:r! ~!,!gof ilie la rge,~ dU:Siter~,~ MS.~ J:Am (J'lem, 'sillI'. U9,.lO.lO.21t~076<'l~;71i1
(lODf),

ii,;jwthe
Q

rotaJtHOIii lth ~ ~I!lt'li:rlie~orne-~~r.- '[iSO' e

Ph~ Rev.£..~H.99!.lJ32~Ja!. (20(l7~.

~~I~II.I.I~-rolt!,f ElE:Pilla''I'IE/orfiOIR.13

1)c~1'!~'dI(:ell_n~j'
M. Iili'::!tlftind
IU'tlSI!illolii!iA.

~~!t; uw~

pug LI'JII~~ MtIIl, !.t$rll)ol!r

I:)i~MI''''l ~I!UO~Mornal II!:,"~D!lb

J!ifI~t!!,

I!IJ.!.V!~~
I'uLl'lUiMENrSTsm!!5 .!!MD' 'UI'i!I_OItIl

I~ih

~Cinl!~

Iltrniliiii 1:., hIIliii

BlplWi!1

ii,:~~

(I!U!!~Qf!!li!n

:1~OO Ut!w'YoIit Ai.iien1J~ til'll WiuN:i'igmij, Dti!~

l!dilOOa~2f1:e32li~~~, WOO2>2iM"~S~2 ~: ~:":]~U~~t.m:!G~c:n14~,~'

i!ah!nuJI lill'iilH" 82418 Hi~ilrIRoMiI '~mbriil:ge:. !JIK ClIIZ !li1Jll! +4~ ill» l!2:n ~2~s,oo. ~:A.'(""ot~, to) 2L~,~~ .~,MMI
SU~~MM~I!IS~lII1i!m F-'~J ~~,,~gl) ,!!!Idlr~~. !!li~~fIc9l i~~~!i, 11M (If iJitim, iii~tI f(!iii'!I'Il~b. ~i'i~ jiiilJiOO~1 qU>l!5tloo~:~,6~iI!~4~ t2:ni') fjf ~2"~2~~~4n, f\I'J;);.~~4i~24,m~_.~ilillgl ad~~~s;:~, .~.Gl B:ru:.~~·WI, ~1'II~hil1[!1'1.On.. 200'l'IH],1!11 {)IA.A!l.5M~I!~5!lrvi(1!!,

roo~lfork~ll~. rIlM \'iIaslJl~!ltcJm, OC WOOS IIiUil1lJ,1101l1.n ~~r~ Llnlli~i ~,l.ea~~~~Ll2112"1~iIl,·.:l,:l'5~ lor .iln~ qUil'~Hl!!l~f !:n!iIl! !1'!~:t!~!"! ~ . 1200
1!:1f~1!!I:I;:: A'Ynlor

m:

(o1i:frIm~t·rl~ l'n~wln'f!S ilal·j~S~'·4!lJiS

!~'!lU~r!~~ e-oH~~-nU

!,:!:R!jj:l'l!ii)"~~@B~~r~n4.. iI'~X~w:~a,{),etlL~~
1II.Ji!1U_~ RIim! ,MN, cmliine

~~·L!.a~~!"~.~~t~~~DiIo~I~~.«i~lrn~· 5lJm~

~ 1frl!\!-el~: Il;~tc~!l ~,p~lIll'fpp!tgitkli.:ll; 626.2. prianIry.'(jd~ FAA],ltl!I,;

In:!lUliim,~~ 'W/MN_ ~IULoOII.

~~~~~~!~
'i'1H~r~,~"fit
~DOCnD:if

uol

!'!Jbllclii~~~ !\'irn,c~h~~ctnJ!lli'rrnl.

UililiU EJ:i,li11t ~Ilillill' 1)_ .!>2mmm~ ~U1tU EllIolilli~ !lI!Wi!!~I,II'~JtUI~~ ~l"I1l'ti1!l ]I[lhill~~, 1~:"!ln.l!~!'1l,T'~eb 1[ll<!!;g~'T~~v1~ fI_!l'fNtlU~ID, (~ll[ll Ailiot Ii:mM·G'fb~ l\ Cldn" li'ollIlm,]', H1m~; 1iI11I; ~n~ L<I'l'II~. ~l1rilOli 1fio!J~ ~~ttMllIl.Ml!t:imTim 1~~~DI..l lIliula.A. Kibm~ 1JHa,1on(l, t.m ~ [;Mill! ~T(I[iJ]m!~,!J.l'\I!ilyll. F'i!Jrrnl; llB!rt~~ ~~ ijy(;' ~!!1'~!!\:U!!o!lh,.ij, Jto,1~,~~!!. "'~ilVlfll.Q!'!. ~:lV!d W~s;' jjlU<SIJiI~5<I ~hEJtm)[J{ll!l "'!lin 1lt:01.ll1l1~UI.!i,'I~N~UH1!)A: Dd)(IJ~1h Il!hoer~,· ~DI)IMoE EIlfiIIIIi:~!!ak~ 5.. 'I'es:~il;. l~ur'~III!\, l:ahn. O.MUII~ IEIIIWI:S;~alri. :iffl~ ~~l:Itd;~~~r;l;ll~ fl!Utll>p., ~I!!~~ i[lli!JI:J!III1)!I~ ~lnl!!'1 'Ii: ~~MIQ~ W<~I~ .~c~ QI!"I.Ij~ iUl!!!il't!, ~l)~rt ~r'lld~ri~k.1\l,~ S. N!il1il,11li~ I~!! RM'.ii.!l(l["UlUi.lI'~ Mikh~tJ L~~uil!'.II!!'!,i~~ T~Nlil!'l'; ~1rt.UJlJ,I,uiMif!jm I;Wlmn!Nlt~lltrm~l'!I L Sliita; ,1i&'I0000i!JJIllIlfl~!IUI! JIl'nllritK ~m~; I'iJkd~ Nididl:;Gn, f~riilill'l/'(..;;~l17Iin;~'H'I~JiI!1i' lillt 1!f_~M,_II[!I'U,iIIIl!!l ~~III"!!ItJljLIAlUL!.GEIt Tai:e;!ilIIIl!IIl. tOOl!!\! m.~Ii!i]i!'Ilr·1!!f IE,[ook (ylliDia Car,iIl ~!I'!VI!l!:C~¥b!l;~!oc!,i,T'!! £m.mt.!:~11SM!lII~r; !!\Ui!lln!f,c,!!!Jln~~·.lo~m . 1'10'1\1:, H~r~ JiKll, ~~li~r~ ~; Ordrr~.1i"IiIl~ W-1l!!iD:ne~; IllDJn:ttI ,~'(!r:s.; IUHflIIIUlll'U(iEll5I)III1J1I.W~it~rr; 'torr ~lli5Q~ fn~h<!fd;oIMJIIlI~Mli I l:aullln Iollinoc, fell!r 1i'ic(IJ'I!!l'idl?j 1lII11l1RJ1JiLUII!tIlr.lL!.ll}lIS: (ilm~nl K)II!\ "~~Q!"!,,l,mMl,~!IIneW!~~ it M~IY ~Ie~ !': 1:!1'I',~e)',A!h~~ Ch'.!mdler. ~~~tl' Sl!i~lcb; ~l!~~:!!I, ~!I,wn P.illf!'!~tQli!!.i!l~ EI'op. Ch:r!~ Il'lard~ lil!'ililh,.Wmd}'Wiii!'; IrmlI1IiMlIlo.Jl.lil MlIIIKERIMi"r.iOOI'.IoGtIi 1NI1mly fiI~~lruu •. iIDi ~. (jli'Jl!l~ ICrffily Hcrrrrr" U!i.l.1011n:Klll, ·S!!cti.1>'ill~ Toll:Y ~tlJr~; ~!I!If>!l ~;liKII,J.'!1I!l .~.~~!'!irll)f Re,~'1!!I: "J:.QrJI!ICilll!)lm;~ Rillmrt·oo; i'!rimlflil]i[lJ!'. tlrnitll Wi,n~. E"mMJiI.!..W1l'1'.!IIIl~ Emily 'G:UBe:, 5iiitiatii!i'l!titigOO ~i~~~ IW~ :f,liMillwB fiMi~Ha~n~f~tI: ~m I[Kj[i;J;iit "Mrf>d~ ~"'Jl~!c" Jerrmlr~r]l" S('i~'lt; Ul);liIIMI,ilMo_ Sltftl~:s, KtlIt~r'~i Ij!.!.u~mcmlt T(JITI RyiIJlI.:· ~5Ul1_1 ~11~~ [dr,;;,;ii!l.~!!.IID mm'O.III;~ . .~UlI!'In..IliE!.\!lilQilMaI¥l~ "Iad'nd II!M(C M~!)Q~ O>o~!~n-'l.Iq!.!!o€dlflllIK~~ r.!!!r~)'l!le:..~1!!~,~f!~ H a.!~n:ll, Mi~ :::!JiliCl~ U!!:i!U'P'>I!!l!Dbm }JUri Mill"; 'mm IfII!lIQlI'!i!M: ~b~'11 "'lrIm~Smilli, ~hi II; If:soli!ikfidli!; tlllJrn!)~I( 1111.~DlA! ilL!i!liI.6ll1J lhafu,~tltr [oootll. Elitlt ~1:!It~nl, Jtltr,~ ,P/,l,Iems, L,~Ii~ R-cibnJil.; (~l!fI1nllm!ll6 ~ rrm~!l; I~·~l~~'~'!~' iri~t!l, S~yt!l~r: ~!t1,~' ~iI!lI!1!Pi li!i! ~mllkt Elii:aIN:!!t1 CuLott.a, Poofll,~ 51111l11lll!ll; NE!'!~ _11M 'tiiudhiji! SI,!mf,gld; ~~IlIlIIIR. ~1;tiWU(lI\Itll!l ~:~m".u.r mU!2f }ilDI!S;;' II'll!lloDlII:J.lQII !l1m,"J(i~~{jJ\ ,Mrlan IOhQ. jtlflil1flH COIIllnl, ['uMd Grimm. C.~II~nc(' il'HiliWlffi Nii{h:elelliDlh~illlln. Kimiu!~y n5!~~ Hddm,ia(l!lyn 1K:alser, IlIHhardA, Kerr, E~ ~n~~h... Andw.ii' La"ilIt'I!f;(r!.l1!ili Jlrft,f;rn5lll~ DI~~CJU'llKit1!_~J;Jj'U1E1 EliU.MaIi!l'll I~n~!!andl<,t;ll~MlI~~{,~~r,jjtw:1I1p"'t!ln~. f.!:Oerl. r. S(:mtt IJ>~['~ N!Vi.~, IiriK Sllll:~l.ai!l~mlEU] Benjamin! I.I!ster; '1iD~11RlI!!IIlllI>(mru'H'(lIIIII!!tII'i "'R!II:~lII,~ 'l11i~'n(e.....il!ih'~rtl~irn~@i!l1laUlP!l!t (~A5!lI!;~ iii st'1)M~OIl:liIl~ l'Q,u·~!l'ltlll~IMii.rrill~ Ol(l.;!-30!~-~~~IZ;,i.lI~~f! Flj~~ ~:nlilil;Nil~r!i~ ~1)'.1l i!:ilpr~ lilfl (Q1i!~fl~" ~!Ii), 'CJiJ:, ~r~J :~rbr!r,Arm ~bI1e1l5, IWbrilUnQn, MIt.:iH Wlit', CMI~~(. M.lrnn,IEltljoil ~]';J1iI~~ (l~Il)rTilul)~ 33Q-.1lIl~-mWj I'A._~ ~3e<-Il~S"}OU; W1ifl~~:I'il!fl. 'WWIiI j:co~ _ ~t!I!roltli !b~~~1Curr;!J~, H:od<l ~ fElla~II.M(iIIli~ IG~ili~9; 'l'bUI"I!I~ ~SIil·m,·22611; U!i.1m.!.SL'I_o,lU!i£llj,(hrnmphm :81l!!Ii:n:!l;1'j)· ~1;i]jntiliijjjiiJ~~n~S(htif~I~~MMk" ~]jni~ G~ti!ilfl: l~iij~cNro :l12-tO:Ho. fAA ~4~-!i~2~,3,~; ~!oI!I~tt;O~W!~ !.:\1~'-~IILe ,i'leld: +II <! ~nglla~d: ~7~49·?l!!S~, .Soall DiiI!lJD, o.i. ~\6M'''2·'l:f52.,F~ 7.ro. ~0 1~23·32~5-2:4;. fM '1"4>'1 ~) 122:~-] 25,5.'1,2; lJIiIM ru.~1l;jo
~~'ilIiILIlI5ll~EII~li5Mli'

!)mWllK!r.slIi~@alilal-,(lI9l OI!:I{Jj)~. W~~r! IMI.W; ~I:!ml"'~ U.~~r.Ii M.lm,":;o~ ~,~!!iHliil; '~~!lI!U:!'!~ l [au rle Boi!ru. LiiCl)'oi! .(iHi~1!i; l.<J't~nd ill [liirmofd; '!;IMrl LI~t!1llt lil';'1J1,

~~r!I~~I;

~.QHt.~-l?q(l

"C'rt~ SOOS4~.~'~'O!r ,,· .. n~~~T;. I ep!l~: Ill1p~' c'. c(l]ttoc~-'C{lm'pgIJi,iiILootn.!llt!! ~ntWI)r ,8; :5'milihUf~ lJl!u taint!'! 8(l). ~2,4f-'l~; :5~b.ar~\lIP ~flI'!1riim 20~1~~~:t7; '!,lip ,Pl\iIM~ .!'ielill'ibl!!i
I'!ltf!l(w.w;~fjm~fbM:r,(oQIT'Ii'd:!I'I'II.\!'IitlDib:.lilm~ WlK .6!:fJ~llliJ.: AAAs Ii'K!irnlli!len.iiD3 ;t'iU·3l!iil¥iU' 1If1'I'MWiiilamernbw.(lJ\!j' :~i~IJ[)J!:.edit8rs@~<Iti ..oI'!l1 1I'1If gm~JaI !iilliDnai '~Imle§:) !.IC!?I]t!I!:_II!Ih!I!1@\!l!iilli.llrij Ifmr~;urll"il:!i; ~bo lit l~ti!tlr5~ '>Ii!!1X~~~@iIiIiISc.o'!l1 ~umiJ:ljm~~u!!l!lipttli"'l!'."(';Ifll' iili~1KlI! ~~J!I!oniriWlilill!'AI1!l If'nt 10000 r~",if!I\Jqll~ncl hJb~ih!!!l ~ lb~.wn(\lkilli ~[j\1ti~n flJlr IlieMl~n~~mmt:Df Stie[!;~ ~ S~~ :s.:1Im '!C~!l:'l!dMtI.,~ wr~m far 1]1>!ip!'e'itf!taijO!'i ~nd discrmi'lln llil imJ!lOCI01III:ism~ I\I!lal(;lj ~1I1.h1! ud:"~n(>J!niIellt ms;:ieJl'OI!', Intluillng i!1~ Iflf~~fI'I:~Iti!!" vi rniOOl:rit:r 'ilIr (Qi'I!III"':lliQ point:, ,rJ 'l'lffl

,r~

i1liREtlrOiliin6lal1dl)',: ~BIIi~ltlWol_1t ~lld(r ~. Shilmle ~,I~T,I;I!~.i.\I:!!*li,E~ Reb~~;11 ~~!ri; I~~!!I'I; ,y,~~mil<!Y ~r~ 'Ch.ri~ ~1'ilI'I>Dt!l; lI\[[itl.!lIU :5;lIT~' i:,:ul!Elio; IhliruQt~ Q~l)~~ ~ri~ 11k lDfl'Ip~n!l";IWoIiIiER~rlU~ ~ieg,1~r;'lmloil!Bll_eMlIiIjil:~ .Alir riU~'!'IQ".Kelty l~ud<:ll~il ~n~~: .!&!i$(HiII-!'Il ","' fIIQ!:It>t AaI<Jcn iIMr~ IItw!.fttil\OMOrrl~IBll~eI. ~1l!3r1n!l'SU1Iif1;n!f,~~"wo~ HolIJ Bh'hQIlI, La ura (~!2ljlli!l'. Iilr~~n Hu!!y., N'a.:romi J!:e.viti~!Jala.. .~iQ(j[l;T~,~m(Ol, ,'Af'k!!l~ ~ 1!H"""'~t!TQi\'~~~~' il!.t~!!!
.5!f.t.E';II-a'lhIllElltiMtA"IllilM AIL

cfo!jfJibrt~!",ill
'I'j~~

_~I!$~_
(OJ
!ifl!~~. ~fl

il>il~n~f:l Sljjjlfl~

~3~~~ ~9!lr!!.~~ +~'1 (Q}

ssus :~Oij~l;~!"l~~

~fI:!en'! ~O~-~~6-6A~(I
.',nl!<'l~.. rg}; lilli, ~6'~~lr1ilEltir ~ ""~~ .-.Z,e!;r-6:r~~ '1!!II~OliS~

'~!!I!"!I~ 1111I 'n:g:

,~lUrnUllMJlm'ESU'_n ...

A!11~~1iIi~lr •. ~~~-:il;::~~Sl'.:
6~l~,; ~.~I11I1!!.l.:!iil·Tgll~

ElmyUAnd~nc

20i1::·li!:~.ilii5~3;

U~IJoIIM!:!'U'"

1!01tT.ji~s!~~

!itiDtubi~I:: ~&.;!C~~:iil-~$~:); 1~1l!)I,~OO~~il~uEllib FQa[d,.

:H"Aub; 2g.b-$l~·615 77;Mlr~T

n~lIliI1S:~Q'H:;::~
Itoha[l

N'idl~l~s

~1#j)~I'tlC~~nU:@:Rien~C"~nl'ICo.u'l:)' IC!IIC!i!!i,I,;!!!I1jiYM'li!~QL W!!.~!ll' ~iEIIlI!I~IEINOOII'I!IIt!l';[,[1J:i',rs]I~~a.~~rmk;rrnll' 1,i1'lP'~nbril"lk; jj1~!i)tE~rr,P5; 'Camlfne .A<Jtr~ :~t~lb, M, Hlunl!t:y; 12r! $. ~borlil!:. ~1r,IPIrM ~I rnjl:!.on·, f\ttt~f ~~n'rlt m{!(¥.H Itaim JQ~III1~ &!~r: NII,tll<tllL !IIJ.~HI(l~ rk!OOlllh D.J!'nmimn, R.ach:el. Roll.ertl;. AUi(e

~mlu.!!.ndlllM',MI_·!Iu~dlen,

I.

E:dmon!101!, S!1irl.q''eo!.ln:,!); iil,1U!!Qf.(lMii!li MUSM',Q,i;GlI~ Tf-'l)' !iHilrntl: 4'l:~. (Ill} n:23 ~H5;2S; 'FAt-I'M ~O~ U2!l ~2!liH2;:w.l:!i~~liiullm ii!~1ld~, ~~ I'-ilhlle-r; )!.~e'~~!l!lr,\l. :S~f~tl'!tt: :IotUo!;ll ~1,~Ul!~ lAlullie Il'kl~r,~;iAMJI]iiOOlIl'I~n.n;akloot. "*81 (1US ~ 157 5300. fl!i.hi!llll:Jio 52
')'~~ 5~'~~.;~II!lMl~!1!!: il!l:O!>yg]:!!~ O!!!l""~!il'IiiI, 1I,l,1!.l'l:~1Ii [!I~lb!lHiI!lt

l;!I~r~Il~[l

i!looptej f!'Ill:i!:~Q1~'!lAm Whii:~~j}~'!l!.iih!lf~~r~~~~l~, AA.Mw~ r~u[>!ltd :~8 :lim in~a.!j)ar3~d in 'lii!7,~,i!i~ ~l! mlW!l~ I~ ~ ~rellIielH~and umaeoollt,hr'OCI!l"IHJ~lhm'll'lJrhlrDrll'e Ibene:l1ld i!JU pKlpfl:!, Tloo'!joois Dfifr~~oo1lll:n :ilr!!tJj;Jmll!'r{'OlmiIUhiurIiDlial'OO~ !l!'i@llt11ts, '~Il:!li~HJj~ ~h~' ~~il::fI1l\"'!ll('eiIlttrtl1ll~(!JJ2iI HI!IJI~(lnln !.lriEllCl! iI nd .~ i!,p'~~mrn5< 1I[{]11IIIm H~ I(!5JlOO5iH~'oondu:laiid use 'of !l:Iei'lft arull~~~b~ t4i~1M t!IiU~lon ~m lId~~ Mid '~~h~lc:gy rl!!
~1t!~~(!rl:l!i: _J}DnJl!',;cn~_elfu~ ~nce ,ilJoo!«h ndi~!\lIlfI\j\III[~ ~]Jd idr,asIlnK'" Mfl:ill'l!~ p.libl~ ]j!Jtlc~ndn[! i!'I!iI ~~i~la1i!M il!r~ltlnal ~l!!:I ~[(IJ. flJ)1i!g;;!!11!!l w'~fIlI!'!~!l ~YP,II!!I!"f.tlftbll~[1JIil! ~~~~~er!~pr.iH!',
liN UI~;rt~110~

~'tI!ub~i5hin9 ,on:1y ,111IOlJ~[.DIl'I'II!lio:h ~'~~~5lH hilS ~etE'fI rca@1~d,llirol f>!iilnjl', <l,I~ ~rtl)d~ ~llb~~l\tldi ill Sl1l!:~:ft='iJ1lclllidln~ E'di1~1i~1l;. ~~~'~~!lffim!mt ,~~~ r'~~ ~n~ ,~fI~r~t

~'* !II(! 'IndWidui!l~~nheautlia~anilln(/ldfKli:!I~lt!sial'~

If!ih~!c:'J~ tI!!l~~Ij.~! •• ~L"!'(I'.I!!~~!l~t (lC!!'!er!t'I,J'l!I. ir!1IItl:; !1m!!:;EI.iY)~E 1i~llnlrn.lTruJdm Trill'!§.; DEI1IJIII'~El'llu_lIlJalli~ C~Ji!I; U!lIrilI81J11i116 tU,Wi._IW mrh\i!~ EI:!i~~r ~""ri~,lIoh.nIlmimnOm (Vifjll'l,a)" ] iIIillr~'n ~n,sru1~k (t!r:n~IM-~m~MIi j>~I1Is.), Gf~ldem ~d (~rLln); IIIWI EIi'la1l.e1fJ Quinl
AD,~~ilII Oflirf; A1e~ C~pOlilriQn.. i~k.Q I5lilokil.\. p·Li!i1b Tatn,ufol. 1M!3, Htilll~li ..·dlfl" Lllu~ku<, Oiakai"lih~ fi52ia, 5.4l!.~6, lall'lln; ",Bh lO:'~il~ZIlZ ~;zn• ,+i~l. ·~lGH;Z7l; IIC1l >iii I .If,~r.__; ~~ ~~" IHl'I_ itktra,irl SI~n ~ (EI!'ijing: i~!J)n(l@iI8a:; .. r>g , (moirl!:illlIUllill6 o _lJ!!iilG:Utllllrt! ~~lIoi~ tjllrmi!~ I]OillMn~ .r.~li IWi) j .3391 ,!;I,~(I, FJiil{ &lM 3 5'!l!ll6 jf>~1; dlt~!m;I~D'I,oom); H~ l{i~ ~lNa:+ 86 (Gl 1.0 ,(,307 ~:iI,39 ~J 16M" 3~Y iI'A:t:. ,*,il~~m,~ 1[0 630~ ,'B5,9,:

'f'OI!'l~k1A~;
IilaTd(a~I!e<;

UiiltJ_~ ,*gli<jj~'iION i:l\I)(~l!.ili~~ UlIll{l~ 111!.!imf II~OO(lW;lE [l]ri~llilii!'

•.J~i~'~!I~'.1II11'I' Ll!1ln~o!.l~
.MAS

R'tl~ni B!lld:.. A'ff\1l H~II.: ~IIB·U(iI;ll"liI~

~1vI Po. Hddroen; Il'!'i.I!IIDllliFtLlJ:rllilil~], ~C:lIIh.I; u~u~ I!)~'l'ir!~ .Shii!'ll'; OI~f !!m:Urm '[)FiFl~E11,,\Ii!j"J lli!~h!ller; IMID .[IIr~h~ I. 'E_ !lX!~lmg, l~n~ W,I~~QIJ1!-t:Su~t!1M. ~rtlpm~(k. AI!" G.nt. Lin>ll~ 1', Ill. Kaiiltrl, (h~rli7A. ~rlily. ThCl1lluliL PUliilrn. KillilrllPlll. .Sftllivilli
IIl[11j~ ~fIDII~fmlllinnllllll, ~~~lIirtf~Il."HiIJ'"

fiUl!l!liOif ~

~bllfill~~

.r~

au

!i1"lr:!yJJoo'@!!Irni!il-i'll.r:r.tl;r!'!l~ B!!~!ilIS!!!!Iih
211.96;pfb~Ilii@~~H~m)' ,

~iI:

M'l~}

1'1 22n
.'

1F-a'II, Aum,HO.'5, 'lJf

S~e IPi!J~~~ 1.~ ~.nd~2:1

!,he !~ Jl!!~I,!~1i)t' ~Ji)(!)l!UY~ ~r ~:(>!l~~, n~i~I'!::nOilm~.o~!!mC\IJtU!i!'l(olrtliil1ll~ohrOI!'lM !ini'!l~

~.. Iii;:) ~ng,

@n.1rib!]1iin.g"Q!IfI~~

. !1ll:).~".\I~il.c~1!'!l

"} NOVcMBE.R :~007

VOL 3-18

SCliEI'NICE,

'ItVYII"IN"solienoomillg.org

IEIDIHD

ElY (ONSTA~(E

HCHDU4

M!1iI1l !Hooll::iiml9!'~xp;re)SioWl iilllld unr'e'al (OCl!t to~ro:r-i!IS WBU.as the fad:thatUll~lwo IphotO$III!I(ru'~ tray ~;aclly Ith~ :same< tiig ~r but dfif(lereV1t1ly IP~Sg~cf!i~dl ro~i;~Q1~ thfuaki(s mo:fie' lik~l.y Uliat :!iOmie--

ene IPla!ilitec g (~~dboowd t~g:e'.r ~!iIi

the· b~5hes:. f~ ,Dezhi, a b()t~f1,ts:t aUhe Chinese Ali:ademyor Sdel1 e,es;, adds tIiI~~ p$il~ts th~' are l1!()too scale im)relation to,the
tiga, .Lhou" whl(JIWil~p,aid
2Q,(lI}I)Yl:lil ffii ~.::)2 6) fllr'~he M iI'fll1llg)f!'S, ~ays~ "I ,gIJCJra"~ee with mrj' heild~hiilllhe plim,~oglr;[lph~

of rllJ~11bullfl'i3 s 5lill. 30 (1m b@'~CiW' I01fDg:4.erm gver.1.Ig:~•. Bo~ts ilr(lJr'~~~lIlg lfie 'on: mud, Iiodk~ IH'~lPokin~ n:D~h~mJ butt iIIiirr, 9 ,1.IniJ r~~1i! ~rm~lfl d !alk@sicie ri'~~row~J'5 art iln w.a!Khing the,jr lilffl'lr]ll:!oodsdry ~p. SOm(!faJC:ltar:51illal tl~la]f!I U!'~I1TU;:SS: Till Ii! ~~r" 'fact;'! t~iillIp,~f~t~re()'r the lak'e has mYS;IJef'io~ sty ~i:r;iN1Il1·,5qC$~fiCe' 19'18-fWioe as: f~Sl'Q;'!l t~e'~e~p,erah!lre' Qif the' $l,Ilrif(ll:lndin:g .~ir, I~e,

,aJfl~r selle'ralweeks

whkh b!<!dt] ~v.~p(1t(alioil, bes be(~i~e ral~ (I~ .sl.Ji~erriQI',.and IP~ooiiPbtiCl!'l has: dr:oPlPoo lScm ,[II ¥el:lr 'r'fOlll1lltle allilfiILJa!~a'!le rrage of eml.

are ilulhenJtk."

Ra.,r@~Tigr Photo Fl.aIP e M.a~e5;Fur Fly iln China

The Sin i:ldin~i FOITe5tr},' lE5mea.l:I ]5 pllShin glatliL~tj.(~ w:ilI:li1 !l1~aIni5; ather[,or o~gll1 )ur'iJley iii mdllll ti;glem r~~@rr\lE!."It'stre1illlerril' dlom;ly e\!:,ojilin 9' 111E!W:5,.if ~t1:G'lni Ilile~l:I bs~amrti;atedr ~ saJV.stiger fl!!~P'LNt Gary Kc~h~~r O!rw.alsh~llgtQmI

I~u~. big pictl!Jre relililail'lS Illmdeam, flH~ ~We knew ~0IiY it'5 haplPenJing, bl!JUihe whyI d!on't klmow, ~ays hl{cirlDliOgiist Cyntl1ia 5~linger " ,oBne N<I1:ional Oc!E!'1I11ilkiDutl1illllil1l()(5:pAeric i Adminis;lJaliiofi. One Ire-:a:soo" experil:s say. is tli1at ,driliIl'ClIt@. modlet5 <lreDil't Vllry~ood til predidiiliBg: '9r'eenMlu~e ·eHilK;1S 11'1l!:giQlllii~. S~fI~e$. r

decl~areditOln~v
ing

j;I

~p31per ~,:ge~"aHerr5lCnJlin1il~

the UWlOg1,i'ailabre images, A~ih(llli!lJ1il tne5:~ec:~~ has beem) docLgred

eid:il:l(~ " re·p~lrrI30w tigiE!J <lLij¥iiL1l'in

loo~ for hal~ SP1l!1!r;lS Of :ica!t~ ~Of9 e~e'lk.ll!eri~,catkln.

stale's 1D,e-Pi!riJ!r1,ent: ,(If' IFls<h @nd WHd[]feo fS·d~Il('f. 7 Septmlb.er;p. 1312), Ii!!i'!l!t ~',~st ey ~e~to "'!h

A~a:fboo It'!illIn(lh.l~il: 10,0 00 thri'l~'s; as, (Mn ,a,~(j h'iUTII1lI11 ha:tr tarns ~(jd~iQ ~\i'esiil'!tol !IfM.!sic,aOlij'il'r;i ~ike ad ny IraQj)!), ~iilth~:s, il1!1!!l.ge ~1IY li!iQes

~he iUlfliversity

ildlded'~!tal~l[I by I~eseal'dilers

Cl~1 Ci1'ltih~mj~,. Ir'l,!ijrle.

at

'1f1lm.Ltlioolally

(he h~lIi'l¥f.ore5;~OO Qiflil'i31.MouI'ItaJirni s: pmrm~~ted 9t1aJ;anXii ofilia"l!> to o~f'e!r <I reward ~o alll.Y'One able
1.0 phatogHl.ph ,Ollie (jrthe~!llgerrs ..

tean Timesfor La ke IIIp erio r

.s

AM rr,adiio W.!f;I'les (~lI5<e 'nlhe '~I[I~ 00 vnl~fill~ Iih'ena:n~lerlrk fie~d forC!es: e!r&trn:IiI~i1,a.t ·i~,a.!iI etedri!:alCIJr·
mNit-OI!Jt.l1r Us :liiIP.The (lJrrent diete'C:i5lfuie ""j'b 'a~iollis, UlIIilvBrtjlllg. t'he w.al'iJle1; ~o"iOIJIlil d. TI~i!!; 1IfIoliithin NuJl'o ,r.e;Uers" Peter B~rk'e (lind C'htnistopher I~iutherglen Ireport us~ng~he delili ce '~a tlra.f1~l1IfIilm lisic:!I'lI1Tfles5ly il ~mo)t iii 1ITIe'ter hom frflilPlod to tl. $peakerr. Sdell~]!i1!5. .are lillldinilQi tfui!lll ri!lldioh~q,LU~IIl(f:~) are W'fU:-sUlite:d to .!iI1a 1iI~plilatinQ1 llil.JiI01ltl~l~H;i2!~d parts, h.lll1lliu~r lopiIlnil1g ~pn~w hl!J'IfiZOfli5 T~ f1anlol:~hno~ogiY,

At

iI 12

15~,ouI.Zlh'N1gIo1i191,.

~a;!Jdfenrn 0'[ mrs quest to pihGtngraph the bee5,t" ~ Gr;:I,'I\IllhilQIto wUh]mJ :20 ll!Iel>ers of o,liIe ,and snap'" iJ,l:l'IgU l1ililoilg.es. Wmul!1II 't:~m~r.l·.snaslmwoot ~Ih~ ~ ~mt ths ~.ilgfMrGilIr~ il1i1dl !~~~!l!Iilp;ealr,OOI. SOlidI. Il@i 2l i!!I :S;k,~tic~~ dtkilJ fact(M'$ SI.fOO as tille' t~g~(s !!l

O(rob~r press m.nWer,e;fliOE1 Xiillrl, in ill forme-.f 1rn1lWltelr~ t.old <I; Irap~

This f.i:I~l.,l!he WilitN lewl of '~..ke· S'I!Ij}E!rim, the IWOr~d'sla,mgest heshw.a.ter lake, dipped below ~he IT,ecom U5~. ~1iI~'~ D,u5!tIBOM days (!If ]1'9ti6. II.ASeptefllber. Ilhe lSil[}sqlU.aJ~·kil~om~1!er rnalkeoliltlile C'iillliladillllil bon:lf1'r Wil) lilt nit!) Ioii\!e~l sinre mwrd~Ji:@~ping 00g8~]~ lB6O=rolilh ~f1 ,ai'l.!'t\rlflg@ dlejpl]f( of 183 mli!l:~(s. OCi!ob@(s; le~l W~l'It Ui~

~
~I

1:11

~I
i:I!l,

~I
~ "! ~ ~ ~ ~ .... ~
e :E :Ii

~I
'" :5
5!
lz=.

f2 ~

... ,.,
If: Q

C1I1!lllld<li, kI IfilJew Mle:KiciO-HIild! fmlll'lslII bi31d:driOp r,or~he Ilewly A bliei:l~Jhtalkililgl pallil'Ora1iTllii win gr,eelvi~mLor.5 to tilil,e (i3Im~gileIW!uselilrlfll Na~m.allIH~ls~ll,ryin Pittsburgh, IIfIlenWl:5'1I'lvanill,~hentine 'l(lO-ymrrm.ouln~e.dl~l(e~e:l.mll'"in till e h .. ,~i., ~llilcJhjdilll'lg iI1I gi1ialnt ::>CLUropod dI~fendillig old DilrlOi.5l1li1r IHa~~. reope-Iil~ IlIIi1 :116 NIJ'OI'lemVerralFt.elr <Ii lelilg1:1il¥ B~ 1iTllU,- her balby fmml an attackllm9! AUr}5'li7l1fuS. "Ug~Yes. O'UIlI Selil:fie (4 iOn!;!' Y l~im:J r,eMva~ijGm.(jreJlI~f.l;~ y artlsts R:al!l·~~ Wi:lU~S; i:lliuiTe:5li II(l:MinlligelF b (j ri'lllil1lll~ffi' da y 150 1ltl,~Ui(D :yf<tlf:'i a:g 0\.~ liil)lS (,lJIra~or Zhfl-X.i L UIO. n of PliIiI.ade;tp,h]a, the: l!ft!!lraJl M.re~(h~5,55 m~lerrs ~r lW0 walls am.d: lr5 "'E\I\erYlI~inlg I~oo~ SIO r'!ail." Wabeno alfid I<!tssin9'ef iii re iNolDItil'llg Oil ;1(, ,405 me~~r.5~nglh. Ili~. '~pi(flj, d ffilllhe ]ulril5i5k MoIll'~.~o!1!Ifmmil,tiolll or '5ernJ1l,[j m ura~, of the l!ll!~ iCr·etO'lGf'OUS P~'nim:l.f@r dll1!olh er ~OI~.l~hdJtWiIW W!ll':n~rrl NQrth Ai!lIiI!!;rr~uc......:whktl sU~~(1fI @:5 ~ Rllfil Sa:Sik,,,td@,w.t.i:n., o~~nJro@'X~ Y@ilrf.

at

me

~ o
~.:s.c~ell1oemagi,org:

SCilENCE VOL318

9 NOVEMlBER2007

EIO~if'ED 8V'WDHIUT

IBHATirA CHAIR JU:

DUI! .AIN [Ii iii HIE ¥O!I.IINI'G. l'he~RO:Yi!ll Nether] O'D1Ids cademy of Alilis: and A SC~e]miCe:s (KNAW) has elected ~lS ym.lJJil!estpr"esi!d,cont ever. Striril,g Ih!::oJi'~,stRob:l\;Iert Dijkgr,1I1lf.41. p:ro:rIlii,ges to ~:lel'p rejuvenate ~1mle :~99 ye:ar",okI1l.c<ldcmy andtuen it ~nl:o:<IfQnlllm~or dc4D1;rute~s lIJOOl1!l science <lind socilety. Th~lei'l.dll(.;r of a biSh.;p]ton~.e Si1l:uP ait the IJ l!iijvernlty '01' A~rut~r\IDmn,D.ij~~nnAf is best know'niili1, his own cO~]iIIlry:tiS~lPirolific new~p~peTc'ol;liim~d!'lt,. ,orH~d \'i'i'i~r, :!iind TV gue:d wl'iO hOils :~Ottl,g
z

ch<MniJ'iQ:l1!ed~,,!(l f.gilJS~ ~f~i:e~~tific ~~~ernc'Y' C Hehas ~~~O <1'!dd~sscd ~h(; lf~dk ofsdcllQC edili.lca,t:ionin Dutd~ dcmC:I1!tflIJ sc:hQQls•.EI'(,)I: ]~l:Sta:ll~., he sWlen!tS(J!!'!i!C Qftl'!e Spi~Ji)z.:aJ,Pri~e ~~om,}y he \'i'Q~~ in 200311(,) 8Ct up a; Wr;:bs]t:ewi!i:ere stJ!jde.~t5 fl!ld~eacher:'i cawl fI:nd fl.llill. hawds·on Sidcm::c experim e~1:s. Besides strong~:~en~llgKNAW acthdt:~esillfl dJic same
~a:eas,lD~jlk;gT<I!I:f'-.\II1l art lO\ierwho inteJ]1i1.1(p1Jed ~l:i!!i1)1Thysk:s HEliui1lllig far 2: y.e!l:rs: ro IiWI!a:dly ~intrnng'-hopes, to enco~r~!1:,e excha:I1I!1i!es

beb-'I'oon :l';c,ienl:i:sts: a.nnd lWti,iju•. W~th li11is pl.1lyitlness: lIm:illelilt!wm;:iaJs'I1IiI. n.ij kgl'aaf is, the :dg)lt man to mnderniae tn,e 220·nThcml:ter .KNAW,whi.cih is "st.i]1 a bit like a ~.'9th cel1rury society semetimes," s:2Iys .Heorumll Vedilll<ille. 3. lDun:h ]lllys] cist ;itt Prineetea Unwets:ity. where 'D'ij:k~~;r'lIilifdild;jJ, pestdec,

1TIIMIE TO 601' :FaIb'liQ' lJ!s~i, ~t.'tts, re'Slean:;h M . miillls:tE!lr. wants 1iO make room forr rr,eshM,~e!'lt alt lhem!Jjn~rry's 02:. staiN!! "H!iiver.~ities~ So' hE(~ proposed lmllering the ,o.m(ia[ r!E!lJIre,me!i11 dig eriOf n.l!'~ial1pmft!~'5o.rsrnlDlrl '"151070. "GoilfD,g thi5: wacy. 'II,Ie! e.~p,~(j! 'M sariJle' I'IMH'~ m,aney tiO Mire Y'(JilJlng ~~eofi OCh':M:5:,.'" $ays MlJIssi. who~$ ~9'" IlIlbo:ut l'!edllldnlQI tllil'e oo:tirem,eni aglein
l.~Y@i.!lrinCre.l1Mi;J1ts
O1ffl'r UWil' flext

OIIi!JI 'CAM P' US

s.:c1e!1ltlnc rnlus,illll!!;lswith

me~t chal!mnet
III 2006" !Ill
,at

iI PQPUlliH

emerteln-

(UWiI'y,

!:I11Il! v,o[ulio'f1auy e

theorist

~~U~ I~Olldo'l"lScbooll Q~

~.(OWN)11IH(s.wrote

an IE!S)CtiYor the! British Br!3ll1Q TIl ne~o~ik f in wilkih he ~ald (HJI{~Pl<iI~i:!iible5ice'nli;llrjos;~ f,or honlii hUlifIll<lns mi ght !E!vohllf! ove,[ tinE!! nlf!::d mjlll~ion lle:aII'5:. AitholJJgih OnlY :lI1'Itld,!l! It dear that tl~ Ii:'! e.~e[ldc5e, was pu r'E!ly s;Pe!CIJILaltive;, Bravo, lJ'iUed his~deas as serteus res:e:aITh.

lhQll, triglger'ed ,a flhJlrrlry of Irrnedia reports. k~'recast,i og,a mong ,oithe'r thri f1g:s•. t~,€ lefllerg.en;ceifll~·e !le~rl Jill ~[~eflnll!'!m (If ,~ ~(~Uee·(Q~Qre;d'" I~Qlce. Last month. (~.rry fiinaUy ls;suied ;;a state!mel!i1ltdleda,rinlgl ~~at h]S essiI¥ wa$ "lllll~endM as ,a's(~elli1(ef~Cli!lJn' \ll\ayofllWhJ 5;trrtil[i fig ~o.lITie aspe;(ts: of e<vol.u rnOlmiary theory ... .tIt!I'lGhe ~ a(!ds; ~IIdo nOlel1d1ors,~ the ('(J.ll~llIt or these

'media wepolft5."

Y@liUS.

Deaths»
A GIfiANn! IPIR,IES'I6:NCI&. As: I ndenesla' s, "kll!mg ,oif pal~e~':;II!Iltl~H),p.(llI)9f~"Te~lkIlJ! ]:.i;I,cob ,UIl! I~edi Qyel~ ,j;J vila l e !I.'I~lie'cJl(l 11of h:olm~!Ili,~ 1 fO~~jtk Hiewas ~ ]or1linidlalj!~e skelPtic ofile l'·lm,et.eIH,aUt "hQIJ~oit'~ rerma~ns f'rqm ~~e 11J11J~,one5].a DlliSi~QI Dlidl~f Fl(l~es,alrg U]I!iI.Q t~at tl~eYili$ltl;!!l,rn reIP'Jie$'ent~dl .\lldi~ea~d IiinIQd~r.1'!1 I~jtllman.. Olfl17 Oc[aber, ill.! the .age ()!~ 76.,~he :p~'()ifes$or emeritus and forlilile,~' '~f}(!tOI~' rOt' 'G:i3Jdi~i1I~' ,l\I'Ia!~a:Ul'liio'enky 'inl YO~ly.ak.8irta dlfe,d ,or UVler pUl'GbLems. ,]aalb studiedi·ossil hOif11lil1'~dsJ.Jml@r'r'alme,cl I pak!:ol1lI!oLogi~t G. ~,. R. vo:rm Koemlgswi3iLd,. then foulnd i!'l'~ was (Ullator qf many l.mpo.n:a,nJl spedmelills, palfl:ku~rly of HO:lmJ!'€ffcw$'.~e W~5 a ke,Y 'Ji>gl!l!re t~the Ilmldiof!e'5ial1 ]1Il[je~ef!d~ le!rI!oe mOVemlf.H'It:, maklng 'Uila'tio:naJLi!i~ Wi'liHo' brOCilldcG1~ts aHerWoli~d W;u ~Irllurl11i19 the CIlI~ r!ltl'1/:S; 4"'y~e!J(j.ght:r'Orinde'pelfl'(.iI ence'fro'!in ~h,e 'Dutch. "I~e blllil~ '~~e fiiE!trll u p-Ihle ~$' Ipa k"o'i;lI!dhrlo'PQiIQl}yi n :~~d():IfIIf!~i,aQ.~ '~!Jli't.e i!I'vihii~.e.·~ly5 ~mthIl'QI~lQ£ii5t i'{IJS,Sirdl Wy~Ue O'f { X o tltrJ,e.IUlln]'!euity IOf C!llki3igO ]1111 Imm)is:. n:~tin:gthOilt ]~H;!Ob~l'ailll1led IIl:clIQlrrD>f~si~mlS: ~~li!Idylhe W fQ5:s·jill!s fOI!!lod iUilf lheijl~ (a~nt:ry, "ill~WiQl5an rll:dl~ge'1l0U5 eUod,"

5 Mm:sj

The IP,llan. hl eh w

arm)'!O'l!WlIi:E!dl iii! I all ~ ~~ bliil( U!llk '~a5"lrnQf!I~h

~ ;;Iitt~e!GOOGvj3jSdeln1cce ;<i: IFe~tii~al,~;;Isblee~ ~ grleewedl Mil~dlleel'~ fmrm th~YQl,Ung aifi'a g'r~~M]n,gl firOIirl selnim ~ d,C.ardemlcs. Feldell~QlI MIg Lli1Il[do" ilIr 3;2.;~e.!il~-oldl #i ~hy:k~Sl at lJ.llli_ve~t;l:lY r~~$t;]ml,~IYs tts O ~ needed la, re'V1t:tllhze II~ hili $(H~nCe, BIiJt. ~ .A!~mal1do 'BalUalrJin, ill 66"'!I'1:!ar~()LdlllP,~,ysk5 proj f~s.'5m' at ~,e IlJI'nfrvellfShy' of Bologna, pr'E!dkt:s. ~. "the~@IMU be igrea!t fes1naIIillCE!'" W:~@n'l~e Imnn~ 1'Sterin1.mdul:!E!s his 1~lalniI1IP,arUalne'iliIt

~hi:

11'11

'"

'

~ ~N PIIINlf
~ IBIITEVOUR fOiNGUiE.ILike Itlimysichol,ars. of ~ ewlut~omi .•Ol:iver (uirl1t ls alill f,or-exp'lai!llllm,g ~the t:opk to::! '9enera [a udience .• BUit flCiIhi IE. he !rv1she~ he Ih~d~'l s;l~are,d his less-thenIf: Q

~ GQ-t <I HplQf this pcgle? E:·ma~ll[!(\J;t;Joplel@~ilI<l~,Qfg

W'o'{IN;sdelloem¥)l,orq.

SC!IElNCE VOL 31.8

9 NOVEMBER

200,7

895

Universe,"s,H 'glhest~'En,elr'gy Particles Tr,ace,dl Back to Other 'G'lalaxies

t:r.igger.s :3!1l~IML1!3:r;I.CM;e Ofp311i!cles. terns ofkilo:~ete:r.s ~ollg ealled ,11111 e~.lINI1:5i.vefl!illi:s:lm!Owel:By !!31IID1pli:ng the s:liuower '!iyi,th deteeters on the gr-omliCll:'lhysici.sTIi ClInooteD'lrn:lil'l:e ilB. dli.-eot:uOIJI glre<1:te:f than parti,c[le .u::c,e[,er,lIItO:fS h,tII'1'e <lind, helmce~ the di:rection of the 'COiSln]C fay. reachedL Now ,lIillSWfirs :may be ]1] s:ight U:irra~ T1i!le:s'h!.W.iCr.alsiCI~'lusesmit[O'ge~] mol.ecl]l,e~,> in ~~j,sINffi!l:;rgy cosmic ni:)'s 3]lpeaF to c:~om,efinj:i~, the air tofluon;::scc, :lioon O;ooi;lleSiS nights, ~,ei:lieilhbo:mooo~, of' certain :liIiearby,cl!lilu,mllg special telescopes can see the showers. g<1~";t~es.phYSiio~sts,li\iOikialgwiih th,c :gigaflt~c Beg,U5eliw higJ;!estlel,lcr:gy'cos~~,ilc rays ,~ITi,v(l Ewry so oiEn, a: :;mlu~Olllic p3rli,c~ec;ra5lmJCS ~~~~O &:rd~ 'l; armosphere p~c ki ~~gaJS m~~ellD. e:JlIeFgYas all3!l'g,c, hai~swne_ Phy.sicis~s have stf'l!1ggWe:dfor decadesto determine where sndml lldlrn.linli.gh"·ene~·gy cl!Js~iil,lic laiYS eeme fi'01I1l11.wlliat tbey mflsist of, ilI.11ld how ti;uey a~'e am::el,m.'Hted~o energies :~OOm:iUlolrn,times To 'tt3!ce tllecosmj,c rays, the A~tger 1I:am cmpl.~d aJ d~recto:r arroyll.1urge:r tl:ia.n'icikyo, WhC:fla cosmic ray hits the atmosphere, it

O'IJtergh~iw oflliilc big ba,Jm!g. thecc~l1I1Ii.c rnicro~vai'l'l;:Ibrack~und. AONs ru:e thO~llI1iO be ~Yl:le~"IfI<'!I,g:shi(; b:]aek hales, at t~lC he.a~1s'01' g1i!l1!~[c1'\ timt are 8halJling i.tpmi.rtli~ ~l(I ~pctvitlig t:adii,.\'ItioJm The eo~m~c ftlys do not point .•

proci~~I)' 'IXlU\)~ A{3N~ •.pr~811J~rH~blyj, ur o gablxy"s Hlagllot~c: field dc'ncct:s them ..iu ~ransi,t. [)ctailsoftbe atUlio/sis SU:gW;:SI'tImt ~~mc ():!;C

m:e, pm't\)ns, The 1'e:sw1~~ bn't:J)Nji~ AGNs are Siournes d On~1em~:s. "Anything else thars di:!>I:u;l'I)uterdli all th~ sky in fJine!>3me'\~y <liSAGN s c:mdd befhe SO'l]l)re:," W:m~on ,saI}'s.Fo'l" ex5[ll]p~e • .gaJ~IDtiieS tendl to c:;lmnp" so rome otiIDe~~ ofg;.'ll~axy sort migtiTht be thec~.lpl.ruL ]lame,s O:Ol,lin, a 'pilu1ide pllJlSi:~,d,s:~,lit:tliie, llni\lieJr"Si:ly of Ci'ill~CilI.~:oi:l1l1 lI~ru~ ilIiCl~!'>1iilil!d1 ec-fbander of the proj ect, $lily'S the k..:-ypoi:llIt ~~thstcoseaic ~:11iYS lIiLOrt arrivein do
tll'1ii~,:r~

Pie:rre Auger Obse:rvOiIto:wyin westera Argetn:i:n:are[port on p2l;ge '9.3,8•.T'e fi:ndi!!1g WIllms at1nn 'big stCjprnward ('iN:pla!i!l~ng the

,,·aite{),ness loon OI1liC ~[ sql!IHill,e' ki]omerot' pe~ ,C C']!Imty;. th e AlIgct~.fI __ 1IiI1.'I5 carp eted m 3000 square kHom«c~ of Arge:!mllimt's~m~
at
;j,

eq ual li1,umb frem all di recti,otls" S uch ers

"awi8otlfopy" fmggeSiS Lind reseaechers are

~ly.u.eri(mS pa:fI:ic]es, '~:MillllCr~ ~fliy" "This is ofthe g[c~~est i!ii!liPortance~" ~ays Ve~iiSim ill B c:rez~ns'ky,a~~mClorist~t G r'"tlil, Sasso. Nalional.laborro:tm.'Y :i~!" .J-\$sc:q1::u. haJ[Y. "m~' it ~seorreet, U' g~~v(:'"m~(:: ofl:hi~; puz"~ p~11 zlecempletely," ArnanW,u:s,ol1. alfill a'str!o· plillysi!ais;t <lit the UIl~'iler5rn~ OifLee~dsin file U 1(, mmd Spo~!i:s;pel;!im.l.flY.r the 301}~nu;mber .Aluge:r co]]ailom.ti(l'[I. :lmy:s. "For ~:uY:5e:l:r, if's deeply s,at]sfy~n!l: to lrave g(lU~m the to b~,:i]mlni:ng of the: ,eill.diof this whole riddle,"

A:!nariUa ,'\lith mll)r~ '~halJi1l30.0 d~ICdo~ii!IlCI .~

d:epl'O}ledilbur ba!tre:ri~ {lf1desoopes. Phy~i()i_~ts c:lSW"e b~ e;nel'g,y ofn~ IlLg'il!m e~~ ,e~1el:g:r :rays: in exa-e~Cleu'O'Iiil1 'vol~s (Ee:V).
'f]in,l Au:g.el" t:eaNntl frnds tlUit ~:aysw.brtli1Je'lu~igj(.'S ]ruig~ler than 57 EeV-af\vhitlh iliey see: 27~euel.;anycome,rro:l1l1l dUI"eclk)]mr!i;with:]!} .3Q< f o

fiJ[!JaiI~1fOi!'l'n:lfu.e.ua]1 oft:i1emys,' m,~bl;;'l andgM~ ::lci(\f!tisM 11~CW way [10 vie\w ihe heavens, ICremin 8fly~ "h~~:~{;: ibegltmilrrJ.g ofaln as:l:OOnoroy ofc(I8micrnys at~l~ high~il; Clmcrgics.·'
Others ~l:ad daimed t!!)mu'c~l1c: 0!".~gifl3.C}f Iheh]gl~e!>l !}ne'l'1'Ymys be;FoN.\ .hl20[ll, theeli~b;Pc:~er nlll~!!Mv,!ill~ '~,goli ThSichcv of ~h(: RU:f>s:i~llA!t:!Idellty ,or Sde!l1.ce~ in Moscow ml~lY21ed dam frem ]'a:pan's: Alk!~lIO Oi.mt A[r Shower Arnl.y (A!GASA). J. l.O{l~S:CJImll.le~ ti.l.ometer <IIl:my oll~ide Tokyo, that too']; da.1a IJki.m 1993, to 2!OO~, The h~g~,es;l ,~,~el'gymys app ea re d to com e trollli1. olJie"ct:s ca Ued .I3L .lacs,g.aiRxles>!.1:uth jets, of~rulli8!Ueiiaad oo.el;g.y slium:rt:i~1 (mt efthem diiredly at EiUl]ul. they repertad, Th'<lt elaimwas di,s'Vi~ed ~y rcs~al'c,l!!Icrs'i\1or-k ~n.!:1:wilh!-h -Res, 1",," in bllitte:rics of fhllow.sccnc.;e tei:esco[pes locatCici lODtIS~-ay. Utah" tb!luook dllt~fiTom 1997 to ::Ii 2.r[I06. ~~t ye~r•.11i-R~ ~:g~iiird~:er~;o\iJrgijOOI~ 'twat th~nl w~ s iH) co rre hni ol)fi,~" ei the r !!!

·'actTh¥e gnlactio :l1ill{.\lei'·'(A:GNs}~lat liew[ih.ulll roughly 250: :l1l1Iil.l.ionli.glrt~j'eaJS of :B;mJI:tb, IJ~m:s close e~liLough that the' p!lrticles al!'en·l

sapped oflih.cir~ne:Q!Y byinteractim.lS W~~ll, the

t\OASA~ dam -Qrtlleir

O'IVll

b~!~-~~t:dlC~ \\{f!S
I

i
~.

C(H~e:latiQn in th::k data i.f~~l.C:y [nchld~d <I.IlDthersu~l:r'pe or B~ Lac. These clalms s;~tf!:ercd fm·.a ]\:JeY \Yeflkness" says "fodJor Stanev, ,!1J ~1.~oolli!!1tat ~lC ve.ffi'5~ty of DeI,tI':Ic'V3fC,New.u:k. The skyis, fil]:~ of pcssi.b.l'!! seutces, :so by se:lecri:ng the seurcesin w Ji .J-1]511 the F~.o.~rd ({,'f,'.rese<lI:(:,Jiu~n;.callml in9dv,er .. b tently IlklllU!fucmre' ill, specimJ.ls c{)1i1I'lid~tiOilil~he say!'!. TI,1Ie,oimdy wa;y ttl, gtliil:rtll :i'I~ilmst tlm,~ is ·to teS't~,le dll~lll.1ed COiJilr"ei<lrti.OJl ml,lI m::w dam set That'swh a l: the A~etream dlid. First,
researchers

i
ti;!

Urn~ ~,
~ ~
2: :Q

s ~:
til

~e~rchecl dillt<l. c,o~lec~ed frQm ~ .~Janua:ry 2004 to 26 Mrl)' 2006t(l nnd:a.~· [:l

"} NOVcMBE.R :~007

VOL 3.18

SCliErNICE,

'IrVYIfIN"solienoomillg,org

CjtlITc]iB:tion; thell1, they cOlI'ftrmed the: eorteladan by aooJy.zimillil oota, ,oollectednonl 2.'7 .May 200(),~o 3:~ A:u!:1iU:§t200i' lJ~~rlgdle ~lm('; erite~.''T~c hjJ~1t od~lilbw~ti;MIw:~ IboonCi'i:c(;ll~!!l:!u ~tting 'nherliile:5and tiot deViiatir)g 'om in tihem f'Or. ~_fly~a5Oirlt,~' SWi!'!C:v \iayt StiU" not c\1'eryom~i:s ooll'!tirtl(.';cdthat 'I:~,~ o~~e:r'limlt[on win hQrnd up as Auger eollects rtilOIlC: d@:taJ. Even w.it~ til e chee k ~gahlil!~1::~:hJl:l sellmld data set, the A~ge;r~eam esnmates tj~\i:a!t fllE:,S·IEA.RCIHI CAREERS

thereis a ,~·irl!· HIOO dHllm,c:e:lhe car:re:I"'t~ 011 o~.rdiU<,!"'fot 3, correl fltmll!l;",jlh AGN~. with AGNs is: a me;lIni~~essfhtke;" 8tllltis:ti,g'J1llllfredi by their first Ibi~reSllult,.&e AltglC[, ,eally iSpeakil!l~. ~lmflt'mllb~ ~t3, "t~'1TG'(;'"S~~1:!I" te<1iITI ]S pU:5lhii:1'l(g to bMild .1!J second ,UTay at ~e-.El~ ~]roe times la!:'gG:tt~~~ NQ:r~hcm ll~m~U 'Ob8,~VViUiO!i. Si:liy~ GQrdo~! 'f~Og80!i.a!:l 'e)lpenme~ltc!' a,t 1.1!U,geilllUniversity Pbcalsphere, which vroiiAld ecooll:Jle: hoo to view the t il!w~y. New J ersey, <3!nd<l.m~~~bcf of th c ef!Jt!rre sky, R~OO;on:~~c~ hope '~Ofiub~'D:il a prolli-Ies telllu. "There are mal'lly thre'C-[;ig-ma PQS~. w.ic:htn '" ~;ear, Cro:l1l1llsays. M~Il""M~e.. ~igrud:stlllfl,t come: find glO,~" Thomsou ~:;\'f:rs,~ut t~u:or~st~have ~ plltzl'j,e :hl solve; E~ct~y hrn~ he 1,HJldsthat Augc:r':S ~:I.8!ffim'''i:li suiJicilcndy Ill~g:~t an AGN a.c'cc'h;;r01!i~e proten ~"o:;;l,Icih a. intercs:ming tinaJt: is! po::;.td)oo lIl1rcli I arc rook:u~g~U' l1l:ili1td-boggrui1mgeli1tergjlCs? ."II!DIRl!ANIfliiD

A new Slli'V>e)" ofhmlfyoung

bio]oSi.sl:s view
a

th.d:r prespectssuggests that th~ main 'COI1ili cern fow women is nQt a hesnle climate bU:l i:l'il::-J11II,ft~c'ient t.o jugg[e the needs (ill' fam'time

head ofU1!c!:aJsik foree, Bethesda, Mflryl!l!id,iitlcI1!l!de~ a .c;am for mo~ogil1itSue RO~:ll~rQfGoor~(I·:iC f:il!ffiily-fr[,cndtyp,olic:ics :aJt U.S. gla ]~s t !t1!l'lC '0 ft:Ctlinl~ology in Academic Aspirations re~eare:~ illstill,lt~o~S. At lant:!'l!!i!g,rc'cs~~Ha~ fa!lmli .~'i'''\lVih:sJttheS1ef:il1din~ aile ~el.lling U1;is 'dla:t f"'~e:llJd~y'po~.lei.,esare key. Bum::she tI:"iver!>lt'ies <ll1d fnwndhl1l,~ ~~1,~l1~]l,uioilS ~'O need warns '~!J:!l:ilmJ:;t undere stima:t in,g .~ '~iLl:l1le :ac!IJd,e~ni~,")lll~~em to fl~ene;edS1'O'f the: 1rn;0\1;' gender du!;c.ri:minal'ion IIA'ects WOliillen, espe[iialily a.~h~ghel"nulg!i wonmell:' &l1YSliiJa\le1h Ma:rliinez.l~ad anthm E .~ <lindnforme;lf Nrl~,~poIlMoGwIitQis liil.QWa.pl.ml'~ otUTIle acadenrtcladdee, "]1 gets ·~milloo~ID'i:liIstntc~ol' a.t~le UntviCl:$hy !O:ffix;lIs cOnlrn1!Hoated prettyquicldy," she s nys. a.dding th ... ~~,umy r fem ale 8 SOllatlinIWIl:~lel.·n .Medica.1 Centc:r in DaUas:. .~ M artilliLez: and her lmJineC(HI.][I:OOiffi1iJre mc,_~ fac:uruty members faceisola tion ; be~.'.il oftl:lc Secend 'fiI:i>k Force on tIIl(~S!;ruliLI:SO'f and disi_fis:w,e a:ltiludes thn:ru.gh= out tt]c:ir caroeiliS. ~~lH i,~.uT<Iln1l.lf~~ WtunenS,c,ielmtists, ~l1rol~ fl[$t :li:1:l:lSlIOO <li rep(H;t u'lI992 (;111ng t:'or cqw.ty In pay h S:dw\¥Otrtz !'lays NI Mi::o a.lrcadJy Marriiif!1I. MarrUif!d" <liddre: s sing sem e of the; task Slingle :~ and hiring :prllct~cl'S.) thiS new rup!:)rt no-,coil1l1l·, drijlcil.e~wutil'cih~ldreUl force's, [1ec:ommendtIUio'lilS. Fer :~ MenW, thil,ti:l1StilllitLO:f1~ set 'If!pii:rHime ,ooi·· :$ '~jOw!S,fQf jpri:l:!!cip1'l[ ~~:!Vestigat():rs (11s). offur llilul!lIlh ch,Mce. IFam~ly~~sprmsilmI!i~ie.s~ee.m~o f~ec[ c~~~er gl(la~s examp~~J N III ~Igi!ld OlUOW oli!lly ,a to '[l~w~ililH!n O!llt~ ~e;;j~(!;m~t1Irr:!ld: m.DIl! t~ll'i thlX'~ i)'r iiI!~iii. '[(iJ[!ured i~ve5t(g.~U~!':~ have to '~ gfiliifl't ~~PlP'I~~l~g'W hi~ q'Uwifi,ed !l;f'i'O~C5 oW ~ IltOp:ara'te ar r6[~ttOd proj~(;t:ii. ilifidprtlvidc :-Ju!ff scientlers, Now. te~lurec~mpJe} 5"7% oflbil1l!alcpl)8~OCS who ~ ~r.M;k re()Jearohc~ C~il request ~he~'e s;~p:~ O\l1ftbrd,~b~e c~mMc~re IQ~~:~~~~I1Chcffi. MSilTfed InltwithQ,1,1t clll.i!,dn:e:nI s:alud.[haJI.'laY~llg fl! NtH. ~s()~e of the 1~lac~wllJ:cre Ihe system ~PQdfHhcy aeed to \~-'Q~:k ~rt time for ~hQl't p childIJCI1\'VOfl~dini'nlle;l1lCe ~hcir C<1U:el:]lJ: c~mct'S stints to takecare of a child or a f~mi.l.y '~i:s'ol.ltohvhack The s~a:re of'wo:lUen ruuooghs melnlbe~:NUl. a]so e;riIJCQ:~tm,g,e:s research C!I"SI comp!JI!mdll!.fhll, (rn~.y 29% ofmm:riod IllC:rIi ~ 900~emJJ[lfed Illvc,:;ngMi)I'sh!l:l! barcl:r bud.gedi~ :lii ~hc piElSltd)ecRlde~ fmm 1:8% to 19%, !l1IDdthe: to tcl,ec()lll!nlilll:IJe if pos:s~blej' sheadds, witharut chi.kh:'e~lIJ.S~milady. 31 % of married '~ f~glueliu lel]llll.'e:.;~rack positions lirlHS 1.'eTllil.i:Medi 'W'Gmel~, 'ex.]1l·egsed~ WiUiilln,gnlCSS to .I.mke ,OO!1iI'But PlJo\"id~ng a.tJ"ordllb]e childcare is aJlothe:rnmtier. MQf(l'ihan ~llmOpeople. nreon a '~:at 29%,. (By cOIil:l,p"'],~!ion~ women received eesssens to necennnedate their spouses' a_Om! [iliuuu£'l{l% of it]lC Ph, D.s III 'l:.Th.e fe 'SCI~ h \!'I"airiug USl far 3.50 5I{1l:saiVfl]~ble on nnd off careers 'l;:e~5mj:2:~%of the men. .~ enees <R\VfIIlded .DIi1,lheU:t:iJited Stil!~es during the t;jJ,mp.us" s,,'lyl:1, &!:ilwarn, andelro~p~b,yees rerei.vc At the, sa:me time. m.de .nlld.reliliHl]ellost~ cl:Qc:s said! thOit ~!l~!eY ,eqlll1li]ly cm~rn.~or1:Dible pJiem:r-ence,. Tl:mt m!lire.sitIDug;linl ml postooc::s, felt B: ,,"'l1ilil.etnnetr<Wil1:e ..) .0. _ _ i]1l theJi:r 'WO,;kEllg cllvi:roelUl11ents. "O\'i(m: di:s~ whQ met.ecJ.ulicaJ,bYIir:ainees. "BniiLl:iul.!;l. 1IIiI;Qt~.ler .~ "flu:" SUf'!fe)' ·foulld. thot more tl:lmll jO% of .~ tili.e. :iJ'Ilnl611 ,~,r,\ile tllieiir sigiilits set Olml1i P'~,iPosi;liioilll C[i:ni~llotliloll ooeshot: seem robe tliil.c ~SSiU!i3," dayc;i,re cerlteT on C<ii''i1p'1!U.~is <I. 'prio~ty;' she S<1iys. "'but tl~ere no iH.Oflq;;.y a:ttW,~ :!lI!l.o~.nent'" ~~cm.l,p,lItId with only 5'0<%of the '~\M,~l!. (The 8ay:s M.'lrtiwez. Thl'lee ot:l!l,e:r lilllrv'ey~ 8t~U .!J re81,db liw;::rcpl.ibUshoo dle 29' Octooor i:ll~!~ be:il'ag ,lllill:~yl,;edlby the task fo!!c¢-of~ure":YIiJDlIJirJi BHA1i1'AI:MR,JIE

II)' and career; n~ swdiy of ] 300 postdocs a:t :~~~~ Nartku:!a] [m;;tiltltcs ~f He",ml (NIHJ,im.

of liMBO Reportlll:.) Men were <111;"0 _ore, ,oo.n~ 6 de;!:Vt~'1 ~nlll~!!liin CJif ,59%t'O'.1IO%-t~mt t.hey\\QL!M bewfiu~ P'b;, Or!c: .-.warelYlm.::iiotl rorrtbe .gend!e r di sCl'epawcy isthil~ worn CIJi

track Hilldteimrod ~nvesti:g(l.to:rll,stdf scienfists, 'l.ndte:lill~re.;tmckresei[rch~iro whohilld same thing.l[\epQr~s jO~r1 Sc;hw;att~> ass:istitnt

left NDH b,etore gdti,ng:ti!(l!l""r;:~Sil,y

dwe

arPlP'~rmoro\l<iII.it_Il_g to m~c c[lre<e!"8acritillc-es forUle: salreonhcir fa~Ueg (see grn,p'h). For

direc;tor

far intnl1l1U!r~] li'e$oon::li1,

ail N~Halffi.tI

,i:i::

1Ijj

_.

,.

..•

...

__

:N

--

-_.

.-0

.Q

.,

..

'W'NW.sdericema9l.o,rlg

SCIIENCE, VOL3:18

91NOVEMBER .2007

89'7

S :IEN, ESCOP'E
Fans T~clded Plnlk
Alii

Sp,y',ing On NewN,e,uIFons Infhe Human Bral,in

ne ~1iZll!1i0l.1.
roIbk)[ogy. It also m~~d slmv ,of qt.cs,tio:o~ i.1! ~bou:tthe fi..ii:1c~io~ ()ftIm:6:::,~ new ,ce~]8. lim, recent ycar~. rOlf ¢;(il~"le., 8iCie~tist:sh:mJYC deb~i.ed whet~lor'~lC\l,~bom ~lcuro:l'!l~f!tdh;;:~:rn-, hl,g find mem or:y ,8 m:l. whethe r o\1!bc:rm:l:ions ill. a:dii,llt fle~trog~llIe~s cO'l'lI'l"lbute to, disorders s'I!lch
as dep:re!>!!i](lil1l fS:ctence.~ f7 Fehmary 2006,p. 938; 8.Auglllst

Pane'

~~5.M OI,e:

llilas: IFII.aMiinglo 1

1:heMlIi~nlfllla]il,lfl bmi:n p:ro.duocs nf"W aeurons ~!i;'ellinto rndll.lltnoodl W;'i,:5 ,11 're",-o:~uti,on h~1 ne~a

mo.re 'U111m,11decade ,;lJSO'Ol<1,t

spectta, ~t 1.28 pilVilSpe:r • .i.I,~.i;onfp,m~ the eenverrtienalanit in NMR gwec't1ro~copy), su'ggei!itsdlrn:t i.e~ fatity ~ci~, I:li el~S's()it'CQI'Iil~ j), p01Jifi!d~ t~Hn iPl~y a \~id~ vajf~e.t:y ofriole~ i~sidJ~~dls. Malet[c~Snv~tic:~ay'S. Em::QUf1.!:gcd by their ~lwse-~~ss,~eexpe~iilIiI11(;:lltS, thC'rcs:ear.¢hcl:s neX1 looked f~r the

]~hmllotiolfM'l ~:rQrt.m promtlTamanflilll':!j Lake lr:llatrclO,th~ onty ~nOlliTllbf~~ingl slt~fo~ Ea5~,Afrka'~ lesser U.ami!1 ~()S, goi: ,~ Iboos:tlast

Wleek wheJi! g, tE'd~rdcal gd~iro,~ l'I:;Jnei re.c:o:r:n~ :~e'm!dledfiej,ecdOrii! of the eJi!\!'irn!ii!!lf!!ef!t~HDl1lPaJct 1~la rii Sl,IbmliUoo by a. talii'iPllli'!;y tlil:;ihiYi1!I!i1'!s t!], Ibuilld a sod ~-.a $ful ¢)i!ta(i1;klli! Ipl:;imn~til1~,~e, '"We' sugge~1Jed thallhey go hack to ~he d ri'!,WimlQI bOillrd~ "say:s Lola Mel<lrilil<l rri Qif the
Wildln~f> (onserr'l,'atio.n S,ocie~ oHafl.zlIlilii!li:lna a member ohhe panel, wfulk:h i!ildudes [ep.re5f>liltilti\lle5 or ('QIIlSle:I\!.a~i\on roup!'> a Irndlthe 'g l!il.dI~'ii[m:all'Dark~.He~5a~rlthl'! Pi!llfll~':5 fin d1ililg~ I a,r@!EHipmeodi tor be'~m:lor[jjJ9d1 byTdl'llarliiai'~ Nltlt~olrnfIi~ EinVilronm e;1fI1. Marlflg anent COllin~[ 1111 rleporl ~.olh~ Illlliviro:nm~ntt mriniste[~ who it!; wm ma:~e the ftlil,al d@d'sloo ,Or! 'lhe studiC!!s1tine d'~~~()P'E!f w:lU, ~~ .r.E!q,ii.!ir"e,d~.o co. IhtiCiClmpan}i •. La.~ Natmiiil 'R,e.solir"~, haJJ ,~q!I;!~S,~ed p<:!rmi,S!Si:OfllO oolilslbnJd: "~i'!f9e: pl"nt: Qlt ~he ,ana~!'Iel~aJke,vd1,io~bas ~e~l1!Bl!e o:nl:y b11aNI11 br~edinJJ gl~ouii!idror ~st#!fri(gJ$ n:11'Ui{l1il 'l(! 2.5 m~~~ioiilles:jerrli1!lfiliInll'lg!i)S; Jlor 45 year;!; (SCierfla'" 22 .5ep~elil'llbe~ 2006,. :~'.17Z.!J!1 The adll'isom:'l !ril<lUle!~.filll!Jndh8itthe ~ :~Iaunladled S;e'Iie,rral,e:sse ntiaJ de:!aIQIs, i31!ildlin~lIf1~ !bers ,qu~s:ti(l!liled ",,~etfuJe,ritsl~ra~osed mitiiga'· tion '>traltegJies woliid I~rali!!d. t1H~Hann ilngo !breeiCl'iiIrn!!jlare-a. ne (ompafly mnffi~di5 that the> le:draflt,l'afli pla.nt 1HOuldlirnOit hurt. or drive iilway ~he D:lrrds. -IIIiGBERr Ik"OENlG
r

2!003.p. 757).
NQW,reSlemrC'llliers: may have a IPO'l;\iel'm~, ne,'!i'\! tool, to 111,e[prnic~de

t~,lese !!]r~e,st ion s:

0],

non invasive

:m,eUu.xl fOlf detedi~lg m::.'l!~"<I] Sreiml c'e1Us in ~hi\e 'l,liIim,d::;--,ilIiLChldi~l~ ~~m<l~s. O~[!ilge 980.. i:liITH!]t~di :scip'~~ml ryteamle

d by child Ml~fOla'gist M~tja:rl.aMa~et~f;;Savane (!If SU'lny Brook U~iv~r-

u.

s ~ty in New YOfk $u:~e dc~criibes

netle resanance
'~odetec'l:
$

t~~(; tcchn~qtl(;,.\·ihk:h uses m~g~

spe,ctro~co,y

p:oo<~elliror eJ!!lth~tgi ve riseta e

new ne'l!llr(lns.
Ot.liDer researchell'S
U~I.C

IbiOliDm~rke:r for fh,ii;l

i!I:regU'eeth~g

warkw:ith eXicitCn1lie~:ll. temIpen:ldw:itlil fI, healthy dose, of'cau~ !~i(}n,."l]iIIisl.'I1iIs,the potet'ltlOlt to ope[;l

Judge B [I[J!!I::iks Pallent Ru'~EH,;

A U$. ~·ed¢rall.jLlx!gie hals rem1Poirarily ~b:ked llilew piCi:ent.ru~le:s 'r.ml~ized 1:1)1 ~he U.S .. P.alelillt. and irrademarrlk ,Omoe thai!: wou~d nmit (:eIl'l:a~1Il pa~JentCl;ppl]c:atic:i'lil~. The nl~t"5,.miigin.a;lly :se'l to take eUfcl iastweek .•1I'I'01liki ha~leIliiTillUed meedl il:rillJMcim,mts, Ihal i!I~I.owi!I~ptican'fi5to ilidd
lm1fmlllliltiolrn~O pending appLica.fijl)l;(s. tast w,~f!:, ltu~\f]rr'g~nifl d~striltt ]lIId'g!l! ruled in i~al!,IIOr of gj]rM!]lgna n~ G~axo.s;mitht::lirlEl, sa,ying that me :nlilliits wo.!!lIrl h!1!v(t"nrl.ITGlItI.w.ely lI~t~ITrfld]1h e bili'glJiin" th:a:t ~1iI~en.mrssud! filS Gi~K ma~~ ~n
'tralld'Uifi!!jJ! r~eillrd'iSie<:r!!l;s,f,or a: j:iil!U!i'I~.li;IIUJIifi!Cilii()~lf a,fld~prtJil;iijdeJd] iii dR~iillC:Mtiw to ~Ifi~ir irigl ,of m

the doors to research th,u cirndd nat ll!<~¥e-been dooe in lllliuUlaJl.lS before.. "

Koroshetz, deputy difloclnt grIlle NmtO'ooJlll!:ltl,tlde. of

s aY:!'iWtJ,.I~e:f

f'@~k @lu;;it!H!'!I'i!!1,t. A !'II~W mll(,Il!'i:l~ IfCllC;\l~~ ,~ b]()!Il!iHlk~r (l,t neu r(lg(llii~fiis '~l;ImL'! Ill)iliil the h'UJm.afl h~ppOCaliilipll!fi (b!J:(,~'.

Neurolegleal

Be:dleOO:<'l"Marybllmd, '·Iri:t~ valida:redl. ifs: the

Disorders

and StIJoke: lli!!

ooolc;,gt tliIing since g~i~~d b~" ~ay.i,OO!urobi~ ol,ogi¥~ 'fhooPabn~r ·of S'I~llbrd U~i\!\.~\1ily i!rr! Iloilo·Allti. Ca'lifbfilfi!,i~, Ma~cJ;ic-S~\~ti.,c ,fI!~ldher c.QlteQg,ue5,bcg~i!il! t~~lCir~e:aJr(lhlbr a Ibi.o:m.arker in a s-erks of e1ll.pe.~:im,entsw i.tFn, en hured. mouse e eU s,
ILI.s~ng :~m::le,l:jr magnedcre l>arn!f1 :'c (N .MR) m :; I)!(':C wo SC oply to. C om.:pm:e thee henri cal <:: l~ulk,eup oflleu:mll~lroge:rJiiJor ccll.srro~a ;~ cmbryml~c lrrai:n ti.ssue ''I'itlill thult of ot~m,er .~ ~pes of cc'lIs" i:ndl.l!r:lingmall.l!lle:Jm~em1)!Illsalld .~ ~lilli~ celis,. 'Ute NMR spectra ofthe nemml ; Ip:ro~e:JlitQr c:e]]:s hll,d 11.Di£'CinineJiilltpe.tI,k thll,t j ij W<1Snotpn:-senl' ~n the otile:r ce lis. i;lil;d[c<lll!Jin~ I~i,!i!hlevel!i ,ota, ,oompmlnd specific; to ~.letfi:'ld. ~ . f!' t.." .1 ;1lIIpinJgeJ!ll!I,~or!l. ThIre :Irui;utlity Q~ tl,Ii:!:l, !I;,~OmpQ~lll~ '. ".I~"

s 1lil!1ii= pdi':i!e.~p as NM:It butea~ be U:£i ed ]e~ thIS ~~!'i.tM;;!:S found in ~lii.1iny ~lro!Slpit.aJl~ ~nd n,ls,e~.mh 'OCEVtCf~. At fir~t., f~e s;pec:trn, fr'Olu ~~rnJt;:lh'era;te:;l;m:'crimreli!lUl "'rer,c messy,
'iii'; hh

~28-,pm bio~l<1!t1l<ier in liV'~fllts.For thts work, they 11!ll!rlJlred tnmagnetie re:sOIl anee gpc:ctro!iloopy, :i'l mct~o~l tha:t works en the

~nd.lhe: peak at L281'lJPm WAS: a tillY b~~pin a sea of squigg,]eiS,. But \?I!'[th tihe ~m~p of S:~ol'ly Brook. tr ~livern~ty engiM:ee'l" Pret!l'l" OJ m~~~~the resemrc:~eH deivelQperl ~.lilHII~hem!l.ricill. ~IIDgo,. :rithm th a[: SCp'H~<Ited, the ~.2 g'p]JI:I1Jp,eak fmm til e lIiIIOi:S e.. Using ttbi s al'[p:ro~dl. ~he :rc;:,semeher.s fOIJJliird Td .. t~'IIe~y .lighk!v,e~,s;of ~ tiiLe ~j28-p,pm ~ioml,lrkell'il1li the hi,pocanwm; of adIli]t: I'F1Jts:,~'lher'C previou s, :studi e's ~l,<IJ"e fOllind nCllrl'i!senl::s~s'i::OD,]liiilfedi to the ,cero..

app~!',~t,k'fI:S ('or res~afChing f!!~ 'ph aHirllgc'e\llticaJl proo uots;~The rUl~eswin slay offline hoohf·ar IflOW, .A,judge' w~ll~Iri'ke~:.r!:lear ~liIe c.ase .eg fIN l1e:t:iY'egr. Mea ~l;\Ihi ~e, th e Sen gtie is set ttl ,deb~M~ iI !p\ai~nt~re'rmm hm thtwoul.d Cfe,ate' .i1I!ilew' sysJem fair 'chi!lllile:ngin glgr<llnted patellh <lind
,if!'~ ~telnt

.tlisn't

known, but its p08iti.oo {H! the NMR

brul cor~e:A.,wbcr~ neug'iog,eflc~:~~ :i1'<l!:l. ~liIH beenco!1fiJtnl.cd. Mor~ove:r. when tbe II.,·
SCIIENCe:
VOL 318

:set GBI"tai~ Itilil'!i,lcs'(l1:!teg:;:1II I d,[lmillgles iln Pii!~B!l'l ~uils; ..A.si,lm~,ta,rversn o.n pa"i~e(jlill! ~Ih,eH.ou~e i,n '5epllmiJ@lf. ~:EI!!IKINTliS(1!I1

WW'i'\I'.sdenc:ema9~or'g

91NOVEMBER :2.007

899'

NEWSOFTHEWEEK
iH:llll~lli:s~e:rcdel.C!c~~:OCiQIl'l;'~I.s:ive s1u:mk~whiclln, M1CI'e<lSes h~~POC"dil1l1plllmlUI',oge,," nesis, re'i1d.~ofthe himn<lfrner~lCl.'easedns well, Finally, thetea •. applied the: method te l!~ hea&thy lmlllIm<iJmIvo]ulfIleel'S W~~O sat for fII 45~mwnutle s,calm~ng procedi1!ll.:re:. As: pli"e~ dicte~ the speetra revealed hi:s,herr .~e:ve.~s·of dUll b~omarkJer in the hi:PPooailnPUiiithan in th~ cortex. In addJitiol1" levels ohhe bio'mark~!' \'\'e!:i(; eO!:'i.sidc!'ab~y h~glier iII the YCIII:iilig(i:.n ~lIbjects {!lIg.cs,S.to 10) compiltre;d wilhthc oldest (~gcs 30 ~o35), 'r::Q~~iS~!H witn, prC'V.i.OliiS ali1llilll;;)J :studies i.urudilcaH:ng d.oCU:~"'lg li1Ieu,mg:clUl&l:flwhh l.'!!gc, "O:il:~ tm,c \~i]1teUlmw stmlliglhis m6hod
re;SC:ruI:'C~lef.s

is" [1lti(ut]it [oolb. v,ery poo:m~shlg;" says Gem .Kelnpennaml, 11. nm~'Olooielillrist ill tn:e,Oeuter fOif leg!.'lm~ratuve 'iliillJ::mp:ies in D<.resden. 'Genilil~Y. "The 1.1&.PIlIn ~ak: If-e.l]ly :soee:n15 torep:res:Ol1.t SOHLetmng :rei]afed tiOpmgeiDilii.tOli [,ens." Ae~:" ,oiZi:i.lm;exl &tep,. KernpOOllilnn iumd (ldlefS say,w:~n be roij~tUC alll!t C;"'<K:t[y 'i'!'lrlat ~]lIDebilOll1a!rkcris lIndi wl1ethe:ri~ 'l:11111::ks ,overa~~ Il'l:llmber af the p:r,ose]1!i.t~r eells or j~s'~ ·~lm.os:e thinllreoi;n! the process of [Jm'l:ifc::rnti!lg-a~,impo:it(:!'iWl distmdioii!irotii1!i~~if\reti~,g C};;p~rim~fIlali Aii:1dmgs..

a]'[~.pli.fy [ng ~l.cd se ~nillea.d. But if d'oic ne;'I,!!! method .dIoe.s hold Up' to additi.onal. scn.ui.ny, ~le:re:s Imo mort<i.~e ofidclE15 1IbOill~: iru~ to usc it. MaLeti.c~S3.Vlilti.c hopes to iJJlv,csligate whetliLet neurn~. prngell~tIl;v cells be,liia.ve,:;!bmlOl .... mi'li.~.yilildi",om:e[Sofbll~.n d~]qiJmet:lit sueh as cerebrlillp!.ds.y aud JiIm;ent;JJ~e1!i.nlaliOi[l. :hlmeJr snyslbat 1h.e new method CQuid help e",:p~ai1il!1l!~ cosni.tI.v"(; dec:~~:n~~OMe ch~]drell! i2jo(;p~:i'iencc !ltl~frecciv~ng r~d~a;Hofi~~~~!'~py tOr Ca!lcCt';. A valid b]O-Miid,~,fcouldt(:l~t the

1.1'1.!dditi@, ~QrntJ n:Si.':f.!~h~f.s:['Ij[t w(!J!), dm.t f theum:1Qll'\I'C:lWtio~laT a!goli':U!:~iIn usoo. to pull. '01.U
the
ru

hYl'o~hesi~ ~~~t the imp~~fmc!m!ts ~SI\.d·~hom rgld:i~tio~l dJ!'Im:a.g.c 10 ne:1iJ!:r>ai[progc!.d~(lr oens

afldpol!enli:3J~:~y hc'~p 'C:'!k'l~lJa~elrM.gsilUe'rl;~kd d

rCi>QIi1I,flIlCle spectta

;2:8-PiPm peak frnm the no~sy m!l!~~iClic (,ltH.dd yidd a!liil{f!l!cts by

to

p1.·,'o~citpmgcnuhlr ce!~s,

'"'iGRE.G .MU.!LE.R:

One,viel'o'!!' of' the ~.l:~I)ipOC:Elnrp'us,. based Olm, ~.numan brni n- im<l!;jJli1g stlldi.es:mid otJilm datn, :~ fuaJt i;t ~s ;::n;s~'I1I:tialfonerne;liIiIberillgtbe;p1!st:, as wellas fut il:ru'lg,i~;ling tli!J:etigre (Sc.i,(!:~iCoe. t9 Jm:Lnitt)'. PI :3 ~.Z). The rel,'ltively new :id:et1 at m tJwis,priLril(If ~e brmll1 hel.p~ p~nlhe:fultllC g.ct!:i ~~:pontiom a paper to ~fue N(Ji,j~n~-r f<s~e 1

placed ~.·i'I)t'swith such h.d,s rnnto <ru mod:if]e:di T·m:lI2le O1:nd ,ve:re ab~.ew ebserve cells in the C A:' area of the hg.pp e camp y s as the rats

V!'<i.lked tl1r(Jug'ii1 tlle m<ll:e. As. the: iIllllJi],1;a;]s ",em:,tied. s(l-ci:iil.ed p~oo ccUs,. ~ileurollSth~tfi[ieiJilli response U~lPos,ido:rl, !\\igmdod wherein the
MO'l~th~mlts liven::, Such afl)8cr\lll.tioo~ hav~ bee:n ~t"'Il&lrdilr!l '~'he llippocllmpalli·t~nU1!loo for 30 YC~!:'s:.IB1!lt ~liIe a,t~ ],~:a1V~1\:11 been cQl1IIlionnded byadil!lid 0 'I:iooa] :fi:ring~ willich l~!ls been d.iismis$e-di.:':IS ~oi~~" The pNiltlieI11i:[; ~h=nnel1JlOlrna& f:i:riwg d!:1Ita, o. spuking. ;[:Ill'! ofienavel:~~edl~l:he:rj whkh bluestemporal ~SO]ILI.~iO:l1l',. ,ex/pl.<Iins

E.er:YB:VQ~1111 of.I.JlIl.'WI!rd .mdtheMlIiss1l:cl\i(l~ selis, IUnstitutc:; oflieihllOklgy. h.l ccmpuiati.om.d. ellJ,tU~'iI'tI.]e:l1Itof iPlltti~m;g ,llllother leas on .1 iwi.gh-p ow,el'~d mi,cros<cope, BrcnN'1l <ind his 00 ~~eaglJ e L()\r~1J!FUlllk, wh () :is now ilt ~he ,

too

of T/~~J()~mi(lt of Ne.!llrJscie#C€ b:y A. David Rcdi~b :aJ!Ki Adam J'O~Mon of" me U'!mJ!v'ers;ity of Millm;:~o~,. Mil1inea'p,o~i$. WUh eleC:lmdcs

_p~antW into the W.:!ins (}f:l".Ms~ they've: eap~ ~d, en 'l~ );¢~;Ie: Siillg!e ~:el,lro~!;,l!Odents of ~in&:il1lg ~hendabouUhei.r 1~0'U11eS ]n a. :nna2e:, "J III i. ~J;: t~l.epap er's elegant ,.and h's going ~obe <I C.I<lSi5lC," :says. Randy Buckner of.~:larViEIII:d I[hUli.vcn;ity. "They I.'efli.~.y slm\\'\' a clomp~illi:J1lig e'x,lImp.le ofthe il1iU:Su;lpreseJllll~ ing ~n their bf<l]ntl. a series ofp(lssib.!e &JJture::s 3]IJd usiIillg~:hat totest what they're: guing w do ]iJ.ex.L" .1 thel 930s. E d'ivatd t:ohnalflll:(ul!ked <l.t n deci SiOJ1L-l!iI!l.akgil£; by u si ~gtl1lc T·:~n3u~e, 11m. which :an~:ent eomes to a "chaice:pailillil" and! rQll]st ,t~ddiewhe-lhc'rinll bCJt~rtOi take tho ~~cft or righ~brafiJcl~ ~l puoo,it of a :food !:c~vaiii.'l. '~Jf you look afTbhTIafi'S [ro:iiefli1Ch]~ aiHl! l!\Ql~ttiililit

U!Ii~Rlity ofC~mbm~l..San Fr--(UiI.ci8CO,. ere<1!!too an (.!1~Qri:thm.in 1998thrlt :f!l10~~'CId ~p~~ ~~~mb]c~ 10 00 seen a:l 'Ih~ m~m~~col]cl tunc seale at 'I;;vhtch n(;l!!ro'l~.al firing acl1!.l:t!iUy occurs. "Jfyou .caliildo tI~ !uu![)I:f;is a:1:~li~ resol.I;IJ1.on ~t~:o,rJid.ch thespikes COIU:e il'l;" ~::lIy!; B~:,o\vl'!ll'l·'you eau nl0ve o:n reeeh e:r. ]rn~:I;.'l:re :i.n"l~D:II"Il:tnt !)cimni ficquesli:OllS .... In theirnew ~.lMdy.]loi~,nsal'l allm,d R~d[sh
h¥ellkedthe ~dg;ari.tlllim and. use<illl.i to
"rC;:N~:tI~.

tha~ tll.e a;p'pflre:l1ii nois e in r)]ai(;e,.oe]] tiring:; was acn.l,[llt~ys.iglil<l,~.The: lIdd:iti:Qllal. m:ml)m'l<l~, (w,i~,1J.S cO:I:re~po:lilds to plaoe cells represe:[Iti~.lg tlwPOltM fmvtard Of\\ihere the rat is s!nITlld~nJJ;. 'fl.e firi.IIi&'!prooeed!> in a isequelliLcei.aslin!i); <I

fc\.'f .lnmm.dJred mwm~oc~J'gCls;. At.~ ciloicepOlvu,t, file rat ,ause:s :ru1d ~oQkshlt\P'~!ilC(; oo~~ f[re that cone~PQli1id 10 the .Ienpa:l]rn even
WI10il

~oolli~lww thatk~d

{If ~.

parad~g. migM be

dQlle [nl1iet~r:a~ I\Cl:iIllS.ym.D.oome~Q tfulec()~c~~t··

Skllffi. t~~:at be rats ~!llObab1ry have iI. nelll.al ..I1KlC11ll· t a!llism to prep ~HY 'wfu;a~might hllppeD ne:,~t~:' ~ys BtLCkner~ woo' ]ll'{lposcd tbll [(lea in 2JOO6 \~th .h~SiHm'V1IDd colJea;gneDanid Carm,n. Redish ;t)Illd JohnS(l]m.WClf1e ;iill:rea(ly :Se.1brdli~ mgmr S,lml113. decfs[OI1i~making nlec~l;Hll:iSim.by P(utti~J~eJectrr-ooo '''~1<Lts:'' on nl.1's. "th:e,s;e,m'it3Ys of,e]ecrroo.esn:p~.ntecl ~lto the br".uns of :mts c~lIn det~ct 'rlin:el1ilri:ng of .100 arsoind:U1,fidml1 ~.'i.enmllil's\. T.he rnt"$ c.:tilil mO'Vieffi'ee~ymld oo.~~· ~.all.y"'i:fuli.l~resraJircLllel'~1~"CoId111,e~' fUj~ll <n::h\,·· : ~ it)". ]~th~ ]lJjC\l{ ,'V<oirk,. Redish a~~ JO'Ji1JJ80Jill,

·thol!Sh!the~e; c~Ug\¥i:;re t!l,oug)t to respoli1ld Oi\]y whe~ ijfi ~ni.ma]W~!i!(1ijaUy<\iil i rllrtic~,. 3 1<1lr IJI~ce,W:lii~~leru:t lo6k::J,right., plac"lt oolls C!iTrrresfcmdi!lg~o 'fiherightt p~~l g·CIIQ If. ~~I'! .~ thQug)~l. the 1l"!I~ we:rc [maginillg ' .. a.I.king the 'mlln:e, Co,gm,itio~~. Is f:!l!ster ~:~mn bC:~~:!I!V~Of~ ~ ~ eNp'IJa~Jt!l:s,Re:d]:&h~ ~~'\\fec:nn :b!lJO\V sre~ ,asAdam d put: i:r, d~:e ~l~.lnld:UiIJ_g mil faster d~a~~.v,valks:;" h .:: .If riru]S can ViS:lHl~~zet~:1.ei!l· 1'{lrn:es. the next "" i

rese;±l[t~1mllqiIJest[oarnl :~~ :how do they dlecide~'\v:hlC?b ffi Q p .. t~~. c'l'il.oose?' "there: ,m:ere\NaJrdl pathwi!LYs ~ to w[th~1l ~;liiilebnli:JJill:S ofriil.t's lind hU~'~'lall!>,S:<iI)lS ::::. Buckner~ 'who predicts tlllail stlidies,w~U liJrnlk

ilulse, path\\I.,1-ys,'ic\r.itliithe
IlnlHlgi
.[1 .jj

ntis"

decisIDll'ilmk;~ng

:::Ii

11iI'f1i1:hl.at. A'S a r.ait locI ks. lilil (I n:e d'i'r~(l](Jo Ill,

<J.te<Is.

Cheese, anycJlkl?

·-K1iRENHElV,MAN~

~LJlr~[I~ r~"'It~~llItirnQ1lha

l p~W(l11

HiIi·"f~)lir~ 'I)W~

~aU·s~("l!uil p~niod.• VOL 3.18

lti:anen Heymall is. 01rreeli,an (ill! mite1l in Santal,Miolil[;ral,

~~ifGm~al

'"
w

tl

"} NOVcMBE.R :~007

SCliEI'NICE.

'WYIfIN ..solienoomillg,org

S :IEN, ESCOP'E
Bfl'e V~ ~ndieIIIiic ras
A n:~gellletk almili.y.!lis, m be IPulil~ished ne-x:[ ,ITmOilllllhin: !tne- AlmmCr1li&ejo!Jf1Jal •.,>~g:ge5t.5; ~hi)l~he vJIFlU!> lijlil~edl{]'lIle (d~lIapse o~ ~(j!Iil¥ee m~(J:liliH~ Inot~_m1ve in the 'M:Iil[lJed .stilte~ vi<! di:cl 1~:mllyHilllpor1t@d A.ui5triatiial'l ~~" In: SllptlN1l" !ber, ii~eillm or nl!seiird'ler.~ rep(lirIJffi CIlillfl!!l@in .sden~ltiiil;t mUa!D~d I1hr,es. 'IIlIljon hiil,v~ a,iecte:di a's:mafiai" .t:i1S: 25 % of be,~keepet"5,

ljljfnd wi(~ IliSiia,e~a'i.i~:eparalysis iiifu~S. They did! !'Io-! ~'Iild 'dle 'if!ruSifi bees collected before

\ve<semuch mQfe U~e~ythan: ~eai'lhy hriven~ be

u.s.

IF'e~wMutations DiiviideS,omle' Dlrug-R;e:s,iist:alnl T8, S;lr'ains.

TIilefirst genoMe ii:ooIYSii:s()if <Iili e~tll:llru !iNdy dlriLIg..;resist,illillt tt~be:rcubsis (XDR- TB) strillhll
~:1l~.fom:!dthat Olil]y a

AliistraUal1 bee lli!1ijpo:rl'S,began iii! :2005., and :SOl 5w,p5cnon r~l~ ~lheAm'!uElHanbees. !Bl1t ~e Oml teglll1: be~nlildllme new ,ji'Iinalysis :~'otJllild e virus hil 'ah 1~'e5£!rved be-ell dlatiingl back t(D2OQ!2. "It seem~ to I~et.l:ie< A.ustraiiam, o1fwltie hook/ SlliY'i em!tmrI!DIo· t gist Nlidilo:las. C!il~dremliiu~ Cornell Unil.rer~ny. of
"'.ERIK .smK51I'AD

~tndl@.rtnd a d§ug"~C:IlfS;itive:one. Th,u

llim~lI Ill!ltlibi:f ofmlltlL·· rions di~li,llglllljdll ~tiolltl.a less dln]£~res[strnU

~ICian~

thrn!(ln~ XDR-1'.8 ~S!{l~temild! t\VQ (Jothors~ ains,

separated rhe XDR strahm fr(lma

Scientists at Ii3:to3cl ,<lnd nOJ,fv.ilr-d scruti~lli7...e.~ dnJilfli genemes ciOvering abo1:ll,t95% of

o U Crl nch

Foriec:alsted

The !lnb~~!lQit'ionlal~ne~~lY .A.ge!iJCY'1(~EA}i5 ,~a!td:lieJfinllg U,p i~s ICOrnI~lN'f1I<IIbOlJit pe~kin.~ 'WlIrr~d

:tb,U ch!rit~~ng U~emolecular basis ,of TB dlru:g ro~ismJ1;c~m]g]ilt tl(l!t 'b~ O'I~ dtffi,cl.d'l as SQ~'~ had C:l; PCictCd\. &f~y~h(;f'C8L::: ~l!itcn'l
flrOliiJrn. theHroadln:;;lilU~e9!lilCi H~ryud Scihool ofP'ijb'licUe~hh (HSP'H). OJthc:r :S:C.i(:llt:Ust('l" ~~tI'I()!~.gll·"l;','eh~om.Urn;g ~JrnerLe\!lOl' data, say ftr i.s: too

:.n ~ing!o·nl1c;kloti&

trom Kw.m;Zt!hl·Nilhli. They t(m~dtha1: ,mdy

PJ1'ymQrphisms. (SNP~)'
dr"M!g~,

~e!f!shivc strain, and 29 SNP~ di~tinguiS:hcd tiI~() drug .. ensutve f:ittain from an MOl 01'10:, s
'[lJey a~so~den~.if'ioo $lmal~TIItUTllitJ~ of o.th~r a

oils'iJppUe:s, t~at ~(!II,J'ld~lfi:~ger' p.M:cel1ii~~. ~I'I ·its ,~n~Ura:l en1ergy o!)lltki()k ,e~rea5!~ thii~,'ll~1t, \ fhe8g'~flLY!i'l.ra m~ th81Hl r,anm! 0'[ r IIlle' (lil!lt <l ~sul~ply·s;id!eo ~run:Oh" 'in w~rld 01& m.arl:!~s by 2'0]5 <1:5 na:gg ing oillpmd IlIIdio'liI :s~mggle5to ke,ep up with '>oa111119d emand, Mili,o[ a'gelil des
surh in IlEA hav,e 1lI~~1I~~.ytls5lJ1med~h<lJt Mliddle Easlloil prod uce r:s,would make uj;D~h~~hortfi!lli I~Btw~eml !il:l:ggilll g' 'globill ~.lJ(rndlJldij[!nI~lncl rii:5ilil'g

!loon tQ~eR
1'1~i!iI1lI3ilys,is.~o b~ pO$tedi this week ou the

~1~nil.ta'l:iQns, .indud]llggenome: im_;erruonsl ~nd d(l:~C'lion~+ S-e¥cr,a.] .ntations \"''er"Cpl:evi~l,.u]y .. kIl0\!i!!ll ·~o lbe :sJss(K1uate:di with dl'liJ~g 1I"eSiS~~!I)De. "We were: lSlLup:ri.:sed and d)dig_htedi to find

dmli:lllllcL ~Iy~ BQ~mn l]'liIi\!\mi,~.y @Wrlomjj~1

R;obLN~.KflUlhflii! 1IlI1'I. N ow' IlEA p.!ilOjlliC!:5 ~elli [.:Ji)"I.l!!\If '~@IfIII!i'i mJdl'growlm ~lhi3init did ~aSl1!flliilr. ~W'~"Ir:e-re1l1~ytlit, tlilli: knir~,,edg e~ 1J~,wee!il

Bread hlstrnl!tc::~'S v\'l(:::bsite, oHers. in[tia1 U::SIJUs ofnn '[1i~nb:iltiloo~i:nter~!at:iC!ualprojed: that will. eV\'lut1llil~ly 'OOmlpoiifCtliue [m~.l[p1ete geJ.lomc'.'l of se.'!Ier<ll~ deeen TB sua:i.Jlu from .u'01JtllJdthe globe ..A tnajor ~oal i:s [0 !ene(falie enouglffil m:oleclIilli[f d,ua 1:0 speed tb,e devel,op,11T1lent of

so few di:lif?~)mces,,":rJi)'S prQjiectleade:r Me~ au S

MllUny

QJ"HSf.rn1 .. "Ibis simpUt'i.es tiue ISi$k of IJI1.ve:St[g.ilting[hosc muhH:iofl s to d.e:tennine

betl:oc di01g11OS,'ti,c~ec]m:]q~H;lS and 1lue~lIpLesfur ml!Ltidflil\g";l1es~11W1!t (MDR) TB. wllk:h causes

~n esti~l:ed 45'0.000 ~e'iy ~lfuc>'ti"ll1sa ;yl'tH': [)el:OC:U.'ld Otlity.!I.~'V:r¢at\j:agoj XlDJt~Ta ls ~venmorechl~[~c~gi.ng tr,ca'l beeauselns 'to

~ce()fl!d-li!l~~~'l,'CU!ig first-llne dr ugs, The WQrldl+eahh Or.g;~!lj~atio!m (\lilHO):ilill aCl~ev~ Switzc:rl!!~ld\,estimlde$ thai X[)U:.-TI3 iufeGtsail:)P'Ult 27,000 ~,eoiPlle lwr]d,.
1fi,i;:-ii]SlfIrat 1:0

which <l:rel!el!tJitedto drugres~stm~ce'." Scieuti~1:s~iso WllNiltOCI identify so",c;ruilledieempensatory ~.ll!l[t<liti,[lns e:lili1ible: 1'13 bacteria ~o that tiwrive dC:!iIJite drug·,ros;ist:ancc 1l1!IAtaitiOns ihfd lfili,gln QtiliC!:\visll;1i.veakoo tlm;CIfIl. g,ebil.stien Gil,:gJilCliUt,\,'I.1!lo studies TB geno:m:iic dW'Gl:8ily at th~ Na;tiJOO'I3i~ I.l'!St~MClfuf Mcdic~al R.ciJc~r~in :LO~l.dO:J:i" h}~d :S;'cien.r:,e tll~t ~eq;j,t~neing U16 }(",Vi)ZuliiA·NiUal ~min!S, \'Va$i~~~p~rtam b~lthat much ~!II(lrc SNP d~ta,
Ilrom a :glob~ l C'l"~~etloao fTB strai ~s hi e ~.~eeded~o lIIlli(lcrsl8:1Thd Iilu:nml:eCl!!llar basis of
drlllg res:istal1o~~

d'~malii1drlOr oil. aPiidthe wor~d':s abl'Ut'tto' iiJ~

d UCf! it, :says Kali.!rm~nil. -RIiI':EIIA!RDI,L IKEIR:R

ArlgoAllloV
Sdel'ltistsothh rl'illlfi"tliJ hi!l~ fu ILy deP~.o'y~dI ~'OOO' ~realnogralI'hk Haallll aro~ndilh~ world. ooml~l~tngworkofil ami:B"}\~lr.;(lki ne,i!N:Qrk
de.stgned to l1IlIooil~OO'"e'1fi10r~(J':5 'Sl~a5. IDill!! fm!ilii

~h~IlQa:tsnave a~readyiu~t~dS!dffi'~slS d1~tect di~!lig€~in the S~gt~fnCQliloJil(lf wlater$~,i1It ,~ff«l.

UfJ@,~l1numt:@' or gI6ba~.~~ifi!dis111 ciima1!e. Clfiiilla~"'fforecasti!1:g '0 cel:!tei'S ar()ul1!d th:eworld a~51(!1ll!.1seA,rgo ab. d and a~,ltie da~ 'Sell; e.~~:;III1d. dil'll'laJl~ predktillml$

!ffilaj;:rrrood \lI~,S i:!liIdlint~rpr·~t

:~w[dc.bl;lt

th,';lil' IlI,lDbcli IUS uaeertain bCC1111J:se

~ di,agnosi s is d~mcw.t and ~uC)srI: ,casesg,o '~11I1re" !~lpafled. Tll.leTB isolate :seqiucllDlced :~u BlJoad ~i:llJ thetowfl of'l'ugcla.lFmmy :n~1 Soulli Mr.i.ca.'S :~ KwaZu]~~Na:t,[ll] ~lOvi:l1lc:e ~n 2(O,S-200IJ., What .~ Olulbrellkkilloo.52 ofthe; 53 permrl."liti,l\fec,too, ~ <11 II. .0 f WbOJiilll, weTe .1Ih.oi,:llIfec:: n:dw:ut II 1~lnl. .~ :Si~ib.ce;theil, :lIIilotlmleli: 450 c,);se.s ()if .Mnl.-TB ;~ lti"iVe Ibe~n rc:porte<Ji wn TlJglClaF'e;rzy. ~Jd :mOi'C :tlt1wp h~lf art XDn Cll~.
'k;! iB:;

Clinicalml

Vfll~mc.sma,y takielong,e:r.

f'm,d

".,,,,,,,,t:._'n .,:b", L.N""'.··""'I'II{'Ii ..."d·vDIl) "'''Ii..,.",,"~.· 1Il1.!lJiiI. ILI.I,.,..,lJj;J,.t~;b.,;;ilirt"I''''"I""",",,-,I'''.~ - ,A. -- _·'LI\,'U Ul .... dl!t.~
~fI.uI~IY.'"
IiJI

NlU1Ml who· c![!!O!ldi:na:t,Clli t~:le dw_g •.r,e:l>isliliut 'f~ ~ernlm.1~t:Wl!lO. cautknu; thal .improved! di~:g", ,

~,msD.c

loo]!> b"lSiOO. ,0[1~ljew Seq'1!IJ~lce: illI:IEJ

~rooaMy a ftml~!,U!ii off;"wllel~s Ii, l1ewgellerat~O:hi1 ofdrngs l'lV"Owd tak.c ].orlger: TheB'mad~I~I"nI'iillrd sWd!y (lomes :11 ~,l,lonth ~,fier a Smiith AfriCOiim. gtoup 3tllnm[IlICed the

".an'e, dev,efqpJ.ng

fi,rst s ~:q'lA(';[H; of the fll n, genom e; of an e XDR·'rB~in. !~h.tfM S()ll~ Aftic<1tld:wial!SCIIENCe:

VOL 318

sl1~l,Iitdl bell(!lme ,Iilin)~e ,QCC::l!lrate. S~$ D:eam! Roei1l:lmndh Olr SoriIPp§·lnstn·Ud~IDfi of I~'alilogra· ;phy im! Saln Im.eg:o, ( ..I~for~i<l, wino (!o·chairs tthe s't~eriflg(!oJl1llilliUee, "'l11his~~IIl~ key '1.1)1 proving to ~lhe clOOllrril:illltin:g m~nilrit".!i 'Unal Ubi!> eU'o:rt deslfwes .al51J1s;1a:i'liled mlTmmilment," he 5<l.yS. Argo's $< 20~rrn~t~iQIiI.a/i'8iIF budget (m1l5 frmll'll .23 (ooI1Uies~ -NORIEEINP:AMKS

WW'i'\I'.sdenc:ema9~or'g

9lNOVEMBER :2.007

90'1

NEWSOFTHEWEEK
:w,Ot e't boon jbill~y aSSel1Jirlb]ed or PQllwd on y apub].k:; Web site. The TB researea 1,1Ib(]I'I' A.W]ll~11ilSrnrm ofa,e Uwversi:ty ofKwaZili.In~ NaJt~~n Dummrupmvwed tlme XDRi:solates.~o bath ~:e1llll1lIS,.The; li'I,ILf'I."<I11:d, g[ioup's main Solruth Afric,m cO.lhllboTam:Dlll, Tmm,1:l'll]e; Victor lind Rob \1!I~rren oftlm;(l C'elmlre ofExoellcocie fotBi,(l~ ~,11ed&cf.l1TEl: Research 3:ttliille Uni'll'eJiSuty ,ot'Ste]~ ~iCnbm!C:hiliil,Souili Arriea .. !Jre pmvidiliil\S othiet ~1rai~fur tle ,ii.iid~r Booi:lJd~ilal~i~ The B,to~d~eil.in,il.tse:d 'hvo !'lequ~imcin,g
~lil'illC

lee hnolegie s, :8ay:s ~11s.ti~ute d ireeter .~iuc: l a:ndJh': T:hlc dstawere genera ted usi ng r; Sole ..... seqaencers=a ~ new, ImI1itlSsi'!,fe~y pO!Ur:,. !II U'e]~echrno~ogy-a,m:illl3J lse erossehecked
enmoee tr.ad:iit~m.l<l~, sequencers, The South

Afric ailil,tem~1~18,cX1,I rival. nI,PW sequ e,'UiI,cing technol:o!sy. m~Roche GS-.F:LX ..Silys L1mder! ".1\8 tilliC s,eed and emc .iem::y of l:~:ti'c:r"lb]ilJ seql~~e[t!g skyrnokets, wt ShOldd. bepo,ssi,·,

ble to, cXlr~ct ~n~rmoU:-J a~ouilt~ ,ofinformathjil aJb.ot~lp,opuJuio!i;l variOl!ti.on in TB

a:wd otl~:er infectilmlsol:ga:~ls~m.R'" As, parr oW~Jmle wi.der pmject" FlSIJl'III tllm,d] Broad In ~tit1lmle Sic:i.~Jm,tist5i sequ encingi so" ~ateSi p~'ovided by iIite]'iJl~rim.laJl rnai;ls.aICe 1.i]],E1", [yzi]il~ dezens of "evollv,e:d" T]3SitlJ"a:i~;l'S ~l;<)!l ~ld!llde s;e:vel:,d XURmil.ci! M]JIR.~!!ol~te-s&orn the same ~'cfflons OJ!co~.nnuni.tic!S. Says Murray: '"At the ,~.dI ofihc·da,y. "NO\\~~] J:l~vea OOITIJJtth!!J:rnlive; list ~fpO~).~l~JOI~phi~lS asoocifllJOO, ~~c:!l;~ui!'lilio~ ofdlmg resi$mnc~:;' wi,th
-liInURT IK06INI'ij,

SCIENCE

I,IN CIHIIINA

[Ma,xPlanck's A.sianl VelnlUlr'e R:e'lhink.s Ills, Agenda

~5Ii1AINGtlAJi-Atiter ~lIm anspieioas start, it '1!.I'IlIiqM!ejoint ve:rrutm'eot't]l!e science a.mldie~Hies of China. and Grnrun~I'IY is ul.weI.'g;oingfJI t:oug~~ tmtside, :rev:~e!j.\itfu.at (lQ'wdll!ead to :S~.piifi.c'Ul;t cha.l1Iiges. The P:mtne:r l:ll1stimle for O:mllpl1it<J:~

'~iQn;)llIBiology (P~.CB.),fOllrniled .2 years :lIgo byt~,l£ Chn:nese ACI!id:eJ.m.y OrsQ~e;lJioe$ <CAS) and the M,fl~Plmiliek S~~e~ (MrGh has '!I"~1i1: prrusemri,b r.cil!ilmtifi.c tl:Cl:ivities., Butr:evil(:!i.\Fa ers and otiliIDetsare coneeraed ~h.o\lit maf.li.lgc·,

inp:ressirnm, that ruJml um]e[tak~ng like n p11l1tner i:urustitlltewm dJevc,[o:p slmigllim1, smoot.My, im:l(l "'!'~thcmt thct~\lns:;· sa:rs ,,1):1 M.IjIIG oi;ufiic;i.81ill. Or <IS ~f;rflg SilYs,"U'sli:kie, <I Ge1rillU'I.'I1 baby .~,'oo'" i~: Mil llil, a iQ,ine:se:v;!.(mld .. ' ~ Much c!ifUu:angst is O¥erwbo :S:lmm~d controIP,I,rB'~p1!iLr~ 8triiil.gS. Theinstitute has <11 '€l.S mim,l)n {:il2... mi.IHon}' bl]dget. two2 tlilil1ds Qf\"!"~,li:l;;h i,s.supplied by CAS. Spe,11IdiQg

leaclel1>.. By traditicn, Max Planck i:lThstiblite!> ha.ve: :seve:ra1! di:oo:tm:s .. WEiIm. Mf\G llIJl'id CAS a:d",er~ised the djl~ectCir'SI.1~p pmilt!>~n 2004, Dress, who h<ldrelIiil:oo ~n 2tl03,m):libIlB[el'ere:I:dI U~,liV'ersa:tyhill Germany,\\i'tIsinvi.ted to~pp[y. Hewas <IIPJj}o~lted ~ibe3clof 1:'112"O:l'n~i:liim(J.ri:c::s c

and geometilEY d,eiP'lrtm~mt ,Melil::llIlwhi]e, :Sin@-Gem:!an ::>~aroh OI!}J;l:UlfiJ:i.'troc tervieYirccl m

<I

,,1

d.Oile,1:I C1\ilinC}~e cllll1.di,da.!ies but affe:rod

~he

Mem trouro,ks are p!1e'!.lC!lting: P'[CBfi'om.real· izing its fum :pilrt"C:ntlal. Ma ,c]o~ sessien on 23 O~'II(IOO:r.P[cB'~
cJiUttilldes(1:lenijllc lldlviJsoryboard chc,\\icd over
31.r!!illD,glll oif'OIM1CIII1S). grcate~~'al!Mm~()Im~'fur~le inslifWC

cl!oc;i~ionN [!111!li~t arn'pmvOO, by CAS:s. S:rn..~.gbe ~m ~1Jl!!tlIil:l.l!t~:[illbcr ~fol'Pgical S~hH'!CJes (SU3S),

'1':'I.'11ioh \'Cf8oes PillCB. S~ BS and otl]cri:IIW$I:itllO

job to nene,
Formc;r :CAS vice :pf,c~idl;l!U Che1iTlZlin:u. (:~if!!a'~ 111ea'IOI m~!ds~~J!.~e!l rociIl!iit¢d l ge~cti(:i.st jlil!Qti'j~d MfO ~Pj;J!x),\.'c~ hi.~s dlC Rec()ndd~n:::cror. Jin ll'mW vice:presid.('iIltl:~f FudaH Ulliv('l~.·si'l:y :i.~1 S~allgh.a.i.• logs only Wt;)!I,U a '\~~k oiWeach 1Iil~:on~b t ~he ~Il~liuu.l;l" ~ But: Ilii:s cantl:ibut1!mls ue~lJlb:sta:w:~i3J~" s:m!)1!1 Dress: ""I,'le's all, e:l:loel[e]ill sGienliist and vah:t~s m~ institute.." C<lncillid<lt!esfor a thrul.d d]irecwr,.., shi p ([!nd :fo~'Dress's iob afterhe rer ire s~ poss:ibly ~:l:itri::r hi.s,3~yearr coIlltr.1lc~is ILI:PIUE11l:l yeoc-were vened :i~l, Shanlil~'nni month, Iflst M3na~enumti:ssue'Si aside ":scienl:iflic<IImy, me .insti.nne hasdene qu~ iI.!11oodljofb,'" s;ays Rlll!l.g.PICB~,s !'dloliln;h~p l~~s: dr:~ll'm pl1li~e.
1'10';'"

'~ion8wili:la ha~d

~ri. P~CB

sometimes db net

see t;1e to ,cjic on ~rioritiCR Om;:: recC:l1t e.xam..~ncludi:wg, ~.'e:CI)],nme~d!~l1g pie is Dress's: r,ji:mto,esta:'blis:1!I areS!e~l!r.ch een.s.iye<iJI"

a!ndd(l:~irrug it dDwMlal1beruil:i;

COJllracl n1il:l:$ out ~,n 2010" acc(llrl~

M PO official lis,t \)!'1CJek, "empha:sb!.~d~l:~tlMi:ng [l'[CB.isi ]!lot an e opHorfi;" ~ays '(;ASpr9gmm otHo~~hl1.g Qi~~lg"

iwgtD scmmes;imfol vediJilI the d:l!l>= eusslens, The bO'<ll'd is now dlr<lil~ ililig~,'econ1mc:~da.tions [~l<lt ill be w presentad aext month to CAS Presidemlt LuYol'llxi<Ilngml);d MPG P're,~idel!ltreter Gruss, who klget.'hiet will dOClde:,rn(: Ill! f<llte. Lu, ]n 3: meeting ,,~'i.tiJ!fI sentor

1.1!£:i!lli,ght~ i!lcl.ude~~letv (;Ol~li'lu,er lN~,r;;thoCi fiJif IN%ap,plil!l.~ pretein netwerks in eells tll<l!t ''''llg pl.!!bii:S~~;Gd lllMature Df,olec/inalGgyin

Oc't'ob(,lt 2006 ~!1d ~ ,c(;)~fl(;rcn,:;::c dcdJiC!.itOOI 'to th~ 400th m:i!!i\f~fiHlry efthe Chiffi:e5~ The t\;\<Q~cie)m:cepO">verl:lily~&e~ Joint ~ie:fs:. ,M!alioomoItkiifllflAnd'm.il:i [I~$S (f€fi) ,and ~lletkiiistJ~1fI t~ ~slaJtiQn ()fEtulci~d 's f!t.~ll!(Jfl ts (.S!';.i{:i'.ffC~. ~~ve be C:1li,excha.llgi]!JJg ~qd!e Ilts 'llrere lap,pedlD lead lhe~ilmn.er Inmtute rmr(,Oi1fi1pultationa~.Il~,o~gyilli :2 N 1i)'\!C:lilm'bcr.p •.73:>, •. snd facn]tymembers since t:Thteate l S~i!lllglhatit t, nll'i'ii se~~il'lig alh~ I'd IC!irectou, N,otiung !ru(';h::lc:lhlevew~e]mls. MOO md'(AS ~.97Q"'.. PIC:Bi!! ~~u:ir most a~~b£.oW]ci,f1~~sa~~al'it .onth'.s ~mleet.ili!lJgfm::oe'~'MI.ly ~DJ.· mI the~OJjQoomQ, the: sJ,).wtialaHallg,emellt tion ... ·e~de·alV,Qr ye!:,. and oos:ervo:rs: s:a:y'tha.t the: mgM!oo aga:~sI: dicssoEving, fhe hlsriMe; S!ouroes i~l!Stit1U;'I:e 51ud Hs 1~m,8i11ilbljndi:roetm.mIDItl:le~ g :l[llderi:yi~]gmefimcli:OIl<Ii orga.lillizalion oFpflO-. sal}'. "We a["ew~mmlg (Il' try ne,wt)m.iJlJgs;· slillys :mi<lticiiil~, AlIII.c:rneas .DYes!>,. iii:re m~ki~,l;g[I,I:I'Ia*.. rouns a.ndp3.'UI'e~lnc:tr.woJk!l i.n cells .. Dt~t:s:s :!la,~ Pia.lIIIg.1:l!"110 no~:eslhat Lu Imst'!i'iceek tUD~tecl~le Ores:!> hillS dlemoMstr3'1e;d] "iil liOl ofpe:rsomll le !'ltmg:gb'!:d fDr montl1s ~() w:un Hlppowl.fur ide.:l Qfelmc:ollIM:~ing IIt'.K:B to exp2llnd~n!ullin.. ~ ded [calion Hud enei'fID';' says Jr~rg:en]IOS1:, the ce]:l.ier tiiom GeJiillla:ny's science, l1iI~:iIl.tstry 00,11 ufjuDlior sc]entist!ilJ]m~ps ([t cunelililiy lru:1lS ~ o cllir«tm oflhe.M<lx :P]<i:n<:;kl.nstina:~e, 'far Ma~'a i]il ei[Ii'~Y 2006. S~l1ce the~.1,f'~CH JruOlS be,e:[1 tWO)i~l order to CllhivlI.te fnhl!l)ele1Id.e:l:s. A. ~ emah:csin the Sci!e:~.1i:e;sililll.e'IPz:ig, Geliilllo1iJny. . W3:i~ngfor SinS" CAS~ and MIPG itrore;aciil alii trickierisslLerorLIl mild G'n:lli>S is,'!;\!,iruel'neF"mn:di ~ Sui.PICB's oonip!l.ex iIiIiI:1iil~g!::;meim.t Smt,Ca <I!1ljf;elemcait tlO re,iea,!)e theru.iilids. how, .. pl)ecociO:1!iI.s,y(m~l g i:nsti.te with ~o IJ ~. ~~re llirH:l Cc,IU\lOO p,roblenw frmndl!.~ b~~]nnil1.g. Oiilie IO'~P'~CEr'8,bi\gg~8t c'h,Jllengc~\, ,CAS :llI1I<Il'lter\\l c.m, be gm~Hed ~110lieltccdo;mtoillLl:I ~ its,ov.r.tl al'§l:ifS. ~U;;URISroNE ~ ·'N~th('T MPG!'!or !CAS ''Vere u~dc:lthl;:;!'!i1i.ve i1i!1dMp:G afl:~cia~C()il1C1i.lr. h:':8 been :find~.g
y

"} NOVcMBE.R :~007

VOL 3.18

SCliEI'NICE,

'WYIfIN"solienoomillg.org

NEWS,OFTHEWEEK
EVOLUTIONARY (ilIENOMICS

i 3,(8), to n,31~gelile.s. 'f]iLe arm01l.l:Ilit oiITIlNA ta ken up by tr an spas a bl e ole.i ents ,. or rCru~ll,tcd regions of DNA. varied by an order of •. .rugliil, Dt llU.ffi the e, cOIllSO:l'tiUHl repol't:il :ifil H~,eg N,m~em~(;;ii:is~ll!e ('IfNal~u'e. Fr'omllm,i sm.1l!te:ri al ,. 'th ~riS g~IH·e he r~ pieeed tQget~let CVQh~ti·onary!~lit(jiifies, P'roib·

illg sek:~.lil]m-:plioteil:ls.

tlililtreSeEllll:,l:Iieuha.cl

~101~g~H\;re;rooonm.li011to ..

Mal1o']]~ :K.cliis oH1iIDeB:.ro.<ildlnsritntein C<llllllblf,~d.ge. M<lssachu:ii~tt!'l, ladan !l.:SSiCS~ITIiSn:tofi'lO\'!;' each typ(l gf~;em~ iOrre;l!~!lmry f!(jgion ~han,g,ed----Q!' didn't eh<ling.e-from

n aJliDEI]S.

ing ~, bio]ogic~lp<lili~~'

p~f~(!lrn~.er ~si~ ~h~ng,cs t!'!l1!m ey.o~i!.!I!~o~S!ry

ol:!c sjOOcics Ui ilien.e;<;t .!'e\i~lI~~ns spec~fic ~ignf!~!J,!fl:8, .K.ems

,one s~)edes to the ~1(:x:t:"l,ets you.~e>c ",,~iitere tliuel:lC'se\l'QlutioMI'y 'prc5:>U'OO drivi.ng the ,oh!;l!nge, ", (l~ys Andrc'!ili" Chl1rll: 0 fComc:H UmJ .. ve['si.1:y. 1ii:s g.nJlJp looked all theili!J.~p@c·r of pa~limlog:eni\kThey ,e:XR!IU]l}edthe repertoue of giene:s ~nvelved ~n~·'e(;;og[l[.~~ngmi.c::robe 5"
5igrrli<lru~:ng an i:lni\Side:r~i!il~iII'e;senoe:,

nud ~.r()d:tll!cjng, texins to thwart lIIU~cb-245genes ~l1Ii O. meJall>ogm;tru" <I~.one;lJrud 1200 ncross t~,~Je1.2 slpeci.es.

aliiid ~thc:l's .have :i:lil(,';o·lipo:ra.tled t~~osel!e]Ua]1;: patllCrnsiflito SiOfiware to ~ookfor tle same path:;:rliilsu n o~:I'D,cr:speci e8 te p ~n poil1iJl~ cacih ly pe: 0 f DNA. "Th is al](lJll.lI;I's IUS 1:0 ~ ss lgn :flJllleli!on ,., 10 some l:I.,:gi!ons"t'hioorugh c()m,1)1;I~ mti.oIl alone," :says Mru:gulies," Based on D",;.omluml.paH!e:lli1J1of i:IiISer~.mls•. deh:tio:ns" base 'IUS:<I~e'l <lind :SIJJhst~ttl[iCiilils:,Kellis aad ills eolle <!I\!!lue,s detected :~ u I1di.:s~ 92: covered [lJm~ei~t~codllm~s:e~es<is 'lIVen i.I.~ '150 that do :IJiQt f()I~low sl.aodard fl~e8, l'y,ilcaUy; prnteincodin g genes 1111\,1(: a" s~op0, ~~GiI1!lLe[!,(;e tlrat sig]1):ah the end ofdlC: g~!~.Bu~~l tl~sc l50,cases. pr,omll1-()odi:l1ig ~~lmre.s exlClrnd~ IIlJ~yQl:!d t~!(,\'~st(;!,.""'If~<lh\tay~ a 1i1:~I!f; HI~'b[ing tJrn.~lt tihe ~f1SR~m1p~ 11.0m. '\:ve 3/l:e Ul!;Ig~u: .11,1 c:hool dlo $
:IilO~

a$i'p~yacms~ ~[~genies;'
.lliulldmll,.

8~~S

Ew!ul) .B~I.'ney of the EM .. L R E urepean Bio]nfonnalic$ .. ~~rnlstlli~

mtem
In lfil,UIJllyl:1iru:if. f:1y species .•some :f<llniJies ofgenc's ~]ulllltcnde fOIl aJnt~~jl:1ic[ob:i;al peptides ha ve be enexpaude cl!, C lark an doth er reaearclrcra fm.ulld. The eCl!p.rl1:!lio:nmlll.es ~e;f1s.e,lIS a flywith ml~hi.plc oo[jie:s (If the right genes;canpreduce m,orctoxinand meum a 8t:rolill.ger defell!lsc;, i(::~~tkxplains, e
i!m~·p"'li"ticulmdy

UK ..

WI,ill til e::5e:~ nmv toCl~s;,'Wldc,h

use:f:1lt1 for :recogni.zll1l.l,'l

UNA. KcUi.:s and his col[,eagues havepieced tQgethe.rt'l fruit fly I1lf;ue ileglJli.<btOIY netwolV'k tfro at i.ru:;OIr~,J()ra~e~s 81.m~crDlN.As 1l1lllicl6"uamu8cripti.on [actQrs. "The ITH::thodology ud plfl!l!ciplc;~arlll .;'lilOgolluuc[y :~;enend,aJm!CIthey are applicable Altho~gh rhe s:r,ol.!p djdn!t fiiifid Gillmhc :ns; t(l any genome,' s;ays:l{;eUls, Oth~]'Ss,ay m~!:'!y dup] ~cU~ d p~n1~Qge ·n';CQ gnili ot! n that 'th~ !nodel ~IHl!l eeds j',cfifiing: '~Q recon.g,(l!'i.!i;l~"th~8e \!(!(ire 'the fasll(lst CVQlvi~g. d lie it with '!lixp~rim.eli1ta] resu lts, But ~ll~m a Singh c r McM!1!fi:~r Un~r cl~'ec ~i g '~henee dfo r ever- c~ a~g i!lg g,C:!1e~~c:i n I:!I~ d'e:Fell:.5e~aSmlcrobes ~ons~ntly CQ.e 1,11' v er l'1.~tyi ~~. :l1liili. ]iiQ:r.I, C.an ad a. ~5 q ui '[C w~th '~ys to evade: detl::cti01l!, C~amBl1dcol.p'I~8Jsed with ~lm!isbeg~~11l1li!Thg.Be:caiUse mly l m leaguesreported onlhu;& NO'll'eliiilllitlc:r in fhill.i.t:fly and IUl.:8J1l gCl1J;es ~~:ICcq;~livfl.~e:rlit~ Nature GrmeUcs. the ndVv'O~.'k"ts gOlil~g10 tell US a h::1l ,about The C\l'ol:ilu.i.onm,·y 3J:1~m:y:se:s y~elded sn r:. 11UIm.~.mls":·' IPmdi~C~~;L he prises <I!> well for exansple, CI.~rk·steam 'f:l'n.e aJlialysis bode~:5\!Je]~fm: tlil.c urilill:y of fOilmd that HI newgcl'te c~ned dro:son,ly.ciM, bird, nk1JrS'lllp~!j], aad :repti]e ~quem::es ~nm.m~ w~dc:hcedes fOf an .E1nt~fhngal eempeond, ~.y"zjng t].e ~ir~man genm.l:le. It also i1D:k"l!l!es lIIp,ear~on~yin D..me111:flogt7S~flr and ·'I:s osil!, d seql!liencin.!i! 3:nd comparing all UUl: primates, rehltive:s. There are no. due's. im;m~e:ver,.lIS to s:aiysBirney: "The t ..ke-home Message is lim ... th~sgettJ,e c,lIIineto be. Anoither s1!a:rp(fis~, thin thereare 011 ~o.t f de';!!Itwlil!sfroiTIt domg o 'e,lme from:l:1i!te8~p'~cile~ wiUMo./,ii: It<IDoe:sn't !hit! sort orlevohlriOJfk"uy !cnOlmic;ll," I), -iEllJllAlB:ElIiIIIPENN~!i1 seem to brrwe g~f;l:-i hl!m1ll1oeprote'insco:maili1,'
re~1lt]<l.tory

ror

... NoMgiitor.Bi®cl~gtst.Mdae~ W.· slands][I :Iwon: at~er '!\!IIIII ~r~1 ~~!i'll'l,liIg~I TllltFi~ 1!f9~i['Idiiry~a:O'IilI~In~ pl!()L ~ them. l;k~"\idid 1:lti:Qsepioncers ~nantlge to get berc-?

lndeed, !mow docs :ainy cre<l!tll..ureltiuditis w1l:Y 1lCI'OS8 fe~lrurel!ess; expansec£ suchasthe

heme Ocean? The qlw.e~tt]olllfilsci.lliates

Wlillk~-t !:lindIlias,cemeto d~f~ile; his: ca·l'~et eo~p~t.i1!iig theories hav,~ bC~j,l propo~ed 'iio exp;Jain 'Ihe 1!Iifi!e~~ilfiyotietilceritlig o:filiillilllli!l~S
<\ij!;';

d~vef~~as birds. b~(l& •.~!ld fi~h. A d1e¢~d~

~go. WaIkJcrr's tcamga.I.Ya:urui.1:oo dllc; neld wid:! the di:soO'llery of an on:gRlIl t]m.at 1~1;&y fMnctiQ!1l ~s an int·erl:rJ:aJl (lomp<lS5~ aJ str.ingo'flnagne'tic crysl;a]s [111!l.e l~OSCO'ftrol]t (&i€moe~ 5 Februl8J~:y 1999. Wl'. 775). "Wal.k!e:ris def:illite~y a lpimleeli." SEty~ bi!op.hysj.cis.ll'hol'S'~en R.irlz of the Hiliiv,e:rsity of ealifC!nlia,I:JJ·v~ne. Now Wa:]lkerbelieves.he is.en llie\'e~e ofd~nch~ iTIigthe case that lJI.l<l!i].netD;te the ull]vcrsO!'II. is <unDim..] eeurpass th,u: !ic~el1;ti.s~s:ilnc been J se,ek~lm~for<i cCllDiry. Blltlille beliefmakes W~ker ,I~.nav~i:c~,: Most others ~Il the~':ie,ld
~IiC

cenvinced tha.t <li!l]~ll<'1~Shav'~ morethan

ene nilvi,galion ()~1Ii~1.

A hybrid' mind W~lke.f ~!iildto chart ~is Ol¥npmrth to, seientific sueeess, ~H~ mother ~s,of EU[iOPC<lf!
8!IlCJestry. his fflJ~ht::r.f1. fa.olls M.~olii~cadt::r •. "and Jkept f~lO!'ie halves of my ~]fe ~el'~I.·a~:e ~ndpa>alld~" he say!>. J~ere:W,\l)li: the Wailk:el~ T who diolllJ:lfrued shi.rt Sind tie and keenly dC'iI'oumd bi.s IPlThys!cs!,exitlboo"s. And there W!IS the ~i~.erw~rnQse M8iods:rd.ll1idlllQ!tl~el: t.aJl.IgTh!it myt~.l('!kJgyand t helunar sy:sh':m binI fOfp~a~l,tingfUlldilish:Ung. The result, he s~ys, was "a lmlybrid lIiIm,ind:' It \\f.1lsn'l ml,lilalleF a Paci'fi.c odyssey (If his own-a P'h..l). atthe Llll1liver:sity of Haiw1IiifuUO\!,ced. by.s yeiAn; of,ostd!ocmral. research in Calif{)m~ll:-thaJt"th~ 11I0\ii[vcs f~1l1l.lly ciinlc tQgedter," Wal.k;cr says .. fl.!g~'OnWa3 'I.r]gger~d by hh:l ~11.C:!1~oriml!~f o Maori science ~studCf!Jt!ilafter liclumilli,g (i() hi.$, .ii~mama:ler. t:~eUniltef8ity ,ofAl]clltlal:ldi. . in 1990, Ma:!W)' ofhis ~~dC;;~lS· st"Wl:!lggl(; will:! cultural di:ssO:lili~ncc. 'W!!;lkcr, S3. hi now hc~ping: t~u~m e::mll):mce; ~oth eulrures {see s:ideba:r on p. 9(7).

Seeking Natlure·s

Inner Comp'8SS

no

.Mii1clhae:1Walllk.erlilas nalll'il!litated 1~ltdtllllres ami ~olUlied t o.l1Itr lver:sy· in h~St ql!U~SUDIp.rove tlll,at nfefornrls posses,s: a 8ih.,ule o.rgalil. tOlf' per!cBliiV'iillg maginetiiic ne~ldI5r-aSBIIlSiU lbaseld 'DIIlIlalfU~~iiltB t
l l

A.IlJiC.KILAIN £I,. NIE.W· .ZE.A.IL.A.11U)-Mi chad WaJkelr S l.i.ps off hi s sho es and. e!:l1IItersall eaermeus :Maaf] c;f::rellllu)lIIIli.:1JJlfOonl. theU:l1live~':s£ty of AllI!c.l·dalld.'s ni!l1lcnuianlil~.g~i I'II~U. :PadIJding <l;CI:iOS:SiOIlil,g\\iOOde]lp~1'Il,d(s. th e bi!Qlo!ll~ exp']ai~s, til.l e siwrnlifi.c !Inc e of st f:<liClrn, ef d.o:zeilills. ofpai 111,ted 'I'!'"Oodieu Ica.wi,wgs

"He WillS the s,kuppe:rof a canoe whieID sa iled to N ew Ze ~ hind fro. III til e Coo k I.s:]<lnds."i'or that uneivaled fe:.u. 'Iuri
g:fl[lleda plaee
iUltOng

:lial\lhiD!g a lm:ylnid mind Caill a~!:i.mtil!e:s pl:O~ dnm~"d:iscmmld'o!n'~ ~nyar~r OMm, sldn~" s~ys

Walker.

Inn i.1: has advautages,

the gods.

l'Iu,e c01 0,1] izatiolill

ef'New

Zea I. <lin d

he:rnped me to bflaware th:9t there's ,f1]ways :molie than one~y to do tlli.ings,"be slIIys. f o:riJilis tanc

"~t has "" ~

~
=::. -.'

oliii.U~:ew<il:ls <IIlld pillars, "'fhi.s is Turi," he says, po:il1ti ~l,g cut il, highly stylized hUl!!illlfloidi whh a £~eC:rIhim on its shou Ideli.

igati.ort Tiu:fi rst Miaori. visitors traversed thcusands of kilemerers Q,fQCeM wi,'~ll ~.ot h ~ng but fh e sun and sters to gui de

about: [(100 years .1JJgo, ia:st oh1rnle g~:ealt the F\}lyneislimrnlm~gralt:DQ\ns. is ...marvel ofnav-

Ze<lru"]lidl's~1in,t: Eun]llN:!~lJJn visiter, the [15th il 01 century Eng~~sh eii:.pl.orer h.• Ceek, ~ es cl'o::i~edthe oceanwith the help ofa m1'l'~g- ~,

e. he :poi ~rn.U utl:l)ut 1)1

New g ..

netic oom[p1!8S. ~nddt!g hil!l,ship·s. po~.it:i()f'!!

"} NOvcMBE.R :~007 VOL 3.18 SCliErNICE,

'WY!fIN.,solienoomillg,org

NEWSIFOCUS
Qna. t'WO-,dbncllsi,Qi[lal !!!:Ii"ud. .A:~oin1lighe' way" • t Cook met Macriuavigaror« ",11'0 aou]d i:S~i11Ui1d,,]u,op more rehllibly usin!!!: pol<llr coor~ di:l1lale:s based on s;tEIr~zenitbrn pO$i1ions, and kl1lOW]J1 dli,i'>ttiJ~,c:esbetweenislands, W<li,keJf ,~I'Es s~ihld the PlJic~if:ic us:il1j!iJ:bath systenl'S,. He has plU.~t1il1lt ~'Kpelf,~e",(;e:~()use lin lmis re:se4llI1d~,01'1'bi,o~o,ilc:al 1l1lVi,!:l:.<ui<eu'I. "Animals O1iIre imi,~lllfUn rll.at thl.liy use di~fe:rent 5'trate-~ gic~ on (I.in~rejU~cf!IG~of lim~ ~TI!d space," ~e ~ay!'i.A bird\\liil!lging :iiIN\ilI~y b~t:k toi!:s says Ritz, NoOt only Is Barth's magnetsc field J.himDJ1:-hullilcllmds: nftinms, '\;ve~kertbml tbtlt 0 r ctJJ ch ~~ b:tirm1ll!illlfl~;-butfoii d's <in nnhnif.d to track its pesition us.iug field
\"l;f,UtuioIlS.,il MlISa detect ,clil:<I!llgeS as small m;; I, % ow t1m!lIit si,gmd.

sfly:s.. WQr.kiug the] r way thro.u;glrutfll,C head Jn th~lil.frozen slices under a m~:glii&llt[C; force Inicrosc up c.-ag,e 0 log is t 's to 00 [-th e

resesrehers

found a group

of eel ~si 1m. 1irue ~

S everal possible rlleetmrrli,s,M:S eilflr!iler,ged in the :1 970s. One L1O'I'I<1, eoatender is a f~de bio~o,;;i,Ciil~COli!l1pa;$3 m,~de of magnetite. A.J~Q known as,lod~~wne;, iililJ,flgl'tCt~ieis the: tri(i:M mii,g,i:le;t~c form gf iron oxide and
loccU!rs ftla!h!f,f!!]Dyi!l ro'Cks.tiving, cd ls (;<'!!l make 1:~ine~rQWllti.n:y .ma.g~m.CI:.i1:e rysta'is. c

nose Iii d C,lIiIl 'W~th st:rilJJ!!l,s,of llU~,lII~llleti~e eryst,11 s, Cruei ally ,Ilite cells :iCf''=wi tedlto tmlc brairrv III 11,11 erv e sen si tiv~ tom agnctic fi,cl,ds, "'This is [\e,~,lly t~lle finn ittllly new typ~ ,Of!5eJil8 O:iy eell to be d'i8 covsredilill 011 ]o~,g.\'vl~flct's~ys lK]rsch\;iim:kw~~I()\.li'ai!ii ~Ol an ~lutl1l()r 'ofthe: Nat{41¥tp~p(it!:l, "~If 1ler e is
l

~es,t \l!S~8, visual

t:hlC Sl,]fi

from t:h~ p08ition of to t~c 'lay ol~the laiilld,B~t(he sa.e

CU$~>

~ver '" Nob~1 "fi;t;lr;;for magntlti c·~1~ld pcrcept.~(llil', W'a]:!kICI:'s nf):IiI!!IC will be en :it:'
Others arc not' convlnced ~llaJttMs .~::ll;he fhU s~m:y"ftiu1Il a]tenm!a!rnl'llc ll1.eclili8Jn:ism for .!R~le~ tereee In ion, known ~IS lh e radii eal-pa ir l1Jod:e~.~ms g<I!~ned ilil sl:ro:ngro~~owing o'ver the; P<IISll decade. The idea, is that besides 1J:S~ID1g m1,lIp,et·~te to detect tJrn!e ush <lind puU p o~E.. 1; ma.g;i1,eticf'ield, rth an]~ ]'iJJiJiii,]S 1i]sok.eep track O'fiiw~t~l a che:IllIIi:C~il.reaction, U W1I:8 (),~;lIy thegterti caluttti I

'I:Oroccp~orcalled c:rypliOdlli'tllnle was d!iscov~!1ed inthe qt'S 0[""0[Fl!iI:lI~sas d~vcn1.eas ftuitflle» ~l!l!!CI .k~. Whc;,11iglwtstrikes thiispr,ol tei!liil. it prnduees t.\VQ !po~si:l:lle il~~ier~rn:ed]at:e s:t;lltes: diJfe:rhmg in iItIono.l)() ~:n aq,~~r.i.!,niJiJ o:rie!'1Jt:s 'I!ite cOlU'is:\rur3~:ioirI oif;S1s~~lgle dClCt~eH;liO\!;rBlI:d home lilce !I co. pass lHlli11. 'fhe:hr ~"9.tio d'el~ends; on il:he ali f:1'I I;Sit [on of c:ryptochrl~lne~ w~th cl,8I:'"'s,..., . . '. • of :il! lnprincip le, Earth 1; m3,gI1Ie:hc ~W!:!5i~P~tSt). ~ ~kelr':5 t~~!Iii found l1i!~gJileti~Q and liiLenoe.tlil,eoilr,~~l'lta.tiQI:l ~~lC ~ field :p~:ovirdJes elrlIOU,~~il Il:lf~ar,ma;tio:n ,ery[)Mls (above}il1i. the n(!o~~ o'l'llslh; (lither Qrg1lJli:sll.l___'re~.athre to Ha,e a:mb[~ "" tour an animalto cress 1m,oceml , by res e a ~dlle ~s bell evel iflM (.,rry pi I) (.~ I'(jm e en 1; nlmgn eli c f'i el d" Bee au se i (mode.1 oli $t:jt~1;/1 n iIU!iJd:o!iJ, ls an ~lt~flrHlt~ a cryptochmm,e ~si ~,ltlrn,e reti 3111<1,. ~ fin Ol."WllIDIg, without gOlQ!i1: <1,:str,fly: mi89I1ietClltrn(9:ptio'.1il organ, :tl Fmmmest p].u;:;es: Olil. tlmlC planet's .[litz aad ethers have proposed surface,. ~Jrul.e m'l.plclilc fieldpo~nts. t~i~:tIJt tFeedisfim:!ilnetic ~ in form<l~ ~ 1111011:1:1, so knaw~,ng wh[cllru directiol1l you a!Fe tien to' the bro.:illTh1rur-ough the optic aerves. t hllJd td'il1l1l:f1g,iM these cry~t<l,I,::;; ilren'l there ~ faclngisthe easyp!lN. Chll,Q,g,e\\lWil 'I.ficld~ < Bitds,for lexlilmp,le.!11aijl "s~e" E~rth!\i m~~fO:rnH.I~tic dielec;tion." ,antic lmc!ldl. El1t~JW<'llkelf. who h~d ,;'I]r,e~dy madJe a netl.eruold '''>'i~th",rew,qll]c'k ~1J1f]lliS ~iilfi.tcn8,ity 0][ <1~gl,c,.wl1ich ~enC'ndly gW"'1 "Ma!llYpieces, ,ofth~pl!l.i~e 'thatlWv~tf1:t nil~1ew:idl his ]!11:l0'iiU:iv~ behavior:al i;l;ti!JidI~ 'fltro'l1g~r.nd ste~rpl~H' 'loW~ltdli~e $!,ole::;:" a :g: reve;;!i hm'l'i,j;d~. mriJdel h~ve ~tartc>d1 k;~ofn~hi~~ oCintfollcdmagnleti,c ne[d~. \i,tCrn~ with the mlI:g:lliet~~ ~ Gauging longitude h tfieki·e:!'. On,c U~ bCCii~tie \i,>l;jdded to 'thc JiimJrligrictHe Model h:i l,1!laJke a: k)t ",r sen!lC,'" say:il Rib.:. O~J(; of ~(nn~ ~11~111Ial:,:l. pamtic:~!la:!":Iy blrd8 \ ~ ~pprQa(;h~5~O nme~he :fruf1~ pOSiHO~l as i~ dtwing, a po~tdoc 5,~i!mt in CaJIUbr:I1i~~.";h~'ic ~he8cis ~~l~t a:n:d~mphilbi,a~ls~ dJo not see- to be S!e~ls[ti'i,l'~ h'e boullIiccd the :udea o.:ff b~ophY:\li.ci.st ~ris~s aJl~.d~et:s" Beo,a~lse Barth ~rn:'i~I~'.ow ~n HI pol.!I:r:ily~ rewcrsing!l fIeld"s Im.orth 3Jl1d !Ioseill][J1 .K:il:schvillk oftJn,c CaJU:!i"orniiflllnsti:lUN.H;,~n k]~ler"fl'(nn" rlsm~gn~~iG ,~XH'~the ~ sun's, nllJ~~I:S!Cct~(liI'IJWlt)m.he ~rnQnzmm, clulrI.!1:e.s t south p:I]~5 hiJ. the: 'Ialb ofl~1l hills no el"~ct 011 tL~'~e of TbC.lm.ol.o·gy in lPa:,m (h~1JiJ!f1, With hi~, behavior.. "7h1l:1 is a Ilredi!ct;io:nIDo:f~her2td:uc;S!~~ :5 :syslelHm:tlcally the f8:l!'t~u:r eastorwcst: you g,eosc:icllces bac:kgrOlnld, K.irs:dlvink ~s the ~ go. PO]" ~mlf:nV!I,ter !lJl[l.i:m.!I:~!>,. t~lel)e is:;). :me.sh pl.l:yS~(l:S Y:iu 110 WaJke,I"'s bi.o.l.ogy Yling. Aa:e:r plllirlnec~.li3!n~sm:' $a)f;sRilltz,."ihocallJse it O1mlly the duo extracted ~I~~jl!gn(':dt'e~ruke crysl,lII.[s. delec,]:s; d]sp] !loemenl foom the nO'l.1h~south ~ ofIllmth~smIth m<l:H!;fIIctkri:dges ollU1Jeoceilln ~ f~Om'-()l1ealed by tI~e s;lJlire,f1d:i~Jg ,e,ms;t iI!;[Id fromil. tuna. (Sc.ie~we. ~: May 19:1il4.1!J'I.7:5 ~), axis., nol ~.fJI~piPing of1he ~::d!;.'" & Wtl~kC;r\\i<lJs. 'COJ~,\I~nced ~:lil~11Iir lfeywere OJI1, e! U til ~ Mu::pei'i.odk mever:sal olT E .... th'l>mll:gneli,c .A 2004 s~udyin Ncmwe by Ri.tz <lind tma o'fthel1ea] bi,IQ~.ogicll.~CJOmplilss. ~ lP'ok:s-;~lrnlllt C..1bll be .enlO'ri2led. others. pfoOy~ded anoOther test. The Cili'YP~ B~,t <I1.i(}Il~~!i:talIilldililg riddle j,s,wli<efhel' . The MlIW,1,et'ite mode.1 sUlI'ged with two. ~;och [iome COUlpas s,. but 1'1 at mll,gn e~'t:itJe. IE. Mi.m~h [<iln det,ect such siU.lbdef[lIcbH},~· stilllidli,es ofr:<I]lihow '~o~d tll<I,~Wlll]ke!['S 'Ie,lin shgu~d 'be di snlpted by oett,1Ii~ilfteq,ruel1ll.c ie~s ~ ~jou::;;. "!FO'~;fl.l1:1<i1gne't;or,eccption or._g:lIrl to ofeIJectro:m:ilglJieticfi.elds.. Eiilfd!$ e:~po!::!ed: 'flO publi::>hcd ~n N~/ure: gn W 'I <lind :2;0(111 "We 99 ~ 'I.'I'(H'k.h ~HlJst be amllz;i ~.g]y fine-mned.'" studied t'e fish as if i.t WCil'~ 11 toc;l.," h~ thc's e:flie<!illi,enciIClswew di 80~~ e;fliled. "T1iHlt

I
31

bim i!l!t seaw~W~ d:ie 'wit:lI!lout Il1(l!OO ,giIJid,mJnce. Some mnd-Ioviug bac:u:df! make 'm;:;JJg.Tbe sun i:lThd~ca:tes a head[ng~ bus 100000cr long a neljte far orh::I1I!;adoll. find simUaJr ,cryS1:{lls fuI~n[ eventhe sliglWtes,t: eress-breeze wU] have been fll)t~lld~~la .tMitlJ~de of hrug:h.e:r cause vast do, sp:laceuu!1iTh1:s. ,H Dill-V does the organisms, M,~I.gne~:item!lY !>,el''Vcotner hi:rd ku,o,w i'l: .has: been blown off' QOlIil's:e?' mncrimms. !!rtdl! rlS .I.o{;k~ng 'ILI;P exeesshoe, s~yslGe:~.l:Im!eth Lelnnann of the UiIm!ive'I.'sh;y The sb:,lh :5eIIll:5ili! of North CaJOO li JfHI. GI:I~I}e;l. llill,,\1!!'!.lOoS .Ul .1:1.1 tliil!!~ 1860$., Russiian zeolagist Alex<!']1J,delf lex.pcrl Olm,mrt]e ]1Jlli~~;:rI1.tionl. U1!I:t Ws very " vall Midden dodf frntst: '[J ot~eed that some bi rd:smi,~;r:<Ite a]oIilig: fixed [l~ths. ~a.t~r i",ec:<og~ :m1il",ed mi .EiU;th~ u11i1i!!lueti:c fi,e.ldline,.::. .. B~lt lit: lool another ce n h!Q'o,(: fore be h avi on] bioi ogi,sts demon SU;ll;t~;d lh<1it~ll:1ilil,l,als cain dJc:tect[1l~g~let~,C~~]~~ds;. SU~ '~l1o~~gh.a<t<ta:c;hi.'!til: a magnet to a! pmgeon's beak i!uc;rfc!fe;S wit~ Us 'return to the reest. Pcra ~iI!I~d< reward, fhh C8!n be t!!"ainled re~pOll1d~(l!magne~ic flehls, And alobster 'l1"3!:ns.pl{lnt,ed~i.,,{ll~l. sea

W 8. when '99

a can didl1'lre milg:Ji1;";:-

~,:s.c~eIl10ema.gl.or:EJ!

SCilENCE VOL318

9 NOVEMlBER2007

905

NEWSIFOCUS

The'ln M,aerl Q!JIfltOmi 1nflt~HW~H~d1. iio 'g [lOW 111 ro:lifs" Sih~ IiJiIlllIst ~~fll:GI )Ol~lls·f1roIirlUlie hrajnl~ e~ .AU.CK1AN I, INIEWZEAILAND-A mJeetr~I'I,()~ of (,[I11:1<'l:~er:5" .BlllIt in. M;:ro r~ '(UmtJllI UIl\, she :5,c.J!lS, MilIO,1i .s.deri!tiS;ts: beQins li~'@ no D1tlii~r. 1111Ii .s~m~ "'~I[H!h~'~ iindll~HlIiln~re tiffP!), " a !!a'QJi~dIbod;Y dl!l't!IlXti~"d (:onf@r'~m@ rooit1' at Ihl@ Univ.ersi~v 1]:[ part lhilt muS-I mOil ilE' taJ.lilII~f~dl/jii~h. ,i!\y!J'kli!liId, ;a, ~(]Ulliil~ d()~~lil ~~f!~lrther~ri~tl!" 'c~ 'F.!.i3lthrtirIh gill! b"'!;I!Jlfill'!litl'le Pn:Jij~(t, CI1w li'!'Q nl!me,~ ~Q ~t\!~,W.m:ml.llfLi:ty [or ,ardJjJili~1 liIl[isi" :She in. :~mit~ • and p'f1~ssf'~(~Iil~ads tlO!;ll@'thlf ]1'1 a hcmg} ~ret,t~liII,g: It 'r~cw1iml!!J1~:pee,ch 'IJ!~, M'~01i ~1l!SS~ii:I 'IJIii~ :l!lr,ob~em~~11 he~' [,aJmily,th~n Mt~ t~e ,~ldie'~Si f ~er Uiibi~.,the: N!!IatU stalillgHi~i. o U~I!l~ue 'inllliOd !:J'ce~~ibe ~'~CC)m,e:r5, Ofiljl~hen .some ~:iIIlIptored l~eiF no'lhJ,"iIIlieS) with mplJ, ~ s.h~ dlQes the ~afillJiJ!ag~ sWr!1li:h to 1S1~,gt~sha ~tI ~h(! SQiVS:, (:Idlers dis:~1:siSedH i!u'!~i~g ~Of!"saJ$ ~i!whl~le 'u')ipkl»~cief!Jr:e, Tbisis; H,oriZi~rtiS' f In~~glht, Zel3ilalildl':5, o INew JnI(3I't"S dis;ea5<e;~ BUit the elders '''Sl!:!Pl~Oll't.ed ~he INilI~']OIi1illI~ ilifstiM~ ·of IRe!>e:nch ~.)i!fel.lelll,cef()lf pllwpos:e 1lI,f/tlhe 'Ij\ICIIlrk.." she 51I1YS,. a III dl i:n'n'led (he'lmg'~IJe<lIrlll, ~Im:lllding meirr P~.lg. (3d'!lili')er, lMami Ili)e~h:Jipmfml <l11iId! ArniiJilIlneJernent"--knowl:I Ridif(3rdrfi,l~~~ til 'ta'~, p.<ilrt. Th~ oom!Wai'l,I~~t,ed ial1! here ,!!IS ~~e Maim:; Re~B'l ~dh (Jeni~[e. locla,y. ~~adllIi1lle :\ltlldl'l1i~ Ollll !:l'ntier !a,fl!!l1:ts: are '!l~'IIimgclilil entire >cillly,l wi~h <3: ~lIIg f\DRawing ev'l!!rJls~~e(b. UIIlll~ilteiIlIn1J~eir'WIl!~~. N'pt mlly di:dl (he'~l'IgfiH.1Y rnej~trr~ilb"~':5, oni.e~ w ~uture15cien~!its..Ml.laal1i]~ CIhGliUng 'klm\te~'alKlfelLCMI The Mliloli <I:mB II :5'1!I(i!P~S,srorJ!' ;among. P!]!S~- 19;radiJIi3i~E's;tJjdleillt5atcllri.eilJUlNln'ity of A.uciltlal!ld. iJbi[)tJI~. he pmjlld,~llIow UreYilllhD lelh'~.f'ledlly ~ ~IJiPljil~rildl:.. 1.\. slliesi3JYs. ('ololil~:a:l rlil'~~gemnUi5 l~e~!l~El~, billUJ'n:eV ~.lill tliC:1l! ~E!I'ffiO.lllS pmblHrl'5:, Among New Ze\illi!lilllders~ M;aIJ'r~(jti:~m:s.ii3r1~~.ilIrd'~ned A~lhougilli Ifi'i,l'li el.d:~~ ~olJ~daM. d1i31llig~thl! brailil~ :s~:a,bJI!j j§ "¥I/Jj 'UrI ~ 'wi1!h 111 dis!I!!IHl~CDrill0Il111~fl\lV Mte of po!jl'erly~"aru:g, aiJilI!1e_,i3Ind v:i~temt (r,~1!ed ritual!! ,~!bi1ll[lllrl!' new parI. of her d!afly ;~flbrQutin.~. l~fO\rt,~ and ar1Je;r h1gifl clime. MilGri srude~iI511ire War~~~ [iRJ!lv thii31i1 ~1los'1l!,M ,E:jjWRlf!:a1ii ,aln~:~'~~ gsoliJltling i.tllild~[j[t,i!ifill:g il,tlU ulllii5, she' ~ary~illl praJv,~kI "ad.lIIi!!JiNteGI gi~~J'i~ lo,h~!S.h ,Qjfl Qnde;rg r:ad.l!ita d~gr'~,~, elil!~Orle ellil~,ef gr~duClJt.e ~o'hool. AlTI'rJ PJlr.~Glnwille' ~1iI.~pil:ssed. ~1!l~ ~lIitil~; L . 9i~ ~hdr (\\imily bas gMI1 IUS.~· :She ;a ~Sl~ ~ Illd sh~ \l!lliI'WIl'9'~~~·sewho do.•f'~:ch OQse 'stief! (~. BO\lsd ngMilliofi \l!cad~liIi'Ik SU:C7 l~rT! ~d ,g) ':5001'1 bo ut (fOOi~·Of!. "~lillll'~limes ~.siililQ. $om~tim[es OiJiI'~,:~ c~$si$ ill 'iII«~:SS~I'IiY stal~~1i;Ifl'9pOhlilrilJr eq!J!'iilI:ity~the ~e:!1I~er"$ ~~'H.$~OO(l\Or, Saiys. "'It dep~~d!s, i'f t~er,e ,He Q'tifl~r r'~$~iilIrcht\!rsrQlnJiUllid,il!WI,dJl[ I r~el. UleMi(~ a~l Wi!,~ker l(see ffi!a:in~~Ij, gjnd o,~~eliSargu~. l1Ji1a~:':5; [!we' raf,sQf11 d"etr"e i'!~~d..TheSi!l'I~r,o(~ssesa;.reabol~nk~t\!p]n:~ IlI!iIft:lilitU'!!;allJly s.i!ft,~ olf~~e 5 "y,ear40ldI (eli!tte'r.,II!h~ooa~llil$tl:)i 'hrh~rl(i!'l,le m,e ;sodal gJnde~r(!n", Wlhlat rniW seem, ~ike il!!!! ex;1!'~ b!!l!rd~!11 ha~ Iproved tOI be .i) boon, Wifen IliIIBilI!ailln'ei!Uh (If Maori (io:rnm iiiI'! ~til~as weUl es ::;uIPlJ()nM~()1ii Ph. D. stu(h.eU!ii'~ sta ~tedl .~elli·Ph.Ill"j Cci!S~:S ~f HUlrlli!ilg~Pfl'~di:sei! Soil: w~r\] !!I! n!('f!'!)wr:I d!eIi!Ui, Whe!ill~hle ce!1lte!'.sM ~~ed~it h.oped ~ob"~ost t~e' nill.ll!i!iiber o'f :IIIIia Of! i1Imo:!il'~tI'e M~~ri.IBid1rHer ell!g:~g:ln1g1 ~,er~riibe,~l:~eQP~ $ta~!:edlc(l~~!ilg Ph.D. s'~l!Idents: ham (3 few d,oilellenlmiredilll 2{)02 'lo :;I~ tei31st 5,O'Qin frnxli\\!3lrd.,~ ~he'~,av~. fOlilr l]~e~y eases h(3I~~ bee!l\l dlilaigj!'lo~ed, i!lUQdi 'e:n'e'ill!i: g C{lUJiI!lE!lor,l>a~ Ii'IIOrl!Ji'liI!!1 illi; .:ol11i mmllilDulilitie.\> f.pJr'~lfIe·Hr!lt tmlrne· w .. 5: years. 1iIiI~'I~lldtOOlitoff a.mead Qf!li~lfIed~~,. dlallkin.g up,tlh'~ 500'th Ma~r.i OeWJI'I.g's:e'ftlforts: a~ rDri~gilil,gt~e"II':ILdt.urne$ ,arel!ll!'lg.oifl.gl. ~IIIII IFebOO[lfY:, P\IiI.I?!. :st,tlde lilt lralst.)~\'lr', Ollie of 1m..'!' ~1~lier'rS, &n igih :achielot~f5~Me~<lnie Cheung, Wflfl(j; )tx)'~heIIiI,ea:a 'we ar;e r'e,tl!lfl1!flilg :In ''lJi~it rn)jlll'ihe' 'wit!hom e;ntir"e' rt,eselarcli'l !£I roup, of 60 or ! Oi[ lbe' mill g. talll~~. "mpoop~~ <'l'liid'~heir fialil!liiie~,"smeSay51. The rn~lbeis eBgl'rl'CDr ;anupd.a,~Je (Ifj He'f p:riOjechnll H IlinU~gI1Joni's di~ease b'eQi:lnlrill1iliiolii a~l.ye;noogb. ~lhe th1eir p,[lJg:re5l!i. says. Ira' ili1ll.l'e1l)1ll.giJ~emalt ig~nt be gitJin!ljIWR},liIg ]liIi1he bralill15, 'd" p8/~"retlts m C!IIHu1ITiJ11. e,liI!lial~e,l!IiIelllllikeiJ1his i:5 IilIOI01illy ,[I, ha.ppy ll'U:l!Wnlle' Q'W th~ Mall,n RiI!!).5~lIrrn (~lJatre':5 grtlililt5:, !llly.sW.[lU~IlIl'.: ~W~ r,eqllllired .•' Eve f1/' III [\I~'IlIIh:O suf:r,Elf'iill'mnl HIl!IllilililgHn'I'~~ ~he p~1IinliIetUo de'll'(1'lop.[l1 IlJlOdell!l~irlg tabQloowril rre.UJOIli5. Eier ifIypoth e5:l!l, is 1hm ritJiUilY mit.oQlll'[lltd ria. t~e ,relfuWM I!!ct.irlcwde:si iIiIlfI eltement OfWlfrllfJilUlllty se:[\)\ice.. llilie says. 'Va!:! haR 10 gi)joe bade" ",:].8. dl:l!flil'lmo5. are il key i!I,al'il:of tl:JJeIPu'ule.
1

in

result is, v,ery

difflc:uU ttl' ~pl,jlii!1ifbi:rds a!!1e all! L:y 1J:S~Il:g m<);:netite to ell,icnt tllem!Ye~\i'e$;"

.~.ma:g;n(l:lOire,c~iPtiIOJlIW:lS~lIncb~rat ~!'g!]n~ W~lkelf ~llijQys t~le jougtung.'·Thi~ ]S !Ill vi,!:il.V a 'ctylleciiln:~c WnS1;itl.l!te ood g,tatc U l1ivemity ]11 OID1!I!S s,c]enlifi,c de'b1a,te;" he S;!IY8, "~1;dlri\'e~
B!~clk:slblM'g, ",Q!llycitimg p~pe~ ~ha:t!l;uppon hi$ '!fiG",!!.1 1j!:idig~Qr~~lg thc:regt'· PhU]ip!:l, !irgM!c!'llhat th,e evtdcnce fbr the radka]..;pair mod:c~bl all :Ica.,~~" oo[~d:fl!~~s~[le e'>'idC!lOCfW

vcn'iUy ·ofOlderniibl~~,g, Gennany. W.!I!fk,ef doo'e:Siiil 't buy it H~~ab~lg tbe ve:pQr~cd 'cfTcct of crypiQ(;hronl~' targelcd ~d~ali'oll 011Qfi'Clli;!I!t~~1ilJJ s "Iloise"'r,ath,cr t~:M.'I!!l a ev'udC:l1ice of .fIn miteu:mti'l;'ii,'l m~gnc1'ic sensc. Thecrypwc:iluo:mc .ode~t he SfII)lS,. h; on~y :SU~11P011cdill b.inb!llld !IMphi~,a~l:S •.i:mp~ying t~~~t hil:S belel) gol i,ned, and. lost ~'e:pea:ted~.y H
cll1lllirin.1,1l; vertebrate: evol.uti!on. 1iv:l:lmrc',fl S WilfIIg;~ ~ :~et~~nd,. WaJlreir lI~glill:es.i.ts 'COll]ll3:S!>limc# tl .. ... -.. - ... .~ ~m.lil~,1;<1S; :remOlined COIlSt11U1l.t The. ui/ea. 1i:1ru1l~ :i: evollilltitul, ha'Smaintll:in&lla. secol.lcl m;p!r1 lOl' :m.ii1~etDireception is "'<ImI1ilTdi1y." be s"ys,. o ~ W<i]ker's lIiloom,r1Om~sitlS posi~iotl hs ... ~ ntc:ii nra!ny 'collk::a.gm:s, '~Be oomplleh:ly ~lli:ii~
[.!

8aY::l;bh)]o'gi8tH~Jm;rik Momits,cen Qihhe tr!ll-

the d~"e'~a,mclril!t ,ofthe{)i.ryil~lJtW '~x,erame:!lit,

~repre8e:IW1S 'me field;" gnnnbies John "biltip~.,

aJ:iid r~e'i revie:'!;l!I' t:vi!~~iQ'W8~li1J~{~$OlU'" Thr.l is~epwy be roso[vcd:moo. Mourit~!1! andPh~]]ip~,. wit~ ,(:ryptQChf'OmC)·hoclo"u Inagfllet~tc, "B:,otll sYSl'CIUSi have beC:1limainmkleir:li l\j!;llid, ~re c(llllf~de:llt th~t ~he:dc:tllUcd tA:um~d bocims>c~'hey do diffcl~e~n tMngs:' he beha:vJoml. s:~~td:ic:s m p'I'OVe thcr2ld['Ca~~:~r w ~ays, O'Ypl!Oc~inliOmelsthe more 1I"enalb~e,oOlii,'" 1ll(}C1ellb~'OinJd Ii! deniM. M.ea:IlVilhUe V!/a:~"eri pass for clictermin:ung a headll.~g.Phillips sayS;, Kirschvi:nk~ ~nd 'C)tJ~el'Sjwrt ]a!lli:i.ed13! :$] J4mi~~ wJim'el11:'~S a,gne!l:i.l:e: nlm,y ·iJe· mled [Oir :I:liI!1~PP~llg ],]Oli1JJgullI1u:wm IheHIlUII!lII1, ifrrnl,tier Science m disp[ace;lIIiI;cllIils, ell ]Ulllle, .MmlIi.tse~~,wlhi,ol:so. .POOf,I'[,fJlU.l. gr.:Ult wiU lIi.~.ow thelillil to do ulLm~ a T~~e I'i:ne .stltoctUI::!I.i studli,es of f"islin, In:ll:gnetite tTIulil s'tli;idii!es mag'l1,etoreocpti.C!!I11 in II~ ngrees: Ids. ·'Whether. or U ot tiu,e story ~S P lIrrs:irnm:li nus., c!OuWreV1eai,e....a,ct~ hm'V it'il;'orks, the e:vide~l1Ice shows that tllitem <Ire two syste;m,s b \IV 21Jker 'reachu n~ tlleen'l d of hi is for SieJ.1sil1gm<ll,.g!I,u~tic 'fields,''' odiys:se'y'?Perl:mrn>s. But wll<illte,'\/,erhe fi'lil,dsin th.ell0ll5e, onma.efi.s.b, Si1iys Ritz" "t1ii.el'c wi.[[ be Kir:sclti,vi.liIlk. I:ike Wa~.kei:.d~:sm~sse.s the tWO-in ,l,gne:lo:re;ce:phn hypedl e:s~8" "TIHt~ <t trlily '!~"tmm::I::I'bl, story," .simply does lil.ot lJgt~,ke .8(;~,1.8e," hi; 811iyS. -JO,MIN IBiOHAllNIOIN
SCilENCE VOL318 9 NOVEMlBER20o.7

~,:s.c~eIl10emagl.org:

907

I
has been so sm::oe:s~dl:d:' ln 9 ~DutlmiS. pla:lil!eftI.ry :sci.cntIDsn will return to sec [f Ihc:::;y 'can agree 011 ~ singl.c hmd:ing s.ite ~]mt:s both :sa,tI'e.

and e.'!:c~i.]ing. A. R@!Wdila:Uelllgle FivccliiJ.lfli. ~U Awmleri:cllll,. have

],uv:led .011 M<l:fS., T.liLeirst-two Viki.I1i!:1):I:ta!nf d~;111 th ..:t S~'~: d!owli1 o:tll!olln!n~; retro]'oc~ke:ts in 1916-\vcnt i!1!!1e3rly blilmJdion a \'viw,g ,

sllc..ce:ss:fully

and a ,r<lly~r.Til e tv..-O' hii!tc~t----,U\lc O,poth~nity ~ndS.pirij·~ r'r.)V(lrs that foUed onto ~h.c ma:rtjali1~urf~S!ce encased i.tIii! aJi:rbag:li.-LM~in'efited from )"ears-'!(l(fIg ;!n.lI~Ysc::> ofl.~m:l:iliii,g hazards and the prespeets fer good Slc:ueli1l;ce' (Science, 117 J$[Iunry 20(l3,.:p. 326). lnfour 'WO[;lksilops.]ntereslcd pl~lu~1:aJry seientisrs wmpos:e.d 185· hludli]'Dtg

M,aj,ol'r'iity HUIlies in IF'inldingl A Path for t.hls' NextM,8,lr:s R,ovI'lr

Pi. few ,d'[l.zen :SieU~sel[e·ded :plalnetalrysciieli1if:i sIs ;a1rE! wtti li1.gtjlile~ r wal{tJiB'l'oilimgh~ mill1l,ei'i~e:ld Qif f~scail,and scie,otif1c u!i!(iertailnttybllt~e PUF5!!l11it tmiiJIftian liflie of
IPMAIDINA.. CAllroRNIIA-;W'I:!eli) it ,comes to exp':bring. M3:rll. g·e(llo.g-ist~.II000000Crock:~.:~ngiImeer~loold:fiII,!l:~D :Ia:nd~he:next M!IIr.\l:mverhat~ dil,em.Throw in r~er '.i~tarl OOl"it)vell1,n~s.a l erueial design f!l~h;lTe !I severely Hmited 1iI:[Jide~rst!Ud~l1,g M~:rs" ilnd a tl1.')h tolaimlCh of :2 ye<J!r:5ffi'l)1II~ now. and d'IDeMars ex:phmll,ti.on cmum!lIl:li.zy bas a. loUo talk about
Sc:iC[lf~Si,sh~l.lI sm311 pl.aililct;<i~.'Y town ~1]]

zones

for the MllnEx.pl.orOlftio:l'I

0li11

duelve

lO

Ufc:;. hey T

aJOO

.iidoo hu[!:~ng brphaccs,

tha,t .ight

sti II harbor (llJ'lg:atIl]C matter fram past Q1" ~I~m ~i:le"That raised '1he barf 01:' C8.lrli-

:mlee:hIII!1] here are hel;pil]g sost ()1[lw]ire[i~ the bi WOH"diol.laJrM 3:U Science Labora'l:ory (MSlq rover s]m,ould be,landed!.1lI NASA':s d:ri vt: to 1lI'ldcntOl.['Idi lifebcyolllJ:d the home pbll1eL AlWr dO~lS OfSOgf;tilil1l~sboa.s]:en.lwJ v,ote:s· y fl. grab b~gof ~oo~aliS1:8, most ef their b pl1Opo!S6dllMldil1g:iji~ laY'on 'me ,(;'1n:ttii!!'!g-roOlTI 1100r; "I!S 'tl'iC1!e a"J'~ing like this e:lsC\l.t'iI\icrc ~1 ~eiiSDec;,?'" i.lit3hd a m~e'~ifi!gorga,ni1';ejf i~~ 3!n O\1I~;idc~ NQll:i~dy~ At:ihe end, of the M51Llpding fi:fu;: seh~IC::tiOIl y,~orksbOI~~·:'1irn·lici~Bnt:s had p.fll:ed their j 51 pl'Oposedi si'~(,'S six fOl" flJl't:i'nI,)J' CiOllsidcnbto tion by- NASA It \VaS a paiM(I[ if dJe:Juocl:a.hc lpiooces:s,The' S~1Lmeproredlm'e had gone wfOin;g. enee befOl1e. send:iin:gtlle: SpiJ.cit: roveli f.OW~lllllt I.ooked ].we aJD 3i1E;i!eJ~tlakebed ifu;nllllmiied ont ~o be a barren l.av3.pl ai ~I~". An d this time resellu:hers ~f\e ~m!just "fu.Uo!.viJliJ\!!lthe water"
0[1 Man ~I.l se","IIl:ch ot'pasU enVli:[\m.mm.e~lts (;,011,. ~concl MSlla,ncllfng, SIIJeV~ F~~h'Qp..23-2 5 Oc~ob ~~, sp.oliIso,red by the IMASA·ap;pc!~l'Irud Mars !LaJilding' Site Slee,ri~!l (olTllll'flit'tee .and lh:e M5L IPfQj,e.cII.

did~t~ la1liidiug sltes, 9S didlhe il'igl~llCrC01'nist:raint:s; In~s:s.iO(l'ieillgi.l(H~ershad top~~i:le Ol~ wli!J!eJ.'e MSt. G<lIlI;fJJI.ld •. I,n n~!e'ell~ the l1IiI~<ljodtY"n]l.es E1P~\)roilC'~;l f<J!11ed\7!/'c:::,II "We've J,1I.1etty ITIlIc,h captured all .• (lite· types' of ~.<I.nd:i~m,grnles\1l'h~ legetti ng s down to just SI!'!:, :!i!Iysogeochenliist Di<livid Des MaJlIli:s ofNA;SNs, A~M.esResearch Ce:JmI~e!"n i MOUllli'.1J!i:n\liew, Ctl~ifornm.'''.1'\ lot afpcQP~~' ~!itbverted tlieif ]nlle~e.:Sts: [in a. Pllrtic~LUhl1f '~:~te] lo the 8C]ctl,ce. Thig degree o;fcommlmity .Plllit~cipll.timl is one :fe!J:SO]'il the Mill'S progIC1il'll

~stim~nc~ of the: a'bund.anc~ Or!11]~g,lOn~ll!Idin.g b(J!uld()·rnh)O small to be seen from oru,it, Al1i!I~ hetter ~pcctrosc~p'y poifli~cdtoan eln~,(ling !!iite~oadcd \!,~m~ nlfl~iner~[ t~~c: llel1ulfiti;:: lhat fli):rm@.on~:film. Wll~el::' T~dsc O]~1.i!fl'iil Sij.ppor~ed selection hypmeess reaped eousldersble rewa,rds. T~~e rovers liUllided sillre~y on 0f1poiS~tes;ide~ of the
p]anet:
~Q

Mo:re:-detililed ]umg~ng rr{)ffi OfihitiJfilIS !jpflcecn:li. for ,ex<'lmp~c. :allowed '1'oC:U.J1lte

M.iIU.

the

Rov'e;m' (ME.It) Missiollli and ~:hen ]l(lred their list fo the, safe~~iuokii.1:g, i,U]Qst :i;cicntificilJly ~:nteroi:lti:l1llgtwo b~:si s ()I~ ~]a,c:Ia:test ·ob~~n-al;ioflsfmm

fin

d ]aJlll,dh:lgcO[ld~iIli ns muehas e

predicted, A:l1id Oppo:rtulilitty :mV\ed i1!CI.'OSSi plenty of heJmat:ite. 1!IUho~hn~:e l,u:ine:rn,1 bad fanned [11 bll',i~~IY lJT01ilnd\VlIteT ratherthan on ~hepQst[l~amd ~~Jk!e.bed. Spirit, mrn,the Q~"hler Inmd, ]nrou sUrJ)~.]sc".FO:HI~]me;.ail,m]~~s ofgeQI.Qgi .c feanues Ol~. tlib.eflQQf of gi:anl G~8~V crater, Spirit ~lInde:d no,tonU\le ~ ~Kpectedl .ii1l1c~el1tl<likel,e(l 'tn]t Ol~. <'I '!,~~~~Ia'!,ia i plO1iiil'l de; '!{(lid of S]gl.l,:S ofw3!l~r.i O!l~Yby e:oo:im;et dkl ~tCV(;1Ili!li.:li'!Jly ~ reiid;~fi~arby hills tha~ haro·orod ~ cnligmaJtte \~ltef.~~.terOO, :~ck.r. ~, This tDllle ~1:Qlmd. NASA is ~: :sc:l1Iidrungthe HU!Iim1v·eeof I:O"'CI'S~O ~, ~ M.!!:rs~ MSL. which ius 'i>'~atedto ~'. rove fo!l' t,,.o Earth yeR!I's~\1!Iei.ghs ~' i:mI at three~qLWil1el:S ef'a tOil (more ~

,'~:!l

U~,.um,~ourtinees
O.p'.nOI.'lWllll i.ty I~

H1II0

mass of ~

spec:iaUy fOT tms: m~!'lsi,(ll1.inc.llltd- § i~g III mc~.il.<IIppin.!llI~s.e:J.~dlC:mJi,cal ~ aTliiJy.Zier). androns 0'[1 nuclear g il"ou.chdlllWliI'. MSt ~bGVf) caliri lalild inl tight qillarteii:S.[ike :I1'50-~iilflpm'V(;[I". E~IJ! dlC .1a:ooiIDIgl:!y~1c:liIlIi!:i '" l§, HoldenU.l~~if ![top), Ii'!'~u~r~ OO~KlIllnl~~dhO'~ ~~!lrere~l \ll~~l.l:r l br,fl~ldJ-JIil~'1i.~.I!l ~ ~aJlilding scenario

or S I:"ii~it» bO<JiS1:s .2 p :~ liIi.[If,i:nstmme:lJits (eaclll' develop:d S'

NEWSIFOCUS
variJQlIsl.y desc:ri:bed by :s!Cie~~,tists a.S"e:~clt~ i!lilg" or "SIG.~u;y:·' the mve:r-anly one thi.s Li~i1.e-wil1 cl;esc~ndl the final [500 meters liru<Iingi:l1ljgby c~bl.esfromt H ro(;k!et~fe.sliom'1.ed descent stil~e..All this fo:w $l. '1 bm~ioilil. Mars !'Ic:ientD~1l'i\~,;Quld l!<l.ve .~.pp:i1y smt]cd fO·til. coupl.e ef more modest rovers like Opportunity and Spirit (IiI!t $41 0 mimorl eaeh ),. b1!l!tthat:i sn't the NA S.Aw~, they 'expl,iii in; C:Hch HeW mliS~~ij!l _l~s'~b(,jbi.gg.er and o'b'dOlil!5.~y benet. MSlii5 el~at[y']i'l the NASA 8piri,t. "'Thh~ has been :a vcry ~l!!IiI!bitiO\!~ tfl8k~"
instnunel]t~!ladeb1l ro\..reol"arm 'O'pemti~lg dov,l:I1I te -150~G,j<'lir be]ow the -50"'(; ]imits of'the, MIEns .. But ~nrestin£. ~fu;e dry ~ubin".icanl: Illew fai~iClI t1.liI:erjust 20% of itsrequised ]ufetimtt. MSIL mLi.s:s~m~, mm;lage:r Michlld, VihltkiDiM5 of JrlLs~id <1.1: the workshop. R.e~ming to <I wet lubri:cllIntlTllillc:le: OInes~teig:pm .. itJl.c and put s il!lil:y si:tes :pO~\I!i11L!id of.25"SiJili jeoplll;rJtLy. The fQV(;;i"1sll1a:bility hlI.sn't'iloi'Oir1i;)ed ou:~ qUite1i8 ,cx,~et:ed,. cith(j:it.At ith~ t1!1'8tworl{-

]n[f::rpre:~i:llJJg ]a.yel'ed rock as s;edlme'lJlJJ1'slaid down unde:r Iakewarer, lil.eSO!I:id, witham discuss;illil~ less :iuteres.t1111;g but quite 1Il.I;lIU" si.ble aLternatl'll{)s .• such ~ISb~:almi~en,ofvo.~" eanie ils.h. Sm::h 'COJ1lCeiT~lS hel;pled eliminate
ex.qj1!lilS[tdyl<lyered basmswithnc :si.!:,!n

vl.lilflere,~erflowed til ere. Minerni.o,gy taltliler~.l<'lln geology elld~d 1!iIIP banS '~lep:rim,~ lC!tit~rioll. Mo!tt a;tl.elmdee~.roo.k
t~.l t a thj,j;det~ctkjjl of c I~);r-th(,1; pfodtic
t
(jl~

fl1i,G

MS1.pr'Oj:Octrl'lafllaJglCrl'Uduud Co~k o:fdlcJet

Pl"QiP:M1 .~Oliiil ~ laibora.lti)l)I (J Wl) .1 Pasadena, n Cal:itbrn:i~ •.sfl~d ~t~hc: W(1irk5t~.op. Engineer,s :;pcal nf'the ntllllberof'm±~deSlJeq:~tk'cd'l!)ll ,a projec:l:,ilte s a~cl,.!l]ld"t!11Ji MSl itseems we
j

shop. ii'lil.iiifiY seientists Pifoposled ~·go··;to" l~!1d~ng sires. In these, MS:L~¥oYld ~,Hld 5Q:mewhere iu a SIn()Q!tI:i, s;~fl:. 20-kU(llmet~rdlameter Iaudhrg zene and then ddve beyond ~:he I.all'!l.diing Z01r:1e ~iliiillJerlesli.llg but ~
uldarudaMy
]Ut~~l

!il;lli.Mi')' altetil'li:ml of' igilOOiJ:S rock:r-as<l

~sigtl!

U~~~w.@lerb:r.l:dlo~g been !wi. (;()!:!til!cl\,v.ithrock tllere; ·rh~i \\i\Ould bodJe '\l''eUfijr'l We.Clays; arc
al:so <1d.ept !upl:esen.iJm!l,; organfu ma,m:r over ~he C'OIl& So .fl!lil,Ysilew:utlJii,ollt a>tlea_~~a ht'lii.t of
cJay'w,\Is
Oil,d:

geology.

oft:l.e :Ui\lnJl:~I~g.

tI!f1ViC JlIDlOl'e

than

eur

stmmc:'
nl:~r<lC~es carne NASA

Wihim.iing iI:I.rnvliII
Nol <II.U,of therequired
tiilircm!il~l..A~ t]ne 1il!T~j,ecrsmost recent

This \\ISiS abitteernueh fbr S!ollle.M:i'linyof the geob:im:lu~mrnsts; md ;fI!>lrob]o.IO:lo>isls:-~h.e smal ..es~ cmlll:in:g;entiJilI Lb.,:, C])owo,----:feU: t~ulil l I~eople were .~e;J!llilingn the dEli)lsfBlf iDO 111UUC'Il, o .I~iavi[lg days is n~ce,.du:,y s<lii:d. b~tit's not
evel:ythi.l'IIg·. Clays t1:i<lttoIlJIJ1!e·d WiUljJll, Hille <ilfJiOlef'ltMa.rs c(rIllst.for example, <'nc {lIt ]ess

revh:-w,it: <IIJjJC1iile,d thiii.U MSt. would 1l:'X.ce~ed i ~l:> bJ.dge:t by $50 lui IIi cato :$.100 nnllien o. NASA's. Ma;n~pro.gr.i'lm scientist Mic:lil<'le]

Meyclf toM SclcmCfJ.. As

.aJi)esLl]t.~]~~ I)l;uject

ended 1i1pe->CMom]ring. on roiV~fin~trmneJllm.~ Hon,. am(;mg '!,i'a!rk'l!~ cuts, a~d [',edM!dng U~e ~lI!!mb~rof C1Hil;didmc l1)l~ding shc~ [ttl,iQ'l!ld
\\lc:rnlin~~ foom 12 !Q flve, ''''We: have be,cIDilli!c pO\1!in fully aware l~ow C(MI!Ul,pl(:1C antl t ~m~e,onsl1f!ui:liIgit i,s;w selJeet a:~d QelriI.ify .(bWm;iing !!~te;" s:atdCook~ .!I11dOO"s:eqluclmtly exIP'Cl1:!>Wc.
N'l:lw 'il'ii~.a,ging n~veI!lU.ng f:ields

1)~lJ\m~sings:ignpo:-lts of carly ,I~fu then d;,~.in a.riv-cr de'Jta tooncdm a ciale~lll~e.t\::otoolbi()ruogi.st. Da\mlJ Stm:Jjner (,fthe Un~vexsity()fCal~fOm:ia, Dd.W~;pointed to· Ve!'filillC[.~u~r, 'i",hidl! had fmr()dipo ofl] in ~!'!~ttal tt~lg becsusc a ~
thil!!lld~!~lt~!A)'cr btock~ lIfly ~ClTi'!1 8~gI'l!;'!tn.!re:, so !1l:SC3rcliwrs CQl1!ld~"~ tcU w1lC'ther Iday \VOl~ presentBiI,lt Vernal'\.; (ml:poser. pla!lil.eta:ry sci~nt~ist !l1!1~ion An:::n (l!rNASA~s. John!l(llml C Sl~ce Ge:JrnJ~~i:I'IIH01.Jgro!Ji1JJ,."rex~s, ~m:oodnr~\I'iIl!I~ren~O!I1i ti) '!i"rhfl,t:atp:pe!:!ired to belaJke deposies, lake sherelin es, cfuiSlnl.lel:s, and (,:ve:n 110t-1O.111: iug depoiSrnts. Ijh.efi:rst: proposed on Mlm.'s. "These th:ilmgs are :rcaily ~allporialll,'" said SUI:lmer. ·'.1. voted all green" on VerJIMII:. No:mN~.l.e[,ess" <I revotekepfVerm:d o~t offue top HI. nrl 3.fiilfil!ru1arfl:e:lll:loon sessio», tille WOl1o;Sho:p got down~o· a final six by clemmiE£, fom sile~s to' '·'pln·.g~.tmy·j ecaese they he ~.dtoQlittle b iJrom~!i5Ceftraces otlflife' OnU~Cl]rlanding :zoll!es '''''ere justteo boI'iiJ:l;. Tllel'elmm.ruil:aing six ~l]sh tho e~gi!,!~eill1gli.m]ts, although those: Um]t~ ~em~~ :He;;;:jb]c.The projleel flgkod thrIll; .1'iWO ·of

ef lander-

cl:eslroying bou]d.ers.~CX:l1t]y r,equi:r,ed re~oca~ ti~m olthe :rhoell~x.mJd1ng site, t Thelu::'<I!11 of the MSl.w~mllowing: ~ces5 was almost l difuys (If 1;)"'m~;nure preseerati.Oi.IlIS .. dlisc;lI5!l.iOlrn,aud vutiugin 11 P.fIsadena.
.~(Jtel AliI~g[IJe with <I site fiClpro(p\1!se

(and the

'G:{I"11.\1)1, migb1 MSL

!Uiy~ mtoru:gg~djtcrr;1Ji!1!

wi~ (Ia.~:s

to tntvel) ,em]i,d lMI.~e t.b.e-i:riPowe]'F\Jint iiii' [pitch to the1liS\!:lell!l.~,b~.,cd dozeJiil m,ember8 of ~ i~~'H~MS L :lUe>C!'ilJl.i:l! ommine a, otl1cr proC ~ [poscrlJ,~ hlil!ndfill of invited oll!t::Iid:e~;pert8j' ~ a!mlili1.'bll~st~d ·p[lIliMMfI.ry 8c,~elli1:i:st~!!illdtheilf ; gn:ld Mud~J:Vt8. Oi~()ij:B !.>io~roU?~ved\.w ~til

g:on~

{b~u@alld magtwrta) chmotifl.9lPa!5t wamer,.

But In this; tV{lrksl'!.op,Wattkins repnrted th1),ton fbdher considicr.atiOlI:l!, pwjectelillgi~rsex:p~t MS Ul d1rivmg te' 00 "M ER-lik~;"
~ow~l~thii~lg ·~~ki; 200 ~'ili;tef:flp~!' d~y f~,t'h.Cf

OBe ~'!!: onlht prOiii~et\S tor dom;g S,C!I~~lOC ·thalli the ~~c~d $i(l(hncOOrnpe:r day; MSL,.it aJndthc (lth¢~,oa, the, cllgi]ll~(;~[i~g~O~)st[~~~ll~~' hJl'flIS (J!:!!t.,mU:B~ ~hf!rg~ its b,f!Ucv~eswith it:;; ~ ~ ThC:ll Caimc d:le wtmg: a s.~,OWQ~ h~~ld~IQr raJdhi~ Si(:JtopC'thermQel~ClrUti;: gClle:ra:tQra~ld

i
2

the noolfive!andi~g.

;oone~be d:~mon8tmb'ly ~a!f~, bu~alt lh~s pOliD1!ll ~n~lm.c haJ,,~rd .u'nl~~y~is.

!lone .0ftlllC currelll: batch is" Tim.:\: an;: ft)iI1ii~lCr cmleJJ"!alms. the 'wr1k:shop1'i o.b¥hm.;;;;. favarirte ~y,pc ofshe~ evc:nd~.ffijghnVQ,ol~I~Cmll am;:: o far s sotl,thilllilillt 1ihellO'!l'or '!.IDuM !i~eJy have to h:i~r~ ll1HJle Ol'le~1h~l'd ofih.e tiinle, bC!!'ll:nu:fJiIJg amllhmd .. ]ng. And two, oihl::!fS .lTe the G~:stalday si~es ~o popul:ar 'ivith the' geQ~.og;iS·lSli>l]t shlll:lliIled b:y as!]fO!bio.lb~sfs;. StiU. "it III rn ed a,llU better than l\\i\olli]d IiiIl<I'\ie e~peC:fled;" says SUmllf(f. They .... c.'!ndediup' w~th <I divCl:SJe SlInte of sites ,\l!,1]mIClse tiSk~nessw]]1''',oke t1la!e engmeets. to fioo 'lfvJ.mt

:l!i g:roell, yellm~ o:ulitd

use t~~elll.~o driv.el :ratllel:'thiiln dir.ivi'll:g d[l:ed]y ~ qj1!lres1ilons fOll" C(lC1in1 site. Wid~, co m;;[deralli:lI,c mom the .11"0 .."We lmcerl pr.iue Rci.e:IliCl;: widdll <:::'. o goo(J.btumo I.'C d." j osh ~.ng,.voter$cx.p:ressed 1Oki.IOlnete:rs" 10 fthe CCllltC(rof the l!lfldung 1~~.eiT IOp~:n[m.l:S on eac:l~.sMe '"$110::31 porelJlti<l.U .zone. ss]d Wa.&i.mL.l'har elilnhlilited !I few :siites. ,fiilmd Si:mlt JIil!rnposers sclr<LIufl}~.h~ f:i:mdi:l1.tc::rest .. to IMlllIbit<Jj1 for ]]fr:~,1"llst.Of pre:selll.t" '." il'lg geology 1:1:1 their ~illl:d[llg .7J.lneSi.. 5 YeJIOW!1i Ill'ecliomlllmted. Although stt.ucUy ~ ",peali~. the 'IIomngwas Oilill ~ljle:scilence·po'telJ. SOnH.l~ 3.t:tcm de~es'wollde'l.oed antloue! ~ i!ia~••]m:ot ~hem'i,i.e:isr~si.r:.<"L~. <IIp?bimiti;s, ne\.',,! w~.letheli"t'he le'ollogistsmrngilrn.t be !'>qul]~lt1~ng c ~ engJJlIeerlllgliesm.ctmus: were at tmlles: hllctD'r:ed. lIit fhe!i ill lm a;ges aJ bd 100 h lIli'd,. Thi S ,c:oiUld be '''Gusev<l;~l ove:r il,g~i:ti;j s<lid siJl)e,ettOQa ~ijil,. F'ot ex.~lmpl.e>inis,si'M ,engineers had
Olm,

flOur sc~e:flc{l"I)e~at:cd

m~mi;i[l(g <Hill e%otic <B:ryhtbri:c;.q;nt to ~kie~p ~hed:rivlllg .fl!:!d~~e:ring :8)'.s~ms al'!!drlle

~ p.lilinned

SQ(lp~st

S·te¥~;rlll l.uff of Ari

igl

vcnity

Th;lf!l:pe. Some

2'iOIl" Sta:te U:lilii~ !i~re' m~lIly w.m.t" g'Col()gist81,v~n::

~,:s.c~eIl10ema.gi.org~

SCilENCE VOL318

9 NOVEMlBER2007

909'

NEWSFOCUS
GE.NETI CS

IBi o~oglists ,alfi!:!~illild'i lliIg tlillati n so,m,e ~s(!ldill~.n s,eds, watl!llre. f 'i whetlillelr ()Iffsp!r1illilg become worill!!er:5 Oir Iroy,alil:V

illiGI'

n urtll!llre. de't:e rllTli ~Ies

Tempe, ind,ep~tldellt!y noticed til:O'lt 11 ~ ~onle

11~t~ of the red!htlrv,~tc:r!lim '(~,no.m)il'·/Jl'e\" b,wbatus) a!l!d i~l !'le~t.:ii q;Joruiii~ing, th~ othii;jf i:m.lshlwrvesrer ant (11' tugPStfs). iii I th~ ,.IQi'killWS

SlUlnmer 1'31]115, alesend prospective m GlinOOI1S ~c::;avethe' nest 011 :SWflJnn~ mattillU:gnigl.us. iJ.e NI.iilJes die :!litem' ul<IIting: quee;~,l:smun,lcl new G:'!iCIloni!e:i>andean live ron,uooe th<illru 10ye<lill5, fiv·e yean. ~(]!:. tbree teams, il.lcliUdilil,g Gordon 1.. He lms Call ,HI'S, and OJillIC te d b:y J.elll!iJi11er I~ewell·of Aromll, State Urn,!{6i~ltym

hl ~112,tb~; .E1i1;:lislb! !l:choltlif jo,:5e,ph Wt'I!rder d1cdiC[i'tod hi5 '1r,~ati.:iiC.1h~ ::n;:w jJlj1M~mis;~ 01: Th"rt .MoNarcil}lo/ &~s.to Qlie~l iiine.dti.1\llg A
'~~reC;'M!t~diYi~i(lnil Qrt~j(: hiv~th(l ,ql!~~fi Irrr~~i~t bn:.'ed~g andthewoiker.s .Ibr 1~lldi:llig~~ aml her "mod. for.!lging, ~Ild dy:rng ro d'efend ~lThdrhome-,as evideIiil0clhll~: m:!'!!U1re adoncd roya.hy..!B~]lllm.,cl1 ,pf,¥lun c'wl:OI.no~t)gi5tcS ~!I!\le
leamed :SUIlDe the:']11 hasmade the h'I;IC$ bees of and OUll;)!: sClci.a] i~lsect.s seem closer ~Q: Ule AI.neril!Cii;1l dreaD[; Giventihe ~:i:g;h.tntlrtflliill~ ~ diet af:r-oya] jelly in ~lonleyflilee's. or being reiilrfd llt a cC'I.ill:inteimperatu.re il~, lOITIC1I1lilSi$ <IillyfeIJ,rn]eg;rub ~n abeehjve or i~1;i([I ant's nest
ClIiliilgroW

lIrilft: ofqmes:'li.ons, about 'I:inliillmod'e of life. U'yi~!g to unravel these a1!1!t8' ~voh.itii~!l~fY hi~rory, exi.i:CUYW:~iitg(;m.~ dJe'lCmi~ile Ca!lt:c~

up to

'!:e queeiil.

At I.cast this miunlli(;:-C'VC:Jf-~~tIi~Llrepair<Ld;igm was tlle p.revm~m;g\\~isd(}m., b~b.'ld by theooty

~lID<ilh'lrgl1lted:dlo]Jt ~ly gm~ dmt roqLUm:l. (I yi;v,eliO])itlg ~m:!~t KI become n steri le\\'Or:ke"~'1'(lmid

be c~miiu'~g e\'OI!,lJtiiolll!~~ ~i(;idc, Btu a fe,\\!, years !ig.\\1I. :ii(!ICi",i-]~'!~ctre8~f~n:~,,,,.;ifl rocked by the di:s: cO"Y:(:lrytl~at it1J s,o~e at'!t::;~cc~es ~ worllrers and qJueens ~ det~rlilil!ined by i]lc:ir
~enelV-illn >C}the~rw'ctl"d!>,~mn. b
1I1I(J~

made, A!ld

't:llliis

dn!>OO'\ficred IXliI: in ~~l1e obcl!ClIre :r.:ailll torres:i s:pecie'J! bill: in hal"'II'!e:.'>ter nt$. which &ire ~ lliblqM.i.lolis aeressfhe s1:)'Hthcl'uUl1tl~5dStares. ~:lIW been 'sw.diiledf'.;.'Ir :cliecBldes, and m:e, 'even :so]d m;ll inc~ foOJ: ant f3:r.M5. nIJBlrveste:~r ants are the [ilos.wr child tOI" <Iintresem:cJ!nI." till,)?!'! S..rn ~Jd.ms C<lhan o,fthe UI1~vers;ity ofVenillm.l~:iJrn! B1!I.rli:nwtoTili. one ot the c0Q"idi,sc(),\'c~"e.rs of gcne,tilc caste dicte:r~ .i 1I!I,<iltio,n(GC D). ·'hl1.O'IgimlcwlJll.l:t ~he o~~liCr.~1,99 9 s'p~c:ie8 wti;lm,[ !be up' ~()." 1,lldic~dI, !Se'i'!er.a~more ,examp:lef.t of (iCD
~'IU

DNA Inali:e:rs. ,!\"he~refls rhe queens in these eolnnies }\)!fI!IIIC ]dellt'ucaJ~ pairs of gelles, ,at the The tfaJh. ll" ~:Ul"mil oat, h liiIot 'C![jll1lil1:~odto ants, AriCpOf'1 on I!?~g:e,98.5 shows rhata SaIJmmr:: 1IiIilamc:rs. "rhls~" \vcnrd. llL'l;gene.o:; S:~C)ijkl spcde:;; of termhc also uses genies te Sipli~: be spreiRd albcmt between the t:wo eastes all Ineeder~l:'mm.\NQf.k:e!li'lli. '''fhi.s is 'p:rohab~y the: randem in a oolo~iIlwiThi!ch ~l1y 1b.n2L~e can fnl d!ea""mur example :Qf'~lQ:Wctlstc::is, d!e1er", !>[~)[IlO~d~yboornIiliTIe <Ii q1lmen 'Of'iWlit:CJ: •. m~ned in N;:rmires~'" s®ylj) N athmll Le ofilie U]];i~ f'm'1hergenetUc3nalysi:S CIt workers mile! q!lleens: soo~:vedIDmllu'lse ants were ]u ftlct ne~i" ve;rz;~tyof"Sydlne~y.AI1:~m!.b.!li ~~.~iUd)er f the o team behiJmd~ll.e d:isCICIVCry. And srn~;gebe~uevr:, ther E' Df!rl:mfl,/5 lm,or If r:!lgoS!ls but a byb1'iicll of tlre tV,i(l! species, More, cOIll~~liloated sti.~~,,~he that 'I11an~more !i1il'm~gegeMe<ttC 3ndrep:mdtl~ hybrid popu~aholl OOl\S~S'tll o:(bvo :sI'rn.iIliS:. ]0 live sysreoJJilI1S 'mm1itd~sc~ry ~nOC!<c~l.~ngects. each Hes~.dleqllJee-;mI ;u]d ~,lerdtUIgtuter q~~e;ens l!!;(kY!lnt:i iI.repl~bred mc~:ubr;:ffi oi'ofl'" S1r~~ or~le other. Wttook seme hltcku:) reveal h1Iwe::;h:r ru:rl'.'il',odd where-l'!:'i the W()irkelfS are a CiiO!'>S lbet\vccn ~he ~netic8. '''Wewlmd i~ sheer i.lccid~!l!t;·· SfI~S. two !:!ITatns. Tile ,oniy"laiY d~is 8y!:l~(;i[1,1 by cculd loooklg~~ IkbofM Goruo~orfSIa!1lf~rd U~iver" \o,fO!l'k, the.va!i~~r.esc~roh. g!lo~s c011!duded, .81'1:11' ~nr~do AI't!),.C1l1ifom~iI. hc[lfJItf nstural T \\':'o'!S fqMe~ns used ~~m,l~Qm 1I'l~,<l~S;loUlcir ~ O'!>;'f.I H·ai~ll(l make ~Iorlc q:ueC:rl~ and spc:rJ;I':! 8 h~SnlV:ll Isnormal unougb:A singllc queen fr,o!U tll1l!;: (l:t:futer ~lr~in ~Q; make ~"'orke~j \vi:rh folWl1ds 'each nest and~;i'\les birth ~o .S!~~.the ,000IQ11)"'5; \~Ikel:s~ s~er:ll~f'e'DaJes th~ give .Imr· eaeh !I:~t's:eas:le decided llC;lt by its up11l<r" vc~tcrall~!;l 'I!~e~r ame 'b)' gad\Jer~ng r;;ecd~,t'b:r b1!Qt ~hc QOlnbiire:IiOlm, afg,cncs Ureoe[~~ n ~~ fuod. The q1!M':en !!!~S!O[ll!rodllJOcs 't'l\i.e 11Ie%t .!Jlner~ :um pBiienl s, SoqJl!leens lumtHWUIf: with males (if arion of rep rod:1LI:di.ves,: ~ID1tfl.[e.s da:llgblteT and both ffiIDilinsto raise 1IIru:l1l~ti.oHblg colouy. qltee~ls.l1leifueol: ofwl1:ic~l W'Q!rk As ll1l illI f111l1l;!, S:ub:>eqJmmt work has found fhat~<II:¥estel: \\'Ir.'I:~pS,andbees, »!lareS ofh1:r'leste:rfl!lilt species. ar:uts w:ii:h this oel[) doml~liflh::~a. siIl',up of'deoorl de'lle~op fro~nl mlfi:::r~ili2led eggs lI'11Ld SiO have im)U\;vcs;Ie'[ll "fC::'lill:S e.1SI:eJil~1A:nizo:l~'<IL. (Od.l~ to halfols many dl~,'OJIDU:OWlnes aJfL>tC'i,u;EiJles" .Miter ants iIIiI ~JrniS,~Imsil]l.pe'ru:to use diet ID detel1llilille easte.) So far,eilllit !eliIDct~cil.n,y d:i:SI:mcit lu~brid sl:II.uns have been fUM:nd, ooe:dstingin fOl1[, p;.ti,[S of&!~pemh[ltsmmH" :ii1iJlgg~t.. ing tWlal hybridiza-

in ~~~ei.r~ects'j1l!!l(Ww~:at.if aJd~llt~ge GeU co:nliCl:s,

airl)I,

e\l1t,)~utiOfloo)r

c~

'~'1j,Qditlef'~l

~~i()!'ili of~'. ¢rIC <l'toc:rm:m g

~~we;popp~dup, among o~lt~tant !&ip~c:ies.Re~c,~[dlen~~ue~~ : o\i)~,

1~I~bf,IS :Caha.iill are !.low ulcki~l:g
1il!lililen, I!irn~'? llli1~selrelll har~t,er ,H~b !1ie~d!ilnel' riglht ~:e!i!I.Hto lbo~;[:om~ iii liI.ilJeerii.

tio,fI htls m:c,ll!rt.oo:1!~d(jeW) ~'Oh~d,---m~&~~o;"

:(;;!

NO'IVIEMBERQOQ7

NEWSIFOCUS
with R rtigGSiliS ~.n:ight~be:,fII.later event not direcl~y rel ated ~o (iCDts: ori~n. So fnl', biologists h.arve <liUOW,ibgo.rJO,rl,tv~'Jtl(!X to ~et spotted euly ~e~ileLi·cmarb ern of casre determinanea; i1iW1lUill:dthis. Q'lII,eem,wit~l IGCD thai havemated with only the <liCbill] gene's be:h]nd it alife Mlcoth er strain do, IDIot le se all M:IlI:knowll" BM[ fi,lIidin~ tno:se '~~leiJt ra p,t,odUc,t']ji,i!~ ,op'tiOIl!:il: ge:lil;e::::: in h~ry,e;s1ier 1tlli!tS eeuld The:y c!!!H stinprod~oc m,\jj~~s StiHl'IIiII~'dl flel. .. ~'ill) m,s:.R 01:1191 j'e¥~~ lthese tlHU co!U!:{d til ~ h from ulilfetti ~b·.ed,eggs..And lilalli'ili!5tler: al1ll:s (.abwt') and red devcl.QPtiiH~i!Mal p~dl'l:~<iliyS of ll1~'M~~~if~!)t~ l!!yti"'d~~g.. S Q C ialinsee hg~ ts ~n :gc!,!lcraL W'Of~r:.~ alfC <\l!!n;:::Il:dy CQ'W!<'.PUg()lWj~!)Il'.lI.IC'X is g.o~Ilg to dcm~l~d !lot t:orx::()~odu(:!e. so ~lI1esoc:ri.l,iJty' ofnTrutell'S'lni:1iIi Ol~$priiliig :nsmoot. be a '\Iiery :good model to I.ook !I!t mooh~ni~:ms Evc:Jiii1 SILl, Gel) 5CClinS fI! p~rHously fra.gi.IJc of CO'lS,t'(: dcienu:imi8!tllo!lili,'" saysL~liiJ.ren~Ke~]c;T ,pnhe Unive:rsi~y ofLa:~]sa!llne!, S\vilzcrl,a!llJ(l repl.'c::n:lJl.ldi \I'C syS;lcm s~ys cvohltiona:ry bielogis:I.Pe1:cr Nonacs ,oft1l1.c University orOd:i~ S]B~Oe' oeD WBlS; di SCOV'Clle din harvester ;ml~'S.:i~ ]]JlfI!> been fO'llil'ld ~illiii. U.l;llullibefoflothe:r fOI'll~,t1. Los A~lgeles.Each aest comlpetes with those presided Olver by queens ,orit:~ sl!led es, The Sj,oIUllUu:m fire ant (Solellop.sis iPlflrtner :s111'ai;MI food and l:erritory ye4<1]so .\I~tOJu)'[usessper.mllfom males ofll close re]!I,~ fur dep e:lil,dson the males 10 f that: strain fiar i~;s tive to milk!€! \!rorkents ,1IBld spcnil1, (I f tts own :SlJliVW;[l~1. And stn:ins: ,e,IJJlnot e'IIt!lv,e ~,ethenr s;ped,e::Jto make qll!eens. The~:e:!loo also geJu:t[c, by sW<il1ppiiim~series. bec<luse, gene$ from Qililie diffete1lil,ce"s between the types of sti:,rilml wim ~1!e¥eril:ndll]pi1lil1 1J, qllteen from ti1le "vo;rb.IJ,l'in :~eillf~cutting ..md Il:rmy O'tl:iCJf. "It's s~~ch ~~l odd'M1]'iO htlvefl ~OCi,fl] .1!!lii,tcclonic8. Thesc,!'(ottcrs CO'l!II1.~ syst.elTl. Olllie\v(n~l,dthink there cd be ,g:re.lllt in'\1liJm ti s]mp~ aad !'l~" C11 lied s ~I(lctivc d~sadvantagc:s arnd thatit ~dbre;a_k 8!ubcastes, sp ee ia lked for jobi!j such <'I~soldicrin:g, for,flgi~g. and d!OW:!1), btu it hu~\" sal's; Nonacs. The OIf]gil:1 of GCD til !lJ!I!tl1. isal most !IS nest ~mi~n:cnaflc~. UbhaN,e~U(;'1f ~I:s. qyoo~LS('1nhesc speCiC~~ID ~ys;teriol! s as its acliv1} u~ge:s" h C obvi ous ~ T ~ypalh:esis, :f~red Iby HC~lrrn:sC~,al1. ls flThfJ!lt wHh many males, ~'nd 'Wmli~m 'tin;e ~ybl".~d ~ra:iI1S 3r.L'l descended :fi·UUllil3liK,:Uent lIl1!lgl~[il of the IUl1Inver~ity ofLeed,:;. i(:mOSiSlng;1> be~"V(le'li!i! he t'l.lVO p,~~l~'Im!I:~:~ t speelc~, U. K" ~11 d h ~sc'one aGue~ ha:ve The pl:'eJ;ence ofge;lle{l; fll~mbQlh species in fuUl1d thatiu .I!eaf-cwling Sims. t]i\i.e oBi; I)J.;,ungof diRerent males 811:e each strain lends ,!¥e(ghit~:o'thisidea, as dees hiil.sed toward.beiCOming .apaUli'icu,. u~l.ef;a'ct: that whh[n each Pll[I:" ene s:tn.lll':S gcuesan~ more simi].m: to R I"/oI{AeM'!l.'tf. whereas lail':~ioo. of'wm.K:eJ:. $LIgg.e:$i:nb1ig. iI!ai i~n,e otber is eloserte P./Jal'ba'tltS{C'i.i'eH ihou;gh 11"''Orke·Fs£:~:tl1let~c m~"ilil]p pre:~ t'lu,etwo straillillsm '1::<1:01111 look al.ikephys;i~ pauli" di~pooes her towtl]"d, jO~:l1illlga :pllmCUblf suls,caMe. At the· :tiiImoSil ;HltH'lme, meeethau c 90'% of Cll.Uy). Ilehns Cah.m has found tha.t colonies with GCD .gl'ow more qui:Jd:y ~]ultiU ilJ:1tum.e of lIm,me kmf;.cnttruug lInt's o€ilSpri:n.g Cillil devclop M at;i~lg be't\!Velf:ll specles iS dead end beesuse it .I.etuills.to s,too~c o:ll'sf:ring. tJU[ two aspects of illi1l:t bi!ology
OfflC::ilil 11
l

creatures c all ed [11 e!'l:peri ~ g ments he tween male ill11H:I.Fenmle. ImleotcMcs, theteam csbllful.i.sMcd that II:s~ullg[e g\me enthe X dlilUliiilitOSOnlC co:nl:m,~SC<lstc ]111. m[steltlluite spe~~e-ll. g'GI1C comes ~nt'!iv'Qfbin11ill,dJuOOe.,d] Aruld1lB. Two A~,m .11. futflllle makea queen, whereas ffilB.lle!lwiili a B g'ClleOOCO'li11Je :kilil,!:';s. ABren~l.es and A males becO:ITI!a·\'\.'()[,k,,~. \\lhena q~i~~~h1\i, her t\i.I'Q A's Wl:~\vilh W a 'killgf!!ldl .hi:sBgel1e.am~ili Q~sprili'lg will be ~!:Cril(:w,ornc:P1,Lo beliliiv,eslihis l\JJelps prevent d!u;:;a'!i:ng hl'lhcuesi:, R,~'fi'~fIJi~cf·me.~\VOrke:rn CllJiiIJly ecome :n;:prod1!Jlcdves ~f theldng or b q![liCC1lili dlC;fll.rc:moving: ()1!o~m:emical Si~l:all ~h:aJt St'~p~'lres:];es!!I!'Q:rrfu:~ deve!0lll1u:nt[1m IOO!Ji1l!i:r.wsJ:, ' ]11 other tenniee species, SJ~~, workers ~!tIi'i.lehe t InlilentriaJ~tD looOOl.lle repmduetives, p~:t1c:ing a dmin. en t~neC10hJillWY ~ 1.fe50lU'CCS. "Tfuey just sit .m:mnd bei.ng,klOkied1lfh,'!{r,'" St'l!:!fs e, L lo s:~gg.esw:s~],ul!t el) i.slikie~y J1e~!ltivel.y G rm"e' ]111, ants, the lles:uU ef'unusual circemworke rs 1:0 beeemetertlle
ueoteni as, T~l]"oiIJ;ghcrossb!li"ecd

nle

sMIlIiI,ces, such as, :fuI!l'br,idiza1iion, but dllrn:it mny be 'oommml CIIIHOillil:{!; termites because ohhe ki~~:.qlroellS)l~tem [m£! ~ti ,1I~ociatcd ge.JiiliC:l~ .
]r!

citoorpllre R .bmbat~iSor Po rljgam;s ilnd rl~lllt into 000 8l.1ibc1bf>l:e:. ~Iu:g~sig lII!01ivlicKl:ikingror geclil!G1ic d~&n.;!l!ces ool\'o{;el!i! queens it,nd ,~k-, i~:h~~r v,"OIl!:Cf,g O\l!!!(lli!!~OJ'eas.gre88~'!,,\('! tl1:a!!1 t~ooe
of the parollt sl]Jecies. "1 'I:'A)Uldln't be 8~Jjprisod ,m ]!ti 1,~f-cl.lllingll[lt~.

;:!!ifthe;~ ~]:a;d ~oQ]ogiefll advam"ge," s,h~~ys. M iw Hybrid plaInt8 Oift(i~lgI'O\v~;vc]], .~~ liJomt;s oot.

i ti!o.J3~hinglong'~ploiood

lidden I{Qmipl!~i:ty
~llI~,irod by titLed~::ieov~jff~g]~ ilrl!t~, lO~11 d IC(l']~e~g.Ycsa,tlba:rak iLI:t~~vc;rsity if! J:il!pa~, I!ookedt?or OeD :~Il teli"lll:it,cs. U~lHln:: ~Ilt.s and bees~ mrlm~.t1Je soc:ieticshat\l'C bo,th :1'!llmle .and fmnal:e: v,i\Oirl>!ers,audlc!liOh c!olony has 11 ki.ng 3.l1Ida q'llilecn. Uwas MlOUgbt It~.a:t phe:mmolle:s,i5JroHl othe::JI" lm.es:1: me:lililbe:nl 'CO!J:I'" tmUe d whm: rermo;te la:n~EIIe' de'i.le~oped ~nto:, ;81Uho:u.gh no one hml. ever [dClltifi!ed such le..st~detell'.mhrn;ililg clitcmlica.l s. Wurkiil1g!;.\ii~.b the JII;p1lllil,ese:rer~.l1lil:e :spec.ies .I1.'el:ic:ulitermes sp{tn~t!IS,LOoand h~s col~ k:a,g'.ues cX<I!in]ned ~:lis ~Ie;stiolii by ~priv~,ng ,:;;,o]on~·e::; 'oft~l,eir kiilg <lind quee:ii1. wh:~ch induc(;ls :-;ome .I;arv.m; ,amd'lo~many s,te:rn~
SCilENCE VOL318

~ I,l;lX'Ise,I~~s'Cd (WJJa~l~lyscsQ fUoNA f~'Qm ant: ~.ilOOllO!Iilrlri1l:-fIlIl C!llC!:gy-'ge~meralillg strl!JCti!Jtre ~i:l'!isid'elihe ~eDI.'Whhits o\Vfl iilna~] breJm.ome-5l~c Ibdi,eves that [ilile oWesii' olf tlirte eig1litklloIWn 9 :s.n:alns with GCD is .~i1:l0S~ dos:dy :reblted to !it . i'lli .~ mrba!u.!I. nls s,p;:cues" she !>ll£~!>tS.. ev:o~:ved ~ <lin '\~P:Ls:l!ic"gel1e that .made~ ils be'arm]'!> ~Inore

bypiMit
V~C"'\I'

broed~ll<.

fC\l!re:U ~ dHl{)~l h<'!:f:i

oif~ow OeD

i
~--

c.

..•.

'..-

, . .. to :iJoooln.e qjlLeeUS, Siu::h H ~ne~\\Guld ,Iud ~it!S cc1lJri:ersbut 'WOuld .. .IS() ,c:re.lte~ se~eclio'l'l fQ1f ~work:ec'l'-pli'od1mJci.ng ~ene;stD prevent co.lony rE. ~l'!1!:iJrnCtLo:n. QeD irlm.isht: 00<1 \WIy to cope wi,ih
f:2 likely
..
.-

:ic,s" Wfsstillunclear h~vwides~~d (leo ]~ soelllli~!i,sec:l8, s;r1:Y~ ant ~pcrl A!1dlfe~V B.oulfke: of the UniV'crs~ty ofEut Ang:iia,in Norwich. UK ''''~.ero'5 a10t ofhidden OOITIp!~J¢~ly t1Imtifs Iik~igmgde!fiilnm!l~ulafJ~hilit]l!eg~ di:ScjO'i/,er 'l1e sarf!.. No~li.' tJ:!<1!l insect ro(::~c~r~hers. ~ia!'!i'es:po«{.-d some of rtIIJ!i.l!i ooupl.e:.'li.ity, they m~~sta:rtt fIDding li1I11ore."PcQpl,e ha.'Vc been it bit bUnd,'" K~I~erSil!ys, "TI1lIe:y read ~Ollill!ledling: :UIl.S! textbook, ::und then wMen the d!alt8 doesn't fit dl~lil luodd,.they thl·O'WOl~ &e dma."'The diis![lm'l;:[''' ~es. so faill ruJ"e:jll1St t]u,e [fue~nlli_n,g:, hel premcrrs: "'.1 think tl!te~: :5 to HJ% of ,ant siPecies wlliUWIm Oil]l to. ]iJJ:rnreverywei:rrl Hlodlesof D)eproom.rli.cm:' What V!liJm~er '\vowcl h<i.w m1i.de of SltdiIl. r~<lil
t

l)ervi;;:rD:S~~ty iSiim,yornn.e's :gooss. ",:)OHNIWlHliliFIEILD

~ eglJ'is'He p~les. nm ~om!i:thi~~ !ives a OOIntl~lt ~ peHl:iv'~ :ad\fMtagc, :she says, arW.the ci:,oosifj£:

lohn Whlt~ield" <I! SlOle;nce1.Yli~erin looooill, is aulho r o~ III !he: ~l' oJ",Hwrt IJfo, fne'fg;):;, ,,,ad tlJe: (JpiwrJlilltJl~,

~,:s.c~ell1oema.g:.org.

9 NOVEMlBER2007

911'1

\\tOiUldihm~

8~1()\i,Ijftj,

aUO'%

ip:::,lta:gc ~, IJij.b]ic~-

m~:mber grew ~o 1 HS5. @ooord.ing to data flQl:r:Ii Thamp>OJiiI, Sci eWiu. fie Web olf SCi(l]l(le, Dmxc~ !;; PwodUCliv.hy ~ms nOlmii,ly bndg<OO. b~nstl!l'§!)d
lW'iIl:5 .A:MA.ZW m" J. MIERVIS,'5 NE.W'5 OF JHI: WEIEK SrnRY"U.s. OIl!JTPUTF,ILArr~N'S;,ANII) INSf WOil1loors why'" (3 A1lI.g1llsi:.p. 58::n NOlt by the cOl:l.d:uS[Dl1Ii thalt U.S" Sciflil~lrellroo:H(;1ivHy i.s.flm .. i:eJm'ill!:J atilt;, but because <IIpp1:l~'e'.r:JiIili:rIU.obodyinter\l'i.C1ived by the, NSF coul.d~de11il:UI:Y the reasca : JliIlid '~he q;il'I:esholrn,been posed of 1iI.ImOiStmy ·w'o:rlkingst.ieJrn:I:ist: ~ kll()\\,', the simple aad aCI::lIJ:<UIl iillIili!Ni"e]f 'I,1'!'tmi.d hllive beentliil'1lit themaJ111be~: of papers tl'rnllit <IIl1ill\i'l.1r1JUen ]5 djllliLi,n~shilmf1l:beeause 9C~:'I~iui'sts iiTC'lbl~ to spclld less tiilllmle'W:riting pi!iiper'S! Insteadwe s~l1d: ever-more time on the

tionprn,Q:m::!livity. :SpcdtieaUy, ii~2Q02: lJ~W I~.c(!]ty p1liMi~bcd 502 fIfi!~cl~s~ i!l!J :2006 !!:hlJ

TInedecrease s1~IOWI'Iill the OO'Ii'idc:for MICP l;ial~lm;eli11,ruull Urnvcr:sily a1ndDrexel. Uniliva:sity req,uiires.col1ite1!ttifm':stlUJ'el'S. M,CP and 'Dooxe,~ are Clille and~le s;'111~.e1!U1~'I,I'a.'sity. Wil:::l'll D.llel'!.'}e~ acqui:red til:1C aiCad:eJ:ljli.cm~ils O'fthe ba~lltmpt Alleg;iiLeJru,y Uni:venr]!:y oftl~cl;l!e .. lth :Sc:iI~1.ce:s
~n 1998. ~tto:nned ;EJj1l e-Id.~ent ,enti~ ciilUed MCPI~hdimru;:;mi.iJJUil'l Unr\i1en.,'ity, 'ivhi.ch by design '>'!lO11:! dissolved in :200:2and nollongw ~lI,]l:!ts. Th.e compelling rctlS,Oi[ll.'llfly D~;!le i lind MCP Sl!iQ\\fll decline m:r.1c~lty pU:bli~caJdolls

inc.rc.t'i>ingly b!lll:rtlielloo.e adnlilfiliil:itrniti.ver'equiT'elllCilts of c~ld;~lCt:~ ~lI;.;ic;!lice hig~l~!y. 0'1:1 and wrltil[Q!..g. ~\Yf.iti:ng.ffi1l;d ~.i.!'e\m'tir!S: gr~lt <'!,pp]ica,tiorll'i .lStoo N Ul':!1p~y ~iw;:drop8 t()·~taBt~hically :Io.lt ·levelS. As. tile' n'Llm~f ofh(]!U[\\l i~ta dJ<'ly isf:i~i~e aJndWlinc4:l'1I1:g~~g.5O'~th~g has ·10 : gI¥:C •.~fm ditlrl't h~to 8~ndlh~ rest ofl,ibhl J:!il~I~~bisnorift!,griOM.S :half;;ollli!llple1~!!iru!!ti!i.s(;ripts ~
<'!lldret'Vfiling.a.gr.mrut ajPl~I[~a:til{)n. ()xpl;flUa in 'IIi'QJorc d~~i~.
I

~ijknbllc

·1,0

dvi!:lgl992;to

2001

~&

becaJuse CJihhe pro-

]OHIIN P:MOOR!E
Illllipartmillnt o.'I.Mluooiolo9{VaiHii ,Inn IOOlo~, WBm .Medil:at IiIiIIJ C~IIIiii~, CotntU ijnl'1Eir:Si~1I', Nel!l '((Nk, N'i :1.0065., US/I,

f~Uf!!d 8hill in a:tt~:wli~, ~qr. and resources oli1!lhe part of both rf!ct!~ti~ iJi~t~16y'!,!V()][iKod l'O,1!ivardlllc c()m!llo'!1lg~alof ~n~i:l'gr8!l~ng !l~liQIiI'S; lro:'~!lt priVf]!u;: me,dicall schoo:l·ta ct):I;Ie:ge of nl:lll"S~1gB~~d he:a]tJ~ PNlfc.ssiollR, ~ndl ,81

"'c:

iliH E FlE,GUltArO R¥ BU FlD EINllilHAJ A(CIElIERAITEID' aromrd [990i!>r.]'IlIW~.y i:lilb,c:t'~ug outpur the

ofl.laTIil'JJ. creveafhe p()ssfuifti:ty ofl~'mnl no. matterhow uillikdy:. Even an ,exp:,['" ImeMlt in w]i1ii:o]ia, a:l'l~d:p<lnt.s ~U'liS~: p :listt:nto ,I .sl~ippet OhOllg HllIidjm:lge itsfrnn~i~Lty [s subject to ~1Ji]1ge,m!t[eguiJre:rnen't~u.litend:od to pro~ teet ifu.ooe.pam.cipflllltsW:m Illm.ul] ,. SC;iCI1C1e isan cltp]onJ.tion ,of tJro,c une.'X.·
th::fipFaJ"illlICC

of US. rese:<lJrcl!a,er8. {I Mer'!;'i~. "U.S. O.1.dpl]t 11h1:tleo:l!l!S, f!ncli N:S.F'i;l,iot!dcrs; wl~~I;' ,oftl1~ News Week, 3 A1qlllSt Po S:~2). h]cr~3S!edD:oo:ili\l:'li~ roduoed by too oos~ Of~g'.lI1lm!tooy c(mfitplean,;:;~! cxpem.tV'(: ~lifily S}"8le_~,!brl.lii.'!i~lii~ •.¥u!pcr: tlU.otD~ .i!iocrodiitfLtiO:fi" exec~~ve ruqjliiwM6i.l~ fell;C"'~ s~~i'~i;q'uiQn. 'i"CriH,ca1km. Qf:.tcrilhy U:ld~lgcultt~re:!i;, sigllll,t:w:rcsat e've:ry.:::t:e:p,. ~:nd. And, of I:lOIJn;c, the regn~alory diOClImCli1ila:tlon rakes time aJ\V{ly frmn documenting tl~Jc re.<mm:ciJ.'a.itsel·f, Because of'tlre lJl!{nil'l~mc·~lt:8J~
j•

pected" and tfut(;~CC{:lll:~mlint~flr(;S!1ilfIjQcaa:ting.

sC~l(l<oI!.:If pulblk lH~Rhbil:ltl!) a eOIil$()lidiated fu:U~·il1li~egrn:te 1!1:~i.ve:rs~ty,'l'h~s faruidall:)lle d and lI1I.lp:",cedelm:iied u~.demraking was HI suecess, andresearch and :lnlb.lisllilllg ;[lI'(} U(JiW' thriving ai .DI.·e~.I. U~~.i.ve:r£ity . "felling;[I :story"iby the [Jj]];Milbern"alcu:te· c<I1n sometimes llililJeiln... taDe h.tlf~t:ol:d. Dnlxd and ~~ke[:ym;l'nler uniwui.tiestliCCelwt NSF's ci1lEl,]" ]en,~to step up proooc:livity illlid .ne alre1lidly

,othew careers ,,,,,ih(:~1theysee ho\;v scienee is done Utd~y:.Thc:y~re r~I~laccd tho~~ ",,,rho by
,!:i.eoonlfbl1albl!~
d~ ~l(l1lk~lOW tl~~tscience

We mli'!'s~exp~c't creanve swd!i::nts to look to

me~:il!!igit
S,TEPHEiN W'. D,IIR:E!(TOR:

ofM(,~ ·Il~·~b~ ~lrll!'l'~~~'IDrl!liil!llJnkli~r~r~:r. Phil,ad:;!lphi~l. !:Iii.

1'll·:M:l.1l,U5Jl.

with bij>c~u¢r~cy ~~ld who

used tQ

bC~'¢CO~i!,.

])!um,icd by~nUtilJl'i;i~s,_~lldi 5~cmt~nei~y; The 'oldy mt~ys~eryi:; ,,,hy tile na~ Qutpu~ 1:i:I'D.C has not' yet n~med down, HI QcYE :5:, !Ii U'Fit'ua Depal~i!ill!n~.,~r i>~ytiflowgi!': lUi i:'Ii'leJlIii~ uI' jJ:oLE\do,.ifclelilo, 0&1 ~l&06, USA. TIHIE. ~WS OHH~ WEEK STORY" us, OUT:PUT N nllJtren~ .• 1:I1dNSF \!''Olllde.ffi\v!1y"' by J. Me'f1,.,j s

Threats,
w.

tOI Prlivaey

PlnJtectli on
IL.OWRANOE ANII) f. S. (OILlINS ItA:~SE ::::{,1{Cd]eIlilpOlnls :i:l1lIi1~e[r P;p[icy Fonan "ldent:i~ fi~bi]ity in genolTImilc [Cise~n:]inl" (3 AJUgus~"p. 6(0). AsslllLri.liIili: pliv.1Lcy [lwotectri.ons i~i~, I!iloth geoo_icreseaJICh ~nd medicine pl'iflGtic:e is; of u:rrgem: eeneern, A reccn~ SclE':JI#jic A.rnericlUJ artiele (1)

w..

I:,eq~~liredw gBiln .illP[lpl1()V<lJ~o. use aJlliJUSi~ t ..in researeh ..di:SicoOlIr.aged .., ~~l;ve'Sl:i:g!llt'Qf[l l3i\i'oid p.s'I!ling, ex!lP'minlClltli~il;EIIt ~,"eqlll~I.'e, lile\Y HlPlP'mvals" even ~ftheide~ may bt'<iike only Ol.re,w d.a)'s to te.s;t ~ The" £wlt [ies OOtt\\\i.~ilI clOlnmal'Dlltee lT1Ileal.1bers tt)liElig wroo.il1t ...in c'Orhplia~.lre';Vihil!e st~]]~~ir-

eibrt

I
i

Oif JllIXUm3.11I sliibjecls

,p Aug;ust~p..58!) sMes dlat ·~thetotli. oulpu~ of US,. SCilelilih.!J.1S ·smpped gr'Owil:li~ :m the earily i 99{I!1j, 3]jdru:'~i1't biJ1dged sm,c:e t1rl.ea.1."·lhis COO~
'c]u8~ol!]is based

describes li!tmv Gillell d\e~oontifiOO! diit~ can be usc<ll to reildeii!i:ti~i~tdIi.V'idl.ll~~s, specif1cai.ly

!!; ~~.lilting researchte preeeed, lru:t 1C<1l:herwith:1!1;;;"g~ '" ~,dil:!1:t()nl'lt~1a!t to P~\'lmt not OflJy har:m, but ~ i.1iim

on pljq:bli.ootiorg prod~IC'livuty

,\vhcn bit~ ofin~ibrWl.f!itiQn existia

dntlil: f'rQUli 1992 and 200:1. H~d morereceut

daM been u\\led, :aflefJ8t one l!n:ive]:lj~ty.Dr,~~e~.

datf!basts, The ~nicle reccuats fJ~:ew{)rk of

La:liml!liilYll· Eh;l;1"Ccney. wlrno ]]11JmI~the Dm~ Jil".!vacy

p~~bli.'c::

9113

LETTERS
L<I.bOl't1Jto:ry at Carnegie Me]bm, Ullwers;ity, Herresearch f{luud tb:ntreWenrifyiug [IXlfSD~mR~
~~il[Qil1ilm,llltruQMis MeJ.1.10ria]

.f:lospita.l was

!:Lot;

ooquimdtD

(;:0111,1,'

eases of type

ru

paralyt'i,cpIOUov]rm;

iI,lI1Ie1

s~mpICl' thalil one m~~t:

have

.~magi.lIiIed. ~n Oi~.lecase, 11. 1l.:mJiker crossb refurenced ]~l:fo\f.llilm;llIi1:iQll1Ii in ~Yl.l.l)]]d:y arva:i~.i1ble llo!J~it,d d:i~c+l .. rgereClQ"rds .ag:Iliinsl h~sclient ~i~tro d:~r:tI'liflet~ther.ii[1y of his C[i;e;IlII~ hl.ld ctliIlmr.lfthGY di4lTItc 'il:I~lCir loaM. In Ijno:tf:u~rclls.e,. Sweene::{ Iin,!Jld a '''''fly toreKiltl1ltify pa!ti~~'h;:\\iitl\iI,lti~,ti!!iigt~!'i disease ~"t~!l ~A~raT~ i~fQrnmtion ~b01!,!:l~lite D;a!l~C~lShi@d been del~~d from ~~~eir rocords. Shl; combincdkuOli;l!11l :scqt'~e:l'!lc:illil.g ]lldicaJting; ~l~.e dat~ presem::e of the di,~e.asc witilil, hOiSp~,tl3)~. dis,.. d.la:l~e·r«aoos, wh]chi'I'Ic]lI.Idied p.:ul1e:rnllS,· a~e:s" 3CnJd sueeeeded ~Il acctl!l'f1tc:I.)I Milking 90% of tll~.e~"i.mTIitiIlgtQII'iI di.sease P!a!llie1lli,tswiti:l UNA

c~noo

'p[y W~I!l;l,ifll su'biIJCJer:lilfiIDm the Jnstice DepartmeJflil far abor1ian IJlCIJllill:Jfllts' meru!o ..Lrecerds, . ~H:pOTil~n:IIHy,tlite court stated "EveJm,i:tITt.rncrf! were no' possi,b]]~o/ ;[l!a lIil a plll!ti,eJllt's :identuty lTIi~ig~nelearuedfrom b 1I.fied<1.ct:edmed:ica.l retord,~here l;VQUk!i be ,"'llimf~i;OO1, ,ofpri,*l'lCY.

IIlUIU.OOr of deses ,(Gmss]y e:! al. ':s:r-ig, 3) suggetsts I:hu!t poo:r..qlll!llity '\I1Icc'Une lots are bei:ng clii,8lliJenscd dmiJT!ll!!lp.1T.ulJI<I!ry ,m:Jid S'Hpple~ Illcnt3Jyillililmm.li:Zilti.an. The dUI!11CeS of [iJ!ilIY

U'Norlh1;~~fitem MetiLW'ri,aJ~I-Wos~lha[ca:onot sl,lie'~d. i5 :~boftiQt! pMrerlts' reoords film11. wS'· 'I;;rosuN; i~ji.idid~J procccdm,g$, .mOii"OOVtr, th~

reci:p ie~lm.~oceivrun g Oldeq1m1lltc::;i]il~mlJni;;.mtion r 11ga~m:;tthree ,olil'J'l'~un]s s elfatype s depeml,cl Olf! th~ ql'll!a~]t:y 'of OP1V a;vllilO1lble ~OCfl]~Y. SIlJb.opt~ln3,1. iml]ll!iIJI[;d~.g dO:ii~:5 or mh'!isCiCI i!11~ii!liza:~o!'ili tJ,'Oliid :~i:aJd 'tohfH]iiVidll!~bwji\i;O

[t!lcooo:s

Oil

rule.

~nvo~ves:more than nile' cille]denritlJ. ca'l:ion of ~ersonal informalion, as iMmi'll:nted ~'rt~.1e2004 U,S, Aptp.eai.s case, Nor.thwru,~:ef'1~ "MelfiQrial .f:lqspitat w. "'Ol~li .j'slu:roji. The J case center~d olil Ashc;r"O'fi:'s, ~Ue-ttIm,pl sllb~ to poena [QI~gJ~ly 45 NOJl'thwe::.tern Mellmlari,i1~ HospM~'Pfl'ti,t~iJlitreQOJd::imr ~8e in an Uip!DOrnillf!.g trialin the Soutl1l~rl'll Di~trtc:~ of N ~w

Privacy

h08p~tal wiUI!9S'C ~h,c 'C()IiiI.~;]d(:nC(l ef H~ dQ~l():~r,e~(]:nd to!ll,u1lrp~eOP'V deses A&~:y~~bvth();!ota! VQI. cQTI!~rU( 1) ,oU,.; p.<!~ie!!t~.,and pefllOins. \,;Hh 8~fi!t'Ji~iv~!'!1ed:ilC,d b 'corld~tiQ!!1IS may be ~m::Uflookl' til!ltJli clsc:w~~ere vaccine dose :air,!;: liucd in Mill.i\lOIl" of type 1 fm 1I1IDdka] trca.tmC:lilill' 1(2), poli.o'ldn]s,.[iQt-ency !l\SIlays entri- O[l;IIni¥BJlerul' (AR!O:1b IIiSlAACl,ONIIBAM;S!1HII ~o1sli"Ctrie:l,red fOOlllfieid l!.tiflge wouM be more re I:iaWe: t111'S11l !fI1!Y'C'UI'IIlI.t1rnative ~h~rma]color 'G!i1nelk~.~thk~,iiln;ril fiJll!!;,;, ('ilm5U1II:ilil!!l. 1m:.. B:aitiJ'm, 1M OZll31!1, liSA. E-Nlalt 'cb.air.il~Iil@9tRolC101t1 c::.Ii1i!lillges obsc,1J1,J'cd by vaccine vial .1m:mHors. V:!Jcci:ne-vhd lIln:nhiitmfs ~re jmi,t p:l'n!ysi!C<I~. i~Klica.. tors oftemperi1lrur'C. They do 11Q!1illdiC'd,l!C~he Rd~r,elll,"e5 1. !i:. \~Iler.. ,s(AAm, 2:91, 9~ (J!!!ly llllon. period (dMmtiO!lmI)' of ,ex:!)Ostlll:e to such til tern ..
~, nf!~~s.~.m
Oml9l~ mil ur, .2:004),; l1J'il'ldl!W!~ !1l!I rru,~!TI!:.fi ntlIm'l!. Q'lmiliidmcSf-oocstabmn:mh<1sli<1!116 M!lJlfl,pdI.
j\~jall:f.~~ ~"t.I(!MMI!~I1/I, J~;l

York to cha~[el'!g)ethe oon8tit~tioJilfi]i:ty of

the Pan:iai-Birtb Alll()r~:ion B,flnAc'lof2003. Althoughpat'ic!lt: n~Cior~~;vould '~~\i'Jf; bC(;~l \ anoliD!y~ni~oo prior w' rdC:f~(l.p~ic.1l1!~s !lOr!!et~c~e[iispl'o~Ci~~ed~~ain~~~hcm,ft:'ga()Cle~S 10!1 A
g!Ol:Il'Idj~ tha.t!lI~.Qnymi~troilll dicl:oo~: fI,:lU:!IllI:Oteci U.lei:rIwLwcy. Thehospital wenrto roUI!'iI:OO block A!>:hc.f.'Oft~, almd the :p:f1t]erll:s, prevailed ..

IPoll'le nt' OUlesmlolnis Abo,ut lndia's IPaUlo V,accilne

IN n:lIEIR FtIE:~mH "NEW SliRAJEG~IE:5 FOR TfHE
,c]]mi!lil!~tio~ of pollo fto.Ilii!!d1ia"

not i:l'!d:iCii,~e-t1,1e lbi!O~.ogic~,<I.ctivity ~n tb,e, "'110cine v~a!,e.. ontmner (,2)" ~[liIdyertenh~s:e of 1'001: imJT!l[l!!'!Ogerlili;:lity I,ots ,(,;1) fl£gd blilutal h~nd~i~

perature ..lFmih~nnOire. they donet ~jndic!lte th.e l:l:K:reJII:t e.'!i:,po~l.Irelo sunliWlit and weuld of

oroPV' ~liql~alB·~·O~re\"'ide~~d, Wttis a!t~c:mu lPo8:sibJctbalt (h~1J,pare!1!l

absence of ,gcJm,(;t1!caUy divCf;§e!rl v<).()ei1JlJ,edertvedpotliQv~n:lses co:rrcl~te,~wHhll"iekl

,c~ubcr2000.IP. [ .~ N. Grasslyet Iii], di :i:Cl!SS 50),. the: use C)lrLri\!~h~ln ornl poUo '!,;'S!c.(,':in~~OPV l'
a~~i.m:;t type: I pol.kwints. DMlrillilg ~h~ pa:,~~5 yeB!I~S UP'V' e~ic.~cy lin rcla:~ion to 'OOfi:firmed
inrurndia :fi'ol:'Sij:rp~C:Mentl!l)ryi:lnmU'lil!iZ_fUioil'lJ[<1,

(~7 N ov-

usage ,ofpoor·qu8~]r:¥ OPI\!;

SilJ:iIHlASHII(,. ARYA AND IN ~RMIlUi. MIARWN.

5,a;ruiP'ilrmim~rnd Hoo~it.i1l18,II.~ip'Br~ Rn~d~ D~I~i U.o0l54, IflC10li. IEoffi'a'~,~ul!JhasiJij@n.~lf!iJil..c!llm.

IReiI'E:{rEO('Il!5 1" \1lo:rl~ 11Ie.l1~1'I, QJ1I'I!l\i2.B1ian M.anuill, Qllaool'il'll~1Y "U;:~I' 00$ fDr t~~tintj .I)~ 1l'II~:erKjl' alllflal \i~[[il'l'~llISL'd til UI!l WHO iE!:P<I!l!:!e.t;I :r'~i1:mtlf1e en 1!1i!1iIl~il<ll~c~ (WHO' P 1'l6795, 1 6e1!et~,1'9951. 2, WM fm ~~, Te.rlIlD~1 $~.!Or~f1an \i'.ll!ld~ Vr<ll.Mon~tiIf~
Ill!

The

'COll.tr~

diere:fJmJ1:ined lh<llt NC)lI1:hw~s1!m'n

(ORREOiI.OI!iIS

.AND' CLA.RIIFIICAlIO:Ni5,

Newsof ~Ine Week;·I~ i)aUE!f,E\I!l Alt~ic S~j i'o~ do.~ ru the' OOillnt?" .by IR.II. Kerr IS Oc!Ob.l!l. ,33t 'lilt~c.a,Pli~ rvr the' ~ !!Ira phil: :5hol!lld hiI'M"e1li00l.!dlmOfe I!.IIIy~lilallh~an!illtrsfi~ u!l!Idut!d ilm th;e, 'Plot \'l\3SllIif:~erent (rOO'! I:h!l' iln~~y.~ls llIi~c'ws9l!i!11 tlw ln h!\(L ,A.par~i[l~o"lr Y'i!<Ir'5 .5fll3i[e ar'iN!1dm@F@dif:rn tme' iI'I~lI ~n~lys@~,b!1Jlthe lal~g'Hlfliriilru9 dQ'I'j~I~ rd tnllllil!lli~n.clHlil!~hlilr:p. d@din@' i1!l2@0'7 iJ!je~~~I'l!i! :mn~.

(lj!f.~rld iiMWh O'QiI,II'iLJtOOlfI, lfjlfi)e-\'ii. <l.oot~Muwlnl.oili!ltil { ,n ~1)~nlbel'OO(!6~rl!m ~IDild'r.msv.uoJ:il1i~;oFg! me!ffiettinIU'i.J rt~!LI\;.HI WM!, OO!:~,. s, S.,it Omil,ilbll, ,A,. o, 1000'ol-ll,(). 0., ~o" It .A, AudIJ. Aft J. MM ~1'ed.xi, 2,13.,~09 (199'00,. 'l" ~,K, Guei, ,",,,1~"Sjl'liJ!1)~ P. Bhatia. #ttt J, pub,ii, So Ht..rl!i.jl 48.. 2001 (20:04).

IC:OMMEIMT (lIN! "'tt

for tile .lln

pmant HClIr11i1101ll'el .Albs:ci!sic Aciid""

G IP'mtei:n-!Ccmphlld

Re.C'8'p to'r ~'5 a. Plasm,a ~Memlbrnlile Re,c:ep!tolr '

IReSIPomile
(OINIOERNEO ABOU~ th.;: polc!fiIcy (J!f trivakll~ oral p(;IIIiQ 'VaCCUI~(; (OPIV) adl.m~l!ste:I'Cd h} ,r;:Mldrc~li~ ~nd:iaa.'lilrj the poss[biHly of 'low ]1ott::ncy cQnn:ii:bl!.ning~o :IQW-c~kacy o:rlMs wccine in UmlT Pr~oosl'Dl" Thill; oOllllcrn see'm.s to [lQ~ from several nllis~
IJImJdeU'Sla:ndil~gs~'bmli1! 'ihe'~esting. disLl,nlfutio:D1lJ,

AIRYAAND AGA!RWAt~IU

ChriiS'li(i)phierA. J (th,~s~m:H11· rend a 1!fI.Te,m!l,le., Jiii:l~ lif Che'~1¥itIl]un Ga'(i), Emuko till. MoUfrY(lJ!lfh;!. B MI,.JO'I'I,e.s, Da'rludlP.. Sidemvskll Francis 13" iIll'ard W

Liu ria!. (RBJIOrB; 23 Mi!~[h2007, ~. 1712) ll!JI!lrMdilim diJ~AIfab-id~ 'Jm.iJrilJ[J 9@'n@:GCR2'@I'lcOi:h15.il ~'I!..i!iil"tl'<lM'rrU!m· t. "'ra!ne, G! piOlein-.oo",teti re"o~plm!l1rabsooii1t: add. 'We argue ~h\illG.CIt! is lOOtGlk:elylo Dea,lmiismemlrn\MI~ pmleifllnor a G I!1fidle~Ii'I-mUUl~ IiLKe~to:r.IIMtead.IGCFU. i$IOO.~[llle~'ia Iplilnt homlagl,of bacterlallan~hionille S1i'ii'lith~ Full ~~:d:,~t\Wjwj!d~Ift(l!m<J,g,orgf:GgiVmntmlljfuI1't3111f535:;U91~,(.

IFI,ESPONiSE.'lO COMMIENliI'ON '''A IGiPnneiin-Coupllle"dRece'IPtor I:s a 'Ilaama IMeIiIllIbr,anl,e ltIJe,ceptor 'fl)) Ii' tliJlll1l PI;:auiltlfl ,1Ii1ilili(lne!Albs'c:i.$ic A~~ d'~ : Ximlal1~uu, Yullimg ¥U9, W,ei L~ Iitg.8ilillQi Ma
o.ur~!l)Id:y pr.o'O'irlm:l i1J!jIMlrim~!allNidMtl~"It"itGClR2 ~[lIID11I1l1Br.;Bn!!!,~55D{i;grmdi[llbMisi( OO, Ir,ocl!flMIII' tm\lti~r~Efi! wiIih Ith~ ~ G prO!~iill (lc:~ulJ!JJFlilGI?'Alin Ar"al;ritibpm •..AllD'lIl1u,glil'we GiililiffIJI: ru~~ ad i;jOR:2as ililanlh~ooin~ sJ1il~J+tel:a5l!': h_OLog\ our tl<ita iml~te: lh~t it 1i'I1<l)' def!ne <! Inew!1!'j:l'e'of nO!!lc~Mc<!I,G p'roi.Jei·n,..cClupledlHe~" fl!!l~~exl, <It Vlwl'u'Clen~mag'fJrgl_g;j~~o~ulfiIlJH(,3m'S 1.I521914d

a:nd MSC oifOPV I:i~.rnr!ld:ua.

use ~Il~fl.diaislcstfd by the' pl1odu.oe~r 0I1i1d,. sullJise'C1llelllllt~::f, b:r aJ n<iUtioru!~. 'lie4erencie~OlIbm:atol)' bcllJl1e- ~.elleil.se. All b!l.tc:he:s 1.'Il:'I.ellsed in India, ilI,rf'potf'll!t ii.coordui.lg toil1lirem:at~oiil,d stiinMi\w. 'TOOl'S of ~~cb~~lmvid!~,"11 ¥~n!iS"md ,~totl).I.titer <Ire &bill eV'ollml!ted., A :!!pecitlc,inte:r,llJrn:i.o:n.lIly iiJ,£NedAn OJ'V
I1eleaserlfor

9'14

"} NOVcMBE.R :~007

VOL 3.18

SCliErNICE,

'WYIfIN"solienoomillg,org

LETTERS
upon be:m:::,i'IIrnar].; Uterus '~"'l!edto $Se;sSPI)'tcUCY ,(Arya and Aga.rwt'll h~lc,on::rccdy st~h: that

(:for eXflilTIplie. eaeh dose :rDltist coutain :i!i~crsof &'l!bin selillypc I. viras 'lllil.l exeeed 1 ()I! tillsslIJ.e cnh'lll'fc ~nlbcrive dnses), U11l.l!S, the .suggC!i!il:i.Oll
t~milllt ssays: used to assess potency are'some. a howbiased mmlm:]sleml:iJiilI is :ilmcofl.'eCt, At\tc;:r w8!tinfJ;.vll:ccil1lc ~s dnis;lT~bWIJtediJil 11

rc,wrige,rn.led "cold [;!ru1]]11 " tiJrou,giruont 1he C,(]![1l11;try; Eaehvia] OfviLccineincll!ll;de.s <'I'l1~C~ c;i:ne vi<'llmmlito:r {V\lM), which ~ndi(;.ates eumulative he"ait exposure ever time. The VVM is ~<i[ibm,too to ~lett the ,1<1:Ccitliih;Jlf
v·,;hef!l '~~II;;Yi<'!J has be'CQMC e~$Io::icd ta cl1K'tlitgh heat Q"\I'e[' ti!~'!.C to' rcdu(.1e pot:e!.'!cy toa ~eyc;1that""''Ou~d lmiinde:rlhc pro~cx:tiveelfect.

V'VM.~ do :Ill,Qt mea sure hea:texpos'l!n.re, 'Qv~r li:me,j Thus, mltholJglln. tllc VVM docs. not dimcdy measnre ~~o~ency. i~: l1ov:idcs,iJlliil"o:r'= p ma.tio~rn.about the' nUl in fae tor tha t affects potelillcy. V;acci:l:le vial.s whese VVMs,indi." 'C<I[f: that 11iu:eylmlOilive ot been maimained <I.t n the correet tempc:r~ture ~Ile discO\Iirded. "fhi.s sy:!'ite~;n ensures that oMllypoteJllt ora~; polio
V".JiCcilllLe ",Gimin]sleoodto ~!l!

sien yem;n;i ago will:! dlie tr.iva.lcntvacdne. ThlU:S.neither of these :rerel:l~]l~e:l'i SUPiPCll:ts a Sel10rrul,,CoD'lmCern ahout the cold ehairs Gtlp.m::ily
cine etreetl¥ene,ss .. fin <Illy. tjllC assertien tbfllf

in mnn;(lia m> a.pote:ntial cause rOll' reduoed vao=

rIil.lC .. bseace

of

genetically d;lrl,fcr!!lcnt vaccine-derived polio ViliiU8 (VID:PV) is consistent wi.dl useef p()(Jr~
q!ill;~ity '1lacclm:is netnue.The
1;1rI0S.~: ]~.np:lrtal]it

ch]]drell in bldill.

Letters' to the Editor

lr!~t[1r~(~3D[I i'loms)

d&l!155material published in Srf.eJjc~ Dinth e previou 5 3 month § ori ssues of gm[,J oiil inte rest, Tb~V 'Cilil b~ submitted iflra·ugh tit", Web (\'!fIiIIW,S i.!bmil2sc i~n(!flo.()r9;~0 r by r~t!lI'H l1li!!i l {1200 N", York AII!2.,fIIl,lif; Washingron. OC 2~}OOS.. USA}, LeUers <lfE!' i"! Oil a ckno~{!!dge·d upon m('eipoll'lior <lie iBlllthiO!5 geni.'faoll!f'C1J1l5UUIC:d tJdor{: P'J,lbl.i;;:atiOi]I., Wl~her publ~hed: fn; IWilt,Of irl Pill'~, le tler5 <II'e subjeot tOo edi'li!il'Q ro r dilr~ly 'Sjl.He, alild

Monitoring, daM shews on IYf! VOf)' small m~,nQti:tyof Vii.cei!i1C vials o!bse:rvcd in the fic;l;dimiidica!t~ (l'i,'er'e~'P0surr'e 10 heat € less tirual1 1%) (.J'). b~ ~ddtH!!)!l. a. r,ecent:l:a!born.tolry ,evaJ~I,l:;a:Honofmollovalclln: {lind: trivalent OPV retrieved from t}!(: fieldil:! U~~~rPrlldiesh dMir" Lng t:lirIe 2006m:f!ss;i:mm'l!'nlib:~tton ca1l!l~pa:~gTl5 delJlllI!()1ls:1'['a'~ed m:deQifuam;epotency 1I1I!I.U. viBJls, w:uillil VVMs im:cJ[ca!ling pote!l1Icy [aJ samp.b.'!of 345 vials fhnn69 di~t~uc:::::1'~ (l)]. Ary,!! and. Aganml eite :!!U <l!lii!c]e f1bolJlt a. Nis~riml :lELea,sJes, immlll11li.zatkm [pi£'ogrmu, whi.ch is of negli:gib~ere~.e'!,!,EIIme to .tI diisCfIS' s:ioJ:li of the' hHillinu polio ~m)mllt~n~Z<1ItioJ:l pm~
gl'm,u, andl <Ill liIirlic~e.nbOld the 'J;;oidchaJi.n ]U (;lll'lIndiga~h. which, ;:1.lt.ho~lgh India, ~!'i,a~,l in lIi1:e.1Ji ~]im!t: 'eti.im,fIed,wiMpolio virus h'ims:mi~·

risk t'3,ctot for d.eve.lo,;pmc1fllt of ciltC:Uli.ntill!lg V[)PVi!':,lrO\v ]XiPWlI,ffllOiri irllil!1m.Ullity ~eV1erus. If the woc~tie ,~,s poorly imllTlulilogeifilile. lmv pord ation ~mm.1!i!:nity WQuid:ro~l!l,l;t. and on~ wQurnd be li~e~yto see more. riot f~w'Cr.
epil'>ooos, of· dr(il,j.I:adng VDPV;
rill CitiilOIASC. 6 M~$SlY,~ JiI\YWllNG EiR,.:i IR:.IBIRUIC!lEmi~WAIRD~
lD~pilr!m~nl {I~ Inre[Hou~ nli~l!o15il'l!pid!lmli'[/1Dg~,IliIlpl!ii~1 (cll~B~~' LOllldoo. IHorfiolk Pl1iQll. Londa.nM lPG, U'Ii:,

~N~lill~, !Pclio Suf'l'€liIL~liii~e lI<re.i~"~'World HeaLlh [)~anrl:~at~~n~R. K. iKnil!1!l1l Ten!i!is)t!1!dhmll. liffn c.a J\1.Iefiltl~, $<!ifltj!~1!!n'!i E.~d~ ~, t.I~~ D~!hf, i:i!,i;)[n~,. 'nd1!!,~(;iI~b~! ... ~o1i!l E~di'C<lllj!:l,~ l.n.i!i~Iiv~. World H'~~~U~ rg~ni!zillij,mm.2® O .I'!{'j1MW.~ A:ppia,. (I~ ill2:n Cl,en'2'l'a 27',Swi~~ErLmd,
1F,t!;fl1:renlf!!O t, NlltioMl ,f'llli,~ SI!iNi!lllIaiM:l!'P,r~'!!I:t, d~1lli.i!IfIDLallli!, <11
~.I!I!lM~IIIi1d~u!9.

2.. M1J:li1~IY!ll1 H!iIl~I",OO F.i!rnilil'~llIrll,. IilIl!A!mll'lefllt ~I' IllIdiil, ~!l'Ii! D~lI!i; datil ir\!'ai]B,b!~.;JL ~w.""'!lpSl:luOOi'a,(I~y.

Rapid

N athma~ l ns ri hJllt:'s of [ ['I.:ahh A('l:'l:~l"; to Iutc r v crnio nal DQ.:'vdoPiUl:U[

FI,EE Or-lUg O.eve:I,(!IPrmrel~t H~SglllfiCe:s'oll" the A!eltd,em,;~N ot..:r~li'~r)ro.fiif.iW~"Ui,g~uor l On.i!I ool.npeti~:i'!.fe basis, the NWH 'Qfitl'~ eertsin cririeal resources Ile,ed.edfor~he: deve!otrmetTIt'of new small 1,1:':10ecule lher~,e'lu te ~g:elHrs. The N lH allR.A~ l DPi. lot .~ So not a gr~I:[~progr.;l!n, Sllcce.$s;[ui pffi;jec~tswU~g~in aocess [.(D the g.Q;v~I"~~me!lfs Qontra~lro$OWi,:ces. S'crvk:~~ indnde: SyJ!lJ~fuesi:s,ill1l bU~.kof g:m.~U molecules: SYl1:r.lrIesis of o,~igoli1Jl}Id.e()Udes; OI::temk<'lll. sy:l'Ilhe,si s 0 f
pepHde$ SC<'III.e producnen; Dev~lopme:tJ,t of ..np' : ~lm:9]ydc-a.~metl1;Odsj[ Sg]QJtiOl'l and ]"i!:Iir.it1oation of uamral

Science ALerts, in Your Inbox.

·G@l:d\8lllyam:d Wi!@k\v
whE'1it~,e lanKt ~S5uejjf.~.Lteo f.5aertoile Expre~ ~~ !i~e!i po:o~~'I~~se~helaI.!lSl ~~leof~OO~M[!!i·rb!S'~(j(!!l!l!~ Sd!1Ilil't'S
Ki'lQJI\ledge~~·!)t1!ifl\efI!" i)i'I.d ~,~~~mm$" r[(!!!: ~I'tl'!{!~OiJ/ml'\i ~1!!l!!S.n:Ii!I, oows· fflnt~n'!, er EcliiWF~'~I'!f~ ,oQlurn:n, all from'10l!lr'e·rma!l~ rlil~ lfuI Siall! p.!<!eiving !I!'iIlIlO!Iil ul:ldli?it~., o !i)= liiU;pj IWWW;Jliflil,llfti ~m !!i.ors/elm ~ 1E-!lI.!!I., '1!IiIthe~I.li'Iew$aoo r,e:seardri!Sign uIHoNmre·c.'I!ii:rt~ern~~,!loo ~oo.'iill!'! knffi!l

~en~l~~~i1!~H!lIi'!J

products: Phannaco killeti cJ.ADME s;t[~die~.nci.udi:UJlg i

b:ioan[lly~:ica~ method deV'e~opml'm!~:Development of suhable form1l:~I;ado~1$: Mamufacll.ue ot'ellnlcat tr;rial dn~g 5IJpplu($~R;a~].g!:,':-fi~l.di.1"gll ]liaJ toxi~ ok>gy;. ~N[)~ i directed t:oxi.co'~Q~y;Proom::t development pltln~l]ng fIlnd advicein ]ND prep~f~.tioti. The pfl)gfa~'tialso is Ope3], to

$.:i?rKI!PIJOIi'iI EIiI!!~A'!"~ rl.:iIlj' !iB;l!:!Jm{J'Yri'im<!fi

~~lMmzillof!,fl)(

W!!I!Kl'j'ti!!JiI;Qf mll1~nt5 :Sf!OOE. ''IDC

lI.t!ett!"I~'bI~'

s.. :nre,~ssl'l-~!lQ~ Mii;'II!S~U)'i!.]lICd 1Il.~?oMeo

I tiiOll
~

,cr~Flii~I'tU

~\1!!illr\~~ Hi~ias;trt5"o:flfil~ 11!U!;nl: r~a.t!Llr~

1III1b,W!!!!t:. Ifi,S'A\R~
SIl'l1JI'I~fkl:o'~ roOOll!ltJl

IlO~~·.tJ.S. appli.C!MUS:.
A:ppUCiuion 5, are received c:l,ecl:roilically dllrot~gh G:r~m!;.gov, Ideas ~!'i~i!lg ~ol~l.yfroni1! a cQrpornh':! wi.d~ollt academic (;oUabor!:lJtors arenet digihle.

(:¢I1(cnt

scnn:(:~

N[ "~llAlDP:iJotl~'r~g,m'alnl Office 3Il""5~4(i60'~ iIII ih",;rnim1@ .;I!J~rn.ni lIi.go,'", IJRIL~ h ttp ~II:11mro ad "lap_iii h ..s;ov/.ii':~hj

,
I
I

II

SDCIIA.L SCIENCES

L'('!iS~:siffil!'::lr,c;m ~}e·:_pOFita:ru:::e ofs]nl]l~e mle..s. fOf 'exmnple, 11:1"'1:C!:llte prnviclles HI gerlerati.ve: nnx.lle,] of biol!o!il;~[;a~! orgaaisms IliflllmlS iem-tules that viol ate basic ~rincipk;s. m
S1!l]Jpose.

IDian~elllHelrl'l'U!lie:r
·N·· ....
.. .....

of ~y:s~!l:!;~.Wbuld .!\\iIe cOllsicbr f1~.!>an cxpb~ I1l.'1!ti.on? :~ think not ,[Nv ve.8
1

. ...

(;loarl.], O\i(j;ry :book on a.gelilt-lOiII~(;)d m~d~ll>.i!mJC. ·.~.I'l.id1ng .GfdtM!Iti..tIW ..~OCi(IJ { ... &~eit.c~)fcatt!~·es ~d'it.'ii!lOcd pFJ:iSC on
I.

llic

dtl!Sl

cove:rth.;:);~higt~!.ight'S f,l\r!i;:tn:me~dow;

:mQdel.ing~ Ag~hlt. I~rused moddillg, hm%!'C!v,er.i:s lrn.O>!.f ~l ]e:ast .35 y,ca:rsol.d----(lollI11!]11g ft·mn ~ilm!L1 publieatten of Thmn.<ls. ScheUing.'~ )\licf:or~!o.tf~'es tllul
l~rQm[:ilG: of agcllt-bas;\!d

A4,a,crobeiu:n,w.1' ,(l)~aJld its impact an nl8i~ll'

!;I[remnres:earchiililJ the thr'ee .Imjof 1!>oc;iBllli !lci· enees (ecor.loluics, :!>oc~.ol.ogy,a;ndpo~itical sci .• CJu~e)liii'1lIS beeJ:lln.miwdUil contaJlst to, say~drum of liune thoory.Before thereader jump's ~o COJ~.dusi;o.1iIis1Ioont cmlspimcies amo:nlil seien.

The g.en~mt!t~:iltand~di~ ,~pi~· o!n~z.ed i!1~h(;~~ ijga~ •.if you. dIdJn!tg,iimv it. ~!J dJidn'~ ~J(p~~i!'lilt;" Th.i:15ge:l1elill.ti.·ve a;p"n~~ch. of COU:l"Sc:. ~s: lffi.ot new. h: has pl:cd!eccS:S(l:l"S in ChOlmuli:yml Ung'Mi.stic:s al:ld even 1Amnas. :Ho'bbe:s!S Elml't.(!II'U· (2),. T:~e~:c:: iii, huwever, seme tension bel. t\\lCCn iilLl~nmenlS (i) 311lJdi (ii). W~iliic:h IJlres;~hpp'QSe 11li1;l!m'en.~ d~;tjo.1:Jial[I[J.odel. of e:!<p]otrmt~Qn.

'Ge J;iiH3t~lIeSilI'Gli al
Seili!nill~e Stl.!I:li,li's Tn Ageilit-

t'owardprllg;m!uist a,eeO:ll!iI~ ('l'f e:;,;;p]rnmltio!l should b~ K>::1istt1d;

they

Ela :sed Conmpl;I tau ona,!

MDda'~!li1:g! byJashu8. M Epsudn
Pri
rll:

els (l!fftThi!c hook, b!J~ the,),

*~ let a;g~nt-oo:ij~dmod-

,al.~

(ltoli Ulii "H1!:rsi:L), II1l SiS, P

P'ri!'lCE!lOfl!, NJ,. 2006. J71l

Ji j:f. JIi'Ii.lSGil)' $49.50, :E2ij.9~. IS IaN 9780691125473. Pril'lCmolli Stui!lil!!S: illl

a:bsolve :rnti!)11~lo~~JOice-ba!l",d tllcorU.cs.) My~e:I1&C hi< tThiflt m:iliilly ofdm m[ellm:oo in agCI'I!tbiased modd:; havethatli:::!Iurn::. They are too s~,mpk~:obe p:la,u~ sibte, Tfutis ~s: p!lrticI!lIBlI:~Y impartILnt

in the: eicolllmnk

con"

Co'm,!'1 e'Kil];"

tiflic elites t1iilillt rigj.druy ho,ld Oil! to ex~st~ng vi~w~,ilt t::l \!,\w1h 1wcp:i~lgil!ill mind bl!t.O'\lll~r the pm~t (5)'cf!t~ tht1 ~upPOil~dfortress· of orthodbxy. t1ii:or>etk:l'l~ccoo~lillic~iID~IS bOelill1e",l)lu· ~)t'miZ!edaJ ]e~t~lli~oe: first by the bmrodl!ctkm ce~Uy by (he binh ofbc:h!lvi,o!:'rl.] ccon~m]c:s ~Ild llC;tI!r(ICCig~lOimi.C$. Agcl1t:-ba8Cld .odels fuia¥ehad no, !iJmi~ar imp~t. Josbua Epi!>Ie;j,n'l;book is !I. ,dear i1I!l'd h~JI Ull,1lu:il'lfrti:ng.:res:pcon~ to t'tiDls,(\l\i~[lenge. ·.Much of Ge!Ie'r'{f,~,ive 80cfaf Scient:(! is not 1lJe!,"I,!i'. [~~de~d, H1t}St .of t:liD:eook :is e,ssenl::uaUy an b <Illl1il!oklgy of ~~rev:kms ork by Epstein fall w economist at the BI.'Ooornllgs :~nSil:~tlll:ioll}iU;ld ~lais GO<luthOiffi. It should be noted t1:mlhav:~ng .tI~1 ~hese: «onttitrJul:ions: ]1,1rn~Jeplace is not otdy useful but plem;~~.lg. It is :81 d.e:li~h~t:orezwqutlant 0I1c!llQ~fwiths~c1ilgelll'!i as the!;.vork ont1rn:DCluE· 'ml!e. popliliatian. ~nd lbe1m.~wi(Jfoft~.l(; An~i.i7j , and~lc (;(!!!1B[{j;mtk~!'l of civil. ",iolc~ce. FOir dle: fQeler mLll~lyi]1!lt.)restQd ilil!';Vhfltis i!J:etV' ii'l~gi(:!lt-ba.~~dmodle]] ~l:g, the; flr~Lth¥(l
by of c;vl)I1)l!liof!1!:!), g~mt;: U~!e~l)' ll1Jiidmore m·

!I~I1.d1lirgJlUil1e4D.t(~]i).whi,ch af~ fersa l'il.tl:ietdifferent im'lJodel of eXpILa[iat~()iml. This ~ m.Jtji~t'3t a pl!wi~.o5!!JI~:iuic<tt exercise as, ow c ·cfosori~:8JP'Cc·!i1Y:1\ ffi1.uih OI·.Bp~f;in~ ~rgIU.1W!l.~$Uit jp\ro:rI11isin.gliir~~i'an:ii fbrll:ge~l:t~m.::;edl modelbliS-fuir e~mpki m.its: re~ll,tiQn oog.aIIIJ!IiI~; tJliedepc:IlJds oli'Jili\j'hetller \7I.'C ~mleedllJJoo~p~gl:ll!crathe 'C;,,;!pI1l~1~tiO~18 8(l~:ill(;hm1i'superior, The Oil)';. whidh pl.flY$therelc ,oflihe anckm ~g,i~ll)(;': as to Epsteint revollooOlJa,.Ep5rein Wl~lJJ:lS,dlli1:t ~(l 1!1lIth~; Imf!;'I.te:ver.does ~1[JO'l p1iQV~de ~nyJle;:a;5Q[!S central ~~]u!:ionco·nc:@pti:nm:~l1(loop();r~tIrvc why a gener.~tive :r1!ppooftCh i~Sl!,~ior. !!;8!!lllOt pro10 ~c some (lflh.;; poss~1l'l1epl:oblcnl:s. 'COiru·· pille thool'Y. Nash ~l,lr~ibri1)!Jn~ vide ~n ex;p~nl1!ntL'Oill of hm!;' ~u~~'~lilrit~m SI~le$ :.:iderthe: CIOm;el.'S~ of~~me.ge'ITher'dlivist daim; "If 'Y0l!lgrew it! :mill ex:plainetiit," ll~, the: iSJgc'l1Iit- can Ibe ~m:S!inCld. Ti~e faeus on Na!s:hc>qlniUbba~ed n'a~hion, t'ioll!l~de:r~b]e' {~I~~;pha:s:~s: :r:uum !u1i:dul:s SIn.tlc 'lXlf'e:rlies,.11Q",~·el~;, l;C'ClU:S is;

text. wlJaiCre:l\iC C1D1I1Cl:<lsi.!.y devise 3tRlu~gies. that ,wlu.!!ld be ablete olltlpe.nro1nrnrn. ;the propmednl]es.. Dropp~u£; the fWX<1it[ot:lw:~thll generntivi:st a:pproach and si:mp]e niles: mmillY ol'ersoim,l!e:

p~~cedl mm,he:!ftlct that "~.mple"l!llIes t ~e,ftdt,o the "emergence ." of "eomplex" b~~UlJviQir. Ep$~ei:l1Ilp:1"ollJid.e:sanniiac. SOJnmvootll;mgl]e:,..illJ~ clllee:k" wsctlssiall oldie wgmmes:s ~Ild iEIIln'bi.~ .glllity of,en1e~[Ice iIrud.l.eageliUt~ba:sed :riIla!odel~

illg oolmn1!lln[ly., b:l]t the gcnewt hrist s.lo~a~

quite mJl:dir1ted. Th.e issne of how player.\> eon·O:lm. ieql.lilmr.ltaJ hall 'been ~Me j;lJjlfu;jeclef an em:eme.1y iII!Ctl'lr'f,l <8111(i, IJIf:]uell:tiRiru zesearch fIlrea. evo]uttioOilU:Y g,uue the>CIry. TIds approach is 1ll.Qt~~l~.'<iiti'\fe' in the.sensc'of~pst~in. becaase til.c mldleil:ill)dili~g rules mr-e not s~nlpl.e. Ra~Jin.er.
'm'~

chapl!ers are

E~f.i~~~n'=sm~in3:fgUtlllcntis thalt a:wetit-b~sed

D{ldelfl. ha:ve ibec;11 bQ~b mi:Slll~e:I1Pn;:ted ~Ild evallbat:ed by the wrong swu~l:ds. !He CQll;· rends lfuilflt {i)c oJmJlrillry ~o comll1011iI1 be!ief~

~~r the most i~ucr(:&H"g.

aJ.~nl-ba5~d models do s:lLtffisfyom S1:andamR of scie:lThti!llc theories; (i:u) according to many extpltlUatmiY cr,uteriru, SJgent~biiiSed Nlm.ooeisOlJlt·
lperfhl"m :lilllore' tr<llditriclrlalm.odeilsgi.ven those exfblinato:ry s:mnd<lTcls; <lind (~i~)hey Cl?leilll:1;' t IPliiy <I. dilierentl:ype of ,ex!I!lI,amttory eriteri ..

atpprniPrio1l!te fOif "~.e.~e[llLti'\l',e ~oc·ial

S)(;[(l]iJ:c:e."

fh~ 1F~'I'i~~i!'JUS at th@N(irtl1\!jI~~t~rro Iln~ti'lnt@on ;(olillipll~~ $ptmls. iI!lild tlhl~' K,~Ua'!lg$,[hoa'l amMlI nil:g;!l'Jlw:It:, ~~n 1IIrnIlIi'Js.itf. bilI'lSIO'JiI,. IL 6021(18-213(19" USA. E·m.l'im; 'd·!.'!Iier!'li!eier@~·~o9~p'lolth~e~teMd~ r

5if1e'rid~

iii

RtJi!.d!,

LIl'l'ilra'n~'

171<1 S;8:S, Wotrt~~tem ~

"} NOVcMBE.R :~007

VOL 3.18

SCliEI'NICE.

'WYIfIN ..solienoomillg.org

IBOOKSETAL
T1h.e book begjnsw[th the analogy thai: tll;ey flbillild on hlSI.ghh. from pSy'CllOlogy mnd clil!lp1:er Oil se]ecrioib'nl ~mOib'n.gg,I:O'U!)iS. t~'1.c matheliil,l;at'i(lS is .Ii~e Lasn; cvc:ryonekll.lOWlli ~I i!l'utl.mr.s nse all ,ek:galll ~10dt'1: ~O's'hm:v t1m.~: both incofi!1'olilu:e ]earudJmg" aOaiptalion. 1[lThd solorth, U:Jm,Fm1mlaJte:ly,. much of" GVOil.litim1;tll'Y g,nfne few words. blJl:ve:I)'rewpeopl.c can illl1ld.er.stBJllcl kilJ1lJ Sdeot]Oilil aJmd!il~TIl1pselec~:io:n WlllHol<IJches d'n,eory is :soldy couceraed w[~lfbrUlld<lJt~OJ!m,~ HI seerenee.Tbe anaIO&.~~dsagood01!le,.E1sm.lItk~ to i!I.luui:snl yield llruJnm:iUoll:'$ r~k .. As they !e1m~nt~c~s ttllklCS a baiCik se .. ~ in ]11.1Ost biology proremlll1iik::"Ulcre;i s onLy 'OIle~'Ulld ann:m,e;re. h Gljl],estim:ls, e.!il,,,. how to cliil:tII:a.c~eIiuze Nllsh cqui]ilJilFillQ]lIIi1 far g,ts rcfililemcntslin tesrus of \!;1)~ddlbe bad if c.]u!OI~l,ging the ~y we didthe b'n'mlilLMc~]re<llh <lind Boyd (<l;ntilu'opo!o_gists ad ll~ti¥e m:ec,lllianisitls. Muc~lkl:S:8t\<ork has <'lit, rel:l[pectiycly. the Uniwtsil)! ()fIC!i.li.IDrJ1li~, tlttlt'nmtin.g of ~ne-8 clmnged thellll1li~ii.." f{)OIJ,sed oJl1lm;;~lgtheproJlosed dYllll:1l!l111ic lI1IIiI)OO,~ Dav~s,al1ld the UJIlii\'C'rsliity ofC<'l~.iJ()m~!l"llOS One of f.he .,ost ~ntcre:!i,ti1ill!:1!t'OIPiofj els di~',ectly to ~>;;pbli~ ~oeia~ iP'heIfilO\meJ:1~. l\J!i,gelCl'l~ ~~pefOr]lll;i~dlnn~les~~l[m tii u:tiotITll!l'· M>e ElreMwl!lm!1 Woyd cO'llt'!lii~ rocia]l~a[!ltilJ!l'S Ir'hi....... __ .!."-" 0._1;; I'~~ ..., fl."> c.... __ ,~ii.'fLf' -!liI''':1; -..,;~ ..!'" ;-"'jt'r'-'-'I·.,tt"'n"I-lili.-~~ (~"''''m'-'- o.Jm ".~!il",>~ g 'H' - C"'PYl--S ..,.'..... " f"n,. .",....,h'i ",_d -""'-""i!ii~ "I:!ii-'\' '-"_. "'''. _(,)1 ... , pl!i! .•'-_'"" __.. u_~, iion iil~'l;fo~u'l:io~rybmlogy., iHlidi ~~k~M.fi:itil'l _"',, iIJi!.g __ fic~.11iC5to dCling ~hat and, Ion It;~e(lther lm@il,d]. ll\!'t~r t'!,IiI.~10'~iIl~~<l,t1ild ~~lCBi'Mc fm<fI"IL~til:l M!l1l"!o/ ",nimals h~""e fhe <IIb:ni~y~o copy e~¢h in~Q' t~\l(\n'lac~d~), sl!!iooeoo '\'.:ery\l\-ell ~!,l Q~e~;~11:.l!;s. beh~v~o~ Cain be tri!~!smit~d by ~~ref~cih mooeli~lg (:'f!p~biUt~~~ IQ!lfCf{\d by !OO[l"IM;;)d~g ~leh"ide~5 'k;!. l.i1cper,ple,xcd Snm:p~y 'le.fllrl1lns: from ether ;li!1l~ma:ls as well ~s by a:g,ent·:t~scd .odt:;I.s; thelJe seems to' ~be'~mple :mOIIllJ for clo~~ab()!m:don and ,~m;~.verg'em::e, rnliOkil.lg dUmJgh t~\H~ hook w{t:Thlmn:l\':;adling the g(l11eS, In ~.1m.eililtrOO'M:aI:(llry ChfIPliOi. tbe a~ttI1oi.1:rrs d~scm;s ~ g~m:pl,cmodel ~ThI:(I~~~k)~:vs ~I(IcaJl~l)1J!Ie P~rhaiPs s~t(lb C IIf:brn:s oltbr a nmre fmtit:fl,l:~ ,&:n.:.~i]s liiCIliOUgh ~o,parlic allyom~ with even a c:~I,alte the fre quem:::)! o,fcop~ed be~1;aJV]O'iS di:roClio!l1lJ t1~J1Jll the Ol:'lgoingal"gl!lme'l111 over $I.ight ~ldfulaorcql.$lIQn(li.; nbe wok is I~c~ed wuth sqll~ggies.. ~i:tUe letters, ;f1ud SLT.\l!nge. when runiinul3J~.s: es'li:l1IlI.ll!e ,.~yo:lf:st.o p'LheliS in . which spproaeh is dgh't. :Epslciu1ioook is E1. coaelse and looking :Symbol!;,. T&killngthe pinng~.Jinov;.reVier. dccid]:ngwil,el11lieil,· '1:0 inlila,te <!Lnmlm:individu~~, ~rl:ic(l[aJled de'fe;l1ise oftlge:nt~llnlim d .i(ld~l~ reve!l_ls Ullllil theauthers hav~ exp'~:i'li.ncd ,elllch ilnd whk:'liiI, beha.v.imto GOpy.. III tilLc]n' chaper i~lg. Gen,emtiNle Social Seienee ~s essfTltill,~ ~ep o:flhe d,lOSif.lll mode~s: as al:early <ls,poss,i.~ OJm, Hllli~:la[ ommu:I.micaJli.0I1. the authers C:Qn~ feadi;ngfo,~' !u~yone :se,r~o'!l.t:s~yi'Uteresrod in Me. These 'Wi,dd,y used models :s[de~r sndb, clIlnrra:Ji ~i,li:11e~i'fut,ulce t~,le fO(Jlld.a:t kim; and, tj~.epraetic e O'f age!llltr~ rule ,el'ega:nt mrlheirmathe:matr.i~ :h~1 a 1T"ic;::titiollss~1ec:ies t~.1;<Ul M,tIlh!l:ll[ltiCii!l'~ MOld!!'l!> i]mh1lib;its .j cli111111gi:ull,g nvirene bm;edllllodJe~ijlS. ln my viJe'livit does, :lIDotsettl!e cal, simplii!:,ity, 1IJIJd tUlmes,theat of Stlcial[ ElII'lllinioU1 IIlm~nt U !&ing a model (IIf ge:l!i,eth.e questions, but st€lting dl,em d.e'lr~y <lfnd PIiOSle reads like a bedltirm:' A I8lilide ra r th a Pe r!]i''i3XB r:I ,.roviding a clear if!jgld pr-Q'!.'oc.-rl:iV'(la:l!mT;l~nt .8.tory. piro;mpti~.gthc :r~:fId!er ito cl~hllrc coevolution ,{'!,~'hkh £11' Rif!hanj flkE1ruth Ihiil:lk.. haw ~inlpl,c!,. aUow.s both sene;s and C:l]~:tm~is iI1iO minor ,'lcbie\!ie~~,lent .Ril'.dflrJfJer1 8iJfd alty ilTiLheJf,it:6-d mti:t8 'l:Oev,o]'i(l} • E!licll'~"Ipmd8 follo\l,,\OO by R:ef!lf~,niOil:> lJfli'"l!!,r.siity (Df Ch i1c<I'g(]l P'l1eS~, t~ey U~I(.m esamine the ,cond[.!li.gu:idc ~o Ute relevant ~heraII. 11. C !)(Mllilli!!.iI~il(r:tlml:i~1'fS ~:u.lMjf('~M~,' Gh:foago, 2001'trions !']l1Hilerwhioh sQdall~rntl1!!:'C, a:nd a dct31iled appC:l1id:ix (~mlml, Neil'l((I~k,19781. .:t2s pIp, $52. Sii; £39.50<. covers ro~IC ofthc: ~llO('ol~:t!~eli!l ifti,g cau 'cvo[v¢, Dey 8:~miiJ~13!1 2'. r.. Hlt!tbe-~ :'-1ie£l~;!S oJ'lmr War,~1 mta .p,Mlf(; lSIBN 97,602~J$)58264. t1,64lW.;w~'"e!!'!lJ""i5;,aC.l!d'j;het!!'.ltobbe:!l'eiet;a~ ~echn~qUC8 jUi)I')J:l!:!I~!he.tnati(:al fo]' mlOr~ I~md[c~\\l!b~envirorre p~pef, !t25. n[i, huolQg}'" C!9S'>i!C} t'OlltCS sueh :!:!i !Un",ents, seeial [emJmib1l!,1iis f:SJ'llimoo I:SIE! 9?·BW:2ffiS!l21'i. N ;~i:nilal,c()I':I:llicl; ~":!l,]be*l.tk'llt. ()overilldivtdl!.Hllle~rrullg (le~!!In,!lnd dispersalere discussed, .i:un,gpUI'c::ly fmln one'!> '0\\.'111 .D~s"p!lloilldl],gly. t~'ll.1 <"II1iHICU;S neglect <J!!I"ew experience], 'fheil'ie~d of aulllnrni ,evo~lltir::Ulis well-used alPlJro~C:hes.irl!o~uclli:ng, :s~m~,1a!tiQ!I1is still fertilegtl1:J'IlLIld. and tmle ideas pooSlented ,(~Iicll tlruey dISln~$.<;rromjlhe stmt~, stamlal'd. ]11 t~lC a:~dhors" disclLI:ssicm OirsQdallem1l1illi~~ to thin]; ~ml.orc oViI'umiz[I,tioo them.)'. fIIlld dY~laJm~(; p.fo(lgJalrl~F will spur ]illI1iny 3, bio'logiist min:g. Those m,rel~srod]Ilmch 1oo]s f~ind about tire role (If crlhurnJ.ttilllls_~ISi()i.l:l :i~ll. evnm;.I.<LHI.ml<!oUo':s recent !book 0) hdpful. ~utionary d]'lWigc .. Mud] oflj'J£ lmmll~~.erm!ritil~ tbeo:ry ofsociill Mmhem(J'liaJl Mode& o/Sodaf ,lili'Oll~tioll ,e'l,loMion theory stmilml$from triwW'O[k otW. D;. will no dlou!btre\v,utl pSydlOklg-UStS. Siociokl~ s:i~t~ a:nd Illconolillilri;stf)ilrilruli(;:gteili~l, (;voMion~ ~·I~mi:lt()ililj.;;andbi~ f~nl~ f~anH'ep:lOimioontl!y httrles Darwin f<ilM,Cmsly rem~rked in the book.,The tw.Q dl!Jpters aewwdlJO QOoP.· iI.ry theo.l}'. An~otlJe desiring ii, thorough. yet il!;ir.-.ti,C)!l ilnd !:1;dpnx:;[~)" ]~u]:\)dl!~ both pme thai those 'r1lirood '!,vell ll1 MiI!tlm~!~tic-8 dO\;\In·:tto·.E~rtl~". intr·odM,etiiOlillm mod;Ill~~l1girl are Cj'ii.lit'I'(o;'fiid 'i,li.,Hh 8gm(:ihi~gf!~d~ t~ lh(joreti~il!li},!~dinC:IM~ii~ ntfi~~~eehn~q~Ji;j~, ~o(;i~ ml()hi!ti~!'lc()ridd!l't dg mu(:~hbG1,tc:r th~!1! 0\1!!1 ~xtr'd,fjiJill:iie.IHijl~ p~st hit If OOfiW:!)'. :mil,the~QllCad thi~ book. USing Htt[cr!'lo['C thaliil h:i\!th iQra;prprQ;:Hlhililg U~ese prQbkms" "I'he$C: dha,· n~l~tics ha:\i 'lln:ougi:tJl a ,greart dea! of:i~:;righti~l~ ~ers QRe:r a (lom~hC;!'Iisiv,e ~nrr'Qd'ililCtkm ~o' schoQI ~athe:-l1'I!at.ic:s·. McE]rc~th~md Boyd wJ~!ati:l1I.ore,a,.liingly seems a.marrullo~h fi.eld ~m shO\IIJ hQ\:l,I O>lilC 'call!lJ '!~"ikc~ bi.g step~o~I)CI c;V()ihbt[o!l1iaii.Yb]o'~o,gy" ~:nd pe:maps I:brthis re~" som hO@ir& ofmad:ic:!JlLll,mid~s· aud jpllJ$ici $i'~ its (JMfllll;, dearly. the loa!. bo.'It lha:tlhe authon;, ulffiders!ifIH d:hrng ma:b1IJY pe]"]Pile:dng eVDI:~tHonu&e :inlhe.i]' day'~t().d!~ rese!!:rch :is hnmcm.e, t~ock to bio.l:ogy ~o aJpplylhchli lusigh.t. Th:e a:ry PI'l)IDCS5t::S, Ha:rniUon (2) :ffiLoledthat a:hmisti!c behavlon;. depth allld :mnge ofto[piics deaU wi~h~n R!de:r~n(:e5 I1Ii c;Jm'ii1l:d Mc~Elreiiltlh. JJlHjJ .&obe:rtlBoyd.s 'OOlMlevol.ve: ~fU1Ccost: (c) t~.l:M<IIIl~~l!Ill]S'tPilL]d :1. H. KQ&~".Jt.l~fdl'fl1'gf~fiElIJB'iQ/~Jj!\J aiid (Jibei' A4aOutmmirulkl'aflelsq( So.cial /SvolU$iorJ W<L$ ~e:s!> 1;liii<ll11 the oonef1t of til,e recripi!ent:, fN~;emg f'~Gpt~~Cal!!l!ondge ItK!Ii!i, Pre~~'Gambiilllge, kieenly dem()'l'rustm~e how far that '!;:Xltt'a sense wc~ghted iDy~:lereTia,tecfu.l~S Qoo:mdont(rr, c <rb, ;!OI'ii1)l 2.. W. 1(1"i'I.:lI1IIIIJllI'I\, J. 'lIne,IM ..9Ml\. i', 1(964). ClIuml bl,i1:1~m.,. .knlm\i'~ll.rus; l~klil~ililtoll~sf1ll}e:.One ]olll~~stElnc:ling 3". K.I1I:, IF(I1lff, T.W,~R!I!OO6:!,~. L w. I?i:iltll~ffi~,~M~E1::CoI!. , iSiSIllC ~ill.he nerd ofs.oci<lJ~, C,\'ChJlti,OJi1. t ,eOilm.cems E¥ll1. 2:~.S'? ~~:QO'~. wlll,tut ro,le~u]l s:eloct:ioil1l (wlim,en:: ~n ·iilildi,'ii'id!~ .::I. l, Ix~rnilmll, L fLtlLerr. $. We~r.[)" rm~, PtOC JIIfJ11.A.md. Th~ 1'!l:'IIi~~~ri:5 ,iIt Uii~·nllijJ~ rjJj]J]lilnt (II' Behil,,.,joor.ilil EboLog)" 'Sa. (JI.s:A, :liQllll.,~l~6(:lOO;). uals fiJm:-ss dJepends «Ill the success ofthe In:itilute -o~ .z:'ij@klg~. U'n~\I\e;r\liHl!',of Be'm, W~hl.m itf"i~'~ glioup), pl,lY~ iill the <C'I"Oi,(It:lO:!iI ,of a,lvilII:i;IlH!U-a 50a, CIH -3062 'Hin!er~p~lel\, Silllitzertillild, lE·nnait ,- - "'';I n wcc: __w.- .1- .c-d· . __ lJ·. 'danl(:l.r,lI!i1Ufi!@~.uni~M!fJ que" ..~__,---"nt' ·i!I!d·!.JL,,",~80 ~ .,"t I' _~ ".pj:c u_C_f
j- '~'-,!y, ,j; •• j ~I~

'wen~

S;iim pile Maths for fI Pe'rp lexi n g Wo,rlld

wm

,j>\. ~;

WW'i'\I'.sdenc:ema9~or'g

SCIIENCe:

VOL 318

9lNOVEMBER :2.007

91i9'

.
1 1

EtNVltlFlONMENTAl

SCltENCE Oan1agfl te CIlJIP~atft:erirrigg.ti~a:I wilth l~tf1W1ely pure ~yatt~lrfr'llm th e '\1IOrld'.s I.a~est rever S!~ Ml1!Iosi~ d1~aUmlilltil[ln, pl;Ult. reveals a. n,eed fo:r reltised treaibil'~nt ~ta,ndatrrrt5..

R,elh:in,lkingl D8s,alinatedl Wale·r 'DuI,lit,y and Agri,c1ulltur'B

t

~g~:[c~lhl!iC OOllsidcr,edrobe a: glo'ba~ on1!~${2J. S;C:t'lWA~et·desa!lhmtkm, has e:mc:rged ca.;;;; a 'r~:lli'" ble So'~U1:ilOll.BC1.Vll'eJen ~.9904 ,and 2004, wou"kl desa]~ll,at]O~ ca:p~u::iJtyil!'lJ~~s!cd from. 17.3 to 35.6 mH I.ion ]'ID'I,~Id:illJy {J]I .. At present, se<J\.VIlLterdesali· mlilion poov]d.es ~% of the: WA IE R-I - U AUTY wm]d's. dciu]!':ingm1J~ef (4). I)es<l~,i,n~z:ed 'IN''d,ter is. in,lClleIiSi~l;g!y eeasidered II.
so1!l:l1Ce afwater t?or iig.riICllll~

W
. .

~d ..lJJ' ...•.,.I.i!@l.'-,.'oot._.OOI.fIOf. h ..UW!~ily ..... . ~~lgitl~l.dfic:i!~jlt iJlJCCCiiiS to

\V<'l~.e::f

en

potflll.JLe

~.: .. -_.iff~.1f-

aJfld\\!a!t~:!f

sc<"!n':i~ for

'liveiylhlgh~rpi'iccddc~[~nii:~ \~oo:rs. lifiDecembet 2005:, a ~le\v !i:ea;,~'ii!le:i' cl.~~idi·-· I'l<!t.i(llfl p.I~!)lt",\'ag gpcTled f~ A:l<~.lMlo~.. 0"" bracPs SOij!t~llCl'lli Me:dhe!l':ram~aml.cQI\'!&t. .It:>, ! OO~OOO;OOO mli)lrn.r pm!l:h;l()!l]QfInmke::: it the l.arge:;tI\:Ve;r.s;C>-051]10[;,!S (ROo) desa:li l~~ltOll facility pre;>0Jl:t1y ~Il o:pel!nrtlm~,world~""i~c (8j!.

PARAME1ERS
'Water
fniHfJlI

AFTER
Ashli:!elolfQ

sy:sternwi!th a:~ EC higher 'b)i' aJfaC'lar C)f~]mlrec: '1.0 f~'IIIc. BorOIl (6) call.Cellt1"8tio.l~, in se~ .... !!rern~W ages 4.5 mgfliier andis s!.i~lIy ~.~ighe:r infhe Medi.termne·aJl.l Sea .. At these eeneentmtiens, B dees :!lot C!QIrls;titnl!e9 lilre'mit to Jimmill1 DIESAL IIN ATII ON he:E1itill, (10) but is 1rui.gh]ytoxi.c
to main), Ido.m,es.'li[ <il[ld ilJr;lri~.u~tlU l usage ra
CI10PS

by it!:l·cf(;ieh"i~leo!l!diiJctivHy (Eq. The&: ef warer p!iodUl~-d a~ tiu,~Ashkei:o~lde~ilil!!iJilltiotjj p;l~]t is 0.2 "0 0..3 dSi~~, ro!pk!.(:~~gw~iCvlffi)m

a ~lacnO~l;~t diktrlbl!niol.l

V 1). B()lJmrn,in

\l,ihi!chis t~xicmr aU but ~hc ,Q{)--':M, [(1;I:hl (mgl'liitel~) most t'()lef~mt crop~ Hn [Mrg2'l']j (mwl~h!lr), o 11)~~cily!m.lp.t()tl'lS in orlclu:!1Jrd~ ~ 1c.S,] l~mgJ\ti't~~) ~re observed aliter irrigS!~'iOlI1 .2.0...:25 with .eff]i!l<el1t: riginalingfto:m Q (m,gAit~r~ 0.2-0.3: dcs~~]n3Jted nUJlllIicipalwro:erin .Alli31UWlrity (mg!~ite,r.aJs CaCO;!) 48'=J52. E;~rua'l:w.iUTh~ 1.2 m;glliter IB :~I1!JdJUoed.Concentn:.afiO]'lls. 2 CCiI?P wl~~er as, CaeiQ3/) 0,1-1.0 3-1Il0· mglliter :Bin irrig<l;t~ OJ1W3,lel: ,S.O-:lt2 pH also eaused l'edltc;tU()I]1IS in yi.elm rnl pe.ll.lM1S Ulild w.atoe-s really feasl.Me... ~nthe Ne~ev ~l::1il~GniI 2', 13}lCIe·salin..tion Iloi; O[l1y sepIn a.rew OOllllu:riesl, des;(lJ~~nil!'jed brackish w<I!te;w (,wliu,()se price is arates the l![llIde}s~I.·aJIJI.c slIllts&o:n. the wlI;rer, ~~. ~]SO' ~]uleww~d.'sfirst dl'i'<I]illil!<ItiOl[l flJci.~;ut:y is tJipilc;.l.lly a t]wird ofde~<lliIfHlted seaWilrer}is toprodiuce ]:MH:ab]ewater room \\le~wCl!teJ ~t a but also remoV''::s. ions t11<'1t .1Ire e!!l~e~tial fit.! p]i!:m grow th, De::;aUn~Z(;d\.\la:tcr ~,pl,caUy air,OOd)l li¥:idc1Jy usw. b;rfll!l1'1'u;IfS.Ror w~1~13t100j' priee li)e]o~)!\'S(tS-5fm.J(9). AllhQugh(he -22% of lM'l!t~r dJeslIlilili'liwd in Spii'li:n £Pes tc re,I,"'oes irrii11tiOl[l water th':lt previ;Qus~y :P))oA!iihkcknl fllc"ility !!,'1.'<l:S designedtoprovide ~g:neMltl!ral iflfig.atio:r'I (6). An AWltridi~11 SU!I!\.vatte!'fOf hln:mm'n.oo!'!mmft~oo~, becense ofoo:I·~ v]d~d baste 11~.triel!llt:5, ~~kecidch.un 1(('a.:H)., (Mg,2-h ~f,·d!ndf::u~ (SO;l~} :!lit ,~ey fO'i.ij:fidthi.lit 53% of the ~Opij~~ti,O!l c:m~i- ~iIi,,"(j~ moo(;fltpopiji~~~()~i d(j~'!S~tic-s h':l ::<ou,tl~- !nagl~e!':tu~n ]C'vel:s wtUeicnt to preeh.idJ(;j additional f(;lrtt[~Olm!~d dk'::SfiliiMiwd \Witer tii~lgefor ir:tigation ern ~Si'ael, aJ ::;:ulb:litafit~al eroelilt~g~ oflh~ p of\'e,g,C!~bllCs <lsi;rigJhly likdy (7) •.hlilsf;m~l, Ule desalinated Sica~~r~l'deli ii",~~!i¢!fD. f ~esc cI.e~'.(;rl'~, ~ vered to farf'rt:erf1l, promi.:1iC oflll~r! pI'ofh~~I!e crop op~i.Ql1s hu RClccut eval~lati(llrl of rhe etftd oftJhe IPh!~l~'fi, A:~~hO'l.tgh "!¥a.1cr :l'i"Q:mISD"@JcHi llaitr~n:ll!1 UIThS~JIled ml.1lners 10 reqlllffil a]I!()ca!tILO~S ·ofrel,a,.· de-sa.limli.:lcd.warer an ~g~·IC·~lltl]lJe. horwever, w<I!ter (Hn;!Ie'l"lyp~C;8Jny ICOlm1:<1~nS dissolved Mg~'" le'l,i'e:~sof 20 te 25mgfHtm:,. \'lalt~r foom prloduoedso!l'ililC surprising. Im.~g,alivere1i'l!!ths" IAgJ1icuUU.rOlI~ FlI!1!!\~r{h Org;m~lilniOI1, GiliU IR@5~~Hh D1mI,gi~ t\ese OlltCiOines, 1-eq!J:~e :roodi .. theA.shlkdon pla.nt l1l'l!sno Mi-, AHm: [a:rme:rs (!1mt@r, MlilbiI~ PD~t ~~!I@\' 2" 915289 15',"11111.• ,liMilrani (yi:ngruIl:Ulff:~lcr management m,k~JNilt;i!ltioll used! thl5>W3.1Je[~ M~'" defid{~II.cy sYlu,imns 1),E'tpartrm ent 01' O~~ilrl ~CQn.og~, Illa !J~~~iril Ini~i~IJI~£S~d 3.ppem:e:dl in coops, ~ndlldin~tum"!toes, basil, ,mmre:\,.asiml m·oosali]mmic:ml stiilm:lilllrds" ID'~ert iRJiii:~!l'.1lnb .., 8e:rH.i!llrion, Un~1jI~llit.:fO~ the r>l,~gE:Y, andf]o,,"vers., mmd had to be .I:l~medi;ed hylfertim" Se,de ~oqe~ (,jjifi!jl<U!i, 841990 Isr:.a,el.~!fi!t!itlii!lil Ol~Soil. W.!!II~r.O! nd IEn'!1irot'lrnl~!i!!.!!ISdenm.I!,g!i(i!Ji~!Ui~I. Re~~ar.th lizOlIiion Current Israeli drilm,king water EUelU O'~ tDesalinizatiolli Q.r9~nfl~\\~i!)l'l.Tih~ W~~niiC~i1~f, P'QMO"i~~ 6. ai?:t B~ st<ilm!o1Irds !Ie! aoounim:IJiITI '0ii2~ ~.evel .aflO n1l1 W!rni6l1t'a:mil:ml1ooe;uv,e dles1'l~nrnii;zedl ater, the w ID<lg~FI. '!)();2SO' ~ndeL ~£.:(t~1'I sioo SIl'M(I!;, Mini~lrr a! ~]rer. The Imi!ltde~salimuiontrell.tJJll,lent ~I]tlhe lowered S:lIIrn~nity i:s.pe,TCe~ved <IS a benas, AgM(lJ'l.UJre,.IPo.s~ ,ot11,oe: ,2~, IBE!~.I(jilgOi '50251(1<. 80x fI.. I~[~.~I., !llaiCulty IDr Civil and! [nvi rnnm@~t,ill ~1IiI~ nJ~@rrJilg> Asl:l~e.loi1p].1Illt~ses !f.;uln:ric a,dd '~.o d~sso~w bec1il.. t~.le s .... (,especi.1II1yN'I tse' lts ~Ild CI.-) Tllrnnicll., &I·<lilfill3~OOO !Sra!!1.. c;fIk,ite (]ilflm:c&.1one)" r~lIhing,iliil Cail- COililcendinl,~;i1g!e ~Qil:S ~lhlnt.phllltt growtb!, mlcll h<1nIl ..

wre,ls w.::ILVrIi.th 69% olT t!h,egillobi.'llw<l,~er ::;;~:pp]y going te ~,rriga!tion (S).IJiIleSe!1!t frcS:iwwa!t<er reseurces ftimy soon bci~tdlich:mtt(1, I:Ul,()~tth(; gro!!'''I''~~lgCt1.1~!ld d Ibr food ..A rccC:ll!It ~pOOtil. (,6), c()m::h,l:de:~ t1u'lt,. alt~lol:lgh tJu: eOS'l:ll:of de-'53.liI.~~lio]1 rc~mR]ll pro:Mbili'¥'cly exPL'lllSl'V,e full use b~ irrifor gated agri!culh;ure.~b:r hi(giliD.~ ¥f1l'tnJecash 'Q'I"QP> Hke gree:lmi~ lsonse vege1tabies ml(I.li1ow~ ers, its use Illily be ec;O:OO:lilIil~

de~UfllilltiiQmI! pli'lmt

neutr<l] and addic ,euviI-o:n~ ments te1irl:ily passes thrnugh

~,{'(d5fmi) tet-]I (mgA1t~r)

01. 2b(J1. s 15-210

,g....1lLO

<OIJ. <20. ..;::10

the ItO :W~J,Ubr;flnes., W~th,Qt]t ild:diti;(]![l~! ~aJtITlcr!t" Bin

"Mcdi'l:etr{Jin~an sm~'i~h::r lilk:r <

RO\vill!w~!l!ch

2: mgfli~er;

rsoi

un

em

or

,,.m

the e11lvirofllment. 'S.~~~ili1.i.'ty \.... in a,tcri8M~Si~jlI\ed

"} NOVcMBE.R:~007 VOL 3-18 SCliErNICE,

k·ati,on of 40 to 46 :m"gf~iter;'nlisis still ]()w,er

'W'YIfIN"solienoomillg,org

POILICVFORUM
4:5t@ 60mglUteli: totmdi i:1:I typic!l'~ I,smelims'hwaters," Qrlhe~' posltoo f1lhncnt processes, S'IlChfH; dis:~o]:vi:.CaJ'co,l wo;t~l
t~~!fI!1lthe

C0:2"phrJJi[le<ill infumre ~m:m] d:es:ilili~ :m:lIlt]OI1l p,lanls.\IoiU prOOJuce II 'C;<l2~ 'O(l'l~a:[itm~

g:8i~eDlI1S

~ioll of32mgf1iter. C~~cmmi$l1Iolj1!ilS,tarll.ltilii~ entrequired byp~illi!iit8,;i1~ ~11:tun.l:ctiO:IliS; with O'theli' l!iIumelJits, ,1Ifldiwitlu growth·]i~:liting fae'~Qrs. :i ~lc;h~du~1.S:p 1,1I11'D: :5el'l~~ 1I!!lents. [J10\'1ke·s dJi ch~llI~sin ~ts~Qj'itC'!1ft and ~~a:t:iw ,eo~}ce:fi!nf!:~:ion pillctlCtJ!;iij;'~y probl!!;ifi'iilitic ( 14.15). D1J1!:fing~hc dC:il~Hmnio!'! ",(lOCSS, SO 4lC- is re:mo,,,",edo!)l.llp,llCtely. In 1:I\JC Aif1hikcliOll Il~@:nt~ lSldfur is !fI!drloo ooi~~ornde:ntalto ~fttC 1!J1Se OfSlll.i'iuiICuc ,acidii'or d~S5()1"..[ng ca.~ci're:i~l~he ros~: '~:l"eaJtl!lliJenlt sta!,ge. 'Ultima:re[:y; SO} coaeemra'!ia[ls settle at 2:0' tD 25 mg Sj~i:te'.I". ]~ui.laJf'tl) $ t]'"e:sh\?!,gl!er levels.J mm\iCver. slilitlu:~deJkicm::y co:uld lel:nerge: m;a!. preblem in oihi('w sysl:elrli1:s 'Whe:re:!I.1~e{rmttltu,'i,i'e e~hods:for 'Ca!~ fl:l]rk:h~ m :mlelnllil'e, liWac,ticl!!iGJI. lrlilm,t~,1:siveharl:icn1nue.

10 :mg{l.lterMg2"indrhddug walter (.18), To meet ag,muc.llttlUllf3l needs, mis:shll~ nl!nri.~ ents might be ,<ild:cl:ed. desalinizedwaseeiu to the fOinn ail'rertiliziers. Sl~pplying Cn.~ aud ~~!~ at 24 and I.2 mgllite'r.lie-spee~'iI\e]y, costs ..... ${I"Q.9!m1• Di,I1Cc:t che.lfiI1.ic,d do;SOIICn-t the; def,j),linllil:iOi[l p:]liI:rUto inerease Mg~Tiiiilil]SO a tellltiv,e~yex:re~l:s ive alwrnn-itive (..a&lding ,..gO,!M500~i bJ the o·y,endlpo.stttealltlent cost ';iii'.!~.en '~""---I •.,.f~.illd. :M-:.... 'J"'is·~·-,-¥.-.,", "., M ~.C·'I~! . ~." 'l mb'L -- ._g,-8Uill!'-~\;;Y ..8 - -,g '1>1" ~1 a bio rC::1'1!iI1.:t:iiin atkHttOim, of illrl!w~nte.d

d~SCUSS!L)d above (14, i'l), The sla:n.dartis arc 1.'eh~'i,I:a1li1:tm dryla]1,d re,gi:olils. butwilillrohably 110t be:',ooiSl:~e'lkti ...e for ;t1["f'(IswJ,~el.·eawiil::[D~ture does not rely ~.eayi~y onlrri~miO:f1. The.se ,e-x]laJJildedcri,t:elia :n.e:ifueJcontra:dicl nOir rolll1pli(Jm~se the q1ltll~~ty of the warer For l1~mlllfa, cOillls.urnpti Oll1, a~ defined! by WHO (2.1). On the coutr,<}fY, :~iI:lcllcasec:l b1!ilffen!lg a,p~te~ty :a!!'!!li fll£jlt1.GtCa.:il+ <llfI,~ M~" ~.JOnecnm'tk)!l~ m1ikliJ ~Jml!;i i;,'ir,!ltcr more chemic~~ruyiiliiid biolQgi.caliy sMble ,~~tdp:roiVidc: a
sf,ilJ1d!1liruS

'CQ~~t()r ~!lio~~!5.Di~~iOiving d(l,lo__ite rock [C~Mg(C:Ol~] to I:llcc:t C~:i!~, gz·, and alkaM

higher afflou~~ofe~~e!)tiale]~me~:~s.\""huch

lin~ty ,crtt.c:r.laJ ~I()uld only 'COflt:beI!.'i.veen $O,i] ~. and SO.02:/m"J a'oo'lilC the co~t of ,cxist~~lg caldtc di:llsoh:nt:imifl U 7). Yet there are $ cveml potential p~.·l)l:"lk;lll~ a~50ciat.:ed with dlsselverl do]o!mm,itel1ock, .<ostllotflbly tlite relatively slow di:sS!ohDmon k[ne'tr.ics. AliI ~He'l"nRti.ve precess, where exeeas :Ca!';'ions. (gcllf:mtied inttte Cimlm.lo:lilI;,1,2:S04~blllsed c:rnlc~te: d:us~ ~:litea.verage :reccn:l1l1me::uildedl S0<l:!-cQ]:menrrll.~ scl.utillml, 'posttl1eatme-$lit pmc,es:s) aim': ~-e:l).I.n.ced 'kiOilii ]~iflF.~~ti,oIlW'I,ter ~s 5:8 mg Sfl i.te!:"" with Mg:l:+ :iOililiS mF,i~ilm,a:tingfrom se1i7li¥1i,mr ,(ext~·iI.ctedl~ siJI1(jg Sjpeci;f~c iQn~e~,d1l.tnge Whe:IiC11i~ the nJullljmllJlu,coiIiLce""ltl'EltiOJJilieC:l()m~

cQllmll".u,dcto ptlbnc~C;\l!~lh. De:$cl~~laittQl1lfacll~ties 1!:H~~f.lt'toda.ywUI 'bci~ 'p:~a:oef'Or decades, m~irlg pl~llIrning ~l!l)\l\f~:>(.Ilu:iaJrn forlong,-tc:rm im::.f1efl'Scd 'eool.lo.ilc pml$l~erity !Ulj~!l"gli:,icu~~ tlllral prodll.divl1y ..
R!1!:fl!iI1I!n{lI!!i !lndl
1, P.H,

~rbrJii

(;ti!i~k,ffie 'WOttd~ wa/~ ~Q.(rj~CD~: ~ ..a~l!]1lil :

'CCl8t-~~th!{~prioo (I ~'. lfthe .ill,crals r,cqui redl for ~griCll]ru,r~ reselt, the ,quaHt}' onlmJCfinal "l,:.l'llI)Cr actually .ceta:liPdI~.l!\\alfde~iJlii~I1ii)II.pll[ . d)er~tvcred to farmers.is um'd~:a~e+OO 'iJI-'aoods .~i!1:.nat:!ldd!cd,at t~cd)cs!!~iootio!li!p~ant. faf~'· s. ,G. J~eII!Ii!f!~ 'I'll III ~ede<!l.i<l, ~(1h\1",r~ 1I69 ~S"1' mOOli!l I()w in cl]&:(lolvedl sl~b&tance~" ~vi:dll itdlc 'bunbr~ ,en" w:i]] $Iced sophi s;lic.altcdl,.i mitWe 6. J.Mi!lrti~e~ Beltr!!!l, S. ~~hri!'rl~, Ed~" IWQJ.w~.>!1Ir:.. pc:ndCliiiil ,rIatw foi'4gnMIWjjl11:fJp~~'Mo (fIliO'.Ill~\ ~!()Q.6t h~g call1Sicity :rel,!I11i""c '1'0 that offlXls:i:lwa:~el:; (;om'lliol syst~ms: i.111 orden: to cOI~'ew~th the r. :~, OOliiil~~f', l!i.1.~~(Ih~!!F. iiH!!5!!il:~tiiinat ·~I~ Pfl!Hli.'i!t!I,ii'l!j~ LQwblllIerillTh,!!: cnlP'~cityilliH)!''C~S:t,'S .. o,ftCor~ va!l"~allrl!J(:wa:Wr' ~11!.l~nl)l~SiI,Ich !S~s~e~n!i)can r;isk. of 'M! .lliNWII. ~r[J,eficafilli'l\1lsU! 'MI<l:I!r ~od<i.tl!iln) . il"l\iolve fa.nu~sca.l!e WB!te:1i storage f<'l!c.ilities,~ :roisiOri. 10 ~~ctal d:USlDibution ~~ii;~e$.It also can 1)@1a~IfI,al!~11 :5lJllMp~illrll. Hi~II(IIIfJII.I, i tll 9' ,Morif 2:00,~; <I'I'<Iilalll.e <llhup:lilr,j).I.ID\II:lilW..iIlIG:'!)mlllll@L(flfH~ [~OO&l. ThI:f1'!te pro Fm.md ~lnpll.c:l {In 1P1~1 a. fO:l1td agrio1Jl~ water~q[ll! ..lit'Y mOllllito:r.i!l1ilg egu~I)li1J.lien~.i'lnd. 91,. A. Till, 5dem;e lil.l .•lI01l1 ~;~J)06J', l:l!lml. pJ,1)dnctruvity} when the w<liter ]5 mb:.ed ferti] ize~,,"pmi1:1:pi.ng far:::;iIities Ciili);tlb] e otre~ 9' .It f. 5<el!'\llce.. 5t;ie1!ce 3:1l, 100.8 t2:0ClSt whh other somtes,. m::'lilThg. ~Ilpulwater too qu a.1Uy, l'hee o]mi~fa:m:l 'MI. r ].. 'lIl!!fT<iy, ~;9!ii1. Tgxi~al.M!t,"lWJ~. iil~~g~ I ~1:~?s). 1:1., ~. 0. Nt~Iil~',~, ~~ ~i!~I1r~, l (1- p~iJ!l, .iillIJ'l!' sai.f~.?3. ,tmiphnl cests of snob ,eqll.lipmC:1lI1 Mkelyto 1[1'(: l!l:[m~'i), IEi('oliIot:rlic Fa;(tor'S OO1l,oh :$ [(I,:OOlJper i1lilriclIhumI unit. mId ]12, 1\, e;~il~6 y, 'S11Iil1'i1, P/(tIl.f'5rilil M:Ii'.211 ~20<m. n'1I.C cost af d.eoo]:nHIJOI!l,g ~lJt~ c:rf:Sf:lIiWll:1ier t ~Jine f1SS0C ia!wd ope:mtTh om.ti. OOi:'!ts 'l!'~M <lddJ1iddi.~ a 13.. li.'krmfll'.!JIi1!l. ) .. Zilb.~ITI1i'1ll. A. ~II·~II. It ~'~rn. pa~,r As,hkf~lon pbJiltwilS $0.55 illl 2006; in srtl;lllelJ' tiJoml1 e-l{p~lses, to the eqju1Itiori. prerelll!l!ll illil1;~ w.r"~d (:Oll~rm 11fSail S(i!il!J ~~, PM"'~~p'!\'i'<I. PAW 1:0 1'5 J~ly 20116. ~c]]i'l:iCfj, theoos,t ll!8:i]il.gtlill,e !i<'mIM~.roc1luJio~()gy :M. U. "!'e'rrnflyllli!! eel!7!, ·lr"!J;ni~ngl ()f"~pZ Wi~h 1ife;5i1I~!laM!~ 3• Dii8 emu LnCiltlde~ oon]dfleflch $l/m B :(O:!I! dljS:~IIi!!iI:i; mail'!1" l[ilill{~bpe-\1Il (Ri:iJ!CIlII.suomil!tw !lID(iille'f S(ri~FlMI. rento'lfidfl!l!ld addition 'Of:S04~' C~~,aJnd!lJkaWfdesalinhmd W1i.'ler w1Ii!ioostinoo fur l1;ricMII:wa~l MiJIU!i!y iii A1JfBn~In.U11! ~[id1 Rural [)i.'~lrnpFll,~M, M.JWllJ, ~ra(!L ,~oon.li5pp. : ~ lililitly by means of a c<1lki~!;i-d:isootntionPO;Si;- tl]r~d us,~ a]o!l!s., simple bljc;~ldi~!:l! tri.ttegi~:l; 1!5. 1J.1'Jl.rrniljmfii., 1,~5h~lmil fI,'Pd~. IIU)looa[, '~~tmcnt: pi'QCCs~. ddi~iO!ool c~uidhmC;;TI!t gf \.V'Oi;~ldl;i(;"j 'dle!I'lO~t p:rob~d)~e ·eooo()l!Ji1k:aiJ ~Ir",n,· A 1:1. S;1~~·enl>l!r9. pj'"{1JjJ ,AlfJJoil. !i~!i,i44(;!006J'. r '!~~ d~Sil!~~iHiJti;jd',iii3!NNwidlMg~'" \;loiQliMrn~l:ie ,egy,.provid:imlg sb!bt~ iJ:oo high ".... ater .quality. :1.6. C d\~ Kre-ij, C.S;~I!ne"'l!eLd~~. 6. W,ilflm!nl:!~!ffi" N. St~iI'ier, G(lid-eVaI~,5;/o.rRl!~j.erlC fkmem COii'lei!H·HI{!legeiab/.e5 ~;r;: pric~fh~l~lC!,. \':'et.i~ !no~rypicai Cf.!Se$j' li,... he:n;: 'l.v~te:r :!1'ulP· !!'.r:I!1 fJl).lM!f~ imder 'C@l!ll: ~t.!~~~ijk,~lt!11 eer,~rd ~d.• A(lCCl!min{!: to- 11m-VreCOliiIl.m.L'!ll!d!atuoliils far pHc$; bot:~ ll:l!UI1~c:i.:pal and ag:r.icu:~tiIJml1i!l"e~,~ - - _. ,~' -M~tllefIaIJJ!!I~,.199'Zl. de s:<IUni[~ed \Ii\fllte:r ~lllsil"3e~ 1(.1 dis:'io~'i,led ,eeollo.i!c clih:::k:JJ!J.ey mqul!re5 iilJ b1l1ruming of 7), :lii. .~~iilt: :otnmltli!~·~IPpcii"iI:i!JilI bj ~:!f;~!!l MII'iI~'V !iiI C (:a.2 ooncclltratiQIlS should n01: iltfcimcrClIIs:ed qU:8JI.ily. :Eline! A!l~iciU!l[UF!!~~[1 1Il'~n. ~ O~'I\J]!~PJnI!Rl~ riil ~~~~llN<1l.@!r , ...., cei~rung lS based treab"liiiellt costs, drink~ng.'!.m~r basi:. of 1.'eOC1!lrl: ~.. Piulliorit)'. "Q~<l111'l' 1 O~!Ialinatf!d! WatN I'~f A~rifr1lt!1lre~ 0 beyond 48 mg{il~el:; TIlls ('3-!Ig;r:uclJJHunll ibem:::fil:S•.On the [Fin~1 r.ep~li1~ if! HmFe'"~l U~r<lel ~Bm [Ileflt IBhf!,\IilI. an ei[)01~amk cOii]Js:iderali:imllSi,lO :m:in~m:i7.)e ~smdiex~1iem:e, ,'Ie :rec.Olmnend ,e;ql~[ld~llg lif.il~~ Onobll:r~()1). p,an.l.lilI1e;~ea:s, de:salirultioni£acil .. i:n 1P:IJOb]emsl1cl<1!ledl tl) exoess .oo.m:ll.€l:ss for lI;SC!(1'S watey..qGlity :l!$. WfiO. ~ilieli!) ;#~riii'#t.i9 ~re,f {w.aL'e~~!1i~"'tiOil ;!~dl H~I,h fro~iiilf'!;!I1d ~~,~ I'lilt!:!~n IEfi!.!if~ffiel]l~ iI!IIiIQI, iIll, Urle [lld1!.iSi,rn:ual aLud nII!.I'[llCill!l!!lru SlectOlfS. iHe!> Um~ ]ID~fIIy SUPlP1y "\I~~el' to farmers (see: 'G~!fJf!"'.a. 2IDOS}. AUhQil]~h m'l,gtle;si1JlID ms; notincilld.ed rnl !ocm] ttlble.p. 92Q1l, Th.cpl1opoiSedi !iita.ndaru:.S uJtIl:' :n'll. L elmli\;!lf~ O.llI'li~1,!. L%1!!ffle.!.~\~.j·9e.9 ~~O~. 'i'>'nl!er~qualuty cmreri;1I,it is we~.c()im.e~in de::;lI]i,,· bllsedl onk:.sslOm:lelllli'ned during HiI}eirl~tial 2Jj), O. l<l'lr,;w. L. Birm:lluk. !l~aimmiO'Il 2'0,7, ,2.1'16, ~2!1107.), :miltedwaiter not O[l[Y for ~.griculliliu'r<lll, lli ,1I:llilO ope(mtion ()If the Ashkel.on ·p]allit rund Wd.m:r b :2.1.. WHO.liillitkllillelIOI!'"Orimlfll9'Wtl'tl1! .QUi:Jliry ~WHQ. ,('iell!e-\'<l, 3rt! ~I •• 20®41. {liiilp.l2. ,imllex 4 • .iilimna,nhe.:a~th obj e!::ti:ws: 1I1ilc Wotld~l,eil[th !CJuality :b'l.]i,deliim.es, tlmt 'ilveife sub:seq~eil1Uy Orgljn~tio~iI(WHO) :rooommcnw nmWllfilgn·· rocQmil.nend~d (20). ,11~ wd] ,ill:! t1!tei1ici:llliaJ,lgro·
1, -

MC~ld:edfbr romrl'itlcs ~s m~J~J~ hjgmer. [41. rn:g: :S/liter (j"OJ .• Dcs;1linfl,~d kriglliti O~ water illiil [s[,acl is ofi:cn ~l~$ld!ed.."ft~ other\\!!U(:r sources. A3 ,II

re~ifis) ~,aJsbeen 8l~ggeswd..T1wisahernative ~Ji,':~]] alance SO:~&-. ICa2-. Mg2+ ,1l.]k;aliuity., b ,a.!I'!dipll oompos;itioo i~ desal i!J!lted ,"lamer a:l a

fl.epw,f' O.1r frl!31rN(Jl.1lf{!Iemmti!~ ~I!L~ni!I "f,I!!I~. W<l~lliITl!lID'" [)(, 2002}. :1'. ~5,.PIXI@L PfI!(JJ' !Jj Sa 'lid: too f~ lffly'({liM iIolrmtldtuil:i' fil'llDrld ~'l.W~In. IWillillillgfl.lll!ll ,1l(,.1999). 3, I (fw~rAiltillin.ai,l);:i~iliOOllm~ Alioootia1ii~n Inlrl.A~. ·~~i~d'e !)e~lln~!:! ~nw!1iL:ory(![),P, ~p~ M.W, 1N~m9'l[(i1!

(~rHulffi ttg. Gilar~nb~f'[I.

~.

Gefm'~I1)', lOO4);

wl·fI\\lW.!lii:9F1kL~Orn, EiIlIlll!li!',;i II (omrni~~kHl, E,1IW,~Olllt'l~nM1.1'!fhmolm(ll~~, !'i~t1~n ~hlln. ~~~ d~!<l.lInatioollrrnlrk1!t i!mll!'~!.iI~il" <tEe Brl1~~i!ll. 2:00i,1; 1~~Ij;I~/,~.'!!~'~PiL~lIIetll'l'iN~II:Ii:'ii'!rut

-"-

-!-

~.

i~g ]cv'¢lg· of 1.I!bou;t20 to 30 mglli~er. C1'l2+and

IH'Jmh; cons~ql!C~l.Ce~ fOf loca~ farmers

SC!IElNCE VOL 31.8 9 NOVEMBER 2007

W'o'{IN;sdelloem¥)l,or9.

,: '

' ,!

I'

AS'TRONIOIMV

W,il!ves simiia ~ tiIJmQse 10 Iil;'ed ~Irl Eart~' s atJmO!sllli1@l~ may strtmgty in'IDlIUenl::@'th@lnillNllifJ.l. :itrlll(tml! o~~IilE! S:ullalle otiu!!!r stsrs,

me

gud~,.1I~t{) n'dm:e ditr~ren~l:al r(iHi,tio~,b~ttlil'Q(j~l!h~ tadi~t Hv'(; a!l'IddlC co:r:w~(,1~ivercg.i{ll" yo~ ~I!:\!!S;~ ~w;lt!de !,!1!!;c]~~r~"cJ· are f;iW~rl';d, Tlig,eil1ll:pact Qfg [,a:'!,!ily dons dla'~re[e:aJse c:n.e:rgy Q:l'!id proy,'>a'il'C:S; has 'been ,exi1cnsive]y d1!.l:cec~c:meliiln ~yQ!fld Thiydrog;en. Furlhe:G1uolle. you have 1.0 describe studied in lh e cue of the Sun, in whk\fui, the c(mvecrivc ~~OW· CllClIlY is C!)Fl<,[c,d~hro~]!:1:hire t rcgkm eldeJ!lds (!,'!,(;CI:' the outer slali. e~l!hel'by photQl'Is~ ,deI0l~1:r11i!5. 30% in [,8Idi.lllS, Tm!e wav~ air n:tovi:l1Ig nmtter" rim!!!y. you ~UlUJSil spin Y(I,Ur starr to SIiii,8ipe the iJIKillm:ed osciillarliol:l. oOC[[r.sjlust ~~il['CmaJot <ItioI1li as \\iCU as the, r bel!(i\v,. nil the bou1fI.cllairY with S:';!hJ~~~~ \!i~li' @Hh~ !,!lti;nolf I(I~t!il~ SI~1ilU~) olJlil:(i Qif II mg~ the :ro:adi .. ,t1,ve,zo~e. over about ~n~,l:emaJ di.stl~iIJiUti.O'n D,f c:.hiel~li.c!l] S~rn~d~f!dI :$iIl!lk{!:o. :sl'olili! star (right),wh~ro ~rr~\ils: wiIDsmll, i!ld'dies:in,dk"t~ il:DIilW:C:~r1i1! regions wlilt~'rte eleimml~~" You ClIll then Wliwhyo1!lLr :2% in mdi.lIiS (!:lee tiruef~giUre), ,emifgJ'i~ traln$portBd b!l' large-sc8!le- Im~li()li'l. ll'n ra:diatilJle' ~,e!llii()lm~~e~9Y iSIii'.iulSe t~,leorelic<l~, tar ,evo~veand see'1hiit s paned bJI phokln~. Rl'!dllMtr:arl'!~f:;li~t 1J~atililillal1dIb~llE! ~ indicates: !>!rn!J rtl'1ai~ion.1ThE! w~~'l,~j!Je~iodon the order of <I tUlle model rejproduc,'C!i tlrnlC :m"lin S!!)lrl hosts ~ wn'lfocll'iw ~JilV'~lop(! th~l ~'l2!11.er~~~s~!1i!~mallgr~iI,i'~tv lI!'a~\Il!i m!1jicilil!1g dec;uie (51", A.si~1 ,dllow.;m"l~ o!'b8crY"'Jt:iolt:lil~ fufl,tiII!.:_!"c$; of real lmli'llud 'tammr:5). 1min1I®:~e Sun's Iillla1l'li~Ve5tars hm:tililgl a mlilv,eah!'e cere, 'grilvfJ~ li'IIa'ol!~"l stars, t:ile: mUIHo!1 ,of 8taffl. suehas oN'!:.m1!U ~ __ pcro!l!re: 'trav!!:l m.1tr,i·artiL In botlll cases, Iher~ \$ a ~hea~ layer o!SCUlatiOIll <It tiM '~mm,tt~f COl]'Irt,';ct iOtlW!i'M:; has gh;!\i\l~cI ![ll!dlliDI!1inoi!)~ty. UOl,\1'CVCif.; Y01iif dO\'iffi dil:l!ring its illt~mcy.Tl1!U!!:i, ~Wl£~fl tha lml dii~tj!;l1l .llldl ~(m~~ctiv!2r~i@~s. Wlil00el\viU !'lot IMlSi8:fliI~the tests. [1'1 U1!C ICOfe happened tOI rotau~ p~rU:c1!ll:ilr.you \li.lO~~t pn:dik~t rnJ1ln.lllt tJ~eLnLIC~i~r $;t~C,1'n'~Ve:!;1i~r,e 3:11ilIUpo[tS!~n p;S!~tof several !ll1!lJchf~"~e~tha:IiJJ the ~I!:face, hi~lavo:ucdrc:t .. T ofthc SUIl, the ~~i!"\rve~remol;t ram~EiaJrwith~ loth~r phe~!omc'r!~i!il OUi!' ,~'MlO[ljphcre .(Thc~f !l'lgrnde waves, which caused th~ cere 't'lf~l(; . ,~srotlil:lm.g ~lO'i.V'ly (.I., 2)"I'I.or "I.MIU~ou [pr(lpe:rly .1i!I1:.rcspo.lm,sfbl!e, for 'CXlSimpl!e:,fO:rthe derur.~ai:r )"OIllJllgS1!I11 to ~~in dQII.l'lIljJ (In ~ 'l~mc: ti'Cale of a ~:]' f (icsm:ilie l!he slu:faclC OOIllI~O:li,i'tii!"m oi81111-illike lr~ruulen!)e ~1'D,~Mise·ared: by pia:llte ~~'3!sl'l{!in~l:s few~)t~ndrod :mi~~~oblJJ:reaTIl. D,thillh:mew('lr1k: ;S!lld fQ!:" sb:a,to~~he:ric st'~dd!L;m'~_mil1g,l"$m:ed !>13:r:s.. ~<I!' \vent wrong? a. SUlOO'th .mtai ion IJI'Oi.f:~~e.s e,Kpeotf:d in the l The most serieus problen1J is U:laJt~:he by U~ie diRf!~pi!:lion or'p~!aJletary IMIV,CS.) l1u:::i.r I~resel}t S~~!}. OOl1Si~"Ie:llt wi.·d1 l~!eriQi!lei.smrlo]ogi.tliley pmduee lUlode]:s are .Illlssing: a pmeess to rigid:ufy tilia.e ,OI'TUcil3Jl,eharaeteristie is ~~;llllil ".BJ~ o'b~ervatlJL)ns. H.enoe. t:~e S1![[1 has 'weaker un,lterna~ ~:otahQnof the sta.f andreduee the hyd;r'odynlluillliciJmstabnities that lead t~)iaJ SlUl", memenram b'H[lS]JC;L'iI;~llitilt cmu;lcri be modeled 11:5>a difi:iusu'\i\e POOOO&'S (4), ~~,l,'te:rJm!lI~1!UIiDnwJ,ellt mb,[ngfmm; li1iydrody~ fil.oe dlCndc.d co:mmpos~rio[l i'l1, <I~eJflI1.eoJluwith uasn [ci,nsi;~b~ ~,hies, To better lJa~,dJe[Stand sp~C!tIJ',mCOpi]C mfuism.t:mmruts 0(6), In sik"lll.'s.,du;: ]m:eu.'e.st~.l;g P]I,{)~lCJ,'ity ,ofgarav:uty t)n.esee:ffecm, astn)phys:~ci:sts hwc been wa""es :Ust~,lartth.eyp1!lmp tlJl'lgllJLnll~luomentmH .Bu1 howfar m.lln we. trust this ~:uode,l? :rl1eekfungins(piralton frem Oil ne:!,,", SOUKJC: teri fro.m lhere,gimlll where they 2Hl!: excited and Thank::! U)Itm:c,~m<lJ. nOOo~ptJeric Iphy::si(;~,."li'C ~:e'.Smtd.<lnnospihere p!1yslci sts, In the ['960s. 1J111dC:JFStaa.u~ ge J1er.al pr'O'pe]1!:ies. of grmity the dump itw~lere they are dila.llped The nonlecal 1):tm.os;phe1,~c ~cient~l'>t!sweraintrigned by <iI n ... re of ~hi!Strnll!l[port makes ~t<lI,!!'e~ effiwai!i,;,es:,such as p~:l~e ~oogroup '!,i\eb;~tie~~II1c1 to,s'~i~pedl(l ~itl,roin<llr«ll.tio!l of qtKI!'!ibh~ntdal o~Cma:tiioniwthll SLTa!to!iiphl'l:ric ,ei:;ru~.rot·J;H!~ d3:mp~llg. \¥h.~Jti:g still. u~lo(;rtlli~i:8 t~lCe'ftlwind 'li'cl,ocit;r ~bmr~il1luhr~ ,~qu~ti!)r; g<lseo,1!I,s bodies. am;\' ity\MtlVe8 are exeiied ~;i.c~'icy(Jlf , ..iflve· :wel'ic:r.!!il~M by '1'M:~oo'I~!1Jt 000Ulld~~~l aliH:lH~lt~1IlI (3) H~'l,O\'i'Cd th~t gt is i!1~id~ cOfl!v~ctive rog[Ol;1g( see th~ fi,~.llre )'" vcetiorl. To this day.st~U!W modelers roly 011'1 c~ug~dby w~-indii.ioed j][~O!ri~~lum tw".i~:;i.- They '~veland~re' d!i!iupediril the,rad~(;j,tivc r~,thcr cfi.IDdJ(jpri(;~eript~oi!mJ~ $'or !CQil\~,cHg)JlJJ. port It til,rrllS out t~t cli:;acUy th[s mQdlaJn~sm rcg~Q'~l veil' distall(le~ tha:~ dlilpe:litdQIl ~he,i:r Consa;:q1!.!!ent~" ~~r;: :spcctirl,.llll Qf tlil,c wav~s o IlIl;;1!_ybe '!ei,eYaJnlt~'Q preccssea inside ~tafS, wavellcll;!glh a:!Thd :It,eqM!C~lQy,The:se waves C!<l!:l ~citoo by oofl¥ecti.\'C: l00ti'()llSin slarsre;i'l1@;!ns 'fhe:ll'lail'l w,Sr'!.ICS re:spcmsib'le fQ1" Utis osc~:I- ber@irQg~dC' Qrprl)Jg~de,--tha!tus., dley travel elusiVe, To, refine our klm.Q'W'lcdgeof ~lIi,Ie lat[Oliligre lhc s(H::aJ]]oom~el"J;d :gmvh:y \WVie:5. dt her agaull:U" lOr with :s~e:ltm: retatien; the e.xdtat'IOIl" \vcnwBh tj]u: oueeome of threesa:me\\'ll'avet1 .aJ~sopmpaga1te r.m:li;lIm~y" fI'Qlilllhe T1hesew<I!Yes, 3Jl1cpresent in !'lh"I1Jt1ficd mediJ1l dJmensi.omd s~iMrul.am:iQ([Is, ()if Oml'lJ'lec:ti:cm t~ulil 1::cprodlJice steHBI.·c()lnd~t~Ol~[i], e aJl.',e Im.ol.in W zm~)e Illorder into the faJd]fflive sm::,i'I ,11$.Em.1h ~ atmosphere" wfuiel',e d~:ey aJre ,co~!v,eclion to~al, dIul'kHi:lSiS. howe'l-'cr, oec;EllIJse the: mm!e. . excited ~f tbe Imbulollce ofl1lear:i}y n:~OIls. .zmmc... mrrerellitiial oom.tiollu~du(ies it .1[)Q~p]e:r d:i:l1~!e~lsiml<li~.pms(ri;plii:oJ.l!s'i\O'e. repmdllc:e use s~mi[l in UUlli\!EII.velreq;ure,lfIldes. tliila~ 'is dif:fel1ent far prog;mde mnd retrogir~,cl)e 'MI'lim; tha:l 1(;0111,· the:p0l.vc:r spectf1!o'm of the SiO~!IlIr :plie::os;u:re C. Ch~rboiifielijiJt Ihe Giln~<iO~e;f"',iilory; Ui!ii~et,~ily m Wa'lleS, se'en in heli.osei.!I1i1ln!o~ogy (i).~IIi.. ldni~ c \'~y posil:ive, E1~ld n~~lHve ...liI~ul~lUameJiltmn Ge"e'I!:a. :l29\1' S3~rii!l:, :S~l~rl.ilncl" arid ~hfil~Ioor~~~e r{:s:pecti.'''lely:. ~iilie re'5lJlt is a klc<lil o!Scill<l!ttng t~ollll".tlj1.e sec[lJlIDr ,evo]ul:kill oUle n:ntern.o[!IIotad'A$~~QPIly~II1II;I~ g~'TOO~u$A1' ,~~'~ F~~, ~~i~!d1~N"lr~M~1 ~~ La ~~fh ~rd'I!'~[i.~~tiilif!I:i1~. Uni'Yl!f~~~~ Pa:tJi l. SllD~Hi!'r SI'1J!~<lif hOi'l,tlilteis not Sttoirligruy deepei:1.clJellt; Oii!i,nUl ~~itiil:i:ilrt(]! the <),m:tosphe;nc qu~!\!i.':biew~ j;ol!l~om'e .3, 3].4(1) ioolollS@,. F I<!I no!; 5, I\ilI~On in llit~ is iii,,, Ioscill:liJt1iOiIL Thislocall. SOO'<IIl'til.1en<IIC,ts <15 il detailed 'I'I',IVe ~specWtlil ciit QifI the e:xm:![ iinpI][ 11l@'p'lfl~rn@'nt dill: IP~iqlJ@, Unw'@rsilt!, d,1!! ,MormllrlJ!\3l. filter: ::llml.l, woJ,y,elengJtfuw1I'\i:CS ilifC aU d1am;ped nH:c Qf(;;~~ei:gy in the 'lill'1i.)le::1" ,Monb'~ilt PC! liB{ ~7'. {an~dil; [·lI1IiIlil: (orinne. Ch~tbonr;r:,1@obs,u~iQe'.di; t~lonf#imrO.l,jllfio:rnlm.~ Wl:mt ab~~l orl~er stilfS'? The st:iiucture1i!:lt:l lhr.'::I¢. viiiuUe thehn~ \1.;a\'il~ngth\\r'<'I!'!,"(~;S.lh<l,t

o ~mll!dIU~a~~row a camr~utcr;)',(MJl neCld el:1lJll!<1,tiOlI1!!:l, _ d~(:'ribjng Um~l.J>iShf~V~OV of g:fl!SC8!:lllder tile action o,f gr.fffiiry.

tri.'llfQ~fl ll~gl!!ar mOTVlen~1i,qm

me

PERSPECTIVES
IP.Os.i:li.ml.ofooll¥etnion
ZOJru,~ VaJ)'

g,ass <lIOO tlg,e. As

with stelltllr
tI[ie

Im,lg.st:andillg

IPl~1r:-s about U:Jieo]l.emiG<lll)in~

5. p, ~Y!l1l~r~), Ia'I~r!"k~,Z.ahm'~/~p,J,.
W}9:9'),

S;!j):, 8:59

OlI[it'oSU]t. grm1'izywiliVC;S

expeoted ~oiillrer s.trL')]lar Pl'OIP,eJTICS di1lffelie:~ny clJepe;lJidruug on the star we look at. ~or stars More IIIZH;~VC t'jtg:aJlthe Sm1Ithat l1os,t ,1,(;Otl'l"60twc cJOJ)e (see theci~Id plliJ]e~:of t~:l!Cfigl][\e )., gravity wav,es trn;vei, to,\.l'O'lim t~e:!ilin;rmce, where '!lIIey ~robaJbly esuse :m~,ong:shCl'lrsiiindk~ep !~eCI~mk~~()QlUllj{'iSilio!llw!ITl~Qg,C1le(),tlg OV!er ,~, H 'tlr"inth"n""" ,-f .. '-f=d .'":!:'l_(),'. t,~ !.i\!'IJWol, "''"''i-,''" ~"",._~rU\¥I;,"V\';;.,. _I'!~ '__... l_e;_ ....... o_ 'lI"lIa;,,-cs ondlc wcrall fQt~'l:iO:rIand O!lilthe l;Iilli--C'~,'

remn:sobservedin stars tlttiu,e end oftheir lives,. S~:e:p by step, gravity waves are &ai:n~ng c~:ecl:ibi,lity <[mOllg std~:mr phy:si,ci:sts. F:~rst inv6kcdilill the: ~.ynchroili1!izatiIOJl ,ofbioory smrs

5. !C. (llIilfbl!inm~LS, ~!on. 5.rimi£ ;31"9., ,218:9 {:lIQOS} ,,, fl, G~lI!Il~~ldl" . MOl'I'if!l'. . [/,/IID:I~" As~ph)lS.),4:24, 4'6 N P U9t,t),
$, :F.Il:, P~!'f(1~,!O!1l, :S.T~~.,'C, (!'IM!;>t)t'Ine\I,.JIi,!:IO'·g,It~,~.I:Iy$,

madle ]'Oy~r8 ago'\.'!,'1m~~1 imp~r;;t:of\.';·aJ'i,lt:s '~e

~II;!,_ _V . __'"

(9" .to'), l:lro!eYllfCr-e SOOlfislIspected tc transport plIl1:ici,e!;i (1.1-1$),. A major bre.1!kt~]rou~~,w'as

s.
],(1"

111',4,l~)C~DOr). )..f; Zlllm.A~!!lIl\r.k;l.o,M~. 41. 329U97S~, ,p, GoldlFeidl\ F. D. ~~dQ!£I!~oll, AI',r~zyr.J. 342, 101"
1[198.9'),

.iI'

ulate

:I"ateoif such Qbjec~ !re:ml!Ja:iliiil'il!Q ~~~ve~

~i~m-i}d A:IitQth,or jn!ro:ln~ing avel1lirne ~s tl~c 5tu.dy of evolved stlUil ~J~;ait develop CQfWDctD\!ie ~,temar:modems" elI'!j:e]0iPCs !lISlM\lk ~s 95% ofthe sJ!dl3!l:~!!diJ1ls" Ri!~@ttifi[@.s<ilifid N:iml!l Ug,e !lSSoc.iDited~!IDvity w~,ve:S l1I1Ii,ghl COllnner~ 1.W •. ~. CI'kI,pmn, ~.~·ItIl"J1~M. NooJ. R. k:!~M,5« •. 311);8,.~:~ act theaeeelerstiea oftl:le ClOlltl.'8.cting; eote fi.9\l~', . ~mwl.'d the end of the' stoc·sli.[e..llay ,o:n;mti~gan .2. 5. lllWld!lt ~J m.. A!iID,!:'.liys.}. SI~7, IL:n' (200,:n, .3. fl. S" LiIOOl@n, ]I. lit tiit:l11!~1~, . J14lTiIO.~ .Sct 25. 10,95, J osc:illrunllg sbear deep inside the, Sl.<iJf •. the mllro'., W'rI.'-e.!i :l1iI1I1i)' 111 Offi<H:li,zy :lIIIud!ear l)lJmin!1l: in the S 4. 1':. G, ~!!:ph@l'd.,.J,A1m!!1s. 5G&i'r-Til'lIlt'!iltitT.t Pll~, 62, 115:8'7 (2000)" lorute-st~~s of r:,vo,h1ti,on. This could help SO,~'!,i\e

en ~Ilgl,d,~r MOiueliWl'mn .,.t;~S, dc.on~t!'@te:d i.16·· ,_. "p'v.,!\,II) __,g .. I.l'O;;LU__ ~\,nU_,,,,., ~""i'" Y'~-'l''''' H ~_. 17)··-c""-"v~~I,i,fi-'"b"ll-ti~d, poobl1em ofthe: ooh!!!i' i~~~}rul,d r.ot~liQn. r(,G),. 'Vi!e are :00\''' in is! new CI',a b~1 'wh:ioh gr~"',i1;ywa.l'ii'CS ~m:e bClco]!lm.inga key i:ng]\(:~d:iemof ll1l~mle;m

n, \11, Hi. Pr~c!!:, JI~fiOp~, J :i',~1~,~6 Ul?8'-l'.

12, ~,$dTJ,a1l!irJM. Ml.tam A~t'!!'iphys".i;i'l5l •• rll (l'~?~),

li3. ),. MOIltilIIJ.i!iII. .ArrI.m AiJII,o.p/lfJ. 2,r~1,421 ~U94', ]4, It~. !!J<lrdil! p!!l., H. c, Spr!1it .II~rD¢W& js n. ~:6a M mW)H, :1!5. P, A_ Ym~II®' K- JL IK~t!l!rnp.:l11i,J_IiLIRig!ioJ.ID_ Arr:\eil~ AI!ilw~'l. J ~'95, l1Llt'li2,OOO}. ]6. p, ~Uln~r, [, QlJIllill;~rt,.Ii!ilt:Op.~, J" !li'!S, L143 tl9t.l'TJ', ]" J,-t.:ZliIlm. $" lfilLt:lII., mlia~.,Al'lwn. AJ;lJItlplr~.U~~ ] .;Il'O' .~ 91t ~~

:l!R.

\"Ie~d::~I.!!d9~,tlt~ l~m~II!!~!. ~iJPjOOl't Illi tlfl~ ~r'D9r;;jIDm,~ Mation~l ill! PJI~iq1J!! SMl::lrw !PIIJPS) 0.1' (NftS.i1Ir4~1JJ. Frlil1lUl, ,und o.f t11:@ SwI$S Natit}Jlo!IU SdOlfll:~ ~LllOOillll'ul'1l ~WMS~.

MATIEIR.IALS

SCIE.NCIE

Do,es R,adiation Damlagle IM,at:e rla lis,?

H10lW
Elriial!l Ill. W il1:hl

Two e~~,~rnm~ntaJl S'l)u.tdl:esllTied tight s

(liiiI

tb e dVliiil!ll'l lc b~hiP\!'i:or of ttl e '~e~ocu CfE<EI'I!:ed lby raciiia.rtiol!il diamage! in ma'ter~al5:.

ever 60 years (n These eili'tbctscanlbe detrinu::ntall{<IS ~n sIj]]u.otuw ,lmledlll1s degr,tdiatito!l'I

he e,H£'iIl rdrmmm:ic clreclS ()f~rncllCir~the ~f.le'~:ies ,ofm~~eri,als have fu;een .reclO&lffillz.e..:ill ,ad s:l:~dllCdfor diaflon
Olm,

bellC,ficiaJl (a:siJil~le [Qrn heam :proc,e!>!l,~ngf semiconductors o for the'lmmlIcwOeiteclil'mlic!> ~:ndl!IStry')", .HOI!NeVCT,. the IJlic1i[lg~1)pilc;processes thlM llnnden,i:cthese effacts are net entirely lnldc~tood.li.i.liiing researchers' ~bulity f,o pred:ictllhe eenseqaences of ~rr.lIdi1Ut:imfl. Thereperts by hd;otwa (i.lt~~1.(2) and Mat:il!kaJ\...a el al, (3) in th~~ ~&ll;ue high!!1gh!t the :Iimi,ts of k!lOwledg(j~botitnw:i~(~~r-'iliizc-d diiShilcaltion~oop!il i!'l miU;i(iriW!!. 1'h~i"OSli~t!il S:h~ld stimul<\1!Jt::: addlilioml~ weseard:'l to' 'bcrt~cr u!Ii!I.dlerst:;lll1ld the:sc :p.hCl1omcua and 110u::iIe the mrnique diftillsion bchal'il'lor to pattern msrerlals !u:~le ~lfll~lOscak, Ato:mic~seal!e cOlnllrute:rr S:i'I'lIJDUIl:Uiolls are IlOrwlJoutuuely used to slIrdy the ~"3.di.~io[l~ ~1.lcl!m:::edIh111'iSiti(}1lJ :!'''F'ren[k:e] pai.I'l\;'" On v.ihkh o ~ni11 ffi:aIU or ]O!lll 1.'eilIve5i~;s pl~ce ~nt];u;~]alti,re, ~e'avi:Ilii,g ,I, V<lCi:'111CY, <lind 10dges nea:my i:n the c;uysl:a~40000m]l1g ~n .inte,rsili~iru) <In::! tilIle beh<JV~
!QJ."

~IlIilUC~ie.'lII' reacmrs)'

ior of dlJ$~ers ol:~tih~[';t: del:C1$. t7re:l!Ilkclpaili" f01l"llU3!b!Ol1! iQ<CCfll:S :i11 disp~.!IDeme!lH: easeades, i1WDlvi.ng ,81 cha:i]!lliof a.1:OIH.]Ccnllisicu'oS aief" ~i.gh~e~ p(lI.'t1ick~ QQlI:id:es with a l,aJU'ice ~to:~,. Mol'eculm.'''<i.yIlaJ:Ii'IJiClS (MIlir)1 s:H'Iilu]a:liions can :stn'il:yrn,duationm:1l13,ge {l<l'],'C3Jc:Ic,S pl'ochu::ed by h~wu,eene:1;ID' (> 20 k:eV),oollliisim1lS,[Is well as

Si~(im.1)JI:res almd dylla:mics IjIfdefiCel: ,chJsrers ,cOl1iHlhting ~,l~r.drnds of vacancies ,01: ~}~eI~Slil!i3]s,{4-6), These studies rev·ea[ t~8!t both U.lter~ s!iiti.lli~and vacancy c[us~eTlli. c!On~<ili.nhlg20 or

'dlC:

mm,"e po:lnt dc,ft::cts. d.I~:ect~yro'b"Juin the d[s;· p.laoo:rnO:(llt esscades, oeanmmlll :pris;wtltri.c dislocation loops (see the figm:e:)" h~. oth body.celltered cub.ic (BCe) b ,amd f1loe--cenl:Cl!w 'oo:bk {PCC)~terilll:ii, the :priliilTlati,c inref'rutia].;ty~ loop:s bffi'e <I. perfed Bwsel!s \"ecmr;were",lIspris:mlllticvalcancy-' type ~>Op!l ~n ~OC m.ateri,!!!lsem! be pelffoc1t or t'1!!u~tcd<Vacancy ch;i.~ter b~I:i!lVj,(:,'wi~ further ,comp~ic~,t:edlbeea!liS~loop, 3i~\'\iCUas void Of [;taiki~lgf<)!.1!~,t'~~he>&:fll(;():rij1~a'!iQ~~' pos,f~

Theiliilte:ootia1!.

;a$"'lIC]~ilSV<ilca;OO:t, dus~er8,

Th@ ,il!fjUlQr

~5 in lhil! N'L:Id@8 i" ~lrug~IIl~@rililg 1ilr@p.artlJllmi, Unilj\lIrlir~1i' {awtarniill .at BlimReley" B'~r~l!fl!r. A 94120'. or (

IPrii5m~1li'c m,s!roWj'!;I!1l h;lQp-.! •. i1h~ SI~kirlg ~qIU~rlOO of {rySiallilll!! plilllU!!~demOOi!itlfatilil~ Il'~i:;ma~k dis~ ~Q(aljon loop's ro~med rmm 'Illie dU5lf:rin:g of tile di&cshil~~d1 p~l~~~I~t~ (left) 'IWCl ~;3¥~rs;Q~i!TI.l~r;;Ii1H~b,. of '~m1dd~e') 1.00 ~OIiy.ers{If \!'a(;am'b:~;" aoo (iriilQlh,t:) .fl ~illtglle \r.IGaoc~ ~i!Ilf'Bi". In a pFi5mB~k loop, line ~tlll9ie;~'~ Yelr.tor,. wmdilm'i8ica~l~ '~h~M~mi~ ~ispb~f:m~J1tI)1l~ ~~l;'tie)lt, lis pe~peilldic!Uh1r fa; tlllil ~il'li: d'illcno!1J 01 th~ ~oop, l'Ie:riFl'i'll~,ry•. ll'1e didOll:[ltiClrll ~oops dellichte:d ~iii ~e le<h (i1l!,dI!TIidd~f! p~.ooI~ h'~"'t1l a p~rl~d i3!1.1I~IIi!lif'S; ~~aJI):f" whkl'l m'c1l1il1l1illlllll£liIillABAB S'l!ildinQI :i@qlil~llroihIIiOUgh ~Itleloop. "Uihed'ls,loca~iorIloopilii ~ilIe rigM. pallid oo5.!1 ~alltlf1(lllfI'llrger's ItN,tor; ~itllI5, du!: ,AIJ(JHl( ~tac~11il9
~~u~"'£
~IS dils~UlPIW I)y!h~ ~Q~,p.

silire. 'fhe ~[pes,of"acancy duS'iersformed dW',lng hTfu:!i:ation d~pe:l1td 011 H:le l:eib~v,e fiOl'lmI!l'lOn 'Cliii!crgies;,\vhich :areknoWl!l, mmd t~ekircmcs. of 'YaCaJU::y dU!sl.e:r C¥o:hJlimlll. which ,ft!.'C: urn 11ii:I[~y
'tilulbstood.

USt!. e:fll.il~;bdw;ir6'!@lfIlI;;.b~~lll¥.~d'lil

MU s;l:nd~csof j)!I".i!slllata.c. dJiskl!i;:SJtloll1l~oo:ps, s.how illim u.lil'e1:stiliill ]OQpii> (;a'l1ldiElse <Iibi.~gihe: dnu:1cti,on ()i[~le Bm~er's vec~orw:~til;mu:t an .1IIJffi:!Uedi stn."e-.ss: {the(l'lll,HI~:~y:·i]~rll]c:ed di Iillu:S]OJlilI} ,(5-7). 'f,I:te, loop diffbsioll is o:ne_,.dunee~lsionai ,1I10na tliLe Bltf!et;s vecmr and,is cll1l1r<Ldet~ed: by 11st,m:d:illf<i, Anhenuu8 dillllt8,]vi:ty" Loop:llin BeC mc-tids, likeilillll. :CO],ltflmii'll: m.lmmy ii.15

WW'i'\I'.sdenc:ema9~or'g SCIIENCe:

VOL 318

9lNOVEMBER :2.007

PERSPECTIVES
100 m,im:slilin]s d:ili'u:sewilba 1O\N ;El:ctl.V;lI,i[Oll pre-exlWlle:ntial&omr tl:mt deereases with~:ncre"'S:~~l;gloDpsil'le. Simi.lm di.ffitsion helm.vlOir OCCUltS in FCCnlet<lb, like QOIJ.per,'lithou.gh loop d~:ffu:sivity deCJ1et'1SC$ fOlI ~ops containiJ.11 mom~.lorufl ~OOM:I :51} inte:nr;tl'ti01li~~OO(;aU~&e perfect dis!()Quion~ep:ll]filileg imttol:lt'l!rti.a] di·8~0C;!].ti,on!'> bo!!uid:i:mlill: a :g1acki,11IS fin~]t 're~l;Vs;iI'I'n!llilnOli!l-,~:ofp~irmCl:,~eafiCyloop$ h!:a"'i~ b~n~rtbtil!i!M;jl~llii(;jc~u!i:i~ Ul~ are ~ot be·~iC\fQds ~l,ob]ie M· irl't~Si:itialloops" ~
elll::::rgy!U~,(l8 M~~G"'C~fIW ~~~mil~

ti'ae:l:I;uruJ1y ~mIDm::edone4looe.ll,'· siO:liIiIl dil]lS.ioll ]U ~o~d, The l.'I!ut~.1.or.s did not quantit.Y t]mle ]();OP diffu,sivity. bllt eS1:i:m.~lt~teciln :acnV<LtIDn e,ne;rgy o;f~{t21 c¥.TreOOscrvatic:D1l. m-miouliids tln.L:lllen:e,ptD.o:l1. oH.O'!I'l' d];,ff"usi.vity and requires DilCW :iknow]edge to d!e'lcrmlJrnc the diffi.! ..· •

3,4 mu umje:~o

siIlTl!lTu:lchanism. Adid'itih.Jl:l~[~y.ii1l1d petha;ps

more smpming.tlhea'l1tho['S obsctve dJi:rect tm~Th1miifllil!l.~f.ion '1.~rft;cl:,.l:Jirigu,ati;loopint() of :1i ~t!dk~lgnii.jj~t ·t~~hoorojt SiJeha tra~f~)~·· tion, ~Ild .01e liI1Ie~ha:ni(li~\ by which ~~: Q(lCC~\WS, ba\'ere~r;;i:"oo ~i~\it!i.ld ~14d!y, ThkeniQgC:lhe:r, filtesen::sult;s c1'1pa:liid.thc km,wfuldgeOif di!;~oc-llitioo~oo$lbehavior. snd fa~SC' :ncw qucsriolls!lh01!l't ~he siz"t': d!(;f)Olldencc of !Dop diii!~s:ion, the: :mechiMl.l,..m:;;; oom:mUing kx)pa:nd h:npmity· illterm:;tiO:l!iIs, ~swe]]m;possi ... b.l:t~'3:rLSfoI1IIi!!liOllll! meehanisms betvtc"eende:fcc1i dllLl$l:er configtlrntions' 'ill'hL"i will[ lm!1JoH~!ale addilinmll. thecreneel, amnp1lllaft.onal,mrnd esperi-

IllCUt.:l~. ]llYe-stiga.tiou:s. Yet:, in iiliniis, Ilge Of'lIDllilo-. nUIite:,ri:a'ls, 'WIu::re nmlIiplIlaliioll of the arlJ'jjUlge. ment arid o:r1l1ienlng ofm<B:~e['i!.l1 s across raneIJl.e~etrlengilil,1. scalesis becom[lIlg rout~lle.~lle anides. sbould al1m mn.llMil.<It.eiwluMl1ive sh.'m& gie!!. to~:lrern. or :self~:r,!1iI~.liz.e~, dereds <l1IiI:dI sQ]u~e SI1iUCWI'e!S as <li refrn~Jt f olle-dimelilsiofial o d:ilbsioilt. teading tolJu[l1ilb~en'i011rer.ii'llpuweJiities.

IF.hrrielliEIICJl:5
:iL (. fI; ·1ffl~l!1er,. R~al1 br.~'Nrlh £I'ldi~ De(embef l$.

~~mt!!~a~~18Qfi~e~ic"

tiO;1illbops oO~li:aJ~Jl·nn.g more th~1l :('I few h'·~il· .:IBid ime:rstudal.i> have aot ibeC:1l IP'crfm:illll~d. Thi::;; is becllu;:;;e; k.o, m]g.m;t~.Olm, 1.5 lexlpecl!ed.1n decrease to ze:m as ~~!lcloops~::ue iSJppmac:hes tI!i!<I[ ofdn1idoc:aJh'o:lli Unes obse:r!fcd ill u]!liirmd:L'" ated materials. Suell ·'corJ'I'''CIll!l:i<JiIliBI·' di:!i~oc~ l:iolls,.iJfiJJ~te ro:~rnofl:mesn.'lllher tlliUl. loops, do ~:lOt ~nove\\fi[hmu 1I~.1. ~p,pijLedstress, 1~mvevel:. tln.e :S~;Z!e,<l:twho.ch du~(rmal d1i.:fIUsi.vityceru;f:;sls dj:s~ocllltiotl~J. in n'~IP'0nse kl an <lIpp.lied stress C!Qntl:o~rJ,1e mccbilnic.a~ b~i1I~vi·Ofof'rnctlll's. ~11!m:ci.d'!efl:;]f~ nt~ed or saw.;toothed streSl&'5lr,flm respoll1,~e (If BCC!T1,C(tal1iil'l tcn!'riQ,D!It~t8!.$ ~\plaiI:lOOlby dle
kliln'Wfl t~mi<llt: tI]:le iliIlllQtioil of'

:t
~. It 5.

.:l9coW, ~Izy~:idWi:w,Jj~us. ~ j\jgl[!'!it iE.!lEir!W (~m[ll~~r!!n ~!'II1IrL(p.;Ja7. !J~i¥.~ ::;ll~~~~., CU~~g~', ~'94~;. K Ar.air.ail!li!li!!' iii....a:MrJ? llll, 95i1i(lOflIIJ}. ~ Ii. MaI!i,!lI1a\TiJ, :0;, lZ~IDJ.i:I!.! d'~ll!:~ ;);111,9.5.9 (2Mt.t 5 I), :1. B£iHII"i ,~.~·jjl~ Mlld. .M.rlt 3:l:~.152 (200:l). J... ~t ~5(]fjfiil:a.1 Diill de ~[1 Rllbia,AAilor.. MIl'g. Jl8:L .Bl

6\. ¥. Omikye!>Ill.,). Mud. ,M,jj'f. 307. as.\! [:2000), T II ~ rlan el (11;, ~ .~~ $61~, )!44:l!Q:2 (~OOj!),. 8, fJ,_ IfL. (;mthell, 9:, 1B~b-t,.~914?, h;tJ •• f'n~ S(ic" !,(JOOtJ.fl A. 62;. iI.9' (1 'N~.J'.

l2o~n..

i;~at:vcl~:koowll.ln thebll"b~r si7~lirnilt.itis ,

,~~:~

m~c~(.':rio~ of disloc:a:ti.(tin~ with l1aCiarbyfrm.pu.

rilty aroms Uke ,~rb~1m:d ~iU:l)gc!l .Theb~lpu· .
riily

Enhl8lnc:ilnlg 'C:ollloiids Threuqh the ,Sulrfa,c:e·

AdVl:lI(f!,~:;rn loollqjld.a~ s~riaC€l ~h~m~s:try are el("l~lt! 1iI~ Ii1!1lW~~i'!I~eos. s:twct!.!'~s. a~ dim dh ads ass ~~ bly. ,~S:!j'!ie I as. !t! ew r,t:)!.J1b~~ hi9h"~e,lif\(l rm!an(~ d ~ ICes, ~ to

used .i.lml :many m~.d ]m:l·~~sn:ial prod~cts, _~m·lIiIm, ccsmenes and pbt'lnnacc'ut1JJc<l~$ w1:~]sizes hct.'lM:en 6 <IIi1d2'[1 ~IUllilimil,ck~o t]uCIi'" 1:0 ruiliJcsives ;11I11dplitint5 •. 1lI1. fhe'sc: J:pp]ic;1J:tioillll&, ~,U1f1]]y hilcllroed o:ne-diJ:lileJiil6~Olllfil. diifitsion in thee co]]oidilliru parti.des Jre us;u,d ~y iSp:1ilLerkial Boe wl:mrawilh.lI COlU8tfiill! 1.3 cV ncnv11t1on 00li'- lInd have hOlrnliO.ge.11I;COliJl.~ susfaces, If their ri~f,m:lepe:nd.ent on:oop siz,;ec.. he <lllidlf)fS :pro. ~s'CmlJly wu:td 'Oeil1lfluCJi!I.ccdi by mllJ!Thipulllllt·· i .T pose~hat t1i!I:e]oop dilf1i.ulj!;'i.tyi~ C10lltJroUed by i!'lg th~ :surr1l0!';:dlcndstry of :llIcp~nlt~c'I!I!l~j th;~itI!Wruction ,~'ithint"CrE1itil'!ilirnpu,rity a:IDI1l!J fleW o,portt!nitie:s for colloidal ma.reri.a!l~ Ilkm tnfhe OulitreU !llltIDi~lwreSi. ICQulJ(] Cl!iIlIC!:'.I:J;C. fo·r ~1!~ll,le. propo~cd pl~!OIn so:m.eg(;tl~.lhese li'emi,t~ ~,gree\l,~:th C!l.!iJi'~ ton:i~ ?ippH~!u:io:l'i~~~s dle!l:l:ic~~ S(':llsor;",. rent kt:i~!i.l~~, niQTI~ly orue>di~jj!J8,iQn$ ~,Iif: (ip~jC~~ fHterc'ii,{llrjntcWOf!ll0cts--C1i)tl]d be fUSl(llml ef d!$~(l¢aJt;i(lfl ~OQ])5 QQlliilroU,ed by tlme 1leali<'ceodif OQ~.[~id!fl!~ c:rystf!~s cQU~.d b{: a$~:I!IiIQQIUQC~VC:l'!1()t:iiOll of di~~(lca.ri,Ol~:!! ;l.Ild imp~rity bbl. ~nif.'luC'W sym:m:etr.h;:s,wii:11,ISiI"g'e" defecta:iQms•. H"H:l,\evcr,.~l!;:RC [~o[p~ a!1le ~argcrth!Ul lo]e:r~ntp]~oLOIric band gllIipS. Sm~fa(le-nlOdi~ O!b~N;:rved h~, MD s~m!L!.l:atUolJi1Jis yet: quite a~d fled clono:ids flJ(ul. !(mnOiidil m:ysla!s Hl1I!Yml.so SIt-nU c~m.:p~n:edw[th C!()IlWllt.iana] d:is'llJC1b· be 1!I.~C1d in j)1.i.oliO!!i:UUSi[.~ui()roe]ed!.·IOU](l~ laud lions, }-\ddilimml1y. nhe ~c~ivatf.olm!eU!ler.gi.t'$a:1MI !C3;tlldytic:3!p;phcali;mlS. [~I ~l h·adi.tiomd. collo9.dal. system.~he [:01 .. pre..expOl1tcnti.8i.i facto,,!! ()inoqp difflJs~'fily are l!.1!rg~rth;rul in MD :s~:nlllclMions. ,1iw:Jl lit isunciern1.0]0 'slLI:rmeC!!i.s coated w:itllil, Iclmlm:ged uloielies, Wh(l!llller tilJL:l tll1elmal diiiffifl]S.ioll of d:islomu:i.on wlmi,ch SI:tII:I~lil!e,lhec,collo[dsilm, sotUtiCli.1l UpOllill lb[lfJiS and ~;uI]lllcities Oil:CIIlII:S byh~ Si,'U1:1emeclJ. ,myiilil,g. <:I.. c:lose-:p<lc:ked Cio~kliictd crystal up to lUllsm .1Jisthe slresi'"dril'\1li!11ICOllipied d'iflhsio"l1lof
I ~onsmlu:r

aicm'ts 8Il!UTOO!ld~lgadis'~ocalio!ll!rro i~[!.ncd a "ComeU (l'bnosp:l'n!erc" (8). ~ndlhell(lpeatoo !~~OI:iOIl ofihe dlisioc!ilion m.l!i.wylh;Mulhe awo~~~ere,:f~n()\'l,I,ed by dtlfmioiJlil~l:theimp1!lrilie.~ to,the di:!>]ocalk)n. exp~ill:s~he o~el:VCid!litres:!!i. st!:ain bell:a'ili.or: 0:1111piflg.C 9.56 onllnis rnss~1.C" Ar<llk;BI'(w.etal (2) sl.lQi\1I'thatilllte~'Stl.tia.I.~ilype d:i::;I.OC6IdO!I1I 100ps

.C

Il;!f

oUiOi.dal.

[l1i'lir1i.de-S(lre:

l;nmd~s Qf~.aY~I:l>th]ckwith wrying defeet d>en:s;~t[e.s; nlay for~n,Most oo]]oiid<l,~ sys~em£ p$lck ~.llto a&oe"cl:nte:r-ed cubic slruch][ie. bllt oiPpasite1y cha:iled C!o~~o~d:s. canfarm ]oJiiii.c crystals (1). To c;reilJte even mOIr"C c.>Olnplex :!itnoc:tureZl!,.~e ro:Ulliool.p..1!rti:de~:nm.:i;t ex~miib~t diroctio(rnJlimltli.nlICt:iOli!Ht. T.i1U;s;can pmcntii1i.l.y be;ae~k;"vtld by cl~(;~li(;;lliym~di~ing s:ptl:cifiiC
S:y~W!'Ils\:\!:i,tll ,eb~mieal1i~i~otropy h~vil': grefitprum~~L;; for formil:ii.l;l: ~Jew strucrures 'i'iii~hothCf'\-jj,J'i8:e li~~Uf!i~H1!b~~~ r(ipcrt.i(j;~(2). p TIl~Qre,1ka~studies 'by Zh~n~ (!.~ t;rJ.i~ldi,ca:~e tlmi~t col.loids whbli"our a:U:m.cd'l;;e plillitd~.(::s lOll ttD,e ooUoid s.Mirffi'~cethatforIn ~lln.e corncrs of':f11

~~allg of~~e CO~l.oiid:mrfaci!)"

U:!lmhedmll cflnse:l.tfls;,;e:l'Mlb~cjfmm a disordier,ed s'm.te into aJ c:rystaft with d:i:uuo]!l.d ~y.ln·

lm~.etl)' (see il11,lC fi:[Slfigllre) {.n, This :!irrm::~]Jtl1e

Cottrell.] ;E)jliiuos:pher-e. O:bil~!ile '959 ,of ~llis,is:t;1.J.e,.. ~.I<iI.tSl.ilk<I.w<i. il1iLd Zi~11kle(3) denlOllSt!i;,I~e furrtIJri~lmtic¥acrnl!;;'Y"
<I.

n~JlmJltors; J1~ in th~

p!br.all!rI@uil!!c"ed!i! .

typ;;:: dii8~ocatiol1.~()OPSwith s~s. oo~ef!:2

and

.~nJd ~ft~ilil~~",ijng, B:@(k'~n ~lils~itl.!lre llrldFn~d~,rhk < 51~t:· Matil1lr1ilh R~!Ie',mh iL.aimJilliory, ~ ni~IN1i1iy or 1'ili1il0!i5iil U~ba ni.·Cha mp.aign, Urlilil!!1I!,1 ~ ua~n,USA. E~m.ail~

D~p~rllm'~lTItDf MiI~~J1i.ilL55(i8nC!i!' '

is ofgm:e'aJti~~.l:e1:est forpl,ullonic ap;pMc~ti.Oll:!i l::lec;<II[I~e ofdu:: [,n1)e I!limto]1Jfi,(; bll~ll!dIga!pil has bee~i proposcd to .!Xlsooss, ..Th~s strru.crure, hus yct"~o be re<l.lizedtilrougll s'elftO'l sliN;:m.b.I.y~ bllll:recCillt: e>\perim.e:IiIIII~ ad'llancles i,n S)/lilthes~'l:iJII\g:llliil;l1l~8s;emblii'lg cJo[loid", with ,dil:eml-

c~l~y distinct ffiJifltc~-eS JiII!la:y ~QOf! mil!k~ tlmi8

~Of!~

~c~i:~:rv.~ble. FOf cx~rnp.i¢., it :is 1l110'iV p!!.'l5siWe to 5yn,ti'le-

"} NOVcMBE.R :~007

VOL 3.18

SCliEI'NICE.

'WYIfIN ..solienoomillg,org

PERSPECTIVES
..,~ze '~J~~.ms,·' ~:mrtk;leso \',~:tholu:micm]]y distill1.ot Thte~ni:sp~lere-8.Howe.,~e['. sy~uhe;si.s: is o:wy t:hre fil:s~ :stelPtow<Ul1d eJiilJhtllil!oil.lg t1iuie function ot 00 Uo]da~, systc,n:lS,. ASI'le.WiI,M,y must (Iru!lJO be cOIl:tI"()illcd,po~ing: poto0lfl1ti,aUy more: di.fficult [p:roo]em5. Sucl1 lill[llUS oal]o'ida] paJlttc:ic-s l'm1l¥e been :sh~, lUI¥orm mini~1LUln-er'ie:l'bry ch.iliitm of2 tOI ] 2 clll1oid:s( 4) fOwt ~eSli; eruwtef:il Jila:vc aot ~:etlbecn~!'iOWll '1.'0a!iisemb'!(Si~ug a~e~:ol\1eQ:p~ery~i:t'it Ol]lo'id:; \~iithMof,tS eQmp!~ c ,~tdhe:s ~~<.(; bee~!p~M!eITICd u.g]l1_g m~lti~,;;ryer ooHQi&lcry~ia~.&.as ,Si.physi'calmas.'k; h!)\!,levc!:;, the y[el.ds a:relow; aind, iris.net ,qbvioll:show tlilC flroc:es;lHJ!U1 be :[:ici1liledup ~o s.tlniden~voh!.unes of part:uo1.es to, study 3,sse;mb]y ,(:5llu allO~:he]" arpp:loa:c~, mkmspJin,ercs oni~e CfH1lll.C \\ieIJC bOlllrld togeti:lel· w,Mh nanop<lrt~Jl::l.es o:fOI~POS.it,c eharge to form clusters Oiftv..;o to ni:nlecoUoids. T~m,el,olldin&l: ()if ll<iUnop<1Irti!c:~e.s W,lIISi vlIE.ued to ~djlls:t the chJ5'ter smlftlce&oililil mo:stIDy bsre Eo[~r-.edoIl111:i:!;Illil,dt.ylI!1'Iop~nide"cIQver-.ed I (6); :i1Iifsise;mb~yef'these panicles ~i1it15 1lilise~,I~Mymay~ru:ntiallliy

pl'o~idethe specificity of
ol.iellilltat~on nece:ssiilry to imp~rt both the: d:esi:rerl. I!OCi:l~lI~lcl ~on!il,.;[mrnF .~cmliC,.

00

.tIsse~Ilib1y, 'POJf ew..a:mpl.e" p1:iJo~

~oswjtcll[lJb,le surface: chemC<Jin alSo crnilflrol tJilteSJj}.i.'Itillliy de:fi.lled<ldsorrp.tiol1l of colloids onto ,11:-Jurflll:ie 051. r.hotoswilcha.ble collotid:!i eOil,dd, for CN.!l]lll1,plc,bec 'U::-;oo as ~i'~ehal'ilc:mUlifSi!l mfcrofhddtc~.il~'S!1.ill'!iScr:eOl'~ gr' C!OSlltGtk~ th.1l chan~e tlpO!1! istly

DN Ai.s

ail1

~dea~ lig-

lIm:ll f'Or dirCJ(.;ti~g assemb:]y becasseofi~g h~gh 5lfio.;ilt1dty, mj~fgitility~

1llrld ~!liqij~

.a:bm~y W

a.~S\llll'ble sin.u;b:n:es over boththe ]jJifllnO!Men~:r flint! the; m.ic;rometer ~cak.

IDNA. }'l[yb!l·~diza,tionl.lo1ls,j

far e:xamp]e, been used ,LaillliJDiilVert lJe1,w~eill ~Il'iary ~ry.;:taL~ .afile! crirtcal ,cha:l.k~l.gesrcmilin to i3:SSC mlbl.c gold nalmo" ,~oiLo.ldailnu:i&~1iI ~lmili:!d,i,,~~clliiiIll1il~M before e:xdl:ing~piPlical:iolls particles (9) m:JJd.ic~n· I(I~diiHeiFeflit'lrt.il'ol'Cl':[e'liIgtliJ5 (bv!. iA.1l mny be re~~i~edI.nel:e is sli.U nogood wUlte fOil the; hulk meter-scsle [IJOD~tyrene ,c:olloids (U;i).,. B]linc<[nie.]~o and Clo~wo]"~ers syntih.csis of sil:e.,spccific: ·p.lltrI:el"ned IcoUoi,cQs. haVi!! even fQml~d snliil~rn C'()llo:idal crystal.s Ex.a.cl' COlrnitr-olafp1l tC:.i1I si 2Je lind lneetieuis ~~]iOtlg;'.[lNA~di;rccwd ;ilJSiSe:illii,b]y difficuh, IGeJilei.'~,1 patch ft]nc:tiJOIl~.liziU·iQi.1ii

SW:iI~~a'bI!1!!Siys'tf!1iD5; 01l~i(IS;itdy cmlU9~(I li~cx~~. Or~iii~1fiI!l"~1~t ~ III~Il¥ coll~ood:!~ sys,tems, ~'I!'e been shomJI Ihk:]::e:n1JJ~ol1 aplillioa.t.['Qu,. 10 aSS8mbteilillo ul1li;QlIJ~ ~!ookS;lrlluurrles Although advances ~rnifllve U). Ilrl)Ulgih alPproprliat~ ~~~~.:u::~ dil~!fI1'bcenma.dJc ]~l. oon'l:niUhiil,g istrie~. it ll1iiilYPW¥1il PQSl~ib~!ii ~rn"t~ to !CoUoiJdkli surfaee che'Di.stry~ photosJWitdllaMe, b~mny sfS'~ems,Ii"hich

)"et to be el'ilplovcd.

eh 1l1Iengili1~tQ
MOI'(;:

nil/I it n::m,li~ll~ higifully

or

:poi~y~tyn;llle (l,(), ~e.i;l1Iiiti"l~

thr,®gh DNA-di:rod()d aSSCM-, bEy; The ~ev,ersibi~~tyof D'NA IItIly 'of ct:)]:~Q~.ds. [Ilto ~al'g)C~tY!:lIi:di:t.altron nm_y levcn~:llbw seleeIive defect ~:e:l1J.~o'!l;a]. Ahl:lough colloids: with ho_ogel'lcous I[;ootlungs Oif:mo:]e-ol.des h!lvin.g bind~ng Si[tieci~ "diy" sm:::h3sDNA. havebeen s)ffllhes,ize.d\, it was not !IlIIltlim I,.ece:nt~y that: i:l1divi.drn~ reactive molecli.l:les were p:.atterned 0I11,pa.'eOf~e'kKiJlltiO]]S of'tbeoolloid surface, .By pLiI~i;ngi:l]jdID'yidJlIid rea.mlli¥e nlO~,ecr~]es mlil.l.ellol.es of gold p<!Ll1i~ de's. De Vries es al. fcnned mm:lome:rs dntt. ,C'Ouid be PJ[y.Clf.~;red into' linea!!" MI:1C1pllrtide: ,c~w~n:-i (12'). The &ltlliW'rs,t~~t IOOiilil-eclthccol,I,()id~vit~ l.1. si::,lf-il.s~e~nibk'ldmoli1l:obyelt and dle:JJi (;:I«:~rn!rn:1;ed. the mg]~~,k~~H 'me mJO~L'S of 'liow,ar,i!I 1iI00e~ ..!ltmul~l!Irres.1111 the'®retJka~. SUId)i~ a the ooUoid wiO~J'(;;acHvelliylliIJi::rio!ill1lilmolcZhali'l~ ~' ,(11.haVi':~~~m: m!hat II lmay be' 11l1li.~s1ble eales, TIii8~~cl1i'S!I1~eoccurs specmc3!I1J"~,t:I:he 00: f!)ftrnl dii"!IIloliil:l ~rtJ!dlJre,s·h()!lllI(:OIUoid:s il'\lith Ioulr pol~of tl\i;e~p1~erica~pl1!rncle W~'iCf'~ '!he :f,OU:, [lIUJ1ldthl'e pa1Ii'le5i. OI1l~ pQS~ib~L:lIIUlll]1(t~Qrna~n2:a'li®,1iI ~SI(:Il~bl:edi !.Q1m!olaycris ~.u.5~~ble llld e.aJSY ~Q n a ~. c rreate ilu, attlractive:inll:eil'ac:I:iG.ns ~,5DNII\,. leN.cha:mlg.e,.SimUar waJllQ\PIflrtkle d~i8!~:9.lS~UlINe shown grea:l' p(li~:entifl:~ o['!lkal, £IeviiCe.s. S;~tC~:l t:Of :scak: Slnt~:res .. FOr e1um:~:p~e~ ])Irusiftlllm:e',[l'tal, cl)e.J~edco.mpl.elli: SI'l::M!otilfIlCS by assemblh~.~ ()GI~ M \Wiv,egwdes (13). loi!c&al C:ry$li:aJl shells, ,!lIt:interflllces in aJ walc.,.,oi] In ~n m~e~'esring wewap]looacih for using s:urfRce c]ine~.ui:sIllFY to eJlll.oo:l1,ce the;mu::tj,QJl of emu]sion (7). TI.lf:se ·'coUoidosmnes"· I:m\lle controlkdlJ!OfC suzesililillmca.WJ be used t:o s;e.~ec- Icolloidso. :P~md:!e,tJt·lind Cio,,;work;e~'S have:: :SYlli1,. ,tiv'e1y i<lmOW p.el'me~timl ofl:he' :;;heU byv.J.li~ Ihe;s~ed ooUoiill; '\:v,udl,reJ'.feliS~,bly plil,otD~"'itd" E1b1.csrurt1lce c:illi<u~,e. U,o:nill'faoi:1l!tiOll, these; m18 :IiiI,%()~ecllll,[rSIJec:ie.s".~liiIlnn()il:he]f :sun].)'. Icolloids COI,1V'eJttf)10.m liD aggr'Cga:ted, oppoH eJr'ITiIll,noone$ cd. used dielecl:J1ophOl"eS]!:i to si~ei.yc,h,u'ged strl]Ot'iJ.reto ;JI, d~S'pellSed, ~ikeM!Semble ulet.dlic cn]]oi.~s:inm, :self:.;reprn:rltis ,charg.ed! ::'y!ltem. a rU'st st,epkl\''''.OIrd p,hot{lm~ condl;~ct;ivewire's Wi~l ~tiUirhetef-scak~ ot&l" (8),. Thc!llC .ilJp:pro<](;h~ to ~s:-;eJ@lb[i:!lg ,I;Ii!fg~~ w~~ibLc QoUb:i~dcryslilll~,~;o!1 (:-;OOdlC !:iecooofigw~) (141. Sl~clm,photo~i'l'~t'Chillblellys: ~cale ~r,!!IChIreS 0IiI·'Cpl.·"(ro'l,li8ilil,~utt do not yi.eld b I'jtrticl1.!ire5~",irll.locai. ordle~, Upnd-dii:rcc.ted lem~ a,~1! g>e!1er'iI[ro~,de dlt,iving, CQ~~oidlll 'tg WW'i'\I'.sdenc:ema9~or'g SCIIENCe: VOL 318

assemble oomp.le:i\ Qbj~c~ ()!! ~J) [o,ml ~s$ic;l'!'!lb~h:$ ith [~!lgw ~~g~ ord6-r.There hi1veb~ !lU(lee~:res, in di~~·d .Si~lCm"

mi~,ro~;phc:rcs, schemes need to be dJe'l\·clQped.l.evc.:r.8iblc d,cmo:mlsh":'d,~i,lti\:mctio'l!iIls wm ~i,8CIbe Ilece~ary to i:cmCl'llC ~iO!l8'i'!f(:re :r,u:liuer 8irn~le. lmtit defects. Here, m>Jitotiosvv~tcliru<iiMe sys·l:cms s~]O:ll!Mbe pcseibleto 'fO~l SOO~N' lP:rom~:;e, s fU_liIeti(J!oo1iz.u:io~1~oogi.~8 A lll;;iu~re.i]IWC",r~pH()~lS ~:h~lls~!nl1;1y ~f intc! much nmn:: ~()Implc:x: ~~c:~u~
clw.i~U:li' !W!od:ifictill coUJll~ds ~hO'I,ddp!!,,(i\lid~
~n.lpO'rtar:lit fetlidb~ck II) deU):rliiilinc thereqil.lircments for sl1oo:urici'l:y~ binding sU·(~liII.g~l.mng~ Oif b~lmraotioiIL<;:,!lm:llr,eversib]]iry neeCllS!llli-ylo achieved t~]l:= desuud hliliC~.·oot~m~s assem!!!nd bly ~~U(:m.gliThc~memi(ml mom:fic2:o.on oflllil1.'!: QO~]oid S'lJlI"face, Success s.bolJld yid'd lle.W[lliJteJ'ii~ als fOll" pl:iot(mi:c and electronic ,8ipp!iJcm.tkms,.

C'!)mmmc:r ~]~lIc4:s. and Ind.ustrial systems dae to ttL'!; l!I:niql.a!epm]pCruc,s e:.m!ti:il:ed by surf"IOO'"l,1,lod.it'[ed "(I']~oiJdls.
1, Ill, IE.LeiJmil.!:e!'l,,~1 m, tl,i'aiute 437, 2;1S, (~IOO5). :t ~s~ Gl!lit!i.!~•.tII., l.~1.I'i.fi]lIil, l\!dt" ..Millet. ,is, 5~1 (,
1(20~l7JI,
;!1, U54~: (i!lOos,). <I, L. HI;i~,. J\ ~~d\!t!)!, E. I~l!ijtm;.s.:. ijr,~l1id(, J\(.;t1ilO ~e!1. 6. ~Sll!D (2006}. S. G,lla~~" W.'.I[)1Iy.] 119,!iI. ,tlUitkt\!ilI~.Nomil'tJ!i~t ~. 143'(2000), 6. 'il'..!i, d~, •.1. A.!vr. crrem. S'C'{; :!.2~'. 1596a, (2Q!O~l 1. l!i. Dd}ilk~IlH!! Nai.,.S:,,*rll'e2?El, lJi06.{200i2)'. 8,. tl:. (l,. HJ~rrrt~ft!tIii ~tat., .:\':~I¥e~9~, lDru~ (200U, 9. IL,~, ~11I:1il, ft. IL I.@I!!Krng@i'. rt. C, MIJd.c, ~, ~ SlDrIKliW"

RiNeiliEOCeS

a, Z, l :Zli~mg', A. 5" K:et~T; Cli~lm,·s<, c. 'G'illu~r" lollgmurf

a~1;I

N~J'!m,'38J2, 61J:r(19916). li. T.i'IIi!<!!i!J" "'idide~~n, J,(, (Iil(kii'l', !.'II ~, 6r~e<~ l'!..l !l.A,.I-i~.[l!jjiii~r; t;mgJi,trJir l!,.~.lJ03,t~t~Oro). 111. P,.L 8IallCJlnl~:Il~ It), [Kim.]I,C. (~mdix!,~. i!1I1y~ Lert.9~" 'O:S,M02 (2005)'" 1:2:. 6.J!,.l)!eVfie~e"Q],. Sdeme 11:1.5. 3·S81[200?)" '!G. S.,![U~ili~relar"~.~ef.l;,.1!"·~ twml 1lil,t:;. N~ iilu~k.'rtt, A. U!t1ihl'~~~. T,. [tw'~h, l II. ~~i!; R J,:'i. ,1'I'(io!jF~.J•. MI. (l:\I!m. 5,M.la:7, 1>4~,'11 t2005J. :lIS'. M,. Ae<lll" Mi, C. Ge!n~~.,I~. '5. 8!l11l.P.II. Br~III1l\ LT.o7gmT1J! ,!t~, .I:~ (~Q(lIQ), 7'9

m,

till"".

9 [NOVEMBER :2.007

925

PERSPECTIVES
CELt S~IGINAU NG

m'T'OIR" Ulnle,B,shad

..

A.n:J ~OO(l1an!tlriall rm~mlniln~ prmti!Ul Uri k:s:two parts ,~f g sig,!il.i3!l]~~,PI~thw,aJythii!.t is ('~JflbaJl to Cl!~t groM~ a'lfldl l~mLvr\erat1on.

grQ'wth and prQ[Uerati()!1ii!.prQ~citlThS;-YJ1idleS,~l! alld bl:cw,,-dQ'!,¥.I'I. and otfu.cr ptOOf!S\.'ilL:'S"Dysregu,l!i3!t[on of' lJlJ,~,lnl ,1:5 limplk'«l!tedi~1 a mn~e of ~~ruma!lldisease~1 ~nc[lud1ngcalloQl"S and cardS 0~:~Llar (';omlifliom; {I, 2lAltho1!J~h am!!l!ogs of' lJl,e,cOMpDlII1drnp!3!mycill, '(rapSllDgS)!Illl;: ~n use or ,il1l,clinicml, irials tQ~:rea,t sueh dlise.~e:J>. ~~'1Ie ~,llea:IIIS bywhk:h sigillaling UllillOUg;iID mTORis QOJJltr-o'med me !led wen. wxlel'stoocll. OJlIJage 971 ofthis issue. Bai el al. (3) mllkie :a!nnmportotm contributi on to Imderstll~.lIcl1ilil,gmv mTOR h is ~:r:im00I (jim,

T
_

1:a~iW~Y~~l

C~YJIIleMal1m1!1dm!l (mTOR) ~l~4Wg

'mrgc:t of
mafiydil::

gf~ factors, acttiva~~ m]iORC.~ !lfgna]:oog, ~ild~his\W1!s~~()d~reo[]

Wjlt]ml

f~}rel1!t ~lll~~iljf ~gn:td5iU'i'oCJ!'itrolc'O~1 c

dO!;;~~d bi~ldjng of FKBP]'S

.~ !Im~1"OR, 1'~Es,FKIl'38 i~ an cndogc:w,ol.ls inhubi:tol' of ~.u'[10R, ~I..rn:.IDIe!b·GTP ap(pfl['eI.Yl~Y~lldU!::ifS tile release afl~BIP38 fm:mmT01R, t:lI.el1ebj' a.c~rrntlirrug Imrn:IDRC[ s,igI.lBJ~~
im!:'l: sce thefiguilre). ( This model :pl:o¥ides amuehml,ooded e~19~l1IJtiml for the ab:ilties

ofRoob.aT~ asd in hnnmSllioo,. to mlTOR:C ~;:Bypromotrnl tiil,e tiOl.1nOl,tioll of Rheb.!GT:P (8), i:l1ls'l.d:inal[eviiites the inhibiti.Olrill (If
<'I:t:~ti,."I.'I:e

The dn~g rap<!lmyci,l1Iini1l!i,b~ts 5ignaliQg ~mtkedto nlTO;R"C I, ,(4), "'Irnm:u~:riproteill C:10:nlpl:oxthat O(;lma~lS ll1it1'OR.m1'ORC 1 ,sigf.laling ~8acl1l'iltlilcd b~i~s~li:rI and gro~)llth~eto~ as
well as by alniAA ~c!d1s."Thel~tre:rrn.:akc."phy:;· ~6IQg.]c:al sie!l8~:!nroRCl act:ivm();s pm:!ei~l S)i'!Iii[h.c$~s"~r \",hk:h~na' f ,S!c:id~m the :pn::eursots, HOWC'Ii\er, it is sliin 1,l!1l(:1!~r how mJ'lfli:ru) adds S'\:\I'i1lCC;ill 0111. mlnR~C s:i:grl!llhlg. "Mm:e .. W QV'e'I", \~"e :!>I'm.oo.:nl't under];iIi:l!nd hm'" l'allamycin ml!crferes wid'ilmTOR:C~. :lllllct[o~1beYOll1ld. f11e fact t~.1<1i~ whe~]iIJ .na .c:omp]ex with the protein ~ FKHf12.ihe dn]!!?; b:il!Kls to u1'ORCl. w~, lil:ow:r~ther .me abOMl ]u.owi:mi,ulin k a()'tivrltes, mTORC' 1.,~Jl~.eb,f1 smail, £jlk1lllOSilile tt.i~ho51)iliuare (GTr}_;b~lmn,g; Iprorein.ilJlterncts with uITORC W(5. 6),. On]yin 9. GT.f~bollnd :-.1111:e; (:Rheil).IGT.P) \.'lriill ~t cti:vatemIDU.:s a Cllzy· 1'!!l.1t!C1Jctivity "OOi!i[l'E!J.Qtylati!lgmfb~·tprm:GI~l!i

IEndog!!floYS !llIl'OR i!'!i1i 100 !lilitOOl!IZ.ndrlall P!iOt'~I!il F:KBIP38 iJ!1Idi ~11il~WKH!lP12·f"pilmycn!n !(()Illi~lex. ,eildlil bind ~o mTOR ([ItS part 01' mlfORC:lL} aAd 1riI11'libU .sigfll8iIl,f'lg 'lhat prtlllllOlll3()fU growlhi'lilld p r:oml:-~" !1U:1Ql'l,Gilill1'-b\iI!J 1IJI1I11R,~binds ·1tI FKlElP38 (lI'iiDi ~loo'l1(e$th~ r~~~ amdl b O!ctiivarnQfllI@ln,li'O!it it is,l(:'m1:~:~!llQWlil 'i'ril!lltliielrlheSlil imeF<lcl!iCl!ll~ Q~liIr ai tfuie m ita< hood ria,

bu.

I,

bi~I],~18 to a reyi,on ofmTOR ~lm.at<'llprilreillt~.y (r!,;cd<l~;with a!!lOtI~rmTOR oogi(llm.ilalt l'linds to t

.l'ORC]

'by FKBP'J8. FKBPlS

'I:~e PKn.r12-m:pamyclll oOJml;ple~" FKBrI2.-r~pamy.crnpred!ude8 the

Ibil1idil'ilgof FKllP38!o !liJl.110R, I:ikely as a reti'~.u(JIrmlJ!l.Q.m~c(ll'MlpetiiI:~OIIli. ~lU:~ FKB.PI2;~.!.'I])!Iilil~ycin T IUi3!jI'inhibil: mTORC~ 'by "'~ubslii-

~llli.ng' for. .FKHP3:$ ...1,lIl'ere~gr~,. anearll:er study (9) :~dendfl.ed F.KBP38 as p~~Ylng a mlei]ll con~ ~al)Ullin,g ce]] gII.'0'II1I!'1iIl the woomlls by

~lo'we,veI. the ]~nk bellmen nlTOR and .Rhcb c:h.a.cida,ted Iby SOli f!tal. does ra~:~e seme ,qucStitHl:!l. It rCima~n~ unclear how on ~erinemlld~fiOO.1:Iiiioo re-si!dlU;tS)"(7~ H()\~-e\''Cf;, .FK BP] 8amad F.t(B,P I.2~nlrnJl1l1ny(;inil!il.l:ii.bil it! s 'l!7:z~i~,g t~mtlnTO:R b]~ld~ bol]ru to R]1iOb- l1IC~.QIliI"ithFKB'38 (iJSp!ISl)/S cJ~flmete:rinic;5 mTOICI signiding. Rot exa:mp[e:.it~s Gltf~dtoRh(lb tJm,!'!!tis bOli!!'id '1lO Sl.W!!'!O.si~e ,~p~ted of o1!!!l ~:f1:b(:t~r ()if D.~b.FbIr ,cx'~~''!JIIJe, d~b1!m~~:II:(;\:V'l~,~th~~F KBP 12-r.~pl\1!mJ(: in diphosphate (GDP);l:b':i.Ql'OO'll'el!~ theliil{t!(:I' (RihehR:fuiebU\l1,t is bound oo'a OTP al~~ki'ga5sooi.mes caliSe:; the disj;oci~tkil1 ,of the mTORC] GD.') ~iClii..!a[!y bi~d3 better re mrOiR.For ,gt~~ei w~thl;;KBPJS: much 'be,t.t~r~han docosRheb. wmplc;x; Ur01 offiot (l.I). BCle;u~~ FKB p'n 1indi!1iig Pm)lehlS. Sl~~nTP-b O S'i,lch,m; RfI:.; •. (ITP OD~~ \\ihe:rc~s ~ m~lta11itf'011liiI 'of Rheibiha,t C;,'1;n be i50:~!'l:~d f!iQw~ CCU~· tog~l:her "ivitl:! Cllhfl!l:'lCe:l! ~ind.lllg ~o targ,ei:s or"~fliecton;;" Tl~e c;O\mpQuCllls: ofmTO.R::C:I.,. ~t SGe',M:t'l t~fLt doe!;· not blnd to OTP Cc8lro!l1@t:~b:illd. :rKmP38. iIlppm'ent1ype:rverse behav.uar of RI~b sugge:sts These dar~ S;~lgge.S1:edthat fK.B.P38·1fn1~y FKBP3;8 impairs HITCIRCJ s~gmll.lIng with\wrk wi1Thl, .I'~~ru, Ito cOl1itTO~ InTOlRC I.., bur :Ull OllU dis:l'i1)II;ptingtlThisCiomplex, A~so •. FKBP:Jg t~!At Rheb·OTP does Imor Aell Vflile mTO!. Iby direc1!ly billdi~ te it---'.i~1o,thcrl.wrds~ tJl~;at w]r);atw3Y?' ~nlm!iblts the effects of nlTOltC [ tha.1 fflff: selleeal. fot:lllclil1l.ml oveflC:qlr:e.ssillg ~,l.lTOllis net the IJtllJe effi::croin'rorl,~hel:Fm.P. sitive to rmJp~mycin (s~c:h as $6 K l)hQs~).i:lJo~ fKHP38 ~n 'ctd,TIued In!lmlna.Ii;ii11l cells deWtmlf. U:lCTIIi,. is the:wl1ict!onal :mla:triom;,ilIip rY~,i!lti.01ill)'bll,[[ does net ~Ililia:i.bit clo;W:I1Ilst1'f::llm 'Cll-easecli dlC l:l'h,oopllary~<i.tion of~,~IbOSOJnajl pro· to between RIK:b and lliIm:rOIl?'~[ et til. ide:llltn fY ~e]n Sf, l!:inAS(l'(S6K) and 4.E b~Il(i:i:l!I.~ pro~e]n C!i\fCMils ~Ji!I',lt a:re ~Ilsmms;~ut~v,e this djrr~g~ such tliJ,e ffilIr'Oiei~m,fKB.P3~, nrul:oc1iuiml[b.~I, m,en1sites i~ll,4E.~ (4E~llPl),I:\!,1\o well-known tl.l~:getl'lof ;];S tliii,epho!>phC!fylllitllo~m, efeertain IJrtl!l'Iepmrl'.ein,-1l'l <11 direct:b~ld!ing: pil~m,le.rfOJ tIlTO:LtCI. These el:ects 'I'fllm l',e'liimOOiby Bfl (Ill" .~t s UI1Ck':!H why~li!i ~5 so. i 0[[1 FKB.~'J8 and its:cO:lJIlJio~, y Rheb b '0"I.ii6t'Cl'I:pif£'.58~ifi,gRhelt f.KBPlfl: tlliti5 iippe.aifl:i to, i:n11ib~h~1li TOlC I.,3nddlisin'hibitimfl is cWrltet~ ~Xpblill tlm:e ~gll~~ti.rnml afmTORC~:by <'iirtim.o li'hl? il L1~lmris"n th~ nliep~Jtllllml ofl Bioclit~mi:!;try <lold llC,~~ by R.hclb. ryrtal~nTl~,. Rhelbo·O'fP d,$uckhl?' E<lrlier stl!diilet; 8howootoot ,fI]lY;'linQflcid~ M~~.(!Jlm ~icJ~llIJlY, UlliliY'mtt~' dI Britfstl C:oIIl1J:111m.a, 2.350 w~thQurl 'c!t'~a:.'lledlhebifld]~l:g {pJFKBP~ 8 to!li!lOR in proDlote ll1.eb·nlTORi]W~enl.ction Hi!\3ll:1i1 Sdellii!i:edl'illl. Vanwll~er;Briitish (@luliliblill V6T lU, cailadiil, \~tro,T_]"~J'dflgoolb wi~h SMJm. \vhiCh CO!W[.ifl~ altering. 1l\tc ~mOU]il!l 0[' R:h.~ib·(i'f' J). Tile U

R:1:lIeb~bo:lb in a :!:l(;(ie~mi:b:r Pliateitlii~I1.t:en'lcti'O\ns, b,c!J.~t tltvo':hyhf]d. sys;rem )andi:irn ell! !lured m"~lmaliOl:n oe]]s. The anthers slitow tl:mt IfKBP3S b~['gd.~ mTORwithin tliDeoonlplex. 'Il) ml0RCl. They :a~sodtma~tSmoo tlh:i'l!t ~nt(;r~

sc,.~ernsi:!i COIllIp.k:X jpliotcins, ,which 1leg.1Iti'Y\e:~rei:lJl<lite Rhcb ~m mTOR:C.~ (8}.

Hm.

<n.

"} NOVcMBE.R:~007 VOL 3.18 SCliErNICE, 'WYIfIN"solienoomillg,org

PERSPECTIVES
clltlta at Bni er al,~Dldi.cOlI1:e d:i<I'I: ;fJjm~no acid's cliecrea;seihe:fKBP ]&':mTO:RiIli!te:r.lIOI"iO:Ili (uild increase bindjJili!ij of fKBP38. to RliLeh.O'fP. cansistent with fK.13P38iJmlvo]veme'llil in O1I!m~no, acid c:olltfol ()if mTOR.!C L I-I,ow€!ver. cl!e:cre!l;si~jlltlime artJrOimlt IOf FKB,P38in cells d'id lfiu)t rnJirm"Cnt ~be d¥lIDlSp:lmIOry]!},ti:Oil ef 415;-13,'1, :I~!lt: oCJ()~!ilihell C~1l8 a~ ~I~rv~cl,of aMi:rlo
ildel~lt i~c;fJJt ion (lIif FKJ3:P3·8 as ,I regn[ator of
5. ]. )!,o~'LI!h ei.rJ1., Q)j~~ as, 153:6:1{;~OO:~L 6. ~_!,() ntg_Y_ HiI,S. (I rLil-\fl!93, t( ~~ama, 1- il.wlIK:lI, Cm. Bio.l.15, lD\~ (2IDOS). . i. J(. 'lMifLfJ, c.s, Prrnl1lil. ~dli!I9y2~. 3,,6.2 (20M). 91" Ill. [I, Millll'lilrl!}, L (, (,mttt)', l'iiIl!\Ifdj Br«lHll'!lI. £d.2;8,
5!n~:2:(03).

mTUIt Cblv~t~,e-s re.v~o'1[S ~ (,bservatlions abeut sigMl'tIiJ]i:ng events ~n thi spa!h'lllfO!Y, This is good Ilie-wsfor dJe\f,e~oiPi.n.g aItenl!l:ti",-e dlr~gs thar are 1II0t [,i'lpaklg$ totrellit d'i8CI.Ule;;\! that invol,ve mTOH ..,
Rdl'!r,e.nK:ell,
1.~. EI.IE~5tll~, p, ~l,!f~iI~bl~c~. Q\!M",~~'" :251 1643>6 2. ri:. H. ~!!Ie, K.!n~ki, K, lGLla!'l, .!'!i!'!ro'lf.R~~ Phml11.~al. 1 lMalJ. 411, 443 t2,O~t ~. x. 6~1~' ~" 5>!,i~JjI!'~' "~Tn ~H!' ~@iQ~l, ,~, S. 1H~II:!(Jhle;g~,t Lcgg".ii!il!, N, ii!a:I~(eU !ll~.4,,411 I M..
(20·~)_

9. M. ~5!:ter,!{'Ii~r'~.r, Ki!~ta, ~ •.~~!l9~~I~la'!lllr. M. ~ITI. .0. iii. ~11ITi ta,l" (,ejt 1m" l1,~ (;l!OO2!~_ e ][1.,.[.1:3(1111) i!!',:,j" Nat Cd.lBi'tIJ. ,~. 11;!2: (;!OOJl)I, 112" ~:(.!fI'<lnjJ,A. ~ugl~t M, ~Llr(fk'ilm~ 'S. ~m~I:jiJlltil.~, 6. Provd~ ML7l. Cell 8iel. 2!!O, 2S;SS 12:00i~l
D. X. !.J;J'!I!J, $, 'O~ilJ(,lleg,,\ Y. l[1I, l !I\lrI4ll:IQ,J. ~,
'l{l(l,

ffil((i,~20!.

4;r'M(~Oon.

acids:. This t;u:g,g~s~ th~ttb~ Clg!1tr·o] of ~TOR:C~ ~iJJlaHng by 3m~!'iO~cj,(~ does oot
roqui~FICI3PIJ8.
O1!.U

G!~m.

2';l1i~~(~OO'5-~

.AJt:~,ol.:lgh there =:Ul') stH~i.pm.ta:lilit!;lJli'Ps lU. understa1lThcUng Ofili~~.TOR :s~gw;aUng. ~:I!t.e

~JOObll.

C(]tMPUTEIR

S:C~ENeE 5e'!ler.-J'~nM~n:h 1P[()jectrs .:!ife dlosing in on rw,a,y~ to arl~DiI'iihlJrrilanHo I!f'l"ectiwl.y comlflllU.lfIlcMt! wlith ma ~i1iniil!~i n UIatural ~8ingliIjj9@.

Is There P'roglress on Tallkilnlg Sensilbly to Machli;nes,?

. ._ .ca:tc with c.oamp!:.l!lers :ilil ·'m~:lutf.i~'~ lsngl!!age. mUlef tho:mp«l,gr.flm.dlem ~nsymooilic h:~:ng,ua.ge'$ ke PORl'RAN find c'll1th.e U l'960s, M~T researcher Jorepb WC];row'ooM:nfs

s.·.·....pe;or}·k: have f:!Ol~g:lti:W<tYS toCOItli.IP.' ~d;iJ!ili.~. the iI.:rlile.st. ~. s ....of Ootl.llilltUll'o • .. ·.-w."no.e
ri:.

:1I:Y.

imeni\g,ence re8~ltth typic~illlywok .iogic' tQ be t~ lOOiR o:r.,lIIchine ~Ue:U~enQe •.~~ld i,ingllli~ tics was ~tiII :strol1gl,yinf1l!!,;41c~d b)1 NO<llt!] Cl~omskyat Mrr; bOithAl aJnd U~lgl.1!istk~
~s.·q,l!!n~d f~mlt S)lIiL~n sets (lif,[f!)iion11ii:C)rgra~na:r

BLlZA [pirogra1li!lTh~s a!l1 C11t~rtailm,i!1ig slm]Jtlfl',o tLl(lIn I!IR~~ri(l~l thcra]l'isl (.1) .. ELIZA took of words j'lou hOOI aad p.layedlhe. back, as ~:""Ue]]me '7!i'~IYY<l'f~n~e~li.lke thm:!liboul" YOW' f'a.l1Iili~y?·' Itis an ~rony oflil:le lnie'iI"'fuIi5;.lary of" ~,u;tlaIJiniine dialog :pl'ograms tha~ EUZAis rel.IlJilmrn.berod. and .PARRY is l:lOt. PAR:RY ran on the ,early ARPAm,e[ at Stgl~.falrl in ~~e ~ilm ['960s ;[lind lVU de:signu,edby' .Ke:mlCidl Co]b.¥. ,[)

u~oo

iSicluaUytmd ~n~'re!a~ :ua~l 0111l1y ~.fe""l d.~t!! m!lde:~u!pexarlllJ:'l!l.es, ""ibel'e&IO .PA.RRY a:t k~5St had the :Iarge set!:orp!ltt~rns 1JUr1,f1del1ij:l b~ its researchers ATIymm.chrOllllui poii11liledHI'a set

ruies e.·qjl:il!ined ~argc $Ct~ i(lfda:l,l:iilc~"pr~d theorems ov se;'lWteml(les. Bn,n~dOH:r appOOQdl

words gf pm.t~iI:me;U!i!lm'y pt.(loor;::wngB :mparal:Ieil,:Engli,sJi'l,-,f'rc~,lchliext Tmle n1l;c.tliu,od,1",\I;ms Stla ri~-tica'lone thflt '1~lioffl the pW'~~~eltext da:m ..t1iJr!ifltlrM8[alit()n\'i,~~S<Ult '\;l;']!lou1t:crc.1tmg b al':!ly ru]es 3!t~II. 'fhis W2$ O~eftrst .impol'il;'!:ll!t work if! ,~piPIY~!lg ~c~i[!e 'lC:flirf'l~ngto !:i.l!I1,Je:~mlel<~Ild h~sc(}-'\\'ffltkJCl"S WCI,'el1(li1 oOlnph;:reJy $w;;ccs:>tll,l1.~ bIM:t'~liD.eyl.1Qd ~ Sl]CC'e4>S rnl!'e of abcru'~50Ilj!l. ill tra~~d\1!lfngsen-

g1:.lS1gepmce.o.si,ng_

tenees

that lilu~ PIXlgI:!lW.hilldn1t see:1:IJbef~l:e~

m!liG 1:'11'1,\)'main tradiidam. of ~,:e,sil::illrcl,l. o.nbmv io poodm:e machine C0I1'!feI'S!Iitienalists, Bovful sC:.iruoo.i:stake snocf:'fisfl][WO'r.k on speech cogmi::cting.,..vi:th d."lIrn,derived il."Ol:u:l. reeerded CQiI]lveJSalions (often OJl t!iLe pho:~e). :<1!ndseek to d!C'ri\iIC &1RICUI~lI!l!dl1lll~ to

nefie~:dhas nowsei:tierl

psyol.li~tti,st""I,~OW<ll.ltcd tOlllorlcclpilJianoiacs and their he,~Defs2) .. PARRY'\fi!s ( IPllr1'l1il:oid abo.1.J,1: Maf~!1,howsc races, traek bettIJriI,g,. t~,e and hal!~a,11Ir·Amctic<'ll~l!]; ~fittlythring )"00 typed Qould be linlred to them, it weuld :!i(pC'iV out ,1). ~~rfJSf.!'!phofill!lt'!v"eel:iv;e. PARRY w;J:s more fU!lmalfijthc; better~mefit!be:n,;:d ELlZA.~ find] is ,f!!Iii:OllleT ,exanll~'le of the '·"Bela.ax prk!c iph}" (31 PAR~Y was bflsool QllllOlhi~lgtl.l~t CQii.lld be caUeda lI'l¢ol:Y.; ~l:l;\I-~scllI)fCl'~I~.spil:iUo 111m pril1tcilP~~ app:liOm::h rn. s'IIM!dy]uglnacbiM;e, dialog tmJay, l:vhi£h eeuld be callJ)tlI~:ed as 'tlig dil'lm + :s~md]iheQiJ](" ThHll iistPJ\ItRY had it t~nym8itclinil1gpl:og;n!!!In a;llid <Ivery ]ar1,e set of ~,mnd,"Clr.tlfted datlli:. almllli 6000 p<lItrerns itl!Iiecll to :I1IThAu::h ~o WJHlti' ~ ererw:asl)1led tloit ~ ~ In ~Ile-P.A.',RRYIEUZA y,e:llrs. OlLrti'f]c;i,lI]

of possi:b]e: eplies. 'Ihiskind r of an !I\,pl:oa.ch WElS;, aud is, ana:thelilim to Chml1:sky" w]!iJ,Q said that ,da,tfll gtlt1m.eriing is rntlke plJe-G.1I1iicm.lpilysic:s ,1111d can hav'e- no rai:e- infor]iliJ!11.1 linb"ll]stic:s (4). The l.n1tdeilt]yiWjg poobllsnnvi'lh lrUul£h~l.e di.t1i~i~ v~e'l'lredm:i <'I. 1ec11no]g:g;y~ W.ll:S thatprogrum!:ibas~CI Oli!! logic (if ,[i:nfo.rmallifh£.Mi~l~ie~Inars~a!d hI'BJdlittle 5~CCCS~ f'Or l'!1!OFt th<Ull~O Y¢a!f& in
pl."Qduc:ingus:arble OQlllplIl,[i:f1.-

li!IMlilTlRs;e~]mch~ne di,a~~. One,

~!1i;:senroCi
Ste\iC

~yJrose"iudK::r:i1 [~Iw
.a;~

¥'01.Q:i~g

C-ambrid~

Ijlli'\.ef\)il}!:

,a.~unl~lllatt::maclDll'IC
C~1l

lIOni[] mTrif<l!CIS.. A[~ this changed in 19'9'0"

\,\,.]th the asfonish~llg
$IJ[)CCS[l

'.
1(;IQ!iWl!rs:artiil):ii!i!!L '~m,pillllf!iQI!i!•.Vhill

1(.'a~n,gl11c~hod~"ltQm ~~iech
be 1:r;\'!!lne:di ·~o d'lI'(':C[~y~Wi.1hant :irI'terMoointe q,1lIaSt.~hlgUU~ tic; srructures (,6.1,. The secead mUoW'S ilie mll!~e ~le:li.ne.k~aJN.~r ~DQk ,uild tm.ie-sto a.'ooa[IJnu~:ate thosei:i]].glllisllic s~rll.u::tm"ei5 l]l ~ en1J~i:r.ica]]y. lui:l1l4!l; ma.dt~ne
]TIffi:R!lm:agedialo.lg]s ICOIfnilrn.g, r.lIther tiru1'l11 Jilrn,lIkiliill

plXl<cef>siug

;
:J.

lIhe~ut h@Fi~,n Uae' lfk'pa!1l;m~nt ~~ (OIIilPU lu Sdilme, i ~ Unrr".er~~o~ SbemElld" Sh!l!Uitl!lllil51 4 DP. UIK. E'nn,aiI; !5 :rMii~!@da,~I1(:r:J!c.u'ko

O'fF~1!de~-jckJelinek 'S:~;fInl at mBM (j). Origimllly s,peech;o; proces:sing enginemrs '!M)J,~" ing on t:lmJe;all[mnaitJ1.ctf;lIIn~ sc:n.pti.oil1l of speech ~lto ·.,,nt,, ~ei1 lenll, they decided! to apply their datit..dti.VehITKlll ... Od5 tQ lfiIili1clwinc tnnlJ~~,<l,tion,

Naballa!ll' [.iJbbh l~l.H shows the

!!eelfiIi'l9:s: ,a remote selll d~r by of $P'll!l!dl. (.l1ii!1lgI1"'gl 'OO~(lr5, ,and m~\i'in9 Us 'e'iI~5" lIlhe5.pelL'l(h is gieinemated \i'~a al wire le~. lliitennet OHrlli!~(IilOiilI bllm typd' hillill!!t at ~ Wl!;b sIt~,..A:!iill'lilrriliill. llu:illmoatilill

~ fiLlte:~\ils .iiiil,§J.I:itlts itrndiiliotli-

or iii mrnpc li'IiOfl,~e

{mllpiH'ii~ns

~~ydidF). wmmiybcla(.':y~; bu me :mforThollle: lin the rna,tiler

Cil~i!l~\P

m~itl\g

.18

da!ta 2100,

~li

mot]

PJ~ji~(t ~9) ho:!l$ ,ilidi~Pl~ 1N14 ;ilng ~ tlJ re(lC>Qln~z~lXl'ldll .ai~ weU. s 9lNOVEMBER 2007

WW'i'\I'.sdenc:ema9~or'g SCIIENCe:

VOL 318

927

PERSPECTIVES
i:m~:lSClibe spceoh to writre~1Thtel'l!ti:ssmlp1y inS'IJf:l~d:eI1ll 1mtb,e.lmgeJ-task Oifcreatlll~ 3,lmLc:h,lne, ,con'il\e~.'.:>a. tL'Olll<lli:st dml"unde:r"Sbnllds:' f'o.rex1inlijJllc. iW SOlll1em:1Csays. :s;Ol1]!rnilii.Ul~t (]'Onlntdii,ots his Olf !lei,- earlier ~l'tOilJtCtlfiLu:n'l, e:~vmil,ldl ,ex.peel ;0'1 w jJl,~wible ~,~~ch~lle cbm;e~11tion3.1i,s,tlo spot it \,v.itbou.t: sum.:: Slnoc::!:ure 1md ~]le~I1ory., mc\!C'ii'Cf" h it is ~]<tr;dto:liioo 11<",,1.' 1i18ygrtem could check ~1atem~i'!l8 .tIQr oo~hjtetm,~. Om.j:oouiMn~ver 'c'ilpiX'It to '~C<lm '!J) dQthat sl111Ply from daJla.; 'we j:us~do
~[)t ~"l(::'

nmdQin1JJ :wquil"ed~o f1lld:qmatically

dls.!.~.ke:s, C3JiJ'}I mut Web~:[!eia~edl:fls:ksa.ocaru~ ing,]y. and IJjlmml)tre~1~ini:5i!,)ellI0Cs abm~t the' Per:sOlilI'sphato co]l'eotion so as to tmi.M. Up' hi.s, or het ~~fes~ory~Jml\ougi:loom~itSa;ttQn (.1£1), Ik;se'.aJ:'cliiuers!l;ene;rni~:y ;£JJ~e tillii:lt <Ii~thmu~h

~,n1Ll!ch. of~~!~e~ingui:stic a.ndloglcf),l 'cOIm~e~dnlil!t

was ,ulbiund.on<::i!! in ~Il~e 1.990s'? TiIl:a1' might be eloserte wElli[lt O!!J.[[ d\l.liIiI cO'gI:litive SIH"u(:hni(!:,s seem W b(:,.10 illlycliIse,. ~!lllrn.g:ml8)edata will

these l,flmll,1C gU1li]s need :lfWml!eSli.t~l1ctu, speech rocogr!~Hon 1~clmitl;Q~,oSY still not: acc'ur1He is
,enollighro, fbilUi,ld!l reli,lIblc mll(;h~l1e partner ,e3~lbie of 11l1dierntmtl;ding ''i\i'limil: g."Iy,m~k'!8!l it has a ,co~fiii.(];~ra'bh~iii'i10i;~m stored ~(l\l;fl,· ef ,cdgelQ cl1Ia'bh:hro ~ndc:r:li,t!\1!lld; rne:)1;'; rc:ac:~tve 'ch~tbO~8win be no IfglQ:!1C hel:p than ElJZA W'a;S"The C1iJ!j':n;;lltpara.dlgnl s:pl,it, .~!n.f,c&e~!!cb hi, ;abo'Ut haw h: will be :pos[l,iI1i:lic ~D Icapwm snd 5t(!r<e k!liilO\vk:d:gc andh~:ngJMlg,e ec"ipcricncc lU I.Bl'gC enough detail a~md volume te buUd saeh Slss;ist!lrnll:s,outside very s:[I[I[~~~ domains .5'11011. SIS, reoording ;81 c>ompUc3ted pizza order. A [ollg~term ;Bss.i.stalrl.l t:o an astm mlll!.t Oil a voyHge to <lill!)t!rue~.· pIElIlE1,. OJ]"ollie tD hel[lle1dl~ leirily peop]el'ecjov.er tlIl,cir pm'ittil,lli'Qr~.~hC:Oliltver:.. SOl:IiiOj;l1i~idl o~nii;w it in text Iilindiwgcs, ~s ii. mmd:il biltgcrg,oiil,mui: one ~liiIllIItwill require better ~;~,li11clliiilne!ea:m~l1gtechniGl,m:'s tb1U:llnt¥~ beef! d!epk»)'Od ~{]!mr;

'!\,~

mil,c:I·tlia;e~brld W~deWeb fuJifIi!!1, as an ~rK,~pe;crod benefil:dlro~~gh dl~t moms, pro,\'iide.d researchers wilh pOf:eluill]lyinJ1ni'!!J resourees ofd.rum. en hlllll<l!n CG'UlIVefS!I.1imlS •.
feJmfflll:illl, ennal, e W~~z~'ba~nl,r.omlltillJ!l.A(M 9., .~6 (1966]1. :2. K M. Clllil)! ~ oifJ"..'Il,r.q; r~I.;!. 1(19 72:1. m 3,. Til@ ~l:I'F~GlIH!lIM"'~ oot.lhe'lJ,e~i-Il~ thto I~i!' kll'fi'klt wars fOf l1oin~ '!MI~, _di"~ dmirll1ll !:llIll"'1',O~ ,~md l!.9,aOs,''!IIiiS, VoiM m'llli!'1 8fi~r:n;u. <l" 1!Wfi!I.~It.~Llm(Sb.ediJI,~elt'l\1eWi'rnilw:;s1Cholmky %20<1 1I!!f1l'&21l1f1,orgClII%\~~TllIlIldo%I~OTrill'l!l(ripl),pdr 5, Po fi.llrowill el at" '~mp'.lingctfgia lIii6, 19 (1'990). !S" S. 'l(o~llg. J'i!;jM1r 'r'i3~all:ed.at ~I~ II1Ii~rllliltiarn.a1 I Qin,f@r@l1!if! ,o.nSp!lt~1 ,andl ~~~!11~ fT~ ~~fili9\ 16 ~D 21Hepte'i'if!l:!er~aU~, rle~r. 7. If,WilJ<;~ N.IlI'e!Jb. A. ~Inr.l~. HepplJ(,l'L 'ilt~ne.. ilil ~~lIr AMii'('C" mMir~wd ~ang,tl~e Jl'm'if!!ll.r.rrg 11), Ni. t4itlllow. t::. IB~H!ill:Ir,eviI~ G.l\ng~lo:\I'<1\, 1!;./~it~i)\',(dl~. tBEn:~~m;~~,/lrn~n4am, "005.1,, !'Ill'. jJ,11-129. a, liI.tp~fuIDRrnje<il,~ ,~~[fllda!lP:.l 9', ~'!,Wt!lIR;;!l'!iQ.~"l'lf('ji,Ii'(~,Qrn lill 1(, '!\Iil~i. fmwiflmpL 5f.!, ~~; ~(!I.1.45 (,,0051.
ll. Jl

IRl!:fi!reflO!!> "1II!!1Neilii!5.

or heaf '~i!,o1!lih~CJi!!roi!'!CCfl toha~

pIT;o,¥~

otusly C:IliOOt~llt:C!fCdJ aUI'hei:l'll~nsi5,1~lc~e~ tlmat we (':Gi111d spot 'i.nunoo:li8ire:ly, A~ ihc:momClilltj peqple CI~IC~flitcr ma,ohi~e C10n'lJ\el:s:a!tiolla.~ [stili C1n~y :il~!rccre.;;J!l:i(m.$~ c:halt~ bots IOn frtte: Web, or in !kllll~)ile: pNione tl:.!m,sacdO.iills saeh BlS o:Jrliering m:tve:l. lmck!ets. .BUll: ~\'lsea]"Ch S)f!Sl:e:ms:are al:1le1lJdy_lcl:ll:lencr ilIIllU) tilllflit. 3]l,d thenl~l,geofprojeQfS ex~);eCl:edtc dd~:Verusable prntD~pe":s has expanded in n::eeJJliII years; These eJfOim HUlige fim~, tille De-rense Adv<IIll!:jool .Resc'arch Projects As.enCY~B Coy,nwi;!ve A::iflisti:IIIW100.1 Le~ms ~nd Oll1!lIili",e,s project(8)tolhc :E~p'eiin C(;lMrn~sio!l~8 :00,,\' Cml,lp<JWJiotls pr'QJecl (9) to CR'~it:ea 'kmg·tetm

or

QO[J~tional. partoor.q see' the figure}. Su...oha C'(J~]X!1i1l!km '!;l\'(1l][d learn h~I~rSQ!'I'S Eillllt'S and

The crux '(lfthc

Cllnelirtt

teSC1JliC,1iI issue

is

U. ~Y.~lii!bo!!:~O!@,,"~!Il1 U, fhe.alllooF'~ re;e~fth~~pGrn~pe.d :i1t~~!!'hr,opea!!l Q)r;nl'!!i~~iQI'! l1!d~J~(Qlrililt ~'S.]:.IRP·H!l4434 u

[gmpgi'!igrns).

this: WiU a! SUCCe&1llfl]~ lli:;dwnQ~()'gylend lip meroflting Iby means ef a1!U:!:omat~d ]eiilr!'![og

... w~d.emrc obese, ,auld in some westem eeuntries, 11, gTcilter pereemage (2.S% or far rnoire)i:!l atkted, 0). Obe..sity ~ <I, se~]Om'!,·con~ cern IOOc~a1Jn;8e ~til'lcre~se~ 11M;risk of,earug,m~~ C1l1:IO'Ilf di!JC<I!Je~ type 2: dJi,;'l:'liiIeOCls. andserne cancern:, amrulg other h~<iI~tlii, poo!bie~lIil~. hMv"(),Il!T t~on ofpijblic h~Uh ,{)li,e~e:8 ~Jl!d tn;t1;Ufi~nJt {lptiO!Il~ (h-:pellids ~JIQn 1I1J'lJi:mprQ"II'Cd lUl.d!erSif"'!ldi~g of b.Q'\¥ gc!le:~i() <1!.Tl!d C:I'!IVkQlll~~el~taJ fadQrs illt~ract t:o fa:"'Qr~'eiglmt:gai:l1. ailldhmv c'l(ce'ss;ive;: '\.ve:ight d~snrpts lmIiI.eti!'boUsm,B~u g,cUil1l,g 111'Ihe C1;8JUSCS o:fobeshYflud rel,ated lllernJb~~c disordcrs ~s a :fOl"IJllrd/abIJe d1l!d~c.,e. ~Il p~r'tt I:lec$us;e s,lQ mf)~1[Y body :syste•. !i iI.Te .. I:fed:ed, .B!eoolJse di~tu~t!@IIlOe-:sin ol'le'mgEln or t:isslte IcaIilJCl()Jllpll!.'nn~I1:'me: fmX::hOliI 'of" seJve~3i otJilel,'S. se;pmllting ,calUse;f1D](I l"ect ~s oi.ea d~f'" e filcull:. Yet oQmmtmtl,lemes~~'e elne[,~~lg tll<'It
The <l9IhQ~5are inlh~ DHiJlI~r1milnt of ,~\.i!d'kiJlOil.IHI~r_v,j,~ ME'I!!Iica!CII!nltlr ~nd~run~ver5ily or WasmirlgiiOgIj,'5!e\aWle, WA.
9Sl.o4, IIJSA. E.·mifi~ iilisdJwa!t@i.Ii!'la1!hili![ltoMCi!

.. T

(Q!!'I! pari ~onl"l of res:po n~es; ,of IfEllrrijou5 celli ty~e:s. to e.:«e~:lIlu1:iriel:lt:s,:n)~ y'ieM~ pa:ttelrilils th at fig In:iI.y IProvidle iru,lght llilto tine ILCI:U~es<'Inid cens eq ue rrme!iO.of OI:II'~5i[y.

·'.he' WClI'M ll:etlUh O~rga;n~z;['IIti:on e-stlli~ mares that al ~e1'l::it l in ~[I ;adulls,1.,!iQrld~

liil~;«jy

ol"er 11:uiLCW v~eWp()iil1lll. Amoug tbes(;l'i s dlle notiem tluJlIrt~.uetab(l~[c diY3ifu!ncti.o:n arises IiimJlilm. 'xpowre of the body'S (1dlls tD U, e'xces:s e oflmtrie~iilts (2),." A pOSlsibk: exle;liIlsiOitl ofthi's view is th<l~ .1I]thol~ghthe cellnlar cense-

q~~cli1Jees ofmiw]e;rU

diverse ccU typcs~tili1JesllID1'ln~dI'li11.tll.Jre ,of the l!f!d~rly]~'!g c)e~I1!llar fCl:\P0rnle<$ can rae 6b~cu:rod by tll~ oompr~xjty 'ofth~ events i!Jl~eynWate. i In '~his Hgh~. $uc,ce:.Ssful~d~l1tifi,(;atio!l:! Qf sh~!Jed ccUu~r "e~polls~~!a~ ll!ndcr~ic:;;du~~~ mquircs ,~bl)oo.dal'ldi,~ie'grat~Ve :;'!.I~ronc:h Ullat ~~,a)i u~.tim~tel.y I:e\'lleal :1fI0l'C ,clfcGd\IC dbesity ttefl!tl"llii(.]m~: slmtcgies, Flmd!muental~o u~l.de]rstm~Jdling obe:s~~'i s tbe fiJd ~Ji!lrut. !body teul[pe~1itl1!~Mdy fat ]i~e !Wi:l:l'res <11'1:'(m:lillnlllri~y MEli:l1lrnilrned.w~.tIin:iIl a Ilafi" mw r.mm.ge tirullr:m!.'lJl <I process, ca.Hed '~euf:~Y ~rn!o:meos;trasis:' Tlrn,is pmces:s il'lvol'V1es IIlr<l[1l ~Jieas,that ciontrol iliP]):!l:i~e aJl.ldi e'l'Ier-gy liiImlem.b~ ]i:sl.l.1, .<IS v;o-e,lI !lS slWl,llll]slilmt cirol(Jl:ateHl~!ilIJ.
out'llrne body.'e:o:i1Iiv~]l1g ;i~ltbr:lii;lmioo ~bm]t t:1ine &i,lnu!> ofhodyt1ul;l~ 8t:oJf,,"fi. ,AmO:Jlig fie I.,~ <ilirc

(;l7J:ceSrfJ ~re s~mila!rilC'fQgg

~"lIlily a.cids,JlIlldhooll,lOOOS. 5uGh a:siMlsltlin ~nd neummi, hillthe hypothidaJlnllJS ,amd. othe'.f hrnon <lrellS sense these f.1ldarsmIild crn],ooi bath mc,'!:abolic rate and the dc-~]re to e!ltWhen cili(i~da1.ili1g CjrnloCliiltrotrolli~ ,oHh!3!sCsignals d(;cru~e dll~e:~O \ve~g~t less, 'too drive to eali[lote~s !lnd energycX;jJCrdi-, tl]r'~ ded~ri~s.f1.lViOrit1:g the reomtCry o~ d!!;pl,(Jtt;d fil!Je~ !:ifI.~iiCS. C(l!lt:~ly.\:iI'l~e!lfugd is. {~Q!Ii1ils'1,U1tIiled in ,fljIl101\illnb: ~hat exceed e:~IL;:rgy fCq>uireln{'-r!lls, the ,d~·~~l,aH!lg c(l(!1Icef!~ra~iO':(lJil· ,oHhese sl~a]s [Il(mcasc:. In fMs w~y~.ho!mCostm;lic respons:c IUcc~iHI!nisms; i,n d'n,e brai:11I are :p~i:Seld 10 ~:(l~t t~~.ebody ~g.aJnst C:ha~~g.eii:in fall s,t:ares I(U :;wi:l'Ig~ in IlUmr.lerut a,m:~]abmty. Thll~,.obesity does HQl s,i]1llpliy.':Illsenrmrrn. the: passi.vc acclUlmlll1lti.an af ~:llJaess\:vagRn; nniIlm:, it i:nvolve:S tJm.cacl1ve de,fenSie of 3;n e:leva:ted Ilevel oiTboo:y !fat. tl!nd deca:pbelang the- cm~ses. 'of olJesil;:t s:ho.u]d] take- tlili,s,iIllto ar:CjOllil'lt
I:epti]i(j .(J}. Spe;c:[alit:led eerttl[nly.ilildruv]d~<I]ge]i(,eticmake1m:pliliLlIY ,e:Oiimltriilmteto Vii]"I<l:tiJoilsiifl t~.lecii,lIcity
00'

mo~nt the~'C ire~:pon~~. and, m<JY e;xp:~;}i:n why

!f!l!trie:li!!!t~than!ji;;Irt8., &lJ,cha5 g11!!:oo!selJ!!dt~-e <

VOL 3.18 SCliEI'NICE,

8()m~p!!Jopk: are ~oie>ci.ed a,gai:~t\~ight grdn

"} NOVcMBE.R :~007

'IoVYII"IN"solienoomillg,org

PERSPECTIVES
:inthe sa~,l,le I:il. addition tl) reglda.ting lmmdem 1!tti.l.i.lil.~ e.1ItIDng~]e :iOailii,le food •. tian in Pel<'~I)]u.eJr<llliss.1!!Les. n~~·p13.K si,~lm[~ng \Vhell enejl];yinl:ake eJtJooOOis ,mlI.eI1ID' expelle I.S ;fI[OO impli.cared ]u the EU.eu.nJlfiIl[l] i1Lct~O!l1lIS of cliitnre, dK~ reslli~,tilllS st<lte ofm.ilfll'iellill e.;1{c~s.C:~[1 iIlSU[~l ailiil:dl~ept]nU). As~nperipl'!eiml tiSSllCS. theinteg.rity ofnel.lfo:nal. W_[\t3~:P.llK si,gr..ahng 'mgb'Crresponsesm li!!liklW1,Y cell ~;s--,l3I!Ildo;th;elill] cells. (l>I~cu~a:r) {4), hep~tocyres 'Oi.ver) (2). can be uliilc]erm~glod by uutrient e'l'i:lce:S!5(n. S,tud~cs. ili!l. rQc:lellilt modei.gi]1J:tHc<'l!te UgM e:WI1 .yo~e!j (Itll~ele) <J.d~pocyros (5)~ (m.t) (1)\ iUlld Mot'!O{.yte8ar li!IriIf.lcrOP~1fig~(UTIlnwn~ .ce~~s}- s11,ort-terM eN:p-o:sllre: to a ~i.gh]YPiii~iJ.ulb[e, !~~t cuuldgive rise to 1i1111Ctti!b~lic d)ll5I:'urictton. 'Cl1crgy-de~se diet i~uiP~~!n;lhe brai~'s, Amo~g ~~f(;t'<il.~d~~ o~UiiJlm:'" ru:gp(j(jlj_~IijS tQ OO~pO!:l~~ :1:0 i!:isuli:i1!a~d l(lj:lI~iJii.ij~dfiil:d,j;JJO(ld w!,IJlrie.nt excess. i~~11eprodit'tcti(ll!'l 'QlI·[,cact:i'lil"C ~RS-PI.:H{ $~~.a![~ng ~~. be a:m~llgs ec¥crnl O:1Il.jlgenspe>cue·s., T~lr;:&ef:'ll.()lecu~e(5are~C'ller,fltOO Il'Iooha:lllSms;res:pmlS!ibk: :for IleunmOl1II:~$h';tdirul'ing fuc~ (e·\!!!". glnc(l!se or freetil"'aluy RC:[Id!S.) Qlddnt]on ~y ~uil:miho:liitdria. !Imid motal.:mllc [~l1Ocesscsdsew~.ere 11:l. (!e~tbccst'i:ive :Pl'~ the dIlruchon of 'dle!£'e mQ.!e~'I.I.h:!; c:re!ltes"m::.]dat~¥e sllrre:ss:' which calili damage cel.llI~r s.·b"l,K:fI:~re:!l Sind trigger an. inl]:\I.!mILmatiOry re:li.:pcmse· (1). hI some lIeDIs, nllt:liont'e>i:.cc'SiS ~~SO inumpai:rs. ru.lllctioimIing crfthe: cndQ'p[ ....gnllcl:eticn~ I.~m (which processes ueiw~y :S)1nt.he~ ",~ecl pro.teil.1smro thei:r irnIturei.limll, gi:V~1g rise to the "Y!rdbld;~dprol~ill :re~on:lile"i~l, this o~.~~.e[~e. Likereae~ive ooygcWils~ci~s. ~:hii!)ro!lp<:ll!ilOO C.ai!l i~,dl!c"(; :~I~na!!n~':t!t~~~ll. third oe]]uJ.i'!!f A re~t)~l,~cro ~li,1!lirie!lJt exeessis the aecullwH.:!bnl:of! o-UQng·-chain fllUy 1.1.(")11 COC!1~ymi;,': All.lOk'.C:u~e$t f'3!Uy 8!Ckl derivo:a:ti:\re!;'i; ~:llllil,ti~ om'illali[y ~idl~ed by ~~~irochl1l11idda I~:ogener~te iI.de'JiI.o$IlC 5' -mipllOi>phme (\vhuch [pmve:trl;i lllwny De!!~~hJ:r :I)1:ooess;(';S~ MiSJldmg ~~Ult~ ters "'~Ol'se" Is ;tI d!ec:reas:e Clf·lruitocl]Olldria.~ ;tIcliv~· i~iil1ille:s;ponse:to nut:ri.ent excess ..This creates.a "i:ciiOUS: cy(,;le by flll:ll:her .m.isl~.lgthe OOll,{le:lililra· ance 110 ~ml!ese ]u,onm}l1es (/.8). H.B'I;'lng lost I.ts tion of~l~~emty acid d::::rivalives (3) .. :B31;hQflhese weS[I}OiISCS. s~im~ the 110iliity 10 f1bilityoo, dettct an oilll~giiEUi& ]IlCf·eiilsc [11 !body <licttiw1le sugnali]1Jg: patibiloVlilYS (such ~:hl the o.JmI fatstOrnc5, the I:Jm~n OOeJiillmg!y does mlothim'l; to derends whatn N4CrnIliinallcirulsc, ud the inhibitofOt'k.1II:n;pll B ,[;01!LIIIter it RtheJl:, itlldi.ve,ly peroe.ivles to be a. smble,.mJlchal1~ililg a.,omU kim.S\: beta:-,nudear ftll::wr M:ppli. II pathw:nYiii) (2. 4-6) ~lm.al~m(Jileirlf1.<oo;m1n:iOn. Thus. lofbody fliit (9)10 ~lMS., amprured .1RS,-·r'ml Ksig ..· n1.llilffig in ~1rn.e 11y:pothOl.llIm~$. w~.1iIy be a faetor i.JiI!11a!m[11ilt~Oll'l ~PP'~:rsto ~e <I. COl'U.lIWI.OIl endpoint. W1i1I! inflali!ilm11.11iol1 (:,1:111 limit fu:n:1l.elf lhlllt c4ontri.bll!te;s to the d(;;felil'se: of elevated turu, ~xupoollr,eio ~l1!Il!i~Tilt8by blocliI'jSlhi')i11d~~jljJ ~f booy ""'C'i~t :I!!!'Idh!::!1cC to ~OInti~l!.!iOO e5l.pDNl!re iilii,guli~l(2,. 5), 'tile hQ:l"!mll()jle~:uu ~illllt.dm(i~ mili"- to Iiii\l!lrie'liirt e:X:(,'.CSili (3). g]G1 ,ecll~tgUij:kt;:.u;p i~lfie~ts. ~!~~.!Cpl'iOiii:~ M~g.ht si_il:aJ!' ce]'luh.U" ref>p,om;~li\ to p:lla~dyl.inQ$itall-Ol!llkmflj;e (pIJK)nf1lPart Qf.fl nutrient ,e xocssc Cluti!:iU biUite t:o ~'he linlk. ceIl si.guaMllg pathway [jihe ~u:suU:m11eceptor r between obes]ty mm.dItY~::H~: :2 dhibete;s? If in fl;EIJ Inlmui Qllandrednce!d~RS-f13K. s ig~ :5u!bSlmte (IRS)-fBK pa.t:oolway] ~:Ht ~!le.d.i.~~s inslLIllIn aClion muil is. [p.articn[arItYsr:msHove III ndullg we~cc ml'som OCCUI: [n p!llrn.cr:!e!lt'ic il1ladlli'V:ail:ion by .n1ecul!e5 tliiIait pruInote hdll!lJ~ ce:l1s (wl1.:ich prodlllceillsulill). as hfls. hem] suggestod {,6)1., im.pBl.i.rcd ~lls1ill.li~m.:Se!:cre.. :mHilion, Ernm t~lle pEnp:cti'Ve olf :rr:ni:oo:ividUBill ceU.lh~$pn)itecti'\>'e :reslPm"l:Se'_-insum~nres.isr~ li!0I.1'-:W.I.dch ,wlrnlen comb:iinedi w:ithi:n1l:suli ~;l ~n(l!ll-'.m<Jilk:es :semsein th<llt irt liUllltsmrthmr res:i :sta.liIcc"I'eads to type: 2: d]3i:1ete:s-ooul d :rlilutrlleo];u upHII,&;je. With CQIIIllImJ.cd n1!!Ltrient ex~ re suit, bec,ulse: ntS~:p .i.3 K si:;liIrlI ~~ng: ItS oe:ss, hmve,Viet. Jilei~i]rubG1!,~gl'g ,eeHs :mind cIDis.t.1iint ,es::;e:rlItiafoHhe siIiiI:fviwl of U:liese ec~~s (6).. ] 11ruis COimlCe'pl: e~te:l1ds"'the .~,ce]] e'Kh.1ms,·, :~·i:SSILle-s. tM.~reJ;1.l"liilrn. i'l1l'ltllUn Slel~5iti\'e<ll'"eplilced tilt gNi.itet t.iisk. As ili~U:]~~,Iie:!;ist,ltIccpto.goo:sses lion" hyporl:l.es~s (to). 'whi ch stall(,:s th u iflHa.ITIl1lilitiofl '\~i!Jnlrm!ii. a y~ci:oo£; ~"Y(ot(;;CIill type:2 di<l!bC'W!:i l!~yrutswh e:f1pflmgCr(Hllt~c ~. C\'~lveil::i <l,ddu~iQmd Inu-ml,.llmilmi.ltoly t'aIt.1Q;r::! ice!]::; c'l.n no longer ~Meet the hei.glltcm:d a;1l; fecrWlOO by ~.frg~8!~d;;Cil~(.2).. dem01litl!d fori:!'!su~it! 8IecrethH'lIimpQ~(ld by
cmrirlOmnentmJdi

while ot:he~1ii lIIot.dc-s~'l'ite.li\'~ng ~lie

~nsuU.l1Il 111::5stance, i

Til us, oe·~rn ll[ur

e ense

quences

of nnitri.en~ ex cess sim ihut 001

thQ 6C

~mm

t:hilt~mp~ir[he fllm;ti on of othelf t~ssues c;ot1ikipotenti.~ 1.I:y (lonlribU!te to the I.ink between ]11:SLllinresistence .1IIld~~,ce]~ dy:s~ tUllctiJoni:rl di~1befle.spalt~.10ge.lIjtesi'!'L. Nutriel'11 exeess ~.w ~1~ ·(_lel~Dlio1ins 'effucts on 'i,~e1j.dard~~.A nl.'!!jor fu~et:ionofoodo~lr;;]s: eells t~W,tline IJb.loodvesrels ~sto 1!;.~~ero·teIDiid release ~~tri,~O}(ide, ~ v<i~ooiia~l)r. The: IRSPI3K sign~I~'!\'g ~d:nvayis IIkey d:clerm~lmlf~of llitriC (.'fl(~dc r!roducti.olJii, !I:I1id. ,ashl.Q~~cr ti5SU~, Illluri.mlr1: excess m:pud.lyhm.dnaes enJdo~'futeU;fl~, ~llfimmmatiOl~, ~'ITh :respO~l);ej Inoth e;rlidoJI:~e:li:8J~ IRS.PBK mgn<ll:ing and nitri,c O"xid'e ge:ne::r.:utio:l1 arei:unhi'if>irecli ( 4).·fhus ..iile:.l1el>ponse Qf"~~e'!;1m;: .. millatim:,e 1:0 nutrient: excess isremi:lliiil(le~rnt ef that ebserved In othe·Y tissues, <Il1il.doffulCsfI pJ\tu!>iblelink ~nveen nlJlrieml e:l!.C~ffiild cmtillio'Y\asc~lar dUseMe.
I[ammon

t:hrea,di'i.CeUilIlar

r~~orli~~ to

f!U1m'll!iit (l'iJl!;(l'~S. ,~J"lil w>~red

.il!:ros:smIiiY diff'EMemt lU ~yp~s. iii nd Im~ h a.ve (1(I1lil·mo~ O ~M~a'iillts thal~ar:e c~l[fpl~cIM !he dev,elllp(!~ (!obit1s;ity

m.~nil:

,~!'I;d ~:I;s m~ilbQ~,i(

(~:"'S<~-

QllIIlllll()aS. lEft QndopLasmlk rotil::u:tlllm.

C~e~dy. impairt.~. [RS~'HK lS~gJm~[ing.isllrO!t the ~in~,]e k~y to l~m:lerst:llld:i'lilg o!Jb.e s.itym,1d its IOOIu;e1l11rltClrlce$. R~t~lel:th.~i> de fCc~:]:~ hl!Olrm;tes hm'lf ~Ohl~.pl.ex. m~ll~fest~t~OliM;; Ofl1i~,Nabo~ru.c di·se.'1se COTn.:J!d a:rise from responses that are shared. aai"oiSsIlUiliny d~ffeil""' eTIIl QeUrw:>es(~ee ~lfa.efig[J!re}. ~]Th adid!ilro1l1i. to l'ese<IJ'cll,that fbcuseson one ()'lil:',<IU !~ltiii,ys:io~ 'or ]o\l1i.c,d system to the r,:!x,c]usi:on of ethers, m.O\Teilm~eg;mtj'i.~e arpproa:ches for :stlldyillill '~net~bolic disease ~lltllyldtiUmatdy infbrm SITlil!l·e:giesaimed at p:revc~l1Iil:in.g Oll ~'"C'VienJ;i]iJ1 ()bc~ity ~tldits
SCiC]LICI.<"lo.

n.~

RJe:fll:Jfefl(e!i.aniJl ~iW!i 1.. C. L, ~enl'ellll~ J:4M:It 2'!ii. '.lS49 i)'21106j1. 2. G. 5. Ii.Dt~mi~il!lit Il4/we 444, SMH2mo61'. ]., tt I:U1lii~'e~~r, ILl.G.IBO!iI;;in,r~JN.5dl!.... r)t~~. ar~ f~~M~ Mg,t~ll!~ 3:~ ~~OO~l. ol" F.IK~m.8l!·al ,./JtiFm!J!:~:rhttJmh. wr._ ~[ .~SJ'009'
'[2()m.s~.

S. 13,B:.LliIi'ii!U, (;.1. Slltlllj[!~ii1d'ai1~~ 30". 3~ '(20(15)1. 6. C D. f!I!MI!d~~ Sc:ietl{e 31017,. lao ~t"OOIJl. ,. rC. T. [)e5W~ ef d., fmll:luinol~9.11 M6. 41\l2
[2Q~),

a!oo

8:, H_,Mi!iI~be",l~UII~IT. :Bjqii;!:iel':, f!1ilQ(i~ltJ9Y (. 1~S,.4 EB!lI(2:01J;!l}. 9. it 1t.ILeiolin.iI.fic (jllm·.tlkot!l@~, Am. j ..ih}'flo.l'. kI1gu1. J InI~1': (Mllll. P~fi.oli18a. R46 (2000t :MI .. ~s,. 11IiDjaldiTl.,N ...mgl, J,.~ 32;8" 1,2:1.7' ~l~ag'J. 1 ::Ill... Will'~ckfllllWledge'~!Jp!Pl!rUf(lm filtH ~rill1~~lJ)IK ~ 06a384, IDK1,23il'.l'.NS322:~·,. ![iIK6U84I.!O!rni! [)t~7:l:~,i6 "1~gi~PI.!!UI O!~~~~~~~PQII~ ~l~ ~ Fl~~~t(i!1 Q:~~:e~ allullClitlirallll4llftfilLMI ~.l<e<ar~mni!at 'iJ1~ 1J.!lMil'l:lf.~ W
(If!ll'a~Iti~I19~om.

WW'i'\I'.sdenc:emagr~or'g SCIIENCe:

VOL 318

9 [NOVEMBER :2.007

_V _W
expressi!:tg
mlict"
hali!i&t'ef

Pw:P .~.

~!]t~ke wi Icl)~pe

A G'8'n'8~ral IM,odal of P'rionl ,Strain:s and Their Pallhlogeni,c:iily

.~rh:'l'~$a~ 1~1i!1 !'ii'Iamf!ljalli~fi pmO!li!ID~ oom;~os~dl (1f ~g)!J'~~gtOOC:OOIr)(ifma~cm~11is4)m;!iif$~i ;QI 1~,(iIS!t~!liood~dIyoo~~. 9 QI~dwhlkh ,!j!j:ipei1irWtic~ i1udekadds. i'helr uillique b]:ologry, @Ujedlwith thill IPlillDlic·h;E!'a'~'1hmIG pnS@d iil~gJl'I1olilm.ono:s@s ru~h al!i OOVillle SiPcmgif,ol1illl@liNleph"lopalJy;. hill:s:roc:used
IlfI1u:ch!1Jibnt1i!oo onl~llIe Il!IOmetlJl]a:r basis of priOIil pr,op.1l!jI8iliikm illl1dthe ~!ipedes:bi1Irlniel' tl1:at cootJ'oms: IcrooS.'1PE!~€li tramililYissiG!lI. IB!l'Ih arei1'tiim.ately Inl!il~lto IliIlildElr~li!ll1ding how muttiJie p.riOrl ":sitraJil1-5" are enmdelii bya I~BiIil·ol'll.y algentL Ttine 'I!Indem~¥liIgll:ll'ledhani~s; i'iire dei1llm~ of mlLu:hlillilide~ ~nilpomli!c~ (,III"Id,anat:ogOl.l$ p~lEtl4Iila:o;edl ~liIhil'!ri~~UilC~lIIiIedIn3M1'i!:rmare 1~!lgli!jiU!dl ~1'iI y~s.t and f!!lll1g,;I. Re,pern gld~~I)~, ~grJ~st th~t priOM, "~!i'Ii!s~I'!!',e-sare not dlif,~dly fiI~!JlJiiO'll):lI:k~. rallie'r'thl1!lr bu,t P!i(I!p.a{j!i!!,tijOIii i!li\icl~s IProductionl of ~~iC S:P!ld~s:.wh~(h lil!ilQtV I[i!l: Y!li(lil:Il!p!,~r:"~mlnf~ty',

h~gb~,ySUSoepiliMe to Sc23 7 IW1M.t~r Ilnof]S {J6), lhot spomdic; Gl1dnClql!lirocli em m.oslily ooeur!! til iJOdi.vidu..<illilIIDlfilO.zygoUIS at ~llyJOlrpkic resid'i!I\'l ~ 29' of PiltP ;sup;pol1l;S Ihe vi~,",,,, lI~l pri(l~ pl'Opa~I.iO:I!1.Prcoc~ct<: m:Q~t ~lie~~:llily\l.i'hcl~ 1ffiI~ i!Ill~iaclin& frpS~ .mtW :~ are Qfide~tical prim<l!}"sLroclu:ue (3, li. #1). lH,owe'!;'cr, p!iQlIsttrutri 'iype .ails!.')! .~ff~iJD:!I e·a._~of 1m,lw'l1l~~i.ikm to rulOther. spi2>eles. 1l1is :is.').tI;e '\!IISS brought iililw sJ:~ room;: by (ill;) b~11mvlolio:fd.w; I~Y p:ii:lQrIIslm.llll'l.rosponsilJle. fOl'canhll ]]SE~ fiis ~trnimi~: I~ig!:dyproll1i~UlllDS; '1t:l!!1:s~itmil1l:g !IfI~ ci~!l!ilYI(l it ran~¢·of ~ie.<:.oo~ IllainWu!i~ il~

biolg~caiI

dlaraClt~ics

!~lIPa.I~~e doo~~1fiJ

<'II'!

'LW.:·.d.'~!.Y~.onp._ .' .•. ..00.'. :. _.. ~.pro -.• .. -.1 .... J.~i.liL. {l)j m'l ~m!lliW :~!)rUrnl f.lm~"iC1'I'Q-oded, oelhJlillar priOl~ pmlein (1).rf0)is d;lC ~ril'dpal,. and possiMy tiDe sole OlJ1lSlnAl11c;nl ofdle bIlIJlSI!Uli,:ssib~epriolil (2~, Itis ~lroPOIlOO.d:tat dl:ll!>iirofQ;I1f1:], 1ICfr.i! as a I~emp~.al~ I1Irlil ~wmotes Ith~ !DQJ:'I\-'elSioll of p~ I!O PrP'-~ and d~IU tl~~difllo.rellce i:l(lI\'IOO!! !:h~1i;
my" h.~U~
I~O. '.ti!.'- ... ~
•..

oro..d.: 'l~..g.... r .-

i8(lf,oot'!!s~i~ p])Q\~Uy ii'll

It!on andhs Slate of aggreg:al:iOlJl. The Wttm);!'D. prio:n dis~ sRdl as C'OCYlZfdtdt~ J!ikob disease (eJO), 'CoB]] arise sporad iOlilUy, bo acq-UillJ';(,'t! byifiJlredioll, or ~6 i.ll\ltllitOO. >8L."l ainosaol dOl1J.llnaril oondlill.O:lt$ CtllJ1SiOOby mutal'1icm (i!·f llI1L'lgelil.e ellCiooing .~rrP(' ,($), HI!I1'tI!I31'1~('m

ill-~·If!p[1om~ .~:lf{JIlIb!:a~

dis~,,~
OC(i~

::tIDe.~~ilIII~,,'eiy

mme,. lIhh{lJililtlih. they ilia:v~

:~,~qlicre.'ll[~ :rOlilUas a fe-suit. of endo-

cllinr~i~<ltisllH in r~-nt Ihi:slDMyin hpua,lN"ew GUiilllC!!L, and pr:evio1lL~e'p'ld~lni.cs Hiliay ~lmi'll\e ec-

(~Il!I:d 2(0)h;'ll1 loo~ .m'll~nv-e~yn:lO-d~"fi. kt.-ytiln~r:m:i.!'Il.i~ e :1i!_()lalJ;JlyvI/rm ~. I~O g[)ifir..mc e:Wlj~1£ oni!1l.cubJci:cm ~odI,OJiUi!ed, l:l.~O~ifI~-C\?o':[de*iread pqpuliiiutkn '~'(pGsrn:t, stJJgge~slllle need fjJl"'Ciltl~ion '(8),Pri,oa iJ][ocliom iSM!>OC~aled! \!ci~l p:m~OOl.gcdl. diniCl.'lU;y slliel:ilim.~u'balfio:n,pcrioo.s •. \l!,ihjch till 1m· mans (lim ,e:,"I!ceOO. 50 years (9), end SOOOf~dary lr~smiOO:!OIil of vCJD !Dry bbld.!roIlSfll$iOOl ap'~ 00k ():fli.c;~ut (10). . P:r!Q!!!S ba'il\eEl~ia!Sswned!llych wider relevaneein l:tl!lciers!ElJldlillng ncl!rodegcn_cmt~ve and 1()t!~QIi ,dll:sC85C~S imvo~vjug a~oliJm.~huiOOtl. misof ~'o1doo. hO:;lpro~(l:tilsr1Poot(l:!I~-foknfiJgdJ~~~'), ,iilJli'Id an8!!ogotl>li ~es .are d:s,$criibedifiiJ ycas~ im fungi •.CenlJ:'al to n-Il~nd~ng [!fiOIil prq.mg1lilioill. 11!I;';]i[l!:]!lniii!fib OC}1fImi'dn;rl!l:l orpciOil slmulil.$,..... how ~!'lro~'eW! .gjlly :tl1lfecuolus: .asCJ!ll 'C;]H encode h~oonmltiQnr:cql!limdl to speci:5' ·dlJistiflCl disease

tiIDlDCI']lnooj,ne!\'j~e-li wmn.~ dislliucit :P,d?iN,~n~lill}' s:lruclure (NJ) (Fig, IC)., P!edml15 the m;Qlll str~lkhl!!:l 'lli,{8!~lplle of Illis canue frol1nIIrM!sIl~jssiicm. stu:d~lli.l 0 firl!il.'[ii):tU_~ p:ri(m d1~:oos, TfammLwon. of CijUiSLca! C!I:O p.l'icn,<;: to m!!1velt~GollaL mic£ L"

diiffkl,lH er fa~b.,w,l!~8 lralfli':iEl,~[lic!itIi'~e ! e1'!pressing, IIl!lU.li>Ul (and nat nlO1JSe)PrP' (lml}O pll'te'!y luck [I gp,ecie5 bam (6, ltl). However,
despilie ~"1fi'\I'i.n'll, ii.lPi[P primMI}' Lhot of jhe cln&>Lrnl em pdOlti!t" Ih'IL~Iit:ntIfBUJIch morcreadily to "".i idl<l'Ype Ilruice, whl)~ 'm:l1llii-nll~~C):I'IW hllUll!ia.~itlfficl! mice ls il1e:lIi.C,i~liIt(6), T~);!'(!I $I!~lt~, mJ1fOpmgaJl·OO. d.~(!: [11. S<![II1C host :mlly lbus L~¥e oonlJ~'lere~y diff-Crolill battier.; IDiOa1JlO'lI~Ci slXlcies;"lrnllslllisslOm '00rri~ cor" ma, thus be OIi.m.ore approprime tCRIIl (5]'. vCJDprhJ!I~.

stn1<::wre kleJlli.CIlllo

Pmill

11S;~liitIi!5,~5~iil:liWl'~, iII!d i1'YI~i!l:!i; a

'iN ere

MIl~IDipll'" d:~Sl~.ltCl~~raim.$ oiF sernp~e

phellotyp~an<:!8ilso

In hUiI''I8I~avolutkm (4). Antumlpiioo d1.~es lIlcludc ood'clllilic:s<:~re Q·f ~oop ;:md. gooi$" cllrpnic w.a.~illflg di~ (If elk: and dOOr,::tUlcli iran_~ll!iS!lilb~(;l iIfI.lil:lik. ~"1.~pil!aclIncl

ibamercrr~ct

liw S(N.'a:U;OO, species

~Qp<ilhy rrME),[3ov~ne ,sIPQ!~gtth'!ln IilrweplmlQp~"'Y (OSE) firsl: [lptlmred J~llhe u.~u~ed, King,dbm i~dw lmli~~,98Osfllldi ;m))'id ly ,e¥(!~v,ed,oa ~liljor t c:p:izQolic es:u.m.at~dI tolml,'eifI1r~cteOi more lila,1lI 2: f:'l'l~I~.m~ ~.lJtb, BSE 1Ja!;slinoo 00e1ilJ ~rmd UIR

h. is hypol:h~i2~d d~a[ I:'lriollS are se'U'~p{lgai~h~, fibrUlar or anlY!oid fOlll')S (Iii:' .NP in whid~ Ihe ends (If ~'1~PrcOiF,i!(li£~~ingl'!bril$ c~m5tl~~ll;iILe inlkclk~l1.S<enUty i!!K! ~~e e~IXlH""l' lial :risein ji)iriOl1 dler .iis: <I, ocmseql!lience of fitel" thL£n1ellJtatiol~ (:r-~IA) (1.1-.11).,
111il'i!

il~c~udjmgmO$l~f{lpmam 1illl~lJn;U!:d~~. Omda, ru1d1Japfil1, MailY new a!1l1liiil"~ 'priOIa diseases Ilave ;stnCle beetl ickn1i~edI, 'lUI~ fes!JJl~irn£:fro:lll ~nrCJ:lH'On wi~h,
1li1i.3nymUl1Jm~

foom.

S,pedes B.i:lrllfmll:r iCiOliltl!ipt Tl:rmsIlIIi.~f'l o~'priOI!l diseas~ betw~11. d:tlTj;rol.r~. ~~l'!l¢,i~h.'1$

!~rypi.~lly inarrh~~ ,~ffici~.,~t . d'lOUlwi'U~iu~ spe;;ies; ~his is kn~ Wl1 ~~e ''species barrier" (.JS)'. O:~ hi,t1b~ [)~ge o:fprim'ls: &On] ~i~ Aw species :13, ly:p1"~lly !'lolEliUinocu" lamed animals of ~ies,:B slmclImib1mldi d,l~ d:ial do go, haj{e; i:l'nll!lcl'l. 10000.gera1ilcl: inom 'variable ifl.ci:L'bl~ttQi:'ipM<nd."l 'dian .soon wid) ti'ai\.il~ttiS$iof'l ~~~H1&1 ~!~~ .species, wl~ero typically <l~1i!Il!.he OOlillated !)nill1al~ su()ClI!l.n'iJ WiUl relatively ®11ort, .and renl!l.fb!bly siwni.lar, inctiootiO:~iJC:riods. 01'1
Inamifl:l8Jli~
$~~~~.

i~(ll.alddlilJt Cain be pmpa.WI~~d ~niin~~ {)Ii' il~bredlu ice Mcli tHsttll.Sl!l!usllecli bY' d:iS:I:i!U:l Ino~lbi'ltim~lK:ri!(l&~",clI pattCI1I!IS of IIIlC~~ patho:logy (2l)" 111c'se :s~nlius; C91illWl he ciillooded by dl~Crem::£sif~ prrpxl1i1l.b8Jry sirnc .. lure bcc8JlIS!!:tire)' call, be S!eri~Uypropagatedi ]11. 1I~t.rud.mli~ wjd~id~:llt~tal~ fi:f gL:li1il\': {Piwp) ooding ~qjU~ilOO {!Fig_ 1 B~FiQrti.l~or:e. guail1l!\l CilJll 00 1~~.rooli1,~oo ~in rslce ,0'I1ftc!!' pa._~~_ge :~I! InlCl'lllledual:e stwcies widl diffel'lC1l1;prrpl;l~l1illY S:ifUl;tt:!fl'les !(Hi) (:F'.~g, U:)., Adill'lcmgb dlslin,cl strains oli' 'oonwillicmal palhog.cru rnuoo rolplam~. by difft;l~ in tl1le:i!i' l1'Iu.cIGL'C !laid.
bi)clll~e$$clear hG\7I' <\'I IPO~~~idl):cln;'liill oOtlid elll¢od~ m~!tllipl~d:~~ pbe!!iot)'Pc-s, SOJllle S\Nh ~i[lliogicany d,ef~lled

UI'1J~1fIs~,

prim~ s:tMililS :silO\'I,f biochenlical

i!ltiie.BSlEagenl {;n 11'1esedisc~s Cilli1 be Umlil& ]llimed ~~.~fll ~ciCi> by h1OO"lati(Di11 (if di.ceuy ~re, m'ldi 1~ltcrooogniliOil of dl\'j; m1ffi,!\~~ human f,riO;jil. d!i~, \iI!I![jru'il tJl[) '{VO.D),ffom tit'!': $n~d-!99~ {Nr~ and the:~poi)nm~iI;;ll conlirI!lHJi!iO!l ilml i( :~ C<'!lIISed bydle sa:!lllCprim~ strain as:[3SE (5-7) :ro:~ l!lllljOO' rubli,Q.jleali!ll! oonceJ'llS (8}. AJdl~l Ole mnllioor .of Imnw1 'I:f.tIiSeS '~(i .&00
MR! ~:rioo Unit [)l'!l!Drll!lll'!I'l~1jJ1N1eu-OO~n~WJrn.l'! Di~<I~e" Ui'Oi. IlniSiltl1ii~of Nilur:olesw; I..QnOOfi laG, ILItl.

dirr~r.elll~ :~I1. the p.ropagated .PirP~".. For two sl'rnins o~' TME
pitim!L.", desi.gttlatlldl b>-'P'tf (frV) and. dmwsj'

(DY) (22),. linrui~oo. pmtoo~.ys~s prooueed, differoit~ P,dl!S; ri:agi!_i'l~f~t ~\'i!BS, ~.I.'!nffi'i~.Y~i!'I!!;lIlat tit(j two il'il'I3tjil;S bar'i'~ diI"B~ntWf'if(irffil_la!~iOlH: (23)1. S:u~li i<lIfIYj' di!l~im::l Iw:nlO1!R IPtpSi: ~wes have' been. :~denHfied by pm~eol)'tic fm,gmen!, size

wc:m

s!ilbseqtlJeI]i; :pilSS<lG,eof infecDiv:l!:y ti'ro:nlB, to :Ill, lI,ndi ,g~ycoriOnn r.• 'IDs.liJilowi nSllroteilfl<lse K n lrnillSI~l~km pW'8I:nClm:s I~mbl(': \!Iil!])~n"",>pecill!l d~gJCsti.on.. anC! lhus(t ,ilIIr!1 ~soo~llI~c!clI\Vi'l1l. d~ff£'~nl c:l:inioo;pl!IJmu)logica~.ph®I'il!Hype!\, o:f 'lrnil1S1t~iSs:kms~ Earty ~ud_ics; 3Q;"I!lOO I[hat [1,,£ bam!LlW re.~ides CJDI (5, 24),. To ~. ~,Ia:l)I:!lil1ble c3udh::I:n@;!l f(lr

"Vo 1ifflom 'CWft:lPQlildeofill!:e'~hlJllIlci be O!~re~~e,d, ,E·m.alll.~ j.,co[lni!e@e!iio!i!.li!d,ac:,i!j~

i!'lPrl"

p'.cir!l;'1!ry5lr!.!.~lYre

dirreron-cesOOl"VOOJ1! a!~ tI'!;ePllO~ecW!la!!'oo.~i'l of' 8b'rum divcrsily. s ucl!

biDclin::mica~ ~~r-.opcrrles !leoo

ao!!!w ~!'!'d rociph~!!~ spooics. 'fm'!!8~~'!icrlli.ce

inlpooe lheir

9'30

REV~EW
ch~racl.etrim~[c~ ~ ir~ipi.cr.1:~. ,loil~~!lier '(bcy Q,~ fill 1iJ'- ,0_. __Csa_l~ :f'lll-Iff" -at .. - ..I~m.."iil__ 5~Ces. - - [iii ,Slit,d-',- sci Ii res ,__ ~ __ ,~.~! !.. re~ . __
wj.d~h,l1lmllil,p.oon .1lSO~9l;es" p,j'f fmgnle,nt sizes fulkiWlllflgp:roleil'Ii!iLseK diig,esliOOl ,rnre Ib~ilitiJliunii1ledl (ilijl, p8ss.~e iiffl In1insgcl'illc mire [S, 1:5) and, rn1o'llably. II'iiIli:o~o:Wthe [hro~ pnlld.pa1~P glyoo-

Fudher iW~deiiil:le Plat dhllill!i'i~p-tiOiii. m!~., .~a'jsGd~lecli \.v1iilii dilThrent!:lOflfm;l].afi'O!'l! :stalt-s of PiP ~nc'tIiCies ditTerotfllJa~ ,poo~elimlSe Ie d!~ges" Ho.lI1kjnC1ics;, ilaei'iruJii or cl1ruJlropedetlB.1Jl.Im~iOfl
oQt.l[on_iOi~,.d~dlcn!" iJnllllllf100ssay.; il1lfttaR,'d s:p~1rO:OO0\1\lY llndali1llll!a1. bhtdiflig (J6-29); ,illIid lilh~ ~~.ofml'ledtOi:l<:to an~p1ify~P'£.l: (if' prioo.~
ICiUi'Ve!>;

repe.idJ1g ~~.
a'l~!11l!~!~~

QflltC: di!Tl;:reiit g~f~"

C!}'5U1t

S~dle!> u.$lf!;gri'iO!~oc;lQ!ia~

mu'ilbodies 1!I1<1( ~l'OOipiltlte mlm:ivc'PrP'''''', 0l,~1I1(ir with g.l.)l'fu\irQnn~)ecilic .alflt.i,OOdJ~es" ~~&ve Sh<I!l\!!'mJ,
lh:1lt PrP g~yooi.fmnsarep~ysiic..oj~ly Mi;OO~i1klcll :~iI, 3. iitrajm'l •.~~mc mli,o iml Inalive frf'""1I;:: (33); 51.1011. !1:1~llal:ioli'l m!ios .lIma)' b¢ impo~J]I.in. s~abi-

1IIIllIe HSE priO!~ ,!i:lJ,<1iir. is ~l!3!ilJ!tair!ed ,:.w~ scl;'ernl IM.Ii1HlUlaBjan ~ooi:es. ililCluding, hl!lmtll1S (Pig,. I q (J),

Imioodl. OlJelfL<1mC~~.istic:molL:lcl!ll.arsig,~ultr¢of'

i~""iltO (IiI~1 ~'how !auihfiilJ! rro!mg<'1lio!!of'81l'llill···a!~".bt·hn~f . .c<!_. C ar.1.C loc_e_._ -1]1 ·.terisl.i· 1:~lJI~J2'1 ,_os 'IF'. __ ,. P,rion slrnills are ~-ciamd!wilh, cOl1S'lSlen1 fonn mlios foJllm\f~fl~ ~rolcrure diges ~iQlfl dl81 ~ios oiflhe Inil'Cepril1ll:lipalP,,p glytlolOOm, wliOCh oo~nd. to dle mi:gilbill~ il100l!1h.lli~1 (5). dam- cal kmaiumim,1di em senal ~.iI~ ~~OSffi widl o!IIS:Ul;itirnlg~mpn.li~img Qf' dl~i.'; b~oQla,Iil:~'Iliea~ l.h.ll' SiUlmCi 01' <Ii ff~ronl Prf ~qJU!L\\il'I~ (5)6 Hm'l' ehara:~ri.s(i:cs(lnl(l .fl':P ~mll1lJ .:3!I'i(1nhL\lr spe-c~ Il]~gh~.rnlios ~.maEmUl~n$d? OJil('; poS.ill'lIl-it~Ly ig
amlc[
,:l! _~.
__ J.;;'Y _ ~i .

Qi.litiinOO (.5), Ttairnli:mL<:l\<llJlil ~f' OO¥Vdfl~ ~ri(l~OO wird4YiJe IlUOO (ID!~ins, !'!lurinelW't) ~!!!flocliJil pro~pti(m '" • ~ ·'1 . .' @~,1l1W1n,c: ~'i~ Wit Ii-"~gmeliU: SI,z.es~IIlA , S I}-'iXF ir~' ...
f~m'iS .i3:~ ,a~!

WI~nila1l!

li2li!l,S; pMi.cmkir pmlr;il~ coofon_io!'!cJ. A criti:c<!! l~! .(IIf (he p!'t1'!.'ei!'!-oniyhypgUl.esis, oolh winh re..9:Je0l to imlfectivity ,amcli Slmit~ess," " wooldl be: 10 pmdl.lOO di'K:rele p:riQl) stnlil1!l SYIl~
if.tctLe!lUy

mmtmiaUy
lIDiI;I:rI~-d

1~n.~CW d~ff'~'~I!,~ain~_~~i~c 1l1iOp<l!.(l;);tir)ll cI~ .atIJj k~~eliC!lof U~.-.~'!O- a.nd <!igl;t0osyIEll£CI foom. Alrolililmivc~.y, illJldT'II'ildlu!li~ I?rF c liibri~s could! 'be ,ool'bn,poscd of II, IIIc.gtI1M

u~ru'il.is

I'l~:"!llar m~ml mId bioa~3.Yi>dI. i.!]k~!V~I~i(: (f~9949)'flireex;~si!ill!!l'VCr:r ~i~'Ii! level'll ofib;:

saU1ClmIiICilOOdI IIlHOI'IJSehP (IJ}. Anell" rpro~OI~ j]iJCuoo~ralil.pcrioos.lJ~c T:g9949 mtoe develop

.,..mfioo, lL'lXpmsooti fl@COmbim311t N~~~ml~fliaUy !:tibOll~Pr1l' h3:s~m(l.~md ilt~(:I

.~rol'lill dcftln,ccli 0('!~~,nCIlIt!l,

III

[I

:u::: -:::::: ,
S~vliiA :2

••• ••• •••• ••

I.

:::::: -- ::1::::: A ,
!S~~li'io!:i,

~..--"'~--I.·-....... .' •• .... .

•••

IFig.!..

PrDptlg~.rnlni pmiloo strilin:s,.. (01\) PriOOI propag.rlicililproce:oos -Olf by Irrecru~]iril1ielllt(If PrP .nilornQlliI1Ier~ atD: ,a preexis1ililg: Prf poIYllil1lerre,m:pia:te Ir'(l~--ed byi1ilS~~OOI 'to '!;!IilJi!l!'lra,'OO: ~p-l.a~.es iJi!a~!'!~~!aiMk ~(lre 1!I!1!~Ji!!l~f, irlimnrt P,~P' priI.y,lITiIl!r ~ljJe5 tan iPHliPB98ite,ila:mlllillil1lg mr diiH:erent m:iI.il1l:s,.

d~El'llilfled inlDr,ed mire. Sb:ai:iil-.sopedfic P-If~~ fr1liQlIIIiIIll1JI I~ttem:s fvllowng prroteDl~is .ue illu5tratedin d~agiliamll'!l:atic Wesirem blolll (vertical bar~l. ~oth b:t1)ltog~@l and bf.(I(h~mi(a!l~aif! ,~~.a:~a(~~!sti~~re' do~l¥ m~~!1~hloo mil ~riiaJl pthSliage il1llile Siilm~ host '~r!es5in!!ltl1:e ~allile WII'lC.• ((:) IP~,opemi5 Cliff a .single; s,ti~aln millY' be, retained. a~1re!t!p\l5o.~ag:eill! .a r.ange of diflfierlBlilt: I~I~ SllIiaJins.ran. be! dJifte~~l'Itia1!ed by dilar.a.deris;licinmba,1io,an period~ (length of arrow) afil~ n:~~Ifi'(lpailholo!!1V (shad~d b~,Qji!'i.I'!Hlg) W~~!'I! iJi!ooll!la~ ~'iilt~1 sp.ed~ with dlstiml P,rpC~t!e!1!IIIi~. wh~!1! re4~lliamdli!:l th~ It)riglrnll1ost.

REVIEW
ibI:rioo ,cilit~a~elra~;!Oiflli~iMe to wiltill-tY\fe<li!i,d TgSi'949!WiCC. Theb'aJlsmiissi{ll!] QIii<J1adms!ics tlt both. primary !!irldl second. ~i'lSsa:ll:eare C:OIiI.~ SiS!'Cl11wi.th ~roo!llcliCin oif alil.6vcl ]'lriofll :sl'rnLrI. Severnl ·~..y,illlmtic"· ~fiio:n. .snlatifiS ~1!"'<Iebeen .d0,. ~en~d E\':3iII!l:'llirug lite: !'lilmilil! pm~rtlilll .of !!.l,IIeI~ 8)!111I1.t~~(: prirn1~ ([m pr.nn1a!y ;Jrild Ilil,lool1dp~~·t~g.e is compti~loo by ~he fact dlat! prilltary W1~:,tt~a~ i~ocui~edl hUn fl~ice~ru:;k Ihepo~~s]atLiOoo~ .. nlooiilicad0l15 !PCP ac.qluir:es inriUllIll~,1EI~i<In oo~.~s, lIl{)mbl~'" N~Lhlk:ecll gtyoosYlotkna .. aad 1~~ml1ln81 glyoosylplrosplnltid,y~i.1la"L~ol SJI'I(lhor;.w~i~.c the ~H~.I31ivep:ri(]~ lI\cn p~clI in jln~ol': "\lI;)Ijld
1cl.L'l

w"dude.,. t:e!l1ecta~l
U~e!~e] 5ffil;in p~~:G8

~b'<ii!~~ffu:c:I. n.;U~~, m~ty .!lilovil}' :~!illiliieho.~

co:mpo.~dl of ·~SQ.dl

m:3!rn'lm21kll~ PiP;

"fh<l!J;gh llIJli<lollibOOdlly

amajo!'

~p fMv.aud,

I!'!!,IQ ~ey ~)foble:!llS .m:re·il~l th~'in1crp.roCUjQn. of ~II)I(::S£' ,e;,"perimeul/so. f1i~I,. primary p1lSS~~ ef infcc~iv:il:y ooq;liIircs inr<ilt~sgenjc mL'Ce wilh ,extr:emely [~iW~ {...l~.fQl\d.)overe~:pression ot'fr'~ .. Sp(m~
rnlOOI,lil:

dmr~tQlimmt of

priOOl.

dL~~ilropadtQ~.-

d~tltc ~~lehi~h~PifiC SuilslmleCOI1<leinrntion,. [bl[~ OOOOlJliug (be adtltiOl.~I. (lon1lllic.ati;on that the !>),il.tEi(}nic nlm~~~ leeks ~ooum:i~s1atiQI1!1llMiOif~. cation,s that :my be [tnportarnl f(lrpall.~iI'Igellie:iJt>y. HOW(:l\f~r, 1I:1~~ i~.an.O'iII~IiI!fI(l!liV¢Mp~an:ati(!ll!. A5S! pri~1lI is!)kl~ l<: ~a.l[y dilut~d h'l'lvardl .:!. sin~k~ inlbcl!O'li!s. t!:~i~per' iHooli.dU!ll.l,incl:!batioo 'perioosi~CIIC!lSe... Th~rure,. Ille~m'l:g illlJtlbarlioo IlCriOO:!l!;recm ·\vid1syrnthiliti.c prim15110tild shlil;!l!~Y :rellool 11.1(]I"''>' I :plio:rD liiI(lr:. 'WiLl~ l:'eS.ped. IliCiIlh!e key ~~ of t!lu(!Jlcl\at[ng~1!lIi!Ic:itbH3lpl1Operlie:sof prioo ~fit'J!umSj U'li~ i~ fuooamelllllrt ~lp.i)l1anoo.. If I]if/l (!;f prjlll(;i~13!1 cOII~!tet1.1 (!if !he s.}"I!ill~~~c U1!U~ril!ll is UleV!lfOOti~lJrf([f~ hli dl~ ~P,l;ica!:eOldy siowl_y ill Ilulcc.,bi'!J:I'lI-~)!'sical S1i!lll.lLle-s: sn be per.fb:iu.l1eid. to e dCI:enl1~ne rthcir .slrttClUre andp1a:lsii~lpropcl'\~ie.Ijl .. Cm:J!'l!looocly, if Om 'lfaJISmio;siolll I:llna:m<:l£ristics roll~l krw priem ~It!r~ that \\lIQ1!JldI~~ly Ihat dlli.'l
pri"p:ifI£ aooOlil.IY:1l.
liI~iIilUmt!lrrJ(:l~():lil

Ide!)U~.edl !l<UiJjI<li~I_YOCC1UThl.g OIind C:i!perilller.bl1, dcrived surruns. Srnue _[IS lillfIy be possi!)le eoufonmri(DnQl1y rl:nra ~iven PrP sequ~lCe ru'KI. eould ~~i:~;cis.U.:t s:ynn.li£siz.ed.~t1~ ItEmyoolli~d. not ~: htd~fill.ioo~y ~l)opa~tOOd~m. a IMll:lnru 1:\11';1111 QW:imI.~ to l~ffic:u~lr~ cte..1!~~ For the .~ilm ",non rps.~],.lOr 'wl~:iCh 'iI~ :!i~bsmtH:l ~R;iCI~in i![;: SlUpJSp.
am ;:IiIwy~c"l, ~_~y·.sI_<l!!e:~»del d\;l:scrib~"g ~~"S;

\ltraio.5 ~.may

·be·

~rg.~' 'd~l~

diG

~u.!'iJO~r r o

has been ~perim~illnlly valida&::.d.(47).. Ti~js wrnlk sUP.pO:Ii'!IS critical ,mile af~llile~men.lnt~mli iii pro.. pcIuj)~y .of il mukm .~I~[ffiI.in di~i1Jl.g ims itlviw
pll~lnl)~pc. To p~sl, .ye._'lJS~. pn.lm~ m~l '!WOP'agaI~ 31 a mIl:! iflJlmCl>etl~. ~.o;oon~pLlil'lsaoo:f:b,i' d:il()

dill!l([,ollial ~ff:b~l {lif. ·o~U divIsL{l[l. Cleawly. 11!1I~ im \(i'o'o siti!.!1l!~oni!~ m~l!l]1.a1s i~ !ooreoom~!e~ fiW
becam~pmdJOI1ilimmdy poSjUn~VlDlij.e C£~ls .~ illl!fec:led, an 01 1ln.!lIJti[plc ell types and tio;sLL'CS .a:Ji'e c jdilyo~ve(l lill the hraiilll,cl,eamllcK; by ce:Uu[,ar
m)(leh3n~~m ~m'(M"1.l: ImJisf(clklGdlpfl:J~Ll:iim .a:g~m'II) g,ate.s t¥ill be far m{:!o;l iml~~l lilian di~l!n;O:ill try

Q,gyus S~Cf1J ad:u~r (fl!Iinsgell:t~lln¢s w:~I,b hiigla i~. hw~l<i: of PipC' 1~!l~[-OI'I.~lthQlI!~b. ,his d~ !Jot II~ ru,be lm!mflli~i!)~ Q4,. JS). UfI!inoo!lllltucd (]I!r ttloc'k"illI.OO1!J lil~ed.Tg9949111la: dO Ina! Uf~peru: I[od~;\';e~p S)DliIIDf:lOOtiS pa4JilO·ll:D.IDl {lJ),!IldwlI,gh.

of

11,1115

mroOllDbinamt-d~\liOO

p:ul1li);UIl, 1II1akil:tg

p]ly(ili~~

OL;lUgKIWUl

('Iu{!division, atu~O'~gl!l

lihe Sillll!~lIiol1

aad sl·mcl:l.lfiill :S~l!Idies ilrre~kvnll!l. >(38). Tlris questi(pll.cmn be I:c._<;{)~.\~\.-d. a~beiD laboriol1S~)', .by setild tUhruiQl~ oif the Si.}'imhellic ,~rioaillOOlllhlln in

:i~ .lnnsno~ ibcell ~11£d whcdlef illfC!l::l!i.vily I?cas-. sag:eab~ein Tg9949mil.c~ is :~rol!Clll in I~m Il:!ran.ll'l of aged! ua- >or :nlook.inocull<I(;;-d 'fg99491'b!1k:e:. HO'!~~. it i~po~~iMc 19i1l11 di.~~IIlic~.~ "'JXI~~' I~O devc10p SfIDOOilIlem.!.s. ,~e andwolllddo so if dlCY lived ~oag eUQUJ~Il>aJliJd: rtilml onset disease is .sl~ly aocdlClliOlteclior (llfleCillLULtoo by irlool:Ji~atrm~0'1" :[wtbIiPIt:. Sm:lh IlOOI:I:~rroWrsyus rI.ot Ili'l\V ,ru:'ldOOllllin1!l.M \vid.~ ~m oo,int(l(prcIlatkm of\'Vibetlm.fl'll~ce: ,L'lXpressillg ffili~1iI ~eve~s. if O rtf! (lo;ntllimlmlg 'Ole liti(~riill~.ui""a!LMlt I(NmIL) ~ <!I,f ~e h:J!!!NH padiK.i§~lic Pl:P mutalia.ll P] On. (~Il"'ib:~ibr (lUCofiUhe illk~nJt.edplion d'if.e~) I?rodlllCe h~lbc:il.vily SJ:KfllmrleGlJS~y. PIlt<U~vep1.ims ,:rodlJoed de In.crl,;'Q iI~ su~h ntlo~ oo'~y ll:dbct mice c:rq;)&'~[lg Idl~ &1I.IM nlU!Da~roll at alO\\ler l~'Vel (:fi()nm~or\,\hkh do d~veilop SJ)OnlaRLW!.I$paibl)~.-. -,. .mO· - ~F" ..- ~-- ,;h , . - ~) 1"j;(0 il!>..;!'·, , - ,-. - .~ '- • (!!gy ." .al;l!v.Im~1JI ~'t~. \"""" ~n{j!l~ ' n1ay .Im)~'-1,~~n l 1it,1,1v·e i~.!~!ls~nli~~~in~~'l!!ie;,,,,poeri~n~Jrll; ~n rndte;r, ~lIilis:~1t may hwv·e l:eprn-senled.aQceiliet:<li.iOOl Qr a :spollhleQ1!S Ilcurodc~1Nta.ti.ve d~c (Ji). l1l~ gl~lil~l qtllc{ltioo,du}1l!, is whC(lliLm:uIlliG f:!lli~'l:I~f..e ~Yltthelicprifirn5lam .lrrl. f301.priOiil~, Qr sin1ply a.gcl11h'3tlilllllfiiggs:r [prirm. pro{iitmtiooilill:1ii;l!llilS that I

or

dJ.C:I.m~genic Ul~Qr;:. [f tile, fnn>~~nOOrp;!iClDlimais correct, 111£ ~l.npl.e li'll;!lfY dlilurocl mrulY [oM fu~ ,~d wn~W ~nill I;llflXhwL'O I~I~ Sfm..~iltoC!JIbatiou '~rioo.[~' iIh~ :S~lld h~ COttoo1!. l-"i,~Ci!l. ill u)·foM dit!JJl].on, is Uke1.y to !lCSUIt ilII! !ID!1IJ!'r.u\Stni!lSion dmng Inlle Ufc spau o:Ftbe-se &!ltll:m~S. llle liWognitl:ou ~Knootrun lIerilabic tmils hI yeast OO'I:II,ol 00 cX(Ji)ilari~ed. by ool~fDrnl!ilnOIlIfiJ~ swi.tchifiig[:jJild. aggq~iol:iJin. t\\IO j.re."''lllProrojn,~. Ure2lP'8:1Il.d: SiuJpj:5p.iM. to Illh.(\l Mt~Lltt!ire ·of tl!t;; field; (Dr "yea_~pciorL'i"l ;;'I. fll!irlgal ~rot~L'irI with priglIli.ike iPt:openitH" Hct"'S, 1~il:Salso been de" s>cr.i!bed (J9). '1Il1'CSC protei!to; IJa.vc no ~eql!Le,we sitnillFlln!l:}'10 fiuP; Wbile OI~.C' can ilr:g.ue p.r.:u;:ticlli~ dJsd~C!niOc1ilsfrom mammalian p.I1Km!F,. which are Q)I-nsoldcred llatiUm~ly infeclio:lI..'> ~~d~id. pad.lQ@lm. dn¢ ~nudyQf' dIes!'> cl(l.se:lya:illf:lIO~!CI!l~ plll~nlIo:rnle:nl;il has IUllqlll.~$~iOoJ)ab!yl()di OO·Ii';ipid!. aclV~~~'l :tin.iI.\'· ve..~ip.~~~g I~:~es ·gf ~:cd.Bbri! fDvill,!<)" the Ilan ~K!.d;telll()lecuim: basisQF S_Jlrl diversity a!I:l<!i LmnsluJssi,{-m hlT.iCJIS.. :~lJ.dr;.(lcili, )'I~:$~. IPriOOlS • (lQffillposooo:rprordn IibrHs,. ~~i:lgalh:; 'by :5Ce:d~ng, 3I1dPQs~~strail1l di\i'Cf$iI;"Y IiIlfl~ is lexplain>Gdby dir.;timlt;1 oornJG:lIi]~f$ ,,4{J-4)).
I:lImUyililg Stl''a~1iIS .and Tli'illn~mi$!li@!n
Ral~rie;~! C~J:W~Q~!!t['{IIl'!l~gll1l(ffi

m'ilY be di:ff1l~111;~n U1.e lyn!pI'iOreLijcllL~ar SYSile:J!ll vihere priOlilS also rep~ica1:e. Mannnalima.pfiAlI1lS also ,cause InM!>~'\IIeoe:~1dealh, end qlOtOIl!l;Lcilty win t'IC llIlnaJrnrrOC-toir In. au}' model of ~ua1il~ mclkm.prim~ propag;]~iQ:Il. Alse, 3 ll!lllOCUg1ll g~e:a_c1ysta!I.~ ~1!J1tim'$;rure .a~p~i~ble ~n ~lod~li~!1g)i~t pn(1l1:1.ri.tll •. ~y ~ ~U1OO: islWl~.red i~ldl¢
i <1J

m~:ruI!~la!]:(H;'IJ~Lral!1c!"<l{l1M>

iSYSI]:e.Il:l.

HoiYl'CVcr;cihou@b, II reia~lveily Larue !]Ull;ruern- ot diremlJ.~Plf'""'c types :l!ilfIY be poss!.i:ile mlfIDl~gd,lc' filii mnge ·of i:rruaml~.8~~.81~.Ptd:'~1!l~noos, o:nly a SThbll!Ct o:f!!l.~ese: woold! iIDe romp-MiMe \v~th11 gU\lern ~l]e'lo~5~~. iA}, ~~r~i~~ Q\tt'fla~ b~nl'l:Gem I!~~P~!$gl,liJl¢~Urt'lml!Ul()m5 t.r PtFP dooVM room species Aiil.lIJ!clispt.>j~ics B wo1l!ldld~us !1e8li!h:irl relinivcly easy !miUl!Sluissio!} >Oifl!llr~tlG!1.IJe~~erl. d~ese two' .~pec~~-s,w·II.cr:eas. two ~pecLes:\1I'illl nQ
peni'wi$lliblcPr-P'~ ooll:fDli'nllfli~i.Qn$i~. oom:aOOO

~~¥~

}.il[leUligh.l¢\f~l~ llI:m~ ~f1~~rm d'li!t Inh~y

M:edose k!~rclopt!lg spo:nl:aneCllilSpri:Oll disease. 1iiiilil. is, ;;tr.e. nlte 'PriOI!lS genernled. in dleodl".free syslem arOOlly in IheliW:)i$I;'!'lillis:is 'no~; i plllrely f $Ci1i1afI1iciss!llc. r"Of c)lamj:i!lc, .~ wou~o jfrobilibly liIotwaf.t~. tt'Jcl:ass~fy .RUI nmiiroly itIli1oo:ia.t~dI a~nt:c
¢(}ji1c~iwb1)'tln i.lflNij{ji~ifl]Ci~Ui!i1 S'I~" ff:,~.cl:or,tbr GX31:'itrpie, that ijp-i!'&gij~.::t[OOfi[P{'~p~~i()m.a;nld

Kru!'l.I!'Uc

S!E!:lielliof! 1iI.f IPri:I)i!'lS

MmnmilllwlPIfl
~"aJli'Idi g,CIflG:5

are h~~hl'OOilSCrvcdl,
i,q

:m\ddJt~ e~(l:l!e: imilarity ·of hPp:Ii[~mhi'Y :s~o· s

trul~oo. f.olru (4'6),.

10 lijl~ .. bl~ity

~f!!~.d

aC~lievoo I]u!: Sanle1L_Pipaillen'l. effOOl.-as ibei!1£i a bel\~f>een IllOMMlaliom ''pri:on;' ·nhesa~l!.1~icJl1oo :problffU W(]Iui~db~ i~O IUJil1ilOOr of Pdli--:;" l)rpes or, 'ls!irn'fUiIS"1l;1e seen in dlis s.howinfectiO:l1atfirsl :~gear wi~dl"lytle !lut~ dle ~peotJrum ofmrul1:rll!IJima priOri diseases !pre" 111:)1 InI~cnlilooy" l~n8J1s ·w.u~llil .~td~illnc·priGlIs.1llilio h~ not >,e~b:;:mnl !>!!II'trDahly II;lI~sInlll:l~~bcr~Ikliilil:ed Iru~dL 'rhe SCOOIId) tnb!]£m m131~ 10 tnJWtOll;;; ~ Jlsmic: smM~:Uly9Iild IItt': ItOO!ill({II, fe.pHcatc aJ:' :it r3.lrl I~.il~(ljf iIJ,flltl] s.:mthelie prnlllrl\'!, 1l1e[O(trunl~I.:y abov~ Ithal of n~Ulml d~,ce 'Iinl vivo. 1'his !WJ!lOOr tV'nI ICcutSlilUll!l lI~e dlcoretical ~1Q!~(1 ~fOk!!n~@:.d iRCV!batiu!'l !X~oo <It P'.vi~ !Wi~~ (51 rn 6 ::b:2 7&)"."0) (14)could\. m:; d'le ~uth(lIls of pmnissibiea~dI p.a9~oge!1ic,va!U11111llIi!.!RIJvioo

!C!f l"Hio~"l 00 Iti!tlS$·inrea~ spccles. Arthm.!~~ a I.

pfi~UmIla1b~y

\v.o>tllcru h.w.u: a .I;1'Iugc b3!iil'lt\li 11.0' InUISl:l'aismOll! .. Any bl!L'\linissVcm (l:t ~llf1lcliv.ily ~E~n rru;ch tll!,ip ~'~~\wtttd If(}qi!li~ ll. dlial:l~~ (If strnirl ly!~. A'CCo;oohiliS. lQ the Qo:!~fonru!.1:k1!~i!1 iWleotion model (8), hQsl PiIr:pC' Iniu'l<ll)' SUuChMiC' :lnfl~~lQesw~lich '" ''''. -!I?.I[' ,·r.. i}~e' '1'> o~. InC p<lrl.liOUO (I . ~ "'.'11 .1-iI''p8~ ~.yp;;:.s. .a:!i'e tlt~1mooymll_'ll~Ciilny preferred w:idffi ~~ ~.o eol~mffllii31km amdl :kinetic8iUy ~ml~ID!jI during pm!XIWJIloD!..lm tb,{_~ mooa~. Idn.e: l~$nrl.i...sknil b,,"Ifti~ris d~lTIiIillI~ by tilL); d~l:1l~'!!;(l!f (I~r!~p betw-e~~ die !l'Il!bsel PiPs\:: <lllo~~d ptef'li rrod byPrF~ilill the :ho;s! a.td dORm s,pec;~s. Sm~nsoodll~lil~.ssiOOl barriers >CIjH dlcrerore be ooi\sidt}b'L'tI . .ojllOSllie sides ofth.e !lH'l1illC COiiL .Rcrunlililg 111lhcliIi~h,cooss-s:pcei:espadl{!1~> nic:i~y of ns.:r, 1!t1i~ ~tiMI ~y ~~ir[ a.UIcrinodji\aID!l¢1Uyh.i;gl!tyr?i\~ p~ 'Cfjlft)i1litl8!lig(! lilat 'W:; reat'!Jlyi!~,prin:!ed Or! pft;"' :&.o~TI!.~ li'mtse of diffl:.Wlli!. !l{}ooies, aoooWlltins b' ~he ~lighpro:n}i:sctlity Qf lIiIisslm~n.ifl :Imumwl~s.. Cert<lan'~J; rilim stroilftl wa,~ !m~iID1!OO 'by an im:luslrial.cooknng process ,(W!:.'i:'id.mill:g, Qf~;.'l)ilrlvoIVb>rl till. dIe rm::ydil~@: ofh}fCOlivity 'd~3t ,@II~ra.oodi U1£:UK BSE~pkt~mic, andil i~maeedknQlI;.lf.!1 ~peri.•.., 'ill y _0 '1I'Ii-' '~' r3 __~llD"""'!I_1;; . 'flY}' '""'''''l' ("'IR]I m.ef_J!L I··.[ i~~. 11'~ O~,ULy l1ri.: __

or

tYPes

or

!l,I<.;

9'3.2

REVIEW

!ii'•••

'

.... .. ..".'..... .. ...... ....... " .

•• •• :::: i::~~:
~, "",,-,

.. .' .. ..••.. ••. •• ..' •• :: • •• •• •• •• ••

••
11

'M "j"
2

'&A
i

• .a,

Y'"

'

:Iii

"I

... ** A.A ** ...... ** "''''

....

~,O

18

"',,",

--

i.""

"""",".

'

'

~GO
--~

80

'

,2:

a!:z

,. .'
!J
iiI·iii

'

,I

a!

.,

~'.+
~.CJ
111,"'"""",

I~·iiii'-'iiii

iii:~iiii.iiii

___:o

iiMiiii:iiii:iiiiiii

iii"iii·"_

iii

iii"IiI:_

iii

iiiiiii'_'":,'_iiii

iiii:iiii"_~

iii

iiiiliIiii

O\lEJliIlJ!Id'!Imlijl!\!3e!'illi!!erml5S~e Pi~ oOOrdo!ffi:!1i'S in :&jliecl!ls A, anti e, 'Tral'l.imJaloimllbelMlilr:I i"~1!! !'Sts(iv.!ll¥ eas:,li'

i!!'

I~-,-,-'---- - - -- - -- ---'--_- _'-'-- - _----'-'_ ---- -- __--'-,------_-- -'- - - - --- - --fli NO OViE:RI..Af in ;~~bl'efilrP& ,~kirnl!l rs IJls~e!& #Ii or B aoo C resullln,{li ~nli!i'ImlllS~s;slIol'I tl:arrl:er

~+.

••
'••

!Fig. 2. 1tA)1 (MformiPti(i!iial ~el~DI:I and ~allilS1mis$l(iiii hamll!fS. A v;,ide ~an:ge of rnarnlThilLian PriP'~c ,~(:mf(!frnaI:i:Dn'S- are' 'iWSS,ilblii but: only i ,subset !<S, com,atibLe with ,etl~hin!lii...ndmll PrlFlpfiimal~ mu[jjillre. E.1~se ~ tr.tlJl.SIliIil~~ronl o of :pri:(llll~ b,etwree!il~,peciie~ rela~ t,®, o\i'@r~p ~f !l,errmi~~iME! PrP~' (oomi['mmh!'i!1$ b~Mi@iMI p~p lJ1l1i!niHYs,tlFt!rlIi!rt!:sh,orn th~ 'li!'!Io 5J)€1l:~~ lil:(I!!!:gliil
I[eln~erlredlas cklines" p,i[l) ~:tr,[llins mV G!on5i.~o:f .tI'Il 'eilI~emlfe of m(deull~. <lInd trnlil_i~iolil w11l11iifl<itE to' OW'imliap011these I!IDputtlliliims;" (I) ~tr..ilill

'm~ d!olilllii!ant ~PrP'Jil; t)'pe '~h!l:ls,t.,IIJ! but !ii'lpychaii!~

lU:~gtioo (lfs.1rilJ!lsas ,1:10 ,~se~b:te o.f. 1P,~pS~!1Iilo~1J!II~ (Ira 'QtClfl;(l', S;-Itaincs "b:reed tru:e" when p!"Opa.g:atred~1II hQ5.I ~rrl1lt prefe;~rnial"llm\~,~.te5
1~~ijOC!.

oomm

~~ ill Idli:~fer·eliitho~t (Iali that s~1e:c~:I,iI@~y lIlf~agMesa m'in.or cOOilponl!nt (),f~n!lJ IPfp5~ !i!!Ii~mllll!, [,e:rul[tirtg in iip,a;rel1lt Willi'! I1'iIlrtlirtiiDI1I •. ,AJ~tem;IDwLy,mlilil .fI dv:na[ mralifll, 111l0Ciulatimil into - ,hO:!l,t '!iB.~1'~~.Iie~in.gPiJr,p' with alse~iE!:Ii1CE lm:n:lllllpd.tibl,e withttiliio; Ptr~c ()(lr!ftJmM!l~flWDli!kI on:~Y f@s!J!!I!til1 'lranlnis·sjoi!l IlWy dir@ct strain' mmatitHfl. Ihe5ie ill~rerrmti'iol'es .tIIH! 11I0t lifIuooUy excfu15~;"'e. ~t 15 pmd}~e1th'lt 5i:r.mlll ~e~ec~iOliIl,<llndl l'IiIutatiOOI IlI'lJaY' ocmrifll diflf ~lNit n55l1e5 oJ fhe s.ilmE! 1105l:. .ilI!>

w~1l

gs b~~~~ dilf~f~illt h~ Q$. ,ill r~n;lLt(If' Iii~fo.g~~eityif!~e\~ul,gr IlrUl(hlilnis!liiils al,em'lng priOI1 'propillgmOllltlftd clearance' 1~:rJeI:iC:li..

Another iUmlmtL'01] of the cOllfool~l'l.tt'()Uru, i.lelootrol~ modC:l is ~[Qvidcd! i:l:y Illiteco:mlMn ~rru.~ :~U8!n. 'r'PG;.lymor.l;1il~ls~:I'!I (M'~. 9'V),longku,[')w,n. 2 I~Qbe: til by demn'traInant of'g~ra~I;:C S'~P~:IDitiIIY I~.(I!prion d:L~~.Nr,l1:.ibly" ,w~ pati~n~, ~willh. v:C:OI~ H20!)) has been ~~Qln\iZno~ f'O!: ~lhel29m!:ldliollliue m~ele(a genotype seen h~ about aihi,ud Qr Ulc 1Il000alfli :pQPuJatLon) ~~ i~ nppearsdw 1111e: valine t29hmil1mn. hPis mot ca'fI'b1~ Qfadopiing th,e:PrP'~ CQlDfOrfllallknn as~oofute~ with. dmlt!.sEgim.~n(49), 'fralit;l1!li~o .. ~~ S\ldl·a 'Itt.~f Illiu,!L~L~~~ ~lilSit;'litl $"";;icl1:illlM; willi ~.gaIiml. of <i ,~hd <uK[ &!::Il~thres!i.m,..el. ~ig~ type aad <I. ,d]uffelieilll ,c;t_e ~lilen'Otype (~ IPri'~n S,tfari:!1!.S<1:aIbUity ilrld Ml!!tm.io!r! nl~ p1il'c:t'Iomenon of ,SlraiiUl ~ttI!l:atikm has

rooo.gTIl'I~oo i1UatrrlY ~ b:y~la!ogiMt 51f:l1:il~ 1!.yptn~m@n1~odq ,(50), CIih.q~t..1I1y.iI~~~i;iiiS "",Ileu a slrni~ ,dOes I1Ql 'Illireed Ine" em, ~~S.1Cl illl anew limst .md 1.1. distia:val s~miu~is:P'l'O~s:>)led. MI!lItnlio:~ :n:laY {bu'l does NlO( ncoessillrUy)oocur (il'n. Ciro.~i[\g 'ooi~;WC~11I SJl!,L':-cies and !I1,>o (I:n, in~tes Imn.!!l11um'iimn. \?!'In£re Ittim PlflprillUlty

.ror

beel~

:s:etlI.UCI1,(lt! of dl~ ~aos.t dilfel1l from1 daill. of Ihe i~ooyihul]!.for e~anlliPJej a~ a 1'l'!S1!lI~t of i!tl!!'a~ speciesPrP l~l.)~!I'Kl!i~h~!~l "1.res~dl!eI29irn

seen h~ a,sizable fmctilm oreJ,I) braias leSS, '6). In:muuas (5', 6. 4~, :~uh'l!lltum Pc:!>, :resldue 129 plQ.ct'S (lQUlSlraiints C!I~ w~h~chpri(m, :!ill'al!if1S Init'li)' Cerla.i~~y, a IHlIHUll!iro~a~e Sh01WSooilsiclemMe. terms of' Nl"tmu'iltmil. d.ear'l!'flge site, prqPflgal'e., btU:. has 11.0 meaSli1liltMI.'l[;ifiilClOO. tliae diwrsiryif.'l anditsg;lY'oos-yhllii.Q1U 1...:: highly oO:jiupl~ rul'd. fo~.di~g, d!y~ami.'C$,aJnd ~rnllib~HtYOifPtflc, ,~~'1:tnI~ llliIa~. ilS: ,elf~li~ ~edl '~lIlfO.'Ugll div~rne. Heall ..in,:ii~liwlknll' ~liI:Ictie!'ii also Sl!iE!f,~l CQ!~rQml. i~(lllt Qr rf~ ,u~ p~mwm, . or Oil dIe hctero:sme~l;Y gf i:~root!ow; ~ies wi~~~ern'lOk1rulciiicsor~ru.eir fil1muttkm (j,l). S1mi~l Un!lll~!on $t!ilJole: slllbpo;puJ~att(m5 wlihin, a, d~fi,milsimull (j7). Two (notlwl!lmny e."l',;\itusi~)' .poss:ibiIWes: may a:ls-ri0Q;:l![J: on ill~-srrnn£4mssla~ wh.e!'C ~'iil be e:n.V'isage-d. (Fig. 2B): (ij, A S'firllI.1i1i'1 .~ exist hosl and prion do:morh8.'I,IIe:~.~l1Itical .PrJlp ,~~GS: 383, mQ~oori!.l~,ai clQj1IlCa~cll stm~ii'lnltlltal:£om This ~lSfiil1l. .a(iJ~Liumfl~'L'llfeCIorlnack:B~1;IIild iID'lvo~~ g~umwiofJJ of a clii.lltind PrpS" r~; (ii) g~rn¢SQll ~~Il 5i3~LlClian. ($2. 5J),Slmi..mu. !aJ!i{l!l:l ~'ll be .a~¢olt'JJ[Jmd.;I!~. 'w1ih,11:1 ih~ Qalilf()li'. stt'<I1rL"i 'OOI1l'i1~ of a~ 'L;li~t,m]bl¢ C)fl11;)l~'1C~br ::;:pec~: {co:!1t<li'r!ing .<!! dm]'l~Iila;ni:l Pr~ ilype nU~Q!11i1~'led1oil I:ljIpoHtesls: by sefedim'l ofa recognized olil\Vcslleillil blotmdl prere[ell~[any novel p~ oo:nfO\li'lller as: a ~U of IIDslPrpC pmpag<l1fd by i:lslm:ml hoot} f-ro:nJ v.lIlidh, ... less no~. I:ldllgSlbl,e to ad'ofl tile d.milor I?.. P~ popnloas giilbspccies m!iiYoo !';(!ieclM, by am. oonfnn!;1aUOOl. lHOWINe., dl~pl~lmOlit'i(;Wrnl ~-s altemal~V~I~(i..~1 (wh1l!;G: propagati:on. i:...il'KiSl. f31"' Wiilii,'L'IPOrtru.r~ qlll.Cl>:lio:i'I. ,maul sD~iIi15.[[has ~l \tared ~.I!i11~a:I. envdroiUli.1iiiMl),r,~I~i.i,tg in ilil):firnliiiii IOiilgaiguOO Inlnal :!;!milD,S, esn bL') 19,.iCi.llo~kiiUy ¢tOilet! (SO),. nis ispedl).ii'iit:'iw. bys~l p~'lSag~ tlh~lil. Gl¥I.,'1l III~~d~.~~~ o.fi1'Ki!,~tll:Mt ,cl:t'i,i\~ly ,at Uanili~~g dih.l!llOO1 ·of ,m~nocU:~liIm ~liIcli'! d~a~ oiJllSeNOO in. pri:of'l tsoh.i1.es; (H) sewns :10001;: plausi~le. The degree of d1hrern:ily 11M)" a1s:o be il'lifucl.irn~ ln Iilile ~~e:x:l Im,sl is: h~tl:ia100 lb.~!I. sinsie I priom. However;, :smne _ns ,are :lIllrinsically strnim depe~d!elnt,wHl1. s(une S'I'Ii<L1I:kS Olp~roadili.f'll.g dOll:1lliLy i,~ saawe 11OS!ilc..D.it{('.m,'1Il1. eclbjl.al:' pofn~ul~!e.read.l:ly mVllrtil~ 00 aJliIDIiI'Ieu !>IDU type, fnr'exampIG,I.lm h311~~'r.DY stmil~ (23). 11:'1. ad· l:ukll1S1 widlin. 9. sing;'ie 1105:l 'WOI!l.ldl alsoolf~r di f:!jtNmn.~. (ll:fV1lMIDJ-WCS]I:!!if'tl[ !lH:'3in ~~OO~L:(H.1l..~l 1'1$ dl!Vim\ mote Illlmn. cum, s~Ii'3Jn Ik't." fueenillldlatoh'tl. fl'Oan ~rm') ffilA)lU-a.~ priom. ioola!!~ f(l:!t~~ampl~, km~ ~"f! ~l!Ied tl1:;!U;~!I!f~ti:(l!] ·ofSJ I~~l!ilil'ilh a" S1l!eI;;'ll S'C!<'!!,~.e (5<t1),~!l!tW!1liu~rlplePr'f""~ lypes:-are "lym!,l'tO~phic s.!ftli!1!," wM1::h lrnp~~ly co·IO'JIlm

REVIEW
iyriwlmitW ~i~S'!.i~ W'ldl
1f!I
.<11

long jaIgt!cy b~r{l:re

POo",iliiOOulatiom
.. r.~)i4:I¥'!' !,>.! _ype

lod:il3i ~eGCII fot SIe~ooti(}J} ofa. "lLClllmin'!l':llSuve 'slrain" ,(58" I~dil:!ed, di:ffeuaJCCS i~ ~r"'l" '~)'Pe iilil diffcroIlt peripfuc:ml
1~:~S5'I!I~ Me'

e.uro:illlYa5J,OO, ish~

lPiilldue

1e,.'(pressiQll

,.. i " m_oe... \vill- 1. I" ," ':1;1 .m;:lmJ __ '-1 le __ Hom,_a_ ,'-,": iii <! ~r~ albd.lopO.~,gy, illOOulal.ed wilh 80231

of a ~ooiid ~es

(80~82).:

t[1'riO]l, oololilizat&Cln of!.yb1l1pl~t'lid Li~~.es IQ:lfIgp~

w~n d~riOOd:ii~vClllDI.

:Imms~r .iJCiOi~Sp;roiP<"I,gal.e lill~Glnp:I'~CIliiiriOl1lr;

ru:ld
yet

nep~~~i1iaJiti~;li ~f frioili[lropapri~rm :;;Jodi tOi!i:k:ily C<J!P1be co:ru;iclelTOO hlli Ille st~clpolw!t of Qlru;sica!llkinclic~ mochtmiSlils. A fo:tllilU'lImoo:e~
·dCill1iOili!,1JmJ.eIlI.'il. ~paroUDt

ili\~h;ich

H'i,IIea. IM)jj';ut'l<ll lift': SfUu

W~liliI()'I!lI[ liil,l.eaii c

c~d~ rnl,~mIOl}t~1 di~~

Irnrn

{jQ;.,6l).

,1E£'1e[1li!1illy, a "'priM" Ill"}, be co:nsi~~ !.l subtype ,ofPtlrP ~l)~!1:'!er tti!.,U tita.'5 the approt)limc ~OOl)~tres and. fLl'~ica1iol1 kf,tilc~ics IW,O'\,o\~OIll1Csnd evooe ~ost deFe1JSe5 and prop'
aga,tc l!~xpomrlt~i::1l~ly.. Onl~cr. mll!>Cemll [priOl1ls ,me

di'liM..i!lil. PriJOIiI$poopatl~~~ ~lm"'~y 1iJm evoolll!an), ~c6i I~irn~{and I~~~(l~of P~s~) 5~1~ inend~~~ ,oom"'~~ol1a1 (;~in~1 di$~~ (~(J)\ fllG~1I',~e.. ~n.d pa~l;!.~ ,of IJU!esepri.o1ns !u W!liceor Imrn~ reil~l~~inoMv(rnliani!l IITIl!!>:ltl]iss:im~lI!id;l s:lllOli1itflcuibalioopcrioosaifndi ~,OO% ~ed]j~i~y (8(J), L:i~kiil!ll!ll Priam. IPr'lIpatQlii'ltien Kmlllet1:csro NIElUlifOtiDxh;ity

must ooc:(nM)iJo(j~~ ,e:xperin-teI'IiIfl.Obsei"'!.ill'iollS rtilllt spH~.ool'lIfceUI thei:dtm~ li~yofdte. p:ro~g:atimg~mf~tt{]lJL~ 3!lJ.1nt and fi)!!(ic ~ei~ [~ ig iljJc~.;rln,gly pro,~dj !:halD k)oc.ic Ute sP'S'C&~ im!.~lyl'oad di!5~~" ~. in((;'I'II:liJ:ooia![~oll lJ~epal1!wa~ fllf r'O:~l<lilkl~l Il\e ..rnylo~ ~1n.:!.Je>. lulX.'S GB4}. However, iJia d~fis:cil<L'lSk:alsensle, SI,IC:;}) jlillcnllllclffiarus:lllal OO'C1Mi before the fa"l!'Ornb:lie I~

or

Ai !~.bIL'; ~lll.3nalli(l~ i~ Inhal ftri-~ lsits(l]f ~l!ati'~ely in~ l~ulltox,i(:iJty r.esOCIcs ~l:!l.:01! ~T:!JIl!]Icr.; 1i1'bllc,ci~igrnlleric :PlI"P SPecile!i (nruliloo ,P,IfL for 10nh.al)1 gellCrnlOO as anin.ternm.ediiarte Oli slae pcOOU.Cl d.ulli!l!lg priou prapaga;l.kln {80., 82),. NCI.l:rolOXi.cil}' Imy ffi.!Itlim 11.erili~1 PrY-oon«nnrali(!IJl IiIlmJ is ~h(ld !(h,llrrlflgoomVill.'ibPlfl~~ inr~eli~. ~ut ~~. ~~O"wer ~I'iL:;l~ie ineroa~ ~n k of lCan Pirion IlnfedlM~ and lr'l!oocl.ivelileri n Ole cSlIILx:;I~maCil~ly inf€lcloo mioe ToxJdty g:~ 1J1~:(i@!t!p~!:I Uli.ly 1J1J1Cllludmt toxk: lPrplk ~~ve~!i .W'e 110l readled 3). \IV~:Ul.t is the ,ea.use elf ccu. deiL1llili II, p:u.Lo!U, {F~@;. 'f):J[llr; hyp.nl~ is CillTh :!IQ~OJ:UJ:I'nooilte Ole noorood~(lItlelllli(m?' Ii'rtC loss oiffuDCJtionus: nol, a S'I!ItFfidool eause: PtrrP·:ulI~n ~iI.~ioo(PJ'/1pn'(l)am
1!1I13!! eJ(uiils [n a :p~(I~lt iflQCl!!!h.!ilT:! u1!Jyoo 'Wllly h wcl~ain8 sodJi fficuIl '10 'dem()r!~tro;~(l!;l:e!'erati{l,!~ of.symhelk: p:rii(ms. [11vilro~gemem:led '~mdlctic Plrio:tilS~' mili1!Y oo:nsi:sl ovemhc~mh~ig~y of specks ~lIlIm win be lrapidlly ClHlruinalCdina hest TIruus \!,irrl).l~dI~1ailll \Vbyl~lghiypurifioo. WP 1l1.'biJ,yloid ftIJilri1s: aR:l apparolDt~yof lo:~w~ceiffkillrr~(,:livf!)I: ~~1!1'IUy nom!la~ {(.i.e), That adau;Dilllnio:ll dm'Umg 1U!1~I}\I!!l;tQrr)]~l il'l Pj"l~/}'f'IrJ ~nice mi~ll Will· fClm!e fOlf lo~ of p,rPc ,n,!!ncti0l1,\lII,llillte loss or P.rpc Ifuu~cUOR In Ore dcvclOpoo br,El:ln, by i~s sC<!,ucstrauo:n,1ID P:~ nti~~t sl1LU tbe dc:lctmollS., ~s c;.:oh,llIe-d byla~clCd '~rpC dCjplclio,m II~.mmi" rom. of <lI.c:IJj~l1Il1ic('l(tk~J Hrrwcver,. oculwrsioo ·of Prpe to .Prf~isci~iy ccntm'a~.to ~1~o,gGll&'lio;: b~~s~ Pt"Jf"1'J mi1)c <liIi~·~~alDt. oo!prrknld:tsC'~ ou:KI.do net pIDp<lgate :infiXtivily- (64" tiS), So, :~ ·1t~llCllOOltN ...ie? .IJ~V:LW IlcnrolTh"icaty of ~r~~ lind ~ilon :P'llP.peptides has 00en iueporw.d: wDcHWetAML
I

raptt!ly d~J~rad~dI in, vi!,''O .and! disa,rppe..'u'. 'fllli'l CflllCial Imle: of hO\i1 ~~~:kll~ ,~, IMll~ eiR$~lbl~

lymcri.zatt(mphasc nlI'I.ISl reach ai .steady SUlte, that UtG;~I'OOI'lCmur:alkm dl)~ 11101. riss, ll'i!atis, th,e), ~ :part ·ofItJ~~:pr~ntin~.~$ <ilJd !1(lt part. of 191~ O'lUIlo~lylic 'pI'iI~~.
m,(l:3lruu!llg

p.mp~d

AAodil~"f!(lro

(Pig. 4)

p!lOll1!Ji_\1i!l~"'!ecllamli~!'l1 iCair! be
dl!O'l!OOOOll1l!11l.1oda~es

bQlh,Ore

9U1tlJCiHalyilic 1t9lWiC of lli'liMnrmdim~,priom.prop"9.gatio:naiJfld d~e~9.dkof (oxic:i!~y of hP.\1~.,IlIIiI.te p:rol.!l:in.-!IlD![Y ~ypotlID~ lt is a'!:i.(tIIl'I311_C Inhal Npiii!;1a.ct.~.~ IliCl'l1p~am riJ!1' 'U,lep~c ~ 'Pr,s: a ~'Vv~ffii(llll.lW,v.~v~r,. if PwPl'>llvl;<;¢lf:to;: o,t:: oo!!lic ~gent" dren Ule o'~MJied dec.o\I~H!Il.g l'le!.\wcem t!ile level ofPr(p'-"" amid!the ,e'X:I.erll of ~~DJ~o~o.gyis hardin c~!Ii!~ah~" Widlm~l du(UCllIgiing the pro~eIUD~

1ij~M6

" II

«(16,. 67]llh,tn s;ev{lm~ti~e.~ of in vivo c¥:idc:noc lime (d\ay$) :a:rgll!l(l againstdiiKlCt ~.(lI\)lLci~}':Delre art1prion. ~ g. ::1:. To!ddty .and, ~rioilill:!liter. A~oordliillgl t()mepm;~llllSeat Iniladeisll~iJ.!SitJa1ietl 1'1 Fillg. 4, WJilluttv is duew d:iseas~kl \vll:ich PiliPS,:: ~11i\'lilsill!. th.¢D.min, am .iluriWlllp of ,arem.~lated irn,termediat.~ (llrr Sf:::ie~prodl!lrt, tF'r·pl-,. wIiIR:e: th~if1ifledioolli ..agellltitlselil'is nlClt: v:~low {6~7./)~ Ihe di$i!rib'l;lilio:n (It ~~ d~l~dly t()~t. l1h:isgra.ph ilh!stf.aJWs (il'! ,i!J ihig:hlV'Slcli!~m~l:h: 'f0!'11iI)i!he sepgfa:thm I~f.~~ ~ ph~~o(~eJi!:a, d~~1s does not l'!eQ~~y mioof c~~~d'calsijg!I$,. Prioo~;m i;s, sh(lm im b'l~lI:k altd Pripb ,t:erl!CeiilliJfilltioriiin re(jI,(S6). Viwtietul dGlttedi ~ililes il'idi'aw time! of lAm;! rrp'~" not direcily ooxk: to uelillrons ilwtt do :is lonset of dinica[ ~'gl1ls .[!IId ·deaffil. Grl1lim~1IdM ilfe'ill del1lme:s.1I i.ev,e-lof tPrpt~h8.t ,~n be: to'~emated Irlot express: 'iF::: ~64, 6;5\, 72, 73),. F'liIlru~CJi'ilnO'~,. withgl!!~dlin:lcal Sll1nptx)(Ims.Th~ l!!I.~pef. ~l'!kl'ha!dedll~CIi'! f~~~!ilts ;QI leljl'.elof fif~~lha!t (a~s,es, lii!ilical :k".Gl:lkol1~. .of m,mu:(mal. Pipe' Gxp"","'iSio;n dmm,g, illl1~; tlilcfh tJittElrllndi m:!iidtyIMl1es.tllrmilll;1te at c:f9tlil of tlfJe'i[liIilirl~l TiIilellllU!I:baitiOn :iJenllld is ttms the ~iilil'1ishedbJrain ~nf~lio:UI. cmillpliady pmloo1~ time 13ken '~Dr~,rrP~ levels .1:0 'G[!O~S the boond<l,ny .. ~O'lIIrhasthlra,ll1ll mlll1lbil1l11tioolli!lllFe ei~liI'Ipt~iied:I:g:8~[j mn~Ci'l(rom d(l\i~loiP'Illemt. (If diilfli,~l di~$C, mioo ~xp~~~ Prif!Jt'"'lMI:!ld gOO~ oo~ls, .~~!]iil Wid~ mice., WI'U'N'~P_mptOf+liI!iii~ ~p~ at [~:reV¢lr!~ Ilellll.l:I~;l!I,~of>$. and II"¢"Vel:ll>GS{!3:riy sOll/D ,of ml.df.;~e ~El:VeWs. ,effoo: of fttPC IffilpmsiO:IiI le~l (In: ~nfeoo:lil 1o'Il1]h mOOc5e pinioos '1RIMLstJ<:IIIfi) lhe spon:g~Ib!111 !~eli!rop<!I.iIIi.o1ggy1!i!ldl behavio:m~ i!> demi[ln~lmalted ~'lhe ~liIree examlple5. whereas therourithindicatie.s wlW·type, IlIl1Iiireinrfif:d.edwijih!JI al:ulO'l~na:mi:es P'4, ?J}o Nola'b~.y., Iillii.srecovcry h~mtS'~r ($~~~7 .s'lf.ai!ll) pnQI1$ whl!\!r:e tlfilri()!!1~P!'~gg~~ tol hi!:JiIrI k!~b· butdho<ut d~~ia.!t~o!l~~ d!Jiwffi~91 ,al o«wtscles:pi.ce o:m.timmecll Prip''l,'- Foolifcli.m~ .and: iiiO[fiii'al HI~e:~Inl (subdilf'lical! 1JJlifettiO:ifi), flriOOl oopllieation illl ,gtia~cen", Sltch ~~at PrPs~ n.olR'ihle: fil1din~ d\.'tt 8~~p-+klu;lre {Mlh :5~ of i.lndp.moI11IU.I)J:6'!'!h~bmiD!. rMeiltll'l';!l('lls seG~ ~f1ood,~ O:rrlly mcCl1W~~'Dn,.iti~ [Jil18ilsiblG Ih~~. d~Dlgd.te roU1iiPl!iI.G-;l,1.<;'5iill~.p:i'O~iM. from Ptpc lei ,~ SUl.~ rl:~e .il~CoOfivent~oila!i'ttiJk~ (74). So" do 'Wild:"t~ P{P'-~expi:'C$ioi.~}. whLNliilorulatt.oo C al~ iliU~r~d~l!at~ sla:r~(PipL) i~Rln'nOO. IfII~u\.\~ n~oo Ito ¢:tfi~~ IiltP !in.dlot'i!qJ!ical:1!; w1M~RI\,fL n'~IiL'l~ptiQtn.~, d~\I\~!opl~"'('\I~ ofP~ ",!mill3ir fOo tho.~ oft\~i~dl-~ype yel: re!~aJll wen tll~!ll foof .st~!il in Ute p:~or.prP :Illice ~lriam, U!el'l1s.elves.b ~xk:ily Ito o;Ocw1Vltri0U5 f0I111a!!iOll, and h~iDS 8~n1p.l!cs1 1lJ.ai.nifesnamiou dlis U'll.eCIWl:r.s-lml n'mn:O'ls:afitc:rOlel r,?,riIm4y~ OOl!ln~erp::uts: SUlO!~ned~flrsms ha'V,e bcenlp:mposct\iIflCi1ud)[n.g Ca1iI 'be wliiluen: aoomnlts~SfmliI1S, Jii:lecl:~aledbyCIDSS~:IiIll!:cd cc~.~ (umbill. <I, mlllch, ~lo:re [)I'ol(ll!l~din(;ubadQfl smfaa(': frp:: am:lalll:ll~. ~pC Itmffi.cldng .mG ~rioo (fig. 3). fll:ltl~CrI111Oro,. 1~g,a201rr!il~f:1.lC III Jir;~ Iwpolog-y (76~i9').Th~ 3'1{(l;n~3ti'\!'~.:M:'11 Ch3n.~ mrc~,wh~hl ~ :M. aW!!l W·f:Qikl. aa~ Pi'ps,..+~rPc ~ ..PrpSe~~rPc ~. Prr~:'PtI'P1. ~. PiPS~:P~-A~f'& +Pr.PSi: 1@!I{lig·of ·\!I~klj.~yp!3 Illl.c'ill, !ru'Cellln'lnlb (1ILllckl)i W lengoo,.h(lwev1!r; by UI~ :phetltna:1ill~f1{!)I~ .fir $ubIC!'~ AlL ~__ __ y..i!a ,>II e ~-w :l'il'PiS~ ~- "let.;;: :::lI! IL - w. ~'Y"L ,[kms ."'~ _ __ JL_._ -lId·-h~ {hi~ Wlooe]'Prp'L. L"l me' I!o;t!,ic ~i~~ ~ clfu:lical pno.!!! i!~lQc~an in w]llj·l~p~ Ilnimal't lJ~e rc~.<1iliveievels ofln",icily ,!!~d~!1fOO'liv1~y.~. 9lll;ch.~'ef stones ar·e ~!m~ti~lnCl'!lesl,wIL~1.C'd au mse dise~e (83')'(Fig ..3).

·tt

I':!,

1100

.i:300
11-

, i

,,----

BOO

the:

nm

ru~.~

Purr

~c -

9'34

REVIEW
gQ\!Iif:i1OO
nle of
lrlm(!ilr:a1:iOl~

I~ the !'al~o O!f

()O:~\fC!'l!IOOl

(k:i)..EssenIJ

(k:iJ Ito Ule ~

inhe:h~~ti~i
of
ItEi,C

/It

!tlly,

flro.Hfer!.ilh~ infOO'liim.:IiS,F,lI"~ acns as: a. caml:ytic surf:aoe t:Ii;P'0i1 WhLch 1~1I1('l imOOrnl(;!i:!.Lates rtln~' (l;fore 1I\£y b rnn:MQil.l:~o Illii~ P[f>-'lI:'~U«.. Call:~1)t~3!rIlly, liJ,iI~!rr oo!~'o~nlntiOl~ t~n

lri~ d'uring lhe all!~lylic

:!l!'lJtCe5S

becaese Intle: ~plllbliolll of ~e C1!iIfl'" l"sl: Hsclf is ri Silll£l.l!."i:poilRCn.rtiilllUy: TIle di~Te~nre bct\~lll Ibis 1I100cl and 'lbe cl~ieal ~oorl1ii is ~~:r~

is

f~n~;ui{fin·of da$:st~1 hjJ!~umw~ Iilot. C<ru!1y-;&l~;d ~ ~}d p~i)J(l~". ~!~ tlle:C<l!se' of <l! ~ulbdiJdc<1!~

ililfoctim~ [l rolali.vely slow rmc o~ ililit~aloolw~i.lU:!iliofJJ (k,l wOlllkl iIi11e:lIU 1~lIlIm th~~c"vCJl of iPrpn. '!>\I'Oulcffi be iG'!i,~ ~1riilJ!",ilSra~L:l or~!I)S!S IlliIrough Imli3!!UrnilaoUl (k;l!)w'O!lild~OOl:'[ilinarnt "[iI1U$, .~ ~arge ~lrao!,IIilt f'PIP'fS~1)1F o

_••.
Fi', •. 4. Illlluslira,ti'lllE! IllOOdel5 fm prodl!J'utii:(lfI lat frfl..: (A) iro(l(icttempli!teciilll1eml!liled.iiaibl" The! lIFL'Gst rudiirnerlilIlry lirl!ldel. has fCll!lr .~1!!,5o! iilild]ng~ lrnmal cOfIlv,ersiolil, ma1!!l)If.atjQ!'I., a:lild'nlil~nlill' lit ~ po$'Sib~e ~M: ~rpL m~~!t :d~·~lJ<d~'befotre, it is .~. '\.-.~ ~1j-I. _S_Odlj - -,. - ber c ~ ___I!r1:(lt!::(Uw!ii ~.,.i\' -Ilm -I. 00 __ !::",_g, 1!!1i!1ii! -- -, .... - - -"",,~c.~lh '~IIL$is Iii -,. P r,- c ;-,.''';'' - Til. - mll!_rn~ _ D.I,'IFil'pC·-, . i~. --i~ . ~m~.Q-_-_.!iI. ,; -nrV-'+:11 -. ,-,.il m"'PI'nn: -Ii ~_ - r '.' : i... @f@~~""f. !U!~ ~"' d~e-) Ilflot affect Iie Iq.IJI~UQtiivebelii<l,vhn Oil the< miOdli1L 1!G:d~ f!tN'IIp~atedl ~fi{ill I~:lrodu.rt. hll this mod'!!I, lfii'r~~ ,ilct~as stllna(~ cabl~~ fo!' thl':l'((I!i!ive:~sion Qf rr,pc~o 1fl"PI., IrDtf~ 'dl~ la'W;!f 'i:;; ~1iI!Jt a!'l iJil:oorl1!1;ecili;ll!ein tIn~,:s.ynlthll')si~ 'of ~,~P~,

infoct]vity\?{olllld

b1!li~dup, bul with

lilHe ,~oxicLl.¥ ,(!Pi1l. .3). ]3),' oonmISt, ilil Il, ~QJj'(~nClJlhalion: djsc:iLSC such as R~ Ipri:M~f:lfccti(mh~ Ilg,a20 ~[I,l~.o~ (\.vI.dl a hughexpuessioo.!~~(li

of

rate ofiJiliti:Il~ cgli'r~rsiol:l ~~ m 11.rapid accu~:ll!!i~arimJ! f rrpllk and ea_itydealli. o In lIDles:eciroull1J5hlCeS, dJl~rreistli
rrpc)I,flm ilirlt1~()(1

'm~'

l~ighCir p:robSib:iHl:y of fQlrJillhng PlrPS~:~~~ SJ::mc'iffilliim1!lgl~ incrB;!;.~OO.rnlBS ofiilliilooUI1~(Ijj 811£1, lliil.tum! dlL': level offrri::Npl. is eI~I.\ru'iCCdLAIsQ.d.~Ml :iinooi'il cam ¢](plairn, ~1~l~ifI]~s.~Ol'lbamer (t;,lmiliHld!aptaliOID,) cn'bc~ wherepriarn<UrY passa~e :frs assoc!~(Cd wirdl~
''''Q<)'''

,(I:abie

S]),.whicl,l

3QOOjlliJfllOd.a:ti.'lS

the:

:Il;:film",n

phel~!lmi'ii1l";l of ei(poliI.!2mti~1 prO'p;:i.g3!I.km .of hThrOOl.~vir)l', slmilUi.divfI;l!Sily <'IlI'id fIiIliLU:aJ~ion.lmlflsm:lssio;l!!. 'oorrier.'>,. row lite l!!1ll.\xllupling in-

~oolo~cd hlclIIbartion Il~{Ol;' j!ITl(~:ecd. a !lubclil~ical inf~lion with(Dn~ c~illic~i d'~ase in a Inl()nmlli:[~ ~atlll bui where $:1Ibs:eqpell:u passage i~ illL!: same r~ o.i'hosll:lead~ I~O a.ll!luCi'hs'ho:rlUlf i~c1Lloot1(mpatioo alld :hdigh. or oomple-h"~ilihilltilly (80 Prion :adarll.atioo IDOthli: Ile'W h!))~~l;lhgiu. !r<lp[d IpriQJ! ~ootP~I:iQn wil!!!! ;me~!lIilJl!C~clI rnte of intjjlj'l CQ'~'i,I'~rsiQ,!1 (Kll. \lIfldch 'W(Il/.!I:dI 'lhcl~ ~Iilevib,bl) ICf:l:dI. toa highel: rete {lfmnl.lat1.on of .Prpl- aad a. shortcrLllOl:IbaU.on fGu[ooL h~dl~S I~M1I.P~9llli::!~lYxt{lil1termodia:t(lmodld l (.Pig:.. 4A)\ ,~m!(:laflJiH1y 0:1' a !;tmim I~O :PI7Ofl8ilff~eifil a ~~t dLl.b~d-~ '('Ill lihi'i r.'I~(lf bolh fl1~t~l 'oon",~~~(m and of !.w:aW!'t.littl()!~;il5 ability fo Idn depe!llds M i!iie oola!toe of l!lOSIc rotes. Ali. altel:n~tiV\e, bl!lt Ite~aled,.mOO\;:~,Ci1In pr:opo.sedil~whkil~ be N.P'''~
:l'iiJI~.OOl!ilil.lyticall:y w~l'hol!ll toxic (Fig. .m). .ll:JIi}W'ITV~. PCP'll: thei~ i~~fe:Mla~Y'~ 11i1~~Ofi"'illr.~LUi'1 Ptdlc to p.pL of U ~ OOiNlC by ..p@dl;i~t lill n~~ 'M.\e'~ l()w-OOi(iC;~, hi~~4H:er infections. 'I,1j'Otlllld.mse~~herl~le P,vP .~
imlej'jn~d;[:ates 1~<l~!Pip'LOO!lVlejSfun,

II"eanaJ11i ng 'W:LC\11111 oO'Jilsi~mf!l1t of n:qUiiiring G'n'ly :Eli ~ngJe !Ii~e p<tlypeptidlil I~;Q' OOi~stJ:mtc <'iU~n~ of :ior~ct1ivlil .ood. l(f,l(ic spectes, E.~tlUl~111ny, lIi$phooom:~fI of pn(}Ji'I. dis~~ padl(l!gel]~is calli. b~ ~!(pl<.l;i!IilOOin. I.emli$ tlil(l kiID1~iCsQf~rion p:rolp<l..,gad~m. dewfI]]'!!100 by hJ-

~ec:~,V.il:yfwm.

1~.elQ fO'tOi1>licity,whf!e

or

or

by Imn.8mis~iolll sltldie,'l i~ inbred iaoomtOlY m.Oliilie: Uoos, AlduDt1:gh. ~n 'rnll!ctt~~ Ihi'loot'l'li'tll:se ~t.l,:1! iltki. '1'1 olrhil]to._~ .'Iieatly d. iS~111,Ct P:iITO.1li 81.', Rltt'1S <1..,... !!oolmed wilhlrrpr Ihat calflMt beMoch~nicaUy diffem,'el1~ia:l!;id by Ctm'ellt m£~l00s '\'>111 IlIllm be o'Oserv.ed, mlCil~r Lillis gCJilml. (lootein"!Jrnly 1I100J:l. sll.(lh bioohell:r1cal or biap'h:YU:aI difftm.:.'tloos :~n. INP!'i~ n~l).Ist ,exisn"a:l'I.d 1I1C'ilIiIOOC!. wo:uld i1mdkt lMIatdiffmn.c~ ''''i:)jj!l!d lbe o1b~e:ii'Ved Wl~. 1IlEl'.!'et dis(;rJmill~.tlI'lg mO:~~uil!aruttJ$:lh~, cll<t:lt¢[ilglrlg t!~e l~is;lmi~! (1rin1'-O'J of bkdog!C<lJ cl1!iS'S~fi~~m!

le~<lY W~"'lI!Cl~~rim~ _n l}'1PC {dmJlf~lli11l1t :Pd,,s<, ~rianslll'a'~IlS. p<iIYU:r:Jie;r' .B,lfIdiis ell5emble) and. trssu~wst env;irof~mool (PIP ooql1imce alflcll~::~;poossi.Qf.I le\l\e:l, Wl,~:er ~mptioCatk!lu n'l4Ji!ll:LIl(!;l" gmu1S, and dG.,'WIlce JWLlCI!llmislil11ilJ> ~~J» 'fhe i.ilJilflr'~\Ii(: advances i~ii~ lite fj'Bl!dof ~()n of prufllfl\t\od. oOlilfl;}m:'l~'1'8Id~LeU1fl\imI.~I~r.ms- y.eaSID. p:rim:b" ~lrlv\t'l ,dloat~y 1~IaMUsI~oo.lI mllch

or

m~~$lkulllxJm~rll_N~fOt9.1{~.e;fy i$n.u~d1a:I~ lJy a

PrP s:pecles.,i?r,q., di!Ilanc!lli:mll PiP'itt bU:I Cil131,}~ed'by' il,i.'!il~dljooclllts: 'W11~emlPlY-- oo:noetl" IrnDiOJll passes a. :lO\':'ia!lWilri:[c UireShcilld • .Rapt'Ci. Prot)" '\1®Mio~ (~.th II .Imst-a.&ptcd slrnllin sud iIlrn·jiUilIJi
Of

wid~'f lJ~ol~~~i~rtamt;~

ofpri~f1-1ij:~ PIl;)-

isp:rorluccd

high klvels of hogt NpC' ~;:(p:~~on) I:'e:rults ~n

rnlets s'lmv.

lll.Wl.m!iirnilro:roxtci~yaifldl. dLlath 31 ~tmii!,.ciiliic iltcjj:ba;~ton ~~~ Slow propa~tiul~~~liI:iloit il'l'fOOUo'R a,cross a llI'ID15ruiss~{ln ~;l.!W~ef' or '''''iih tOM!'!

eesses and lia.v€l ~Uowoo direct experi!lle!l!a~ oonflmlliltiml g:l' uKil6Olid<l1 :U1il!cffimnisHus propos~ r[m~ \VOrk w.h'h iIllBlI.Ulmliml. prio:R5. Unacl'Slm'idir1g dli':SC p~eil.oiluml~ wi111il:~1Il1l;l["!I~l'lP~ tiilvoh'un~ ~Mte~1Il1!l1M!folditmg and !llru!iIi'Cc~"31i.(i!tn, ru.'bd. p:roteilit.lJa.~d!~li'IherilIlnOi1i., w:l'l~ch el~'1[l::t l'la\i'¢ raf-~li.cil~l~g imt.1plk:~:ltio[ls ~.I.lpalh.i)bil)I~~~irn.~~

hoo!.

IGI~!il!'l!'i!lM11!d1(lil Howl'W!!l;Y an Iffi'a~~~ ~~~"Irol:WOOI!, bc:bmll;gihl ungglll:~ TIIe:l Irocl,,'Ul 'L'l:'tptlrin~~il'!ntl t;lvlitl~i1Ioo for

.aimi prolonged! pcriooJ! orSi ~'>tlliil~ cameu sttlle. n(l~l'OOp.t of ~riO:ii'l !>DmiID'lorigina!led

Ptr: ,e;,,;:~Qm)

andihe evO!l!L~ion of·oe~lll!l.mr IJroc~s"

HO\'i,l'e'\!'er,

re-sul!~ In ~ow lX\um(l(.>.;.icily anci. ~l1IiOre vmi,ab~ein(;ubadQfl

fro.lw

I!lhe..~ 1~~i!1g COJ!oepIS !f!Q\.'I,l ;ll~a\?J8 a ~~er& '~looe'~ for ~f!l"!ll~li!ll!]~~p.!'i:O!'!!S I!O ~e 'poo,pose($

bi.cdo~k~l!t i!!(PM"l~liIt!l~lJilt3i1 m'Ol.cffl).llarl,!w(l:~ .S1 dwre ~~riJ.e ~yil~ di~linc.,t i*lf~ti(llas:fr" poly.n1e'~ (P~

IU;LUTImrufOl'! 'priOL~ are dis.tlinclive.. T!II!ey life let:lml ImlIIDJ],'CI\:S pro- e"cellel'rCC-illideed!,. :io ili!: 1'I!mJd~o .• d~iiilkijJf OI~hercn:si19,Ies;or ·illfOOll.o'l!LS diseases widl 100'4 m.C!rt:ality mgae lite carli~<;I.clii:dCilJ ~gntll1 1iI~'\I('l d,~",~!opLj{t PrigDL~: ~i~ Iro~bti!!~ qu:es~Q!Ul:in e\!OI!u;~i,oo.

1~8)'

'11I.3ll::<I.1'I:110'1 00 disling,l!!lisllOO

In '~!1icll!hlr,

~(IW

did! :priorns: !;:'volw as ~uch

REVIEW
f>ol~lIrt p~l!l~@l'k'S,.OOlliJPlcte "vilil iiliIe .<l!1bij.n~y Ito i!l!fect ioiJn lJIle env~ro!tll~!tt h~e~ to the .utd
~11<'i&11? COIJI'IIICl1lDOlialpalhogeuls have ·Oovolvoo;
is, I',. T. )arr!Jil!, P'. t :1. iclnsoory. (1'21113, l.o!!i~, 1199.3)., M. G. I1l~Mm'~ .(1 ,a/" .1loorll!' 31~5.6B (,'l!004}. lS. I.. 1'1..fi;~t!iiO~, II"! Si\m~ tllCm atiId r>ernp~lli' ~M !lJ~lfom. Nll'lOS ~!l:Jtr~tUpJ\ll. c. I,· @j!'Ji.!ii!!iik_ c, ]. Gi.!!bi:,.~. p- ~Pef~ !;~ (y;S, G!i~liI!lI!I;i:lf!t !"ril!ln!fl!! O~5~~j W~~h(FIIgtl:m\DC. ~'.9~~t PI'- 24~2$7 •. lL6, '5_ 8,. 1?11!tl!1n~1 ai" Ct!:l'l61. 613; (1l790j.. ,I!I!' 17 •. II, Colllm,ge, .tII. ~. Pal!~~!ll"A. ),. ~d\loiD,~Qa(:I!/3:.17. 1<141 1.6. M, s, IPiltll'l~r:,,A. J. Oryd"eI!,1 T. i!lU!l~~, ], ~oWin!Jl!. N'oJ~ lI:SZ, ::14'0U9'11l ~9- M. 6n,li::~ (tJ" ;Rhitw. r:r~.5. fl:. 5!J" !!..anffl)¥l .fi /JJq.!. sq. et ~4,~, 1105 {ll9~4L ~D_ II. ('~ILilflg~ ~ at, l'Ilat~ 3'l,8, n9 M~~)_ 21. I-R. IFr~!!1l'.A. G. (llddilMl,. }.CMrp. .A:lrJJ~i!. ,83., 2,,9
U9'l'n, U99if1J,.

~,::I 5:,. 11:. IUl.oyd ~I •.

m.•). !i!!JI. 'VIlDl..r!5.,

J, ~

~'l. F,i, iii,. Kimil>t~r!ll., C, ,A,,, M'lker,

2~71 (~!004), 'Vflll~l$l, 487

(l(i"ll"~ex ;lne<li'lmiSlm to C1mble ,:adtm,g0I1es~~

snd evade dcslnn.K~L'O:ii1. ~f jfrioos arucoi'l\jlOs:e.di tiil!Jl~lyo'f ,iii; !potyp!:.-plid'(! eneoo!oo lJy Idm 11C11S'I,

~,a.w

QlI~

Iil:lllJ~l

vc:;?' ~I~ ~n~~

.ul. ~liii1ii

Ihal

.ari~& flQ!\Ioa.i5 al'li!ltilcl fIl:Ill~~~n!l'C 8YS!~~l. and it lis Ir~lnpti"~ ~et:!!!i~ to !!ti1alpciO!!5
1!1IiI~.li'Il<\dlo
I~iheuefure irepDleSeut

lIlofl'lmlactivily

111Si1.priO:llll [ ~pGeiryd:uffsrol~
I~~L';

IlInllflllililo~ionef an evolved: IIMlt :tms :;'Cl I~D' be ,ctucid3loo. cm~clwOOelllforl1rMtt'loul roq,uin.:.'iI i~.o
,dJli.llC~I~l'l p1iil\\ll{ltype~ ~~ I.Ip

tp!):8siibil~ry.. pa[h~'l

]ik~[i~~ood,. d!lM Qdtrw

~!Utciw!~bas~dinji'!~frla1flce ~~'!I]f!:.Swmlm.!,'¢~I~ expkr~!oo ~or bene~t w.. uWll~H!.Iia~e",or~6Qlt The :IUOli'e ClOJi1lBlIOIru Illleurodc,QcIllCr.l!:iV'e dl~s= eases also iI'JNIci~V'eoo~umulhlti.mn; of aggre,g<llie!i o,fmlt1s:fo!dcol hos1.~nooded pmlCillS.. it 1'U'lS!o:ng been speeulated dliat smlkl {If Itlu~ llI~di:n&:rod ~p~m()llmill)l nli<mllis'ilillll~e, RQOOlI wo.m< h:;l._~ shm¥11I dllilt Imci.n c~iWcLl! oonJiliI]~Il,g P~TI!y~,Qicl d<es~ts l~kem from either Alzlhe~mer's disease I;lmiellIlS or OOJlsgelllic:mecc, exp:~Ili.l:l, ~..ruMyioid. I:i!Ii'CCftli'SOi" ~r:otcuu (A!P.P") nlluiUcoo. p..aflmylotdruis and rnla~cd.p.atl.to~ogy 'W~lt\illlil'lj(lCffidi into the hr:a{il1~ ofpresym~tOlltt~l.ie APP ~J!13J:b~~ni(,': miee (8j) The il~duooo.iI!l.lJ't~idotic pj'l~mJ~ v:med wl~i~ boot and oolliooe ofa-a.eI"Il, fellll!n.isoemt of
j?lriOOl

~2. :B. ~~. :i!S.

It A. 6!e~lof!o, R, ~. i!.ta~ID"),, L"i.i;of,66, .2096 U9o:!lI. s: Bl!l~4ln, R. F. ~1f:!;1!,}. Vitol, ,!!la" j!a:s~ U99,"" f.POirdJ eI ,~i~ArIil.M£'IlffW, 3151. 761 ("19'901. 6. C. iI:eI!~rII9~~ ffl'•• 5,~gn(~.2::1~, ~Oll? ~l W~1. ~~. II. $af,l!I[ e~'aI,. Wal Me-£ I'I~:n!>] (1')9100. 21_ Ii. KlJl:liil;l!j; M. IiI:. Gr,JlS(lmllp.,. ~_ .Med:. ~, ~!OO ~'9),
It. ~It II. ~2J~~'. (WOtJi),

t. E"

n:

tl.97W. 5,5, M. fc!\),!t:!.!HlidOu ·~t ", MJ!lw' Mmfco{ 4. 800 (2'0051. m SIS, !ii. ,fi1" ~l.g~· at ,ot'Im". j •. P~~., ~8.. J!'H (~(116). ~,7" I!)_ ,M_l~)'J~rJ. tt hfiJi~.IL MJ:Ci!ilJI~~, p" l Stei!!~i!', Vel. Allt'mbi,a.I. 1M, 3:3 (19 ~J, ~.e,1'1, ~f1I~[!r, U, E. 'Ilu.!!, In. IDIlilll@5. ,r, f!. 1F81!l]!hJ3r, If',..iIl. ~cB:rid~, ill Pvlrm D,imru"~ oj HJI/fllii"!!: amil AnirIMI~, S;, ii, f'ru5iller. J. {:[!II~Il~,~, '·O'I!Ie!.L II. ~~l1om.. tl~j, m~ l::mdli~l, :l.99.i!'.lI.thap. 2l. 5'1. Ill, A. 1iffi!.1~. Eo Eillti1er.i, IP. [~~r,~ ]1,1!'!l. 1r!i1'J;5!.d!;'. 1- Zajio~wn!t'~ ::15:;1,. o~ (19?Wr 60\. flI. f" Hl111M at lMJ:eI' .:I:~'I, U8IU99J, 6i. ). 0" IF;. acil'W!lim ~Im.. t..:ln!t.t .:li!S8, :1.71 W)I)lJ!. W Ii:!. iii. i3<uffi!, !JI.tJlf~ trJlftWl ~}~~. 5n U'l9'2:)', 61.G. R.~t~II)J{ciil'$ (fj',. iMJ9'O 1, .2:1. ,ro~~2Q()l). o,t iii. B<uel.l:r el iI'iIr~.ceft 73., l1]J~ U 991). 65, J. C. !1!i!!'UfII~. A, B:. GIiIrlke. Pc" !J" ~8!i~e.. !L MtwDfmell, J. Hope, ft,:'w~i!1tI'a!~ ~. ,3~;i! tM'~t 66, ,6" fcrl!liii1 .e~'m'., 1l!a(1llf{J? 9:62, !5-1Il f:19?.;1}67,.(:. !ihelt I'!.t Riml!il~kl;S'ICarnei~ I( ,Maurillirell, 1- (;3~liLlWi,

(Ilheli"

S" lB. FIr iJJ!"1 J1fti.r.. I~& i1Ii!,r,

:16, 2'2.7

g:dler mlijl~loidatic co:ndm~.iOl)g. mi~'lilt.~. at I~~t

]1,. (;I,. f. Wild!~rth .!l't .:'If,. Mar. cr!'Il.efr!!i. lII. 55 U:999). ~O. I). A. i'lod!K1) ii1I til.• Mlt.Wrt 3j1iQ,~i.l U994JI. It. Jt !'l!e:!j!e!' et :!!l.. !VarnJl:' 3:i1':5,,693 tlJ.995~. 3:2. II, ~5I:mli!,~. s,,~, >C. H~I1; C. :5~1~, lIl.21,U5 ~,iOO51 3:~•. A,~h;i~li.!5ILir.~i ,gr t:!l., J ~. lfJirO!i. 86.~6.3,5 (2:0!05t M. III Wl!!tawa~e~' m.w (~IJ ,',6, 111 (1 ~14). 3:!i. Oliir ~ij@rulJtli!liM ~t~ w,llh a~iI ~2.o iiTike, ~6" G. c 'I'~:mlilget Ge-1l!s.~ 10, U'3:6 t1.996t ~.E~ rtJaror !!II al~ lMf!cO 1- ::!.Itj, 241.2 ~20i:JM. ~8. I~ U)!12 1~J:pmmell1:S, ~(I jll ~I rfIP (D.S IIl~il]l \\Ia! iIiKK!UliiUiOO. w!!i!ih ~Q.Ufl!1ie-~ ~o ;.-lOI~ n~~l!1~i,

~9.

:no

,en

C. Sm~JlI,.tJ\~:EO)_ 2Zo 5.435, tmfi~l 68 •. J. (Illlln~ I!l. ,at••. ~,tmtgl~A6.. ~~69' (:ltl9S)" 69. It ,I\l@i!lbri ,of all~ Nr!um~y 4;!J, 669 U!9'92~. 70\, tc:. r;;:, liIi!1ao, .t.ral.,~d.e-oIN\e 2!l!c!' IS87 (i:900t ·~Ji."C,I. ,a lit. S"6ffl{"e 275. 40;,]:~1997l', ·72, A. 51!il'el, 1'1, 8I,l1eJl.~f;.IlI.IFi5J:h~f,A. A!iI.II\illi~ [. Wi:l~5o!'nan~,

~~m~~

(ell 71, '167 U W<I).

T:!. 5:, Br,a.~ ·tit ~~ .• 1I\tiif,W't l'l~ ..3l~9' (1:~'%). 7'4. G_,MaLl~i!!1,J!!!' at, ~l1Biltt ~m,l. :371 Q:lil!fi3:). {~~ (i" B, ,M.!l!lucci i'!$ !'Fl,. N!ltI'lon n..32$ [2Mf). 76 •. L SQIJI[jro~f ,~ f'l1.,. ~Wil{l1 ~U, il:~·i1.<i (2,aO~). 77,. I,L 1f:~IIoer!,t lli,. Sriell{~'n9', 827 U9(8), 7a•. J. Mill. f!.. W'oIlfII..'mrn. $. ILill!dqui~1..Sde.I%ii' 2:9@,]:raJ.

:Ii,.

m"

s,

su;aJns., ]t is :imlIcr:esl1.iIl,gl.o ,~I~~c that stndll~of~[li,lo~.d. Irla¥ develop SJmn,~ l~rul1.'{fl!lsly m Alzl:re:i1ll1eu~~ disease 8.Hd mnglht ClOOirn.lrnle till pibl300l)'lpic 'I'Iari"hii~ly i'ul. ~fI'li.e:uu& 'nie: ~~b]lir.'¥' eoci.'iiI$.,Umruf:oI'!iJ, fhilt 1i11~ gooe:flI~ W-I ·"r lbe m<i!.e!ii~I. rn.mde~~~~.i~ lIlay ik'l!'i.li} wid'-er rel~vanoo 39. !l6. Ml!d;!'!eF ~I' al" iliM~1.~~. G"e!i« iJl.!. 001 (:20Q4t I~ gdliir disea8(l;;'J i!~vo'lvi !l:g prow'!n; mJslbldJ~~!,g. <110,(. ¥. Ki I'!g. lit. !)Iti~"ll>ilgi:. ~.ii!~4:~:!!,~1!SI (2iOO~·).. andaggregallnn,. .n_ U,.fan21~.a. f1" (htem fit fljali-e«, It. (Ii!i~, ]. $" W.ri~!Jti~n, disdnd
l,

]!\I!]. iilre~"jo~ !:i!iit~1 bOru;l1 H4e J!!Wn !1I<!1~ri~l, apprgi!:i~~gs 1i~ 1Q~ W 1Q~ r!p !'!I~r~w~~~, '1lf!ere~ore, I~ [.~mp~~d pnrnatj!.y~i iffll',ectioo~ t]1a~el'i~~~1Jtj11 a !)I1\I~ll:!Uf j:!rlimnl irWllCul.!Jm 'wu~~ mr.tlilFIJ Uj~·ID l~w IliIfloctll!lfii.s runi3" if I~iluti!l\l' Iff Ih~ ~liItliJetj(: ptlilfrl illJt)(iIltOOll 11').1':0111 [(e1~lltdllfl 110 trjjn5mi:~rml~, ~Iii~ 'WG~td im~tl! dO iml~tr~lI~ ulTlil~ li'l1f ~ndi~lItilld ililOOlltOOl omdl toore~re Illill, 'piiol~~. {oOll1p!l1"1eilll d inl

Ri!fl!r!~in:rt@S

am]11 riJot@!l n::9.eil'l.

U{!ilfRHr::.

IL ~c.S..GI1~fllll. WQ,fljU! Zl!i, 10<1~ [1:961}. •.

2.. 5. {ll. IPIilJ:!il)l!f, ScitHtl!' ~]J.6., 136

et al.• S'!efllfe .30(1, 64:0 (4li!Orn. ~" ]. 'G!f,'li~ge" :~. Co l Si~le, ], U!iad:$. J. Ilr~l!'!,if.!1e,A. F. 111m.
4. $. ~ljjdl NfI~~ 3!1l, 6,~~ U/)~I~), li.. 11. F" Hm ~t oL, Na.ru~ 3:9:!jI',~"~~U9 1), t" ,M. It. !lr1!iCi! £1 ,at, NIfIUfi! .:)11'1, 4.9'8 (1'!I91!), S. ~"'l~l!il!lJ!, ttfllllt'.Ilt ~~iI•.~I:ili ti99o}). 9.~. (1},1l~ g lmJ'~f 3!i,~•. ;J'068 (2006~.

~,.~" (:o1l~~, MM .. Rev:.

2iQ, 519 t~OOIU,

32::1 I[:?JDOO), ~~. 'KiII~liI\3I-I. ~~ I!.. Ul1IiIquls!:. NIfIJ1{~ 43!li. ;,~~ (~l1lo;). It ::i~. It [)iail:".JI\'<lbl;, C. y, t:il191 ~. Wrlll~l'It SiNn, D.l, (lI!lJar. ~O!:". Na'lI. ikod, SCi I'JI.SL't, :i!Oi,l1011~ ~2:00~l" ~~. M,Tli"'IiI'I:<r, W, [11!~E11. ,. ~1iIe:~P'iI. ]. '5, v,'ei!iS!t1il!1. (wi t
~J,jj[I!!IlI~II,.

10,. So ]1. WI"l!!fet al." lmuel' :1I6a, 2061. (~OMt 111. [). C, GoJjdu~k, l J1kCIrol'mml/OO! .. :11.0" !.Hl,fI9·e.6L ;1:2'. J, iii, 'i:::!lf!!!!l. ~, 1;, ~:rafi!r; f. I, i, !!..!!I[I~b.YI!y. ffrK. iM'mt .MlllI. $,4. (l'S.Ai. ~', ~W5,9' (l,~~-

m.,

B~a(jl\m.3no,. U, IBaxa,. It 8:. !I\~C~i!i!!r,6MiSO J- .2J11,3G!!<l (2:GOO). 1Il6•. K Wlitlbfj~tk, 1ft RM.M:i<~ ."mr,!fl~ C/~'.!n1'. '57, !!;.!) ~2!OOlli, 'il7. M,. T~I'I\il'I:ii. s, rt ~lJIn~ IB, H. 'rllo)'llma, J. S,.. 1.I'il!fi!~illall" MJJIJli!: ·<;Iila, SS!i 't~(6), ~8. I)" 0, T~Wrr ~'lm.. ~!"h.1IIl!Q1i. 1]9, .nl [19941.
~~, J!\.

n:g,.:t~ (~~).

{l6, Priem til!~r rui'!j'i!S sliawn wUII £q)rnilH!filnail !iI~ .amd Ino pl,at.@.~1Jj Jlllas!l!a~, mlJj~Il!1i~'~i!lI.)I .. I'IaI\i!l'i@r,th,~ ii"ilixM i~ nUll~jli!!nd!!m Ilf! ~[lt!!~iflf ~lnw[~.IPI~ ~il'll'i3lfii~ IIY:Il'!Ilhetirnn ,amI! tiioom: I/f!t ~ IIssayed dilruU~" 3?, W·~ar'~ ·;r.llte1llll~o ]. Wadm~r~lIll!r di;i!:ilJ~i[(l1]J,ilI~d ~D !t YQIqI !",r !l'l~p~~tioll (If fi~u,r.es. ]1.(,. ii:il! direll(l( of, .~I!K!oo~1!J.~,C, ."If!!;! A,FI,C .. ~r~ ~~~~~trli~r:$ i!l, ~"~~I !,I_d, .~ ~~~rt~·ua~e!ll!iiimi!{Ji'.!iI.liglJ1p.a FI~ liLa!. id!i!rn~irl,i!$\, ,:i~velfl,p~ alltd I£(pOOit~ ~F!lipr1~tal)' di.a9J1JJ£..Iic amd th!!-laJ~IJI!~ ti!~~ts alldi t.@!fl"loo1ti19l~'j.mr ptlItlll·~l~n[jj~~ !
,dt,I!!:l!I!!<~.

(:210021 ~'9. Ek C!!!!!i~!!I!).f.!tri" :5"~lKe'lO~ ~,~35, f2!OOS,). lIiJ, fli" f" H1He~ m" Pta:. Na.rL ,.u"i1<'I: sd. I~.I:.U ;1. lQ24B (2,00100" 1'1:1. It 11!.aU!.i A, R3IIrn@~, f!ayntDlft!. 8., (a 1111~,)" G.), 8;, Clu:!eoclll, t ~rtiL 'lS~1!al()6,('uJOJ) •. lI2, A, 1'. HIli, ]. (allfnge,iIl'oo~ MIc\I'~1lli 11. S73 12(03)1 (I~,. M. 1Iii~(Mr e! m., ~1B(l J. ~i!;,il2!iO~,fil996ll, 84,.C:, HiI~~. ~I, ].Slelk()!l', !Vflf. Rev. ~!01I,(eR B.itI( 8,100. (:2001'), !IS, M. U~~·!.~llI1iIilnp ~aj" s?feI;;~ ~ru3, :I. nn, (~(llll$}.

<119. II, (I,.

~a~!lI

~! ~ l<irn,~", 3i()~, ,ar

179';1 1[~(!4.),

Sllp.pa,rtlfI~ OlillVine Ma!tEirial.

CW\!M',

SD. ~.~. iB~u:.e,8t: Med.B~if. 49'. 8;!~ fl1?9SU. '>L l t. Hl~!u tt aL A BitJ1. (f.oBm, .2~!!'?,,2:M l~,ROO!t'll 5~. IE.A. /il:a !roo' eJ al .. :E~O ~ 2~. f>~!i!l: ~'2:002l.

stifi/l!l.ernil91,~ ~\I(!liI'l!om~~llL!tl.llll!~ ],e;f5&~·<lf9~UMOCl Tatite 5'1.

l!~tl~~g.ft!!iI!~~l!_U]:~71a

Miw(J:fju'a. n~ ii.1;c~w:!e 'ltigo!ild !l1Merale'iy mfllcf' tbilWl Ute lal.allid;~I1i[d sl~ght~y ~ab:iiB:l ~o ale Hn,giI!I~~ll:iillg!iu end weH ISqf8.1i'i:Ued ftcu1l1 'lI~
ifiL~o.1~id!>
gJ!f/,

8S,ii~: MlllliJt!lfa,

.Pmllli'~gljlcltum gO.r-

l\1Jnt! lJ.ai,()C('JrlGd(J~l

l~riddleim/!~ooli~,iI!l6]y

_ Illl'd'L~Ql":1Irelna:ic l!L1ilglll~ are~parapll,y~elIic g:roUlp :rog,ard£d @jil an !l1~lCcs;I:l<'il0:1"s:lsre:, Imlt(IFl~ I~O;Uvilllg rl!lrnguful1;'manl!~]s (I) and :~kOO\"ll

u:

IE~JoLoIV. Ge~l!I~ !l!amooar~r Inne :ne!U'~ K~:18iI:il.J]cr Riv.eIi~ species mll'1.1incd. in lilOnor of im;po:mnrll h.erb~"I'OreS iOifCcl'lC!-roic land mrullilllll~, (lrnlUllll!llruJ!lies, (~()Ildy~ Leighl VaUl. V:alcn,
Sti!~<llC01r boo:r~d :qn1mal~ tretl~!IU
miDSt

lC

on3nlOO pm:acri.!!odi. ,&" WI. P:NJJ!lJ!lgjdaflf/J~ mJd (lX)lfmlIIPJ>Mi,~. (lb~i~,uely 'orWn!ed I~()irlri~gn~(! w,a~lwinh 11 ~'Hghtly I)1jiS!erio:!c.~'y<ilevc~()~ m~oonicli lIl1:d9SYI'1I1!1!1~IriClll~'mgOl~Ld, asiu Emlm.!f!i1,lla~mll d.. lltre", ~~O-j,'t clI!oorislidl.palll:iir4I~yc!osiing m Ii~c laloDti.d~ill:g~aU,y. a!> in Pfrflullfp,!ta!1.flll, 0'9).. • p'_'i1JU,'!1.~3nd .8u.ic9:If)(Ja~~;and aI~rislidobHql.la j(lilli~!I1g 'nh~po~!~i(lr irigrn:lidl '!V~U OOlo~'If dl¢ pg\l~I"01<lbi.at t'!;li.,~ ·ofl~e Ill"~I'lin Hov.'ewr;. :~m rel<l1lhre·d~JJ:1e~j~ i()!f laiankl Clk."~<lnd clQWlJy <lptncsse<i,ool:oo:m.fdmd! hypoom~lIlkl f:onning <11, posleroHn~8i1 ereg~, KNtJllJU!mHffl!ia!.nmis .~so ~Qlt1lparn1b~e SOllllh AiIllcncrul M(}1i.twliU8 (3)., to Amongil.1I .i!i~i~ of il~hailic Wlgllilares, KlwYlJ.le1'l!TJg!liaUJm is ,do.s~ to P. gm:m! :um. '~!)I.'lp!lfIGrp~o~ogy eN.C~t d]ilt ;t lacks c:jr:tigw~ici.~ [figure 3IFof'(4)1 and to Baioc'ClmifNl in Ijmvin.~gII Ia~(mjd shm1erlllnCl llan:o\ll'er tI'iilU Ihelrigol'liL'i.1

5pel!!:illlic Diitlgoosffi5. As foil' gemtlS .• Basa~ Iro:.pa:us1\Q1'I and: si.dmvaU CO:ill\I'¢Xil~ <l)fth(\l
IOti.l'ef HlOl;lts aIlf;OOII~p~CJIJO:1lil.clliffll;,"rel:rc~bf;f\;~n

~. tly f'OMils: fmm iU~~&r~yhleoo@l'iili of NoomI~ ,~Il<l!ic !.1l1b'jl).d~l~ C~~01i.L\l ooiht;r:iian..~ ~'Cil a<; aJ.llVi(i'£r~, Jvci!lJ~/'JI!rrt.lNjJ(fmtl()f~, a'f!~'IJf}'!ktops, P l Am~ca :;uld Sia!.!:I,la AmcriC<\ !he bl~ Pal,~'Ioe MciII,~,yii~t(£. Aoc:i1ruic 'lI,gulall!'; oovclq)C{l,d,~ l.md Eocene' oFEillrope",ood,lIDIe Eooen,c (Df Africa and l)Qssil:l:ly Australia. 1l1C earii.es~, ci'e:iinil:i,\I'C abi~i~~110 Cru.~l and gtii~ild! fooddlli'Q1Jgh I:ool.lc.ed h.cI.!?J'Ill.dJilIlim.'lm:cootwefll laac: trigonid and (811011, IliIng!ll~ale!lrt\P'r:cscIt1ioo by I?muj~lgrtlallJJ~l, Q~ 1d\,CllSpOOI!lOOomy. al(;l 'p!i).~si(l!I~ of :alaug~ p'riJu~! l1(1it)(;(Jl:W{/(m" lMl'Id MimtrUJf1f (1, .1)IOQJlilC: h~ollnd.. and c'h,Olr::1COOriS,b(: ilbra~i,{JU cal)l:sing ffOmll lh~ ,iE::ady Pal~octlini); f\:ler~[i) ,of tlgrd~( (::;1~¢r:fIMiQllt1laD!'I, No C~· I!acooll"loondyrartih ~!a~~! y been OOcI!llm.ell(ect E-kre. we de:s:c'ri~;:ilf:1 isolated ~O,\,ICr :uno:lar (ml:u ornu:!] of a oondylanhl'llanl!lirnull foom Ule; U~~C~I:EOOI!IS
(Mil;'i!~cicll~'UiaJli)~ac~.'iitn:l~~

(SOM le~~l."'1i;:co:nsici'cr ·
repr~I'I'I 8:Ul ml!Wl)I~al~

.KltrmlUtnlflgl'ttcmlnl

~Q

e:.u:ly !>l~cin

the CNO!.u.tton of

mcks

i!WIe!11\)edticd '!l.'dUiJ
oil'

D<occru.l v1o]cmaaic flows

CCI~lr31]I~d.ia [SllJppord 1:1:£ Onlitc Material {SaM) ~l and fig; 81], 11m tmITb is caI8lb;g,ooas WUJ1jr~131 iilndd.oepcn(!,iI~. in 1.h(1l Vtf:U'l·
Il.i!rn~e P.uw~IO!(lgy
It\)ry'

L<boM"

ofJmuU'l tlniw.l3.iw, CIa:ss:: JMammii!~ia ,L"IIll" aaeus, ~,75S, Ol1dier:: Com· dylarthli"3 C.ope,ISSl"
FaJlfl~~l}! ;lfl'Cr:![i!l1i~S~dis.
.1(J'tJm,1fm\l!~:~ill'(JI,i 'iIl'D.n~lIi gi~!1Ii1S .~~.\':l.l~es;
~Q'V,ili,

Th~ ~~IK:e ·Qf amaFCllilli.cungli!!~amin. d:]e: hU~! C~~il.O~u,~o.rl~clia~~1!'J !i(::~~~ tlw {i) aro'Llooc U1Ilgu.lartes 'bad <I. ~lm"Gm~.dWill'!i!J] isLri~ d btiJdoR,.a!J1Cil!dleolr absellCC' hl ol'hcr landmiilSScs 111IlfIY 'beiliu. arMac~of l:h1i1l.tClclif1dd Mwestigdons; (H)KJulf-,,~'mr"i~~lgil!,!(l\rumli1lll11lligm1.ed to ]ltd~afm.in '!Nes:I~m. A.sia, whi,cl~ had a divcfSii]ocil ~'>SJM)-' bl~ oJ :zlillL'lliesl~d.'l (.8~ mi IHorm. y~ agQ)1 rogM:doo bys(i!It~(') as a:l1ccslmll:(I ,ar:e'hanc U1rIgtilates (j),<:lllholill~'! any c:(mnectioo is dis(pUiICd :(~ <iud (Hi)l d~ dfiO:inS 'Indlan IstabcomJ:Un.ellt mayha.1>'e ser'll'Cd as ,liI cemtcr of orl:gjn for IlIa1!lY Iilk'lmmaUM oro~rs ilitId oUWJi ¥erI.c1br,w,c; me!: plant ~,
1,

Rl!:feUEliii~!esall!iil INQites .1. 11 Ar·dliwLilI, Ul'i!iiI': ($]. hrbl,

l~

sri: :12:2. 1. (1982L

:;;:, ~. 1,I'¥1

3"
.4,.

Ii'! 0 lo~yp e. V PlUUI

l:Mill, iso:l,latcd! Ingh~;lower

(i'eA e·!fij c D!~II9 11l10'~m 5" ASlfmJ'rI0uiia!llqrmid wi:der iHud l.(tttg('!rUl~. tiI~(IIn.id,. bill. OOuswsps, ~OOiid !i!iigllJ!" iy I,a'bl,,[ to the: linglil.<Ji1 !WJ;l~1l, wh.mlinoosprolfr ocrnid l\ViC{l as ~atge 2S ~lil:lfI. tUllo.~:ar,

5" ~.

V<!~~n, ~ l'~y f Il, 45 (];!)!ro). C g:~MllII~~n,. IL. Ci!iI!llJ, '~~~f;ilas ~ ;;l2~l! 1 t~O~), lllEiIII!rLe, J, I\. lHIi!gf,~n, 11.OCJrp Ml!tD'l:l Gtco.r, .33, <'19: (199;ru. l n, AI"tllibaliJ, 5,ritffi'2 il':l2. 1Ll)!(l U ~611 ). It Wltl@,G, w. 1Iix!!illJ~1!r:!;1,i, ~I,NitlM!l~@Il:,. I~.j. li.sl1@r, lV1lWl'll44il, lc~n t2~07,~.

lFi:g.ill •. IHoICJrt:ype

I[)f Khoffl1em.flfjuJat'U.m Ll!onll'Oteni genu!> retSiIil e.eiell nII)V~., lSl(llilt,ed rig:Jilt l!I)W,~ l!i!lolliaJr (!'Il[Of 1~~VPLiJlUJlMlU~I. ~~dI. !I!'llirocOI1l~Id1; llily4. hypowlliid; IliIy~d, h.ypOwlllll!i:~id~ fIrI:!!id.IiTI@1{Jjc(J:Ulid~ o~

1', G ,\i'"I'l:,~', 'iildl:nmvtlllfg~~ 5l!!Pp!l'ltfrOni t~, ll)ejlilwtl1l;,;:1:lt IiII 5tiel!Ke'ilI~d '!\ed'nolog~ !DSD. N~rI' l)le~!~j9J~!1t,ne, S!W5~I~'~4J.200!!l' J\"s. tli!.a!l~ ~!!fl I~ii!n ~t~C1Ja! ~(I~~e; A~~rny (1&1 ,gfili1~ ~~PJ$5J21006J'2all:lL, iil~1 CI.. V:amd A.K.. are ~IM~IHul '~I!I ~I~ (.iJUocillif S;rh!!nrff'l~~l'Ii:I;

tJldi:Mrbl. F,l~seiOllitil N@w [J~lliin!l .. S!.!p'PD1rting O!1iI~i eMaltieriO!I, n

OS'T; N!~P!!!11~l)!',
7~[lCl

omti.d ,atrrl d(li;G!y ~S\\tI

1~4J' ~.~,

IUle ~.o!' ~,OO!td walJi sT~ghlo/ooliqtrle to U~ I01,S: IL't~,entOC'(l!l!kismaUer l~iIIIM Ilypooonllll~.d~mdl bnsliLUy oCHIljOlLm:.dm it

~.Qr

uisti,dl of!l'liq!ll1l; p.a:d\, p.alra[oni,d~ pa, pre(ijn'[iI:llI.idIG!lI,spl!l:~e; Bind prdi" jjlleM,cooid~ight1~ !pirQtl:ltCOlilid,. I(A) Ocdusa:i vn~, (I) Unlf! :r:iraWiiililgl QI~ I(!II;~. ~() Pos.Mri(l~ milw.. (!ilII} L~Iil,~!)i',allvim,~E) AfliOOrl~rviE:w,. (F) l"bia~viil'W. tQi Pi'PI.QQi)iiiie]wid~

.'Wm'i',!llielVllllll.'lgJ,1I@j\OC!lji!'Ccrnnl!l1liTilVL;'3,:1IllI5.&'S,2{9,3 $!J\l!I T,e..ti ~ig. ~,IL

~~f'~!~~

fonmtng 'a.!ilaJb.:Hquc posmmlulD~llmlel'i!.'St, hypooomi" 'id. Ii!: Itilt} mostva1.u;l'Itil~~ l3~o'll~.d t'l1l!>p,!SJ~·oufcffi "'rust" ,mi8lnyel~d: nl\'pU~.a'b!n:qml'ly 1r.31fb.....

Olilioos {.i)..1iIlIe m~holo:g)' ·of .Kil.rm},!ef~ll1gul~tum(FIg., ]" A 1[0 F)is ~i~ fmt·of dlC: lO\\~'ln[lwmol1Plro~ogy of arehane lIffiIgulalieo;>, 'ru~ ~g~r are· rola:lhrc!l.y~arg.t!,and hm.!CllOOIlI!il tim
OOirlOOOO( ct~l>, .KJjt1~,}.~l'Cml.~q}l'{Jl.lff~1 rtltr:D.lflS :m1V1I~;)'

oo".eli!1g or: c~

J..:ij; AuQ!lI$L :20 Dt; i!c.olpt>edl 27 ,SiegNenl~r 200[11 110, 112Qf5cief1ce.U~!.l2:6;!

veme mlonnd ~fe" 8W~Sm:;lU.er a~IXJn~~ othe!' aro'haic 'u!'l!s.ui~ (SOM ~~

I~O

plcsiom!fhtlC drl~d~ 'd~ OO;:!.I!rvaria~iy in P~'DI"'j~rIQmm" O.ll'JPJ1JIUit~S, I!JllirJCrmodmJ; <lRd

OM.• lildia, z.cfl'1.~~' If ·l!.dt.ll'l!leiII 5UJdy il'1l Geology. PilnIIiID { 1J1ilrr.e'(~i~.Ghi<lllcligiillih6(1; Oilot Irdi~~ 1 . ~To,~hW'l corre~p.9f!d~m:e )~wldl be idl!lf\E-im:!. t·~"'ilt !!'!ulit!.!p:lIi.wpila.14I,£I@9mafJl,CiOiQ

IDl!'jlartrn,I!IU !!if (ll!lll\!agy, ILlIni~f!rmy iD'I' jaliliilil'iUl

jal'lfiml!li lBID

IC,o,rrelalli,on 01 'the Higlhlesl~,En,e'rgy' 'C'o,smlicRa,ys wiiith Nlealrby =' ~'lr8g818cti,c Obj'9CtS

1

baJl'd I!Il!lelEa~lli'! flfO!'I1 ~ilCe ilnl al[ diroctitn:!lS

(1)1 A ,~ 1il<1~!lSloundl~ am,g '~IiI'e<~i~o:ncW
~. 'L\:Xa.;cdOO1Jmi~'

OSi:nl.~Ci:':jysni'!l'i

pai1i:c~~Mdl mlIDclei 1I\.''it b(iIt~.~

of EcV,. "c deffee'donis, ~m:\I'~"ISrj Ri1IU'I11 ~.1 ltihal d,~ p~

:I.OOS

ipoot of id~~lif~~s:~ :!'liMe'sooroos becl;n~

a reai~it.Y.
S&m2004, dleAt,1@.ff

~OO EeV (1 .EcV "" ~O'I!3I!i\I)~oo:rt'rn {i!flrnag~

voh=

I~itl~

~U!d!

e".~n dIe

WIll!'e capab~lil:fesof~ ea!fi!hl:y ~<l!I'Iic~(laooele;r~

a.tlll". :S!:Lich al~C:S
C''\!lfCit1l~

occ~so IWo!i\l·e'I"U~rigy oo!il!lillic: rays <ilppeal~ tl:l' I:ll:~ginla.~fr,ol'll e'Vlel1ly distributed S!!l:I[lI'1~!1t$ '~bl!ll:e d@ts), I:i!ll~Ut~ (lrig~I!ilS of 'dl~ hlgh@S4t=€flE!fI1lY ,~tms ~t:roSi~~' ICQrrl~tlll MtI1i th@tlIjls!m!lju,~,tliolil of 1~~~1!!l mm~f ,as !l!:~f@S@'JiIt@tlIl y b Ii'ulliffrhy ,,1(~ye' ,gal~8it1i( nl!l.dei (red .5t<1rs). fhl!lili" il,ctilo!legiala'Ctlk nl!l~re~1 area I~i ketyoolnc.e I(lf thase ra~: .high·~ne:rgy (!!lsI'1I1k lua.ys"

Ob:scrv31ory Iilasoolloctro. a ilmillkm ~ti.Cl~m1i'[,·\f~I!l.l~ about 00 ~wdl ~~ ooC'~es cj{o~i~ 40 &~ ~ e!1~!!l wliIicll 'iII,!I:l e)![~; w, bel,lIil1 iR) .sood13l:i!u. suip'" Sky
II!II!<lp (2) !ih~ng 1OO~1!IiI~i[; rays. ,cje'ffiCilea by tin!!!' Pii;erire ,t\JUgeu Ob~erv.ilitIHY.

IdUI 'dl.cy ,OOJldl arise m.oolly the loost ~olc~. platIl\! ~n'd~ Imi~ \I~" O.!'!~possibl¢ loC3llim! ~s: w~iili!i!l! ,acti Vie

gal!acuc

,r(}!;Skm. (I f l[hie G.zK clTcm~ Firs;~. we eX:1l1lliii'lm:JI.11m dilll!a galhemd kfor·~ J!!!f!e2006. "Vel expio",,'d U~C,!!flla~!1!1 Qf

Iilllllciei (AluN)..

d)('J oooolJation ~amm.l(J!Jaus8l1dfIPPlied .helll) lOnew daliIl! rol~.cNOO .afl:er JiI!Iiill 2ta06, DaIn.eclJa:c18d .mo~ retlllnt]y,. i]il:1I.~1 l!IlrtlSl 2UO, (see il:w;l .flg~). A Cfll'lf!rn~dJ Inh.eoo~laiii(lft I:Ii100l]lrelrli!!:cIl!;l oifOle:se ~!.i!,t~ me<II'UIs f;Qllle cau!l'O!lL We <H.~log of AGN I~~,il!ns, 'knm~fJl.to ooi!l.oompietc. i ~ll)' i!1!! di.l1OCtLm1SlU wl!tic~ '!,:V,ep.e~U' Il'hoollgh I~hc dll5ty ,lane ()if our Galft.... and bCFOlKi, 300 millnolll. y ~.~glu:;'y(;8FS"l;'~y fmlllMl1h,. {his i1OU)b.lethat WllOS.toiflbc flil,,, C\fCil~ Idmt a do ,,0;1: a,~peajl" to !be near AGN are ~nldlliid SO:lIlewha~. near I~ibeGalaeltc: pl:al1~) The AGN lllii~l~~~'iI\~I~ild to be di!;IriIr!lOOdl~Dlg dl~ II1~Y g;;l~1.IX~:es.O'IlHd$0 ba~. on .he $Ia!~.isai~ ·Qf QlIIf~~:it d;!1<l! w~ ca;m (m], air 8h()w~s both 0:111 dilegt'QI!md\'vilh l 00 0 d~I,~:lom ~'.lC,OOL5~.n~ ~.~n ;>lHd lh~<'!r~.\!l~w,':l!:!gthe bri~ffl~hor rli!!m.gen n~QI~~elJ d~~ dle~!~ d:li,ll Uile coomi~~y OOI!l~ ·a;reoorrel,;.wtoo w:ilih. '!he ,dl~l.unior! of in cXl;i:ilbl:g OlIfie'f 'Ihe slilOWCf passes by (the same !:·mlll)!]!(If!!S seen frmn ;;]j !l!e~ !wa~;, fnCt~dI~~g AGN. HQW<tW<Ci!i~ b~,!,I~8e ,or Ole 'e!f!e~elic p~ cesseswidlin dle1m, hGN IlQ,veh.1llg been COJilSidered. as HkCiy sQ,uli\les of different stimfl.ll,iusflll,di o'\le~' :lkllngeriinil:c sesles as ~1ilI.e Ammtl: BOliCSilis). T~c .Pi~ Auger ObSCI'''V8ItO'1j'' II:.I~S lhesc Itwo d£teclion ~M.'icllll~iq\lles COSlll~C; rays. Ourdoiu. ~'illg@.cst tllfl.~I~ey rcu18:ilnl ~J~e I?riiweCl'llildidaA~. rou:tim::ly at lhlll S'Q,mc' tii:ual.';. The :size of ~lI'Iedaioo. sell iUlOW' 'L:;X.coedll that SIIi!Jl1m.'lry IRef\el!"!!!lI(;~~; from aU (larli~ i}1'[pet!illlL¢nt~" i, J. II!.!, (Nlmm, f. K. Gai!&iet, S, :S'<I1,!lIrd!J, S'6.ARt :21'6, ",.~ 'mafl~al)' 1097). Th¢ ~l~>c~i'Q!1I(lf Ihe pJrfll1<l!ry lI;;osuiricl:?Iy gl!l 00 !l~©liI~lI1iIlIc~dIWdih 2. tqv.!ll aF!!'a~~!I ~I'i~fil.\Ql. ~lSeM ,eqiia1 ~.!tr'!!II ~liIl s~ .. TIIi! iIe!~l'ai~fiI11: I ~rllhi! vertical good pfillll;;i,~i,g!]-~owi~h.i'll(!l Qf oo-by ,!W!~~rg:~md dl.,\·ecoo !'8,. MQ~~ li!iil!... 000Im<il'1Iiliii!: 10":.JO":.I!i1tlI-&O~ ,af@ rIMFkOO Uriltfl nliH!.I.Il~ (~Ml OOsi!iVdli:t)' M~I 'Ii! {~W Closln'ic~my ~iIIltLcles <Ire cll~go(l .mcll Slolheiirlrajc,OIDries .11Ui'C' 'be lilt 'by ,!5tl( -3QP}. 11~' Mlrv.!t~ 1!IiI!,IIl!:ft ~J.INI~I!!' 1.0, tlit AG~ ~Dd~!It~ lilli i&'IIr~~r' S".;l'['S 1l~11I tl~ iIto'oo in li911l~r ~I~ d' re(!. ~1iI,em'l1IJ8iIl'c1~C;:Hielldsin Sl?iI1lCIC., :For ~1:Iri]~,}l.es iOl cncrtli!es~bovcl1lfuw W

IIlldlllllY c::jool va.'>t. 1ji!~~1II j()t~ iirrlto il1ll£l11tdactLc spare.. .As. c,ooi1lii:lc r~ys; pl10,f!'1Bg3llXl, thc;~:igh\':Sl.rnl!~gy paf.tkl(';s i'~IGrOCJl ~troU!.g\)I witl~ I~he !!!.bLlQI!)!!~tO!M'>cg~i(: tJ<l!ckg;m,ood mdmlijo:n ~IU!d!lmiC seme emetgy, l1:!llJ,~, liliH~Y COlin{I:m~y 1r~~'C::~ ~~llnited di!!!a:I'!ces !!.f!d"cQ!1!~ sequ:ently. (hcirmU'.",IS ~l!,pre:5';iled. {!he ''GZK eKed'} So the ,S'Ii!!'Vi\li~ (]I,f !]a!e high(lst=Citlctgy' CClmllic f;ays as; 'I~hey lU"avc[S!e S:p8C:C~ is lmIi.t>cU;8J lji!uzlc. Sim;pily staled, we&:m't irllQW'tWillIlt I:]N~)' ifIII'll:, w~lel"C:Ihey Cfiffie fnull,OO" ho,w IdDey l?io~hl!ffi'C: from. ~llil(i;ro. 'fhe h]gl~est.cm~rgy coSiitlliiC~ays;flim SI(Thmlll'l 1I1at~II'I Uw:last SiOyeaID:i, (!lint)" ~h~liIdriuJ~or 100-E~V ~rlid~ h!l\'e:oo~1'Id~D~~~d"nl";low fl:lIIx '. ... .. ,.. . {onJy 11 ~pcr 'l(n~-'QJ1l E<tn:h p~ ~liI!iU0Jrlni!J!rnn r~'Id.el'8thClrdll'U'C~1 deI~ec~on i_n!teasib1e·. h'~,lellcli. ]~s~.mme!1ms \llfiU~e."'t[lerIl6Iy l~e co11eccing areas am dc,pl;oycd. and SiliIfilip'Jed'I'C slw,\MC[ of sooOlJldiuy pfl1iillicl~ produoodi when tkc primary oOOlllicm.y ,"oUides '!'o'.L~lhEardlls.~tI11Qsph!lii"c. ~I'~,e Pi6ITG .A'I.Igcr OlbsM"~touy streMltes oV!CI:'"O(Uj,Irn,l!i ill wc..sIett'1l AiJj~ g;~imina., ,an area ~h1lili~t1Ir kllllIla~. (lflhoo¢ 1i;:I((II'I'd. It flile;:lSl,lII'l,\:S, ~1~ll'rt'11v\lli

S~lM::i~ I1<lS'lil:ug ccntra:l bla.ck :iloles d1atrooo. OJ} gail and slITl':S:

!QQrre~alkm bet:wcC<1l d~c ;:m1vn! dircc.~ioo58irlCi. 'die poG:llirnll1i..of klocn~\\'U,A.GN by t~liiWnlll :~l facoors: a OI.u:olIfor lllIe i'L'ls,'IIll'm1:IU dlm::lll,lro of an AGN .a cUl:oif lOr 1I~(;l n~:i1li1imlllin '~lngy of oosmic mys"a;~dlfihe
:!Il1.lWilIlar ~L'I'ln $ olhii'l. ei\'\ltnfoo:t'll SO~ AGN. W'e fOI!l!ld !l ~:lS $..~t{ilrl bctvrooo Inh~ (l~.c·my dimcli():l1s ;.ul;! ~y AnN. Of !5 ~m,\¥ilh ,~e~tl1: ~l~f tl~alixmt 60 EeY, ]2\lI,lCfC

~oc:!!lOO wuihin; .3.~. ·of AGN closer ~u.j'51 MJlC from Et.'lrih (allJ~t 25:0 lb'JiUiolD. Iigl11t~~], TIne liikelilrood of a r<I1Dd-ann1 i~nropic sm: of ,amv!il
i;I

dl~'Cti.Oi!s

o~~rl~

~:olOOl w' dliis nmdl1 was sumaW. \\lc filJi.OO ill"" val\ttes (OCf

.,....

Yom

III

9'38

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

RESEARCH A.RTICLES FUlL-LENGTH ARTICLE

([QnlO:b~;:i!~~ ooi.l![(i~.

na~,."n¢llU<WU.o:UiIs

kt.iQ~VII!

as Ute Greaser!, bllsep1liii, oa!i'\! KlW:Ili'!l

(GZK)

IUising ,1:11am ,l:oUeoed at: the filml!' ,!\lIJgler Ollsi!!l"II,ilw.y dIU nIII1g1 "Ule! IPilS1l:1.7 YE:ar,~. WE! dernminSi!:ram,dl ,iI GOI1l1l!liatiO-:I1 !beMl!iE!n~hE! al1l"Wail ,liiJll,!!liiol1lsi ,~I,llOI!im~[ ray$wilil eJAl.litg)r iiJioorul! ,6, '1'1:10;1:1>1ledJ'iOlilvllillsill1ld e tllle· PQ<,5itilliru ofa,~iti'liie ga~iI,~tl\ic:rulld.e:j ,(AGN)I Ilyiili'lg wiilln,ilil-715 Il!IiIegapar$e!~.WI! re,jedll"ll!llllli! liIyplotililiIi!5~5i an imb'ol~i(: Idli!!ltlrilblu1~ol1l '1lI~: tlilese: l~o'Sl'l'l,k ~a~ witlil ,at ~~st a 9'r:III'% lG;omid]e:Il:lie leue~f~lm ,a pre!!,mbed ,g, IP,rilllri 'h'J:s't 'iJib ~oi!li''(;!I~'I)~1w~ 1!;b~l'i!fli!dlr5 roi!'I'IPMllb~(!!: witlhi 11i1eIilYPMhli!'5~ thgt 'lhf1! hi!'Jh~t'-el!ile",gy pal,'Ud!1!!!'5 l[l'ngl~nart@ ~r'OimI IiIl!rarb:y e:dr~giil~aJct:i,[Soulml:l!!swliIei$i! IL!Jl!IC,lililS not, ~eern!iii.!bstililltian~ Il'@dumtil l!loy ili'lW:ra!liG:1ilWiIlI tlil,1! ~oom~[ Wi(lll:gJollllnd radiiatialil. ,I\G,Ni or olrij:ldS Ihlilvilng i3iSilmiliilr spiilrtila~,di:stli1iilliidiGlrl a Ai! pOiS&:ffilllll! ,5'OI!l~'(jes.,

eii'eJ:lt, from tlle Il~.mes of the drree pil.)I'5~cis.4S dimt. p...dialooil,. i~it'dt~ .SOllOOesof 1.'Ile:~losteu~ " tH'gl1llDic ,000si:t.'li,c m,:,rs ~oo reial~i ~Iy uem:by end
3~ Iil:Cl~u[fli,fhrr.nly di~ilribut~,t 1~IlI~n, an8ini~o-,

IirOpi(: mlV'(lJ1 di'lmribuliolQ !g' ~X[H~c~. p:mvtd~ th-e pa"li,d~ b!3ili'~,S! ,s;u,f!1ci~~IUly small chaQg¢ timilS to be minnnul~IYl'Crtrurbed by imltcJi"'!ilenil'lg m;agneli;c fields. Anisotropy o:l'dtc: ooISDnicr.ll),.!> w~1lffil dlC: h£gI~lM!'~' :liI.()Ql!lBSoor!1l~djfmtn:iW(':Sti!lS(:~l!lSi~rong e ,(If c,~n~s 1!ll)liIl individlil!lIl point SOl!!~$ or thWQt!i~ih th~ l)ol'f,elal:lolll oifawwiva:1 dirOO!i()!lfl!~ Wilh !!, C'OUoctior!ohmm!rno!itlk::a:Jo'bjecU:. The A'kcno G~,ant,Air SllOwcr Arna;! (A:G.ASA)

a!~dIa ~mciei!'!Uy i'!lgll ~ne:~

for dle:Wd1ire.o-

Oif the~!iI(lw~ al~lI!rldlev'~1. w'herea8 U!eFD liew ~OBeVID ~ ey-andl ~ cY. The :~.w;of (lQS;fI;.'(lmds. dte IQl;lgi~llli:ruml~ pmiflk': of the: sl~owe:r [Wille rays ~ Emtlll, decreases wry rapid Iy '\!,;r[(h doring:ilS de:'IIclopIIlEIl~ [hro1!lgh 'd~l::: tlillOSjlhcre,. a en~,.~i:oml afu;w (JlU:ticlespC!i!>qll9re ,ooolfi~ hI. flg. l, weprescnt t'Iltl: ]a;YOtlJt of lD~e Obse~" :ffiI.l~~Gl1~r soconc:i in Ih~ kl-''!r''-tlrn!lrgy rn.il:ion I~O valli:!]' as of ]H) ~ptemoor :200i!. ~e.~N [han. a:U!.e parlide: Ii'~r sq~:ar~ ~d~anu;~L:lr TlliIL'; Pi(llro ANigElr SOUill{)tn O~r!;'!U.o:l'}' 11;)£ IOO(}[I tak~rlg, data - stllli;l~~1 $;iruo~ Ja,wt'lryiOO4. Ifl~oonhuy ~oo\H~1 ~v; Theid~!Mil]~.1tioin. Of" (!I,r the S(Dl!!Irc:~!l: -of ~dlrmi.gffil-e!],crgy ,c(ls~nic :f<iJi':t nci~c: IDiposttm Q:ri!.!' :g!'O!:!!!'!d..-.y, COlTIi· (UHECR)wid~ e~em'gies ~16w eV bas ooeri 11 mUlled. w[MlftC£l!Lrnre C1levgy and mrivill~imcdon grelU dUI~ ~euigoe since I~jhey 'WCI1C first ,ooiServed IllC'~lOOIS, ,~l:ilbrm:t'd and, veril:'ioo. f:ro-na Ole with dlC :~]uoreSCellGe detoclo:us, im~1962 (J). Because Qosm~ rays nl these en- hybrklopemlio:n ergi:cis ~rn.o!~. 'L'lXi]J!2Cood to, be 'C()f~I]I1ed1 liYy 'proV:[d~ :anOPpon-!l~mly to ,exp.locell!l.'l SJWiaJl {)(tfre1a:nio:llOOrw~oo(lmIc r:a~ and tltcif SI(l!!lJt't.'ei! ffiI];1Igm~l.icf1e!d!s ;n ~~'11~ i~ of 'OO[tg3J~ilXY, and d i!1li:l1.~·~y, imdl~ed ItO sil!lIDIii'i(,'J,ur~ ~)!e~ fllOm iIlle di~I!i(!!n of Un: MilkJ Way I~, ooen Ob~I!'V'ed, ~tV!il Ifooo:m:l'C rays wi:U~~l~~Wli~~~l e"el!'gies <l:f\'; li:lhily tlml1: ~bey or,g~uatc (!IilUside [lie Gl;lihl;lty~ :predominat~tty ~rotmrn or l]uclcl,Ollilly scurces Ur,1!I-U now, {hccre ~lIS been 1~(iI Cixpcrlm_Cl]WL~ Closer t~~Ml aoonl .1(] [) Mpc frOln .Erur1illlcru:! oo:Dltrnb'lJIC 3p~rooi:ilb~y 11,0 ~~~(') obselliVoo.ilih.l:.-'i cOlilfl:l1:milmioll of iIJ~l~sl~YtPQ(besls. ,a!bQve60Et,V (~. ~(l; V = i0 I~ cV),. }lmtoo:fl OJ Beeal!l$ oJ theiiliveryl(iliii:V nllX, UHIECR 6 c.affil ,onlylIll:ll dl3h~c'~.ed lau.rougl~ tiI1lil:lr~_I~I('t3ott-Q'I~ lDud.(li with CI:tl'lrg~es !I!OO'i.l!L'l 0 .iEeV ilUlll'lfli.ot w~th lilli,,,, E~llfik;,s t'llmtl,s:~hel\~" prodJUd.ltg a w[ll!. the ~Ml'I!lic n:uiCll),w1'ive ooc!.:groulnld! (3-$). cascade (lif b~mons of pruli",lesdl,n 'ex'C(~te.n:i~ leadimg '1:0'a SlnJn.g<J1lUl:CI]IJ~.dmt of ~~~eLr~lIIx I~m'gen. mo:l.ec~~les h~ da,e air ;lIoolllg d~c:iIi pllth, ~uiLdpread ,ovc[~~ar,ge ,8I1:e1l wlLel~ they l:c~C:b s I~~lc gr<:lol[n..G, li1~eP:iclte A.llIger SOIJI'hem. O:bser~ vatory (2), mllYW ~earl'l!g complcli!ln.~1l Argelld[fJ<lI,

t»WflIliC: luayg ~ '~~~Ine ~piII1J(>I~ ,ilil~~ !wdrai fit)fl'I ~;tOO; IfiI~..smilteEallifh'fo a:~F.I--1-'" TiIil-ir _ C!1f;,~iEes .- - . - 'fI~·;rll ,:, __~J.cre. _e --';- - -- va!:Y-fll,- a

1l~<ho;ul!i..>,j~l~ilIIOf

air~.lurwef"

p;lf:':Jmt!l~iUS. nil:)

SD

!lleaw~-s

lhI)

hj!fo4i~~s~(i!1!l1l1 ~al)()talslt-liIci~l.!!~

ColI800rm,rol]cl~~1I1cd. :some eXOO5!l o,r c1,t:t.Slll~r~ ililg 81 !illiiaU atlglll2lr sca1cs ~Olil1fp3r:OO. lllislOtroPLC ~XPI1CI'.'llkIWlS (6),. bul ~~liswa.."",ot !;Hipportcd by ,cllal;!ll1Gi,lt'lrd~ !by U!G H~Rt)$~:~II'iIt1~lIfIl (1). A 1~1y.~~ ·(If d.:M;]!'l1icoIfclQ~ by ~veF.li:~ ni". showell" eXiP,e<imetl~'8 ~c,velll00 .!e gem:rn.1 OJ:~

hnion. Wiidl d~c; dil1!OCli(:m of Ute su:p'~flloclic plene (8, 9), where :scvcnl1 ncrumy :gnlill'!:~cs clUi~r, Inlt Widl~il:ll.i~m.~Ilt~tca!. si.!r/1ilifs.camlCC~ AGNhave ~.o",g boel~ co:nsl.de.oo 'si.lf'l:S \ld~ClI"e.
elil.()rg~tk·p;'Irt~d~pmdl1ctLM m~ghl !t.m I~.a('(: alrBCI~¥'llilI~~ ~(I!OIO~:S .;l~dlh~.avierm:lol~i c.nol(!1 be ,i:liocCil.em.tcd'~p to ~~l,e h:~ghe-st, energ~es yet Incasurodi {i(j; 1J).. H~\!.re rep-Olt tire ob:scr---

v&timru o~' 11 Qo:ool;(ltam~ bet!wooo Ole arrival direc~ limns or ihe oos~n'ic rays w.ilb higlmsl em;rgiffi m,L';3slu:ed by 111~.epaellil'l: u@~ OOOtlli"\!i!iD.ory .md A 1I1.1~~tiOI1lii; of imm;y AQ""~ from lIlilL'l i. 21111. edil~on. of rule (:a1H!lliog of ql!laSlllll ,;.l1fldJaoliv'(l ~ocl.em by V"C!un,.cc~ly and V coon ('V~C~!<J!~og) {12}.

was des:igl1oo. to sl~:n;ult,u~,oo.u.~lF Q'lOOmlC'

1~1til~S:hOW~f

pl3.rtk;les at" .!Fo~md ~.ec",'el and.

Iil;l~

.u;sQCia;ied!ll~Q;r~ce!~oe H~ht g'C!~e!.ttedl: in ihe a;il)1J;O~hef!C, A large army of 16:00 surfaee deI~QC~01:S (SD,s), I.!dd o,ut as an. eqJlu~l@teml td~ a.n~Ui~ar gridw:tlln, LSOo.m, 8pa:eiml,g, eoV{)r,s an
area. .300l(}k!frly2 and dd~(lI!Sthepaii1i.idoo at grohl1!ld ~Ql;V~~Il:y~ m~IM oJ the (J])~l!IkQV 1

or

1~d!fnliaUi 1!~~-yp.F(l{h,l(l~i[lwat~r, At ~l1of fl:n.~r ites a:nd:lc peripheli)!' oflJhe instmlnelfll.ed s a!1el1" ~ixii~Wru'd-f<lcill£ o'pticil le lescopes obsi~e tiile Siky .on cil,c.w IIlliOOIll~les$n'i.g]nts:. These dcvi.~s in.eaJ!lWlE: Ole; ruI!I'I~Miihcrill' I'II~JCi~ l~cenOO ]ight~ooUOOd.M I.ln CXmml!ldvfi air ~h{i!\~r tJ3~~ ihro!!lgih tim flclJ of '\Ii~\\;1;. Th.e !~WO~eel~iliqi:!leg-~~~~ Ds i!i!nClI~Thi~iiiO~(K:~rnCG S n
{I".ill>.i:)-.a:!'~ ~lrov~de aQS!l~~ecks
de;tec~o!S
()ib~@lNa~:ooo

'OO'!l'!pl'~lei!!l'm!)',1illdi

011510

Olnd reci,1l!11I1:b:l!licy 1J1c .trn

,IIi;\I',Mid1l

Pieli'~ fillger;

Salii Malitlt'l I'JIM~

Fli.g:. 'ill•. l.liV'~liIil: of the lP;ierre'AllIger :$oillth.eullil Gbservat1ory .•fliie doEs Irepre:s:ent the po:s~~iofl IOf e'Clch of

](1'4, (S6n)

illiJQlN .C:o,ILa,DcatiOn2@,~nill.qiOO' r

r!liillamgu.~; MeliiilllRa,

l!Irgentin.a.

E"Ill'illil:

the 161'!M) CI$t~~i(I!i!~,1ih~' S 14i~O $!)~t,mi)!ili; d,~lt~Y'~!}!lcl i:ll~~t~d~· Ol~ ~1~~~~be:r~07' [ie~!i! !.II) the ~n!~ shaded bitue. 'Ii'~ 4 FO iims ;are I~ab!i!ledillll ]Jelkiw. with: gr!etilll I!liifiesilldic,ilitiliiiglli'i!liieki of
v[~!IiI

"The f!illl ~:H ~1.n,!!!fI-~!$.~li1Iditf!ei!'~f~ili"eiQm~p,Pellr~<it the l fndi 0-'1 ith~$ p;!fer.

Qif Ute! six te~~~!llQPe!> .. t ,eaiclil site. To g~ve 'thie'~caJle, ,of 1ilile OIIin~el"lJ\am",. the lelng:lhs~il'lfthe glm~elil line ,~i)r!llspofld to 20 I~rn,

RESEARCH ARTICLES
lilatOiiI :set and m,~iIh(idl., Tillie datOl! ,~et, .:;U:l,,~ ~yzedl llile](l cOO'!:sisl5of I.heco!i~lic.,rny evc!i)ijs ~l:lcorded, Ib,f the :smfac;eMrn:yaf the Observ~ a:wllY l~mm, J:lImJI,my 2004liO 3,~, A:U,gThl~~ 2007. l h, c;Ql]l:ail:\!! S~, evCili'lIS w ~lh lfCloons.ti:'tlctcci, C:ilcr~
3,liIgJ~!S

SD <ind U~eF'.[};d,le seecnd ow.e !,h~e.s,ev,~il" ~llLPig In oil ~ ccial fCgfulIQ ·ofour array wl,refe
two sl!Iirrnm s:I'!I~iom; ar,el:lli<l, in pairs ]1 m.
~mt alea,chpoi!ii~<llil :EV'CnI:!, 'hl1lll:lrig£('lf.(m.m ID

elterg;ies ahove 1.i!1I11S!II~r W BeV :and aD 3IjJgl!l~.a.iI"' rn.'lQliJJtion beHl,~. d,:an 1~1Iii8!1li60~. Tmi~irnUi\\gmmidi G'XPOSi,U,~ i~ (I )Ii; '~O~ (l ~.'"IS. j,6)" ( :km:'l $f y,~r;, TI'I~ ¢1il~1'ID' ~ f eaeh evc:rU i8 ·d¢t~l'iJlni!~~d il'l We or!ly ~~serecord:eCl eV'CI!its:iW !l!,ey ~l00t J.l! t\vo-!!tep'pmclool!!le. Tille shower siZ1e S, !ita stlicl cl,lrenn wi,d~ ql.lrd to il'Ile qlll,:lIlit,Y of d1C rerCD"e4~Cie di.s:t:;u~ce mild! :zen.ith 9If1gilc', is eelcJUlau:d.froan tJ~e sigllil1l.~, dc~ec~ooin e3c~ Sl!llr~ ~ccm~stn:J.C;ljIOOl ofd~cir C4~l':rgyMC!lId~reetion,. TI:l~ ~lGCti{m or llliIoslC ,e'l!'rornsis, OOllC vi~ a faee SlOlilo:1il and, d~ll.m00lilVCi'1~ed.'DOcn.cl'gy widl quality tngg,rn' (J3)i. w'hich~~only 3J fllilCJIIQirn, 3Jlineall'ealllll:3JtiOl~ cm"it~ ·ba~ . on ~~!ll.'l nuo· (ii" Ih~to;p,I)Loll;Y of'dli~'foocpnJl[ ofthll; ~V~lfI!t(!il~ filliSe~ll;C1L'l. II~l~(),~L;l!I:IL'las!l1lrepn~IiL~, 7). TIlL'! 1!1til~ ,W'ooJ,d. lillis !rigger req,ryi~ih<lt Itbe' deUll()~r;il.,'l~n~'Gye~!ll~l:il~g r fit(H'll [hi; ad~IU!SIlifI'I~I:il·of I~OOlo. wiUl 'Ulel!±Wl,CS:! s~gn~l must 'Ix! surdle ~t}Wer !5i~ll\, tID!ii;loof'l'i,llelSio!il '10 II ~re~llce least siix :!!lIlIrface stati{mslm:v~

[l:i(;l~aoov¢ 4.0 EcV and ~~b'!ith

a!iid the rUin ;;iocep,tiUl!ce Ibr ~~)iij~~p 00 6fi)'> ~~.ilihh iU~sie" A :Ike)"elcrnellt o:ffi'01!lr$11lI~dyis l'Ile ~ro'bnbU'imy P filr J.'I sel; of /II e~j{cnilSlh:ml ~lIlIiisollropic nU)!. mo 0CiI11:.f'iill1 Of l:rn:G!fe k CV{'lIillnJi·aJt a m!Mii:trlll!lm rul~.u.lnr disl~~ .~ .llmUlln.3Ii1Y :!iI)3~b!Mt of a 'Mn~"mio:lfl (!!if

~dtd:3!~~ .poin~ :OO~~'L wl~ere ~e tP!l:~~~rfJ I!~ e

p·Ril

6v~~jn~liIi<lJ1 di~~miQJ~

(\!I'e:~hlcod by the c1xpGI~mre) defilned, byd~e' regions ar ~n~~,ar se,pma1:ion less t~~aIJl ~lrro:rl1
!ro~.oot'I.'J(I SOllroc:s,

.~. !ili!e f~cllgn of~e:f>k$ .

I'~t0/pi ( 1.- ,»,"-;,

,gu"'~I'i.lry ,ei,Umu~a,. [h~

iIIII1~,c,d~e' fi'lllCiUlII,mionlirmll :~l!nd1iI~le caUbratiofl eurve ,amOUI1Ui, W8ibo1J[~ not ;l'Inobstool~ID dCiWQ'I~li.llg ihe c)dstmlce ~:s%.n,e a'b,oo,ltlile cncr,gy seale Is ~lWIlI .by of ~nisooro,pi.1ilS blJll.n~ya!ffocl: ourabi~iily mo thi1l ~l!llQuescmmLl:m~:romoors ami. h~ !1 syg. idJi.'t'iofy 1:tiI.L:; COSlirutN'l1Y SffQJID()s IilDilltIM,g,UCDllSly. Irlrnnatic lU1Ct:ll'in3!i[l'ty (1f 21% (J8), Tma~targt.l~~. 11]~ 'catalog oontlli~ ,694 :3cu\I\iligal.arxiL'ls willi!! redshi fi::;..: :;; ~l02A,oor~5p(l!~di~g ttl' W~iiliL~ sy~ll!;1;l:tI!13Jt~c ulic¢rtaili!tY:ilfi8~ !prill!!i!U'~lyf:rol]'iJ I) SIlii<ill1er ~ha'll ~IOO Mpc (19),. Atlm~er disl'he: ru:dVOll diruct~o!] Qr~ cesane lray is n :~ilinooml,]llcle kl~owled,ge oUlre yield! of ~ho· c;ru:ci.ii1~i~,groo.iCllll in oll!r S1:udy..n,e eve.nt di~ l.on.~ from Ihenll.oreiilc~uce of a.tmiOl'ii,pheric tanees, BBC! around dile Galac~li,cp~anc. the cataiogis jir.aeasingly iilll.c.omp~cte. IUCC~OIl is delellll;linedlby:ll :fIt (Df lhe ru:rivaJ. Idrrro,gen: (~.4%),lhc ~:eJlcosoo.pc'C!!Il~brn'IiOJll (9..S%). ; ExplOJi01ltil)inillildl l~o_irlTrlMil!lfl. Using data, 1~:iln1es of (hie ahowc;r [!"(JIlt at ihe SEt TIle preBIIld 'd~e ili'&oons:lrllcli01~ [l:n:)i(!edllilre (,I (r}~],. d· A acq!li:iroCl beiween ~. J3111(1:±1:l)' 201]4: ,arid 2!6 Mrrry cision achieved 1m. tim mmi'!.'al direcri(ln dodition.1lJ~ !JI1.1Cl1llrta~nt)' the e:ID1lrgy ~3Jr'l,l! far I.Il mJ·~.ds: on ~,L); clock ~(l!IU1n~ of eac1.1 de~lOr the set of lIigilJ'.,.el:iJcr:gy e.vernt~ I,]~d in I~:h~ 2.i!IDt'ii', W~ Sic:rul1r100 lffii~ nIin~lllU'l1,l 'of P' Ill. dte for ~p.:tre &6iU!~d by and! CI~ the: th~~!ii).!!ll~r\(}ILt.; 1.111hie lin1~: oflii!rr:lwl t 'P[~~li!l ,<iJllal~is .is d!IJ(1;e tl~ ~re~lI!~:iv~~yl(t!~);.1Ulr~>-d!urm,:~:!iigUl,Oil!~ ~]c:~ t o,f (hIe lirnl p.rnntic4c (14), TIlLe 11!J~g:uhllr re-so~.l!!I~ stui stkl5<l.'II',a;l]able f'Of c~li~'mtlo'Rin Uruls eu!l11""'1::i!l~u!l1 ru~~iIf sepMttl\Q!1iS 'IjI. nla.'lI:lnUJTIirod1~'iOI] is ,c:itC'iIlillcd as ~lle !utg!lllilli <lpCI'i~!lre RfOITIIl!C:i: '(.IX!!)!'mll:Qe. shillts ~j!i,. aad CIlCIllJ!' tlllI'CSh.oldSE~i' The lower. an a.rrhml ,dlkectio:n (If CiOOI'l'[~(l my.s 'w:td~ln E'lilel1U>with ,oocrgy ~ :3 EcVrure roooroe:d I:lmlit fortl~eSCiln m. 'II' C!~.slxmds ~Od,lC' llIiDgularrrcsolt~til:m {llftitc stlrfaoo 8JTIlY. Om scali!. whtch 6:8% of tlWl s;h.ow~1i'S IiliUCreQOIiiltru.ctoo, ''I'o<ilh 11i'l8r1.y]mf)~ c:mo:imlCY o'l,l~r llilm araaeev1m OOL:l11gY thre:sl)QllC1-aI1tC!maximum .dJiiStfflf'lOO;Wl.\.~ ihis re,'lOhUlOn hS!sbeen Vtilifled!'lx~ ®r,l~ 'L\'Irod by tIm Sl~Jrr300 army; 111i'l l'l(mJtunlffIlll:'lldly of m,{'lliv3JtGd by I[lm ilSlilllmlPliioll dn~ncOSJrue rays :rl1!Ll>lU;anyM~ffiI. trvl('lI1IJl fO!r\'iiltti.cll. hllfO inded~.e eNlf!!lSUreirn, Hglll a~ll~rn :isitKltow l%, [l~r1Id~f:l~gGOm~tn(;<JJ~,~Oirnlslr.aelioll'i C<'Irnl.b~ rn~gligjbi~i!lil Ilteoontexll ,nf tI'I~,,~~rnt :!i1,lJIlIlyslis, \vio.l ti~~high~ ~~ieN am the 'DI~lhal .(11r'ei IiJ erfotll1,cd!.. Tbe fi,r:s~ 1!:eS'!;'UC'S ihybrid. 'CYC:IIllS. The d.cpeudenc:e of Ibe Cl''1lOSlilOO on deQl:f!lll.il.don least dc~lec(Qd! by ilLt!;.'lvcllins 1l101!Dlel'ic iiidldlfl and ~halD have 'nh.e SIl111UeSI; probability ()if ~\' .. I whk:l~ a:r:c 11J;e<lSlured cSilllullmcolllsly hyllhe is cililcwiiWcd :fro;lH lIDl~ hniludc of the dellel;lwr
mlilltded

byliveacti

Vie

ne!llli'(:'slncigitbors,

and

thed~gn.'fl of com!,a~ic!1li (!!if OlIlrdlaJa win~ d!~dI~ti~rns .(If A(iN ~ f~[;•. ~iVleGd it) d]~ \l·C ca:!alog (i2) •. l1~iscal~:a1Qg does Hg'l. COiI'!U1i]~ :;11 ec1(i~6ns AGN and :is not t ,sh;o'Weilito stlilOWiJi, m~:unbi<lS~ Slalistlcml Silmple of ~,CI1l. Thits is

\\rtl .:malyze

I~~~~~, luooollstructeci shower rore 00 iIlSk!'c tile: an 8CJUiVU 'CqMillali(;\Jr!ll1 trialll,.g~e ,or d(}l~to.rs. TI~us lropro~l~t~a~. Ii:;lTicitllnlt quaJl~Y CUil. wh.~lli'lgu:lJr .. allJlfle~llg Ul:at OI;IC~lI!lCi3] infllil'nla;lipni:!l mis~>d for II!lie sh{!Jiw~rr~(Iliill:!l'l!'u:;liQIfI.

frolll

WI)' dJ.!illllltSOlllroesd)LlIC i!O tI~c GZK~t[~l

(30., ,().
Wif, frrlll,nd am:irnla I:I1IIILl:illofP for ~IDI®paran1i1li~el'$ . = :3;. [to, ZIDlli~ = ,(:to [ 8, (Dmul:~ :s: ., 5 Mpc;)i. ~

ailldE

III =:56

:E¢"V" For

nl~S¢

yal.lJl;l$S. ~.2

¢V~litI.<;l

.
o

_3f}

'.. .
•

~mQlllg l S CQr'IlCi<!lte ~1IJ:~th~iI1e 8i1;i~OC~llldi .A,GN, wl~eN<ls Oldy J'.:2 ~,rCl:e cxl}ected I~' ·ch[l,lllce if' tlterhlx w~l\e iSQl1Jropi:c. h,ls Qbserv<l~rol~ n~O" T

fJ

ti'i!'3imdthe dctilllitkl:lll .of.a lcs~. to vril~id8!~.e the wi!ffil. 3:f!I ind~!.'Hiooml'l da~a sea, \vitl~ pafa!lnel~s sped (jed 3. firioril"al~ ~.~Iffil:I1,Iirud rry
r~uh

th~ A:!JIg~-r~_I~ :lInd i(lI1iillQi:ropy !Il$'l~~hmm;lilb.oddloS)' (2'0,2 J). Ii The AUiger seru:·ch, protocol w,as desl£ll1ed. ..~ liS a. seqmmc;c of (esi!!; to be !i!ippHecil IIRer the O~SCrv31kii1l (If ,ea:c'h. i}e\liI (w·@1i'I1with en~i:ID' 3M('l :56 E~V. 11.1ii': hJlal liloobabHimy of~"e{jf~cl~.y [12j,ool.i.I~.g 11lli1,G:fso~ro,py hlt'po~:tiI!~;i'l alcll:tg: thtll ~~I~ilC1L'l w~ i>~~ I~Oa m:axiil'l'iWit'i Cif :1%.1Dlle pararlleliet'l'l fot III~e 'prescribed ~est IF'!g. 2. t!inwff pnll:ecti~!111 of the ~ele'sti[ll splilIBJrE! 1111,gl<llillcillil: [j(m~diMte~wiiith drde!l ,of radil!ls ::3..1" w,ere cho.sen ,iilS dl'O'se,. siveln~b<QVe, 1~Iil<l( led ~{'i I;)'lli!'~~~~ at the .a:lffiiv,i1'!~ dinwth:uilis, of m~ 27 ct:l!llWbk l~gJy$with high~5t '~m~rgy !:n~t~ctedl by 'th(l: Pi,~r~ the :linin~mlJlm·of P inihc' cxptlorntory Sca:I1. Augillr Oliae wiI.1@ry. ne Ipo-:s!luon!S, of thl1 41.2 ,A,GN \:318 ]n thefi,Iil'ldl ofvi,eMi' of the Cmel¥il!1®ry~' with Irred!sh1f'i:. ::of: CUll;S, (D <:: ]'5 Mpcl'fimm ~~e 12th ediition of the«lltal~og '0" qjlJiilsar:s, lIllie!<lC.ti\M!: nll!lCI~e'i '[he 'prot.a'bUiry of :aC~11a.11OO COr,Ii'lil~8rliQj} III tim z' < 'U:~)ar~~In:dici1!~d by fWl·dO1!SIfiif;:riSks:.. "l'ht;! ~t)ltd LlI!II!l:~'preSc~!i!'tS,th~ bOf\d'eJ 'Clftlle frie:kl (If \liew (~'!ili,th chos@n, ~il;gular seocltll of a, sil.~gh'l oo,wie ~" .. 1Iilnlgilessmallll!r ~n,a:iii 16i(f'~.DilIrlt:i!M color imcijCab!:s; la~ger rE!llamre' expo,S.1lH,e. IE<a:dlil c:owr1ed liPan!!i h:iCI~ wi.O.~ tlif3 !lcl~reclH!S!i1Ifomomi{':3l {)bj,~!.~ l P = e!q,rlialil:l'll~~aj~ed i~~peliSmie.Ue daJsh.e,d lin~i .. ile .~!lpergaladiiiC p~allie. (elillauru ~ A., lone lof ,~nIV 0..21 if lihe nlU~ 'WeJ1e is(llI!tOp,ie. Tij!~ IC~ wa"; a,p~ied!J!} data roUectoo, between 21 May doSl~st :AGN.• ~s mi1!fk~d ilill WMM.

_"'.

'9'40

9 NOVEMBER

.2007

VOL 318

SCltENCE.

WI!\lW.sdenaemag,,()1'9

RESEARCH A.RTICLES
2006 alidJI AIJII£,'ii! 2001, wW)e[i,(~U:y .. L s

saiile ~OO!~st!UclioWi ~lgorithi~lS,

,emetgy cal ib~ biases. AQcicl.'e!MJoil oo~~liG.m~V'Wh ~reg!lO..nd

AGN diiffce,rel1l fnnn I~!h,e .nctua~. sources
ii1:drulce 'M.as
tti'WD:m .. :!'ilil:l~~icr Inal>l.iitl1i~m SiOUKiC

the

!ili!'iiJi'ii?~tUQ!~·of P is :!ia~.1~.(j:liinr~X~iUpl

fr{}ln

irillim1, and qU•.'l'I.~.ly Cf.lt:lIror·e\lellll se~ecti:O'I1i.~s ilil InI~.ee:.:plof!}J[o.ry sc.m. In lbii.'lSlc llm~lli'Clild!eillt d.~:o, thClrC are 13c:'1!1cjjt~ 'Wi~iIllc~,rn'm' above 5,6 Ee:V, ,of which 8 ~::'I'!,i!('l 3rnv3~. diiDtsclions ,e~o.s~r 1~~8i1fi 3"1';> fiC'o:n'l dll,l: pO(l~liolt'l ofAGNI~~ than

mlEi)'

tl~!~ <'!!V'mig:e fot C05m~c ~.~ ihat ~!l:'ive <it equatorial (Jaladk latitua.es, because 'iI~ey
traverse alo[lgi!;ll' ,t!t~stall.ce ELC'fOSSlI:in,y regtl~ar
GfilaC!~:iclrl8,g;I1~Ii;ce<nl'l1~OneI11..

These

eUoolS

diSit8JOOecS, wMlieoocldlmts:l

~orreiMron

wi:d1

di~ant. bae'kgroll.n.d o~~m:iiy Irod1Ll~ ~lIiIl1lop" '1iIFila!lnl:iiximun~8iril.~II,II,a1'~~:!liOti b:y ii..fuc1>~

75 Mpc .~way.'wi'U~l..1 ¢)'iiP~led. Q~ ;'I·v~r~e. n!~ p:robaJli}ili.!:y U!a;~ tillS ro!~ligllrn:liQl$! Wo!,!14 (!I'(ltallC'by ·cl[Ol1I1iCe if Hne flux we're i.sobiopic· :us ~.7)( 10-3• Fo~h]~?iI':~n\g; sleardh prow col rulld OIU based em dlc:ililti~pc:ndell!l: ·mlll. sel~ aleue •. \1ilc lrojset tim h)':pol1il~ls of l"'o:Iro[~:yin lfihs di.~~ l~rFiIIlI,litu~l~ i(!,tl' 1!'1¢ <llIival dirocliOjjt~ ~r oOS!llilii~
a COflrrt!~ncc I~¥el. bSl!lts. Ha.l;'ingdeuC,fimlh~cdOliU ,m. !InislOl"~ lropy e:d!i.ts~ based Oilll d~e a pdor:~ :presc:riptimni. we 11i"eS1Cil1iU:mdi fun dasa sm. fmInl liIlI.e Jan.lIIary 2:1004 m 3,1 AlIgrUSI :2:007 I.IS~l1Ig IniU3 n·!i.(ltlt'Q~ d!Lmt':nllL';(] abO\i~ to Sl,lb;Sl31X~iiU~ ~1Iitr; o'b~~ Clo:rr~ 1~~ilO!lf!!. u~ds:l~p~ We (Dr O. 1Q ]11 l~j in (mu:) I.. mge: :~" ::;:;.f:::;; 8",. !m,(I ~l.om :~111: •.,~ •. in I!lc 'I ~iilr:lge [I::S .z:"~"N.::;: O'J124. We,~l!s:Q used a 11e\V·er ",ie!rsii,01fl ·o:f o~r roconlstructim.l andC01mJr:ll!toru. aigoriUn1il] tbat Jlii.ves l;[ig1ilHy d:ifferom: rocml~
Itra)'SJ

d~G~~~'

am i:ikcly to hsve some :tmpai!1t lIpon the estimn:'lJtif:of II!ItIll il,lmlrl,gth of tllLl: oo[rIiC~a!iiM. Si>:: Ol!ll Qf ~~~L'l~i.&ht'~\l'i~:n.'!i tll;<lt do n{i!'i corr~l~ \t!id1 AGI\~p~Rilioniil w~tltnIQ01!l:f :p~'lcrib~ pa,.
r~!Il~l,en

wi~Jtil Inh~ hiWJI~1elti;l~i,es witl'l ~ll,~l

9'~

Undcr 1~Ih!es~~llphf~~ir"~ ~SIH¥!p~OnS o,fa unifo'nn di:!'ltriblll.t~iIln of SO~IU'U! with 'eqtiHIi~ il'ltrillSlC ~mninQ!>it;t .fund ,eontilfllKlus· energy lossin d~C1 oo,i>llr:ricmk::mW!iJve bm~kgmund due 'In rhe (JZKi.'!IT~,Ci~ (3., .f)\ 'OOOJii, 111~~lII,rpli:l~ of ,.-EV~I:ug a!~.' ~ "7!~L111 i~l:Ii~ (;X.·Ct;;~dttUigME¢V (Jri:si Ilamrro:1I11 W'1!t~el~lIfLl~H 200 Mpc. l1~is 1(8Qme1J\li~at !lroilr<l!!"i~y del'ine([) "GZK
honmn'" deeeeases mlpidly wid11 increa<>hn~

,a:!~dreeo:nSlwdico!l! ood'€: liel~8

Ilih<l!1

'12;:i away fro:nl the (ilill<lcticpl~nc:·. Dcs[plte lts Sill'Clltgdl,. ~be co~ia!ni.{ln ~a.m.we

over '\:\I'hid~ weobwrw3. s].gnifica'!lt cotrsl.rutiOl~ comp:atibllfl whh 1!IIlJ'"firl1l~ltiC(lt1ymlldt': '~::l .a_~:ilunm.pl.ion tll.M. lhe hig~~l~~I[I~(;(M!:!ll~C d.l!l\( ene:rgyrang~ an'l '!w(lton1>rl(lnrll ril6.,'lJrby as'loophysiC3.1 soWr:ces,. C'ld:la" A{]'N Of OllWf mys are protons c~",pc'rile!~ingpl:Cdlc~l:ldl GZK ,euergy losS!es:. 'W'C !m~e~ha~ the 1;l![l~J:c~ali}ml obj:ects w~'~h.<l shnil<l~ spatial dl~;lrib!]l:ion. Th.e IllunlDcr 0,1' h[g~~~~ergy cos~uic",,'ny in;c~easesabmpdy 3.t the el~e:U',lJY ~h~lwld. of 57 EeV .. wffilicilc{!Iiincid(1;s with tbe poill~ ~WIJUS feoordcCl S~ .far by ~bePu~m A'ugcr Ob.:'H~rvato[y i1:uldJail1l,~l}l':zedil~lhi$ \l,IOI'~ 00<1:Qrlch:e erl~rgy spectrulIl) [;i:.:cendy r'~Orll!:ld. r~p{ll~ds to ~..2 y~:af$ ofopm:al:i.on or the from '~II1i:l(}bst:lrr\!at()[Yflt which d~~ il.liiX is ~lmlil~,ii!led 51~~S Q!r dil1l):l(:lio:iIl~.hM[I fllo;utl3.1il I1edli!lc~d I~y -50% w~II.1 [o~sp~~ loa poweU'- C{ill:l1i.p·IJ~t¢ l'l:oJlllIiI~I:'Ii :a:rr.ay.The di;ili!! S~II thai the .!pI,lter h~Ju.sl a. !e'w UlQII'l; !sQ'i!!\:Ipicdl~strtbud~m in l~roPQ!'~IQn to ~le !:el<!i~ I.~w edrn[p'Qbiknl orlo~vc!'"'~~ergY' ·Qb'serv@" QbSC-"'>'3J]Qfywm lions {.n).•. Uve expOSli!fC d~e Q!oo~,I"!,i'~Qry, PerfQ!'mtng yea~s sl~oU!ll:lof~e:r ~ bel~el.' 'C~~I'lCe ~o 'U.~ml~ Iflhe I:cplar coml~neBt of ~rnlegll.I@C:li;c bigl!l:om~y :[d.cnUr, the sources., The IJtdtem aJ~id~l]dca! sc.am .:un: tho~ :sillmla:i.ed. :S3111"les I~O tI:t9t3.w.~ioo to d~c re8J~ data, 'lYe cibla:in, Ulr!lgnelic field! is oo,hc:re[l~ ow" scaJ~~ of of corrolatiolllS of oOSllill.c,.;my evc;l~l.. wiilll~. sm:a.Ucr Gf eqJl!lari \l'3J1uL'ls ()if P ~.rI -I. a-sol' the th~.r S('ffl1XlGSCo1ilk:l alScO:l$S1Slil'll c1Cl~~lIliIlJing ~.kIlO w~llliI. 11 :!ltnic:lDgdtl. of 3. fU:\", !llrG,.rilS imlithe i:nl{lf\.IC'lul'Ig 1lilIc'1gr.IL1:&~C" caood! by da1.afro:m ~l!lclJ~t'l[; ofpulsaJ'l!l (2'2), 11l1~ the: ~'oopea1k:s S~filll1i1t&l.d1:imcl:ion ~ts" field 8tmc'lI,n'es @Ild i!~ p;j!i~]c[epl'!Ysk;!> c~(lbSli1l'!'\I~d oo~~aiioo Qv~r ;1I'1 ;'I!n.gIl,lIM"S()ii~L';lof W~ ~I)~~rnt (Fig, 2),.'il sky!trl<l(p' .iril,GataGti(: p~(lr.ailig:ru;.at (he b,l!'ge8te!iic~.ics. ASi.!!m.UOIT:IIY ooo:idinines ()if our 27 ~.igl)esl~rUl)tro' evelilms OIl!)' a Ih\.v degrees f'Of E - (\O,-EeV ~ h~d~· the :Ca:li\'e Ul!ill m,ool. of ~ffi:ie prirna.rics a_fe l!lail: ~,ea:'\I)' bmoedl on ,oo'smIli,c !"ay:sw.~U~ Ihighe~ en(E:> S7EeV), as: delem~n!Jd by ou;, n~iOslIre,elill v~on or lhf: feoonsDotion ,code. 11K) 'nudei. Crgile5 OPC:'1iS a. ne',!;l '!!lilim:dlJ·w 01,] [h.e mliilll'by ThesQ r~:3:IDI!Jilc:fl!iltreOOi~~8Jtible w~.th I~;hc I.Imivcrsc. ailLioolrop.lr' l e:lmrly \l'i"i~lc.W(l :fl0111i lheprm:~ .. ii~terpr~matkm. tha.:I.'lhG QOi:fel~ti(!!i1. we ObSCf\liil in1i~yCif severnl ('!I;II®i11s. dQEl'l to dle stI;~erg,alaettc ig G:v~C1el~c~ri)r Hus GZ:K. ~ffl1l('i'1 :.md lni[(!l ~,lalllC; Md. aim 1Il!llt two ¢Wi~!cc~arriv>G; illltin . .3" w R!!fellEllI,c:e:s: <1l!!d l!Ik!Ites hyp:athellis timt tl:le bi:El,hest~ne~CQS~lie (i!rGL):i~Uatjl:'iiLi!l <riW; of I~t¢ d~ A. A(lN ~'iark$cl :t J. li~let, PIljlS. l'l~. LeW:lilQ', 1"16·tb63), r.l!)'sre<lci1ins: Earihat!'e nlosUy p~t()!lS ftolr:l ~I!! '~~Ue om the figr!!.l!le. ~" ll!tIJtaIl~I~~' m. ~f>i;elif~' ~~r (~ll<!b~r'dii~nl. Ii)~S'!ll!,SS~O!ll.·\.Vi01 Ole s!atistics ·oro~r I~re~ :nearby S()'UllreS. lilud, !ru:fitUJ:lt ..M~i!1nill.tl !512!3 5 ill (2:00ll}. .• The ca:lollo,g AGN dUIil we use i.s: in" sen:l dll:l,iIIse~. '1~I}e olilser.'cc:IDcorrebll:i,on :~s ,t t{, G,pe~!;!!n,Pii:yt .fleW, ~e!t16, 74e '(1%('i). 4.. 'G"1. 2at!!l!pUI. 'ii, A Kw:rnlJl, ~oo. P/I}5 lnl' Ur~·.4, M ~ea:singly inoomplcte lIIe9rd~~, g~I,ac'tic f~.@!~e, ~i~i1l:i.~k>;;uil.~ Iliufllxiimnn di~~l[tlmcs 11.0 AGN fer (:l9M1). W~~L'[(;l 'i!:X!lincmiol~ rm~n dust. ]111 tl~.~Milky Wa)' {I,fU!p l~iO! ] 00 .Mpe, for lI'IulxilliUl~nril!lD.gu.l~r !l. V. $. IB@r@!i~~,.. ), I. Grrgpril'lviI, ..tsll'flJiI. As!I"ilWiJ.~ :1.99, s(l[J,a~'3:I:i.()ns .of I!Iip l'O, 6,Q., :tnd fo;, I.lIH11"g-y R;:d!lOO~ lilt:: ~iM,i'livil!y of oo~~r'lla,~iQiin~" D~" ]. tH(le~. 1!Ih:resholdsa:ro..and MEeV. nos~ l!lllilm~lIe~ flocl:iQ!il~rrom '~'h~~())~~~:i(; !'fJ!~~n~t~cf!,~ld 6\. N.l;!ayQ~!'!idli!~~ .~I",.Pi<%. 11iW. ~~l; 7{,.lOOO

stfiJ.:Cled direct{Q'liIS and crlergi~s. Tbese small diWf~~rllc~~, ~~lwi~l~if'llour ~COrl,slruc~'iclI~ w ~mo~inmy, m~lify d~!,l r.naL~I,\':~l ~~oo~r.Q!lli,. but 1!lPls ~las m£nor (lomseqJYe<!100rS 0:11 l:iu;: value of 1~!I!le ~iBt<lllletcrs~. liii...... Eli';. that ~m:cilfnb::e <lnd. ~~le cor.relatimu. stgnai .We sllln~~"e S.a!:I~\iV.ill~ 1~!Iimff'l!'M~. of higj]aest OOCfig)' !lfnd8id.d c:velt~s one by (lIte in ordier of d('lcllells,il!lJg energy,. dOWlit to Elgl=~O ]t;e V~ Slmn!!!:aoa·~lruniorl fiignllls occur tf"or'oo~)' 1~h_res1IDlds OIDlJund00' !eVmKIL :sevem~ CO'll~ ~illlm:kms of ~lItIeolh,ccr ,~m.me~em in i~iIle wmlS,e W·:::;:6°, and Zi:r.l"'~::; 0.024 (D,n,u <100 MIl!C). The a!iOO,(I\lI:ne m;i!udIWII!II:I'n v8!lue QfP Occtl~ :for ~1Il~27 e'i,'UI~1S ,vil'll lhG I~:ighesl ,~erg;illS (!'iltlove S"IEI;;V ]ar! lJhll'lra.frwaJilalysi..~~Wegen~m~

'ii'iI~crgy .am: .d\ro!pslO 90 Mpc ro~'en.ergie:> ,exccedimg &0, EflV. TIu~ rclari\ll'n, bctw'Cen 1~!1I~ posil!iOIiS. Sudlr} oor.rek[{lJIlrtS .are under ~iIlve5nig3A.;liI]l::Ul~m:tcaJ horizon di~~:aI~ol.';a"d. L1le v a li1!11i:l 0:1" D~l~;>; 1Ji1:llC~ tiom i~.panlCl1i1lar fm dill ]nfrn"~~ ullllilimi:zl'lS 12 l.i> IiIOl 3J siiw.lp~e (!!Il~. iIilivl)ln IIJ1115 S.aJ:()Ui~~ (IRA.S)I ~a];U(:v~ Thill 3tlIOOO.m':l~i1lion ~i~n~l (If !n~e h:lgh~~II.e'rgy l;o'Vel:'l~s al~ is :~tblL'l bi;:h<i¢Sil~ U~~ ~lhoo.WMehhml DOll" imifrJrul'l sCI~[i!ivimy over [ilcI'UIIIlgC: or pillrnlMu::rer:s being ilflvesl"gi'l!~ied.U ,~:how,sdepolflures frmn sc~nncd. h1Crea!iill~gc3K1~og inoomp,lellCIlCS$ isotllrtJpic 'e.'I,;pcctaliOilS .m:t olIDgul:1lr sc .. tes be,.. Sel:'l!es.SiS~l'lil ru:Id.i~ ~lliro, :preventsC('tufLicfiendy SCilnl1in~ o,ver SlOll!l'Cts tw,e.el~ 5:\1) anJd] 2CI1~ (23)amd a~ distllfn,cb'l :ullm::h. ~@I~.cr tim:". .~00 M~c:. tional too~.t('j klcilI.tufy dille sipaillia~dlistributioil. of Illiu'lSOl!ll'(:ell. Mo.~ol~'l':! 'I11~ l\oea~ d.e'!i.sity aad h:llil\il~o.sities .C):f ~IlI1CCS Clould 1!.a,,,Il'l $.igni liic:alllt d.'~i3!filJmS 'CoIiI'i!ilI1:l5lliln. W~ ha.vc cfOOlO:llSl1rarod !.1lL::~ni~o:firopy of 1I1~;\ITiva)dJ[~(:~ons; ~f Ihcltigll¢'il&01111 1~1Iil·~r!(!QifO'.¥mity a~sllffiJwi I~ ~~iI(1; GZK

obs:crvewIdJ Illca.my AGN :frolllli ~M:: V~C erua!{lg Ca:I1Ii1tO~. be used 3:tOI1l,(:l asa proof thal A'ON ;lft;. liiliL'l t'ourc~+ Oth1.)!1' oour,~, .:ttl: I~g as Iih·~nr ~~lrib1,!Jli!OI!:I'\",u~hi!'l111I1~ OZK hQrix{l1! ~5 d ~lI!frk:ie!illl:r si!]1~Ia(' to Ul;Jj( (If ~~le AGiI\~jcool!d1 lead 00 a. si.gl~ifllcanm: ,eor.rehniolil between Ure aimvIl1 ditec!lim~s of COSI1fl:iC rays~Bd the .AGN

kQrl~o!'! seale for

T~l:i;h~lg huo

,cQ!ls,idcrnllO:Ill

addHklJ,l
ilhctcd

tOlhc

thresbolGL tbcsiC c~""e:ats. in ~Ilceniili~ty :in ~~le recOOl."'

lit Clle!;SY

ghro:n

CiI1crgy

orisj IJI. OW" o~rvatlmn

OO~!1f[~C rays

a,nd [i~clr

e'){~~g.:d,<tCtic

('llillilrgiesc, th.(1; IiB:Hge; of DI'!'!!!!': ,anode,,!

s.are (lons:i.stt::IlKwiltib, the Iffiypotffiles:i.s. l~hHl~h.e nlpid decrease of nux I1H:a.<;I!I:red by Ili~e .l?m.G:U1re Au,gcr Obsm:vatmy a119ov,L'l 60 :EeV is du{'l '10 Il~e GZ,K e:il~ct .md that m:('lslofd!lL'l OOOIlilL'C: my.s.rea.CihiragEarth :Uri

or

a,r

j•

or

I!J>C

~obe

'!;Jj~(l!l as: indic<llil,'c

:becarus>c lJ~e

,.we aliso expcO'Iedi

~o be8igt!!litffica!flI!~y L~er

tl996.).

RESEARCH ARTICLES
"I. fI, U,. ,llItib,a~ ,!!'f' !!I~,.Tllill lfifb!!~ ·(IIII~bofal~orn, A!;:~jJ/W~ }. 611.0, il7~ (2:004), ®. T. 'Sl<i!lIl1f'l. I~. ~, IBH:f.milrm. J,. U~E~~ll" ]l, P. !P.achef!l. ii, A Wi!t!<D1l, f!lIyJ.. ~~~e1l:' 75. 30:56 tl;~9~), ? y, lJ~hri!tIiHi. , ~;!I~D]QJ ~. T~k~. oM_ T~~~ilil<l" M J.lLg~!i:l'!~Uilim~~n[j.AA W~~lrnn, Mt~IijtIa"t. f'~'_1], llS;:li
(2:0.00), USA; Arruflil(~I2UfIOl I'oirnnl~d61~ Acddiimii~-El.lfII.pffin (:.o.rnm~nit)'ll1ijglln EII6''!!lf ~rC5 I.;atillt-~ll'Ifri'<ln EillJc~pt~I!I' Ne~Qrk. alldl UNE1S((I"

n-~fjF'aI.-IIJj:@f OI!lIIlil1i~Oill, F

l, >MI..I~,IIl! IL PillHiiOOJ]~ 5. r1lt!:ff!I.:l.ll5IP •. ~,f!lrnll1(il(t.4 '1(, Pil1l!Ji',~B Dk!~lfIiIJ11 N!J:(K;~ OoogPllIlln1 N!j{K,.:I 'T'. M. ~11I11 ijli, ID A.lPi~L,M R, f'i'!!~.'~ 'li'.PierQ]ll,jI' Ill" lPil!1eliila} T. f!Y!ID,l~ \1'. fir. ' 1], if'i~Il'!;~ ~~M .. W~~1iKi'}1 .1,~!1!!II\~ t f- f'~\;~r",eM ,M ..pr,~~" n 1;. ). fJ~ ~

Fi~1I auNimr li~t~!tKlalffillii!tioM ~ ALr<iI1,w, ~ ~~ MilEl1/ III N,llli!lllli?

"~ lW1b~~1ll1 u Ii. ,iW~~~l.Il
:Ill,!l!l ~

f. j\gillllT~, ~ p_ AIl!i~'5,
AJIlOi'!MAIlIih,!O

]!.O. V. L G~i'I!b~rg.. S. 1_:~:rl1fn1,;lM:II,I'},i!!' Drlgifr GfCO!iiI:NC Rays : QPI~g,i!lifMl\ (}Ifillnl1 il'9.64~. n. A. tit, liI~ltl~. fIe~, ,ilgmn. A.ltr~. 22~ 4.250 Amm, (ll9:B4l ia. ,MAl', \I'~r~i1"c~ny,II'. ¥€'{lrI,~fJ;tllt A,${r~y£' 455. 713, (2;OMl
l.3..

"JtJl~kl1~,6'1.l\lk!fI,~ ~', IIIIEsaofl.'· C. ~ar(!',4'i'J.

e. Allard i!lt @t (Fi~FF!!~l!IgI!r (1l1l:lboF~iM~, ./WJ~l!li)l>i'~.a'l'a1ll!bl! at. Illtlp:/lIili'..:i!,l_!Il~al:J6l\a!trO-lilm,

MD~~

14·,.cj~)~~r:ni, lt~eS!;ier,Sclwn, E.l~. ~~nto~ A, ~~~its. ,ilfI\il;l<iI!ll.e <It ~~p'~l?:iv.!lfflliiIl'liI010S,lB56., H,. c" ~~~n!!1i ~f'ie!rE .{!,U!Ji!1 C~13!:IDf;llti~~\~ firo{~(/i",p in, '~l ,91ft IJil(ern,;r,I'i~l (~sm.K'~ (~jgf{;fJ'{~,. lliJ!ile. rl!~ !I)d~a U:alil, II!'!$tl'!~le ,all ru~da!fii!'#1!t~ IRl!seartn" 1!1!"!!i<I,
20Q:5,), !,i~L. .li1, ~.li 1~o.. 16. ,fit A:~ (JWg~r CrnliJaooratiolll'.
JWI'ij.~Ii,~

Ii. J!J'Ilalo~,:I~ c, N,ilIlI!O;:II. '5" ArgIro.I:~ KAriI.lka, U E'. Mfie~iIi.. ~ f'. t!!n!te!Kl'(!}l 11'.{\!1Ilf~(I$, III T. J'I6.tlIl,~~ '" ,~.~ re:y;-., P .ll.5.5i-~ 1t·5 \ 'l!il!.Ji"--~ :ll!.! ,,,,,,,,,11,. III 1\ .. zz. '''.' .... .~ .c--' ..._'~!n!, .' "'.... i··.,~i .'.,~, C:;,ll'yik u~ :El3d:@~ z. O. ~~91i~~~ T, 11,_ IF~ B<!~bQ!"~P ill B.a!fmliilj}~ '5•. L 1(_ 8;arFD!Ii.,2~ f>•. B:uillf!O,,~! IlIB~:ttt:l';~ r.18!!au\~a fi:, 8mr,1'i' K. It. s~~r,~ }.I\ Be,'Ii:I~~~ s I'!@l'llllt.3'! c. ei!lil~l~ '. ~rwililii1il\]] P. 8~ffilI~IJIk~.l!4 'T X, 8t!:1~.Illt~ P. l, B~nT!iI~n.. 3~ IP. 81f1oir/] O. 8l.ii11C1t!c~~s.Zl ri'. 1l!.Ia11(C!j 1,1 ~" iBLa!~,]'U1C. BiIMtl ~ H. BI~mer?]_l'i
,fll. B(l:1li1g1i., ~i'to II, 8~DIlI, j M. IEllrOlli.1!1.~JI ~ J, ~t";{k; f, 6"~~r,,, ~ ~', (, :6~f!" 01:\ IP. ~!!<!JhllO!1.;~~ u A !:l1J~1Wl;,'" NI, 11, &Jisg,~,l\;1~. '50. CiJj!:li!1~r .. ~,JglB. CM:~I [l. ''iI. (;31lni1l...~ R. (ar;tJ!1!".~ 'W, 'QiI1lllIIiQ, ~~. jl,_ 'CiistelliM.,] 0, Ca,1aIairn,!~' G_ r.:rt;~ltIf,·;u L '~~~ibdD,;l.i II!. '~~r,!.!ii ~ 'GIl.!lm.ri1,:Il! ,Ii. O1i:ii;'tl!s.:!.~ l A,. Oll'il@llatlll.,!!11 A. (rol.l}.'i~ ~ 'GIi)'!!!.5i9' P'. ID. ~ aar~, 51. R. allY, 52 IE. Col.omoo,5l fit COi'Hl.e1~~,\.2 B. C.ffMCiliy,]1 F" ~Mtraas,~3 ]1 ((jppeil!!)~._!i~ _ A (Qrdj:~,~~' 'ootti §1 S. ~D!Jl.I.lI}~, C;,Cil!o!'OIIIlt ~!, A. C~eu.II:II;.~~ iU. (

Aromfll!)!l.~

EiOWiOlci"jO (.

•...: .. ~

N, S~l!lllJllalllky~. Gr.md~§] A.~miial~ __ ~11 R~KI<i,<tiI' II sz: ~S' mljYl~ ~ I" ~ <' --, .. ~a.<:. I>S' ~. tr D· C,,". 1'1111< ..... .. 1~ I'll.". ~!iI1I,yqll ~ ~ IF" ~~~·el.:i~11! f'_s;.wmlli~~.:li! .i, Sit.!~kifll"~ H.5i[iiimko1, ~~M~ ~14!'!r~mi,. ' E. '5!1!"~~1ii}'~. Stull; I~ f. 5L!a,~tl T. MmijaM\"~ A
~m ~:.

l\ RaiJl!mlM!f!J.~!lo S- R-ellWl'1;, IJ' 8, ~~iI, ~ ~, A. S, ~.lm iII!)~~ ll, litiiij,'" Sd!iggt.·~ tW. ~~]I) (_ RIW61!Iif!.\~2 \t I~ l~ ~~, iloOOil1!!;lI!I C.lrtobl!!db.\~ a 1\l00rl[fiJf!1;!~ Il\.l\:oor-1"gug! IF,rll~61 ~', RGdllgtl!!! IItlrtl'lKl', 611. 1~,'(I(!lig!J!!l; 8Djo,\,2Ji I, ~~IM!l'.C:j'oo. MI Go I\'.{!~!U!I. 'R~®\,:uJ M. R(!(l!,n &I. IR1:iui.1lt""Glfi!m'i~~ E. I':&ufe,t" Ii.. (, RMrlll,,1'I F.. 5<iLami~ ~~ Hi. saliriiilf;,~ 6. ~~~ iii. f. S€!lII;met&~ r!,!;, S<intOfl!!fe,r, ~ C E. SOI1tl';;l,z t 11'1, '5.ai1t{l$" ~~l.I! F. ~5.3I;lthj" u' S·. ~r~r.M' R. $~o,<lJ 1.1. :5t1I1!I1i11rl,~ ~. Srltri~r.,~' IF. Schm~n:n t 51:mmltlt,)l 0,. :5d\Qb.'I!1Il. f>. Sclioll'iW~ ~il! I~, S::I'111mr,!!r,~ :5, J.s.dlBlW/5 ~ MI, S(Hjjj'~FfIIll.Il. ~iilj!Il!tG.. u 0,. Sm1k61; 5 lUI, S~1fOO, J>I fl. (,5111!!~liifd..~6,J€lI'Sid~lIla 5] L lB.Si![lffi.ai' G,. S"gl ~

all'ailabk!~

Iltt!il''jI~i'I'!iil~g!ah!:!1llM9,2.1.2!;, If. ,M. &l~!ll 1[F\l@rr@ Alil\lti Colla b OI'il limn.) , 1IJt\!'~pJI~I{~; ,a\I.'!Il~blle .at IUlIii!"Nan:[v.wwai)~a7(l!S,~la% .. 111:. 8:.. It 11)ii\~ Ifi~rre A!Jger OJ:i~lilll<irali!]ilI, A5rt~.I'5!tl;.
,~<!H<!b!.li:.at ~1lp'!1!!;Jn;ivM;!'~b~0f106,l.lOS.

w.

I? A ~~m!l J~~f~$~I1d~ ~~ ,~ !i!jl;lO!~e 1!~ U!!i!'~ :;.: 1(rIQJ:l:lJ ri:Jr a I!-Illl;i'bti! ICtmSI'I rll.1:Io "" n .~!I!'l ~-'1 ,Mpc.-~., 20. It W', (lay (Jni!\ff~A~rC01lalic.fat~~,lii ~mg.~,iJf ,~ NJUi 1liI,~fJX:l:ftl~fJ"qJ(:rumk ~ Co~Il1!lCIJ; t~uklIDA. ~EJam (Unh1tt$ll~ ACll~ITM( ~ft\!S,'rll'l:)'(i', )ilip3fl, .~OO), wL1., I'P,4.:l:1-424 il:ll. e:. R~I!UI, l[Fi~rl\ii{\liIQ\:f COlI~bDf,iJ~illrn'~ 1'iif.!~f!" ,rJ/ rIr,~ J.fJ'fh 1!'11tn!1li'lr~m (>Wmi( .!I1ay ,C<Jrrftr~(e I[ZDOOt r~!lI.:. In!!i!l, 1S, 22~. ll4 Hil1F!. (t ~. Mamcil.atl!f. A_G_ G.,i, 'Qiao, IN, lI.afl St.r~t'~JI, ,tr,frO~ t- 1142, :!l!1i.~

~"me.

lB.

24·" 1IJ'e art 9ratehtl

,iI\I~,iLaIrl'i!.ill J!!tp;'/l~l'Xi",,.w~Il~Oj'Qj,t.;r~~, IOdielQIII)\,"w ~iIi.!:el~lt\~ ,i)1M!

D~;<IIli~~ti~~ rOf Hn:lf:!~~l ~'lJjlpDrt: 'GOi;l:iemo

(2:006), s:. Ui!k1leril(~

.I.Cr,(:im·I'\\~:lS; 0i!gG~~~~!:l~ ~~'~. i[).a!Jm\IIer,,'" BIRo :!M~~ ~~It ,~, ~1WeSd4'1I C. I~ !)~10.."~ ,!U!' s:. l~ .jQ\~'!o! G•. De IL;!V,eg;t,~ w i, ,rot,~ !lIeUO~~Iw.~I' lIE ~ R, 't .iIEo,M~ID Ne~.~1!! II, [iii:! Mlti+,JiI ''iI. ill! !::ua,]~1 Il.. dd ~~r.-.t O. iO~ilI)'r 11_ C!I!:lIl! S!b.la, n L ILX!IlI! filiI[@, ~ H" Vif!fl'Ib1l'l~tIl C. [):I G'l!i1J~ 6~ }c C. 1i:M:z,.~ C. ();oorI~~ ~~I ,I. IC. D'O~o., ~~,1:1..Domi c,~ A. D~llIlee~. ~l J. 'C. ,iii!}!, lIDjM'z~ I M. To, II.'IiO¥\l,~· 11). D'lJIoo.,tuM!, A, OY'~~!KIi~,~4,tll IR. 'Il'~}~ t. IE~-e,'"" ~ Erd~r:!m~'~e.G. E'ilii;il;lar, fl" Eld!e~n..u ~I [;I. :~n l~iii~IO fI- f~:!t!f~,'" f~Jrar/ .Ii._ (. F~!!!h,~g .6, f!.!- ~!'!tnl.<rl' A- ~f~ool~l,~' F. ~i1'oi!f,!l!), S,. ~F!fil'j/"I fI, 1Fidc,~ A. :Fu!i;l~rn. Jlc fiS~~~iIt 11. Aoc~2~ It fIilnll!,"~ t it:.I~f.l.tfllridl~~~ S] 'IIi. Fi~glft,l IB, Gao, lID. Gi'ircil!@amm;. ~J [). '~rdit"Pilnu._~B
v• t;]

f~~"

O. Wiiil'lOOf'!J" Iii T. Wal.d'~rnaf@~33 P. W~Jhr,'5il V"W ..!f1ll!@r.ZB A. A. 'W.illllfi,],I s.. We!ll.eroon..w (I., Wi~~rek..71, Ii. Wiefld!:o£tB~ :Iii, u ", .•~-..., c. ".. .m ,", "".. """, .~~ II.. ro ••• 1<: ~~ .; ~ • ' .•• ·.t:11!.11l!" .... '" "011\111 ... HI. ~1L!ildI!i!eil'-e(,'] ]l XI!!}1' r, Wniomg]t!, ~i p, 'i'(K!!!!K, ;of
~.~, 10

ii, II). '~l!i,[!I3miM-ky;1i!l HI. S' $i!rI:merland,~' J,. ~ill,I~' L 5.'!~kli/~ .~!.aki!I1asI[i}~ It t3iila:!~rro,B~Il T~rlibII'rm, 3] f O. 1ia~~~ 30 R.. T~a!l1JC,~ ID. TiliJllms,~' ft. T'I!lIilMa, 69 ~l, Tiffilnb!l'rgI.,.!S C, 'T~ll~lIfIl!1in~!s.II,S5 W',. 1il:aU)'J(. n c JI. T~11I ~ ~B 8. ioll1fl,2.A. 'TIlI~ilIlilll;'1l'i I). '~rre5i.:l'I IP. 'rr~i/FiIa!k.·t11 A. fIi~!;lIii" G. TTim~ilm,,~' f5llnelllii~llIIw, D.. ~~ rrr,.T~ro~ ~ ~. hlll1i!;li1~.~1 Ii!. lllrich<,l1' M. U~." M. Ulrba!l,j.fi ~, F. \Ia'l~ Ii'!!lcia," 1. 1;!'a)ifu:,IO L 'II~~~I{)._ I~. ~II !!~Belr,lt;\li, 1Li'. Y.<II1 IEIi!Wi"l'~~ it 1I. 'IJ&~. Xi, D,. ve:beliJi,1iIi A, V~igd.~.!i ,,-. ve!.a~i1e<:ffl T. W~I~i!l,~12. VErll,oI'i .fit Vide-lao·! r, V VRla~ii1l~.53 i. Vil~';~~ L ~4Q HI.Will~bi!I]}/s

II), ~!l!i'::',~

M- ~rtmill:,,~

J\~~bl'u

J\.~~~:;!

[i.Io,~i~~t~~ :11Jni!@r~itldTIlCOOI~~iI ~'oc~~~I,. b~lf!! M~wl ~San rtiliaeL o;S~tma!!a" ~~rna,i:~rilt~rio de Il1IIiIJ'lIm;:!'1t.ii~a'D ~ fi!ii~a1~lpellillrellll3l, de f'ilniw!lir~ ~nd~r.l)ljl_uW Sl:l~n:lll 'r~GI1Iioo.\.P.lOOQ;,H9 1~5!Joa, l~nLl!JiilliI5liwtQ' iii irl6i,it 1Ie~~SpiliiieIrll)Il!IPI<!~'!.lfflI !IWW., UI~tJi dii Toolleiloo S~~ I!Nm,lOO,2S'lf~"r1!Q,. t!iJ1!f.·UIli\'ed~d! ~tI!H;CfJ die !!~8, F\O~ SflZ? ta "a; W~. 5!.abcratm~Mtro'P~1iJJ!~' ~ (g~, Uiithi!!!r!!illi! f'~ln~ !iN~j>3~~~ f.]52)1 7. P!IIi~

~Pitf1l"'f!

~r

~l)l£aloor,alijDill.

tI:stf~}'li'io,

~, I;;r

Wr~li,ti~ (ferlr\eI1fll'~" !;(!I!!lI;Si(J1 ~~ticr.lo1l·~ ~!1~~1 Atdmtt3; Mi;inritf,pali(!ad ·ifellt~na~~" IF.1u!oa.'d0F1 AAlJJpcm.a~ At9'~fLUl1l;l!i [Iii! AillStlfilLialFi IR~!i~r~trJ, (imilil:rfl
e~rl!!~ililll Noo;cfflal llIil!' ffi!!!~l!Ii'\IOl...sm.e,f~Jt) Cie;rlllmko e 'T~nll!l6gi~Q O::Npq), F:ln~nd2idurii If! ESru~fl~ .~ ~rcl@tll~ 00 tllbli!il!erf{! d~ riima Il 1ieHH)~ogiill jjfiNElMltcn. ru~da~iio d',!!.l\ml~~ ~ ':e-~ui~~·do IElta;oo de J!:i~ de J,m~HI fiF,I'IflfRJD. IP,lIooa~Q de AII1[ilafD iI de ~~~® ,!!!~,S~ R!llJ!i~,IfW'E5P:l. ~r~!~f!1i!l'i~!!"y ,g.f EfI~Ln~1l.. '111M!! ~ncl$pi!~~ mf 1lTI~Q~r" lt~p1!4!lirj ('~M:f·l! alio!1al. de Iia R1!o1~fl:ill!!$rien~fillu~ N ("(NIt$1 C()rl!!~n fiif!4lolaa1. il~t!~~'f~fI!(l!. ,00001!l~fb@1i1~n:t ~by!;I!ll;Ij,~ No:fhir~ C:orJlllI!{lIlailrt ~~C,IIN',:lfl'31!!:'NfIS}. ,~1. [)€l2rrt~rnreru 'S1:ieoc'llsde r~.IrMf.~ ~llV!J,1 fol~'1r.ir4erS~ fraFH.e-; B!.lIoo~5l'lI~11i~lIlrilrm f(ir Bil~n ~ ulldl f'orschu "!! (@MIlF,), ll)eu~tlge f.Q~O!:lnL!!Rg~:t'!!lei~CIioli!'t [lfG)" ~ Wi~~i!~!l1rlll~i~ri!!!'!I !!!!~n--",[irIj;lemlberg, ~1m~lu· 6e1f:H!~~I!.'I~t Det.I~t!llI!f ~~f!!(jlrun~1i!mri!m (iiiGiA. ,Mllm~l'!liill.nm '~Or 1l\!1~!li!iilKl&aJt umd IF!II1f!5!lh!ing. N~flfilli~n "''!!~1.:I1~n,Mlm~ll!iiI~m mril'li~~mliflil.3jil, IFII~dIillDg lIMI [(uflSl.. Sa~n-Wliilll!!!1IlDer~, (i!l!ITMI'IjI: ~M:itlll(l Nal101llll1@ dl ~il,l~1i H'IJd!Ni f"1]' (i~~:M),-,Mirli~l!~r'!l' d~tllL'i~ir rl'~IlIf!'. w de:litlJlnwenita 'I! d~11.:i IUlCtK<ltMtlJR), !t:tl¥: (OOiej.{l N~i~I!<I~ !!~ GIlmi.a )'T'~I!!I~i~ (OONAC'tIl',I, Mleolii~~; Ml,!l'ii!:e~~~!"I O~,"~jl, (lJll!ln!r SI We[Enst~p; N!l!d~t~n~~ Clir.g.ilniJ5<i~;~ '!l'OCf' 'we~eru;ciia'PJ!El1iit ~Fl!i!Ii!k. iJlM/iO~. '5Irdl~m9 'iOOr IFIJI'I;tiamf!iIIt-e@~ 0>IW~Fl!~1l. .!I!!t ,M~t!lil~' [ffitro, N~[!IIM!,fl:lnd!: rmFii~1l)' of S:dm~~ and fI[!jJu@r Edliicrlt1on, Poland; fumi!li!~:h ~I'i! ~ Ci~ncl'a ~ ,a re(nol~la.. ~oFrui!la~ fflilli!;~fY I~t fI~er iliI !Jf.iIli~1L $citl'!()e, iim;~ 'T'e;t~_flaloo!r:l,S1~Qiiln ~ieitrd~ : ~Qty" S!1!)"\I\ellia, Co!Il1!.i!nida4 de M~lriill, 'O!imejtri.a, ~ ~!!!~O!ci!!r! !Ie l.!! O!I'I1~!'!i~!! !Je. ",,~~m<! .L.o!. !l!MU~, fEDBt rlilDd$" li'Iilili~,elrio' !Ie lI;ilfuGdilrin y' Ci~rn.l.3, XulUa I!!!

:;:, Gai1!ldtJ.,~~ HI. Gtene!!l:,31) '~mlItl;I~' Iff. ,@ti1U1lf~.1~ p, L (j1~iII] M. !:iiIleI/i IH. IGIaM;,. 41' M •. S, (;ow, ]'lOG, G!J1llp." Iii. G:mltl Albiirr:il!::[1);2~ Mn~ ~rig,' It Gihnez H11mlro..n P. !'.i!:!I1!Ii3iI\lli5,lM, GoI)I;;a1WS eiJ tIm:lr.l~ l~ D. Gl'JIll.li!eii;:!] ].(i, ~o'J!~~~ til, ,~t~,~~ ~.G6r<l\~~~~A.'Gf!jr.gi~ Pc. GQ~rrrJl1" <II' \I, 6r~~;45 A. Gri'lg,!7 (, '(ii~I1I~~i;!,z~ Y. 6ilIa!F,ilIina!fiii, ;!'!. F. IllllarnfiO, ~ G..f'. GiJ!!1fe5. J!; :I- Gut"i!l!ffU, ~~ j.. a H8o!jLi!.,19' i L, ii!arllrillll1l,5 1'. ~~,!II 0..H!ar~.6

e.

"t

Ill!)~x OS,; l~far~~iltIFCi

AI.!$ mk'9 9atilodl!!

(mEA); 11m1mrl

5:.

HaFFlL!lfn:!l,1~ ~, L H.!l1:1i1)II;~EI,I<~ I'IJIIlf~~ A.

t,~1.

'f. H!!I~d1l'1dl,]

r.e~~~

V, ii:. ,fI~~ ~2r. Iil~,i'il], M. H!!1'!'<n;.~ "" Vi~ ~

Ii\. D. iiilfl<ltjl;

H~:b.Wl:r."~

(), IiIttd:?~ (. HI1jr.I8I;~~,

1[, !i!1l!!l~~

l!als!!!HJ, (!jNCM,roJ. 94011 FcHo ~1!1. ,Arg~iIIUJIii!.lN!!M' 'l'iUrk IJilt~t!f, NfM' V~rk:.. IIU 10027, li'i!!i. BOlliG! Sl~re Ulliivmil1j,
(.owN, 'OM .!(I3\:!lLO!--l06]'. USA '~lfit.il Uni~d31l A!l!:~ '~?!lIe,Nir\ 72500 f'Wlib'Ia, M~t~ lollUIlivllr5Ml.iiti de SOl1~~ ~ (~[;!Ii$~~> ~!!57e~ S5l'1~~ ~ 01i!I!P~1Iit~.
~~Iii.

H'cCr:aIildr!l,~~ A. 1iIiH,I\d'rer.'J<I M. ~ID!i~III

fl.. !I~~~' f, !~~ 11 A, 1!il~~U!\1.. ~~.'!:1 K iii, OC. (I. ~rlh:!lle-r,-J!i [ Klo!!IlP;~~!lIlt ~~lal\er,.~Q lita. I!:la lit I<Ii!if~s. ~~ l 1!.l!lid~iller, !Pllft ~~.;lIi ~ tikr.!lW\ I~ ·ilt ~rlill},:n A t:~piililn~-..L9A. ~ri~[IIlr,,5] Q. KrcOI1l!l!F.!19 [),. tmilllp!li,3D N. IfImlk.iJll9 A. m~l~ 'li iii ft%il\ i'I (. l<EliliIud', S B. l l.agl!il~ [I, lfitll'llil'li 32 IP. ~~er~II,;~9 .L Ift.i~ A Il.eigll!illl~ Ol~'e'ira, 11 A. lae:s,ie;:;li!!tillll1;i:Ii g, ,f!1, i.e!lltIIi1!;1I, II. i!!I61nr-'!I\'Q1l, Ft. liwl:l.:~f,J" l:O~ !Ig~I[i, m til iii'

1.IS;e~[IfL~ [N~

1 ~m(!

lBa~~(I,"~

~,t

;"IMOrlih!~a£lerllUlni.ml)'. ~:mDn.\ m. 02:n:~,0!)'6, Usn., ll,unl'i!'!(Ii,H'I (If ~fl:!'i1:l\ 1!.Iil\M'!u~, Wi n~.lH..USA.. ~'1s1i1uLo iii AsirmI'"r;:lf.iI Spmi31.e @ fil1(~ (Q~mdl P~lillioo U~~. I" 901146 flalef,lro, Ital)'. 15Um:.,reriila iii f~1iIO ~OO INfNI, 1-]'!JlI:2S 'f:Olioo. IltiI!)!. :IfIUni!M:sil¥ !l)f C,ilIIrorrria, l!l:s JII~ei5.. CA 90005;, U:1fI",i1!W,f,t\I, 'Li!oor<!lJlfi, ~i!Jl[gm.lli dl:tGriillil5."l!iW,. I,

!Ii ~PI'I~" !·OOI!26

N;ij!;llu"

liraI)',

~oo.ne

1I'!'lt;(;lIrept 10 (. ,M;3[]!]~!fiO,J~

67010 .I!$~

(l'~ia),

Ita!}'. 1'y!1!~Iilii!klIiC!l!!1plrte-n,~,~

sc W:ld~r.!,~ M. ~iEbio!lt G_ M3rnrat~~;I,,~' M.lt M~liIfi!liii!l,B.~~ [)., MBli'Idai~~ P,. r!.\.arllScl"~~ .11. .(1;. jlla1'iarli'}~ II. C'. I'!.tirls..·n Il)" r!t31~~Il,;U~,Ma~~'u (1 ,M:~lrrH!:! E1:r.!\itI;,~ ~ Wi~!\n if-n.

,~ Ma~lliIM't
Ii)., j;l,

m.a mrn (10, Ii iii.

"'1;.16),

A. ), MilLIllflm; 21'(,;, Jliatlln1a!..~4

,M~~1I, ~1

(I., lI&i!Ur;. Q9' 1... M.((<liill:!~.lZMt,

Wad~d; IE.~.:l:1!3l0,Ml'!iilIrn, S~ml~'for~tliiw .EFllfilllti K3fr.F~Ili!!', liiI!ti'll.lt riir P,~00i!'1!l:J!;M!lW{!ll!r~UJI91 iiOO E11~rnl1lk. 1)-70021 Kar~FUlill!l. Gl!rma1lr)i'. ~'i'Pi!nfi!~/t:\',a~ :~~l!!! IInri\i'!!r!lLy, Uinli;<e~il)i f':arl!'.l?tlllifi800-.t.3il10, USA, 2'\~ooro!iljjF! dI! 1~1I1J!! fioIi.JdJe'i!ilr@ tl.'~ Hl!IJre.~ IEi1I1I1iMl$.tlmm!>it~ ~rls 61lM 'l', 7'5252IP~nt

fI. I.!'IcNiliL'61 .M. (, .tilfdillil;iI GI. ti\ililfil~'T.l!rIUl. ,A, Meli. ~ <\Ii ~., Meb, ~3 IE. Menid!<'l.li. L'> A NI!lm;dlik.l11!,j;~ G1r'.I~ii:~r,,~ Fti'l\e~!iI;!!l.."~ M!. !.M';trn.elettii,~'G. Me~e-,i~'IN, ~Uletr;rf s;. rJNil~",(jh," ,M_ ,M~~f,IU1 10. U~liIm(:;r' Ril!l'1l~Iite;S~
It=. ~1~I~t321i!.
M~''dl.e!,~~ t ~F~~,

'.e~

00., h~!M;.e. i!2UIl~rljlif

~rClli~

lJHiro Fermi l:Iutiune'.

l (, rI.'.IIfi!fllil<.~~ (.

G.:ill(ia, ~p.aIrt:Seli!ilC!!arnd fedii;,iil.~;F~!iJlljll1!~ ~jj oo1L UK; ~~part1'!'A!nt of E;1W!IW. N~I!lOOilo!~ :5'IJI@rnt:'Il' Fool'lchall~ml.

• .lIE, MCf!!nq.~ fIMII-n$. ~ r!l M~~r~ ~~' I'!c j.!\:lll~r,~I' M. It MiI!'5ll(,]5 G, NjI'.\!Uloil;l~. L Nm~~3 S, f:.IilI'iil:!'u L Ni!!a.i!1i1\&~ C', ~1!!Ml~IHlblme!,\lII I),. ~E;\I'I!iIi~.1II,]!I! 'T'. 1r4!l1Il!'fElI lhi, IU N. N~I1t~inllO~r/D 01.. Nitl.§~ ID. lr4;)llilk;.I'1 L ~I)ll:il~q~ J. 'Oi:ti1li:i!:II1ili[J!lr, ]~, T: Q!!mIij, l~ Ji" 06~LIlI,~-l.l 'IJ•. !It. O!I1!1~!!;IaijO\IO !~. O@,II $, g51ap~~~Q,n l 'OUi~'!!.~ [l, I'""'~k Sielrnl'lDei,01oII M.IP;3~ll:a}!ll"_llal!I;t~,1 C:;. par·E!I][.~}1:! [. Pdi:t,~' R81:i~\l.r S,. P.a~t~f.12 M,.IP~N!I,~ I.. PaulF :~, V,. f>-.Miiki<u,. 22 ti:.lP:,r~ Ji:1. Me ~!W:!. <iI]I. "'k<lill!,?~' R. p.i!la~{~

O!Ltilillo, II~ 60!6~;,1!Jj,.\ ~~rre l!i.!ger $~,lIhIINl1! 'Otllerl'<I'.J)I)I; t5iGtl'lM~r[l~, ~n)\I,.De ~~~ ~.;~" ~'\!~t~ 5~1I, !)~7o()6o$ $"egel. fjell'II.;uur ,1lIlIIm~~d Na(n~1Iat ,d~ 1:lJF'~a. lifl!.!ilitJirn, III'! Filh La ~'G00lii!j1!l' ~d[]ma,1 ~ i1itl'l!rtl[Jlcknl!!! Cii!lilllfltll~ y'ri!cr;irrl!!. lll9fi.!l} IA P1:lita.\ ~irn:l. ~'\:~Iro l~jJsllI!t~d@ W'!l'5qIil~~ ~tl~s. CEP .222.90·1~O Rill de ~!iilliili~ ft]. 8f:j~1. ~IJm[ofH:!'ldalill E'itll!:l\Jal. diD S~iloe~ ,ma, Bahia. 4Sea.~900 VllJiN 1IIi1C~IHIU~~,. IBA Br<lllijL ~~!lWr.i!!lic Sl!il~~ l!I!1~f:~liI'. ~!t '~fli~ eOS23. t!1S,l't '~~UrM¥~~~ tl~' Ne\1,l ~l1it;l;l. ~l!;i~, lt4f1! utSA. Xl6e~~!w I.Inri~t;31 W:~lE~I<!I •. ,[)-1I!~W 1MijJpem~ Gelfili'!iIrI', ]\:~lIitibi.1 !J~mily, :f!.lerlii YOlk., Mi; 111l001, U&i!c ~lL3lxif~iifi! II'! f~ Subat!~ml1i.U! !I. ~ 6l!lTIlilICli}l~ ~fioI2nf(NI\S, If.

m ann

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

RESEARCH ARTICLES

'1IRE,'1Sii,gnalingl A,Heets C,e,n Fate DUlri'lng the Unf:'D,lded Pr'oteiIlRs'sIPon:s'B'

]IOlilaUliil ri H. tin, ~~:il'" IHari l~,il'~DloliIgLa!i VliwW!iilllirriil.~· Hallnnalil R., (o'lilelil.:2 IChiao !hall1lg"l.JS B;a ~illalfll, "anl1iliiilg".2: Kev<l'Ii1 ,M. Sholm~.:li5 M.!'!tth~M. Ib(I!V:a'it/' Pdlr!;fWailt,erli,a:

,~a~

rgID1im~ healUl ,dqlev~ Of! Ihc!roctlmC):.,of dlC '~~8.1~~ smt sud mccl'll'ro by (')~ut~ 11!lei'll lOOiils, Protdns" ci!dmr s~dI fmmdte c~U (I( Crnl1hcd.&d l!l. 1lI~(.'l

PEltK. pel!Sistedi U!tic!' prokmged 'ER

Sl!'CSl!>

and

W'C1!e

sum c\,vclcn.t JOhmm.

;SMggMtcd

(~1l
Il'fii:i:P(I!i!tt!1$ stH:i~~;

ilIflQIi

stress; GilSon:. d,'Ia~.'filoc;

lin13 Omil'SG:!l

bl·IER

lllG..."'!'if(m:UlIgJi

~fiQJ1t:iJoo-me to !t!iolti!.Or~l1i::m'-

V;lried

of !dm,illdD~

lrnl].~t !T!l!!.CI] {If U~~5 ~nfi:nH1!llkm. On ~he In.'il\,'i of IU!eiiC sigl~k, Qd~s fl~ake ""vial dedsiQJ:lSwiD. !lld wlli}re 10 dlivid.e, IlIli:gl<U:e o[a11lIlg,e shflPC, ,dIi~hmlial£, or die:. Cclil5lllila~1: ~1\ffid ~Gl1lrelil:aUb<msl:o eliL~ lillil ~(U!I1lr;y\~'iih
~ro!l!Wt;,~I.

IRlEl
.

-_._----

._.

rroiomgoo lR!E] sigll~u"g i!~ ~kefa.cc of pcrnrs~cln ER ~, CeU mlY~v31 cell ,wr,facc. :Silringcmtq,ml~ily '001'1'" \1I"aS slg1lUl.cant~y ,(mham,:::cd uHm I~m~.is lmposcd, b}' the C11dQP~8SJJruie dl~ (lOOldidJll1sl dcmm:u.-'itwl:miltg Itlmt mt1.cllih.u.l!l(ER),lIn.13lllbr:ame-OOtmd ~abyrillili. oftnk'ian(l. sae.... \?lIill~ dlf: termmMiffil of [Rf; ~ 3.e~"'ilyisruli i!:n;PO:~l faCi.Qrilfl (1nQ\l,:i~.~ c(.lll Vif:!i1;.lilinya'll ~!a~E1J'(I. l~iIl"h~)~~d Tille umfoMed pm~il'l Irre5pam~~. M(Umulatio:1iI of m.'is'l'oLdi1!dI prrolffil'!.s: '(~R . d~al :;.tfk;r trfR ·ac~hr til(lJl], .. ~C~. ~ro'l~~rIIll:~ijn 1II1~lf jountey s'tr~ss) trig,g~rs I~~th 1i~!lIlpr,o;t;ective Qll1ldc~~~. dil:ath r~SpClnrS~s"but with WI:, V\~ :fblilld ~~:~ l~qTIe-!lclal~. 1[0 d'!;(l;~. O~~y 'pro;pcrlylbl~dI dll~rti,nrt time: C:oU!r:sES, s'wildlulS h~ jfige'~Llllt ohlilelWR flD'k\ir(flsm-e aUowoo. to ~cawal~ :m~ (froIl1001 p.mieo~km to apq:m:!S:is) :im, :~nis:rQJdoo p;ii\]i.eins are de>gmd(:.'iI. :In 1~W.is ''i~y, ,ooUs ~li$p~ayJ ~Jl~,ooly O bi,gb.qtlflHry,. FlIilllcli!llJl.a~ :~uot;e:iJiils. ~mjRl8ilmm\;:~s.of;lL herha:'b~dCYl'liim~.tiV{J l;nn1~~11O~.ih)'-m.'tinili:is j?lgili11im.t()R;a_'!coJJii~iI$ pl!Oro.~PtQfooll~ d~~1I~ a ~$lJl.lII. 'i;lf I:h(';l .~~si{1!rI or 1'0 ~naillia,111 fidelity,. iheooll rnlood<i to f()M pw1£d.llS as ,th.tjy .aw made', lI!iiilfi;lldl,id rh~'Q~ll Iwo1.~~I~.~¢<l:djtt:l.gtoMillidm~$., O!,W tindijrng~ IlliIM and Ihis S-Y$W:IfJ]rn~& to iI&p~IQ I;h(lJ'Igqlqg~OJ'I{~mOlt'l, 'fh~'l f~ll$~hi~v~tW ~y .<,'1. ~l Q,ril~~i;i~It!!4lr $iW'l;l.ti~1ll 1).w;(i_y",.cQ~I~ti:¥~ly lem~~d! d~'~!JlI~. PrQvidL;; !I. 111(n1§i;l!;J1::J,iV ~tlQn"l~ fQrhQ\%' eells oolliirQl w~,~th~r~ol:t-¥e 4t¢ ~tr '~xmlW~mA'edl IWlER. S!~, w ro~~dlp1Ul~il~~!g' CU·PR)" whicl! ~I~S w'he!1 InI~e ERI~~5 <!ctlJ- w'!!e~~ P~iing Il:C~.~ qu.es~iO:~~lldl.u:de ide~til)iil\g i~lIeIfINmSlllll'S by whiCh. :1ll11l1li."lt'CCI ~oo mll!alli)l' ulnilbld~dll?r:o.tei!lls. "I.e UPR dJ.CB ac~.vatcsIrnIliSQripli(m (]If OOI13i1:l gJeIl,e!'j tnrulscn'Ie toi 11Cre.9SC d!e 'E,R..'·spool:ein.rold~l~g cap~ as ,dJitl)'~ll Vli'R bioilllliles mUTtbe sell.ID~ivelyoolJln)~led.PiIl~hal3ses moduJare iP.E:RK. ~mlJ1.ch oo1iv:ily (I) ond 00l1M alsa illlNtuel:m [RE~$i~lilll8. onh.er lJleooed. UP:R 5igoati.ng am l?R)1oolodls OO~lil, ~IlICil .RR slmss by cxlP:ilwldJ~n!ll 1~1IiI('iatl~j)UI~!. of ERin Ib.h~ OGII, Ml~ancil:tg t]l~d~i.t;!il Ofll~i'sfo!d:c,j 1m~~lionaJl, l!l':.1i1lli!a1iMriJ],a"c:lixt.i.ur..uI$Jauornal i:'C.gltllalO:~ i1~~ha~~nls
lfli'Oti.~fi.~.imd ~iiJcil~dje:~di~i<.l·ori!l~v

whu~1 proteiilrls ,;;00 fokied .~nd,~111· bier.[ b;:mre ,exiJQJl ortf<!MIJoO!1 d)o, d~e

PERK

v.id1:lill UPR ~~~~ iIDlUll@lOO IUl,c ecll~ !!!.Hi~ fate ~n~5e ro.E-R slrell.'i:. To!ec~ I:BlL, \\re de\rdopOO a dkmlca~,-ge:mc~1l: st~gy to w~1fOl ]1E1 ard ilLS d.QV,!'l~n 'D~ ~ cll'Pendl:n~ oJER. ~\\7e C1£3~oo. isO~l1ichtm.lOl~ OCU~ dmt ,exposed al1~1I1.Hiciatl iIblg-indi!JdbUl': lIihlII~ant ]R!E 1. wtudl ..illO~w.OO~ ttl ~~II

~ ~~hlblnsh~d, hO'wg~1i, UPR 5Iigmali[ig,ev~nbUUy im'!~

proleii:lc",.rfho~is
~I[

CiifiViQt

d~d.l'by

1]1ja:Ylil~~"CDtllnribu.e.F~tdfi~'iO:ue. d~.If~~i\iI ce!~ ~ m1iy laitQi' d~ UPR CiQi' 1I~~if 0\"" 1)~!l5. \VIlliich~'l grille m~law~·y ~QaU.ce]ls ",~ld\.vhteh are

<iiPQ~8~,1!n ,elT~lhfe !R~'fJsOrf~e;;~il\ig 'OjeO~!i4s!illi;Qiit rog!.i¢~lls cxpressiil'lg dysftand~onllJ siSJl1~liI~g nro.loclllks. How dlX':Sdle UPR s~td] bel~en dicse ~~~~tmUyinCOl:l]jP"lliible~ife alld de!lJ!1I1 f~~e:!;rn,he een~ t No bliwr :t:hi ER SIreS!> 1~8!.~li:de:nlifted ~ il1~atselectively elicilS o:niy

I.Olerance!e'IIIe'll!; W :ER ~? D::il!iss~lfS wiJtlli. [mhetCl;ltly ,d:~f['mm IRE I , AT,F6, or' PERKoctivi.ttes dl~ll.l)' ~'realer or 1e.~rresisttl'rC~ I~Qce:l1de..9.lihl upoo ~IKii.1(ltLon (lifER S1lI'e'iS? Md~.tL!QnIQi~tL'OI:];[l GitHJ:iU1~'(IF!J~~UrR b:rraficl~ djn,'CI. ~n ..prol~irn.Dnlll~i~~may ,allooool1!rn~~ ttl d\~ lJa~1m'I ~mtilCu.v.~ li'eS.poru:i!i: 01'01111.)':tp!l!p.t{]!S;~, JMl£:3di, .lER sn~m:'lti'!,!!'I1flS all UPR ohfX!plooiN.. '1\.Il'tnut~iU~antREJ,. f(lf !(il(a.-ll1[:lI~,a,.~i:am.~ WUi1i~ apoprM<i"'" tfiI~ s.~~~~imlgpallm;".ays, d.~t!$by suntlJ1iarnIlO1;l.illy p~uei.n;g .(milll1,rfiirltb"tic Ol!,lflUl"" Toad~ lillIi~ ~%1!i".wO)(. ~ d~v~IOoI'Ioo. ~1·~ 00,~nin.~ 1l1~J11QI~ui~ 1)~1,I!~~n~Ii3CL-2 pOOOOao ralll'ii.l)l'I:l!I~mbt;P.l BAK iind BAX (7), LR.m !':,igllMi!Qg,tcliv.Mesihc IN.K palill!\¥~~. pQs.o;;ibly by di~~Uy pha~hQ~~a~.rlig tI~~~Q!, .of l1~roo~atmJle,l ~~.e5 of d'le urR-~'I::Nen'bl.'db'Y ale E.R·~~s amia1'[ton 'ofER Sl~ W:iJth.d~~ersC SCl1S{l1':S [irE I, 'ER'K,!lndi A1F6., resp«iliv.el,-"h~ hum~H ccns e1>::tlOsedlo dog~re.am ~f®pt!> (3). Film:l~,; hUlllan di~~Jt'Oer, diiiFIbcu.c-s,pmleirlllopadlics,andi \l'im~ Ll!lfeooOI'lS~l'llislt'lt,pl1<I.mmoo~.Qgicall, ~1.KIIuood Bt SIreSl!!.. As ,e..'q}eCl.ed~ lIlihr:ec ibrlll,.dl];. ~ es '\m.'Ire acliiw.\'ttOO.'l!pOO ·in1Li11!.1101] ofER. ~ h~ '1.I)~p!:le~:OOly,.tim OOlil.'llviOF' rai!roSdlepogsiibllt1.y of aUcringpodlogencsis l !by I'IJwlipulllili u:g ihe UPR.. Ci!,f IlldivWlll'l~ s[grnalilng patl.r!c...ays ",a;rioo m:nk.edlly Wilh II.illilG: ifi:(lf 'ilmQ:litS~ 3 :SliImli]iiiiiY Re1iilweIiCe~ C!rs~. n~·.,..]~ .s~..im !i'IlO1~O[,1 via~R.E] q lJiiddy aU~l11uaJtoo\,'irill~iml8: ~. I..INIl1'!fO<l.H.Zl:ingl, lit ,p, liliiroil)!l"D. ~Iil', J. Cdl £Ilill\l. '153.• llllli.1. ellO OlL Wio.1!J~ d~rr~ lilie p.m<;(i()l~ofil~ slmS.~; the ATF6 ~li~!l:*~'?Joo ~~ " ,t;, ~I~ er,gf~ kim{~ n~, '~n (;::·OO6}. 'wlW d -1:1 n-1, :a""'nu"'lioo.. ~&;e.. !1,II.L"r. ._)"co. ......._,...c ._"p<l!llS"" !IJt~.1]"j"-1IJ,u -: .3. F. Ur.a!1~e~'!71',,,, 5mll(e .~II1. 15M (2:000)(, ..... -l'l_-!Yo;I,i! ......... _ .. _ t; -' . Ii fI1l.... n'"'n'''''Fl !d~ I'!rul.' c . s- ... !I>lI.I!.....,I;.!I_:;I

lailQred to ~~'I{l~),r dHTere:nioeU

l~5

to· "di ..I·~n"PI~5iolog1c311yOlppoo~

nl~

~I~e

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

RESEARCH A.RTICLES FULL-LENGTH ARTICLE

IEl1kdil!l;plil~rrnli:(: Ir~ti[llIlllllm, ~ER) !il:i~i!5iSialcti'ltilt.es a :~a1i 'O\f sigJfl!alling IP'ilI~hwia!ys, (o,Uectiwlly ~eiilil'U!d t~'El I:Ilnl'olde:dl pr1ll~ieilil riElSPOll1,SEli !!JPR).TlileUllleil! !!JIIR br:a n!:IiI@5 UREl, PE:R'K.,illiUffiAU6~' pli'OO11IllM:e· ( I~e:~l s:u rWv:a~. by l1I!!chlllcirng llllillii5l1lil'dI~dl pmrt!!~n 1~!!viE!bi.I!J 11'111: :r;lig,na[.iirn~lid.!lo IPr'Il<I1IiIIl'tl!~illPi!!lprotilli: cel~m de:atlil·f:i1 ElR. :!;tre~!> is: liI,a~ .aIIJ~l'lIIIia~:eii!l.lttow th,e 1lI111A: im:egra~es: its; CYMpfMe;d,;ue and pr'Diil.p'optoth; IIiHlltputs 'ro s:eited: b~~elil tite '1)Qi".ath ceUfattJe~ l$l,llnlu'llollWl .• W'e:mUlnd l1:at ~Hl alild A1iF6 Qldlil!!'n~E!'S ~!'1~ gU~!'!~~ed by IP'~!i'si~dll1!rrt ER$I:~$$ i~, h!,!lm'alil,(ells. By i(OMlt~~,t.,PEIRI!; ~i~gngrliJil!'J. ilndl!!tiii'lfI!g' tiransla6lDlliill'l il1llhwbit'lllillit nidi p~oapoptO~c. Harn;c;riptl:O:IfI' Ifeigl!!~artof aw'P ilfl,[JiUdio,lil,. wafS Imiilinlta~nEldi. Wl1le~ IIRE'l. aJ(ti'li1l~y WillS sUUi.!i·liIed :am1iiic.iaUl.y, loeU suMwall. wa:$ @n'llanced" sllI'!1IgleS1:i'n!gli[l CHllsial ~ink: ibeitweemdliEl durMJiOIll ~rf IIPR. 1l~:illll(11I si'~lnllllililgJilllll(iJJ lil@ IUIi' deitlm celW~ fdlteilfter IER !itriEl!i!l .• IKey fillldlin'!I,,,flmm our S1ucli!es~n (en ruiltur,l! wer'e .Mcapi~l!Il.aed 'iin IWl!hiotol'iei(lepklr5 e!Xplre>~in:!lI1 rnJIlltant IihodiGlil!rilUll in .3Illim3IlIJ[loi!l,et5. ,of fe,filllllti'$ ~igililll:!!ilto$a.•

d~GIWER ·o:it had :;wq,ui.!lOO. tile~ Qfrieliil~t:ig U\e e'ffec~ ·of ~e ER:s~ h1:odud~,g<l,~~~ To Ihis end, we ,e:x:a:[Qlin.(l(i lillie glYCOOylJrntijOi~ SI<I~l!lS ofvnsoularr min ruihe!>ioflllOO~·OOI!IiIl}-.1 {V~~I),
::I bjli\>nlLe<:IUmlne

protein

dUll is

OOG[mlt'l]ati·Qil~ IEu:aaiSf~l.ed

any il~~rtM. in'110 d~ ER I1IIIllrnlibrnne '\ih.~roil

b~~N -g~yoosyh'i~(!I (11). .~

HI@I{29] c~lls.witlllVC.M1l~t ~cll ttj!l:!i~~in. ..~d(lo,n1fl ..red ~RIH<1!(;livity w~llli! I~heS!tyca~yi9~o:n smU:li!!of VCAM·~. (rig. I,Ol'. HEK293 oens c..'~:prcsstng VeAM··] spliCl;,'t! Xbp,i ~lllRNA im a IilIDnll.c·r iI:tdiS:ljn,gui~~a:b~efrOln,d~at {If 'MM", ly~ (\\iT) ·tli.~lll.al1tl.:'ij' tm~fcal1lll¥'Cilit 1!re!J1I~1, and, as Iml. In.]Jnl'l1lllsHt:t~~e~U~ ;!1Jf_'J'-J!l'hRWA ~1).l~i6ng
pro®lie$Siv¢lY~C<'I!)IIoooot'k 00 basra~il~Il

wiOl ~~M~>edlreMJl!~!!t (F~~. 101. VlCA.M·l W.as fUilly £llyaosylmoo. !llie(ore' :ullnicanllr}'Cin OOkIi~ liOn and lim bcrnlm: pi11iaUy @Iyeosylated. ;1111£1. limlll IlIJ1lgil.)!Ioosylarudi (Fig. lDJ. Not (lldy lnile study~ .~1 but also ali Il¢\.vly ~Yll"id~OO C1l1'!.i~rmm!1i~ij]ccnndilllOM:, 1II~~udly p~Wim1g ER VCAM-l W~'l ~rn,g'~o..~laE!W m.laI~r limns ifKI:llIlS ual UPIR tIrg~t~lt~fo:[t ~Il¥Ha!fie~,~xp:~!isiOtl (f~g:.liE). ll;i!rotcJlIfl FOlding ntl~lily"lIpol'! "liJ.l~tigaloo ER To dei.tnll.incif od~cJt IRE.I-depel!ld'enl 1i1.l!1C'" Q:r~le Ell, cl~pero"~B:iP pm,ltoclS c~lI$ ~~nll!ER ~~. ileUPR ;<1!t'>Q "M~!;is. t~m!lS WCIi'e altenruu.edl! ll!l.:;) U131U1ef ilktn.ooXbp-J liIlli~cl" 1illI~lIIpooiuc:ernUsfQ1ded or IMlfll1m::~oniilil,g SDJ:esS (9). wIU."CiliS CHo.P;. a B.z:lf n:al1scriiption mfu...~A.spHcililg, 'We c..xmn[ned the ac~ivati(m stafactmim:h.l;oOO by th.e: PI~rtKhmnch oflilile UPR, j;uote:iinls, ceIlsare elill1l:imne<i,. pcfi'llllps ~" pmtec( lm {lF~Jl1lf1N.ICnilliinl@IIk:i1lilase (JNK).~I~ :re:spOilSC proll[lCUQ> ce1.l deat~.(W). Pamdo.:dmtly, .aU Down ~hc '~lisll~hil'llm~e c:eJll.s lIJi'ml·dJJ 11;01 mcci.\I'C orrre;]a:y signals property. to, ER ~. [REI f[litr.,~a ~~md Iron~~lilmll ER ~es $ill!'IIJIj!tmeG'us~clid!. :pfl:m:X:ll:'!.I{; aut! IPI'IY!.l i('l~()gjc orpad.lO!o;gUC [br~css!&S tl.1:al 'Irr.xie QI,:ii~pult~mrl'!ldle: Vf.R,and. it has remtlirl<l~d p"'lI!L'I~ U1M activ:;r~ll:N JNK (12)1" Jill H:Et29.3 [ ~~]Is.. ~NKw:fi ~idi~yp!·liJlSphOryIi!UJoo. 'lMlnhER UI~lI,;;aJ[ ~ow lhe UPR illJlelID~. '~l¢il~o,p'~ing creat~ "'J~ iJllbOll;lmOO~~\!\i¢~ p!1Ot~il[ !.bIding slmss (Fig I Fj, The inilIlUl 'bu_~U!lph05pl'~J~,i.~ ~ ~Qi'!d"'l!ldl ~p;l;city ind~.ce lllilre (JPR ~li!KI!.!lg:I~ 0l!I~p.u1r." 00, ~ri ... at a ~i~'Of d~lh dooisio~. Ell,esLdemt tma...'>IT1C]l1b:i·nJ[el'l·o"!:ei[ljs_;~R.E I., liBEl. s~~!lillli!fl~is ,al:eh~d dlurinQpi!f' IJInOIl\,rm fullowcd'by a loogresshre deerease ill, PERK,.8i1IldATf6---:tlmt act illS :S13lliSG:US In ttU) :rutmt. EIR~, To dctoonil~e llile ,fl;etivrution plilospho",]lN:K levels, n tread lfllIHitparath:.'led Xbp-i InlR:N'A ~p:~icing (oO:~ll: the ti:tIll~ [ilUUillS ER lUlllc,1!I.alflcli trnns;llli~ ~!liieilnf(ilnn.allOl~~o ttlQ sua:tu.S of ~RE ~ a:llcr E-R. !miCs.... we 'eN8I[Qlinoo. lresi~.of IfiI~.tlo!3~1 (1). IRE lis a ~Jlialh<lm.el1mibl'<lffil~ X.~1 mRN'A .sp~icirnlg by ~'ffi(,; from 41HYlLlrn to 200 hOllrsin .. f'~g.·~ \Io'ilfiln.dlG .f . tii3t'b~rnp.tiou kh~iLqel(lndOribownl~I!3ML'l {.R.NANe], 1i11:at, i1ip!)ll~ polym:LlruSi'lchah~ ruactiQu! (Rt~PCR) h:'l Im~n.;,'1n 0i!,I,uiv1ilenu dm.GpoinItJih~ f~ m). f1tl!lS; cells ~,lJtoncl~~ ro ~nmIlig;Mf,d!E;ll $~ by ~r.rsl.a~)o !imi""ali~. :inAtiat~ 1II~1l'l n(i!I~i)OIWI~liQra,t1!] ~tic'L;:\IftII~ir:kidl1.ey (H.BK):l;9] ce~t~ (Fig. I tit), \'Veobse'liVed t!teappenJmlcc of splice<i.- XbfJ-l '~r.gof'.MJ.rl"l flllRNA (2', J)\ ~,Hcw,Xbrcrl wnRNA li'il'a1i!J~ mK!. dlCl~ alOOlln.lmfillg m:m.<Kiuvhy. eneodes I), '~ra_nsaipl:io:J:l aclhrlil.t'or 1I~.n00ves ,EI!~h!i1!¥io~ IUfo ,~Ifld PEtRiK of s~gnalingwlll nlRNA afu:r lreatilllg ~~~CceHsw:ida. U!!lliCilimlllrcin pfillili,istem: Elstl\iiiss. Ie, assess; Vlfh.elh~r olh~f 1~1I'al'iSCI:rp~iOlrl g.~m:s sucil. as ERc'lmperon'CS, of ordJapsi:Qargju: agcll.l.'.'idbl1 ·clic~1.EI str:essl)y brsnehes 01:' tli'mUP.R eUc~t khn£d:C,ooh~;'lkJr bloak! ng 'N4it:l%cd gl!Ycosyilali[oll. nrinhill.idng Wh'Oi';"',:prodrn":ts di!lOOclt.y prutLlIJipt'll"() in, ~. ~'I"{F 1~.edBrl fiOMing (4). PlS:RK ~sa tmIl~im1ibraU.e, :ki~ Un.ciER. Cia 2" IPwnp.,~ctiVllily Sil.t.wilw to lihal c>lidt\lcl b'y u{:EH, wemOralM!!ffid. (Fig_1 B). 'U1lAl'F63!nldJPDK aClavi'ue$ {lV(.l[ time (alrer UPR r.:1.~ 1.!I~a:~.~~oophQ:ry~aw'!dl¢ ~l'lll:a;UYQ~icWl[!)$;1atii(m ,ex~C'IL:;dly. 'we. fn:lInda. SlrO:lIlg dim,iumiooh:'l ilflilllall(1l!l! ffu:lot :2 5U1lll.iitt:liL 0: I(i,l:1.F'2f.!:~ 'd~~f:Ilby .Xbj2-.l miRNA Sr)lldng widli pml{;!llig.ed ~l1:~~fiIl 1ar.r.tU~tL(!!I~).. 1'0 ~I]re A1F(i a(:tiVall[,}ll!; W'C !rodm;t!!g ~rotdn sYHllh.esls ~.Ki.CQ,1,mte!<!,Ctm~gE..R, It:! "ei~!i!erdlrog (I:"'!,g. ] U). 'to!!~l~te!lt w:tu~ ~Ie fgl!owcd :!!l.e UoomtioH ·of i~cleo\ved cy1l~rolHC" . f:r:otdn oV<:fkmd (;S). ,el'l".2a 1~IILQ$[)hory]atlm~ ~!lo 1I1,RNA, s(:ilicllI,g <i,ati:, XBP~ I !lpxQ1e.in~ le'\fels a rrn.~l1i~ll, ATf6~ ming <l :F,LAG·~g§cd AlF,ei a.nOM lffile ~,led:ive'iransl~Dioll of so:nlclnRNAs :(Ihelbr:nl of XB~\..ld\;;rivcdl f:ron~1 its SI)ljor.>{I 1:~porrterd'IQt r,r;.c~pitlliatedl ATJl'6'prooess~n:Q, Qpo:iililJ.dllclio:n of ER s~s (1".3'). We saw rnpid. ~IIl<lloOO1i:ain SIt1j(~,Uo,pen,r:ea.diin,gli:amlo:stm, lhctir ItlR.NA) <ilso d~a&'id wlJillil pro~.m:lged dru~ prodootC(lil oJ A'f'f'6tf aliter ll:;j(p(]s:~mof HEK:293 .5' rllln:lll"ri.ru~ f$~oru;, 'I!be:~y .Ieadlingto tire Imc:amHlll'll[ {f'~g.iB), o.liIlIcr ~1JlmAI!lC~n limes 1[I,rod!1Cli(}J!l()f t~lliru1 ac(i",:alorrs s.ucbfb.~ o(lh IbO EFt s~ (Fig:, 2A). W~dlproloog~. 'ER $'&IQ"iJ,!I~ qualimti.Wl1y sin~~~af 'L'lff~c~,.:3!Ii1Hri!l.gh ATFl!1l (6). ATF6 ~s 1!11Ufh~np!iou. f:la¢I!1)f I.hllil!. l':l .i3J d~~yd:Lff~rod fn i~l~~ (I'b!l~I'Vif,'d till1)irn;g <II' ~1~L)it l\t~i' AifF6r hw~l"di~njl]isTri~ illtd '~h{1itt1111i~~y 'n;lll,'de~liitiaUy as @u E.1l~:cl'e!iJl!. 'llmI'iS~le:nlbt.illWi .ai!~d shl!to·~; .a;s: wen as hll the d~~reie o·f Xbp~J dLsOlrp~cW (Fi£~ 2M. l1~lJ!s,,~ike IRE I sf~I1i;jI~ fimn. Upon ,ro1dll lu:iSrold:iilil,g,. lie ATF·'6 illg, 1\1'.1'6 alOl'Lvuton alsodiiDlilil.1Ished: alJlet pl'ilF mRNA. splicing (fig:. SI). cyilop:~asmic ,di\lm3in (l\;1'if61:) is li.oorn~edfi:om 101~geCl sires:!>, <l1b02~t wilh diiffeli\.'nl. lI;ineti.os: Ell Td-n...o;.cer:larilll. IJ~O!it!oss. of Jlbp-lmRNA splic" il~:gitt the la~~.i.~polut .. w~ irot dille ~(i,ii19o· Allhm:vgh [If] siglllliimg doca:)-<oo1wtll&lin "8 ~o'I!lrn! ~l~m~j~.lbmn~e aJi1ct~OO" ~ooguilaooCl.p:ilO'loolysis e(l!ls~~lio:UI f A1F,fiifprOOuctim~ \WJ! nO'l. ap,filG'ol o ~\I'atim~ of lim ER :fltre:SS~ndltcii1g ~rujlS. we
CUHl,prises a

sel(JifSl!W~lin~ ~M11!~ ·way.,> l'liml ool~co~h'Col.yadjlilSt lillie cell's ER pronei:ua foldltng rnpru::ily a(loomin:g 1.011£00. As :SlIch,. UPRs1wasi~ing IULtilflibHshes h.0I.1l~ lSLSil~ l.he r~G .ofehfingi IIg dC'!l~l\op[!)JI;llllal ~ m

heuPR

:(7, 8). The 'tI':O'I!1-s:cri.ptim.fi!ctollS thll!$pro(hlu::oo {i.e.., XBPI, ATf4,: m~d ATF6f), oon~orn~c 1:0 aclii.VI.I:leIJ:PR targetgc:mes, thCiuOOY ,cou:ttoJling 'da,e: Cl:;IPsrresponsc to .E.R SIf.t~!!S. G~!l~l.ic srudi~ hil!'iIi~~l)jI~ to iWtglll eyttlpm~octiv£ or p:ro@~;P(,[)tic :ru[l(,'!cion~ oo'~ndivid-

le~t~

oo~~:

nl!.k~

lHiJImlrdl H:lJjJhil!-:!.M.edicallm!itiIUll!'.
~'1Jl1fran Q~(Q, 'SaiD

l:Jniil'@r!iit.!I' ~ (ali~QI1:lIfi3 <I~ ~rilmi~m. CI!~411SB., USA ~~epilflllJiiern ,"I

l3iOllBlermrfllUyllfild

frafl~(Q,

:53" F,r;a1'!6~oo.. .0\ 94:158, USA. lDep,m!llents. 01

ll1opb,-.it$,. Urnivel~il1j

or Ca~!orniii!l't

!i.a;1iI

fatM~g}" .. md QpalMhalm~~y, Uli'lii~r$lty« QU~flt! atS",. ~r~n65.CO, III F'~.~l'uj~~o.. 9111158, SJt·l1llif~rI!lIIl~I'1~! mI ~ Q!i. U AnaltDtrI)l' :ilrodOphlhilirl1~~ Uni\ll~.r:511yDi CitJifllillllliitl ~.tSaiD ~rnnrnro, Sanr m 9~,1!:5:B., USA. 5D1l;partmmD 01 (e~~Iai!;;111£1~I.@~ulilr Fh'illlMmlD!j!l'. UniNeI1~[y of Cilml'ornl'~. . at ~n ~iian!JiD. S~nl Fir.liOOi~c, Cl\91!\l[IS!I" Ul5.!'i..

~.msm.

lrJi!iili!l~~~dI nwdit1! .mntl HEK2;9'3c~ll:!l U'i:!il l:mtd. OO~ilI ~"l!!L!.d \Villl~ nmi.c&nl~~ oit d.'kvqi~i1 fof' 24 111Om'S llill'~ ~".~~~.Iilt:le ~/mRNA {a. spHei!'iJIM,S; see,J~)1 ~oplale,s ·0:1' ~ihj' Ul1ltre.~ed 00]'15. A Iter 4 hours air iItcubmiOlililTh (lo:JildL~HQnoo mcdi3 •. Xbp-l i~'n}RNAsp~icun.g wa.~imldMOOd tt],~ d£gmeindislilflg~.~I1!lBhI(;: 'to tEllllil. .~oof1Jun ci(:~1i; '~C1 W~I.!I,' fro;sh aget~c}l (F~g.. I.C).

lili1fi~aJrer ail.I~.

11~e dY!1~ni¢s ,Clfjhe '~stnplioti~1

oflRBI

·of conlimUfiiJl1il slim!l. lMSet.>:: alld AlF~,\",ere oo~isleillUwid~ ~e~n2iQllOi:I]}_l

d)yclion kinel'tcs of ~lese ER.,prcrxim.d UPR sii.<Jillml1JSdu:oer.;.~lldllu:tio:n of 1#1' mlRNA, cmeodiing au HSP7().c~:iL~ ER. e.1Im,P~ronc:d~8t is
hlli<:eripfiOiliaUy ~!!.ffilIM~. bji' bath ATF6F m'lr!. X:Epq~ (4,.7), :~ed !II. Shol!ll'S itf!Gii drug lro'atrm~!1!t nd tI~~l dec~!!er;t ~~.!~preimdu.cli(J!l a

'Vo whom wrr~~~IiI~Ii!U: lon~th.il!l!.Um@ut'!~.ed~

$holil!ld b~ .ndtessed, tE-m~!l,~

Wen.cf'!t tes~oo.1f. at late Hme PQint.s, oo!1ti~l!!cd to aooYI!ulit.au~ 'rllisfolded ~i~in:s

oe]l11

i!'!

levels::(Fj~.2q.

RESEARCH ARTICLES
To ~ ~~·acliva!io:llbW.e!ics Qfd.\e Pm'K ~!W'!cil, of the UPR.,. 'iAieri'iG!1i:~lowcl! di~iilCC!.!:!thl1~ ~a1Jion of flImspl\Cil)'lated :Pru:tK audits dQ<WIn.~ S'trerun pn:xlll.lct fl!1~h.oi}'.l~G1 e,F2ict PERK advaHon did! OOl dirirlinjsh c,VCI~ after pt'l:ilm,gc.dl
Eft ~ (f'~g"18) •. O;U1,.~1'll£ltlw.1)!I~Ii'lil'l lfhtdnll& lfih~,!t31\L~~li:cun;'llC3.p:ieiry of c~b I~nru~ 31I[~~:U~ a,~ all tm]~ ~r 8!~S (Fi@:. 213). S:umillatrty..

in

(~:mi~I[·gE!iJiiletili;. ~ciilnl,~~ $tgji'i(l'tiflg IREi ~ ~mam ,(elbi:. 1['0 <l.">k whelhc!' tli~ <!inooll!ailiOfl

of IREI<iQt~'!flJty

hod! ~lilWSiQIo.&l:cal oo:nscquellce5,

~~u~siti~l~ ·of ER we obser\loo oO\Il6U:llU,. ol!lsp«Idtl'Cl'ikm of AU'4 {fig, .2B}~ncllitslrnmF scrip~io:n:ill I~arget Cliop'all:1ie;lr Eft stl:'C&i {F.ig .. 2ql altlII01!Igh I:lilere \!i'a" mltlegmcilgsi~ diminution 8t 1~_1!ale1' UIDG: pol!ITll$, Thus, by ·tlOfitIa'll to ERIE ~ iUl(J ATE6,. PERK ~ndlactt",~~iO:Iil .il!l 1:3WR~ly 8\:ISn.,9i~n~!'vith ~IIIQt~:fi.3lJooER s~

we ~:m~ht to seloclli.\ile~y (lontrol [REI ".eli vi~:y:. \Ve fiJ!~lO'wcd a. !lit.~ Idnalpcrmined ,ooe:luicai~ rng!J:iation. Qf fREl~: RNa.iIlGaeliv~ly IIIslllt,g; I]I~ adLm~ne 1cip.'I100plial.~ (A.l"p)8m'll'It.og 4-a!Jn:ililo· ~-1t!"11·b1!Jtyl.·3-(1 '·ril!lplqtl1yl'DOOnt~l)py~lo{3<,4-dl selce~i.vel:y
ladle:

642 (J1e642)]1 \)ila<; cl}.mg~ 1.0 ~Iyci!je [Fig. lA, "WRE](1:6£1:20)'1· B~ttsC OO!!LvooliQnal t!WiSb::-~ l~oiil .or Inm1~sdll:Clfulmgelle·e!>:prcss.i(i.1~ activated. . ItleU:P~. ,ool~lstirrlJt~.\!e~)'audc:au.'>\J11 ccJll death (15,. 16'j, we used niWa.\l!i.1"itU1d!wcd!. :s:il.o'SipooUic .DNA reco1l'l1b~lirIatial1J to ~f1Illro·fB:Uc{lIbe ·dirugS\"lru:l.i~i2~ lRIEJ(I.M2G) m~l all~l~ dij~ty W'lo. lUte B~l{l1ill~ of HEK2:9:], <ooll~ ~al~ a
11\')0. (iele!~'Ous

A
~
(.II ;$

{_'IBM·

h'8\1ri""
"ii'

[EI !iim~~Jw)
tm

foots \1\'e;Ii'C, observed in Ihelrnnsgenic 001:1", ,e;x:~ pn::ssh'l.g ifihc:r,RE~. (]~2G)aillele. TillIe UP.1l .",'2i> oo~ng; .00 IC]JOH1ll4O.&l:JIICI1:te,[LCU1i'l'S_Gly1{1.74.5G)JI :l'ntJ· ll'Ot COliSt~~llt;;'I!'('lly illdllLced in dleseoolls, lIS 111= dl~d1 bydl>G; a~li((lL:t 01" splilc.L\'.dl'bp...1 mRNA .. la1~iO'Il.llI!Jid(\l.fficl yea,'l~ fRl8:.] ool!L~~i~ to ] NM .. PP1. : \Ni.:llltt~:fu~ COl!ill~W'C~ an~II~I~ o:r~:lliln~~R1E1 (Fug.. 3B, O·hoI!Jrs. tiID~p!)ii~t),. AfHlP~i~l:i:c!1] Qf il'l wh~ca!l dieO:~lbQ;ll(n~'Ol!!~an1i:n.o (I(:rd [i'iOl~c[!ll~ INM··PP1 <1lQIiL~ iim!dJu~ !~!Mit ~~icil]~of' .xhf1~1 rnRNA irllRE~.(]M2.G).e1!!p~!'!$ oo~1!l~llro.1md lID< ,effect 011 .)[/)l~t :vllRNA ~'Il the ~illIelllElii cells
kinase don:J:L'Lrll!l. oUR£] mlU11JIlFtHls . el~lru:'ged A1rP~j.llrli!il. !>i~ (14). A

~ri!ui:di!i!e 1(~.NM.!fPl)' I(Fi~. .A), which [b,in:ds deAJ!f!edji1 srt~ (7)" 3

S,ifO\\\Ilh~&

1m

"ii'

••.....

~-

(F~ lB~ By oonlITilliS~ d~e IPP~.~llL'l:imim:l. :oHf!lc ·1111 .~.

~1~1_

QOJiIillSpoI~.dil1ig

~:NM~

~ifCd:oolb

ER

pmtcill nilisroklinl(g

Md!~.NM~·'N ~Wa:~ H/JCl Itt)

1l:ir, ~um:a!il allfl'ltl, l1iIus,pmVld~.

I;niRNAsp1eiuS.

,e
~lnnD 1[1:i~

al
~

.~•.J., :
.1;-.

*"\. l!-

,~
,1

-. p....,

_.

":-

10 VeAM:.;~~
!lI!lJ!\fCMM-

0'

"ilCI

,,6

20' Il:im~ (h~

,lZ

'=i
VC,ANli-1
dgIVOJUlll •.lII

20 Urliui~h~
ptl'llli8pJtn:!...!I~NK.

anilQ'lG.c~S\vl.d:] '(hilt cOI!M 00 OO.W~ ~y ~ N1VI~ pp~~ ~rdIe!'!S of ER tEJmleurnfQldillng ~ •• We lL'iCdIR:E:I([54:2G)"'IZ.xpreMin!!ll cc~·1:sto leSt ifwe oou:ld ~1ru1lipll'lal£ Xbp ... l;u[tNA ~~~j,olJ:lg l dnmingpro!o:ngOO .ER snress:... MUn,,\rr ,oolts, :im. li1!lflabsilll~~ ofIMM.FP1,m.'bw;t }{bp-.J mRNA r;pliein,g.~l!Uffid !mi. thL:t trniflS.!l.~rniC!)~11s lmJOef dn:\g trea!!I'I~jJ~ .<'!i~~ty tUrtle po;lrlll1l1fill lfih~!~dim"~~~lOO mlate1li linre poh:s (F'g. 3. C!!lm::I D~ool:lll}a:re lop prulc~to F~~IA).. 11m£,. tbe e1(I)lieSSiQ1~ !,]if IilCI.ll,1Jllillufiliole had! 110 deleterious: effccms Olil. »tEl I:l.cllvatim~ m;M~ooillalinll bypmlollged :E1t. stross ..~yoomms,t,.iliii tl!epr~~·.of l NM·PlPl, Xbp-l mRl\IA sp~ic:illg in Wirh~mlik: {;.flt~ 'Iva.... IlirIdu~d! ru:td r:eml1illooel~vaud ~flg. 3; C 1I11dD)" lhus. !l!1illcikd aCillvanQ!lli (If nm I.(h.':1'42G) by ·INM':P['I:I o~m t'llc tttwll!"~10n ofnm.1 aet~y~ty seen lqlOl~ iProtol~ :m SiJrCSS, stlSmru[~il'lg X7Jp-.l :IIlR~A sp:Ucing atl'ev,c!s approru!inllg 1i1tI~ seen at early lin:113 J)Oinns (Fig:. .3,. C alId. n, boll:OI.W jfllU»$ls), .A:llIl'Oughl.NM.Wl acH'Vat~ IR:EI.:(~642Gr(i :R.NA~ <'Ii;livlty.,~ &I~,:d Il(} CQll1Pl!:!1!.I)~!ll aetiv ..I.i:gn o,f JNK. signaUng (fig .. 52), h~,d!~c@l;h~g1~<It. mRN A. sp~i\:itllg ~;~n~~ ~ d~e tkm (I r 1,[~1!11(~642(j):fs so·hx:Uv~J.ya(:t~;.".,tcd: by lWM.-:PPL
IIfIEi adiivityelilMIIilIie5 liemvi\a'sjilml:.~·. ]NMIlL ..

YPI
IF1g. 1. I<iI1!€tics ·~fIIIREI S'igjija~iflgwilh 1~~r:S<lst~ ERsU~~. I~N' m Ird g;.w'+ !H lFdl('i-4-I'!iIOl!Sl:l~rnb1iYO Inbmlbla)15 w~re treated with ~l!In'Lt:almycill'l(td (5·!JIglmD, i3f1dX~l mmA ..sp~'kil1lg Wi!I~ def!enliIinE1dl ~y R-T~(R.UlilsP!~'k!ed [~')aIPial :sp!~i(!ooi!s) Xbp·.1. mRNA pmlllc.t5 are hlldlica:te~lillhe: .asOOrisk 1I1ldri~tes: t'he cc",l<:'Cflof ~. il.J!<I.. ~·---;li.CfI I,<;n, "'BP4s .,..., •. ,4',..",.",,~ lfurc 'i'---iLlnl~"'"\()~-'- 'il.. o;!J"~~.,,. _'!l!vyl,!,~;V I~_.. ·~I;I·. _. ~ ""ilf.rid· ..mp.n;IL '''~' t'I_ _ .,,,;, r.!!l!.!ii .. '~ _'I -'if!!JL .. ~.~_'I\l!!Ii!~. t:~"-:_fi~l-d·::_"".1>~'" IphQ~!lh.a,t1! de'hydrngeniilSlI! (GA:PDH) Lewis semi as .aJ pwteinl llOooin:!!I ,G(mfi;oL. '(B~I HEK2.93 al~ were ~~ted with tnill (:5 ~gI.mla I(tt ·lhapsigar,giill {(!l~'l500IIll~ for the iliU:li~~ times .: ttm.. red halr~ .tg~ htl!le l~ail:S~RiesU:~1S ,QI!'@ Ir'~r,e5@!1!lativ.fl: ~f :fil!feindep@li!dent ,e:Kp@rim~MS. ~C) HB<293 ·oe,1!~s e:f€! t~eatoo with w lllgillflt5 lor Ute! illlm~tIi!tUiiirmlll!i. .A1t 2.4 Ihm~n~ me!liill,oonUilinililgdlliil!l!ji!M!re tfillll:sf,etliiliE'dlto liriesh mills. Arter ,q.additional.li1oorll, Xbp·.1 mIilIMA~pl]~iimgl wa~ de1terminedlllm.~ M·peR. Uiil) HIBK2,93 ~~~s;.tr<lmsfeIiJ9rl wilh I~y I~ -,~ClR:.Matu:['eillrl dI degJ:ycJfJ~a~ '((9) V(AM-l spooe.s w,ere dmtlmm~l1mby imn1llll! obwtting. U:) ~EK293; cells,.tr:anllfected wilh v(AM.~:l.pweUif!Ueatedritn, ·lmro:rr tihe ililldicartedtfiimes <llmdwere pulse·

CQUlIrQI

.of IRE! allowed!

to

~~dl¢

p:]j.)'$~(lI19gi .. ~1.t;Xi!I~'l~~"1~.

·of IREl ~~!i\l~i;DI1i

and "lle'nlJ<itlml dU_ring the UPR. hi 1P.mi!oolar, we asked wltedlel: e]>;(ell;ded ~RE~I acl:ivali.m'l. woulcID ha.vc .EI bellielicial elTecl; olil cell vill'bi~iliy

UffiIDlilprolongoo, ERstlmS. iER .S~ in.aoooo. by both Ul!~k'.l'ii!fl:yt:i~nalldldl3p&1g~i~is (aCidc Iro HEK293 .celht .Fatty.~igh'l.In()lifl>i~Ilhf\r I:roa.hUk'tiI., less dl~l 2% ·of d'iliiW'TOOlls 11U.af'l·ivoo {fig. <4

and fig. :530),.TheacldJrtion of ~NM..iPPI lwd

!ID

VCA!M-:l. ~~~trn\~d

with ®1IIii ~5 IJg~.!rItJr!)rme ~ild~~'OOd!m~~s:..X'b:l"l mRNAsp~tdng Wi'lS d~ift~dI

W~

suhsltall1h ~I ,efr:ool. 111.u1iOI:!igb~~. dl~,ninislhed the: vi<lhiliy ofWroe:ll:s: s~ighUy(~2:S% redl!tCtion~n

viable C13I1.UJUitlber) .. B~aonlriM>l,~1NM-:PN II:'C:ruU:'l,ell.~. HlEKl9.l of ·!'!fIJ~ ~!IIi!!i!ilyn(;l;p~edpitaijolll, Th~· dQybl~ ~bi!risk O~ni!~.p:re:si!iljglR.EI.{J!642G) .irl~niJica~tt)i':111\1 iilldliGME!'.~ ~he l~as,lItiC:Jfi,(if !Ii 'iI1c:lfispedfic: oonid uied .as; !Ii l~ea;ailfi!iilwilltro~.(F) IHIEK293, Oi!ll~illiE!rebt!Med Anile 4~·h{l~ [ime p<1lint, With ~ f·OI' ttneindi:ca.ied times. ,a:lild:phm,ph:o·]NIK IliUoM1l1i1leveLS: were ,a~es.~edllby ·ilil'1lm!1I1i1101:iIotting.1Cltai~ pm~d1lnJmir ~v<il

I~i:l!b~, ,aild !'adt(llabi:l~d:\If'CA~:ru

]t'iJK prot~~ l~ls~I~'(!iiiS.~

~~(tOO

Loodi!i1g OO!lJDlI.

(ie]1 nUiriloorsafilIL"I:· d'!ap.!lj~rgtrlrn~tW

tu!f:I[caHWC~rI

'9'46

9 NOVEMBER .2007

VOL 318

SCIIENCE. w#w.sdenaemag

.. l1'9 <

RESEARCH A.RTICLES .A.

GUD:H

,
'~~~'_~L~~

ll~i!I'"
1p.!!'teRK:

IG)I

'"

11;2:111621'3101

~!m~!t~ \,W~ .5 ~. 201!im~ I~L8her,~ lirvely; ~$lUl.e p~~e ofINM·'Pl dw~ inilsabseree {Fig. 4}, 'Even. hi ilieabS:IiiCle Qf~~~rillil:allnl idildiJJO~O:Iii Ell S~, of rN}.1.JWI.pID\'(;CI b(Bf~ cialin, ccJllsexpresl>illg lREI (~64:2G), s:fi"'O:i'd]i1g a.-30% ilirnlil!lil~nJ(lf.tl of c~n gtXftvlilil. (fi:g, 4 and fJ:g:. S:3l 'Wh1)jg. mii!.iEl sugllla!in,g di:~lfy '~irihalWed c~nviab!Lli~yLt! U!efl1ic~ Oif E:R~I:~~, l!IIPI b~\rior ~~I~d~l$, ·o<f retirritis IptgJi!~fiI'lus:a. The UrR :h<lS:beelJl ~sWlm:ed to pia, <II. ml.e il~ the jpliJilhllg_eille...L,> of 'pmlIClDl mniS:~Q:l{li:I1rg disea.'WlS (IrS). .A:!lIIDoonDal, damimlnt rel~nilis pigmonll)83 (a.drItP) isa ~Iilmllll[Pf(}1n.J£I lill:il~ri}l{Jing di~ I:I'iIQBlOOl.iI!:IiD)Ully CNlJ!gLUlby !:l PItJiHn~oIlig~iclt!ll!(,)l'Ii!ili.!~liO'~l!lItpo.lli~QJil23 {)f :J'hOOop.'l~m (P23H dlQdo;ps!!a) "<'III I~&s 00· iUl: rell~lior!
within the Ell (.J9-2.1). IOOthml ~h.olorooop'Q!ls

IFilg. ,2;" l<ililm(S of ATF6i1DUlii

PiERIK

c1r!pressing P23H Imooopsin uillii.lu.tcly dia, lead" ililg Ito 1l1J.1~:dIile.__'<S.billt tine uiIO,leeularpalhvmys li!ilk.i.iulg rlladl:i[I)J!i!!nJ Iru£ft:!J:ldim.~ im'!ItihcER W ct:)U deatl~alil:i !J:iIldw (12). To l~plQ~ wlmll:i.er Ih~
lIJP'R .~i!l"!JUl1Il~!lIail In f1')6a;l(lj]oo1~ dbailh, ll;;'I1l emll1il~l!!ed.ts <101!iwlio:n S!lIlus 11[1rCe~:ls e)!!p~!1g i

M1I1I ~e~!5lmn:II ElF! stllie!iS. (A) HEI<2'9S

F:IlAiG"'taJg;!J~d A"I'f6u. UlIO sa 30 ,~'O'I8!!!,~ell!!!i wo@rt! tr'~tea withl .tg (5.00 nM),fcw1lhe (% 'ul!ltl'll:!'ah:id~ IlliIdikamdl tim,e:oo" lililild ATF6fw'a:l; d~~:md I~y i!ili!mlAfI,(lIj~@iijrigi. GAFOIH 1.~1s sef\l\~ g~ iii; pr.ifl Lo:adi!i!g (~~'ir~~. 1H1~293 !l:1ds, I(B.~' Wiere trmwld with ~" .and ph~phQ·P,CRIK~ PhCliSJhQ·~IIF2lJ., and A:TF~4 le'lllm wm dewnillilile,d ~y lllilmIllJiml:1l0,11I:ing.iI',Q,l3l e11F2~ Ire'!i'e~51medM .ill pr,o~i1 Ifllild~IlI!l!~oot!liaL 11i1,liI\ie,oortliom p.meb, cells were ~~d with dnilg~(!r th~ wdll:: 'tlm~a~d ,~~, 11lll!!~~laooledl, .QiJ1d:JadilJltS(i'~~ 'i!i1c~ii1IlJwg"ti(l!li m:s 11fn@~lIImedvia pill OSI!!lI1iOOIlli].gfililg. . .-Me1tcys. ;!!l,S·l.:Ibeledl m~lil1iO'~ine!tyst@rlil e. I(() I[;@tiswererrellltm withl iI:gllli1l:li ~tm, red b'ar.5; tg~,IDlI!i:em") foo ~he iind~ffitedl hDIIIJIfS,.lind 1i1O:f1fl1'!!:liiledDiP (kip panJel)i!li1d I Ch", (botooml p.:t!lletiJl m'IU!l!A le1iE!ls 'lj'Iiere 1iIiIl'a$!!Jredl by qUi!I!i!:tiiitatiwe P(R .a!ild!~hownl relatil,l'e to lMlsin Ii!ln_atec:l a!lls,. IEnolif bal'S represent. ,!lDshtIiTil '~indllpellfld'ent f')!.pt!rim!!ffi$..

celis.• ~P~!i!g

P23Hrt~odo,Psin, We assessed P23H ~~ooop:>~n's~lbm~ym~n~ c:hJOO :fit SIreS!; j4~ Itmrll'l!feclcd :HEK293 (!(!IllS,. ha~ e~nd lJ.'iP ~N'A ~v£L." w,~ deteo~ooin. ccn~
~j(p~ill:B h¥()! oo~m! lER~l;l!r:ge~cd !f!wldrl;il,

A
IHumlililllE'1 P,Ql{ I A i E I..C.AA- ''''1 ¥e-I<i1:!Re~ f IL¥ I ALE I..l:lrt L- 'I'.5Q

IB
. i'
I!!!!!!!!!!!!!! ~~I~~.......mI~I~

VCAM,·l .a:!'d \V'J dlodo~ (f'ilL!l. SA~ b!!.!t!t()l . ~1 ,00Us,ex~ingcytmolic.QrCtJi! .~l!J~oont·pi'&' teil] (OW), ~,ndiootlt,g that hlCr,e.as;il'lg ~~e P:R)" tciin [olding .100£1 of Ihe .ER induced dIG UPR. DiP IruRN'Aexp:ressioll w-as. mgJaiOOant~y htglt~r IIiI.oolilll C1(iPlh~~ng P2JH rI.tOO:o~n ,as l:iOJillpared \Villi O~n$ ~r.~l'ig '\Vfl'hooapsirn (F~g, :51\.),. 11.t'" rh(lldOjpsilll m:R.NA l!e;ve:ls '\%'W'i i<!t\ntk:alhl cenSe.xI~ing W1ll',:lI~dim~n<liru fon'llS ofd~c' protein:, Thl~!,P2j;H !il:1000psmIs ~01: n~pmc:lll
'lJPR.ilndlue« l~hm~M:" IiillOOOPSVIll, ~resJlI[lUlb:~y

D
1II1l'K111N trn

beeauso ofil:.s CoMing d~fuct Wif, nexl~.ex8!nllilOO BlP8!I1Id: ('1wp mRNA II}Vl.lis, ira, retina.'l f[l(ull tmillSg~l~lc ~. rI'!I~S Oif adlR!P d~;'11~;rip~ nJ:W'i¢ P13H j]!lodop.~i:!l ill

::l::
.l;!:-

- - - _" -- ~-I
'lSI

lQ''W (.1i',2lH-JRI~Q Tg)Qrltts!~ (.r',2J:I1J-'IRlII!Q Tg)

le\'e~s (2J. 24. ,In 'V\J1" SprnSlI.!c".Daw,/leymt:> alia,

iJ~ose eCl'll?l'csstngd:le P2lH' lilooQPsi~ irnl~~g~IK: st ~~cr, k:w~,.lJfPmRNAirIrCflliIISeJd,8JIiI:crdl~

+~ N\M!·PoFI111~

tm~l

'+1HM·P1P1

birlh, of

ph(lfO~~Of

IDcOO)ns~tflliillk1l

day ,6

(mD 6)1arnd immrea.~ !l,y!' Ito .P'ND ~0 mil (F~M.':58).. Tl~~fiI(lr~ BlP IifiRNAI~w~~l_; 5~1~ tivdy &o~ il1ixJlhlRi!i&gcnlc ~tnesel'!p~ ili.S; .P2lH fI~.od.olPsi'i1 {lFlg. :5.8:, topp<i!il.e~l .By oonlmst;, (,1wp Il:tRNA levels QO:l'ioom~la1l1IJlyiill~

,~,---I.I...

IF~g. 3. Ch~mi(iHl·g;eneti((i!lliltfdl IDf hlUlfI!ilIlliIl IIRiEl.. (A) .All~glnlflilenl:l; 'of a ~omDIiII o~ ~IiI'E! A1iP.I~,indililg dmi1ili:l~liU of yeiCIrti!llld IiIUllIIiI'i:ll1iI IREl iClre ~hmfll['ll,. nil! IUHidIJe mllltitediro gly,dlileils,~horw,lIIili1. mLm '~2'8). The ~TMn[!ltll!.!r~ ~~~,A,TiFl~!'Igkl!g, lJNlM"fiPl,i:s ~~~Wliil b~~C)w~ (JIf ~IU IP;QIrei~I!lI~ i!' ~nd tfansg~k W H cK2:'~3 m~l~~50 expre~llfl'g ::l!'f1!jM·iP!~l:-sell1:)jti~!ld 11R:~E1!I'I!£m:l[re,ateaimlrthll im d'it;a1ed time. wrthlN.M." ~'P.l1!.('5 pM),allldIXbp··l: mRNA !lpUdI!l9Iwa~ d:etelmlllilin;e~ by M·PCR. (,e) Tr<llll~glellInic HIE1<:293;C!eUs w>~rii!'IJ~ea~ d tm (:5 1J3~~Q :t l~M·lPPl (~ "rl_~t X.!NVl. mmA sPlkiw.gl1!'.!!'!$ .a,~~ss~dbv'IIT~P(IR lillliildi,q:IIi~lntmed. ReSiuluili~~ repr!.s!l!'i!ita.tiv.e of 'fiv.i! ilfldlepen d~liilt e~i~er~IiIiIE!l1Its.D)li'taliiisgeifik HEIK293 ( iLe!lls: wert!! 'trE!!ated wi1h tg 00 Ii1 ~I ;~ 1!N.M-PiP'l (5, JiliI\M •. Xbp-1. mIRNA. 5pti:ci~l!Igli'll.!ls: a,ru.s!>edb~ R:f[l'IQll ~!Ii,d qg~.~I:i1I~edl.R!~sl!l'~~ g!'l~ r~pf~~!ilta.ti\li~ ~ff iJile hnde~!lid~M ~Pt'liiiii!i1il!'l!li:ts.

creased tDI aniri'Ul!ls ,ex~i~lg '23tH: ~lIOOOpsI". bllltrei~'W~noo!O'i\!il~ 'Vf an.i!lit1als (Fi.g ..5B!~,. tllm.pai.1~). Theui~(':oo~ .of .!liP IiIDfNA d~ cliule aud ClIOI' IliRWArire qgl~l[yW!l!i!:lt:ll'!~ lijlle mle (If reli!1ntdegle!:1G'ali:o!iIJ ill P23H dlOO<npsilll l!IID~nie 3n!il<);1is: (flg, :5, C .. td D~ ful'iih.erIna:e, tile 'I:ll~m~ lin BiPmc!. CIJrJp rnRNA ~eve1s i.mrn~mlS ~mf,\'5ingnlisroJ.chd rh01lo~~~, :Ifnirromd 111.1('; ~l1Jlnsgoorn ill. e~n eul~iI!lfC.ailffi~ ~m]OI~gcd. ER E;~ (OOlt'll,pam F~~, .5Ba:ndl .2C'} TlI~I;1iii, slees tive ,<l:Mool!!O'uiiola Qfcyoopml~ti'i,l'eUP!R .oull1l!!t CQ(~p]~tW Wl~8l!..<mli!'!fld! CHOP p:uooJuo~ion,...-seerl

947

RESEARCH ARTICLES
IF'ig.4. II 1~9:i'I~tf~gl,eliIha!iioo~~~U ~ VilabiU'Ilf. Ptilr>sm:aIWT ;an\! tlllllilsge;nic .HE:1Q9S a2l.lswere tmeailedwi:tiIiJ the il!ldkated ,!1!ig)eMs. :aJfld adhl'lr,~fIt_.. (re~1jI ¥ic~~t=StCI,il(fJed posilitll,w, ~e~ls were' (:.Oil n1ee Iltlffil!e llldlC11.tea: nm:es· glfid a~ shovm l~kliJi\11iltQ (l;l'~!ilts· of lifnc>dif;,"trearted Cr~~~ ur« !liars, rl~" Ire~s:ellirt from th~eeil1l,dependem: S~ ~~!peu~Vliier:!lts. The armli!f5, indi[dl[e' P\I\a'lUe <:: 1101 WIl@n·tiIi!~oo!respond· iJIIgl samjiies .~ mm.:Pfi'l w,er;e. !com· l!!'lamed (St;l!IdJerII:'s, t'rest).

..&r dnig..j.1t1uJ;;~ protei!~ mi.srolleii''ig iJI1vib!O or, m fhe 'COl._~ of P23H rhodQ~!i;, CQ~tlifuthi'e !ll'iL5foldl:erl .proDein, ~rod~lctim~.in V!'iI'o-contribuled, 1:0, cell death., Discuss1!!liin. UeUI)R, eUdms ~araOO.xGI OMI,..
pll~.~mJdl:ldn~ C;y.!£!P:roOOCi~i\'l! :[W'lNion~ ~&!!ll~,

J. .~
-'"

~Mis'h, IIQI'lilOO~~a.<:~<,: 0011 d~~m~tivl.'l run~~ol'Fi: and d~~u :pronlO~~poptoo~, \~ fQ~oo Mha1 'nile $'Iontdfil ~ betwe~ c~cpml~h1ei and~vtO!l:k: '01Ilpl!ll il.i:esin. pm, in d~edJumt'io:nof ~lid:i'l'id'u~1 UfR. hmt'icllarovi!tW. AIt;er. rapid i,lli~QI. nc~ivati.OI~of !:III UPR branches by m. Slm~, .IRm. si~11l~iintl was !.mIOO:ive!y~"1mIMli1a1BdJin Inllnm.oBlIJl, ~l,J~frt 'Iih.crugh ~t~ ~~lI£IOO. ATFi6, ~igrnillillgalS('l dooHn~ \\Iid.l g,1ower i(ine~ic.'it,),(;.l PBltK s~~~~r"

... ""
7 ,,.

~OOcllJ!lueh I~,g<lr it:! d1.>e~rescMe(¥r:I!!f!ill~~vgaJ_edI .. *

'"

+,""
...
~

UTI

1,if'

~'!lI

..

\1111\1 l·P1P11 M

A
!r.I"'Ji

Sling UJ!-OIl\ll'Jo~

ai
iliJl

~lH..j R1:1Ii~ Ta P,2:3H·1 IRlllo Tg

:I ; 1;
I!!i is!
:I

;;;:

i
_l;l

Ill:

~ al
of
''r
~,

I! e: :~ i: !!I'
~I

",

..

.~
'EI

J!l: '101

if

'"
.1:1

,g,

'ER s~\'fe oIEerwd. CJlillmJb~OO, ClCU S'UMvlll SIller cx:pcrifllcn:taliypmlonging [RiEll !>iiw1a!~ illl!. IfiI~.croby dCIillO:ll5lr<Ulng Si causal. ~illlk LwtW{lOO lR.El 3dil"viLYilld c~~ S-uNval TIiI!i~ IREl ~ IllllUllg atH~~t(lll~ 1iJ,y l~i~I~li1l ER ~. ~mcrw;s as ~ ~~ $!~ iQ]n~ak'ili~'ih£) hlbo:f d~1ja d~,:;is;(II1 !liFlerUPR~'i:hJ!clio!l. 'Our resL!liL'>~l a n1Ode~ by whtch d!~in.cI: comi~mmiO:lJls ·ofinrliv:Ldu!!d. l1fR!'i~gn[llliD1g pMh~ ways d:Clenrnia£ II. cdl;s f:ate8lfle;r Ell SIreSS. TIl'; mitial 00ll'i!blD1OO. acll\1\ali,oo o:rrRE']. P~K, ;)ld
A:TF6 [Irndll.ees CYlop~"Clfive aIHptlilS sueh as ~clltt~t~IMioll. ~I!II]I<1!~~ R p~ E fulling

:E

iP1:2:

IS' i!:

51. Bi.P ,a;IfI~1 mop @:I;1~SisiCflirl ~ni'IllIa'~5~PJl!cSS"i'tg ru:~IH rhod'opEin.. (It) HI::Kl~3, ulls :ll'lere tr,I!I!IIrdi:rned .ill5ind~· .~~ and !llIHI~iti!OO~{Jjp mRNA le~~s 1Itf1'e: me.Nf~ed ~y qllill~e: P,CRand
Fig!. a~e:$hOM"l ~L;rive

f1liDffIfime iliide,peuuJl\:mt '~:qHlrimtnt$" ,(9) Norlilill';jljiiied 8iP iln(J aJ'P ~rr'lilm WI' $ptralgl!II'HlaWl)~ or traf15gelilf:c I'<lll$ exp'~liIgI P23H rhodiops!llil.at high I~P23H·,:m .!Rho1"9) or low '(P231f3 ..Rho 'F~) ~~11:s] by Qluantfta~· PClR (i!lldalf@ ID(JlM'!~I~~ Wi 1~lsat ft'IJ[I· 0: (iP6)~ aJtinll€!' 1I!hm >195,0/0 of me Imimlme c.ornlltemnt of retimillphurnrie(@p.m h:as been g!!llile.JIilit:ed,Error bars H!iiiRSiimt S[l~ 'ffimm tluee "milll'la~l!s,at: etl~~a:ge. "':,Ii':: ,1100-3;-, Po:: 0.001 [as. rnm,~amed wiltrl ,aiJe~IlIiIMdu:!dIWfalllima!1ls 1~\tl!Ide~~s t~tH, UJ lig~ l~orog!igJPh~ (If H~pr~~!ii.m.uhi'l'l ~iIrt!'!~ ~cthmsfr~r:rr! ~~·[lr.r~ri~r lXlSU'loor loolllililtlS of IP2~:Hi·l, and ,pz:iH·j rat511"i:~e]ndti:limdl ilg~S. iiU! OOiI!er n:utmam ~!yeir ~tlfIi,ILI,wh~,h fi l~m~:n1!iona~ to p[no,tmeooptor nudifli 1lIIlllllilbeifS; tliiillllli iI5 pfilotore,c-.eporrs degenera~, ,lllnd ~ood~5;n· OOJl!~lhhl!g I(!I!I~ .~£I!ifi~ ,~~~ds) .shQ~~,S~kl :bllJ. ,25 11J!!II!i!, (I) Tir!1'l' ~!1!i!l IO~IL ·thtkl!~ W!l:S meiilsur,edin r'~IiI!!iI, (00155 semoills from 1lr.a:IiI~gelilic and'WT I[a-ts· it th~ iiiicl)!tate(li ag~. IElm bins r'e:~resen;t SOS Oif OWL 'thidJl:le!:I!l. fiIi'MII three till six ,aJiJink ,art ilM,~h age. 1ITh.E! om;et or ONl1lli1nn~J!!lI 'in M1Il1 rnans;gell'le5 Wa5M PU ip <: (UI5), Wiith. PI'!:)g!~ssi\!e th~m!!1~!ilg ft laoor age'S f/" .",. O!®OOl) (S'tl!d!l!Iilrt'S; t~)+ a

lI~lls. V~lYes rnpft.Sim'l the

!f1;~!iI:s.::t Si[I;s. mRiNA ilmh were lD1u!iiI:!Ur,edIi r,etlffiJil~

to le·\liel,s:

iiI1I

IlIli1tream:l

ca-$)ooi!l1y., c~em!l'Ccof~ulsrQId:ecill .EIlI]]~~I!I_S, and. Illo:ITlg \~~tb 1)l"OIlpoPta~cO~lll)S stroh as CHOP p:rod'uClio:n. CymOjJl'OlOOh.¥e OUIjpIilS wOlJld01llt~ \V,eugh P~MPtolie footors at 'd~ispoilll, 'whkim. \vooldl 00 l~el,rod try tim re~at~vl3;l:ll ali1gerIllRNA ~ arnd prollSLn.hR~f~Ii\l'eS of ~tor:s s.ur:ill ,a~ Bip !(2Jil l1\is I~m.~ of pred<l!urnillftanJtiyb011dcla! UfR OI!!IpUt" wo1ddl tll!Mi p;nw:id:c ,ill "w!!ldow of o;p~!'" uimu~y"fot: cells to ~jlaSl their]Mt lmo 00j~ wirth s~. If'Gacoo Slq""lSfaillollCCStal)~ish, bQjlI:OOS~is. rlml sigmaJil'ug andd:ten ATf'oi>igJillllrung am <lII:I0ii1I:Uiated, ,~iillg 3I~ i'unba:1.anooill \vh~. l.u:~'hdoo. proapopl:ani.c ou~p.ul. g-lI.Ikl~ II~I!~ ~n i.l)wlI00i. its d~I:lii$e.. Th.e'>'1lna!liOJ:I iu IREI S:igil~~illgk~;nclt:oo @Cil'QJ;S ·dl!l'erc!~~ ~~lIlJrIJ~l ~~Ilt)'ipe5 eng:. Sl) n);;1!Y rene>ct dlff-erel1tial. stl!SQ~ptibn'iI1l.y h) :E:R. :slt!~~l!tldu.coo, oe:~1 d.e.'lith,ffl1li)~g diffel"eil~: ~'ls and orgaru,roinJorcillg growing m~.dmtce lllll. I~mIlm~1azoan UPR .ts ltai~ood, t{)\'ilan;ddli':: p1!~logt() ftIJnclimlS of pru1ikIl1arrug,a,llfl :an:;! c~n ty~ (26). n~,~~rirr.lb1IiaJl ,goriidJilio:~ ~~.in 0!1;iW ~~1I cliIUure studiesinilll!oe if!q)~lepoole~n :n.llsfQldil,ga!~clI ~ll1lble P1!.t1gO:~ogkil1l.rroo~ :~I1.
w'h;i,hinherirtcd :1l11]~0Il!S prodlilce IInis:foMed. prol'll:iiii..!i, I~.w'as uaexpeeicd IIl:a1:fin. fi1lh\2LldGgc:l~m:l'I:Dioo.~IXId£I!!il rliOO:opsiin ~1'Ol\x:Ui!L::S bearing '[lie ~tnive miMJattc!tl artil~ di~d~. clilUI.~ WI UfRacllvijly tml1U ~e!llllli{,'d llli!~ QooervOO !;-\!j(h 1!iI!mlil~gated s!mress .~ner·dru,~ lireal!~lt.

m,

Whereas Wf relinat QeU~!indlllced .lBiP ool]!Oo:n~ j~ruu w:irlh.d~:e devel0J;l1l1ellJtallteeci, llJ feld m:lIe amOlm"ll> ofrhooolPsin,.ro~illal Cil:US 1,f,'(,'n:.."'lSiing InIMliIut. IrllitOOap",~1'D is(1:~uvd:;t slm:D d:ovm .B:iP' prod:OO~on llndil1Jef@.lL~t:~d GHOP procl:I!I(l~ion, sU!fW;~~~.lclQ_·re.~ul<J~(n~ ·of [R!E ~ oolllple! whh~l!!int~,lJ!oeot P~K !lig!mlIn~.rnaydlrivc
j

9 NOVEMBER .2007

VOL 318

SCIIENCE. WII\lW.sdenaemag,,()!'9

o~~ cell

dealll~ s~~ \cvl!~h ~le 1123111 m~'1~~ ~.mo.~ ~o:tiOi:l. Shnilany, i!'!!8li!:fficie!lt!lrhl'ibriiat!~d1 UPR OtlltPfL1 oolli~d. lso Im~.er 001.1 e I~ iill other d)~es
~halruriseEiiorn.
'lL.

p~<;l:l.:nl ER snress..

U. IF. lliraM' m' tW., .fl'JM~r 21lfll, Ml1 ~2:000). B. II. :Sheri, 8:. PfYl'I!l:'!, M'et\llod:i 3~, :l:82' ~2{1Qi!il U. IF. ~. f'<Ipil,C. 21l1ll K :S!lwr<iat. ~. 'll'fillt>e~.Sdeil1Cel~:!:, BgI, 1~·3j(20m, R J. l~ai:J~lfIIt.!In, D!V.14., zn.s. (~OlH)l GBIio!'~ lL6" }(_ L, mng £t at_ • .EMf!O t. 1.1. s:;!oa (lL99~}, 17•. HI. tR,'L~~i1I. 8.. ~,'1Imn'i III}, ~_~Jr.'a 1:U:",~n
(~OO).

27 •. 5:.. Ht.. B:lO:I!., U .. Sdlrmdi~r:, K LIM, K .. ZIIiImg, R;.~. K~ll'Irllan. o\W~.tho~ .~'!IS

~~a•. Siir!9ie-te1tef .al~altm

as,

~2aoot

rbr ~le iim'!OO

i1(jd re;ii~I!!i~

l~.

W,rtr<r~~.~1i,

~~1

lID, g~!O'!~h"II1"

Iii- W1~lihi~~,

Rri@r'~frl:!t@5inl(j NOtt@5 I),. ~QIl, ~. W1!ll;er. NnJ.l!til.. .Mo~ (1iI1 Blat. .8, "i19

~2:0'Oi).
2', .tIl, (.aUo~e! oJ Mr/~f~ 41~, 9Il ~jlOOa). .. ]" It YOSll'idii, T. Uirt5!.:!ii, )\ 'til !r!iI,ml(l.1O.. T. (lkajj'.a,

Ceil lOll',

oon

1(•. Mr.:IlIi,

~" 11,. HI. t~~. N"

2:'1. 1.,.,a (2003t U.9~J.

U!OO'iJ.), rtJ, tw<l~lidl~t,

I~ ailll(itH;!!r,~t

rei!

~t

1.6. M. ~~hr~r, IItL ~1Jf1t);l11, M~U. 1l9:..,ftlochem.li'4,1H (OOM). 19. ~, M, ~!I!l(~i e:14I" Hum. MW\~~ 1t7, 42: {2(!Ol!l :lO_ C.f·tSiIJl~~ t g, Oa~>ei!1P:lI~IN!atllali~ /. )9'iQ! (/r.~.
2IiiB.:!!;Q6<l:~ (1;991), 21. :5. t(aIliiMI. H. ,(1;" KIIllIT.!rIclI~ ,Bfoc.ho.1t1iliilr1! ],3, ,&1L21 U9(l1i). U. HI. f. MBides, JI. 'o'iI!I Ifllfi ~JI!IIY, }. Clllil~l!::. i!.I.i.. l 'tillEelll!i'IIl,m4s M~ M'ffi:. ill, 1 i1 1200s~. 2~. RH. 5!L~~berg II fnve:;!I. OpklhfJ.lmM. I~~ Sri. ~:7, AS~",\;gn,~or ~~~~Ir~rnilllVi5i(1B .~!'!d OIlf1;!!i!,,'t~Lggy

.iIlte:~~ rQ!~ )\ ~ C, cys; !l), 11ipr.1'. G~ilI; f, rlile;; ~ Gl.y; !ii, ~.~ ,I,.I~ ~" !..yS.;.!., ~~~~\, .~~I;. Nj .~ p, Pr~ 'Qj 'Gi!i; ' R. Atgf S, S;~r; f. TIt~ 11.'va~W, np~~M Y, f~~ 2~'. WI!! tlilain~ Ihl! Wall.1!r la'lP, Eh f<lfl!!ll!; ~. L .(;arii~(i1l; .rt J, ~B!iJ!i"AaIl.,. IR. lillil1:!!lIev, U .. Mattlllt]s, Il,.• td!ii'~m.. J. ~iI1llil,~rt!.~. p~, F. ~5~mh~L~au!!8.. c1'~B fi)r l'1}.rrlmoef!l~,prnm101~ 00' rea~~ or ~.~dlllli'ill m-il:~ ~ .. Tlns'I'!'GJ,k '(\\ij5 ~ul!POned C:I''Ibe' J\!li)'GlFOI)!1iC l.l1~e!:Oll :S!;~er·~5i~ J\~!Ki;r!i~1!i1 U.S.IDepM!!I1en! al'IOe>fe!'!lie,

liiiur:Kia.ti!!In' Figlflt;iln.g ~liildM~

.l'ohn ~1H!!l1.3~ ,,~~!t!

S,. iii.•.tf'. H\!Irdlifl\i. Y. ZIDilmq. D. R~1'l. 1fI';ar,Ilil~ j:~7, Ul. D, iii .. P.. Hamliing d .a'l., Mol.. ('.ell ,!l. 1099' (200@). 1'" t:. 1iI~, iii. ¥OIhidii\ iii. '~Ilil!ll~ 'To. 'itlIIr~, K~ h'lDrI, ll.l'eJ. Bfa!!. Cefll:~. 3ll'8~'~'l9991. 1):.. i, 't:e' .:li 4f~ jiM. (~,6, 1~55 ,~,()OO). 9" .~"A.ll'Iiirn~. A l\.1[)mrf'le'r, C. A. ~dW~lrd!.. t, .r,t !lIi!_rdilOt,

r.

M!11Ii!~lDl!f'S ~lu'ld;ilt!.~I'1, Na,tli!lnill !?!fI'! U1:!~llltl!.M[H., al'ljj .R1lse~wl 1.0flil'i{!lIl. mim!!"-S. P..W" aoo tl::iIl;S, jr~ :~'lIrti HU9Ii@S ~'!!k<i·I. 11I~1tuti! In~11~1g@Ot1.

m.,

S!.!Ii!'~,rti!!g) Orn'heMaiteriO!I.
.w~;~iM,!~Il\3Q!,~fQp'(mt£olil!leI1!!!\1Vl{~]'l'll5il!.'5.~I'9"<1/I:1(l rl'~teil,al~~~iii!A!!100i!i~, ~Ig:!_ .5.1 ll(l .5..~
Iiiif!'l!~~@tiIC1]s

It ~.tl.a:ull~ Ii, J bM rlW1l_27i!,011 (19'971 ~ID. H.. llil!!':!~r~.~· " ~g .mi' lie .... iit;~.982. ('1l998"~ n. l LG~fli!~l. E;·I. ~iinit~{.R. 5<. Hf'!I~. J. F2Illlntom, i'rl't'1tJJ1t <13:6. Ole;) (t!00i!l)1

;!l4_

(Ml\JOlll!J,$lt~tt319o, S69!1!(199'6), '5, Macl~il!liil elllr~ln~~_ ,QpnIJli']iI:m.W .. tlil:llf!1I .~.r:,~,1I.

:3:2(1) (20M),

2~ •. p_ t. ~1k0;1.~1!:11a Il~~ /'1.11251BI.o!.. !li. 3111 (2!lD6). 26 •. 0. A(l}·$I.h,l\l~r (jj {iiI .. M",r. (J]1I ;:;1'7,sa (Ol,QCJ1).

l:l! Ju f)Jl .~lOCIll; am1pl!l!il

lJD..1126-fS(iefl(!!.1146.3~

'l Sl!!pti!moor 200]

-,

I.

II

Tlhe SlimpllllB'st DOlulble S IIIi!: i :Int:e'rferelnce and Entalngllemenll inl Double P'h'Ott.oi.onizatilon 1011 IH,2
ID.Pi~ouryj:l!,2 K~ KJreJdl~,j:1!.r, ]~lhflk:e,.1 Wlnl, WI'.l~OOir.U! A SU!l!ldtl!l!,lM. S:(iil;{ni1ew.·~ l IN. Ne'UlliIIlarllll,1]. Iibe./ IL 'il1l. 11'1. (hmrid~,:lI A. Czasch,.:l!O .• ~ag;utl:ki~ 1. IH. A.. CO:!lif.a1 IFraQtl,~ S III.. IE•. Grii!iemti" 1 R. DSez: IMlilil~'o,,3;N •..1\•. Clileli'e~m",.4'.S. 1(, Sem.enDIItI',.4 P. laniklwffic"s IC. L. Go,cke,.S: T•. O.5il~OIl!~ IHI.A~illtI!,iya~Ol 11. C,. Thollll~IiOIil.,.6, .Mi. HI. 'iri,@,r. 2· A,BeWkac:eilllill"O! Il A. IL Lalilnl~er!'i.•6 IHl. S clilmidlt:·.Badcitlll,gl ~. R.. Damer1•

emLifiO:ilI. ·of IliIn.® IPltot(UlS .aN~ Ih~ mlallVC: p:hffSe d~Ii~~p.;:ilh'WilYS of dIe p(3[t!k:1i;:IIl')tv:ru:d Ul~ d.~C~IOD', aJlle:ll~t ~r~ 1:0 (til '~~:i~11Ce,
bt:.'fW~

S'!I!cill d~h.cre~oeof ill. qllllntimlli 5)f5~n earn, 00 camoo. by s1ngle o.r :nuildlllc; interootions wirtil ..rntI e1'!tcmal sys~.~.ml (6).ll1tJuitLifl'Ig cases are OIre sll'l@.le ltardirucraction CfIlM.illg 'du~: i:&."OlrU.1t'CiIDehy 'e:til" < U1l1igl®meill wid) ~~('l CCitliL'lrool ~lCrlil an.dmllitll.pie weak CQ~In.rtg;$ to ,*'I~t pertl1il'beirr5< {for 'i!1l~tl[lJI'lC¢, a.bath) at ~IlimifJIdK~ eldlfe!ll!l~, A grndl1a!

~'a,nsitiou ~!.we~J,l. these two c.x;1'!leiI~.lCS has boeerl. dc:t;u\lIliS!mledmr ~lmlr!l1,1 scaltering i(,~ '~\!Cc-1Ijpleu'h'nlClilimlly dlZll'l(llllSmJ.too ltiam: a ~'S"" kaln. (If two ,~I(:,'(:tOOJ1lsh; a,lr.cady suff:k;i{ml toot. sew~ Il1Im inmsitl0;ilfoonl a. qllW1111D'I'iI1 iillcr.[crol1loo ·The wave maru~e o~ !~aFrtijtle!> i~Irralrely oi1l5'er'J.M!:d, in part OOi(CIUiSe' their 'v,er, ~l:Iort d~e Broglie' lof' w<tI'l(,eleIllIQlt'hs inl mOflts;itulations. H!owfVlfr.,evelll with w<trvel.elllg~n5 dO!>f!m the sn~ of the;ir patronli tQ. a C:~assica1pai11c~~~likei.nmn djR.. ~tty ~ilIlr,mundin;!1I$, tlllie palmcl~es!l:oUIP!le to tllI.eiV ifnVar-oliillfl;el1lt (for leJo;;al1llp~~, y girra>i'i1tJy,. (,ol!l~~omb, b ~buJl:ion ro:raill.iudi:viduaD ¢*ItOI.'II, ~n~~ q~an.im~!liacth,j!1. 'llI'fth~fmg,l fadlatig!!l)', Tih,esll:,oolJ!!p~i!1lgssl1ift th~ ~~'I,i~ I~ih~!~. o.f! mli! ,all! l,moo~ng[~!OO IMm OO'I,e~~·~ is nnt d~!'QyOO~. IID~'I.~Ycr,but walY. and me: reS1l!!lt!ln~de:~ohe:r~l'lc.e:. or less o,f phiS!,~e: ~tfIt!grity. isthot!ghtw ·btl ill rn~Ifl"'!.!!s~ of t,hl.! 1:e!l1<ljns in lh~ euil1il'l!ledb'llf~leciwn sys~n. ~ra;IitSrtlfiOnl Wnl',1ifIIqIL!1iIn~!JImw (l~a$~iG1iI[ beha!viow. How !rtli!,dIilir:t!terawom is liteediedwilild:I!!,le tM~ :By m:easllln.I:I!g '~~e comlaied nl!Uncnta ·of 00111 partic!lcs, wc:iUl1Blmm ~lI1IisiiD;ltm[~retlCe paJtnem, ~ril.rnsilJiionl~' HemlA!ll' .~how that ill I~hot()emectrotn .a;IiH:l·b\io protomdorm til mil'lltl1llU!iIiI p8im(le/£~it sjc51tem wldchis Qidlef'iWi$eooncea.t~d ~Il l1lle lWo-body <tlnlc:l fhal: <llsi n!l:~lf1ad diilionalL emectr,o[l mill mtIliltie"l .a minillimlllllil etmmn IiIlI elilt. I nt\erfetnernce ~r:url g~'s IObserr'!Jeriinl tlIiI,eang:l1Ilarr distr'ibmion ofa silngle ele~1!!noli1lilIlm-eL(l~,t·~.mlll:glll its (oulonnb Illlter,adio:ri1 wa~ fii_uneuOll" With. a ~clOndeted:ran~ tlli.CTl!Igih time rorj~el:ated mlom~'li!iI:a ,oftih,~ ~liIr~'lIIgled elecl:ro!1l p.a,ir (!oniili1ll!1:e ·to n~id~of lli".,mlI~.:3J h(l!!'IOC!I[iJtI¢l~f rn",t~~.t¢ ~~!hi i(JlI!'Q,!ltti"jjill ~Mertf€!rl~o.!, b'¥t. as tlt-e S~il·.scattl3"il'lig ce~ter ·of <lphot<!!er~troll g.oes 'OOc1i::. t'il .<1. pilper 11!1d:iH8'hed~n.1966 by Cohen. fl;.w~ ·fur a. single pruticlelfud'ly~~aled mm ImdFwlo, (8). Beca.lIIse of rUhe oo.'liierenaei~.d1e ne of the InolS! poWoeit:rul [!D<lrndiig;ulSin. dn~ '~l1lv:j£'6mnootl( h.o~~f,. lIDIis id.eai~·Ia.oorn• iil'liua! If~.o~oolLl~ar .s1ili1~e.'dlea1bsm:p'~io:m of ou~ , ~1.l£uPtolmt'im~ qUlan~iiil.liWC:~lill:niCS ?f
is. tim, dOhllblli2·sltl. cxpcnn~C<ln. TI~O\~uSls y mil.il~:was Ilhe ~ir...~.I~O~rFl)i:'ii1ilJ ~ooh :iIi} exper'" i]IJ~ml:,.3S .~y as ~SiClIt. \v:i!~. ~d;ght.I!!. I~OOkurnli~ 1!lIile late 195~ U),Ie»,g ;l'Itc" the ex:perin'!e!l~"~ ~llOOf of Ihe 'wave IIm:!1U!re ofpart:ic!es was I~
'il'iC:il~edI~ [Or !l sa n~Htlm'·GXpe:rimenre

10 ~ camee!.

01iU

b~i:1J d@ffillOli1SI:rart:t.'d forpan:id~q :sshcaJVY as' eM (2) :iIi:tcl. fOrOOIil[ld!\lI'ooOO~ in~ld!l:l!I. hi~~!y !:IN.~ c~oodatom (1). An ,of la~ese '~!'CriJI1!~1S: w~ aiwTI!ooii!l.ll. de!llO!!.S!.nIiQ!1·of doublwlil,i!e]fin!!.ler~

wld~

el!eelWiltS.

TiOI::by, !iiLliCh ~xpe:rnmeitillS:have

.Iruy S<1~!!ImioolSilG~axOO. and d~~q;lLimlt:t~n~i!I!r~ ~dtl!S are ~IT~tiii.OOinact with lfihe '~r.viroiii.i:ti('lifil ~i:l :~.C:(iii~U~dlilunifl0t. 1ffiI~ <!l,UlM!'ilU~J] iUltM~IIO!!l Ullt)' be din1:~rlislwd!8'Q [hal the particles st~ ~. Im"..j~1s:iJ'lm tncgsinsly cl!a..;;;sica1\?t.1Q)' (4--6).. RooeI1lU.y. HQckemliJ1~ e, et (fl. (7), lIil11've det:HQI)" sh~~ClllffilnsphooQmL1OOn by sendiing ~~eamdC!;Il Cl~UJ;k!l'l'Ilnln.ro1!lg!1:!1 dooblc slit The: hal ~1ilolec.l!llru!
~a'lS·of

S~~1 D>6~U8 F""riltWi:irt.Gli!rili1an~. \<!;Me;tiliI:e' ~rkelel! N:aliol!al Lallor.at-or)'; Beftelle-y, (A 9-.47210', USA, 3CJ~lrO de fr$ic;l d'~,.M~terlat:t~· ,amd IDo.!lIOSli;ll !'iI'e~~~r!r)oi1al f'h,~$iC!! ~i!l!~Il!r. 200:18 S,;r1"s:~ooll!ian,.Sp'ain. "'S,",~ UmiM"llfSl~y0:1

llm!ituti'iir Kernphl!!'i~, Uni",er~ilf p{am~hll1~ ,M~.:tljlon ~illlIe

ooupl~ v~a II.w:,(lim!!!J!~onf ~i~~lf]Jl[ill ph.oI.Ql1!!l W o

Uae~.!lVmrml~U1l. i'l!ld a .~~~rr~ro!l~e :;;)Sa

.Ai!'rmiP~Qe IlmliHI111l~nta'ti~n. ]90000 St. ,P!!U!rliIWFg, R~~~ia,. ~D~!fI'lrlr:1iIi1!n.t ,Df, ~lIii.Ii5i1::!\' K.all!lSas)~Mi!!IUnri~@r5il'l'. 'l~rd~rell H\1ll~flMnh.a.ttaPl, K':S 661506, U'$lI. 6iIh'lp.~rtlil1ent .of FiIir»sil:s.. .Auburn Uni~~r,iit:l', IWbuf!l'I, .M. l6>B4!j1, U5Il.

funcdo!1l ·ofjhclrl~mp/;lmll!!reiso'bs~.

TIn;)

~To,~hW'l corre~oo!ffl~;e )~wldl be iliidrEi:sed. t·~"'ilt .~Off!i!errJjl ..nlOnh~!'IH'ra"krurtde

949'

REPORTS
iPhO'fOO by Ute hO~)OiIll!.td,ear ri~~~.yle JaUilc~~~ I!\I,'\I QQhe!lel~t e!~troui ;''';';liVes <ll eaoo of !JI~efifo1~~'Ii!> of • 1il'Kl!~ea:lle (F:~g;,I. A, ru~ B). T.heim:" 1~!.'lIfurem,1(i: flGU£n~ ofdllesc WIIVes should be visib.lie ~n. IfiI~c9Qgllitar ,cli~lih'jjfiCi". of IfiI~ (.'l.cClIDiil, '~!ffil~, ~~~ I~OHIt': loolMi!I!ar axis"[n K s1mUiOOl!~caI~tcnof :h~vy dnaIO:ifI:li~ (~~, Nl:mdl O'J,a~ di~w~~d by Cohe.l!!lIlm .fano),~nt~rt)mn.ce !."l visible 001)' if ~he ~'W!W!l!~ (s:~e or y~e) (I:fd~ ItffilcoMlc''wid~ il, :~'~~Ies bole 'is rudllvoo: ~! (9. HI), fior gJUl!Iltd"s"lale H:!"'" and. Il~h m~1ecllllcs, (m~y gerOOll Oi'blta'ls Sil'e PJP1II1~alfldl thm 1ili'L-w
~JS~~ilt1li: 'ar!~ ,eloolfol~pair.

mirorpt~oj} o,f a sin~leciroula:riy PO~lIri:red pho, 100 fml'nll~:be H2 IM~OOtIk: (ESq. 1)

ioni~tiO!il lllJ :shlldyUle t\VI;I~od_y ~!1!~~.Ffuret[Jce of Thiseletb!rui pair ls: e'tlli1~e.d by

~a~utiJIlu.~ 6lrnl~ ~'WS

~ar'\li(lf 4"~~1~
~ (!Iun!,

ofdw 1000lflwlar axiS (12. ,11)" AI. Si:gliI.:JI11l.!l1lC the of ~tnlllr,fi:roooec:tfud I~as llateltldess hccl~oo~: in d~ 'iI,'avelle.WI'l dbpenil.lmce of eleclrons cmined. fmnrn.a IIml{birnly ,(J!fiLWIIl'd i\i3t'I!i~¢ ofH::!.ItI1O~~I~ ~y Iofil rrn1J.llCt ionfmtlOfiIJ (14. 1:5)" Wt) C:)(.lie.ldoo I:h(';l id~ of C'OJi~11 and F3illO foom s~~gllelihm:oioin~!km 1.0 d'oublle ~lIoto-

~;bVJ)ha.'lOOI bam cam~ ooc:am;e:il ~~i~ h~w~d~e of lillie iJroalO!~ d

.lwet1t0.!i1

on S:~in~i.hllo:ui3[~:ld~y flfO-

\'!.d.tem

SiH!Iil!;)(;

be-

llphO!CKU! ,of~Ye!1cy"', Tlhe el~OOIl1\lln ;are djs~in,guisl~~bk: by laa.ei'r 'e!I~c~.:,:,\"~ilkil~..Hows 1~.l:S stuJclJy the interff!l'reltoe 10 'pill.mrn 008. Iflllltcti,crn. of 11:1{; l1i~IJii8.Cli(l1il !ro"glh i ~ or mOml]f'lilI1!lJIl el!!~haJllgl1ldlb~\'l,I'@~~ 1~1IiIL'l' two
l'Il,IO

I,,,,, ~ooli.~e8

~rti,d~
Si!1~I~ IP;I!OItm.~ O~noo.1!ml.riJf!~S 4,0 {mil'l l J)M O

dtc: A,d,vanccd. lJigll( SoU!l'Cc .~. bwr:r~mre :Bc~ke= d-etermil!l!oo. O~~Ly1I!re,epartk:les ,Cl"~rQ pfOOO",,>; ley Na!lmml ,Uloora1ory were '111800, to ~ho~oojccl m~d onee~ec:IroIl) need 10 be detucl.ed .. 1Il11e1lID" IlWHIUI[l of laac second CIOC~roll, ,(in thepresmt oonh C:lool.l'OllB of eaeh H:1 l'Ilolcct:de, A Sf~peU'.;; ease ~c:.mo.recllergetic Qfd~c' :U~();J! iii dedueed S\]nLcH~. ,gas jetwas cl:ossedw:i~, lfilne IPhof:ou d.~,mugJlmOlnmlU.i11loo~atiQ~ Qf Ih~ oomJ ~a:lin"FCi!r rulch go:n~z~ I:lJaoloculGi, (he 'if{i:Clllr ll!iCi!il!i:ieltilaof all &agual$rntpaflkl~ool.h io]1S ~rom" n.c CoolQN'lih GJ(pl.~(Jn.of Id~Gl"li!i.1'i:) p. 0011."1 <It 1~:H1~~uilibri!1lm dli.~fi$~C(l ,f Ii.! ·of i~.4~ aJI'1dOOUl (!~.oo~!1.<:-';\.~ d~~rnl[noo .in,00106· denee, Tlhc ,rn:ie!]!:atL'Ol'I!of the H~.molec;yk~"or mOlluic UiI~i18(alii)yiekils nk~n~ic e!ll~' of<!!bm.!l hinrliu:g eu:~
10 eV ~r proton (/fJ), .mU(fi,dlC totiil elOCUiOn;ic of' H:!!. is albo1!l( 30 ,eV. The, C1o!pOO:Il1CDlt 11ti~OOPCr:t'ol'illl:lled. at two diITcr:c;nl

.~!it,.~~ ~5!.l~CI fM ,~di [~gu'!:~ootati031 by delectbuig the eii~k';siO!'l di~,~ l~on:oflfil~,e '1"'~lop-mIOl\S, Onc:e~ dlC two Ci'lecUXii1l:S' are eji:Xlted~ d~e p.'I'OlmfisropLdily my aprut ~Iong dile molcmJJ1ar ,a."'i~, m'!;'~n by'th.eir iflil.lll1ill1. C'oIJkm,b'rMpilsiOO1, A mullipru:tk:l~~n"lagin!l: !1.eChniq~ (eokl. latg~lfOOl]lt i{Uil'l:lom~nlum ~.~L~(X'}Pi!} (16, .11)1 ~oa><;!,L~d1 detecl ..<lin parlit;1~. 'Ili1.t¢ ~o !o:ns <n~de~eclro:~ 'C'~!1i~e.d 1m! Ul~ i!lre;~lkU1 VO~UI~'l!!~ oftl:c 11I1.o!Oll iil'lldl gas 'bemus: W~ ~ui)dcd, by 'Weak c~ootmic (SO Vk:~n)1 mac! magncLicflelds (8 'GJtovmrd 1WO SCparnl.C nll!lllticht.mne~ p]!atc &"'t~('irOfS \,vitil d~&fuylil'l.emadOOll1fl(18).. Flmnidl(!: pa~;Iii(ltn. oifiml;lacl. and 1iliIr; lil~ ·of ni!IDliIl:,. Ut¢ mi6alvce~0lC' ~rtlJom~:lIl!1.]11 each li'~diO: ·call . be ,of
!~O~~Cil!~.;JW d{nubt~

plm~on ell;ea:'gi~ {!!:f Ey= 240ucl l60 ,~V~ I.ea~ng llWut W90 <l[Jd rlQ ;~V~ff:rn.ergy kiI be sl~
anlol1lg

U~ II'Il.U ~I~rt.~

!~~li.\f~ly.

At d.~~

hlgb liI'Iot'Of] cmcl],tes: 1!Il!!;dteroo!l~klemti'Ofll:tere, ool1.blcphoookl,lillzl'IAioll 'Oil' H:;! lea.dsi I~ moot cases to· one r3S~. ,e'l'oolro!Jl 'HII.1c!l srollJlf c1ecDron (2'0),. OJil€: r:1~i!lre 1D ,:;1iJO'VlS1 fl}:l" rmru~za/lion. by 240~V JlllowtrtS., Il:!u~m~'mred :mqgllliardi51~rih'i!lti.O:llfor 3 higMy Cll{''f~}ilttc e;leotl'(m I(caned! "l"!!(lre) fir energy eEl: ~S5 <eV«s, -c ~90 ~V~l1~e ~ond cleclmn,. !UnQOOef'\led h~. <lCqlldre-s ,;}I~ e!1crgy Qr on~y &2. <5 ,eV,. D'e a:m~lar diS:lributkm, is :UrI, d~cpIHII~c pcqlC1wiculartodfl'cpliloton p:ropaga,~ lion, voonQ~, and ill(l; 1'I'a.oIOOtlIar,a:>:i:s,is Oll1rnlled. Irorii.Z<JllIDfilly ill ~illlaj~lanae. (rim dsta pI01JIt..x1incllld('l lWt'1lCg cM:l~~cl,L!CUj'(uljl ald. d.t"" IfliI)Il.Cicu~a; aN~ He willilil.~I,I() dl..-g~1:!)f 1il~L); 100311 ~h:n~~rpe!'!d!C\J.!il.!I"

~o the l:ih~(1J~ IpmiXIg<ldO!~ d!!I.."Qi;YO!lj

1,',he e;l!J.~riI11C'Lta1data show a s]lro!lig,in.kll'" patl£m illd l!lood Ir:y a !::!en.aMe SilitFor 111'10 opttcaJ d<m'hl~{I]ilL'lX~riml1:nrlil:lJ whit;h dmiutC1:JcIl!.:.mce: ffi$"nill.. foom 3. s-t1;P~n]FIosi:it:UQI~ ~f ~wo C(ahsID.JlIt
L

rer:encc~ IP<!lDien19mt qll~~,ifud'i,l\e~yr:cserit:lbh;sd~c,

[iip1ilL);ci~l. wa\i~.

Ih(lil~~~t!}' distrib~ti(u!. .I '""

given by Eq.2
IFilg. 1. (A)Sd1~mi:!~c
{1IiO,ttlihe

whkh ~OI'~ponds: to all electr,on ~n~rg!i ,off 1~91) flU: (8) Ph atoiOl1!lira,tioll! hy oCircut'uly -ll!'ldJI[ll'ii~dl ti:[Jht 1~l!!iV'!(h€si'! OOh@fi~:.sph~~l phOltu.ll,lildirolJl1I ~a.\1~ ,at ~Idh !1ud!i!u$ c~ th@ m'Ol.€(lule:m~ i!!g:1ilt propag~~ inro the 1~'liIe·.(() Gemlileiry ,ofthe pr1ese H~~In'irllleAt drlCiilll.iirtypa~1trriruil [ightool1ll:~frUlniilfilerop. AIL iIImguLar d'istrbutioo.5~tnOWflj [n thi!> papelr <l're:in the plan.e perpendi(1lI11a:rto the plim'ttm lpml~i!igi!ltion \Illl1:oor.~nDli!!ilh~ gl!1gle !:If th~ ;f~t ll!i~OOWOOI's t!'g~e.dt)fY'tl)i m~!'!i101~l;;~lgr ~is. gfld~'1H! 11;. '1lIiI1l: gr:!gl~ IbertWeillili b!Jthi eIOOlifTOl1ltrilje(i!iories.(I!ljl Meaoof1oo eooctmn <llngulilr d~~riblJltia:1iI (¢I~-IIi~JIlfnu~f.:I,ster Ie-l.ecllumi'rolllil' .d1J'I!Ib're l~o:t]JiiooizatiiClfl c~ "" by .clriCJulal~~\;poWa.ri:relll l~ight [he Illliientar]tDnl '(If the I~O~oc~t~ b~Q!1l!wJi)~t LigM pi!i(!!Pi1!.g~.~s·ifl~ t~Il!' l~l~!Jq~of ·th·~figt!f(1, th~ ""wl~:t!l~ b n~1ed ±:lI!C,!l wi1lhin the p,~ane showl'll. E" ~. 24:0 ,e:V, .(inti the eliierlgy ,o,f th Ii! :~I.{Mtel,edJoolIIlEiz ,~ 0 00 5 I~,.r,~uil.tirigin fi ""l.8~m I~'O e.V. (E) Ang.ulla.l" pmffil1llhiliIy di~tribll:Jtjoo!l dle-ri\l'el~ ,rimm ~q. ;;1 '11~11!I;~ l~ir1Je},RPA (all~~l(i!tl~a;I (~,~l,,!1!!1I(i m~ttii.IiII:~~("m~nlng, ·cak~~ailit)f! Illbli!(k]I,

~m O!r !1!i ,d(lt,!b:~"S'Iit ~anQl~elflt, A ~!af!1il W\W~ a pprnadh~,t!TI~ sUt ~ll1m'! t,h!:: siJII Silpiital:imil ~5,lL4aiIJ (tI1;~ inmm~.IIl:leflrdilstalfloil in 1Hz), and ~he wa.vernen~h~s, 3.7'5 al!i~

(2)
[n OUI!' 'case, R is lheimel'!l~liI£lelU' d.ig,lalllu;;e ( :1.4 ,Olil!!.fb.. H:;!).. 'IIJ<\-"~::il, is: the a!1glie {if electron e;mission witb reS[peCl 1(1 d1e in1!Z:rIlIUclcrn- rods ( 12),. Kc. ·iJ;.~~t:lI'l'aOlllCmltll]"l'l of lfilm tl:lectro~, and C IS .!i. pr,~~olla[iroyool~ltl. A:~.(lIOOIroIi\ elilin'~' of 1.90 sV {M lJli'l Fi!g~1) oo~'lpr;mdg to ~ .", 3.15 ':'l!!.Thc d01!lble-slit predij~ion ()fEq.2.~
by

5h~\~

Ore Mlllcliflc in Pig. 1E.

9'50

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
11.~gde:Viat;o~'i.s
~:!li

d~i@d(liuble~~it ~:iiI;,-dic~

ck~l!.1ar.J.:i ~!ari>!:~d1 In£"ht .a1Jl~ fll.rt.I\~ilml 'lh(;:y ~l!,!;,_~ ~"lC3p~ rli'l;Iiu~ ,h:~ 1'!i.~~irI~r Coul.(lmb po1!~f'!!!i<!1f1irUl!~ I.wo, ri!tn::l~i,1l1.e:Iw;lid~ oru~.eU~I~t ~~ad's riO .~ slight dl.oc'kwise mlIlhQ.1fl of ~ae !lIlF gulordlis~lrib.tfli!on, ~ ~en ~n the 1e.,>,;;p;crimel1laodl
I~~le n:iiOrtl
Ill1tem(:tn.olil
c!~'OOmtc'

1!"0I1l cen be r!!!m~stood f!'a~l th(ii :SO!f!lewl~t rillOre e~aoornte 19n.oore!icaIDl1eatln~n( s1lo\~'1I1in Fig. IE. By '~r.ea:lfiIli£,the eleeeons as s,heriCl'l~. wa\res, Illim sim;p~~ a~ro::tiimali~i1,inrEqj. 2: ueglecl'li: Ih{l! fact dlat. d:l~ (\lIOCloo:lt1l am. ~1~~Lld by

caloolmioru;;.

]1111CCoulomb

with d\fl rfllei(Ji has

11,'!.10 a:j{!J[ll~J~1S.. m

Fini~ 'nh.e w~.V-e~~i~~I.b.O:fdlQ' ~l~1fO:1il il~l tim". ici!~il;t of Il~ ~r(ltO!~~ is: silo.m'f d'ian ~1tiI~ M~p.I!(IIM ~e. nil;: pro~rt.y"looijAes; inparlieular. ~iIlIc le~nissiQn 'probabiH]¥ aiollg ~fl~cIlJolecl]1Imr 3.xli!;diJJe to a. 'pIWlC s'l[ili1:illl lnin: lilear~.c~:d1 (In
Soornld,.iI1l:c Qrigjllflfl. 1)_1iI1 wawelm~r:giillg from OHmof dlG: f.[~cl('li is ~~I~~C1 at 1D.~i.'l 1iJI!~tgltbot:iimg rnlID.d(';IJS,l!J~by ~aii.lI1d~irn;g :anot!l:u~1'1~:Mi'ti~] wave, TiI1~, dt~ ~I!aI >d:iffmactio.n ~a:UI~ u£ ~~(;;~nD~r'" •. l;1Io.sit~Ofl: o:flblJlf (or Iltare), coherent (lom!riblll'" IHOllS: ~e. tprhmurywavcsfroJnlhe ilCIii a!IiIG. nsiilt

I("M ",,'~. .._ ow: ,-·';·r"f·-Ill __ 'iN- Om>~:r\l~ K.I .. e:x.pe ~e_. ,e 'if.~' .0;"'1, ~'[Ji both l~1.ecCroniS il1. 'OOiB(idelfloo. 1111,eref"O.1le wc emil. d~.emiO\l:ewIMlJ'Gren,t~a~ .Eitne.riinl! Id~e rel!1!livc hCfgh1 of rdle 'peaks,. am: 'line· hlilicimy 0:1"' Ihe ionizing i[lve!>li.gate 'd,tiS en.tang.~.ed. lW~~a:I'ticl!e system. ~o pholnn.ii~:cti!lC"iiiigi!l i:'OlfMiQl1.ne dClni~sof tljle SC8i'Ch.fuli Ith.e Qri.g~iii.of Iilile a~aoonlloss ofOCl.. .30 n'iOI~lJilant ~ltiJ)ial diffel'~!~ II,t¢ eal~cUl.Mtrn.\'lt htm:lIilOL'l[rD s. ~.IfIg'le-;p3i1ic~il ;silltq~JiIi.rfgll!lm RPA 1.i~::l!Hiitk's~-Foek PO~IM'i;1:I.~",ibro;IDtil31~ RIH:'I!~V~ dt('l OOl'liclatliOl'l i:HIi liliii~~l"'lJl-~~ ~.(l;]tilI. d~nT!.!I.lijpl~ ~C3.lilcrn!'!.s,~lleY!llatiQna~!\UfillC:S r>lo'O 11:1:11; ~~rum me:.'l!Jlg!1il (lif dt~ eloc~!~ ~lOOlU~l.!j,vijh !'eo;pect ~o n~e!rioloobare p!lCillln-"l. ftill. ca~clllJatLorns treal t!~e cilliss.ion, ill uliar 8iX1s: (L e.. the angie dual" is ~,IQl~eClin all single I:~OOI;i'"oITh. riDe.rerore, llihcir good ~recl'UU:t111 T oi1l:eIl' :~\!l)l!Ires:~. D.e vcrl!icmJla:.'iis is: the11illgle bClwamdlCl: rlWO cl!eciro.1ll ~s n:ilOln.!.'l11Jlj1L nl~' ]1 wiDh 11m CX!lfOrillilj.u~rul data (f'Lg. ~I ohtainoo. be: he:lpfuJ. 00thirikQ.f:I:h~hotizl)nlal a1ti~ as the fmmcl\:llilbJr::: :h::¥i~lozallO:ll nruigln 00 Sl,lir:prising~ [[hill ~i!.Ig:g~~ dlat d:lIl);:!I(klliliO:lIls& I,lmi~ltm .pf a sl~~1I! t;i~U!!;;riI~~ Q.f cloo~~n 1 byllle dl;)l.lbl~~IUl:;iIId ,~tl;i~lr-OO~~ 1'1.(118111b.."ta!'1~i~ny illk;r llle\~v~ ·of the 'iI'!l'.'frili:cal 1I~'!\!Fi:;i" Ilfle~!lXitoo,ri n®a:nI~.:1e be-

pl~~ca1

lemlimliI'iig !the

r:ea~~ the hVo-ce!a~

pOO~~!]

'Of"liilthnol and ~h~,

~Iueif':.erc~ de-

. ,'" l.Il:_l1IS

filJigle:s

Ule~"'ave

fll!ildiol~

o!f(he

blo'lJ

!iU~

n~

m~ .~

fasl-

ne

or

U1C:ra'i~paj~iele,f(y.!' ~llile r.mic!.l!larca.~~ in. wMcl.l dIe: e~.ecnmn pairr OOIlSi.'!tS of' it if~!linCl !l. vety slow ,eioolron, the diffm<ltkm of a oohcrclt1. elcc= Iro:Iilpair ·CfLlIlOO lrea.tcd by simply neglectullg [h~ sl(fw ~1(lClmn.

{\vetlU

terns lenlclIgcilll. th~!> d~b~ of l!IiI!e ('!'.'04Pl:I!I111iclOC: w.alV\c RI!ncBioUl. No vcs~igc: {)if thcse l;latDiL'lII:t!> 1i'C-'= lnilill111S, however, if the: d1~~lIiruli.Ol~is~mIlli:gmlcd.

the '~~cl.r-Qm.Maik;ooi!"terft.~f1lce

pat-

auelel
waVC-5

CliC3i~ed

and the :sh~gly Oli' lil]u1t~pl.y ~~ter:oo. H'u~m'mnlyin rlllilC ll:lOlec.tdiBr

WcperfplmfUOO r,,'I{) caloolOiiiIDMl'lnO Inruro
ni~
'wru;

,otCl.tnial.

1~liIcteli~)' of I(h~ phmon. as well a.~I!IUl~Ii.p.l!e I

NCMI~I!l!l: etl1f~L~, DI'I~()~ooou~l

firnl~cm-

lau-(]II] (!lCd. ]~ne l!!i! F:~

HUldolU

~E)

~<lsOO en IJte

f:l~Ia..">eilfJ,~roXhMt:i(!ll~ 1(RPl'\) (22), t

~~le seeoad ()b'lac;k :lim: lu Fig. l~cn.l1.~locll a iUllt~tliple .sCl1ltll;crilngM~I.a~ic}il'\"lu~rei1n. a $,Phc:rii~ cal \"l,i'8\'B is lauochilld at onepm~(Jn (tn~TI~us
film :liImllilply ~1!~d1iliil thi'lI!iA''O-oeI.tlirn' ~H)m.rniatof rwo! plfOtOOil; ,vlilidl ~,s l~[ltll~"dl at
wai\i""ei~

,tuild

a bcll.!!ldiou:y. The (!j'.el an.d IU1l!~.tiple .scalitered waves afe llwil ,collCfenily ad<ied and sy'~nW/17 l~mdL A:I!l'Iil()Ugh Co.n:oeptlililUy vay diITcl'ICttlI. b{ld~ cak:ulalkms ,aClOO"l~lii1l for all. Qf dl~ oo~evarDt

951 eV end .s ,eV 0( E2 0:;,- 25 e:V {Fig ..2B)I. ]1IIi ~e liJJnlicr'Ca5e,I1LC' rusmhllui(H~ a:PluoillOlle..'J tJile isalrOiPi.o lieSuitlwidl.m.u lWCI"Contcrill1:cr.rCrotJ1c.e .. By ool1lp2lrlnlg th!i:8e data to dm OQ[l'ffilXln.dilng ~e· ffelil,ca~ ,['Sllllna:!l1S (F~g. i:~ and .D). \r.r6 cam oow C ~1iIQW d'lam dm absef'io'Qdi ll(l..sf! Oril.I~IL';a:rerunreoon· 'Imlil. l~ ,a~suil n.f iC!~'hel'(llllce ru't~,n.ol. of tlm d~~g,mg eJ,eoeu1.1n wa¥e~~l,gth.
lbel:ween. I;\?{O {~lec~lall.c:ill2.ill case} does not d('Stm"o~W,llnascs.~~,
ll;llemcl~on

Ui!!l slmpile mil~.IXlflic]~icll.l!l'(loomp~tl}l.~ p ~uL~il'i ~~RiIri(t~ wI~ 10'l,¥cf" pril~:i!tyWid: ~i~i!~f SCllllcrod. eled!ro!1!enqie!! re.'i!lII:1~~n !!lr(mgeroou· p;liDl!!l bctweOOIILe, eloco:am~ r-i~lIIre. 2,. A mad. '8" shows. the !l!eSliilisror differellt eneligY 1.:k'lttili()."lflS of lim firslll.lIldii seeond clecoxm aJliIC!r kmjn~iQn by i. 60~V rlJhotollls.. \Vffilt':ruaJl for E.u ~ 1~0 cV IllliId~2 -c I~V d~eint~rf~1{l~ i8 ~Iin vLsWl~ r(Fnl'1:_ A),it (;(u:!ll'l~y ditf.fW~ 2 wih~ E. ;:0

and IE).~ :L~roSIll ..... romed (Imre. '~I.,....., :ils lnile a1ilgl'e be1iweCfll both ,il\cc.,. m:m ~jcCI:o;ri~), Ho'WC,wr,. d~lildiru!l oa rd~ an~l~ Iilctwecn I[lm d!.lC1roI1S 1m'!he ~Ioc..rodl S'Ufustt j of Inhe·dam, liliIl';in~rr~~n~ pfl.n~JWI. is lHn(ldl.O ,[I~ right (fi~ 31q ocl~ (flg, .3£). '\fi!hou.l!.t iil~~ sl.t1cm:m OilS oolatlve aQ~le, tlLlc s'hiikdl ~il1ini.!n.1 mnd. IlliL'!:tlna CiU:tCCI. ca-ch .aliter O~. ~eailln.lll. to r(lle alnIDlSl !smropic dislri.bllti'Ou oifflg. .m,.. TIm; iI~ICiiirCrnl'alli: 1fn&"i:I!M am cOUlQ~lmn:oo
W)

q and <1>_ - -70 ± 2:0"ll (f[_g. ]'.

c1>lamilled,
dle:Jil

O'!.Itllrrn1~l1ii!,,'~rtica.lai(Li!:.. M~l1im [;~b~I..~~f dlO d:r~:a with ~rncwd1iing ~u~ar~g¢s ~rfJ'~ = +fO ;to 2:o (f'i~"3. B <llJdi rdne hlilerJel'Cllrep3l1.em

of

ahmg tw'Oimrizmt~at

IiIICS,

1b~

in!'l®.ll ofbigh.e:;;t

IIfneillsity I~e at a :~l!ari'l,l!a1i!iIlgl'flof' aooul~IOW bet ..~oo Inhe rW(I ~I,e-cI'ii!OI!l'j.,lIi.s di."Ir.ib-utLfm :li.~a l we~l·kll'O~wn :rndlic<lliOJ!l of ~h.c U1eCIil,JiUlls;m 'W~~en:'"

COlll,kmD

qUI1HuJI.m. 001"

111C:cllmlllic.f1·~ystems s

it en·

by ~l~e <1/boorp~ioll Uri! simgle ·ph'Ottna. by om;: elcclrOl~oon :Llldlll.c:e its cj~cl:iOJJl, 8iS well as Illml: 'Of li!hl3otllcrelecU:'Qo, aifl~r rfih.l3irNml't!l!Y oolUsikm.

(I

:20

40

~.1180

;i.

'1::11

·'1810
IFi!g. ,2. 'lAl 'ElsOOrO!n angullar ,d'istribil!ltimll <15 1111 . .~igJ. 10 bllHfur ~ "". 100, I~'\I.,[1. ..;' 1 ~V,gfi!d fll ~ 1.10 reV. (lii1 ,f"! ~ 16'iJ eValild !) Ill\« ~< 25 eV, Irre5Uffitil1lgin.f1 ~. 88 to ]!O~ e'1l•. I~tIld m'l' Angular a di$1;rib~:(I!'!1 o;f @I.S'i!'!gkl ~~dflOC! of '~!iil~'l!! J()f ~he ei'it!IIDgy d:imibm(II1i~ in (A) a;ii1cll(B), respe,c:~ ol1eLy:. Rr!d, Eq. .2; ;bu,. IFI:P:A ,calruia~on; bla~, liI!i!!.!!mtip:re s(al~!i1!l11 I4!h:l!LW(I~.
r

-'180

00

1BO

(I ~o-m;lil

90

1180

4i,'~.mool [deg]1

,[de;g]

Fli.g. :i1Il. Cl)fr!mtioo Ib~!ilI~~fh @~oomoofi!S fur dClI.!!Jbll'l·p1il,~i~imi~~~fI-ffi~ ,all: f,,,,, 160 ,~V c!:!fld 5 I~V.;::. Q <: .25 eV,. rorr:espGfu:ilJrgm 11 :Ei~to lG~ e:V 00' x .aldll: .lingle o~ f05t ereCU10rl t®lIDle IlIru}~oo.lIalr .fIxi~ .. (!i~ m;i!~rr~'see Fig .. ]l(:~JI<lnd y <l!Xis,a~g'~e ~Dt---~ IWelwee11l1the two reiectrolll!>. B,otlh el.e~IiOO:sallld! thle' .. !I!O!eOiliOO ,a;~~si1lt~ed ·t~ '~kl witl1~!11 ;[ij;lWoU~!1l I~J~1)Irt~oo~ P~i1!fWi~+l'tmt ~. ~.~.~s gr p.roj~ct!O!Ii 'o~~~is: " 6g!iln-e ICrno the liioril!2DlillilI;l iliXlS<. (8) IF'r,Il)~:ecti(nfi of W OIiIw th.!:!' hoblZomil'l aiIIisfor 50~ <: <I>.L'I-(! <BOo. (C) PiIIalr Ipre.s~n:'ta!tnolil of 'th~ dlartll sllilmwn 'in '~B).~D)Pr:oj;~timlillii ilI~O~1lI5to ~B~''ror -80'" .,;::'(i~-!I <: -!5101"'. (In 1F"(lk!r preserrtatio!'! af dlaita ShOW,lIiin !~D)r.
1';:'

REPORTS
= 90<' iil!.1.d ,~~_~, = '-90<' to a !kick; of tlt~ :seoorul electron, cidlerno Intle left 'O:I"nJ~,e ~l~t staron,s, eloom:iin" n UtiJs c lecnrouCoolo:l1lh iMI:l~ionmcCfut.tcs dae d~1lihlie ~o[1izntf~;m!l'ildlcreatc::;an m~l~;l~i1~~i.1i~bcl:W~i~, Itlh~ 'I\VO' i~iIO'Clm:rn~,Ellmlro:li'l ooUi~o~ of llli1ilt ~rt in, boun~ ~~nM: ~1:1V~ ~I~ d~n'ollL'llm:~ dirocily~n. p~rn~·p:rooo~~~r:in~!II.<: (2,6~,. l!i'hi" 8~ttq!1JliO:r! is:m i!~DmW!lo.l~cl!l<P' Vers;Oll 3,8Calwri~g event do'\~l!ISillream,of IB, OIll,Il~e slU d (2i. 6). \V1~eni ,e[~jl'leli"phooolils (6) o. pEi:rtic:les

(10. 2j:~

co~pand
j

n~e ~l~(])'~~

or

(17)! are s().[uc:red lirOIl.l8i bl'::lIi1n :ancr I;lWlSl'ligC I~IDIroogha d(liJJb~(\': slil~, InlU~~aJlllieriin:g,ilDdil!loos a I~ha~ ,~hill:,which th(1ilfiI~$ IreJ; a :Shill ,of tiM):

of d:~~5siO'.Vi!i'i d:,l,ti~g fWnl die ~cl.y hi~f:y of i:r1)~W.!]~~j on.Ci ~ill'Gicre ean lbeCO!}· sidered an observer flml carni.es ~1lI'I!i!l1 :~llfo.u:lI1i}" Ho.n DOOllll Ole aliter part~c,le'a1ildlL'nSpath ~lIiIinlIgil d~.c:dQilbki slit T.hc Ol'nl(mnl of whicih.'ws:yil)' tbrn:niat~ot:l,~",chm.ge~ ~1Ji.l,~rn ~1IiI~parllcl~ ill liniliil:ed by thill o1Dsm'L';G'~~rliel~s d:~Bq'li~ wa~~~lIa (261).,. fIte I*~ dil'~~t'Ce berw~"fI l 'Ole si'll!!alio!! Q.CpLeted! iut Fi~. 2A (whicil ~lOW.s in,ter'.fe~) amil, f1tl. 2B (wllich, SIlows: IUlO in· leufet:'Cl~oe) l~lIiIa~1Ic:wl!Jwl.cl'lgth ilir thesooQ:~dl, 'il!i ( ul1'Obscrv~d cle!Jlt:ro<nl is m:U1(!h short.cr in Ithe: I.:;mcr
qy;;U~I~m
CML'l,

8, H. Ciltl!!!l'I. 1I, Parrill. Pn~~ Rw, l!lQ, ~,6), 9', [). RiOIl.es .f[ (I~" ~(;)r,rm! 7<J1S9!, (20(0). :101, )L liu e~'Ill'" J. Mys. ,8'[19. 49<Ol!{2001611 !, K~plan\. A. M~rk.1J1\, S'w, ""')11 :DOH, iliA, ,3i(I ~'U6~}. 11;;:, 1i1. W!!H~r,i 16(!gg~ j,. M~ ~ J;~ ~S:!! Uw9),

'11

.ro u

n.

][;1.

J" F~r,fI.3~ e!!; m

Q.

foj'Clih Jl p.3lar~. f"l!i'lrtlli,

f'hj'1 M&. 1i!'.rt. 'JI~" O!!1dOOS RnOI1l!, !lIt N, ,~Llollf!iftliit er !lll~ ,Phys..llfN. bJJ.t ,8:jl. !02!32till {2~OIL ]5, Ii), ,MiH1,l1 (II at•• P!l¥>- .Rru leU. 92~ ][f:;U()l I[~DM'" :~6 J. Ull rithft •. 1/ep. Ph~,Ei6,:l.46~ ,t2Oi)~" It Eliillm oilt aI~ Ph~ R~ 3,3:0, 95· ~2QiOOl :!l8, O. Jog iIll!d e! !1L IV([I{L ~rum. Merl\JlOO~,~ 4711', 2:.:114

n.

m,.

f',~.

1l9'" r, weber et of, .Natr.u:! ~U. ,iI!j7 r2,Ii!:I~). 2:01, .\, J.(raapp,~.!al.,.f1Ill~ .r?,i!\'. lt2tI': 89 .• 03]:0i!14 ('2002)" zi.s, l ¥tJdfJl, :5" (il>i!loo.~~ A rl. B,!IOOr.31J1~ t: ~ 8'39', ~2,.S:,
,3. ~.:tL l1i nOM), K. Sernet1O\l;, ~, A" Clil!li[oi~I)bw,

(:;1'00:2).

iW!terl@~llice'palll;m. Iflh~

rnlOn~~nnu'll1~1i~

~"'ot ~~'tt!!retj in w;i!Qcidence (~, Illile V~8'ibj'tity is: lost, [Iil this e:1>!perim:ent. bodl etectrons
arcinUiitUy d'ol.oca!l,nzed inside tile: 1I.101C'Cui~cil,l a com:tp~,el1:l~y 'OOlliCGmt sil~:gk~ 'q;I!I@il'itllllml ~. B!('};.

rm"~e

~s

OW ¢;i(IP~nrm~nt Iilil!lI~I]1!"'~~ ~lan !wmb~ of~~<tIII.id~~m:lfic~ 'f:,!TII.Il00

~It.'t~ :1 V/iitY

ro~ ~h(lllt)a.bJlorp1ion. both rn~lro:l'lS ~e.Qn(iInOO ill d~L:;ily<ll1l)gpm.gro~.1iltW ~. whiciltl '"" ~.m!i.(;mc
Wiijc '~\e~'Morni(: C~IJ:~. l1l1)L~,""~ obsel"Vecli nol <I. scat~erins bclvtecn cl~tC{l~'Owin]i~~t

Cla.<t8~t:a!l Ipro~~j5lIl!Ch a~ the loss of ,oohet'eI~Cie" A fU!IJr=OOdy syslienl" suchas f~'W.cmcd ulJOlOOl:Jlar ydrogen" Del!;; as 9.ool1llblc b slit in 1lIlIc;: SllIISC' I]un oolnllrelloo is lost jilJl 9,51111, SYi:ll~'ll o:f"~IaIl~I(ltI ~I~tmrn_'l.. Siilt1':h afu!Ildru'ii'ilOO· la,~~'i!cro:t!IJ

or

OOl,i!1d!W~

111!/;

J. PJijos.
1

B ,36, :liAID'!i

(2'0031

faciliIiUr:l!f!

tll¢

study !!)f~h(lirnllu.¢n()~

Op<tllr~. 6,. Ki;lrin~ fflf5~It<N. ~efl. 86, 3,Ul!) (l(lOl). M" hmt, It )I~l;!!!ho!~t, t'hf!. !lIN..A, ~,n,. R~61~(995). 26, 5;, I'j!. Pii~laFndll:. fl ~. )rlflll!S, s:dtt:ll'J:!' ~!lJi3., Ita [2(1):l~. 2~7" K, ifI01illtl@~@'l:r ,~tm,., Phy:;. iltw. kl!:,~O., 16<0400

Fl,!),j~l;M~!;:iil), l!lql~~!~!.,r.j. ~rg" IkAli!@'j~ C ~ Fiaifr.ey, ,~'_'A, '\ram l!lil~,J. Hij;S.91 5,. 8S'J' {<!(l1l21

zs,

calized ~mticles 'nniilQoliIeren~ Cl11illlgl\e;Jne,1ll of InbC u,ve[ncliOO1 of Ibe two ,cooelrolls.

isirnslm(:t~.'I,IIe to lIIiliui;. ,of the ei(')£;lmllic t1J!,il(). ~y.sl:efll2l:ll .spHt il~~{l);ilS sLL'bllfysk';msafld I~ooon,si,~r ene subsySlC!l!1! ~ihe(\[lvioornm~mt O!f 1~,1i~ o'fil!L~r. 11ll1~ ~lfoog (:(DUigE1l1b ifll~CJlt{li'l
]t

of il'l[(:)rell~IJIOlIi~r::: CoulOlnltJ irl1~~1I{:tiQJil'KOI] Ilml~ eeherenee ,m;peurlies 011" a. slng:le elec~J:l,. h~ solid· staIle,. llmlrodi qllllilJ]~l!ImOOmp{tU ngdevtces, SlliCh . dctlron.elieclrotl 'ill.ternctL\lI~ mpl'CSemtl5, m; key cl~i1I~lengc. n,COOVW11'3gt'OlIS!llSpe<:l oifdlClillil~ O

~a., 111. Woo~le<r5,W,Zluek.

~200:3).

fi!hys.R.ev. .0 19', ,'*13 n,9'19).

2~, IN, \oI~l1Ir'(1i,~, i'. ~!'!i!t, 1. Reiti:Qoo, C. W. MCI!:IlI!'ti!:I'. S;rii?IXe .:I:HI, 17:B1' ~200I~j, 3 (It. IF.~r;Un e.t al.,.Srdem: ~lI.5. ,~~9 (:t!am). 31. J• .rml~iilj! g,. S" IPiiiil.lo~, F,. Ilicl:ilcilearn, J. Pliys.. g~1',

hody

S}'simn ~1l'l,!l~tigl1i~OO. h~ro is d~ i!h~reliem'ny" i!~ iii. fl!l]l:ylmdilhl~ <'J& 'preset~1 1(2.9'-J2),
IiIE,ftel'eflce.s alild NGt~s
1. C. Jlflm:i~n:, f~, ,A ~6:l. 45~ (19".1)" 2. M.Arnat~· m., ~{IlJi!e 4~!l, 63'0 I~ '999~. 3. ~> N!~t C S!r!lli~ !'!!fl· ~~. U!'~, 15, 1:25~ ItJ..~~t ~. E. Ji!Iii!5., HI,ZEh, Z :1'11%.8 '~? 22'~ i[19~~, s.. W:"llJJf~k.. ii'e~ 1I~d. pjiji5- 15., 115 (2003:1, ,~, 0-. A. K~~rnfQW:!!l1, J,," rP. (rooin. l. (J<,.l1iooom .. 0. IE. Prltd!lo!lrdl, .Phr;. ~~; W,t. ,96,. ,~l.t;iii.;20m)" ( 7. l HildeElllTlml~r. IK. HClrntl<e!!l!llF, B" I!rel~~r. A. :Z;em~K.Jfr. M,Arnd~, .NlllIl_q~ 4.2:7, 7U ,[z,004t

c!J!!3nSk'S the (\!iI(I s:ubsys~ll~ .;;JJodleaclS Ito OJ, I?OOm;OOl4e:pen;d~,,~t ulOdi.Hoattorl ofp1~OlSe of
~~le slng]&!~arlk:lle waNe ftliLctklll1 tlJlsid.c eac:h,

s.

iL3 n ~2!OO>ll'. 32,. ~, ~IJru lias, }. "ll~ .i!I.l7. ,t'88J ~20041. ~,~, W~·tllalll( U, ~~lt[!l', J. 8riggs, lli. t!ilnjret~ IU.Bet~r. I). RVlle$,IL :~Q(i~ UWi!" M, .Arli1llt,. iI!!ldl.!'I1. A~~et.l~r It. fgr e~LiiI~t~lr~1 dj~!!Ssj~. Weite~1!Q\'!l_ed\\l~' ~y.~t!!!1!!i!l!l :!~~rt by ~he :!!<!fI 01 ~!Ie.,IIi;I'\I",II!ll~ Ligm~ ~liI'a!.ill p:!tlri~lJIll:l1r bJ E" ~li'i!iiho11, T. '(lI11i!9i H. E1llilliln. ,~fKI l rylilli:!ak,. n~s wmr~ Wili~ ~u~po~~tI

o,fdte two. :ru.bsYSI.mns. T~e cn:~~ngtlm:rmml1 af lire C'lootml'l8i1~ tilL'lpairi:; directly vi.sihteil!l lI~eilr :mliltuaJ at[lgu~tiJrdistrnbilUioli 3Ildi8fW1~:i(';r (::vi<JtllloOO by theabsr;;nI:al'OOfil tlhat sel~limlg d:te'
nlOlil]~ltml of' Ol~ ,!ll~eclroli!,;mik:e.s Iili!e ~~tli.'uf:!o't ... ~]!Oc p<luem onts piltt'llc.r lieappe1lf. :In lille spirit

by ~~e IDltut~:t~~ f·Dr!!.(i'lI~IK,I~I1li@iIJi'l.5Chliir't aoo il')! 'lh~ 01ftee ,oIIB~.rf !Elwlrwt/ $cfA!oo~5, IDI~brilln, 'Dr (httflli'c'!)[ :5li'efllll~ or tlt~ U, $, Depill'lmel[L 'Dr E~r!lli' uoo~r [!HIIJriW! EJE:·A(o~l!6S~OOOge"

::Ill) Mil)!' 2007,;

~~,eopbed 1:8 Si1!lteillber :20 O'~' 1JO, 112~,ie!Ke;Uil4'9S9

Accelerated Ulplift' and IMIB'gR1!Stic IntrUl:s,ioln 10 tha, Yell'Dwston8: IC,alld'Blra, 2004,10 120106;
1 I '

features cI.laract~rize Yen{lf\,,,'Stolll~ (2. 3)1,~Jn.liia.r rollw.,sc Qfodl~r Sii~Lck VQl~all.k:i~efd.sSfuch a~tOllM Va1.~~)'. Cai~i:rOomia:,a:ndiP,hl~~bl :Fi~l{j~h Italy {4, j). '~ooe]ic :lllCa5~ll!Cllls QirY~J:IOv\,'st(lln.ii;; :frmn 'I '!l:l2J to 2004 u&~Ulgprcc.~l\.,"I[1iUIIIg, 'G!?!:! {GJ(IIba~. Pol$il~ro.l~ililg Sy,slemJ, ,anu:i, InSAR (lnlieu:feromJL'llrtlc: $yn.thL;lHcapiM:'IJI!I!i1C md~iIi) 11avc r('l'll,ea.~ed.

1l1:!.!.lttlpiL'l ,--piqoties
ThE! 'lI'lEllliflllliwne (dirleil"ii' be9i1na Irapid e,~~sode of !l~OO!P1dl up~il:inl mid·200i4, lliewa,led by GlObal. .i?o!'>n.uoning Sy.stellli!,.nu~ iint@~erom~lIic: ... tilth~tL apertulli'e. radar IlIIi!eill~me!m~ y .<It Iram's Il!Ipm '} iCi\lliltn,melews. p~ year,iMlic;h.ili: o~'r thr~ie tirnle5 'f~ter 'tha!1i!1pr,e~Clusl'y (l!I!l~rm.ledi:l'nal!ioll'l rate~ Sour«! IlIIi!odeling ,of .ljhl'! d~f(lrm~oo d~lsugge.sts; an eocpali!d/ililg Ij'(Il~:;Ulksill OIf ....12!SO sql[la~~ kilQUlilete~ at aJ 10!i~nC1ilflfl8te:r dlep(h b@fl@atl1the: ~akleril1, ((]in{i)dlNlt whh~h@;flOp ofa s@i$lIMi:a~~y iiRilag@,ili UlifiS:taJl 11fn1l1~1IIltJI chiimb@r. ihJe: moo!!l.i!Jdl~ of .~CUiIJOOVO[Ullllle il1lcrease is 0.1 (1II,h:; kilo;lillIe1errpef r ynr, !jimitilr to ~lju'! iilmOlil:m o,f miill!J'l1ailiUrwiibrl ~l!Iired to mp,Ly the' ob:serW!dIii~91ii hm.fI.ow of tIt!!ca~derlll. l1his !e:'Il'i!f:efl:beiS'ug:gem IfI1Ji!llgmlil re~tli!llrrge illS the, malin medillllln:sm fo~ ~ei!~celerated Il!Illlitt, alth.olllgh l~reS1lUlrizaJlDtan of 1IrnI!JI1IiI<l:liC n.llliirl~ci1linrnot be .ruledl oo:t.

{If

(lalideilIT:.lIi)lp~ilil amd $ufu.,

[~\~rJJg.L;l ~~:fl

[!;id~ll{;$.wilffil,tl3i'l.i!F:I~!IlI1~

(!!.W

-1 to

2: ,cllwyc;'!1ge~,m!ly ce!~re!led iI! H~ two ~ :i!:tiItscn~ dOililCS, SOliU Cmek ,<Ind. M<JiII.mJ ,Lake

(6-8). In adl.iiliQIl, an: <'Il'ea IIK!I:thw~sl of lhe cald~a ~.e.'iJr or.ri s Geyser-Basin ,e.xfj(Micnc~. N
pcricd.« ,of5l!lbst:ail.t~at grooncl d(lf{jm~i2ili{m (8~,9).

1l~

fle~dQCc!!!Irred640,00 () y~;m; (!.~(l. cr~tiW!g 11lJe gfOIl!:llt.'l d~r(nwna~i;on. '\I\~ry ~i~l li!~trtO'w. a.ud 4!()!·km"wid~ by 60~k!111·1on~Y~noWl5tO\Jf!recal~ U)e;w.orkl'sl~csl. di:sl!ril~l!tio!fl ofll)1ld!rol!e~liUaii

,btl Yel iowsttnae voleanireflBldJ :is tile: br.gJ~s:t iI~ .·I'{ord~ ~.Im~mm (F~ lA).nt~~IDIII~,tlSt . . of 1I.~lre(l:glalril~rupho~lll . 11:h~.~. fl}r.I'I'cd 1Il1e:

··

~Bi~i.aJl ood: 1~~~t.J). \i',fIii':fu.ttkii1Sili! dl~ Ye~.aLs.o CO!ire~3'~ wid'!prn!!O'Il!!l'COO cll'm!l,gesi~l reiSJlli:C and ~yd!I"lHhcrnl!!lac:liv~~y (9~ .10') (oF!g.1 B).
]GW~Q!~~ lm~ !1rtah, .s~n! l.ail:~ Wl', U'l'84:1l12" USJ!. ~U,S. (;~olDgi E.1L 5u r¥1!)'. 11'15'97'11, .Mi@nlo P.alit, U\ 9'402'5, UlJ\,

dilii'a. Dis elMlllio:n wru.~ folloWlOO, by 30 :>1.~l8.U!e:r ~'iIi~lPilil.Q:[lg foomiml.ru;'lll.y ~byQ]u~eflmv;!;, Ill1m o y(lil!lf~~,l 'O,.oOOye:m:: 3i&{) (1), &II:1qlliakes,

'!o~pa rtl'n1~n:t ~r 'G~c'!Q~

<lind G~h~'i.~,

U nrilJl;!r:~il.:r g,~

~T!J'whl!Ull ~(!rFIIifJOIIKjlt.rI[El :lihoofdibe illlId·r~d. ['rrmail: '1'!'df!<![)g@Eialiifih.ytah.edl~ 'Mi,··L.Q; R:$mil"@~<!vl".I.!I<!h. ~,UVB.S.)

9'5:2

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
-- V1Ir.!m.ul':iY -~J ............ h~~~\- Oor! l!OWi -Ilim, lillY ,t"id.~~-- -, ' (Jl'rY"N!I 0,,,,, eve iUtlOOrdJ~lli!il Of'S SA.<ltiOIliSifi Y'elkiwsto:m: tomon,c i~

'rhe [hl!~V'It~(ly oftrlfi!l!h<LlIicli llheP~!1I~:B'OiUM~

siiow 1 to 2;@ 'of :8ilIb-si~'iCei~'i

i~:Of

''IIm'U»iilS()f dl~

groUIK!, miC!VC-m~m U I), -(f'~g.ll AjJ T~mjID:um, vertical, detofilii2itL<:!n (Fig;.1A)

djli~ calc.krol! {~.,g .. ,all, stllio!~ LK'WY}a~dlriJ pH A:,il~i dll;lNorris: ,~ {alt sta:licu,1 NR:\lVY} du rillS lh,efim 6 Ul0lllll:is of 20M. 'Thc'cm.ll:i!rn"a. motio:1] Lh,en, !rudc!leillr~,y r.e· versed eo IiIpli Ili i~r July 20M ntUIt~Xp6mOO,

!iii!~, -7 Oimye.ar <iil ,l;MliO!ii WLWY, wlieiiCa;s theNotris.wea beg<il'i '1.0 subside [l!bout 30 Iillt:mllhs later" Aoccl:eriiued ~~(lriz~fn(al. l'IlLO'Wi'I'uml!> (1Ol1rel.al~d 11111 time '\v:i~h,dKl cl~:rn,1t1:Cs ~n vCrl~e,gjlmoli.ons (fig, sru). T~e Gil'S di!lfi"i.

high

alsQ, rov~ali!i

nG3lr~!>im:!lllaJl'lMI,!l!S; i[l.cep1~~om af

up!.ifl aemss th~ ~nt[re cakHern.(Fig" .2A)j :~m

eO!1JliJtag IIDII:} :previous ·oIll~rvalij,o:ns the
r

tlll;'lt deilID!~ S(!'Uf

Creek d,Olrllc towmd rl'he Maliai'd Lake deme in I, to :2 years (7). [nSAR mneasW"ClIlI1l1JUI (EN'I]SAT IS·] ruld, 182 IliiIIXI~~r from 2004.r~o 3006 {iJl, \~dl.:1I'i:\.pal~_3J
~~lmiOlfl

fom'!ati·ol'! 8hi~ed~!llje!'aUy

rr-orn

~r-JH}

!l~ .C(:JI'i$L~Xl

n\ I1:lvl4'1!1gR)l)lllid nloDDon~ rnh.(ll ,,\lid'! !illI~' GIPS ,obs~,Mio!liS (F~.

111e:il!rl~atiian

2'B and f1:S, SZ).

!;i!:miUyoowaro

imlc;~ses:

g:y!lf!fL'U~l-

tll:c cElkilcm liCUlwr :a.oo111 daelou:I;l

Mis (n.ol1heru:~;.sou.l!'I'I"'leSlA wi.dllbe hl:gilesl !rnttc of ...,1 ci1m/~m ' d1C SmIr Cree.k. dome iJc:il:1ig, 1i1~,~ to fivr:!im.cs fasl.(\;[lI'Iillll :lipliJt mt~s in ] 92];19S4nndll99S-I9'97 (f~.£}IB), 11t~ Nom..:: ~1tJ..
S!id~itl;;iS L~ ,..;) ,Clll,yILl'llr,.

mo:ro

~lli!1I!!ll

l:wolil~

guea~1:}.I!'lhand1CI996~200~r!l!p~inrnl'e in this1ftll. lhe GfS ~lOJ:i:i'iOl.~ml veloc;i(:[es, iJI!l ru:ldiition, indica~e ,gromm nU~lil!lls direoted! outward fmmdre C91l'dcm11& 0.8 I~O 2.2c:ral(~r and imllmcl (odle Noms am.a. ar 0.1 002;0 cmfyMr. d-ero!"JQ.IlIU'O:I1, we joinUy 11J!Si_A_Rdata (1,2) rorlllie
To e:wiluaoc: dl(); ca~~C)f
1~'I1It':alt~rve~

rupLd

il1!\<'~[OI:oo

d:l~Grs

m:d

gCOJillel!zyandexprul~ slon or OO,lltmcl'iO!Th (If OOCtiall£rll1m- disloc.1I!L:O'!Jl> ina .lro,mogeillcoU!S: e-Iastic l&lfII~f~ace 10 s:~rnl~ u~alCl:inJi!ll~in.g and de:fta.'ung V.Q~C8Jllic 'OI'o!.umas, ./\ ml.{1n:~Ii!!t'lar Qptimi.zalioJl 1II1I(JIffit.oal lli~ W used to d,eM:r.milllll the soure L'l ml,lOdi:l~ that nruiln... - C'OntiiIFlJU:oIU8 ,GIP,Iij,

10
B:
~'iI"u;ri!I~1

,-

T:r - IP'!!):SiI~alrd!1lI:':!1!I!i!',(I!I~-anilil

station
I!.llEIfilt

Hrydr-otli1:81T,i11'all '~eaJwre I .. ILate-Qu ailema rJ' fau It

inruizcs the difdie,,~[I(;e I:mh~\I>(l:el~ th~ observed 'predi:oted gI10Ulld ~l()'!io:ns (/.n URoer"" taimde;s of m.odcl pruran:leIDe!:s we~ ,cvillnuC!:l, by ,B xJ:n1e~hiod. r(Jl). TIm besl:.filt~ilg, sOil!lrcc.~lbr lh.e:Grs aad IS2 ~:uSA'R,bua iil.Cl.lldil:ai~ GX~flllildjng sillOIlrldi

~V,~Ii;i!1
• l.ll'l!II!Un1l!
"tnSlliR'

li!'lQi~Qfl tIIe'{lf ~ iiii)Qt!IilI!l tI1e~r NGB

_.iII ......

o C::l:I1IIpiIIllll~ GPS

n._

tiv:eJy. A jlJlrd ·i!~versloo (If the (iPS DJld IS l dal<l.<l'llso !'Iesuil~edlil!l iiHlI!il,.ut SQUI"Ce parnl!ineDrts, i.l'i1dicatiog the romtsl; l1Iai~lIIlre of lire moolc'lir.g ros-Ild~ {~lg, S.l}. Olllti.'OOdIcls,~U1iUill1,g unifoi1n ca~sIiillI!lLi\ilG: j!lOO[lcrnCiS,~ood:lct ..J9O'lYQ of ~h.,e~bs~rv~dgroijfid. n'i(j~kli'i \Vi.t.bif~ thL'ldata c{!ll~tId!LNiliX'i !in1l!il~,. \¥('i :alr;:o 1~I~d d~e~I1f~I~()if cNS:Ulilli!e~ro~ncily by l!l.'C1udinS lay,ern w.ill!h IFirg. ::I!.. (A:~r V,ClIki!lli1nte-ctoflk ,~et:tting,iI nd GIP'S :!j,tmltiOIi1 loratiof15 0-1 ~~H! Yellow<,~ton~ v(lh:Cln:kfi'e!ldI~ duff'Cren;l e~iilstic: oorlstm:(s and slhowed Umt VlIh. d"d~ an'!!~ rm,q,lJaJb~ep:ial!iioo~f,~(lm r(m:(ioHi~a004,OO Marrld~ ~1:n:17'.S( i~d~[git~s S,oy~ ,Cn~l!1!k theywoUild nOil 1fI0la,o;ly !I,freel, O'lilf modeHl'l1 lre:surgenrt dome; M~, Mi!I[~tlrdl.akl;l reslJI!rgElllilt ,dOrnlfl'; NGIB,. fIi,IitJ rris!.reyserr IBOJ~in~<lllid MIiIIS., MilltillillC1,th Hilt .~p,ril'llgs. G'5: !>iatij:onl 1II<l100es, ineabb:reviat:drof'oum~lmr.arurli:odeOS;. Meal., rmi.lt':tm yearllago. ~lB,) re.ml ts VI). .!Episodic ii~Uimion, er rcc~a:Jj''g~of ~laJgJna mm~ 'S~'I1fI,!;~!i!C~' Qfl!'~lklwst(!!1(l ~rti~i1It grl(!l)I!i'ldli'!Il@IIjQ!iis!'!!!I!,d qikii1!!'OO'fly ool~fI~~k~ ~Oii,li!i'lU, Diffef'ffit li~~O'[hit Ul;lp!:lf erml:1 ~~a..~ been pro:p!O~ as: iii. S.ilmiool~:s.·r,epr'~5eiiit e~lif geocetic m,~:s~r'imiWit~ (6~9). "l'he 1iel~lcw~lIii31d,ed !lirl~ Mf,ihtights ~ne Il!i'eiodl o:Fac(e,leraIt:Bd d,l'forlliliaililltlil IliepDrt,ed~n fhii", studl)!,. Note, tha~ ·th~ 1923~J97b,lIIIIcI i1l'~r7~ !n~chi!lJ!ism for ipreli'ious yi;;UowstOi!~C ca1!d~ 19Mr.aJm ~r~ each d~iOOriiIi!1:Ii!~om 'lmly 'M!'J' 1!i!il~s~r!'lm~!1!ts. h I.!~!ift (J, 2). Inlbi~:OO!lC~)hl!lIIl n10del.m.:sa~tic
hiSAIl

1ik¢ V(llrl1l1:we: dip~iiing 5,>I:o$E (5;~.NW I~(I ~·.5 ~E) ail.rI d~~~lofl O~alil (6 'Il) 14 :km) belletll~:h the Ye~lo~,~stmle C1!.lde'l<!! and ~.co!~trn~d!lg V(1I!mile .dJil~~t~g 1:2~IE (7 O"!\'W ~;o'IS"'SE) at a depth of:Rkm (6 to HJ:J\;ln) ulnQ!cr ~llill!:Norris allea, (fig. 3.). l'he IlIvc~e mlm of \l'O~llil'lGm!c dJ1ange am OJ 1 knr JY~ r[ifUt'lIO O.12 k~ Iyoor)r :.'IrIId. ...{l,0!. lbn~/ycar {-MI05 II.Q km~!y(l:U:) CQ:f Illiil~ :i1fi!l1ati~.!!l lnd d~flIatiilflg ~:Oll~'~,. ~WJ~ !

~o.m:s,

REPORTS

AI

IFig. 2.. (A,~ TIOOiIpoi'al vari.molil ol~rrn&::al Igml!lnd III'1Ini[OI1I;, of IaJbel.edl Y~II.owst~~ GPS sii;atiOOiS. Eiidh dm r~pru~ ,i!J da;l~I~ositig:~ detE:rmri!ilrio!il. ~igM 1~IiIYbarsame-l;·cr ~rroili:S.fWd! and blw dat4am lil1le~ 1IrICIir\K, the: mcepoon'S,
~c.., ':;' "", IL

:nne-of~~~ht ~lOS) Is.urfu:(i~ ~~ ~h!lls~~lbrrom the ~:oori~rogri1!fI1 inrer..,.ell totall!!!p~k"f .ablJut.ll em 'flflthe Vim piIIrt aflleGalder.a and alS: Larg;~all ~ II!I",IIIL d 'El ~ ·'d ' ' .,.::,. ",'eiIUrm:a;~m ,Uall::s,in~wllle ~lfIlllPeJj, ]~ em atit:lim SOur {r,eek N1:9i.1rgllnt dome Blfldl ill :lUOOidElllillie of 6.6 0'IlI n:~ar the <iii. IJf .·1iI,.e .III·'" ane Ih suu~. BIilCie1,J~BLlIJ~€';1. I" if! Basin, VII11im ,i!!nd bI!:idk: ,a!f~$ rn~lWt honj!(i;!iI~l,a~~ ~!tic:al, ~filjUl!fl~rj[!a:tedlli!i!~. i (0) A ;ruu::~ IfI'SAA rm""~~am ~ENVIISAli' ~S2 moo~) Ni!Jililri~ G~!l!r fE!Spew,wlty. lB]a£k ,~~j~es, nd ban ale ISlLale~ ,2-0' !l!rrtl~ Ul)l. a :[1I'OOil 22 ,5eptelilti;er :2004 ta, 23 iUJgU5t 2,006 o,wrl:ainl lMIilil aV8rrag;ed GPS \!'~,tyveoror$,
''Ii',~ootiie;o; [1I"Om 0]' OctOON ,200lJ ilnd 01 Od!9Brr ,200ft. 'Me

d~spli!~~!11e!ilt ~.'s 'a~

~111:pansk!ll~ {)('Iulld if gas di(lldlar;g~ l" mk~11 ill~Gl ~.oo\fI,UlI. Ifih1.'ln'loolilam1i sl'll~lJi~ a. .We ~~U$ s~gges! ~mt il1e 2(ID4-"2!OO~ep'~e rnp;idim;l~e in l1y!d! e.x!l(l(~Il!!i~mfwm 1IH%lHla Clj'St<lU17.a1ion tD aw01Jmt for tllc aco;:oie~ calof accelelUwClinn"tl<m occl1lili'C:d h~ n:8(piJllse to, ~ c;lldn~widl;: n~agl\1l\ reCi'muge or~~e Ye:~IOW'Skl:lle dCl:alill)IHl. !and is tI~IIiISa :I~,viab:lecWllserord~c, o'bSCf'il\OO. d:efMlina:~ioo. \.rrilcralic syslmn S'ucll8illl~gh taIlG ol'ulnlii'il!lSion IMy Sm;IiJCC m'Odeliluigofear.IY0,pisoo(lS ojj'ca.ld~ Im.ve: OO(lltlill'l(:i dITrrling past uplift epi~e.s. fur 1L'jX8Jllp!L'l kl\~il1 UI(l:ltir.;t t:\l,I(ll(l!'r~lil:tg~~5 in IIDlf'la:DiM {i', 111 imply g.~l1Iiltlmes and ,dql[l!i$ l\ii l:liJi!,:!If :ro ~~~~. fH)It1 @r r~~1 b~lmlli.ch t(lc~r bighh~3!I!l1(}w!ilf -:2J)tm mW!m1.rn'l~lc~UII'~ PJ21 :lnd ]976" ~,,~~[lIIhl)i~'Ll~.~rna ~ l'I.io1l:liof '.. o. I """''';·u· , '. _._. ,0 _. raes";r wJ,nn ....,c U0I1Ca5e,. :[)(1,'1 'I O(P 'k"H1I3;;",. '. ~, (rmil Yeli(lws~QIfJ.e:Lake U~ ,um geooj~emh;:.a~ ~7S Cln b!lllO.le:m'!e ·of ~.4 Cl~if)fear was li!l¢lldy w:lfiid,} .are cOJ.TIparnblJc to lh,e !are·soon die above i!ikqID1<ilW Ibe~'ieelill obsefV36m~ {Fig. I B). e\~Ude;lilce (J')•. Sei:s~nic tor.nog;rnpl~kl :Ln]flg~lllg p~ovic!fe;cl, IlliJagrn13lic l1lJlJid m~1. This evidence Stl~ts An a:l~enlill(e £111~rel:ation for ~~elCald~rn dirl~,l ~~dcit(l!1i fur ·11[~paD'li<\'t~~YI.'ii'lollel!l I'mtl!l~ O dilat ]':li'U~rizin~ 1l1uid systCl.WS: ilcarlffilelripoftliie W upli.~ is that illmg,U:li1ic fluid.\l (water aiH] g~) eruSUlI. iillfirgitl2l ro>m'(),tr is, a ,1nQiblesooree: :~nagm!l. Ch~i:wibell OOloo~ljt thecalcler.tl. (15), !eJtsoa\iloo.OOn1 ma~~8ic~slanli2~aJ!iQ:~ \\i!ero'~ iJH~(!h,ili~:L"i~ fur d'l~ jl;~om I!Jptill: cpisOOi;:s. OOfii£1'fI.h ~fi:1i~fin~ae ~b, ,e:clti~~g p~llliriza. AilQl1fii:a1tru;. o:l' lmwP,·\wVC 'II!1i!~it~! li!ip In (j.O/~ at dep1ihg o:l" S IM:~ I.(} ~ 'ij,.~r~~IifIUii'j'l~~OO. :L~ lii liiuiiI ,ofih(l:dj,,~~~!tydrCillh~f!it:i;.'\1S)',SD~mIl and iu l~iijj1 llj;~:th~, ilfi::ligima j1n~[;(j!'i and fh,iI.d p~l.!lifi~ ~ooy of c:rysrta!lH~-:ed mJOtgn'l1' of~4000 kfl'l.3 i!]fl!~l'~~the ~roUin~ ~r;~~e (fIg. 4) O~s~<l!iI.i;dn~ liurl s'B!o11!ICI~' cO!l!sldCredi 01S jol!~lly opmlin~ direcdyuooerlylUf!g Ole ·caklem. -rhel~1 of (h:is 10.1 :km ,,,ear of !\h.yO~I~'L'C l'I1~p\a, wh!chlS re· Jlrocesses ItQel!;pla~n ~i~ea..oool,ernlii.'d lcaldern I!!!p.~in repoorled here, Ilid:rowgh om' c·st:im<l!~e ~!lJ1C of qllired topmvidedle o'bSI.'Ned dlmmli~hem~ow, body and our nrOOeb:l S!iU QV\eillap (f'iS~ 3E)1 8J1~ !1:r3p.p1Jif1g; dre ~Il~j ;1;1] water wouldl ~llIlt~ ~Il vo~un}c inemal~ lrnplies [1m ;fo:l'mneu.~ II. p:ro:mmOO; i~lp])!'in~ dlla! the ,ac'OO~Cl::n<'ltm l]pli:l'lis ·cauS€d IJly li1iflatiml ],1lt}ltru 1~1i'I~ shallow pan of 1I1~'c .%vm.lI!~u].c I.l~a:nt£l.mnarf- (HI13kJi~tyear (3, Hi; !':lYl!ll're il1aoo~L .F!lInh~ fmldcpmtdent .oibSM'ffmio:l1S, 1[I.~llI!g,ma.chlll!mber; MOi'!UM ..~r, to' !1~::lJ]ItIUlJ]ll'I. I11e: l1~~~\{I~f[e,hmvJiM1jr.is ~booi.] 01 ~in'l!'lS!\11mat~,Ulail Ruth j,t~Ir('lifQlpoarnlm:t~~vily 1 01lla:lfI~, capab.~ o~ ~.]'lih~ nl!;k~1 ,.mdi dI.}R'iil)' V.maIJlot'!8 (If d~c m:I'h!iio~ row' Qfo.[ I ~:WJl~ ~~. goo~,;vOOCOl!]de!!l,l b~t fI!i!x ~yi~ <l, rl'!<l11JI%l Ums~ :~"",o~r ",,'Ould ~ I!!!sefullo di.'lO.!'in.. cr~t;;Jjm"'<liI:ioH ra~e {If ~O.I kmJ/ye:Jr' (J), sible ror ~e OIil'rC!i!I lI!pliJtAldlo(1ghlhe 'II·(I~lI!!l1!Ctric HNlgnlalie 'W~~i.cl1.ls
OQ:imlpambl,L'lIQ

nnagll1a.o-rlgj.f!lat~llg,nc!)jiU a.l.w~md¢ pllJrttL'l at dl~n~ (lr ...,50 ~m .a~,~d$: bl.l()Y31lIily 1lliI'It;i(vg·h. 1~!I!!e (:!l!st. '~!'QVtdblS, l!~~!'!'ll.d e'l,evgy to'P'!!"ti rully ~ne~~; cmst,d rocks ilinal 'cn."'<l~e ~~,e ~hy.o:~utic :nmgma,OOI'tlI?OIWIl~t'h'H cI!mrn.ct~zes I~hesilicic Yolca:1i'1islrl. 'fhe basa~ticalilcl! rlllyo~itic lViIagmas I~'l(il!l cf)F.$l:iIl~i2Gllndl cool.l'l'il~,a.ir.lg ,ooerg-y re8po:l1sible .~hf '¥eUocwsloliI.c's exl.rrHlM.il'larHy

ourmod~!ed

S()U1rcl:l

~.~.~r

1~~l'Iiui(l(l [tate,

_;I

..

9'54

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS

IFt!J. :a:. fA) Obs4\l1VOO Y~~liJWStalfie gcifQodl utioo." 2004-~OO6. Bi.a(k ,andl wi~itte dHOWS: are' ve:r1I!iC8il. and hor1iiloota~wlocity ~edOr:5, ~~pectNe:~" m:BMIredl Iby 6~S. ~ad:igmuml rJolors r~~re!ient ai\l\e;ra~ LO$ cmiodfiecsil'1lte"dJlilIIt:M by 1!iOOI~I)OO IIlSM di!~ p;ciioo ('!;Ira.y (r~se~~1U:1:~I, (B)ModelOO gJ()c~oo liIii!OCIOji), SlIl'ffi:u:llpmjernOlls ,arl!liJe IlIlUldel.ed ~pillliu:mg. itmd Cf)I1Wilrti'Jg .sill~ <I:re.sliIlMfI Iby ~dI anti '!ira¥ ~~ ngl.es:. ,~~Mliiv,ely; SaUdi limes hig,~lght 'Ih~cm;,.: ,ortffile sms" (() l'II't(Jd~b~d~OO (I~rrrOO~lFOO.iflcllllfll!o:tiOOI .!1!k!IiIQi th:e-j[i!f1t)tii[e A,4Jt' "ifI (113)1(D)

R!;ls:id"u~1s I~~M

data cmd fiOOde~ l~fmwOfis;.i(E~ l1hi~~nrm~rulOiiia~

(fIromtne ~UJl:iMe!lt) of 1hJe ."iei!im.n~~~ imag!!d magmai

~c

vruimk ~'~I) S~EMi'm\P~ on al 0:51. (F) ICI,~liIll11gl di$lilriWlion orlhE! mede~ed i"flating~iil. We 'fi~ ,~!lJmed a 'ooirn:!irr!l d!ls:klGtiOOIOOn~U1! 'tJliIl1! ca!d~ra w ~dlwfuu th~'gi9(lmll1etryoftii1e ~ilt1iile dism~fltioo VIilI6: them di~~ffiize,dimc 310 pa,tIhes., .'lIu:1 tffiIe opern11i'lJ1 of e\!I~~ wa:5. es-tilmtterl m be.st: I~~affilil the 5il!'J!ltilll
~.g:tl:()fI

moo~ed

vlew

I)'fl!hil!

c"!!lki~a~lm:

un

00. wato; f..xmcl\\ullraioo. IilearUac; ~.ordlelil'l. caldn£lIl 1Ooir1!l11da:l'Y~ "\lliite lfih.e ~t O:rUl¢ caMera exp~. lLl>Jilce(l ~(lcw r.ai!~ ,(If .s¢i~:nidiy (fl~. tAl. V:O~!J· dace dU<lJtlltim1!Ol! strntn hi d~e ml1iQ~!~dtlllg Il"!eIttlC expl!!!tskm of ·cm!im~ oocI:I::...s dMe Ito ~Ie imllll.Cled. (Ii latat'ion !C<Inh~CNMe ~hc j!ll'iilh~1r.d.~ and vd!c~n!c liooks (Fig,. 4), le>adiug lilOfl'Il lnerease rx:l:llile~bility aad <ldQc~~ in ;porepli'cssuro pool-n1oie briiilefmctnrillg. Wiih nlilIds l:nrg"MiI~! from, '~~NQrnsllOgi011l hIm tI~e ealdeea ,carib· by open Lng mli'l\l,I or S(l;~r-$effltoofmcl.UllC8. ADCO!rdI:[~ am. beil'l.d([j£l~ cr'lillildn Ililile dilaJioo .. ZO:UD~ iw.gly. I~mmdtl:aJed zono ~Iilea.lh tim l\'O'rthcm ~tw"''ef'l dli);infi:atlmg and defhtillilg .SO!,]~ '\iO~· c:alderna e."lmI ffi;1~'liOOCi$ IQw~r lpom .~~re I~~,a!ii"(;lil) ~J!l~~ydlrolh~f.rm:d.\~~rvOiln'8 b~l¢ai:l~ [ ~Dfi'G$ (Fit}. 4h Uieca!1dem""Wide .a'Ccd~~tedlilpHn rejpolillced I!~e NQil'ilis area. TIlis h~du!cedl f!1es~ulregmdie!llt C~g:l thereby drive,nyids SQlli!ilii,eas~.'WIllud. into here is in!eip~ <lISnqgnwL~ rech1llliS.e of die i~lIile,caM~rn, depr'CSsu rizilnglhc' Now.ils h,ydro~ Ydlmvs'!Q1le n~~_ !Dod)' (2U). AIUclOllgh. the ,goodGltico'bSM'MioflSand ~)j)(klts do not im;ili~.y l~iIJIQji'IDluil ystm.~lsood,C8.I1!liml.~ the .~lIitdl.'here s IW !;'I!I.1hs:id!~~Poo ...i.Qtl'! S'ludi(lS ~d~ im'j'i.tiJ.l,d: lIliat :m,l ~.i:lii~I.dl~ng 'li'o'lieal~~Cie:ruptiOli1Dr ~1,)rdioolllGim~:'IJ~ iw.ati:l ~e OQ-J1Iirlb'lllima, berweoo. Iliml.w{!J' diIT£rulal 'I,Io:lcallic nru~C:han1.'i\jlllf! (lB•. /:9). 'JI:'I¢ :~niil;1!!;(Hli f tlls 1'IiIl.l,g!lfl]ilIItc $iU calli ino
~~c

<l. Ill. ~, l'Ii!J.. ~ (21006)_

~"

~~"'"

Spec. Pu:bL 269,

'li,

5,6.

I!l!! Nac1aLed m." Gw.l. 5«. to.rui'oo' 5"1'£'" Mi.. 26111,. :l!~.(~ll6l, . 6, Ii)., fl:lliFl~n. K lit Y:1Iifl.t'iltlr1l,~, W'. t:l.Urnrlllliil, 8[.[[ VrJkmlo1.. 516" .261 {1'l9~. 7,. c..lj'jliI!k~,W. Vlllll~dM!r. [), IDl1lriiiill, 5:ti,ma! ,282.. <:I.M

t1:99s:l. ac.s, P,ii!~~,

)- Y~I!r.:,.

9'.C.

:li!J\.G. ~. waIL'{ti It le.5rriilll~ ). Ge.ophf'$. ~s. 107. ])0.1029' :l!OOl:J8iO!OCli5.t!& (20;(12). H,. Milten<il:~ ,lI'ld rne1M00i! <Ire <lVililllbIe~.~ SIIppMill:~ ""alerial en S,imce OlllliRe. :~,2, fliJter ~1!!'OIilrg~ testS ~ d1O~~ ·to Weig:11 IJUl Gl'5 wlOtil)i ,iJr ilie GIl'S ~M 11~,$.i\Rdata

n (2.006},

'1jiI!i(i~,

S'!l!ilh. C. q, .~temlflif!ll. W. I.. [[!illig', 1~. lo.1lO2!i'.I~006JBQi!l4.3i2:5 (20Q7L Ii'ii. TliIili.(her, !l4 Il!l,!lf'i~a,~l. Sio'<!t(. ftl~ il4itl,
[;1:, 8\,
~\l;

1~lliH~w~c::Ieilf'ii'l'iadi hydrod1('irntli:al

iU~cl

Violunic

i~lo!l&on.

1fliI~ am imJpo:n1lmt

(W~t!~I~.Q('l

fea~i!Q:resaoCro~: IU~e !i'!,ortllenl!,~kljera boundlary ~1!Id!ica~ei gh~yrraduroi:l oIDd. pernlealble crus~~ h lrooks" pn.'widi!lS ,a:~lIil'wa:ys rOrI"uidm~sratlocl~ ('9, Ui).. '\\~ them:fore pm:POiKl tiun lhe 2004i-2006
del1!atim~,
!lP!]ll..e

!;.Qins;:I'fooe~

,of a ~<J!i~ccalde'f,l that

·of

,Oil·
Wa'3

:n.

11]J~~~r,e'!~~!.!c ~~~~~r ~f 50 !.() .• etl!~~ tlil~ wJU!ri~~l)Q ~ !li!B 'im' ill:!! lrii'elJ"!iiM, P,. 1iC~~LU :t,fal" J ~j£ R~·t [:m'7. :lClll!D2.!l'1

2oo[J9.:0oooo2

(2(1:0:2').

'prodw::ed by a!!~poer vok3!l1o cru[llia!1.

1:t~~it'!!lJ!nlil!.5.;1rnd NO~I!~c L It L (rn'ri~i:lifll!;l~JI, ,u.S_Grot .SI1fi'" p;tJf. Pop. 729·G

as ,;1!. c(l!l~!.!!e!l,()e Qr~rdemi!i'!:I1alio:_U!. Mo!t\Gvcr, e~hquake aclivit;fchlllrl!!il_g (he derQrn~liQ!'I. peri~

GG~r Basiln, '\~il!, 1.0 a ffid:ts.un1DtltN:lI~ ofl.~dIr'Ol:h.efnlilal

liI.M1

Nams

nl!lna!!!

1m--

(WO<l). .2. It s, Sill/lUI, l. W, Srall~" t. Volrl:Jllol: 6001h=. F/e$.. 61. l!2:i1.. [:iI.9l."!.f~. .3. !I.. 10. I1lQm~'!:r,Mm!. R.w. llimil f'trm~" s'(·r. 11,7"c '13
mHl9),

]l~. P•.,Mill~n, 0 .•0 .• ~:!J!~IL It. ~. SIiIIi!lord, fl. 8, SmUln, }. G~~.l/.l2!i. 82. ~:n9 t1977J. ]5, 5:. i'Il:Is~([I, fI, lit ~Sill:lllh,G•.P. Wa,it!.}. lIairll","llt. ,(j{l!!i'hi!l'm. t.l~. 1]],. .3:W (2QO~. ]6, li)lmI~", 11,.C. ~S>ii!;'-a~, It. O. f(j!illrl'l1ll~. iJ~flL v.,/o!'tl:i\1d !iii2, ,0147 (1l9~~. n. Iil. W. Vasco., C.l~. 1I'tis~5." It B.S:mi~l. c. M M~f!rttrlS", J. (i.ftJP~, 1I1.t.. 1!12, li1].o291100:&]fI0Ill464J. (-'OQ7). :la, M. IB<iiI<l!.lm~, C.RiII~~. F. S~iJiI'l~ S'i~lK~ ZlllS, 2USI

e.

tl~9}.

955

REPORTS
IF'ig.4. Sdi!,em.ruc: dl!1l,gl'iI!i!'I (.If ~I.ai!!$i"
Ible
IlI11Iii~~ilIil1i'

BInd lfJiya'm1herrn:al

c:aldiJ'ta
bolillilftj\)'

rim

pJ'O-

t'IiIUJI

cesses
~~~~f~

r,espDrus"wle~or 210,00-2,006 ¥e.[i,Qw:sl;,orre addlera 'I,l~ift:

'rfelloiw.sfione 6alrle:M'
I

alne:! Noms: s!llImlden'oe. BliIidkd\OOi ~m~: lI1!iallihq,l!lai(e, ypooefllters ham ()!aob~ h ;!lOM 'h~'M!l ~,dh 20017 @;e:ii!,Rg, Vl.r~f Ill!! 'E!ph:emeliS). Thill! ye:lJJelW areiiJJ slilows ~he ~eismiC<llly 'imaged IliIiIiilgma body iii! F.i[l, 3E Elad_~~~olJ!li'Idllooors I~r,e" I ~elilt~ubi~l ,dilairntiOll" mllunit challlgilS of voilu lifIe" ~lUfl!lllierl Isyithe ,moo!eled jl!ilflatin!Q roiLL Pl:uidl~ el{$'ol'\l'edrrQ~1 IrnJilIglll1ai cry~tl~~zal:ion ,carl Ibe traJped IWE!rrlMUI the n:olill'leJmrnediMe JlCuk1l 11IIeaJ!' lI,e I~ril1le',dl,!llro~e traiilsitio:1i'I zanle'"

..
iii

~k'm as 'Ill!! iBOIl p@f~mtilemCilJI, del'lth ,®~ eaJ1l:hqlll'Clkes (w1:i1ire d:a.medl I~in~l' tn 2 ~~I,. 'ttl prodl!l:oo the c:akl€~QJ l!J.!p\lft

••
-Hi
~i

-10,-2:2:110,
IClllJibiica'l [[:lIUalaUon Fclch\ ~" li'tym'I1f, J. ~~/tI$. iliefI. Ut, lO.!l.OO:'II!~0Ill'5;JBD"D374S;WiiQ'6}. .2.0. U,j!i!latEtii GP'S Ilata!.lllJlij 1JiJ.aIil'ui~ ~~00e Ilr ~~IBI'.l~1li!l cald8.a !IIJlli~ 'i! «iiM:1ru.n!'lg,a~ !IlfS:eil~IHI'iIl.1er 2DIIll ~nq,. :5U. :21L. ~. lIt~mIUI. 11: •. L.. BFilinm,. t ~'_ R.~!lI9, 5733 (119:t.,.}. .2'.2: •. ). HlI!ISi!Ii. R. B.. Srnilh,B.il'!I_ SeiJm~_ Sot_ Mr, ~4 .. 000 (2:004,,, ~" 'TI~i,~ Il'mjeU liIiI~;])eeil ,~(O!ltpef.n;veeffwt 'o~ ~Il~
l!;i'" J,GlJI,IMll:iID II.A, Ul1i\1et5iHiI'W U11i111. 't'l::Il~m~~~ tl~ 1I1!!~!!1Q O~,!:fi.\ilWIy, ,m d the- E<llrthSr::lJ\p.~ f~O. IEl>IlI'ISAl,!liIt<! were IIt'Iil!fided by UJe hlroJ'!e<l!1J S~"''Ce ~~ty as fil'JrI, III 'C~t.-l prI!!111U!!:765,. !)i~~~~M ~I! R f.!!~JIlifl;f. C
6. M,f~it~" g.ji. HC~~~I'• .a1iW;!~. ~trI'!M(;ltem gtea~~

(Mic,rro-.8!,a inl'

22:

~~~I1l,
tl1f,~~

Sup!PD'rtingl Oni~i!ll!!M<!I~riOiI
Wllm'_!;tif!fiil!!rna8L~!!!l\k*DiiliI!ilIll!hilili.31315S5215152m(1

1li!'n,~~l.I!!!I ~i~ p;lp!!lf'. ~ I1mL:!fiil, 5:.·H.yUm.~rnd

1!MllffDOOIl r.!!'We<Wo!!f:!

j!lf!I}willell·~mmiitl1licti\o'~ (!Omiiill@f'llts., 1ti@ ~!;4!~rdiJ Vt.~;'l~ilIiIflIIliPl til!! NiSF ~ntrfi@i!lti)l I)y~:mic~ ftJwg~~rn. '!If~m 1II!II,~tlM~l~,Zn. 'Tin!!! ~Mi
!BrillMf! !'~~II~J;ioo.

M.!tmal~:illi!l Mo!ttiOi!l~, figs. 5:1 ll(l sa fablil!! Sl .alllil S::!~ ~~r~fiI(~, 0l,1lII ~~ :in. j!J f)!! 2:00'7; 3[{)!l;plM 4 OctiOllef 2001 1/0. U:l~I'Hie!l~I;i.ll<l,(i.1l:.g2

IOlbserv,atioDI of Ilhe Oln'8,-IOimensionall Di'Husion 0'1 Nano,mei!e!r-,S:iz,e,d Di:s,II'Dcalion Il!DO'IPS

[li:sl!otatif:aIlIS .alrll!' uili!qulltOU5; lillilear (j ef,@dS .andaJ@' repoIIII~b~'E! for mallil, of the IprOpE!m@'s lof !l:ry.s.t.aJllillil!! mat@rii!l~. :5t1lJ;iJies 0111 th~ 'g~1(jl! pr,eC:e:5s,o,f difi~Cll[;a~[lllt!l;i\lil IbllliUk IlrIiIiterial'S h:a!\li8i mostly 'rm!lJI!led '01'1 ttle flRlipOnSe Ilf dij:!illioc;;a~ion5wii:tJ~ IIIlflnlO !ioopic ~ength!i to !merll'l.all~oadingow 1J11il101lidliililgl •• ItiS.~iIiIg ilil :!iitu. ~rralil'o;im5Sionl electmoll!, mkm~mpy, .1i\I2 .~IiI(I,w11111<1.1 1iI.<lllomel!er·.!>il!!ed Inops '1Ni:l!ih .[1 BmQler!> vl1ct,Dr of ~<l1lU>inl (f·.i=e c.;u~ !liln:riellig'i!) Gill!e·dimE!nl;rnOli!aJ di~ril[l~io,1'IeV'E!nl~1iIthe: abSE!liu:e of stM$5iE!'S 11,~t arlE! E!iff,octill'e i~ d'U~iIiI,g 'the kloP5~. ']he loop s,liu! d~~lliId~'!i!ce ~f UIII'1I(1<op diffllll':ffivity !obtgj~noo i~ ~~ij:Jlai!i1,ed by 'the s.m,chaS:t1)[ 'lh~m~ln!;l~~l!jati(lfil ~.iilthe !I!!.dmoor'S (If ,dl)gbt~ k~~ks.. ]Ie llilam!~~ <lnd Iroo-wtne::J3: ,()ifcr",,~laUi,\'e nl!lte:riaJ~ ·ts on~ng\llivemed byd~ genef~ ,aNion .!ud motlon li ReM def:ectslemleG disloo!ltiOflS (.I). PuieviOllS ~~Ilu:lieilm~ldt~ gliCk:

even und'er ;z\:ID ~s (.1-7). 'rb~ Ilhen.'Il;lln:m.o:n. has also been eexIUl1I:illOO t]uoorcl:ioaUy (8;-JO). Other OOn:lpILll8!!.i0J1:ai and ItlI{\(Ilreticals~ud:voo lR1V~~'IW1IVllld~1It dl~ loop dilf!.l~~n pla}'~l1i c~niiralru]$Ln.dl.~ d~gm-dfl!I;OJl p~~~liof m~ ci3.ls. fat I".wd~ li~lQn~ud lIuClear f!,!.;_~(lIIfI. lUiX'D h,gI1rlell~ parttclei rmdllli:io:lll {,Il, /2), iOme M:D study has sho\!!~ lIllm! iI~e b~gb'~y dii'\IIs:1,¥e loops whjl~ b vahv.~s of 'hrlll]imlfl~Pc, wbic.h ELlie ~flJner Ifi!HliUD. ~:t4 rnlllfl. ~.liJdli3j.lil.e:mr. can ba regamedas bundlasof cro'\:lldions W~iliii. [] ~.I[3.il'[.1,'l~ (,61, A COO\",dJ~QIiJJ is a.kindefa '$~If] hl1l~rn~tblalmll(H)j l~ ~~a!>Oli ]o:ng-Fan:ge WlI~pressroH~rnin fiel!d. in a c~.ose~pacled.dir:eoction, ooc[ ilts center uf'mass COil easily mQV\e0I1£,~
dilllQlnsioDlall:y

~lf:.ljme!Sl:hhda;liO~ns,. wllieli! ,~ prodw:loo' l!I~ ,~~e~~ic parlicle~rr.adii1!!ticm, in the s1~.pe ·(If disJa:;. ROOfllI1 l'DlCilooldar dynamics (MD) Mll::u· 1;i!!1'OOc:.<lS .oil' dis;IOOi!Iilicli1.~in hl!l~1k l:ttaanu'iia.lslm.ve Imi.fi1lJl ho.ve ~:rowlll th3l~n :Im~mlsmld 2I.t!oys, fOC1!lSoo 0.11 the ~11SI~ ooF di~looa:~ioll'ls 'wiil1~. (()I;lmn)~ly !mlaJll. J1It1l'lrnrilial.•l)l(;: dl.&loesliora.i(mps: '~naJcroooop].c !~lngm~iI:i; i~O (\f:>ilililil'ud .Ioadnl'log or wtfil~ d!am~l@rs ~:r~: (1'Li'I1~ f~w n31tOI:1JlIiillm1lellIl a 1l!!n.lQadi!]g 0.2)" O!'l me Q(1\ef' i~!l!!"!~ it is: kOO\v!~ ll!nd~~ fag" (lfle-di:r!'h:msio!ls,] (lD) @:Ii~ diflb· 1!1Il!a;! !1:O'!!~6Ca!e·dJt;sl'<H:.:ali<m.!'lca:!'! b~ fO!lMQcI as sionv!'! lite dl!'Gc~i.Ql'I :f 'U~eir BlII.'lcrs:".eo~!Or, b., o

···

b~ild.I(t.'l
tiOIii..;;

8~.o:n,g tbe rods. The c:ro'\?i.railorl !by the: !ll.l~n()StiildG~~iilclr:n~. ilmO(iff 11~~~OOi:I.~4..'il~ijf.mt!t'lro'l'."{]io:ITlsaIMg lfilmir
i~liVC

loo~ in ib!.l!lk!'llllteri1l!L'il by the <l~8103i1lJmlro!~gf ·

~op)'. OS,;ikaIJnl~er~1~f' ",·1M!l'In09<!ok!l". ~balr~~i. O~~;) SG'7"QoO~.7. Jap;m.~lile'P'lUIni!'n! olM;iluiOil Sd~ll~i~, Shi lillian!!' Uruil.!1!fS1~)f,. 1060 Ni5I1lk~l'Iilt5U', 1'!.!I;3~ue 6190· 8504, Japa ru, .Jllimillll~ '01 ,p,Mlidiscipl]rua:ry Iill1'jllNlri:hfJo.r ,AdVil'rtQ~ !i\;neri~l5.faihel!:!J1 UIiIWllrjil!f... 2"2"1 Ka[~hiliiJ• . ,l\l)ba·ku, 5~rndlli 'fB~NI571, 101 pan.. .

or

1Researclii O::llterlor

iUl!ra·1fjgh \l'ol~~ Electron Mi,CFO!~ t

~To,~hW'l corre~oo!ffl~;e )~wldi be iliidrEi.ied. t·~"'ilt ar!ak.a;\'jll!~@l!Ili~em.osak.al·ucj ~

9'56

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
of l!llg. ®~MdiQ~ ~OO%at 450 K .utd 30% <it 700 K.. a~UliOugh j]i~ .uoout1·CJf'CalO:!tls :tG.• $'eci!lii;ctri i5 ml1y 0.8 p,plW ~umlclJcs5~lO dllT~ ool~iJiii Qf''c:o~eilUki~ by ·weighl. (tm,~e :81) {.l?}. We ex;rurnin,ed dK':n:"lOdes dis~~tions;" \\ihich IfiKWe I~e .smngsOOC:l!LfleardKi (l~ti'!,iClmlOthn afmo:mlS ruum,1d.lffile oore( I),. ~n. onllileln(l~jo:tfltJf al.n}()stus:olated il1di.v:i.dtt.a:llOOpl'! {lOil.U:'a5I, ~oops larger dmu cOO"i!.!dio:tlbllIlldi!esaJrl': .abow 7;, wbC'il'C Iille m~niO;li1 :fi:aotirnl U'KI!ltolmlmts· l.y~U!eroas('l!>\vith IGn'lpeGm~rn" re..gard&l'da...t\'l [fil(\! s1f1l1~!i1l ~ooPl' (if the ''\oollfv.emltmnal n~bc;I~.v~i;'Ir· ~f an. a!l1~tiSOil!ll.ed loo[p' iii! di.~~~~" Hm~vt;I'~ !1l,lCh ~t::clidl.njJ( ~l:)W my ~~OWrl i~Fi~. 2: .ami If!lOvle Sl, \vhich ~I'lbowliI'!,H:lI svgnifi.c..'trIt :~:I(W~~lIld~ d~e 3pm:!~~~;l!~ by ·dl~roclion b. ,of MUooihe ~oOflm!!QsOOQ!~ds (6); !b~lOre, ~~elr loop perfo:!'llD""!S l)molior!~"lhe diffusion .~ is diffiictiill\l' eX!lln~IlC by MD. ~llIre JA shows: iilllelll1pOra:l ·\1.Mmionin Iilile m ~n CO:l'lImSil, ,e.x;pcrhlitk.'liillal siUOOies lIISiililg Imll&dl$plaooCriilCnl ot' 'dICpo!>i~iO:hlof a. b::16p,.obtained .by ml.'la51i.lril1lg IJllcoemrn- of :~1:lM!l of Ith.c l.oop ~nissi01fl -electron. mii~oop, (TIM) h::we shown, iniil.3.gG: j, lume .st@.p,(tf 1/30:!l (AI) (/7) .. F!gilIfitl try I~hal. ttlrlOOll~r.s~ m ~fl.ean perf~nll'ft.'Igltde: I~ l l~i(l1 (14;,..i,~. H01.M.\'iv~r;d~~~1ls \,,~ (lilly ,~;1!i3B SbI)M,its:Wl'Iwl~t lrnng:fom. (i 7)." F'OII'(lOlt~· ~i(lili. ~1IiIL'; t(lnl~raJ 'i,1.am.'lti(m !ItO l D dish1l I~ve mlcllbtil ~'il'I1trt10tc loo;plflliJl~Jfl '~[rlot cilear. Vic· l!..d ill sill! .~. Ino l!'!I;iU]l~~elhe !lQoHo!~ pl"'ccn~crU ·of a pm:li()~e perrn~h~ a :r<tl"loom I;i!lrociCSS of mmO:li1lcD.cNized II_.,( IJ I) ·'oQ1fl'VCm.: walk "" 3•.2'2) w.ith. a IJlIlitste.p oflblwillii.ollJu II IlLy l~tOll!<1.li" ~JlCf.lS (>5.9 mu in djruYlctcr) iu {It·fe ·w:[~~. Impt1illg siws,. o.blail1cd by Uletic Mm'tC, Cuo {wq siili11U~a,tklI1 (J 7), is s:1jlOwnin.M~ !illA; ins lfi1~wilyoil" 99.998 \¥cUgltD% (nab~c SI) upml. hcallillflg ~¥!GIJ~ Ir'a!liI.Sfr;mn is sh«v.1il. il~ .lig.. S2Jt C(nllpat'. liinfld~ Ilt~ ,~pttcallOI1l oIn!) ~)(rufl1lll1~SImSSmd lrIl~ligihl¢ ImlljL1mba[ sw~~s. O!U" study tV'.IiIIS if>(ll ofF~ 3BIlJl.d S:lBn,'V~ d~l~uiEll!1:LIic:alt~ fig. :~lot~V':;1!OOIdi tilt;; rMll)wi~g '~~l';nli@!~ b~l ~11liby d~if~t."l~lo;;i'\t .un. 1Il~L]; ~i~lii..:rmqut.'IICY :1iL,..,£io:n in Fig, n:~so[vccl!~,estimlS~ eOlH "t\]!nvcntio!:lal" k!ops .313. 1111.e~$e defect 'periods ~re atmbuled Ito Ille IliIudcr.go d:~ffllll:siQI]? IF Ua.ey CillI diftills;e,. liOW '~PI1~ng oraaedl.i8l!ocarlondm!oo~es; rille loop high is thdr. di.:t:rus:i\!~~:y·! olW d.oloo,ps t111'tci,er'gO by dlSJ~. H s.t!1tic ~1~pl.J!rily ru.n1l~S:(1.3J llUlInQtioll of a loop dCi~mp;ped frrnu a 1~.tIed.ifll'l:l!sk!.'Il? Im![i!pung sil.eis slow eitcmg'h to {\blfl'lblle 1m:;: ~ion VIle FrfOOll:~.~lWO' kiIDIM ofexpennlus: (i) mll~UilM~l of I~h~ d~~[()e of tll~ l:i!1iotl(:m '10~ tiaOOdoolM'iIilOOUNty •.·~BIIl. \~th 11lilillt'l(\; ~r~(lf f_limlof ~oops M '!~.\pilrat~ and liml:l~,a-~d{ii) exarmnatlom 'Ow ~~'.':lor of alnrosl iooialDcl: Fi.g. 1. 5dliu~majc'Ll'i~ (If the obsei~~ ¥ilflil DIll! ofme:1D glild:e: ·rlIIl!J,Uicn ~OO,pIl. Figure 1 ~l!tow.sdle c.xptXinlclllll. ~!llIP fur rnill'l!mmet'!ilr·siiHl:dintl:HeS.titi.aI~ ..typEl PI1:li1" 00tllI. ,exp«illllQli1lS:( ]'1113sttlfaoes otf iI1le 'l'EvI ma,tk !perfect dislo~a:ticn ~IlOp Iby Itthjn[il~IJl\M.:.'1i'C at aJn!lOSt (O,]~) soll~at \W {'(lulrn, set sell(l(tQ:l1l~.y l~ops whoso I~ \!'3J1JU£s [1 ~.I] ,fl[Id: IIEN"- TlhE! relli rifig i!:;a wo,. llliii! t(~ dilrectiion of tliie motiol1 ·oflh~ loop n~: Va: I j) "'\!tire 1illlli1Qst pa1lUe~ 1:0 :Ihe $UjfJ~ fnr 1~1h~ e:)lillm:l!llUL-oil~ ord'lei:Je.hilv~o~ (j,tr ,Ol!~moot pa~dJllel to, i'l:s. IEl!iII~ger5 \lector.
aJteij. T1iJ.Clf!nime:it of tile iJtj():riOi'i
ru

I!l. HiN!ce,~o,ie cali" ~i!!.¢ wl~i!l~~ !lte lw, !Jinde~ tbe dirrU!8tQ!~,~d1 '!.VC: ·WiJi.I1~!i. ~re m !he ~OOll diffiJS~'!,l~!)!'[;¥ ~f1erGllow~~~gp:roooduN:. ~Fi,gtlm 3C sI.'LO·W5 UIiIe 1~1t'ie (10 d~;iCII1dern.oea:f 'lI~ in-eai:li~Uare d~sp~ooC:b"nlimtMsn(,~, tE~elml1ll'L'of ra1 v.~ri(l!l'l ilil.I1i.~·] D cli'W1300l1!1~nt x = :q{i - ]). AI] (i = ~" _<, .r.r)durimll;!: a slUIlg~~IYlO!liom per100 2,.• (8'1J:i3J toISOJI,57 ~)I .::h~!l~OWri if! !F:~&,lA.

Here, MSD' is calcll.!l<1~ed. y ihefollowh1ig eq~b ~m~l_ijool ofdler:ea!l:tziIj.QJ~ of ci]Pdicil)'

ti{1InJ 1lI111dcr ~e

MSDU' ru') "'" (Mi' ~J) _,~W)]2) .= ~

n-J.I=~,

~(x[(j

+ ;-·1)·Aij- 41a -1).

(j=OIL,,)

~]}] (~)

:F£_gtlre3(; slmws Idlilll: MSII- is

3ppnli!(.i1n8lle·~y

propcbfl!l)uml to l; h~, tb~ loop oJ.carly um:I't'lr" g~ Bm\MI1i.:1lill rnt{:!liQn Or :rn(l:~\11diffiiS!Olrl(Jl), \Vc ~Dinw~ IJ Iil.¥ :Ihe ~!;la.tiol~

cNcluding

the period dnrinig wbicll~ nll.m.ec;:or" reiatim~effl1:CiI m:ppe..'iJ~.Fl~l!lre 3D ~h()i\:VS the: tempo.m]. V:ilriilt~Orn1 il~ the clI]ffll!l~i,.ity es:limat~

.or

In

o:r"

rr~

]sdl.u'odli IO~iS, .By ~i~ Ilrooedlme.wc mi ni:1111 ed! mille force .Ilpp~tedl ontod~e.s>c '~OOllS a:lml,g z 1~lIiIeir dif\C>Ctio~ orm.otim~ f:rom. tl!llc slJ!I"m:c:cs. ]u I~lhe c;.:amlnatloiu. of the bcl.l:li.'vior ·of ll!a:niO~t~s;o. ~aOOdl ~ili,O'Ihejr i.lnrotllfLl S'i!rossLlS W~ a~® l~dJuoocll[l) a [~v~1ail."".i~ell Illileyooll~d. Il\,!It ;dillct 1~1til~loo:p ~!la"",iL';}Jt (i.7)..U:Siill~ RJlJ~ i\1J'~mn~ilfl$ d:llal saIi5:n:eI;i, the above o.m~dil:iCl~.we· o~!'Vedl the I]):rqi~c~o:n the tooPII;lOliO:I!l on~o IlliIIC screen at of I~~ompemtllures mngi.liIig. ftoon 2.90 !to 700 K.

t~

oocil:>iMaUy c(;(liIibiffid.iD

lTrKJi~ion. The

d~CUl.c:knce oftlte motBoI~fmctl(!l) aFIili'mlo<ops em ItemJ.~Iw:e and IiiIM .kll .silCi'i.'ioiml f\E} :$] .and: moyi~ S'I "Hr::r¢, Il]~ 1!L1Qfiiolil. &:-~Otl i\l dl:l:~noo .1I!!l Ithe mlio ofl!le :ru;!!R'!betof !woving loops it(ll Ih.mor ~he vilsiMe loops. nc "liilOOlte" ~oops OOC<llllit3 inlloobilcoolow ~450 It (lIDIcaIlIillliJlherelbnWil: Ini(}j~ ttllllW~ .r~) Ol\OO 1JI(\l Sf.i'llcim'!lu it> h09lcd1i ito a ItCol1'if.iCf:1r~me 3bo·!"~ 1;. Thi ...s.tI~1s liIlIaI~. 1lL'! 1 COl~
InilCtl aU:'ii'!iD:>~11~ (/~) of d,l('i ilu~niu.ail ifi~iilri~y al:aiill\l\vflj'hl~~~k diffii!lSi.vJ~y-."ucb. as: (:. mId N ( J'9)-i!lmm'ledi.illIDUllldi'fihe ~~"'he!l O'!PiProa.cl!~ ililS T,;, OiIfldl!111eO1l!1I~OOfl1ilereroC:ks !he '~ooJllslJc~ow T~. eqlllil~bn.lJjrii1 Co:tflOOflI'mtitOf1 of mile in]ipun~y 31millS.lhlltcm:unl~ 'd~c!aUl.losp$lelle ~s o'bminoo lJ'yl~he Fcn:uaj··I)J:racdisnribllDi01fl fUlIK'lliol'l (10). For cN3m,1lI1~. the birn'ldling ellergyliJelwool~ :'I. f: alfifil ~nd an edgedlisl~ro!fl is'~I7eVat iI!I!e!~inlll!.!m VI). 1iIln;:.~ gites .a.reoocl!!~Cllbr . C al(nrlslI!IJ 'W

F'ig.::t" '0 n~·d1~m!ll'l:si(lllil~l motiollll 0:1'an <'IllliIIIm;t wso:~1il:edj

~[U1]

moop art: ~H5&(."WiI'e

lobsE'l'\fi3ttion alOS ~~ apprll(!(n:.. m:alte:~!iai[!Clng [!O([ll]. .. th~ ri~ fh~t::ti(lnlgd 1'J;~t~d 1Sg= 200. TlliIe .(jijiam,&er of til e WCDP ~s 5, 9± o.:~!lIIm•. A. loop <I~r:nost 'oonltltii!~:I)IiJ~Wi'Ilo~:sill gi dij~ r'~m(lililIlPilmallel. to its IB,l.!f'llF
'B1f~.·v,ecrDlI1 •.

ne

--

--

957

REPORTS
anile t~Jjle~if~ fCr\r:;n'li,ai ·of MR_lllIDie drop ill [):II&chn'i!'\g the fCriod iimrn mo to 4130 s is !Ilui:bl1tcd to dle {door~ im~ oJ dil€: oorrenth~~ji1ig symC$D (11)., By exl~:iaJiii:t;g, D;';lil I~:O -= 0 s:\.Vild~lhe ~du.'>iQ:tl of t
by ~~ !!.U!blrad~li, D.ublw1ead eilI;.'Cl of Ih~ ailliErll]1~i'l. !J.W~iirl'laUl Idm :lMi3l ~l3!I!l~ .lJ to '~ 50;1 :;!; 0,4 It'irnr~ 1M. 3p·of IProprialJ";~ i()!fmi~ p:rroo~~b '~in:l!l~ D t"l a..~ll!!OO: \VI~OC! lIli5 ~roooch.!wl': is, lod~~I!!U (!Ib.tilin~ by kMC (rI:g:.SM),il yieldS <I,,rilllJe of D (49.5 ± O,,41:1irnr!s) amlosli eqlm~ to, d~msellinkMC (fig. S2, f;WltI [)) (I7).
Itlh~

~mptmrll.!itC d~deRoe.of fusrimil,

1<Wi():f). Flltim Hie slope gf dile H"e,si~. Pig. 4A, d~c:va!nes of dle aCl~iva:lnon, ,eneD'gy oorlooj) difc.
,11"

D ~tid~ 1\ITI~!~illJf

alii the
COI'!1[pO~

1~.Y!moor of ,~el:r~ilr~.¢t~litialaLom~
~

that

are'esti1itl<l~ed to be 1.3 eV" iI\dq:i,e;ndLl.1tt1

"p~~oo

o:f~llilel.oop, slse, w~,lh s'nSitist.icail d:LSPCrskioi;1StJeSS dllm~(JI';~J ,~VA ,Sll1'1pl('le'~b'apol.8Jli'CliffIJof lIDIi~ si~ d~:~ncl:enc~ ·of'fhe Evalu~s (l!f tll~em'~!.'di¢tl OOF!tW~eg[wl]~ll w~r~ c:a!ll;;:I;IiIw:~dIby !lAD 1(3-7)]
10 ~lI1e~~e!~ItS'e ofihcsc "'oo!!WC:!tl'ii]~f'loo[Js s yiel,w: E -< 001 cV. hLdepend!ool>onllle size. One of (Ill:: or.!l,ins ofdlC dr:as;I:ie s~owdown in "OOl}' vcll1t~mfml"locp diJlflL"~O~ is 8i111!ri~u;~oo almo· 'liCI

loop. N, obt1!itlcClifor E ~ 1.3 eV, is sihownin, ffll. ~B. wll!!re ,DoI'llOt:I.(}ID:I"iO.'l.IS.~ydk:~ ereases with ~jf;'j~alring .N: :~f e. iiiSSll'llne tflULt,it w flOWeii:lai'W oildle !f.,de;pemcDence ·of nl~ is esI3hH~'tiIoo, WL\l ob~'tiIn .D,n:;;;; (23 ::I: 03) x
]O,IIS /V(l}.:ro;!; ~,.OO')

(rml~ /'il)

(3)

111(1:II.emperarttlOO de~nd~lloo of D 3nd lIS ~~. s~ d~~MI:lL'l ~·~IitO"Mlil~ Fig. 4lA tiM):

:split~M'I1:d!r-aM]mg •. as dl'lSim~d

~~ow.

TID.(\!

d~[~n~n.e~ ·of lil~illJ p:~ ... pun!~li.SiI. ~

factor, Do.

T:hc ~oop sifz;e iltdepel~d",m:le of Eimplics imlml ~_c ~oop Ul1;QVCSinot b~O'IletrnmlitiU!l 1l'B~C PeicrJs potct~lfu.l (J )h,m ail O!li)!ilal~d as a whore, bl!ll by I""()rttling amlll1ovuug, d(}l!lb.h~ kink.~ (1, Z).. 11.]~

P~~"OO tJif d,oob1.c l!::i!ilikJil ill ,<11 loop :ha'lbG~1l met~U(l",ed ~r! D :S~l!!c1i~ (3, 5) ruld. 11. d)r;,'Qr~tLca! M !!tudy (UJ). These ~cl'~es relm:e the or;igin or Ii. ~C! 1I!I(~ki~:iktpi1l~ft:III.ul::j].c,a~icl!l1 rocess. Howc'l,iCr. :~III p get1:erilB., (he ml.o-oQfllroUillS proeess aif dlislOCl!.~ tiolilglicl~ under low ~s I:s nO~. ool:ibl('l-knrik k:iu,b p~!il~ at (h~Il'l'!a!~U1i1ijb.vlill!nll U. 25), [11 ~!JLse to 1O'W ~~. ®!~~~n~~lric wilh ~~pcCi!. I~O' Ore cel1!!ml a.'!~ of tIle~oop.dl.e disl!occ'lmion velQcltYlldl is 1r1>lp'l!eSsed as a fll!lnelillll. .(If!l~c'ktM!: 'I1elooi1y ~~k (fig. S4A), (.1)
nUCICllli(Ull bi,Qu:ti!(; skk.\'vise

lfI~otliQI:li arfllliliil (01).lb;l~

lB.' Wi :1:: ~
!

'100

100 Trm~(s)

wkcre ais th.e periOOi for ~ihcfcierls potoo~al ,ami Ck IS tbe .equilibrium !Qm~ael1h:ru!;i(m of311 (pusilive m~d liLc,ganvc) silngllc links mn.d.isa. ftmcDim;lof 13k; lI~e fon:lli8lion Cl1crgy of 111kink 1mdl'e case: OrOle l Silnl!lID].d@J]-i~ype rehmll'l ~ltifl]. 4,m Ib~ ~~.~btelllil[mli'llture-limill.lOOoomes
2.-.~21tEk e:.\'P (., 8l. ).... . c~ :;;~, ==~. '. ~~ ·I~l,t.. Iff '. kT
OOI1S1)!IH~,

(5)

W'h.eN ~1.1.is krmk 'W:~dl, k is lillie ~J:oJ.tznklnn. 8:IilQI 'l"isabsoime ~~lil;pe:uature (2)!. Equation " ~nd:leales IlihilliE. 3. dis!ocaJuioo Il!I!)'iI!OO by a ,d!Jsia~:me (It'" d!!!~kl 'Ih~I1~Q.v~ll,leJillof [;a.cll
!dink" ,\~iIUlavemg;Lli :S~1I!dn;g,()f UCk~I.w¢~n. ki!~~s, llBl,enn~]k;i~~:~ il~\:fo:nned as; dk.D'~b1e kinks,. :Saclrwm1tll:double kh~ks" which 'OOW{ll!llt

B ~.'.' '101''',
.....z.

~i!

~! . '10~~i, !iill
'iijj

in the directkm, OjJlPOSitcfrmw, ~rnH~d~UQ;l:l @r motiou ofdllJ~ d.islocaliolfl, 'CMl$ily tlind(fligo m;!lt(l3]al1lflJJ~bilatiO<lll by 'linG iiilm'C$S; &lllC~, lfih.~y h ~'1llill.nt cffMt1'V(::ly ()Qnlriibli!ll!tl:!.o tilL'! disl~liom

gtid(';l.. ][1 l;onim5t,

"Con'tOnl!o!l!llJ'"

II!IUOO[Z~l)

:stn;:s~. 'Ibol~l

ba~k-

!'.U,~
'ij

ffl'I~

~ops

·a~t)

w,ard double kilr!ksmd fon1l'0lt·dj dOl!ble k~~~ks alre present :~Illhe same 1I11I IJioor on. <I.vera.g.e (fig:. 849)., ~~.dl~ ease, the drifil: vdlocity of line dislocau,o:1"Iis obvioi1ll~Y .:1lrn'O;. bOW,(,'VCi; rhe diffilb... i.v:ity ~ d~~l.'iri~~illoo Ih~ ~ool.1J.'lSljcth.ermil~ by l]ucHiillion. ~.nIfiI[Gl dilim"ei.~i.1i2 IJclnw~L'iiifI tliem.in1beflj 'of f{"jln.V31ld! do.ulbl~ k.[i1kSjn,rr~amd! 1iJa(:k,v'Ind dOlllbk: I:\:h~ks, IJIl

1 li
ClJOO15 OJ061C1 ~HI017' 'lOOt 8 1nrern~~rel '~1fK)
••

'10~~; C-*'"

I .. "

!M')

(1,001.9

IL

'10~~-r:-"""''''''''''''_1'''''''''''''''''''''''''''''''''''"''"''

1 10 tlOO 1000 ~(Hi)!!IO' iNuiffil~illiJl5liIf-.fitor:s.1iU13~~IEllilfi:!i 1m lI!M,p

IF'E!!!.4. D~]1I1L1sMty or .tI~mQ!St m:soWate~I14(U'm> loop!> .. 'WI Arrh.erliius, ~I~~ of the d~]mitJ!>i1JTIly•. Mat.ooili19 ~ymlbob c~!iIlie,s~w~dw thr~~!i!'I~ rnQO~ w~~h~ rliarn'ru:!r d; Th(l! d~rflJ~iivitiru:I}fi ~arb(lfl' aflid !i!11!!liQg~,~i!'l ~h'~ Irnafil'j);, (19) ~re alsoairmili. I~B~ RtlabtOrllsh~p bl!&.iE!'~1fi he p;~~el'ilHllji'ltiliti~'lril!Wlr of ~he t diffu!§l,vity <I IIIdli til!!e .l'Illllililber O!fSleH!.i:llltelr:s,~irialt aih~il!lil"l that CClilililpl]"Ie ~lCh loop. The aJd'diI:iOiIl'il,ai~

l~Si~m.d Uill!~~sa ~Slutt

ro~(fowdioJi)

bi.!:lild~~ ,obta!ij!'!~d IbV MD

9 NOVEMBER .2007

c,gt{l.!iI~.aUi()!iis (5),

9158

VOL 318

SCIIENCE. w#w.sdenaemag.,()1'9

REPORTS
where Nd];:. i.~ lO~al ~iI!an~$ofd~I!I!Meki~k\t d]e By .a.!~e:xle~sion oifE'!. 4•.D us appmxi:li:mlooas

~D difl1'l(!sio:~~ve~ ~!] IU~ea~!I@ifI~ ·of ~~

d~a:~

(7) WIi!.eN~ l. isihc IOOlJ-linelefl_gUl !lI'Ldi D~ is t!lC :li::ink dj.fflllsivj~)'. Even wh.cn. N,fk <. l, j]:1~ ideli11ic31 re:SlJll is Obla1.ned. (1.7). 111C power of N redll:ocs tlfor ,ex:nm:n:ely S'll!tl8JU .N 'bccalll.se ~le 3:ltradi'l!',eil'oroo: is 3p1:'~.hl:dail. twoadj:ilccll1l kinks of OPIPOO~.W: .signs (2).aooLi~~ti!Jg i!IiI~~Ji)~ioo ~f
!'lOtil k:~nk.. so thM UtCy OOiJJ]~ l1~b<l Si!~fi¢l'; thLl: d~~lcl'e!l(le· {lIrD\J.OD'! 'N,. ail obmailloo m lh'e I;lIlrrescnt:study. l1~e t·eJ:r:upcmlure dcpeu.dcmliQC of D is exprc._.;;soo. by jhe 'l.eu:irUDk in~ Eq. 7. .lJkUS ~ oolflunlk:d by lbe(fiQggedimpuri~y ;a~ilfllOSP~ere sliIliIll!uilldILmg 1iliI!3 dil.slocauQ:I't The d~ing Slf;~

.~ ef)j~ti¥einWivli'i.g~oop.s, 11~e-sefiWicl!~~gs are relevrun fOE Intlep.rodl(1t[icm oifdil.elife~imc:: .of mdimion ..l<lSls.um1 IliUlleri:illsfmr .nucle:llil" ~fis:siOfl .tmd CiUifjD' sys.tems lil1 wldeb Id~il:tli!.Tm!~truc~ure.!! I ~ (lQ:illImII~ by!he' [I[1()tron of ~oops famMld uprm 'hi;gh.~Ifl!'i~partic~~ ijttl'l.d!~liItitn~.hi! addilit!llJ, d~~<; ~dy (Ip!):Q:t!) up ~ f<1!I!]l\'!'<liyfo.!f fi!J!1h~ ~p~. !l1en~t i~vestip!:~o!i!: 1I'!'eu"res(lilv~ d.YiV!~~lies of of~lm:tlely SII.ull'l :oo1;HnlmtL~iail !!i~lllcaJllple:xie5..
I:IiI!:f~r·l!rllll'l~ ~11I:dNot'!I!'j

rs, A. It. ~mllll, Rtip.Olll M rllf!. S'U~t:.!l til5tJlflh ~Pt~ic.al OO~Ly, ~~lKIlm. 948;}, !Po .~o. 1 19·. )II_. It lI!rd~r., D. 1r4. Be~ers. AIll.a Me1o.1'l. :L~. ],65.9' t1'906). ~(I. N,~~I~ f>f'IX;~Y~ .sg.'_8 6'il', ~.~~ U% ~~ 2:1. J. tb. M_ II!! HI!!HCro. Sr;1.id Slim' Carnl'OO];[ l.1, ~.~;l
(;197S)_

2:1. 5:.. CilIailmhm·ll:1rIa r;, .filw, M~. PlIjIj...ru!&.l!.

(:t9H).

Ii. ~ottf<l11, Si L [)lldaF~v:. It A. li'orrtU; J: Nud...n.1ImJ!l'I' •. 3:2:5, :1.9·S (ll)(M). l~ .. r, tJleUI1iI<II1II; fJif~'on ffl ~1es@l·~' ~5pri!lI~el:,Bentir], ~~.G. G" .SicIooO!!~~, j n .Oi'ltoc:aJ'J1fiIl5: .1Jl~I!ljIM'l:. F" R. N.. f\laiJani!ll 8tt. (N~IHiI(JlIlImd. Arru:Ml'oai!1:li9:30l, ;,mol~. j:ip. 6,31-1.63:. 2:6, iii. Y~lliflll~, s, Morru:~In1, PMos. ~.2:3, ]167 tl~i:l}. ~:l j!!, It CottJ~l, M. A. jlBiI':J,lcl'I. ~ Fl.: 5«. wmkm Sef; A

zs,

1')9~,

1. JI.P. IHlrn:I~.1. lliatlli!, ll1tmty.o{ .ll'Jdiil!"m~M~ ~11l)\, t.I:e~1i .

!f~Ft19S:;n. .2. A. Si~t~r. F. S(lt1nH~r,~I'I:M~JCGI Jlm'JIlIj"J,~. W. P. 1!.liI~>OfIi, lEd!.1'J\ir:;a(fe1Ri!; P,r·~~.New li'ort.19&6). 'la~. ~. ~rt A, lIP- .3i6,l~Sn 3. I),D. Win:h, G. !ii. 04~II>I:·, I), r!~rwdalij G.. l, 1~!I!<l~ l. ~w:l. MIi'I~f; ~7,6 •. 3:3 (:lOO 01
4_ N .. 5~n·eda. T. (I, !)~ IE 1I~b'i.<i\ .Pniif$!.. Mag: A. 8l!L, 331( (lOll!). ~. 11.l!1alhro {jJ <ll~ Phyt. illeir. .B 65, lM1ID~(10012). 6•. If. f!.I.Os~~~, Ill. J. BO!Illln, A S@l\j'~ S. N,.• Slifigill..

2:8, 'II. I_ A'lsl1i!~ V. l

!!i;iI'!I,W1!mN!9t

Int!e;jibcjjj~

ilii llf~a(o!'ijmn~.m S&iki!l,

applisdlonto a~~mt~(m bydleatm(lllplm~ is g;L)u;I~~.ty~paIDI:iOl\a1 I~O tI]L;lW:L:,.r~ily of 1It@

du.l~liOlflj\!\Illi!(!l~llhe: .;.li!:il.l1l.here C<t!ll.pro~'!pUy

fcUow ti]e disloc.~i(fll 1110tion (1. 2li. 27), If'!JIfC set t!~e propor.tL'OlnaHjJ~y faator (0 be B (2·7)., .Da.. can It! e ap;p'l'O:iLi:lmlled ·\\f.ill~ ~llil(': IIlISC {If EillS!C;iul's
Iro~Hliloml. (22),

!i. I'. 'lioliJtiml', iltMI«..""la~ lB. 6\1 (~m:~. 7. I). A. 'I'·eir~ntre¥. t ~lerb.al fI\. Iiioo, PlIy:I. 11:eK B 7S,. W41(!1e (jlloon. ,B. A. V. B:arOi~!JeIl, ¥U. r.l. :c)~e~~.~. lIB~~r;J~"i!!t!iI~ Mag • ..II a(l..2:70~ (~oo~. ·9. ~_ IL [l1Xlai1!~. P"r!. l1l!iit fI.~I"i .•.l:2)l.lO:5. (2:002). ie, t::. On!5ii.'I\ia, f" Kur.arr:tM1II, 1'1:w.;. fillN. B 1il. O,).;1l1!.o:s
(mM).

F Il N_ ~lft;jr r.o,.~dl [lII!IIll'1I mll~ 001, l!iJriSlI~rda,1lI\, H 19'·6~l. wI. 7, p~. 11.3'-[1][. 2~9'. G. rt Speich\ A ). Sdil'«l'!!llIl!, W. C. ~i!!lLi~'.A1!:'im!l. :rill.!?!. 1. ,um. fI!:9:l'2~t ~!l ttiall!( Nlppoll nlrull1!lll ~ ~i)l Co..Uiil. ~!llr li.e {;jp~r~l ~ ne';lli(I1~11l m Ule ·~_~pe<Ii!!l!ffitilil ~.jl'I:(ill1~fI'l:. Supported I:w. ilti,~ !~i:!li$tfl/ Gr E".dl:!l;ijiifl.l". Sp:irl~, (illiiture,. :!l!.i·en!(I!l O!~ TElC"'~r!!~ !I'I!. ~!ilol!! (1tOinlQi1<J'!ij!!! fa r :5t:i ernltilic ~.a r.[~ UilgiOS,~1Q) .<l1I!I1ioj lP'riOri'~ A!i:!Hlanci!

we

H.

It Tirimkii~~ B;. NI.~il1gll, S. I. G:1l.1wl>ol;o.}. MId. ~r,fl'. 2U-l!87, 1:19f:C:'OOffi. 12. I). Will{lIOief, t.I. M. ilil!Oll!'1uem.~. Re:r. B 67. 064103
(00(1>3).

.rcr tlii! ftlflil\3t.!lin til· WtifIJilwl·id.e Rencw.i\1.'ti1 (iI!ii!E!:~·i!lf G~rol. COlE PFiDgFiiIIl Wro.}~ljt:Cml!r!!!! 11I:(~:l.l@ii'l,~~ .Ad\!:l'llOld 5ttIlU~f~l ..and IFuI'I(tKklul ·ror '&t~rialJ; [l)eli'~~)·"rlIl'Il Ihe foiIm(1 lmilli!llry.
.R1lseam-~-TilI@

SUlllipD,ltln!!Jj Qrn'~lne .M~t:erial. ·ffiwr. ~i!!(timam.arsrMl!OO;o~~~i1IlJT,uW $Oi~'f·~Jli; flg~_ 5.1li!l~4

lBI51!.'J2f9S6.oIDt:1

wh~

b Is Ihe ahroll1te vilillu.'l fb. eis ~nccon.~ o SIru.tilf, ,co is UteOO1~ool~l1mti(m of dmggtldimplllfu,= l~i('S in Itlhenlailnl<. <lind. Dc: I= lJ~,fo exp:( ~Jknl Whb,[.l';E~ is '!he actl'l,l.a:Diun ",Ilet:gy[or l!lim jJtIi.gm~ l~tOfli of dmgg(}di ~mpurid@!l] :64tit'€: ,cl.ifFl!Is!.v:tty (:)if 1~1iii~n~lPl!lci~y i atam~ IImt 1)00il'lp(l~ ~~e.u:~p1il~ro (24) ..H~,o1her 'e(furu: illflili:llcang ./)I<-sudil ..as I?I:Lollion. di1lggjl~ eIOOl!:I;lud'Jrt;jggUug. mid P~ls fO'lallial ofd~e soooodkimd (i, .28)-lIIll: l:LqJiootoo. From Eqs. 5, 7. .iliIid 8" d'V.'la]1!pa'CliIit. ae4!ivatikm. e1~b Inil.(.ld:tOJ'U:$ilOIl <1 ~ of :r;;: ~pteSsoo. ,a.~ _ dlnD B ~ -d(ljJ(l)
~1lJ

B_

(1i~1iI~~Iramil, F\rin~IOrn.. N3..li 91l:~). :H. M. Killit1!lnL, J. ~Jjd M.n'l.r..r. 2~'1. 3:7 (19'91). 2 is. It Aoo,N.. $@k!rnllllil, l{. 'l':aflg. J. Md. oKGi~f. ~2:l. 2.~l) (2:0M). 3;~. t;:, j\r~ta~ .M. t, t:;~II'~!1If)(I), .K. OlIO: ~. lIl.I(lri. P1iy.!l ~L;_ le.l('9~ ·l!25~506· (:20Q9)_ 17_ :5~~ppiirtln,g maieria~. '~Ii! 5.rraE~Onlill~_

ii, Ii, li,iI~jjlilng\. Oif~·

itmel1a

fbt .4tiom~III (-!}"Still):

rab~@Sl.
11Ii~~@r@i1I!:~1.

!il"~"!1"~

M(j'<ie~S,J. ~1lidS;2 l,l': ~i!Y 2001; <!CCijlltedl3 'Ot~~!Jer .2!OO~

lilt l1:2gJsl:ien[E_U':;·53f;36.

_ _.3_ "'"'E~-I-E~ +2"

sr

'VSIC8:nC:y

O'n'8,.. D'imenlsionaIF'asIMigratiion
C,luslelr'S iml Metals
and
St~·Iil.

011:

(9)

Yoslilitak!al Mat;suki'!wa:!J·2"'t

J.Zimkle?

QOOir&'it~i f Id~.c atniJ1osphero

drugging ,dOes
dl,Wl to tl'lie .C\fbr dl~S

mlotoocu[ ,alII!:!1dl£P!lOI1~1l dragging

"mllu~dli" loop bb'¢Om~ O~.I1simi albov~ dli;l n~b~ I~Cl'l1;pemil.t'l.!re. TI~is yields .T!,- E~ - ytkf: ~!fI geillern~,lhemJdiIiOOi of S(ll~u;[es: fl~llop\lreFe dlalltJ,es: dll!: shear lil)[ldlllJ!!1lS o:~dy slightly (29);, l~iIJI~fure. d... clii!iilm~hl1re wi~1iWl tl'.ifeetivl3ly iflfi~jj;~\'OO; thL'l E~" V'3h~~>Tibus,. EiilC~iIl :lli!y ~ + 2:kT \l,.h(l;!l d.~!.'l ~Mp&rJgg the; ~100;p1~~ 111'1':; $n~ pit!babt~ C~~Il~:I!t~eJOfi'trpo~g th~ dragged !!1III1IDSph~ ·Oof' .a~] Ule l~ifII.puri'ly e~eme!il,11S: areC or N. We donol blow ~~le .preciis:e vaitll,es or £~ f'Or C (IIlr N ru'olmdi ·dte disIOO<l!liou. However,if: .v..~ 3!d'opt E~ v!lhJ~ for COli N (E",= 0.83 eN .fm C, E~ == 0.:80 r.V riOf M), {J9l.~bo!l~ I!]m .:t:~V!lIM~ f111f1'~ I~'(t .llvallll!efor "113.lmra" l.oo~ bcooa.~!C ...(M cv. lJ~ingi!ll" 8tn~ ·1EM1 w.e ~(!V~ show!'! th~t
I~~n~r~",ed di~looa!!io!~~OOl]San '~md. e

Ifl,homlP:l'l. wInd! (28) is dominant,

liIll~ m~gratii~fI of pooiM d~~m.s, f(lf ,~ali'!llpl~ JOIf'YSitI'!I. latl:kli!li,l.aCGI!ildes and s@~f"I!~1lia'~ a,IDf!!Il·:i· (:saM. ty'P~cailV 'tU:(lIl!'Sthr>Dugh ~f~dlim!l:!ru'l:ooal ramc!OOiJ a~krlil [~mme' w ~tf:ds. IHuw@wr, menl vlI~nMJl!eS .ai'l~: SIAs .agl!Jhlmlllfclib!! to fVfllilii p~iilililar cluSlm,~Iile! migrs:tmrl mode IlfI1IaymaftQ@. We'cbS!etvoo rniilnclimllrte~~liilled Itlu!iter~ of ¥.aialillcies: e'.mibitin:g 1J:lile.dil'l!len~iollilam (lID) rnigrortiol!il. The 1.0 mf:gratioo tr.m~pm1ed[ll 'l.laulIrncy duster lOOIiIimiiliIil.gl ~lll'Jlieral hll!lrn(be!d WI:[dmieslll'iillh<l mdfuilfr1y higllilBii 1h!i!l!Iillhat of ,[II s11i1!jleva(allil()j wailiidOOll wa!~1!: a.lild aJ li!iIobilily(!ompa:raide til a :s,iIilgle SIA random wllk. MOf~~V.~,. we foofl"dlhat: the :!!J[I' m~grmU~flliiF!ii!Y b~a I~ l~hy~ic;~IIiiF!~~~"!ilt'Smr()r Sll!lf·(I:~a~~~():litof liI~mof!!ll@t@r"s<u-ed :sessile: vacancy dUSfii(;!f (Slil!.~II:JiIi!~ifauU t~rah@:dfOOl) arrays. HI! r!li~SiSi!ilg 1!h·is. :I![D' ltiigratioo I1IlIJC;@ may @liIa'. om (O;lltroi~Q.f efim: !IrlIOQ5truCli!JI~ :Siu(h as ,d!@dj'l,iil! d@~Kit w@iITtwa1 ,and d inmodurnlJlliI olf (l[Idl:ire.d liliil1l00~rr'lIullUl8'sinl lliflirtteriJ'al£;.illlldl!liding ~elifl~m.llld!!ldan".

rom

he onoe..cJi••. .• . n1e.~Sl .OlI._~~,(] .• ~ ..~J'fa:l. n~~grn..:11. of . an IWID~Mftf"'s.izOO defect clus~c!'S. 1Sclirren.t· ~)Iofpruticlllm tnleremifll nl'l:olear m~ri!lls ~h (n R.melill moloou!a4t dYL1Sfl1:tcs '(MT» sinnlla.]i(Hl,'l llila.l\!'~indiMl'Gd:ItlI~aJD.llruuUtlCltll"_dI, ~i!~ dil!ll>Ii.\!~of 'I,I~calld~~ 3n.d gl:~:~eelll!SlBnl of~lr~im~~titi~l OiJtom~ (:S,[As:) 1!J!\e !:l~llIood Io:~.elihe!"n ciI,)nisi-cm ,ca._~es: dwi~gellle!'ge~ic i

jo'n and
ftiml

!!!i!il1ltltllil

in:adlation .(2). In f01ce-(:enrered

clilbic (ooc)nleil<lls, sessI~e "{aCOlncy ct!ilsle~ IOHeri.

smclkin~ fault wmil!ecinJ. ,(S!fTs) ~<II'!,I'iu~3D pyrnmidal slrtLl.1tII!lre ..1be c{)"ii~}lU:'ll:[m~ o;fllhc gl~&::;!lIc· 811\ c:111_~r!!i ~S9. 2.0: ~!~IBlet, W<I. R IDo{ 1 ~.O} priSlll'lalie pGrf((ct dU!Ill.oo:attcm 100;1:l' 8lilmci~ntlJy sn~an Sl!AehlS!~ .c;Mf!. '~lri1ilit ID'~l nl~raliQm
(1-$), which, .~ ~Qe·Ci!l!ire· dUiileroo!~k1!~!l'

REPORTS
iJng~. k'nll ofSMs w!jJba!im(jlb:ilil}!' OO'lwma~ I.;.[e [0 dial ·of a srngle SIA( 4).. nr.ls: :@!fiisotmpt-c lrilli~liiti!Qf'Ioif S:IA .ctusl.ersis cUlil'lcnl.iy (lomsid'credi to have !I. ilotl0embleimpact 011.D~ evoilll.!ll~o~~. a t of ~n:ilteiiai's:i~.ei1U:'O;1fI,"j ~ljOJ-' ooRla.ge mimD~ mld~ ~mC~llro, wht:ch ,d'clmn~inM 111£1 !:I1Ia~~t':!l lifelim.{'; in.n~d~lU'~f ~mVir.tlTUi~l~ns f, '~l (
AlihQl!!I~h SIA d~lB:b1Jltla
I~

SiiJ~;ai;Ui<ilO'$!I.y wl.~~t~ bop :s~ is S]iatt~ MIl \'lllim~alia~ ~.ve· tnd~dI .hat aiily t'iawi~!~.!i'simill S:~Aloo,~ e:.... hiblim 1D U1VgmliO:Ifl (4). A I~re" viJJtJS:l,. f~dI:lIlle:rmti.'l!Ieacrolml for Inhe In ItlOl1ion Wilh~iii. die scope .of ·disIOOS:liQj~IlheOii)'is lin•. 1!IiIL'l toofl,nlauon. is ~n-dtlc~ by IItili llI~mmn)' a(tfvac\!.d foo:na:!iom and p:m~afLgl'l ol!' a d'o~bl~ '1cimIk gil tII1~~;~. "vltr~~ .~p~~ l~ by .Si (&5;10.....· n) '. :~i m .'JI\JtC! N: ~ ..... iJJ__. UI'I ~ .,m__ __~-fi'..,j v'- It:\t, as c!':1ii 0iWn __.__ . 00 . _ im ~..~

tig!1! ~l dli:cli:~em~ ~i!~riJiI¥i :havi~,s: .;l. $ed.fic .. '.-- .' ~.. ,,;. . _ b __ ':i"i·:.· '. I~CY SW1nelry If;.rnAIU-1 .~GL!lJi:lc- ~i e- rUIJOli! Y 0_f \ .clustcrn:p:rod)uoo(l b:r plM~ic defoo)'u'lJtiou iI!t. 000:111 temlPemt!l.ll'ein gpldi are SFT'ii.(19), II r'C,w va.c.q,IJl~ l~ dislCR',3tiOi~~oop,. are also p:rodrLlIOOdi, nose . disl~"I!~iOlrl ~oo~ ~hibimdm .ti':Ci!~atiJl'ig tn~tioo
I

,~:u!'>loc..atiiG!~

Illie(U~~~lrlwilh. Inh(\i~~~d MD silt'I!l~~lnOI1l ~lIJL~,Fi~1!JR'; 3 rundlllovle 81 ;show a.~~np!le·

iOOPI (he 1D miglllliO:!Il!l1<lY i!lVOlv-e .;Jjooof~m~ ivc atomic ditTmian 11lec:hm~islin !!!lot described: byoon'\llGmti.oi~!:lIldlisl00at~on d100.y, Bec.I'ttl.!OO: the line SlliiLlreSof dislOO8l1o:n segln2iusfooi1l1gClii,ch
Citl:'lBf~n.aloo,p
I~O 3m al.wa:yJl QPPOl.lIIl\l,llI.l

s impoG$ill~L:l

glkl~llle wh;Q~~' lOOJ:lirnl 1lliI.~. $3!1i11L'; d![~tiOl~ sulit!UrtlJloou-~t,ll' u!ilder ~~. ~~; ;!S.sl!OII\\t,n iml fis. S [.1111 dl'l;lo~j.il is: p;n&'l~re OCIindll!oe gliide o·:fll'\,'e enlire 100" in tiIIIe!ml1te ·ciliiua::tocmbypus'hing the amms JIIll tIfIcpriSJitlm:ic oo~lJinlllfmJin one:: .side. This I~ype of n})~jol1,wh,id~ .r.s ~raditkmBny C8!llcd IPriSltliiatic ptmd,l{'I'Igt IPoo;~try S~il2.(JO), cali! ~iJ1ldllofld ill ~fic ~~I!latioru:, stl.ch ,:leO;: imld'eiil~l~ilOO"HI:)\,~v~r, lll~ l'oo;p·~m ~i(lll] I;)k'lCrvOO .il~ ilimdi@~edrnet:lisis Ina!; one 'o'i.liliybul. red~!iOC~tes ~acrk ruld.mnh, as Ii'CJxH'Ied by :sevef'il~llC8ealdlet'S (U~J4J 'fIler.c1f'orc~ p:li'iimu.cp(mal~jng dnes OO( 1Ip,pc.ru: W be a. viall:i1e ilrlea~~~:i:m .. A widdyac~ cepoodl I:nOCI'lrulJ~l'l lOr dlC ] DIlJIlgrta1iQ]'I. ~~~l" tl~~il~llilCflli'!L::dlyae~i~d! d:e",,~HlJjCotwlilo1fl of ~l" ()Ol1~litrlit~nll~tJ;()iJ'IIil, "c!1)wdion~," in i:h~ d()ifl~ c ~ooked <I :W>01t0I111'O diJ:~c!ionah;:mg Ihc4ir!B.q.e.l1!i 'ii'octur in. idle case of !be: In::mls (4), as sl'K)W,I~ :ll!JhClwattce1:~Ylfl~gs" ~ aoo. 2" Figure .2 sdhcmal~ irnHy shrrws lt1mrela~iOOl.shjp b:;:l'l,I'~.dl;~loo,p 1Dr :~ni.~ioodllt(Ctrml!,,~on'lelry of Ilt£i loop, M~: bundled crowd!o\irls" B~~lhe iDlliLigmtiol:l IS indi!lcBd by oo!~eC:live rliI!'ItLtm (lit It'lilnileru~ l1eJg'h.oo.ing oflJw,Hons in d\e 1~, tI~·s:l:Ili!eOOJlleliLOIU is
~~Ill!ri~1!; 5:ruilG~ and '1'I!iI~nc'log~ mMii~uoo,Oak ~dg~ 1t\lJ.tiQn<l~. hboril!~IHiY I~O!INI). PO.~tOIliiO!' b2®!J8, TN J l:1Bil~6BB. tJ5A, 2C~n~@r for 1miI11:@rid1.~ PlrQ(l!-~,~Iii~j ~ ~iIrrIlrr.;Ilj~I·11~nlrn~551ile., lifiiOi{vil[e:, lINll'~'96-0JSa, US}!;,

82. HowCllle;r;inl D nlO1iioa .:;I~I f the ·crowdio.1ilS o ililsi<b ~eptism,jHic cylin<icr UIllSI.bi::'lmttSpOnod, v.\hCi'C1t5i: lhe Hncreins!iom. mood only d~_b!.'lS !:be maum oifclUwdio[ftll. an.ldm di$l~.nO:lllioo.. ]ffI MD ~iml,l~31~i}JL~~!ilJLW CnY\\ldiom ~. (lI~U w.~t'i.~~ W u1l)v~~ml'Q; 1iIil~ oo"'M~io!1L'l:1)1f! ill:~l~~; ~~r (as scll~alicainy ~W'\W! in fig. SZF)i Uae n!Ot~oo ·of \'o\ho~e~,.is "ed bydleinnaJ' COO!I,l;,'djm~ (16), A fundmimlDllllDlqtllCSl](UD :is wll'1i1~er1h~ U) mi· gnti.Oi~ .fu; ::llLcropossrbIe<flu vnCSinCY·4)IipCpri.'MIai~ic
di'il(!l('atton
kXipR

ofnJ~e·oo~edbel!av:ior in roar!'!. l~e!:npCrnll!!~.'e.A Slnrulcil!fi5l!ocrutkln klOll(d'ianwter ~Ui~ 2. mn, -I. 7.i1!

vacamci(l!) g!lidoo. 'illlCnllillenUy bacik !lind Ifrn~lI, h!::t'WIKln,two SITs ar an Ql:il~,m;angle ilmn:g tI~ pmj6('!~:tOO (]if ~1!11.'l <:] 10> dnoo~llion 'C~(linalilng
dlg!rtl!lOO (1;1'1to .2;!!lrl~)" Tl.ll:ll~

hmc tJ,y rnll]ll(l:'fro:~.l~·;J1~' (Df 30 r:ran~B.) for r about 4 !]1!i~and Ulef!sll!&i~!1!l;illm!Lg;Fam!ed to <'II'! SFT widlil~ 9. few vidoo,ff'll1m'leS) {<:l~l ~ Ii}. Because

~~l!iom

dMU1i,gM

8FTs are 'l!'acan.cy"o/pc defeclS:it~ fcc StnilClUI'e5 (2.0), fig" :l ,poovid.\;:s INid\.1'nfie Iha~ iUlllOm.ctcr~
si.;zoo'!,1'~!ley loops caj]J@:!:hl1b~t 0. il'ij1lroJ~i(ln. 1 'fh~ vacaJ!Jley lOOflllmnsr<Iltrl!lGd il'looam S:FTal.<'IID. i!fl'C~l~hu~ pi::D$ilio:n b{.1w~~ lwo~~iglinM SF1:s.p:reslnn~ly ~l!!selhe suess fidd {'m!lle loop IWmn 1\'/110 S,ITs 'is ~i1iIEl!l!loodat liIIIeinte .... m!edime posidOl~,.As II reRil.t.a '\\\lC'n"lI~irgJ~ed!8FT

I~y

(1/ al.Ll'>il!!ftmtW.

IJiIIll

.Ioo~ in ood~~y~~~~O!lbie ~) o:uw f~11I1~lafg b~l u~l'Ig .~ !riuwilliltli()!]!S U7), 111C}! p:rodiated In m~g.ralkm. ~maiUVilcrul'C)" 100!1f.IS ·oc.cUI'IOIl ~t:I.] in nOD.lntre !.lqppa: 'm.c, :priSlil1mic vocalrlq'~oo;p! in

powlJ.m~y O~l tID migrn.~iol'l f~ ~o:Y

or

me

coWt<"li"imllil'alialCly :booru:w:: Sl'SSih~ by clcveil\:Dpiiii!ll ilDackiil1lg fa:l)I~l" from tl'm loop cclg~ "vl~~lA.[1. . ri()~I'Kt TIte:y ,Mnfilnlimdl ntl;:: ~oo (Dr to
U'1~gri!lioUl.iJ]

3lT'iiyool:LS~mlllg

n.c~ 11Iigll-0fi~Y

~.

mBill)'

ofdlireC SfTs was. ()bl:a~m!(1. re~i1li, ~lO\vlng oruen.'ti arSFrs.e~d IninwlIgH

rays of m:utCi!I~"1:er~erl

foc oOlper LO:lIS ](!!~V ~d~lfIg &1l1J~

'·Pment addrm~ Oe-parlmelilt or Maten.als 5d~'flC\e'a m:I 1E~g1 neerlng, 1U~~'o'e~~~V Illino~.a~ U!ba~~Ch,,~pa,~!i'I~ ef M~Iie'M~ .S(iie;m~alili!l Eng:iIlli~i19 ~wild~ing 4,OOA, !3tM
\¥~n Gr~~.1~ SIJeO!!. U"OOIIli~. IIL .M.8II1, US.tlb ·flr·!), Mj!1oIl1.[jorr~splMld!rn~~ should! bE! "'d.drE!ssl'd. ~·miiil: ~m2@uill'.@!1Iu -

dYII~nlic o~l"'!1ltim,~ ,FIg,. 3) S\~~ !lila] ~1)1.ujal. self~1lI1lza:liOJ~ of sessne SITs Cl'Jlrl00 acbievoo liluough Otell) migr:a1i!)l1 (am:1 oon,~.on. ~o SFTs~. fglissile w.caocy loops, widlotl!l:tlmneceso ~tyQ:f' ] n. ]t]igm~i(}J:I(lf SJA Chl'9te18.F:ig" S3 ~1t(nwsp:~\li(JI1~ly P:U(!!POO~Illi>d()I.s ~Iroop-SFT l 'Ii-'.i:lrnld ~teOOl:r\!'(;:f;$tono.rdl~()C3tkn~ .~~.LQ SirTs even :~nQl.'I;;sl_w:ng]y in go1d ~l1il!H.~~OOf:!per COlWI:r.s!On (24)1 <!!~ :~g. 54 slm~ ~. orysi1l.!log1(.18). '11.1~,f~-, U) Il~pion OrV<lClll~ ci!.llslel7.l; rnphy oillvariQ_poielitlialloop goo.n1CiJfe"l1~ Figure 4 and.t:ilovlc-s S2.aqiKll! 8.3 S:h.{!W Int~.e ~:D is I110t; eXI)ectedi lJ~80M. A very bigl~ dcn:>uiy of mli.gpltknl, off! vacancy loop tntrodlooGd. tnl!) go1!d. vac;:ncy cirttJsleli'Sil> [Drodneocl by l~a"'lic dnfOJ:'llua·
flU!:etbc gQ~d IlhfOllgh plaslie delmnat&lln ('IX {jilK.'nclllng <oj. ![hen 1.>J!i:~ anllediu 3ilO:iUhwly sin.l",!>~rr-a ,ooilditlOiil!,lihe $Dackiillg fauh eimrgy afgo:ld (32 mJ!mi~):is ~ l()1Iver IJi:lrul. l!Ila~.foroop,per {4.S mJ!m2). \~hLdl IrodllLcw.inJ:o ~9:~975%

ie;!~~gy.lb d<Jile, lllcre ~~VC boon no o'bsm"llihOnBll of ~I D m.p'<lfl of \!uc<lucy Cllusl.iIJi1S,\'l{reroas. sc'!,'mlil ,eoc.~riDl~eIltal lti:dics ~mvc .n:OO ID llinl.gtl'RItiou s of SIA ·clll~rs (U-.I4). Thll'l.oosod on ~hflMD &,It... ~:m l!:!i(i,,~il1!goflho;;elli~lt~isl!I~a1. ] D mir I[lm gratioffl ·of VilCilincy dllllitem ~[\lnOl :rns.lil'1tJile-,~~icallly illl fOCIl:Ullilis(.1), l!lil ~he !p~e;!n :study;. vacan.cy ~oops WQI'e in-

particle i~i<'i~(l~ SUCI1:i~. 1:I~lIDm ~Rdl~aI[rofl(lRd 101Jl oonjbaJdmlelit (1t-2J). BC'"

came Sf1's mre:s:essile, ~:1Jaj!: bt.."e!lbe~.c.¥(lCllha.tO~ self~_:md. Ilruioroslm:clImis oared by ll~le SIA c1mDe:1'S ,ffi{lliJb~!'rUlg lilli~rol'l!; ~tlcy m
elu.~'inrn ~~I. are geom~ll'irutly aHgned! lii!liQngdosepacked! <~IIQo> dnroollia:lsim, fl:lc ~,*ISiIi! wolilldbe

p:i'II'lr~~tiruty~hi~'ldedf'i'i!1!ll'l1l"IiInihikltcol'lby ~~11l~b

rnlgrnu~g SI:A. c~lusreffi. Ho'WeYef"g~le

pxe8ei11l

IFilg. 1.VarioU"liillG!ll'll

ibO!V!figllratiorn

!:If SlA5

<lInd v<I{;l!Incie1l'111Hloj;Elded lOl'!l (1JO.:i! 1:: smaJW atD:1iIil5 Ir~p~serni'!W~ GIlJ ~

/'

1~I.arle %[101] be'~.ow lie lar!l~ ~. ~Ii!,the :r« stru!1l!n, ~n~Le .SlAs
IteeMed art. octahedral .!>it:e5 diel!illm a5 (lJ2. 112" V!-l) 01111 Ih~ 1~ff5;is.,f il10rurc o vellum!! !(OIlIi!lidN.atiQ:JiI~ I~o~~~. it: ~. refl)i!f!:l;~!!!lly !i!II~firef~rable i\Q '~'a!iWgng~ 'i!I!a 4JQl> d~mbb~~$tr!iiWl~~+ ~dfQ!'I dism~uteslie w!Jlii!Zecl d~*liI~mmt oflilfie~IA ill(I:ifi~: ..alO>d~p,ackedamm tlfJe dife~n. Su'M~g alnli3J·tom~i!Je" ~liItrodl!l.mm ,m: ,[I ~CaJil~, m>ay CJeiite :a.del[:oca!~lzed diMe .a.mmmmJig.l!Uatiollil mlililp~elililelllt;irY to 'th~c::no~ cf,()i!YdiOll «110::> voidioo). l[!IJam t~aUhis; (oflf~ll!ratiOii! !1e~~ ~(uf5fO!'!il1.gl.e ~caii!d~
(lIn! p;meferenWllly

..'. ..-.-:. ....-.. •..-.' .. I. .'

•

~.I .-,._, . .. ~I'I. ~ ••-.

a.' •.-' .• ,

I~
.

'._ ...'.• -1.- ".'.'•.~~. ~

.,.". .I

",~, _
'

III' -.

'. -..•. .1'.-'. . .~

... I. .~~. , -. .. "~

.

rn~

Fi~l. ,2:. ~;!lem.ro( smtch of the liD migrar~.DI'i of '~h:~ SIA.,1;rtp~ mdlO>(U(]J~ ,dI~~OI;atiQlillnop an.d its gt~i~~ib~tf1YdlIrn.

9 NOVEMBER .2007

VOL 318

SCIIENCE.

WI!\lW.sdenaemag,.<l1'9

REPORTS
by qli~'tchi~g t!i;;ltilill.fl)du'C.e!l 'Oi:lIY~I!.Ci~.l1ue ~tm\isJ~lissioo dec~l j11k~~py rr!M}ob.~ V:ruI!DOn w!li!>~ecil OliU arli ~.:3 K. The voomucy loop, (di,8ilnlet~' a001l.l1 .3.5 [JIm" -:534 v.acanci,es) ex:l~ib:rliOO o~iliarti'llg 1 Dm.i~1iou for at'iol~t ,6 ~lifill i;'i'hnm&C: sung!'!!: 'Ii':l'C3lltG!~ 'W.Ie~ l:flll'I'lObU1\il: l;,~l!)1~1I' -300 K.i!l:l. gpld (2$), nl~ loop wi~s:l~ irlOOD11iIU~If!I)y, ~Ilok:(lnd 'rO:~,,~~(1I!~, ~. 800i~lu di!ilocaljOlt!\!\tiil~ .. wide vome:1,Y of migrnliCll.U! ,d]~!yIhllW1!S

~04,5- fot 8~~gl~SLi\~, lliie im'Q,j.(i~tm.mo~~nlOO T !l1~SfiI!iOl~isb!iice: ofllle:v;t~toop d ,OS !iim) oo~nd~ 1[0 v - 789 S-D, which gi,\res ,(Iv .of 0.22 mabciul, 0.2.3 eVa s fh~ ·el'feCli,\rell1:~iP'mioo I.:.'li:le~' for 'l.I~o vacam:!y loop l.D itl:1JOili(m (27). TId!;: ~f1fLl(:liwn~igrnlio:n(\\iI'It:lrgy forl.h~m !1llis~il~"'aem:ilcy.Ioop istl'iucffii ~~ll[hrul'Ihal fiji!, t::ill~J\'i
",:;IC.'!ltCl~:liL . ]Il" ~~81"
., 11' .•. •• . II' I",~al~ .l~

~le!~,\vID!~~m'C ~1~6oUi ~ 33 ~n.~. hustead, cO~1p06,iLeiIDl\ge' ofUJiC; loop'~ !i~OOOO&rii1.g ~.l3 ms is: roooiid~dI on 01slJ!fl.3l!e viifuomr.nle,. NC(e l!im~Ih.c 10Cipimage nnmillled the SIli'l1,c, CWI~ after dile i:l'iiOll:cmbeeame mociClr:ecln'bleiu, Fig. 4., ~1l~lS
oj

m·ay OO~n. lfld!t:call.all,

~lInl

d~~oop,

W.\l!l

~'111

~O,iJ,l~!~O~

... ','

for eaeh (lSCiHation. 111ell:IDtl1fllUll'U o~ scrvOOlIl:1iigrnlicm disll'llK'e 'perosciHatkm (widlh~, 1~.lWOvidoo, frmne,g, L~, ,66ms) woo 1:5 IliIi:I1,wh,ich COlfiroS!'J!IlUcElO 52: rum~ dll.'l {I rnO}iliJ!erphlJl:uat dislam~ iUl ~1d~1'I g~n~rai~., ihe QIlu.mlix:lr of :shImi~~iajun1p8 'per ~~I~d in ,""Ih~'i!;tll.y :acli:\".a~~dfOp Ce.1lS is expressed <lS:11 =!<~lI(.SXk)e)'lp(-Eirik7JI' whet:c ~I!l is Ihe 10000liccll'ib:mti!.1llllmqucrlCY ..kis the ' Boltzmann QOIiI:S~FU~I, is tll,llb"OJ1)!" 8lld'fus S absohitll tCI!i1pCr8ttl!re,\Vt; IlSSlUWC cxp(Slk), ... ~. .~br· 1iIit('; sak£:of ~lifI1Pltc~t!i'..1l~i1I1igmat'~0I~ em~rgu~()fSJiI,~~ \I~ncie.ll and ~;Ilglt SJ.A.",il~
tli(Ji1d !lin;;; ~n = 0,&5 ~V1i~d~'D = 0.1'9 eV, r1 ~-I.!I :113K luc.spocH'i,1\e~);1{2~').Wiiilill'll(1'1 •. ~ '3 .' 'I ~cS- S-'~., I,ors,mg I e .... • • . ;;!.;x ~s ~,.'.'x . U' ' v,ocan:cles au'd· .~ 4

na!1QJ1:'!eler-siw:i dislOO<i!llor! kKl'jllll m<1i tiD J1i!~gf'i!" fioDl.ill: illcliepcn.d(IDulfdtC lu'Obilily o:rl~lbeC(msli~" IICIU 1;)0:11111 defuo~s, Ilno! ~s!vooan.cicsin, Iil~is: 'CIi'iSC. llle dil'fi'OO1Jioo oontms:1 im~cs ,Ofll.hc VBMll· C'J loo~ o'bS(l;r'VOOil~ d'm p~~liJl !>.'Iudey :arc. {fliil~ 'lU:i!~l~3! (I. di ..lo>eauoll ~oop iQ'Iag_(;, S~L'>nfml~ :3!il U)~ <]I'O>dJ~liolli' 1l1~ ~QOp ;s in;!11 ed,ID'KII'l view,i,e., visibh;; ,;;l,.~a li!iie: s~,ntl!~1 HQ\'"ll\ler; (2~ dIe< lOOp, il1fl!l,ge ~Jl p~ 4 is oval in shape; eJm~~~wed in dilel D, ,gltdc ·diruccliion"The lOOp, ~m0gC inll/js" 3, is also Mt31in :s11m:pe.'rhis,tlrua.Y be allru1i:filmdl.1e lD

m.oVDIiJ~ ~1]e..ctulil'i~liJsiODially \V~IiIit. I!IV!iP)' shaH ~'ltmi,l.l:i~Sl ,m~~ al~dhi£h, ~'q~Il~.y~ !i~n .• r tile l~e~'R~i(Jl d'eloon.1ble by Il~ p~ntd~!1i!l'itc l[1~11ob>enrati{m di.~red.

Th.~ size orllle Vac3U.cy .!oo;ps:observcd in InI[C present TEM :s~l!dy (2 to .:15 11m) 'is: 1'U~lIiIch, ~a~ dtllm. 1fil~!1: loor 'BXrull~jlooin. lhL:l ] 999 .MD< !SII'I'!IM.Iatkm {~p ro 50 w~t~ <] l!llm). Ol~Inh~b~'i~r tt1~ na~I~Ol~ gil!, I~P8ob1:alued d~fOiJ.I,~.h D M ~ltLlill'Iio ·.·.e ....... r Ioops lI'l;l .es8 '11.1iliji'~ ~mall '.- "·1' _ 3. _~~ .. .. li:L~._ SIlUliJ1 ~OOIE: llu.': cu,11ical size ~e \!\'~ilkihd1.e 11rt'dictooll1lQb'~lily ~,spmclicaUy:zero is:""~ 00 SI:A.s (";1 ..3 liUill) in Cio;p<l~lralilcl .....lQQ S~As; (...-2: ..~ mfll]1 450 K: Th.ecriti(;i3!~ ,£liZ{) iii ~l:lJmay ItH".~'i!il~.111alii 20 ['0 -30 nm (ln.l"hep~IlL"fll 1!!1!!I]erirm.lenrul resulLswt'fc o!brl:ll'in.edin tl. 'rEM o~mliCd III 200 ll;eV; wkichis 'I'!.'\!llibelow Ihe cr:i.lic3! v(!l~.tage to'i.n.l!rodl!lre mnikd ~rnl:!ii 'CVfic:DIlCY andaill SIA) mto g!ol{t necriliea:~ (:~eelIDn eUl£1ll,Y ~br FmIrn~ paircreaJlion. ~.S1-2MeV ~u£~ QiF~h~~.arge m..~ of gplda~()!!liil~.'m.~l'@:n~!1t11I!,lRl: im1~il~ l1y u~~ 100"keV,e~ect!'(ijf! imdLlatlon is !qiigi~lebeaillJ.ml
1I1e SJool1fm.'!lil W'JSdliltU (<50 rul1)rnld ~I~e ele:ClUiD.ll.

dIll;high vdocily ofl D mot&on. MlTII ~~liIltll[fnioJ1ll! 1!1I. fro~ (4). :H;owe'l,l~r. In. TEM lL»':pe·rinmCftl!.lllll1ilUC~ {(lb~auliloorO'$ SlA l00p$) ~~i1IV~ iP1dlt~J.sd Ih:1ll. 1]115 targer 51,A IMPS !l;Nhibit ] Dllll@rratiol1. ,~~v¢

loop'8 Q~UII~lioo is ~'i!li;)U.y j;t~1tJ..p~OOSOO(Jifldlim:e scalee\l'eTll (4), :SuchILig:il-speed iVll(ll!)!OI1 Cillmo:! be caplwcd by d~eplCSCiI;llvidl!lo~oordin~

beill1ill(ljametcr~ras

~C5S (illln2IJm.

W~k:1,1gives

less ~1i18rn. fml,l' tens of Kelv:ilillocal.lEmpcm.lfoo a InrlC~ for 111m ,al()'ClfOllOOam .i1Wl&S used ili!l.dlG p~mu ~tOOy (2'9). Altl.mr!l~h vacancy loops ,eannOI~ ~~ave
CroWdI'OllS" W'C.

5pI;.,,",uJlotOOdliott dle)!'

1~~]gIy d.evel.QP

stua~lll" aiO·,,'<iiola.s: (we tiCmflilh'C~y CIlil !IIlis:dJnlll!~~ Ip·mg. ~:. S!OOJl!elll~e of !lIflp5hO,t;S! ~h:(jJMilfl!l time' 10 osdlfliatiflflgl rirtOl!liOl11or a VJ!I(,8lncy l~ooplll!u:l1 even~li.!a~ pMk~d!<~I 0> 8to1nt\: row 'wklioostt), <IS sl~aMl tifaln~'onTf!!CItij:001 to 11mS,F1II«lifter 2:40 s) in ,dEfu:mllliled gaWai room tNlllperiiWl!I"e" ill F.ig.. 1, Sudru a OOfl:M.~ti,{m does llotOCCUI: I'~$sLng~e v~rnei~~ ~>ow""""''r.:i~.the: .fO:m'ilQ.ra
1111 ~malo~ChUS (dnUle) aWl)l OO!]r:~lJAtt{)n
III,

QI3I.71(] S
"\.,

..

9 3,.1'7 s
1

l{2<I]Oc>'P.]HI

'..

des :~,'eI~efglJ~ng(m an u}} IJl1!im::.I:!Qtcllllltil:l~y

l~[i~miltk: [fI~llal!l~lf(lfU~vacantoop.

·501:11ff1 ~

Slilm
IFig.4. S:~ye!i!01l ~'~S!i!al~5-hots show:.,g t1he1J!) Q.scUL1!.ting migj~.atlli(!!i!, (!f a! 'vac!'!!i!(}I' I)()q;! if'll !~l)J;IIDOIl,edgQtd ad; 1'13 K. The ~al:iilll dilmensio:ifj shOWl'iI hi the fi1ilm'te c,f '99,.77 :s m~1iHiie jUiillP di5i1iilnCe mom the pre\liaus observed IClOP IPoMioo ,at 9~:t70 :s, TWDI;yp:~. of c~t:llnlCl!g:raIPlil'i::aUy ,equiill.alellli: S,FiF"lma:~kerl by x. anldi )1') (
ait~

fllvor:ing InI~i:;Qooperm:ivc ygiclllOl~ Qo:n,£ig;n.~iion. ,ffllil, IUm:l::solV(,>dqlJ.!e..~icm is wl;lctfiJer the ~:D mJi.gmtioM of SM.. and v.a.cancy c!lUSU,Cffiam be: ~~I~tiVlG~y l3m~ed ~(I ernah~e di.~md :2l$SG:InMy 1 ofmcl}IDl.Ql{}g~3Uy Ll~~'lIil'"31110SCl'lJ~~ arehit~hlmes." '[Jl~ rgmlaU(U~ .of!;l!lin.e.;trr'~y (Ii! $.FT-silru Fig, .~ "'l"ii .I·bl·~ , .. I'·f·· mpu~ ·:·l·l·t'·····a.~,· i.","pn~L.e Ua. L ~lay .0 ore<!.e III!rlLqL!e IlillIDtilale ordered! defect n~i~slru:c:t~ by par!. tic:le inra.clJ~.lior;l,The very' high IlllObftily ofillle ]D glid~ vaeam::yclus.tcrs ~na.y aim provide ah.1mll rc.gardjit'ig e'.ffifiucimill d'l'lfeo'l.i'Cfi'ijovaL Cmi.~l mlOt liIi\~Y m,L'lfid~ h'l:il~~qo' gm'i'ilicOi~cli.iCI:OF m~iWr.iaI~,wh.o.~~ ct~sl~D'in~~I!avlor L~~!!t~Uy Ole ~me as .rcc 1i1li~1s OOcal!lSe ·of 'Utclr- s!n~~ar 'crysUII stru~cwres, M we'U all:i !l!Jl'OO.iuotiun of 11.1Hoocale

~re-t~

ordered smcl.wi'es,. R.~mm!iiiii,e.l.'i!lOai~d IN6reS :t Ill, N. Siingl~illl .fJ!{yri~,ffii(p Olml'ltfrMJJ:S:iMfe .~rld r«ilmjfJ!JY, IK. Ii'!. ), 16u>~11!!;m1.~~. (!'{•• ~Ii>.(!il~~i~, tf~

i!ili~'~Vedi~. 'Ii~ !~9:lIf'~.

ywk. ~o~u, pp.W5'11-I'97l.

96"

REPORTS
2:. 'Vii, N\, Ol)!t!k"!!,. D. ,I. e.!l~iln\ fflJt.i. lru.rmm., A1i?t!l'M!: Mfj!. lite. II leO,eJS, f;mOll. ]" .A. ~, E" I'Qrtmiill, c, A. EmgI~5h, W'. 1, ~1l)'!lliil:Jl, Pllfl~ Millg. A 66, 65~ n9~'l), 4. Y!!, N, C!;l'!:l$ky, p" ~I.~J'I, A, ~rr~ ~. lit Slm~h, S. r, GDIl!J'OOv,,"M~ ~g.,M,61 ~[lO~)' , s.], !lI~rt9n ,!'!!, ,mt" ~, Jilev,., 11'~15, Un02 12:002:l. s, E. t::ur.tmotQ\, J. ,Noct Millter. 2],6,143 ~i1l'OOOl. 1'" (I" I), il\IirtliI" Go III. 'Odet~e, [l" M~fO!l!!!<Il, G, E" Wcai." j, M!tJ, .M~r,u" 2:11&.. 33 C2,OOilll. ~. S. t, I!l~di!r~; f'/Jit~~ M~ 831 351'r f2:00dl'. ? iii, 'fnlil~U~ 9:.. NI, Sifl9lli1" ,1'1,-1 t ~llr~,n;lJ1l, J. Ni!d_M(J~; i1!1i!., :2:001(liJ'il3'~, ,:1.0. ~. S!I;tz" PJ,I~ Rl::~ 19" i2~ (1.9:51(1). n. It ,Iir.!i~~. Ill. I'!a!allilli~li, E:, Klif,~rila~O, Offlt), ii" M~n, t:. f'nyti. ,t!te~ l.e~t 96, li1!iIj,Q6 ,[20(6), :12:. M. i(ijn."ti!,1t I, MI1f:,I, Al\:r,it'f. 251 2::t? ~i '99i'}. :1.3-, T. IH~Yil5~~, FllblfI~tl:iil Ii. ~~ltwi, J.1IIt!"{-l.~le'f; K ~!Q1=n~. '1l'~~ aOOI~l" :1,4" litllbe', N(, S~ldmiIi3,y, lI'~ g. I. ,~d. Mate;!': )21:, 2,lQ ~:OI):J.). 15,. 11.;. O~iL~1!I. E. ~Uraifill(lB, f'~. ,~!!v, 8 .. 2, OS;41Ci5, (Mills.), ~. 1ll,~ ,~io~ Ioc<iIBd ,:It Iloo locip, u!nl!!r III:I'I'I!' a,!mi!ill!!r '~]@<~~ barrlll<r'JiM nu~IOOI'ib,iII:I !bill. III t1i11l1l~r:t~dbll:! !.wtt!!! Ill"'! the loo:p 'periroetff (4).Tl'1~ is bilt.jm~ 1h~ FOOstit.iibl't '(tIFI~igmii!lii:in,!l!r :iiD9le~ ~!, dIi~elI: Tne !I![il};~dfmi dle
Iliiilll}!!, 1.oq:I' I;Il'IEfi'I~lI.@r am 111!H@ Ililri'~ 'l1!Hl'lImsi'oFl'l11t! ,l1iSlIlJla! ,bil~!!!n
IIl[glil'~l!I

U]ID

~it@!;,

AlIillOO!lllln ttl!!! \'fIf;3oc!!, ~~[.I

mrm_IJMI]~CfI~~rill.iGf1', 0:i~15~; Mari,lII ~]I(l3illl<ldl flliIl. nDwdi~.m i!ilm~ ,on: II"1HX'~llkelif ~~O«ll!r .altlie loop ~!n~r. 'Thiil f~ ~!Ile'~ irner,ilI1i;!mil: p~efi!tigj ~I tIy ~'n~ gp;:d!~J~!I!: !l!r,~ w.nfiSl~r~~1 t~~ f!iN}JeIla6(.j!, 'l:1~~1iI 'Ifl,e dUmmoo1i .cJ!iI~I~!1lr~I~, 1], )(!i1_ IN, O:5I!t~1. III ). I~a(rnil A S~Fila,''hftlJ';' M~, W,L l 79, .2H (].·X!(l}.. 18. II, P. IHirfil11l, I. ~DlIlIf, fhwy oj ,Clfstimnilll!u '(lIkGra""""H1III. ~~ l{1j)'r~ 00. 2.. 1I9~~. l:~. M, t::i!iitaFfiit! .rrl,.• PM(w. A~ag. Wi!; 79., Y9"J U9~t :!lO- S. K~I)~I'!I~~fall" f!hH~. ,Mag, AI:5'1l.5i19 U~af.lt · "1- ~ •.u,. Gil~~I!ef!1, ~. Wa~rr.3~I. '~.l:1:inf:;l~ 1- (1tmi,p~lj~ AitJed MI!Ii~: ,!)~ 8.• :It ~2Ml.l'. 22. A.§I~o;rI!r, N. 't, ~ml' r, Phillip, ",", ZOill~r, !ltt.rlMi?lct:OSi:."opJI' 39, M,2 U"l'illLl 23. c T'iil,~,fl. H1ll'irniffi'".M, ~i~er.W. ~t:1Yii'k. Appl. M~ A. ":8.

i~~"~

bil11i!ti:<ll~ l~ nm wi~1l11~, !~ 'Vi!dilo!l fr.'otlll6,il 5ee-rm Ir-e<tloo<lb!:~ amme'tmt lI~s mlg~dti~1l,~rtI,~, d 'be ie"m"lll~lJoorail j!l!I'IP:!'~ .;r fe-w h!.!!!t!rIilllIOllO!m~:illll'!e .~fI1e ~r~!ii;)~~ i~I~~1 ~.i~f!il2O[~ ·!;!!Qi~~~trJ!'rIi~iOOlI1ll!n ~,
f,~f!o!! ilirl![!i)l! 1i.1I ~ln..u~iT!r(:!t~~

2:3, line ~1llCl,~~1Ii!ipi! tiril!mgl~ i1cf dJ\Clil<if} i~Llniilen.lmalil.l!' 1m thf!. ,f!liI9@.(jnvllll\¥, zs, S;,. 8, Filll~r, Rndkrl. ffJ. !i" 2:39 (19101. ~o., lhi!; f~r'Gln '!I!i'k1'ijIOIUOFed eyt:llJil Office d' ~tcill!n ~rw 'SdeFKe~U:5, iOel't'lr!:lNenI: 'D~ IEnerw.The mit~:a;arpe fatf!i~'Wit!Mf! tlil\:' SI1Ia~E ('51~1l:~1~~.ro1 E~I".I1l!:i!Il LJl~ F~~llt)') CCillallllr:3i~ R~ean;h Ce!1ller ~~ ORNL.v\iI~ SliP:i!!!IIIIOO by .ifio! iO!oI'Elm ~f .StlBiJIiIiit: U~if !,,;cljitil!!':, liJffic!! 111' Bil,fl(: 8rM'!!lI>'5cil!e,. W>il' <Ii!! 9i<1te,f~!1.1ll ~.n, 09!!t:!~1I'. s.~.GtJ.!I~IiiiA!. (I, N.S1iliQliI.. ~ P.). Kl'irr:'i~ii!lki

:r"r \'ill~b~

'~Olllmf!~t:!,

~ ~1'!l~4]"

:!~.0. ~ul~llI1Ol!n~4ViMll!t, ,M~!~jj'II.n., k 2;'5,:,1 U!il~5). 2~_ II. E_ I!awef[e;. J. ~ Kili!hl!!r, p~_ ~; :1!D'~, U9'~
(l9~n

SUP'iJD,rtllig)On'he

Malt;erial.

'1'IlJ'M', 5lIlj~oIK~milg!,Qm~@I~om~~mlJl!uW3:le;151l'.!2f95~l!OCl

~~, M. triliitanl"

2~ •. W·1Hilidl oot.~~ rd thi! il1rgmllDiil ,~ Nfl ~ ~ IbaIliltl'( jLlfl1PmllSll' ,or~iIIll~!JIW1i1!l IDIltW. TliIIl'llD fI'l1!TiI~O~,Illi

J- [lJrjys..

.~,:

mp

JI!n'

IlD\ lO:3,S (l.9M),

is

M<!!efi<!ls iI!I'!lI !i'!etoo!i!~ SO'Mlf~.rt li'ig;:_5:1 l>o~1 MIi~iI!s :5,1 1:0 S3: 250 ]'LlIV :l:Qi07; <impledl ~. OOtiJoor :20Q(J'

~kKiitiJm loopt!, ,i'! reml: oj' ,~cl~eJt:Iiw!IMIiM Ilir !1U IWfO!1S aLQ:Im ~!I:' ~li:n!!el\l..iilj'~m.p I.ql~'ls dut •• ~.eiri~~!liI!

J.rQ,.1126ficieru.e.l146:3:36

sm.d OOnlI1WsoI1l,mcililme.s InlaC'Nj~l'iiln, of ob:ser~ vatiQnfd arufu('!~ .. Hcoo'\?if>e descriooa l:l'nclhod for 200 of c~O'ud.'qis 8ea.n~"I\:.-x1 :1lLC11OOS Salmil'l!S ac~.ti T~i3I~'s:m!l1toorQliogyO:ll. a.~!ancl),\!i:dC St'1Iil~ Ilucking 1'l'il00lfI!lfeO.1Slilis ofC(mdlm.f>oo.-ph,'lSeQl)mA:;~ ~~.-gC$1l]1.100Il, T~~l, rllcl~d:ungO!)l'l:V~ [f\Ni:d~"llleil1Me ()Qbldllf'lS!lll:(m ~uld be Ila~ I~Y :rl:l)bll i>pecitic al'~iit1:de :regiOlll!Uiil.Tina:lfi.ls iltI'I'iIOdQb'lllnt'!!lU~Jhw:ay for ~I;iJ]IIl;.nl!;l.nlelhiill.t¢ to dia(l 5pliI~r:e o;.~UII~S; ~~w '~]O- to m.S-:lI1m) ~ira! . UV\Lliclouds. m1~r Ilhe: s~li.llh .~le V. 2},. sll!!'f~a!ld! QlQ_S!I~g 'lite, mcih!lHe cycle. gil;,>,Q,graph!.gJly '~xmoolleQ! cl.oll!dls at4~,W.~ttJ!~ w.'Wva..~ diffeJCliK:letn~grw.g. \.V'eu._~ I~T !MM~ (J),a:Ildi ;! :Ilaf!!lecloud ,ethane ~e.af th.e IWfiih :Bccam:c lillieIIcar"iufrnNd aeli'!OSd~opacity, in w'CJi!lmlltffy dlCa.~~iilJltjemldl Il1<lgultmi,e of Ule ~he dc!C!C,~ fOole {of). 1I1~eSe ru'Kl Qihc:li' types of clouds; hflN~ T!tm~i's ~llOOlJbefC .is low (t - 0,:2 at2 ,~Illn), ,ght (I,p<tClty el~hru~Qell.lenls" and. we ~. H ~l,i"ID._fd~nl~lliISi teon of wLd.es;pft'adllll!d.urr.ne drizile: jli'O]lpit:iliOiil. boon prodicl.oo. l!Iiitll.dle TI$C of ool:llbin~lioims of can j:1Il'llt'l(ij~mmto dm!>!iI:rfao~8Jt foom S'tmliiJO:l]1(l douds of solid Incdl3Jte, chemiC9~, miicr,op'l1,}fS1cal, ,rlJDld g~Ule~t ej,rm.!tlattcm wliiBl"e m~lIiIfl]m .8Jb.J>orpt~QiiJJs n~:gitgiMc: (U), i bdiativelmm~~r{RT)mod(lls ofTimil'l!;s sp~im ]i'I ordLl't to di,'ill~1ll1 Iih,c ~.~ghtSGa!imrud by' mrlOO6.~S {S, ,6), Arnalyms of 1!I'm lootllitmle mlaliw doud$, d:ri~~ ou:'idll~~ g!~ 'Ute 1~1I'"~' ~~ ~~tI!~.nidt'~y p~!r;.I.¢ ih¢ H~yg~n~p,l'9~ '@liry ~~~@ h<l"'~ b~l~ !,:!~ to pm~ Iblll~l:tl}:Ight~ (If t](I!!Id M :mggc~lll: :Ui:at !illi,~ is ... oolid.,!nclJ~J:Wl clooo lops !lind.he ael'Ol'iiJl v~jcal51~wre (I,2,,11, j'.;1).. sp~lere, iJhe oO:!"ilributio!ll fm.i"ll lbe swfa_OI3 a~bOOo _m, 2J(}w 30 i!:Ul <llhtude mid a. ligln~le of Ol~e Ihe~lailn cI~l:~el~~esin, lii:lcumrely r.'e" vw:i<l~on {PIg. ] A) WMN1I11oV\ed.5tuD:l~iie iI~ ~he lIullOspliIere (fig. iWiledmlLC ililal wens ltile oormaoe (:i), [However, the Irievins al!!~b.ld!es w,~1J1llhcse Il1I.odb~sis ~lIIIiill i~'he Ii~~tprobed ~e lmiWlll, I'ItI!l\l'.il'l'~cll!l]lilCIis SCGn 3lld~i1l~am:lii.1g &i~e(8) !Ii"G dIN': oon.m~jjmt(ln flutcttCm for!l ]:lruUm.~~ar w:lll'll'elcj~th IB)..We ci~irk .. qll.ai~mOO. 'dn~relative 511[ql.ly I~he.,ql\!'i~r minfa.ll (9),. whi.ch it~ay(fICClIiu dWID'I,g is dll:~i~clJ~11.0iI1 the \-'Ci1.ical. d:i:sutil;~ioi1 ot' at.'ro. race :~i.JIX fin irnages Itaken at IMivnl~iiI.gIilil.s will1l. mL 'VilJli'iattcms in. Si!i:rfit\e('l .r~Il(,"CIi.v:ity eaiil. :3J~OO ~i.iiIiiIi.f!.'Cl,1iII~i:lt:!, with iDl~i;;g:ible i1~ildmi1e: ,~1.'l inllli:l~ s.kiiU~ill2t ~WI ~i\U!jeled, by dYiii::!J:b'~ieal '1'1:1-.1 ·1~ 1m• r -I:I!.;iitr0-I:l'l ill illiI-' ·iVW illI';_~· "!~,,r:;;ru -• . _ Y".!6 __ t ,,~ ..,00_ }y \. ' .. _ .~ i~ .... __ "''''t_n... ooo~fficil;li!lU 'be ula'lked by ~·"'iIl!mce ~loopli!L~~t;; (;jp<IC~l)' op~ci~y by !Inin:mi:,:ins, the ·oa~~g!! • are· besI: Ctm..... ~nt.->d ~~1ere Ole 1f.I~)lgens Il:rooo O~le way '!o Ib:rreak 'Ulf-se deg.el!!emd.e5 is tOo 8tI1l1Ui~. bctWOOfI Ole s'!JIrrace··S!l!b1l!01.C~ed image (If the <llm.o.S\I'I~cre and lIIile im:i'!g-e oflhe ~rirace CfLS. lland'ecl~ >"~ I.lisa!)_g~e'weaOtcr SI<llirnIl CII1mt d_~ 1<!i!100UI!dyiiil~lyze: ~trn ~eiI~ "lon~ diff:'erenl S2')o.ne me. swrnce fhL" in images pmbin~ Ute palllS IiIlmugh 1I1e <rllnospl:tere. Sp.atiiainy I:esOl.Ved ~3 fro:lin ~ Imw d;:w of ~mtSMljl~.ems, :slIch, 85 IOlMr oroposplmre :~ -7.2% of:'tlm Illll:X.n! Img~ i l~lp.3l1IDrnl!l1tm .As!rOOJIiII1J', Urri\i\~.r5l1y Ulifmni<l, BBrlilil.@ij, ,ai ilm:OH"S:lllPP~ilg [1~ff3R:otl~:magingSp'Gc~m.• of Ihl'l i>:~rr~; 'wlIilnch.is QW'lfl:fiMd by (lllIJI: .. R"r (J!, '~46U, IlJ,S1\. 2(oeilii1llri r'Dr ~m~faij!;'~ 1~liIilIilJ)' Sdoem~, gmph. ,~OSIR1S) (/4):u. !Iln,~ M. Keel!: Ob- m.oocls. Alli.o'[· [flrlbImCllm,g d~c SI!.Irface cG:l'lrnlluW, UlIfiill~r~i'l:vo~ Ca~fjJrlili~" er~eley,.CA. ~4'611. USA. B tiO!ll filOm ~'t!!!;l!S~Ihal I"r-.obe 'd~elo~r I~ rNlesPJif~d 'Vo whom wrr~~~IiI~Ii!U: $holil!ld b~ ondressed. lE-m~!I.~ OOf!\!otto!)' ·or dm :g~c~mpli!ro.!' OlJ~;M)ia!!!!> I", lijl~eN ear ~I!l!frnred (SJNfON[) male@ibeiTkelez·edlu sP.1~!)~".lNC iderltt~ Gq;uat'O~l 0lEdl:y .C:h1l!n~~ C<l!l

1111 litallfl'~ atme:sph,e:r~ ·yoe:t.it h~IS IIilOt beelll dIilma:l,y Q~e,rvll!id,. ·ilI'lfldl1the Jcllgijonsii\lih'ffi'e I~alin (I~I!Jur5alre UililklilOIl\lIFl. Here we prlesem. llIe~r ..gnrfii~aJr~~~edril ~[liJm ~he Ver,Y I~ ugelle~lfS(iOpe"lrilal W.• M. '~eck IOb5iefllillt(l:ne:s. that f,evealalril ,eniniillrilloem:entu of ,opa.c:ity 1m l;italrl~s ~ropo5(p,h.e~e O.1i! th,e IIlllIOUlrilintgS1tde of' the l~ea,c1inQ he'll':ui~p,huf!. Ii!:e:trie,wdl e.'(lmlilction I~U'Qfnl~ifS ,i3Irf! ,cQlilsistE!WIIt: with «lilildel'lised iIIiIifthame ]1iI dh~u:ds ,at ".1'Ii ·!I[titude n~i3Ir :;ItOl Ikii:~ClIil'lIe>ter$and (OIIi!,!~l1T"ritailt rn!rtb~li!~ dri~~ btelow. W!,~ mtllSit!.!lre ~fI'Om,i'!:SSts ·ile: ~q!J!!~o!lfil1lllfeg"h;):Iil,(;)ve:r"I"ltalil's Il!Irnglhte$l; 'Qntilile~t Xi.'!IiIIi!QIl!I.~ii'~rfI@1 t:emper.!!~~,!fie: g,~@dl~i!i:O~thGt 'ilI!Us.e Ylllr!il!DfJ!1s: ~'1iI methane Irelatiw lUllmidity. windls:,. alnd NptJ9Wi1IPhy llI1~y eadl Iilte iii ,t:;QllIltriboong fat;wr 00 th.e' ull1lCie:rusatioilil lrililech<lnrism. Tbe eleuds illmd IpriElibipitaifITtol'lariElotprtkaUy thimail: 2;1)mkmomelelrr:ii •. illmd l!II1Iode:~O'f H:SUlbvii~]'Me'" ClJCh .5!uglge-sil: toot the ,droiPlek ,U,el 0.1 miiiUiIiJile:l:er or Large" .. d !iir,edpft.ar~ollli:se-,;ped!:d
9'OO!l"'I~h]'il~

(15) .il:~.I~he Very l;.\'1~c l'e'lc-soopc (VtT), .rure am. ideal s;.o~pf data for such an 3ml~.ysis,. De!!('; _~mro!S mff:Y be lied to crsatca ~j)oolp[C.. Wff:: of'Eru:rrll ~(l\~f .~~1'I1fi.~h~ru ~J1d:f".;JJrfaCC, D!.Irillif:l ()"!Jr~:np.;ligmJ OOI]1(o!~.i~rIl11~ ~~ll.;lm chll:nges in U~.egl\Uba.l(futl"ioo~io:!l of Ti~4il!1I's IlCirorol. ·wc o'bservOO.n~n 01:1 28 :Fehrua ry 200.:5 IJiru.versail dnile (U1) wilh S~-"oN] (B), and: Olil. I i April. 2_00'6 lrf w ~tlIa,OS.m.1S. ro~thcrd~c: t~'IIIoin.sl:ru.mil':nt,'l IProvrd(';if!J;d"l'lpemclm1il.m&a!ru~ m,~ItUS ~f 1l1an. HI. ·dli Ifeli~nl tl[jXIch_'l 3'iIldi 'Ii'i~wit.lg
geomL';llItit':;s, S)'~I.emai!ie~ffiIi'Ors thilrt ,:IDrlNC:l rOOm Inosail!;ki~lg andcorfecting fm I<liUiI:~'s iUl1~{)s:phcre (f\!.. S ~.)!.ali'e SpeCi~I'iC~{Io ,eaCh, ins.lllCI1~.

or

or

or

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
IF'tg.ll. MBOO !'maglJllgj aflh~ cDnrlMS'EdI~~ s:GiIIIellf~ .aI: .~: i3lltiiludell ~ili1 theiiltmospher'e,1lIiIe '~(!IWierl!ropo· slPh@r,~ 'hl~ 20 Itt;ri (;iUiI bE, pr,~ed b~ sui~· tradingl Ima~ie$af vtaV~

l~m~ltii!s Sl::I1ISR-ew ths 11',niatiJJ filS: ilil SI.IWale re:ffi~~ tA) li'rom~'Hmse ~11a1: :il'obe bo1lil,tJlile Si!!F' '~a::e11:0011e mrlmp!)" i ~phEfi!(8:). nile ditifEfB1U! imgg;~ (0 ~~~~, ~ di1!rk.
r'e'a,rure' ~III tliie llIlo:rnlIling if:q,rtJ~aJ rlegioos" 'Wi,~1iI

slJJ~b~I~,r 'Io!,!giwd~ of :ES9'lW (lind 42:"WfQf ~liIe un ,and ~ed:, respOO'tlIIi,ilEiI!l'.Afiirac::ts s!:tdh
al~ ~iH! 'l.anow' t]I"U.!illf

:re\!l,tu~:illl the \ItL T dart:a i1!1l'eumot ,~s.~~d !I!!i~h l~otliJilil~rutlllilerlti., nil' Irreg1:Dn5m'lifui :ICllWIff MfF

iii! ',.~ dil1l'~~ii1!)~im~g,~

,(C) hilll!e lIilU6aJ!iE!>ti irt~ ilil1iOiSlPheric opa,.ril)r,. nil! I~OI!'ii@~ s,ttiil'tQ~ph~rli!! Ciil~ be sim~'1!rly pro~i1!!dby' :sll!!bWi!!,ctj1il91 lmi!:!g,~ ~,fiji)1Jj Il!.Ipper stratosphere (Di~' frollil1 im,i!ig:es c,i time low~ SNilrtc!Spllfll!n (I:) to, IliliglhJ~ightthe (Ollltrasrt {Imom the SPH (F);in, this (~~,I[I~g:E.'!r ,/JJ1F in(II'mlhe~ID~lillig 01::1\) sid~ o.ITInlU~disk: illlbo·[J~ ~MBWilil~(}jiIfl (Fig:, I C). The d;Mlk. :li'ill:giOl~ coOver s~;ugh~:tyi!l!itmnt pl]ll!.ml.'1N aflhe ·dJ~sklDecat1llieof d dileIDelluvi:f}\v!ltgru!!g~Lm during 1!IiJ~ ~\"'(lg.bgBit\.'a~ d'OM, yet com~pond I!:O lale :saulel;m,til!l.1!~ nn Timl1, $0 the: ,obsavatLon of ~e ,dml~ fcml!l~in. bod~ dmi1l sets 'is aCQl1illnnaunn. of tiIJIetoc.alize.d:

dlka~~ !rn:ii~ :s~amrim!;. 11),~n~!!~()~ illiQiilgl!S ~f 'th~ tflilp~sph~~· .aJndstrat(l" !ipll!8rl! hllw lal CIa) pt'llel'iro~p3~e~riQf;e 'of MIF .~. CUJ03 i'lillldl 00.0005. r'~5pecti~e[y.

Ifl~. 2. Ci.:ifii~:in ~liie diffufti:iiiOeimages (Fig.. :l.,Cilrnd .P)ilj due to kiaJl1ized

'dbli!g~

st~UfJdthatilE! dark region, in fig, 1( .~is; du:e taa rs ii±IW~illrn.liIilll!!iIiI l:lparil:y. we

,calru!a~dj the ,expedeci (!OIltrasi: straoosp:nl!ilre' (dmted Ulne).

iii!. ~ltMII::tiO;III. In1 om'dil'~:uib:llII!I!ild~~

dumgc in 01'9C[iy, The Itarure of dlm Im.ctremoo op.adly .~ d1ttr~ unh:t«l by c~~jllg ·fI 1:lliOdei or dm d~~~d datacu~, ALSO- k> 225-,m fO~IQ!JfI'I, oo~:tdlU:lg ~o ~cI!!t Qooe.~ sp<!1~~II)b!;cl.~'~ c<!!cl!I~di tlISh,g
a ~"streJLliH m.!lIBil1:caJ. ool\llDioo (Q. i!J~Rf IJ:!l!Iati(H~ (.1(;', /7). \Ve.~01fl1ted ftl' the spinal. varitadoniu, S'Lmoo:ealbedo bYlIIsiillg a VMaJ alnrl~nrrliOO:ldl Map" [Jlllg S~ln;Imctef fVrMS) IMp oJdw 2::()I. 1't'I ~ a.1bLMb(/~,~illP!ti fpr'ihe: tl'l;lIftu::e rullootivhy. 111'il; sl;!.l£'U;l~ ~1\If:Jl L~ groy wilhltJ!;lf (la~~]~m absmp!iotlfeolJlI!feS U U~Tk· ~~o:t (h~) ~6nc-. l!iOll .tJ. tflie ll'CfO;p~is O.OOZS kJlu-1ilIl. oolllbm. ia~ilu~i\oo'iie 45°8 and i'llc~es lowmt:l dle M~~. by !I.f;'~tor of 0.0065 j;iCr de~e err laliilJlItje; (.13),

kiw'~1!!',~posp:h~~ 'mUd lifllW' a_rn,dl L~~F

I
I I

~liIe

,,0.. 05:. 0 I Q
-

..............

A 1L!f1frqpC!;JlIfi~

~ 11iiF' S!r.llbo~Mf'C

1 ~ S Condensedl C~ ooluf'l'ln v.olUim e Item'll ,em-2)

Ikni ·coefficient (10) m palh len§tlii (Le., wh:!!111l Vlrill!lu'l1le)..A IlOn~~imdlpoilt~.. .Iinadimiil ~ m.l]l .[1 caljbm~iQH m.v WlISl~to,convQ~vedle model ~bt COOl~SOiii. .villlil. lh{i ~~f'io'aJj!ms. [fD:lage-s Aei'O:!\.(il. Cl{]iilCI1'Ond~~ \\i'i~~. Illi~urn~1I1£ ! from 111~.einode:! da:toctIioo sho~v el(.celhmt.~l Iftru~ \Vllih. i\ sea]~ hilli~1iIl ofl 00 .Ia~:t111'1': t1lent \~I.h. i~(},b!!MI'oo.dillii. 81.). ~ {~ig. OOi.Ul!J1 po1.!ar~OoOd {S.PH) .ig. iile~w:td ~ aclGutb.H!iflgof WildiJ. a moo'ei .(if Ti....1~~ ~1it1OOp1~~1iiiid : exilindL'Or! i&oI11 to 70' bl a1~~looemdl :is I~cl 50 'SlIJffoce, VMOO/S hYP'O.h~ fur lheso11!~ .of ~n~ mIDiewalldlof 45'~.s. '1J!~~lbrm~~ ~in.c6ml QLlSef\1L~dllikoontmli !C~lm:e o(rl~.IC) ma~ ,be {O.OOI k1n-I),ooosislellt WVO~:~lIs'hmUJeHuy'" ~-.d. We ca!co'lated; <I cll!EiImcleris~ic~cnm and gelfls.pro6:Jc; wa~ med dt~ooghOOiI dtcl!:'O.I)I).',htl:re. dCI:m:tntlfloo.1I1e rnl4mn~n'.;: in d~e 'W'!i.vel~il~~IiI. 0· 0 Basoo m Ikl· tCIUpcr31l1rii': at ,!l ~ic;i!IInrSJ~~I.iI.J.OO, g.icu~sc~lilll.l:Lg louimag&~ f'i;g, l (0 olbtnin.i!I in {lOl1dtNt'~iru.pln~1!Hl1moo .~oo:~y \l,iM in.al~'tIl &'; no~.tuil'l!llKlI1hlnlCtooil:l;a®~ n~ (.MJFij) tbr' 00lffit. diu,\! 1 a·~~(lrlk~gidm Bol~~.~Ome.ll~e I:lp~d~clI.'lJU~ low'!!!!'!OOf,IU~llC!'L:l:.mdl Ole low'I.'f ~oop-l)e=re. llh~ OO!1~ ~ Inl!e~ I(.!Jc:~nooas !:he .dJlfferenc:e lbeof.ooild:cn,''tld! :f!lell~e is ''Ie lpmaoo ,(JifiIJ~a~~

tween tJJJFo ol_!1.4le MlFlh:Hil a !l~ !ipe£ln:iiH.l :~m ~ w:lfiich tlJnJoodi pa_l"Jn1eler,~c'li!aHged. 11111g, 2, r wep!o( Ihe OOlittr.lst ,expecled.illlil'llillgoe5 or~liIf: InwcrlmilfOSti\'1CJe ,11m::! lo~r!>lrn~osp1l~ 'W~~ti1I. I!!,eoo~mun of ron.dcilJiCd-:p!1!SS@ i:liiflllilan~ is varioo.
Cltrutg,~ i~.lli!i~lhare .dalc<i1Iy ha;~~il. ~~ Wi.fililtiQl]1yroloo ,o.UI. y jliutd~l,]iiml)'~i'Odijdllg b tile ,oo~f\redl ·contrast W~tilileobs~\~eilopoc~y ernhl:!li100lTIeln were OliI:mi>1!!tOOi to, s:rnatllf!i.1fOSfiterk: lWi:Zeparticies (~o.om.nun), l'I:le!~1lillie s~eep wave~ hm~~II'I,cl~;~,n(h:moe ohhc: G'x:t~m:::Li.o.ll. efficicincy wooldl Gl(Mi3p!1lla!!~ ({I, unilO[1lfieal dCipd~ et 0:9'38 ~lln (:Mg. S3~ ~@~ '!h{ol~ ~ila.l\l'~ 1iI(l1: boon mpt)!'!:!! (lif'
<i~8i1l~ ·eP!I~!we!1lel~l'j
(IV:~ Xmadl!!o!' !'!eardM~ m{)"~il1~ l~enlispl'l~'C'. Oli! lheaijl~erha!1d, .~.nlist

REPORTS
III!!mll'i;l{1~l~

!!:,':
,I

SP"'{M,,~!!<

:20 : I'
r
,

10,-"

Ae:rG$(i1 halZEl lexlll'l!CHon ~km'~)

It:M!I011

,(MlIlll!l1'

IFIE". 3. A ,d~~k'~~('~mpgs:mlg Chllud:of t:tlInd!::ft!s~·p1ilase rneitJilall'l~:Is r~taIledl lby goodlness.of-fit fAX,~) COOt:Vlllr5 foo ~evellili,a\titttJ:d~5' amd mlulliflrl vll'il.llllle5 ~f Ilfj;~~ (At Vertkat I~rn!fii~ rCif ;.:.,.m ~I'lr,o'!:dl,~tfu1 cti():!'iat two' lrCi~tiCil1LS, onl the di~k G!&iJ1,1fI!il1 a,lli1,t!!!O@~of oolildmSlOOI m@1!ilili:llili! cloud'tSshowlll1e wlth ill~TIiitllU;l!a~ la~!!I!!"r~aJl(l' of ,i1IWIifIIlSph~riI:;feiJl!!!Inlrlj;(8). lirl]ff,emenmimagE!:!l Iil'x1J;artedl

rroli'!illi~ RT model ~f the Qbse MdIIO,SIIRIS datatlJiJb!!l:qllrf.!obdy rep;ood~oo ' tha (!ontra.t~i:IIL!lfiOO 'by tine' m~"llmemelilt in IrOHf b'olilospnenl(; OI1<ldt¥ <:Inti 'm~5!ClUth polalIT I:lCilol (S1i?H) (,t). 1~,tiiijdi(iJi! p:~olile5holiii'l- thi;! Ct1ln;rer' ~f the il:I!'i~k la~iI C!10S5@Si)',a:lf!clhm tifJ@ 5,PH (bIllie tri'G!!lgles:) :sinow tifJ,@ chilracterimc ~ d~ffelll!!n~) in thE!! ,tlBlloool d~lilsffiIN'i at so,1lItharid equl'I,tmiiii1l1 la:tiiIuml~.
dose .he :rm:Ul~ne cyde arid! 'dIal !11m ,~c 'ooui~ be occlmng ,ovCJI'IlI,c'fldy' 6~ of'll~.!!' globe {f)"B¥ miCilSui'ingd~.~ g~fiool ex:leUl oiflm::IIM1Jlc clOud, we see hero tha~. lihe m0.~iIla:lJle rizzle: iill indlccd. d p~;.p1na~ronf,~t:aood! to. ~tr:ati r~n1l!l. ourul!lnc:ru@es d OOV~i' a ,~oo~iaJ:iili",1 fi1l.ttLQI1J of l1mu. ~~ i?;. o~e~'OO furl. II~ ~:lami!1tg h(:o:!tU~ sp$lCli'l\ <lind WiC fl,rst ooJilSider ,~ d!ulllnal miCch~

(
f

\~I
-~

SlJ!ICI CF!4 @!CilIdi -1l0~,dC\ld

~seMl~ltlrlS

1.60

1.64

1.68 2.00

2.05

.2..10

,2.15

Wa.~eleng~ '(lJm)
IFilg.f. Opadty ti:liUi~dll[l)V ~ doocl of s:cIliGilIIlll@tlllj)nl!! Ipr'CVil'dts ;a1~iJ;r.lilifi'calil:tLyilmp:rowdfit. ~f ~@m.aat illn~DC;ailiofli5; olil,lihe rli~k ..A rle',pH~ll.mtatiw ~edd05IIRilS,~pecllrl!!lm hom the',oel1ffir Cliff~i1e !rri~l5k 'tiack) ~ (~~aredl a.gli!!fli!l!tmod~~ SiP~~Q11li!1'1i~ !htllW' .aJfl:d witlimut (red) 1'1 dOlJld 'of solid mlrttial!i!rei!1l ~~ 25~ 'to

rtiJlallilOilh:ntc.sOOlmo_o:~_ .BOO8.1!IScd,1.{; IlHliilllllle :15 ~too smnn£! ] 5 km (7) in InJiiC l'I!llOilliilg [HIl!IY@,mtS iml£led. arI: looaiilmc Siil~ar ~ilrID fLtST]1 ef 9:41 a"1m·q~a $m~II~(I'r,!\emnght cl~nm remiP~tl!l~ ~t Ihis :t!Illf~l1Id~OO!lld ~[lil]are drqllliU Ihm:aliOI~. (hiat would ~~~illl~ MI' dclzzl~ lll.lli.;: loweI: I~~il~ ,lOilJril1Jg(JOC Obsel"'!'atiDrn;:,il seeulS it\1i,'a;j], drizitillg o:n Than 11lI1~iI awroxi~ m.Mtily U);4:0 3J1iI1, L"ffiT (roU~tl~,y .3 E.ril days sWIm- .sulilrise,),. wbid:l .~ CctJilS,~tiCm 'W[~1I1{;
:H~:Y!l,~nSl1®SrlllS,

nism

Leyrer ,ef the: mod@l. 5ha~ed im)[!l,!J~liIgl[1II Fj.g. 1 and fig .. fi5.
(II:r~~~qrm~dtQjlC;

3'o.km

Y@m(f!

i. rIElgjO:IilSrlil~)j']cat:e .E!Ci1irfll blllfldilPlISSe.S

IU~!id

fur

1~li~f@rel!l(!!!

IGeOSra;phL~(~[8
and co,ntl'OI ~~ll~~

:lllllY a!rrr~l ci"Cl!i~aliO:ll

I;lQJldG1l ....alnQu.

.on,\,; ~~;.-

ubservatimns (Pig,JC~ ArtiftlCls or vafllltiolilS in :S:I!uJa~ a~l1Ptitm \:..mro.fI1m eiN.c~uded Iry :~ribm~iI1lS,a.1fI13JIo-grrus; (fig" $4)1 Ji j:'f~nc~if'tll3.gtng 3t l5 ""isib~e w~\lel~ngflhil 3... '\,'\!I~II~ffilc:I >CO'IlIMmo:m j,!1TI1.Th~ d~ff~~nI~: ~In.'lg~!n 1I1~J(l limlildl (i'ig, H ~8uly ~-Iud~d~i~;(U!iL 55) caJ!lOO :iaood. to il'K[~pe~d!e!iltl)' :rench mH tlile 1Irhea.ililUt:ie .uidlo'!.dCO'lUi~,ll of QQrgdetlsea K~oond !Wile!h~mewerer.l to obsef'!l<llj(l:~sby tl1i.!lilin~;iz~t\g qLl!Liti~tive omu::llIIsiim'gs:a;risi~glIDrud1e i!ltiiefOOl~ l]lCiiJJli~iI.Iie~iWlkmool'?ifeem a IlIDdl:ll. ,fUllsi~sis (Hg. :86), The ill'l;provelil,lentin :spe"!tlrnl~~: ,\'iCI"O.SS 'OO~ih.baild.,>, when oQudml9?icll ~iii£is dill:macu'bcand o'~i'Vnti(mS'> Tilrl~ eland of n~dlru\'Ii: \l.iasiildOOi:llfoond to: 00 gl.oba:l~y \vldcspod:, \\I'.ill1~ iiiICVl!ld~,is mllL.~c1ii~' Fig. 4. a QCil'llim!~lvoilumil:l(if U'iS <mj~ em.~l ii:'ilh'l'l a~tHrud{: Dep:md.~n~ em ~;~L'ian(jj O()m:poF!~liO:[fj~d:t.i1z2I~ eililcrreaJclll tl:le smlfateof mm~ ;1. ~r· nmg,e ~f2:5 L035:bIll (F~~,JA)'. T~:!1Jpern,~I!!!!TeS at 'SlIJfface nwi'1l. t\lllllG'L1,~b laO ,dj[rect d~,ecllo:~ ·of 1!W!esea!]~UMe8 I!i!dicate dW !'!iIJill11me nU~lhe a dIi.7;Zle llaS ~lrepo:~ed by H~IY&lelilS(8), !lIe solidi (7). Triue mom'in,g enitim~ooI1iJel~lor~adty is uniformllnl't_!\ilIae rl1:bdll:S,ratio oolow ti, knl (1'/) is (l(!I1SiSlelit willl mn oo'djti\:m~l oolwliIl1 '\IIohlime of {It25en:f cm-~ below 20k~1il'. llCro Illl!lIuUlf;i1s a roil.""' s~nt wl.lffil.d:\e eV9pota:~i(ln ofm:etllmHl [rom. W Hq,uirnl (Pig.. 3B),. Tim cln:rrcD'L~"e :~nulglll! ,a:ro: a dm,p~G'1J>(21), Wi!: dCI:eetoo: ro~ffiI.I:EUl ,i;Oilid m~ml~ S(l_l~'I!'(!lI~~tof Id~(;l verlieal I:lrofiil~ ·Oftlnll Impo- clitmdacl.2d to 35kma:ndlfil'lO:lilI'Iii'L,g,clri2:2l~ iJc~Qw: ~!l1'!e"c e~iric~ol'!ja!f!d !J~e caJ!~~JI,at~ da!!aC!.:!I~~ .U Imdbeer! !5!.!1S2-~lOO ~lila1proCipituL:O!~tkl!]l wi~i~ ro!ldc~clI~ru~eo:~i~yreprod~cll Il~ s!!!bvis,ihll:l c'~o!.!td'l would reaeh 'Ute ~l!rf,ace and (irptleallymiU!31
2:;1) JLlll'ill

dlUp~cl$(>l[]JI.O~: ~i'I:lnil')dlstus ' W(l1IJiMbe ()p~:iC3111y thin. at

bi lityis IImt Iheo'bsl;.'~ drizilc;is due ~oil~e 0001 iuS. oil'Siir c~liJsed 'by adiVectLQUI, ,~cm:l~ winds mIlaY':pmh a m.ois~: .ai1mt~ upslope, dirlllS
cOOling
l1'01lNPf ~t aq:m driving

,oondClilsatiQIil. Obsci"'!.'lIc

wm

s,,1:00 dl!Jnl!£ have ~"mlln ibal! pn,""\Ia!iln.ng ~~1~ ~!ow 'n~,.V'~ llliIL'lbrigJI.t OOIIJ,tirnl~l1tq!"' .x~<tdt! (2J), lr 'ih¢ bri.ghl ~gLl(ln is .il!1~, ~ l<lPOAh[<cai, hvgh,!h.ell <l,'iOOaslllf' df::izzle n101lY fi:mill illilrn, cover nke Ialfldn~]a.ss. TI~.elrelationsbup bctweCillII~:c,,cllrriizzle :ood lhe bri.~lrel'loot~.vity or XR1!IadIlIlS l!Ii,tdear' (24)~ anditis poggibJe Imhat dl$ ditiZZl1e oonlIilblutes to riil~un.~ itJn(;j bri.@'l~l ~urr3ce o:fdl¢ da& d~~~d a~oot'i:lfha~
1!!1~·OOllin,lii:;lltiOI~ of Ji1i~],111i~ C o(ili!.1g and. ~oca!
1

mli~lhnales II.ogi;\lhelt' ~'rn!ilr;e f:or crnlSiswrU:Ily mis:l,y ~nom~nss: in Xalladl!J.

R.~mm!iiiiile.l.'i!lOai~dIN6reS
]" l!1. IE. flirlD'!lm. A.. lit m~ucl'u.. r, A.. Qiflill;), tlirlilll!' '~lO, 'I'll'S, ~,,:oo~. 2. C. 1\, bM~~~! I'll.. 56ernt310. ol1¢ t!.lOl!l5).

e'

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()I'"q

REPORTS
,M. Eo EI~DWIi. ~~. [. SdI!IJ~,r" A. It Im!lllJfhm~ ~, A lmjilliolScie!l'(',~ ;uo,~n ~~OO:SL 4" (, A. iGrifnrtll el ",r., .Sde,tla' 3i~3, U20 120~t s, f. l, ~nl1l. 0, ii, Toom.. '(OM :'HI:Z. :;BO 12:00.61 6. p, 1t~[iI~~l!,Jl , !l1~If!~~~~~, f. ~!!OO!i~, $, l.!:OO!1(jj~t.J.. f 3" iii.. (i ~,

is,

0" ~ loon,

J, 6e~flI. [I;es, 914. 11l2,1!l7 U'lf39).

~I,

c, P.,,M~k:lll,

'Ii. p, Adlli!trrnam,
111:,

K,. S!1'I1l:i!3:11!Ul'I,

17. C. ,p_ Mc~,

1. f. f(fhna £UII" Mi(j~r1!'.!I4il:, al: Wl11l6}

~, ,M.. ,1::;' 'T,liii1!l1!iOO I1t aL frlJ!ftrnr(j 4~8, ?I!:~, (21105]l, ~. ~. T.lP'effilfi ,Ilf (1["j. Ge.~ ke!J. f.ll'Il.l'!HillU, UOOli ~:2;006). lit Ft, Hueo, J!!. 5~II!()he~-Il.avega, 1ki'~/e442:, 423 (2:00&),

Sd~~

U~ar~), ~~, ii, !!'i. ~J'~~

II, P'oLlii(il:.

CI)!Jrtin, 1{(1fill: SlO-, 2::1

Jll,

2100, (:i!IOO6t

ef !!l" 1\"(lI1lI,l: U!6, ~~ ~20Qit ~9" G:!f!I5.:~i'a!'l.~ll!iilFp'li!llM .:If!! I'J~. to Ill!! !!mHf~i!liflc: I!JoI rninrlmillmg Ihf!< ~m, ~ql!l<i.F>ei!lIie·sid'LIaIJ;~F It~~ 'enrlir.e, 0JI:i@. '!til!! ~[!!it.f1 t a~iji~(Ifi! . lio!!it!!! ,~@'r'I1ralIO"i!I\Ii!l@ngtlil!r 1l11.~0:5,., l;~~.lI.&lt~iiUI :1],,028!1m; Iu~. wil1lll~11 b~lr lma:!iillllumo~ (1,.052. (U)1a. o'O!Il(t.<lOO O',0211jW; <llldl peak: ,~bw!ptit:ifliS ,~f 99, liS. .~1lH! 16'%01 U~ ~lIIf"(\f!

2~5. Tlid~wrn'k \lIil~ !Illwon~d bijl NSf!M til!! 'il'OOIIIlO~iV ,Ctl1tt~ for ,A~,pl!t'/e Q~i(~, IIMlIiIg1ed, bj '!h~U1f1i'1'Blf'm~'I! 'Dr ,QjlilG!mf<i .ill, 's:.all!~ Crw U!lilel '~D!l!,pi!fillive ,il!!liIlIlmenl: A'S'lT~~a.161aa. NAil'! ,~~~(lI; NNlG05Gj!t6~~~lfKIIlf:!oe' !C!:I]~~r fi(~r !:rL!I!:!!It~l~ !?!fIrn.gJ;;iI!y 56~""~~~t~~ Um~~i!y j}f C!I1ifw,fI~! ~t Bier ~~~'. fleIt~ prge'lWed 11M ~'~f~ lIdlii:aiiieil811 tmli! W. r!.~,K-e()k. (J1iJ!l1!f·!litlllrya11i11l1h!! sacl1!i!l1 fli1ll!illIlll'i n (!of .M~u iiOI 1K~~miI at t~ \Ill o,P!fBI.e!!li by Ill!!! E~OOJII!"am 'Smltlll!!m Oh:!@fII~ID.i)'.

lll[, C. {!,. '~ff!l!b. T, Owen, R.Yl'",g:e~~j ~\,{1,!!l1$ 9;1, ~6l (lL991l! ,12:. ,M. AlMnlo\:Q\!f(J, I" ,~ ,pa~~,r, 6.. JIi~ S. G. lGful;aFCI. H, C ,II. !Glrimtll(,~ltl8l Ilfi. uJt n, ILl1SO:!l. (2:'0~), .:u:a, •• M. M.!inltovit!; iI3I .a1~ ,oo"flhlll& ,k '1P1a11e1li} :nt, J:, ? (2 00.). :IA. ]. ~. ~~i~ el 11/,. PW!. 5Jllf ,~E14!1!!, 1,6@i1 (2003). ~~" F, IEi~Rhoill.l~r >e',!P!i., 11'~ ~j, 4;(1,n.l~~S Gloon
1

!lene'~i¥it¥. re~erti~l:I', 20. W,M_ 'Gl,I/iiI~i ~. Sd1rmln, ~ Q:uirlite, kQf~~ lI:~S, il8.6
(moo), 21. :S. 1(.. Alf'!"\,'l! t,~a/, .• Pi!rnri?,t SjXXl: .S'ci. S4, n ~2'M6}" ~2. '1'. T,bk.:!l F•. F~ffL G, Cfi,IMlba.n~ T. Wk1~~~. B!111 M, Fukbr~llr~lli,J. ,~J!lP.. 1r13. (Plt:lJJelil :11l1. iJ!IOij! (2006), 2~. II. D. wr,e<I!~ e;r ~., £(r.l1r.lll"e 3U,n~ '(:!OO6t :!l4. (, A. t;i11i~itb, Hw.w:e :;a:64. f~9?3.).

ao.:

Sup'p!l,mflgi
I'i~. §;11!!J5'6 R>e1i~re~~~,

Qrn'UiOf! .Mi3Itf!rial.

.ml,rI'l\SIl:i~iI1I!llffiil9l,~rg.om~nl1l.tlllo'JlM62'1i4lIOCl Ob~niillnr.!lrl, 1100 MllU.005

a: .I~I'I~ ,~IiI'l';

sn

,~~e:P~l!i'! 'S O~OO~!lf 2007 'liI'bti~l1e;d olllil1>~ Ji.1 Oct.CIber 200;: ::IIO,112M6me.Uo!l,6:2:<l4 lm::nt!!1;:! ~1~,imJ~~m~~,~n ~iti!l!! Uli~ ~,~~" wne~

Faeultative M,al'B' Clhoice D':rlive:s: Ada p'llive Hylb ridI iZ8ltiiio,n

Mitilligl Mthalrl,o~he-rs;pede:s; (hyMdi~MjIQnl) liS otfwnl flilalad'llIip,tliV'::, COln:~II.!'~IiIU1,~m!~~e~ t:YflGilIlJly ,aivJ(Jidlllil,e;te'ros~e:dfi(s GIS;m~il:es. Ciofl]~Giry ro theSie tl(pe:ctai(!f1IS.H!'ITl'aII.e' :spade-wm; lO\1d~IiII'e'r,e mare l~ik€l.y to C'hGJIilSoi1l hete[o~,pe(m( lITIa'I~ whe!ll exposed to elllllol'ilrlOflllfIElliltill[ (,Cl!IIId1~fiomthdJt favolr lhyibridl![(!,tioml,. Ifldeee,. ~lilO~e'femal~es!l'l!nil!lil phenotylpi~(jhara.cterisl:ksfur w!hkh hybrr~di~Jiltion 'is mm'l 'fdJvari!i~le WEre mo~t li~ke~yro ~lW'idil from dhoo!'lijlilg(!ofllSJ,p&ificsteo h['tem$pE~lfic;~; .. Mo!reo!IJer,. ~!'i,viilJ:iIIme!litaUy d~~M.de:~t !natt.~ d!~k~ h~5 ~vr!)~ivedj):!illy iii! p('lpl)!i~~t1iCi!li,sru!d$~(:,iil'$: risk that 1il'!liiJag]!ii~ ~iil,,~n'~ eafi 1~~OOiii:tJi~UV ooiiiefit 'fr,~m,hlybrildli~tJ1Qiii, "I'hi,i!S., Wih~i'! ~he Ihfi'~iI;S. i)!fjjjijM~ !ChDi~e vaifY. fEilffilli'h!s mCl,t 'radlk.aUy ,aLter thei r Ifiii'oIite :sei,octio'lii If'! fe~~G):ifiSl~ tG).tiii,~" own p3ii'iNiot¥!~ i!lllil:C~ tlileilr enlvimnmel1lt, iEfVlIll'lm Ii'le II!!'G~11lIt (hoosing 1IliI\iI.Il!~.off other' :~peciiie~. of

Uldpo~c.sPt~l '" 1.1.76, 1''''00,,(01)1 andifl~. ( widl mal~mal,oondil~oliL (F~.5ii. = ),98,. P = CM15). "lI'OOidi7~~iOJil by S. lxjJ.~lfjrlmJ.t~f~l1males 1I1~

r~~resi!I~l"l in a

lrndJ>.o(f;

HYbrid o:lThp.rriing may

lhC}' C~

hil\ne ~![I'Wa' fmi!Hy

ood reculfKil~t¥..ben

develOp flli:rer ~mn:p!llfe So .b(),mtilru!l.~ orr~ring and UlIlm.)1 liIlIereforeoo 11JOre~ nk£.~y 10 escopoi!' j],

dry]ngpool. C(mseqlrell~ly.dm filnCS'>l'IIcets, or hyb:~.rm~iQill.]doUD. Ihe babitll ~ .w1!idl otr;; ponds, geni;lod~yoo.t~ast~~lh}' ...ones: (1'7)1 lu deep Ci.olilg,·iasili:lg) pClllds. IJ!ll1el &. /)omlJijlr:ms offipri!1g CH.Iil mcW,'I:1:oil1jh~ kfiOfC tiro pondS dry U4). 'lh:lffi",in, ::;i!ldlrl. pond:;, ,S, boflJfuJf.rm.'1[c~1i!1lml VtliJllUtd I.liavli'lhi~(\1" filftocs.>; by ml'ill~iA:g \...ad~. OOfl~pL\'C~jj.Ci5~ InOOllh"iiLSt" lnl ~hrulm1if (rnpldly drying) pond,s, il)'b:iri.d~za1!i.Ql'iJl:l\1ly~L'l~t~~(i;;'ll rill" S. ,lxy}]IWJ't/nJJtt reuwe-silecat:lsel~.}~ri& <1:!:c Il1tOIt: Hleiy ~an.
PlQre£ bMlbif,lQISofIspI,1iU1g to ,e.wa:pe /Ind d~
. ,', . .. '. . .:ill ..1'_ .... " lure to s.UM'Ii'e"~ ,~I. ~·llluwnlIDre'. Q, gl~1] 'pGlilu 5 'lJI,i;ipu" (and ~.ong(Nltyl can vary dta:ll:Vlilh~.a!~lyw.rnh. 'lim, 311'101nl ,ofy~~y raif~f,\'Ln{F~g" I, AanlCl.B~. 11.1II!lS, ~1!ISl:l S lJo.lnbifo()l.~~r~ulflal.esllila:y ~moOOIli.11:r Y~f·IO·~a:FcvariaJhQ:[llilfl pOnd l.cm:ge'!,.ily,lih~y may f~OIi!~i."tlve~y oLclj!JI5.tlhdr c!!101ce fw," CQr!Sf~.&c V~'S.U!.'l !h'ge~erospeciflc Ulaies;, deix:lflditn,g on 11~ depd~ Oir dle.uribt:eoolng 1)011<1. ~.

spEll!!@; d~'i.!'dop,B~~('l hlrgcly !!llll hritwPQl!id

siz.e .trrld!

~nd

d!filfOltLQrlJ d~$ d~[ldl

r&.~~

W'id,~ males of:' d:leir OWiUl, spoo[e-So 0-1). Wl~oo bj'hutd171i!1'i:a~dacs;ooolll'~ i~.iso~:klUDascribed: Ito I:lliisl3k&Q dIU'iIl~> oreon .. _d!SQn, fCllrnalc [I~8JI:>Ii: d.t{j1iot; (4-iJ y~. hybridiza:~ion.G3!l1. solnJ.li~illllGSbe ~nejjcia~ (8)" ,aJ(ld: f~'1I'!'1ait~ mi~l raC:iill~tiv~ly .tdljlll,5ti!1\1(l~·cl\Qice 'lJir 'OCI!;lSJ~fi;;Vl:fliY5 !~eWfQSJ~ecJtl.c ll.l~~ ,dfepel1.d~nrg (iIf~dl~ [iin~ couseqlll~llCes Qif 1~~:i2J!iiio:n, (9-.12). ~dIiI:f@c'\IU.mfi,Y~ S\vitchooin fort:ila!c; I1na:te choioiiJluaydlOO'Cby nD.f.",. d~ale :lmpti~I~}'bm,{!b..alio.-n m:.:l.rould! ¢X.~lsjll pal~ ItfMl!lS ofl~yliItd~I~Oll oboorwdin lmany ~es (8), Spad~r'QoOt. mad'i;, S,J€lJI br.mlbijim~.,~1rndl~l a m.uJ~YtJi'CQ$a, ,n.s'k hybriditing\1i,r'he!le Ithey .00O«l1.lW ~n t'he m1lI!J1Vles:iitl.'llii:l lIniled. Slnles:IKlt'Oss "",20% ors. ban"bifrmM' rnnge (13, 14J Hybr.id: (i!,ffSjp~ilg Jru:i2 viable [mdi.can.ro,tprodlK1C,!Ilbctlt w~~~ rcdli\led fert~lily:H)lMd, litl..1I1ioo bi3 $~~il\i:: can. (H) raltlKli.i~'h. dill fooql!i~iIDy of' ~ri~t!.yruoon,g ~.ybritW !1~!l!]es i~:!:!l!'!kr!o~li,I:~(M)~, and f\f;!Jil1!<'It'e ~ybri&; tp,roduce fewer e.s:ss 'Umnp~ped.es: fC!11ll1es(15). Hybridlizaliolfl.OOlrWC'e!1J dlese s~ ties b1l'!'llitislmi!CElny 'bet'il~ spaUlIlly vruriirnble, 'wLth hl.ybridl rroq;hl~IIIC)' :mlllgi:n,g I'ml.l 0 II£D' 400~ae~
I~:G'U13W l[)!ep.ill1m!l!n~

'~ .. ~. M

I!~1110, ew. f

,irng b~\Wtt."-. n.specU.~.. ,~)'1p]tally. remJ.•~.l'" or ~uah~y O~!i.ng(n

'(.\)!~cUIJCIi1l1y,

f~nm'~,'S, genemlly ~fCfa

po,glul'ttcoos (/4), HyMd].mDiOlflisnlM'1. COllln'l(lll ill: sflliliil po!1.milJat fC'lKi, to' be S!liln(il'lI'iilJI~d: ~ig:My 'eflILCH1.crn1, wid, 5.: fN:m'lbiflV:!ls!enaQt~sr hy~')f,idizilJ£l, IllQrril o.ll~ud"n S: IIl1lltlpJf(xMu ifcnlal,~ (/4) .. nese QklervOO pl!lt1.:.1l1S ofl~bri.(H?.JlilioQrI mifLy be expia~lloo. ifS. h{}n'llnJh:m,~ ti:;~m~cs C3llil !3~I1~ b
fi'Ul:r:l ,~

:1r)!iDr:ikjl~ttOnl"
piXl~:S (Fi,g.

I, A and B~, allddl~ir ~dJpQ~~ Qftliln fiili~1 tomet<!H1QrpllO::'i;) 'bef'O!'e pm~d5 d!;y 7:1. So mu{#plfc.a&:i dev,ellop :mo:~ ll'allit!ly d11lAlS. homb.ffl'tN~s, atld, h&bridnadpoles lwetruwo~m

~rad~tOOt..;: ~ b

inl.~ph'¢ll'!I."

.u

SC)!Q1llUl"dWl(yILIf,e $. btmfb{fR~t.~ 1rn:WlPOl!es (14). TI~fi.", for $. bombifiw~~rll:mill~" hYMdj21a1:ion

lnay enilaJ[I{:~o.pril11g ,sl~fV'iviil. A~lbfiilh.()[ ,~vidr;m~ lil.~atl~;:¥'lPrldizli'lJl:iotl k .ffliiy OO!ii.e'flciliill fQf s.. b(ilNbiJhm,~ .fe!lria~es, I~ili:lrid OfStlri!!:g. bomlJij1'(#,~sfuma~.es ('·3M" tlil· pOles) developed S:ignifklIn~~lils:lerd]iitn did. pure S ixm,/b.lftol,/t> ladpo]£s C'BB'" t8~(oS) when .~. in tllelsh [-o,[ ] 6 d.~s (i8) [1it~G:ilm dil'l'tllr~

"r s.

1'10t.'V8~u:Me IffiIb'hYiPC'tlm.~i:. ..,[IRij(cd. '~"vop:I'C" dk:timllfl by~rrtmn~llg oOl:'limUt'J.d ma~&Choioo test~in ~iIlI(! lab {l8l First, I p~icltt\d thaI S .b(JJ.i~biftr!H~r~l'Iml~ wo~M n'Dt;Hl~lik~.y CI1~¢ S. fmdlqJlicfJr.a 11i1!i!l~ h~ s'h<!UawlX'!ii& 1I1ilI!~rt!ii

deep prnbds. Seoond, beca1!lSe JIjl<!lletf~il~ C(l'ndiilim'l.

prediots:d~,e ~;[keljIiLGOdfia<l~: Oifl'spcing wil~. m,em.~ Inorp~lose. J j;uooicl:ed lI'\~it fJOii"bfIJtlilffi feJtn8!tl.1S $. im1 oohni ~typo6[ ronciiliolflw«ul1d ~ ~nore~l 1!~1ii:l lI:iasL:ii~. gO!:idoomlilkuQ, Ui'~~I£"Unh£itt'ihoi~ ,

iLl:iii'tt',¢ ilitIQ)SfiUf

~~Ml!'$illj oJ foiMh (;If.Nl~~<I, (1lJ~'pel iiiill. ~,C :;l7S99. W,A,

,or

Biology,

C"'IiIlIl'LI!. BOl .32!1i[l,

CC'k.llJ

tMI"

~t28 (S:EM).100' = -2.67, P' =, (lOQ9]. Ad&~tiO!1<lny, foQlf l.mpo~es :rea!1iOOin :m'nl,itally dryi!1£: art~fl(:L!dpools:irn. dl.e field (M, l8). !lIe linml:i!l'lood dlitt aU t<lcl;IDktS ulelll!mOO[phoseCi 'iJ~ a g<tVlenr,tlIplnMle was hi~imu fQlr :13M 19d'polc.s :(UlmHlIICi<i.ld, mlnO = ~U5. p= Ol104~1 :l1l1.d. in· tomas.nd wil!l.1 m;at~nlaIOOlld!lJj):n. 6:12, = 4,70. P = n (W"}\ C':~]~i~dt,,: •.., ruacltf0__A'".", •. '~n ~ m _•. ';J. _.J::,~ro~._ "iil
:i;

-.0,''is

dB'V~kipi~]G:i'ualsI36rt!i1 BB - BM. =

x/

de;~!I!dlim'lg Oil! w~lewl~'i,!~t. S. l:1fflubiflYms re:lrmles W'ere p.oo.s~ledwi~lIi'! caI~s OfCOUiSpcci:6c versu s !l.C;terospea~fOC:; (S. m!llli.pltool~) nlak~s:und.er ·coIKi.itlonlS: si nmblling II. deep (l!olll,g-<iittrnlion]1 poitd ~~ a !)Ih8!~low (~hon-dillrnlion)ilpallld! (8),\\~nill~~'elnal~ 'w£re
fQr cOIl.'5p!3Cil.1es

W:sliMh1~m('llinillli.ll :~II dooppa!!)~ {M). 1'E!(t.Y ~bO\:'!,IIL\'cl a

,;;I ..._

)','

!.!,~~~

__

<

iE-rn~'~, ~elenn~q4i?l!mo1n,Ulmuw

UCi1!!e.~~. l~~Cl!nlOrpI~

(18) 'W<l!;> I,!j~~e!'

fo:r' 8M

aSii~"in~~n~~prere~re Ibrcoo~~lfie ~l~'l V€f\l!)!.'I: het:eOOSJilooi:Rc ca!1s (Wflioo_K..mlslS;ned !?3nk"'" 24:5,

REPORTS
I , = .,.,:,-~ i'iii!' . P=O{109HFi;, .g...--- .~Il = .0.(1] ~ . , ""'1 fio -e8. _.. _ 1~- lC)·.· d' -~ _;eep waler '!rials, irnlividlu<J!i fe.!'i1<1leswere slgnifl~dy cOl1sistent i~.llIiIeird!mtoo~ fll1li1.tleschru:e ~f1esaine S'ttl1mhlS,. cm,:iIvemge. 81.S :I: 2$% (S1Sh4f) of Illie Inhm (Vllloo"'ilil. SJ.f/rrle<i, I1mt = 34.5.5,. ii ""51, P< I],OOI~ 340m!. of 52 rema!~ e:tiI~ lh~ ~.G: S'limuh,l~ in. an. d~ li.ial1:~~1iI lfih~i'l sarn.G: r~na~ w~ I~!OO fotlfLillft~ il!'l a .51t.atl~M\! :poo[ il"'\--;-.,~·ca ~__up. dt·· ~lO\l,'<;;Q 1m·!retffi·o·.-~· \_ OJ> as __tzy ~: ,l'L .6rel\'Ce .'Of o(mspeci:llccruls (¥l!Iiloo1><ol1 signeClm1llk - -84. ~I'. 52. P 0,,24)(Ft,g. Ie). rll!lclL'coo\. dlCl flli'C'IlOOllCYW:L[J~I whi~,'Irem3Iel1 eito,'>e C0l1i!lp~i,:HCS waslni~'ht}uin d~p~r.r1!lS Sh3U(YW l!WN~u = .3.16\ P = MI(3) (~~I (Fi~ ~.C),"..M.IlJ(lI;ngh fi;i'ilIil,s]e:sa.1l a g.r:o~~ w~ mot ~i~nmcantty !'I1,O~ lik~.y II00e1ioos~ QI'I~ 81!11~i!!llU.~
<

.'~.1

!jijae pootl:~ 10sWttdi ~a~e, ~.I\O~CI.a~e, i!Jiiey .C<I!iJi. ~~aUy be._lIi~t .RliJre by ~¥brid"d"g. rliJi,. deed(. \~t;hen bred wi~~oolliSJ?oo:ifL'Cllil!lies V 8.), females w~nh,.[1 hi.g,ber pmpe11lsily ru. S!i!i'il:cil ItIler fema!~cs ChOEC ~11e!>l'1l11:C ~ii~lltli1Silfl !In :four I~ria~", choioo from. COll~cifiC!!ii~, deep water 10 llIenero5pBtii:ficgi~ ~.1ian{]!!\;Vw:ati)r ~tlood I~adpo~~ Ithal rund 30 oUi!.of 52: rtl-rnlal~ d\o1lJ~dl.e;~l11e !l:tnmul[lu ilfl at.II~1 ~~.1fOO: of d~l'bur Itrial':). ThUil.. S d~~(JpOO n~ ~lb\,vly .ham Id~O~~C6d by Jmmh.lfroJ~~ f'am>lil~, a"ln g1Ou,p\.w~~ ,,1(li.~lijkcl~ rtn1i!l~¢s ~11lh.<l! IQw~'~"~o/l{) SlII1JvoCia (Fi~, 10 d}(}~ S. m~~{UfJr_icmo males in s'timllOt\l pond<; 2'8). 11~u5, ~res' re._~9es I_QcI'!01!~g.es in 'iI!!e w.nleIi ~eN;eld~d:Ccil o:n.1I11(.'jr,'oolxijiliion and 'tlile d~Qn~ndccpIK'lIWS, !IS 'preci1Clclt Also as prOOkted.\vlncll'ltlc·a:J~individ1l91re. dcv.el<ltlme~l mu: of '1I~r.' o:lifSprin.gil~ lI?~ species p@jirin:gs,SlIgg~~i:ng [hal fl,lnlls,1cluw lna]c: ~vimh.ccll rrro~'b1. o1IIoosill:gOOl~ooiifics 'im (bep ~f Iro i~~t~spe.(:i~C;flil~!Il~aU(J\'",wnw ~p~[ld:ed ehl)ioo 1~~li!rrornl :Il. iITr~l~ of.;'I f~li1a~e~ (In 1lliIL:l~111il1~~ Co~ili(i!n. fel'l1lil.l.Mil~ru~ativ(lly Otl,tJl plll~~~yp~<i!Ii'id! I~l.i,l:~!fic ~oo]ogi(:<ll. Cm:;Ulll\,o
~~

8ig_i1!~11C!l!~Ij{c{j!j_. ~crl.'!in .

d~eiwf~fc~nJ;)e;

fem~~es dlO!!JI~tlte :S<'!!l~ 8Ii~Jin.dus,Of:iOJvtt.l:g.e, 76.4 ± 2.8% (SEM) oifllle l;j~:n:e(WI~.COX(iInsij~J1'Cd. mIilk: ... .390, .it til! .51, P< n..ool:. ~,9olLlIl of 52

• oor-oond!tL(!illJ ~~ p

~.Illk~I.y

(!I,wr iiIleo1]!ef

i!~ ~il!3Uowwaoor, i!1!.divi~UIal r-~lail~

~Hoo '(fi:g,M). .Poor-...cu.wit[{lI!]

OOm1ik.e ~I[a ~'!1~~ .rna:y be

IFig. ::I.. (A iillildl B) S~ ,1l'.o.ID~II1J lltm~edijlilg p.lild~ V'lIlry iii! d'eptiliJ (2m M (IfIl) ...uuil [ionge1o\iJty ,dllY!l (7 ttI~r,al :n;lOO.ths; IDIi!g;~tyis pC!~~ly c'@r IreLated wilth d~~' in aiiff,e;renil: :yfiCf$, dependilng en meanlounil: of IrOiinri!lll~.W ilIlmdl (1~]1 :5l1i1ow·th:~ ~m~ l~o!ld ha differlllii'!t:y~, [C) S:oUdi ,cird~, !repm~filt th~ meCln, lP~r(tIil,t:1:; stEM '(error :b,us;) 1fiIIlIU~-,S ~~a~ cOIlIIspedfk ,calls werle d1l.00011l, by ~ymilJmri~.'s, bfJ'mbi~' f~U!'i!gl~ iii! !l':l~ated t~,t!:,
A

100

....................................

~ijm~i!~ wl'l~ h11ll" lm~g d~".g;l~p'. ( The 00!J;!eJ! cy '10 ~d.lpaUli)nl5 o:fmalJeChoice li!lfl ~~se to waler ~,evc~liPJPCIU'S ~(D! 1~ii1V'evo:l'\IIOO e on[y inpo,plJli!artiofis and. spccicsdlaui!ik el~~~f1g in, IlmlMi1~pool1mti!tUy~ncfll fll'OrI1,l:l}ibridiza~ioo. 1nd~ n~..c~I()tce mals ID~w'o~n&~,Wi' ,"WiIS[ ~ OO'Q('l in S~!lilkw.' \!,!a~r (8)'], :ltlio~mtc fIB!J:fi:ales (rc~l~~! f.'OPlda~(I!lL!il l:l.i~~1(l S. IJrUttipli4W'tJ. '00es not (]H~£ur}kW !I1lot discriHlim!l!ebetweeu OOIl.~ d specific rum, bctcrosj)(xiHC callis (fIir.ii~&eetJwatcr lId3il.: ~} cllose OQ~spccific call s, 16, o'hQSC .helem .. specific cal~.s, XV~ L99'.P" 0.,16; seoolld d\::qp W,il:[e[ Imfu.:l; r7 clm.seOOILq:I~~jk calls, 1.2.chnse ltetemsp!;·~H'i.c ·cal1li..'XI J.= 0.87" P= (t35; aIiIiZllI,o.w w.~t~ lri:al: ~4 ch~ool'b~i~(: ·~ll~12ch~ hetc!'OSf}tXlific 'Ciil:tls.l.2 - US,; p- (l'JJ9'). ~p!()t~\¥cre, not s;igJll:fLCffutlycllillfereILt runol'lg ale lIl«:-c ma[s (XI::! - 3.01, P - .0,.21)., ,[[hu.

nest:

oonlrrury~oSYllrnl?a:~liic

S 1m.1.1riN.'j'tOUS fl'lllit1JmJ~cs,

ilIUopm.c: S h{mlmjhntf{; femflhlS dkl 110l 'vmy d'l('J~,choke d:e~n.d:ililg om. waruf~mII~~.

aFe

Moroover'iw,u~o1il~ilil 'pa!U(lms; ofn'lam ·cboice SY:~;"iilO::LC Sjm;'I,: females 00 sl~lkrwwal~r: S}'ItlIP'<Ilric.5, muJ.r.i-·
not ~CW!ewl:zcd, re~po:iil&:lS

or

of j:OOter'imceklrc:m;pi!il:i1ic: VerSi!J1S hetermpedffi!C (alb; li8J', The ,aaShed I~rte illillitrate'S .ill ~ualfl'dO:ImI II?~pe(~~!01'!1 of50!lj~ 11:1 d~p 'wate!l', 'rernla~es ~i'9niiri~rltl.y 'obrnse ,oollJ(5pooifiit: till Is n1.Uf! ~1Ieque,lIItlvihalli! If<lm:lom (as ilildm~ilted llilyltill~ a,5t~ris,rdalild mor,€! h~lJIi1i!n~lY than ·th.ey drnd 1iii, ~halilbwwatl::lI, 11111 :shal!~ow II\Ime[,f'mlii!I~:Sil!S aJgvoo~,.showed
IFi". 2.

pJi.cmu

0;,,----------=

De.ep Shallcw WamElf le,\!'e~in, ()ooice ar·ena

IV]O' IprDm:IiI(:e:

{'Qr 'tll"!~~edH'

,c.aUs"

patrie .S lxml.biJ'h;jtfi usOO ~Il the expi.:.11nnenis 300'!,-'e sjgttil~.ficrurilaY!i:rei[~n:OOOQI~~Ht': calis" regardless (llr''''llter I!LW~~.(d{\t;'P W1ilerr: 43chQ..~ OOfl:.ll~"'(;Hj~ caUs, .22 d:lO$l)! h~~~~i~~ ealls, X.l:!.·';:' ();9I,{ii'·~ O,,'OO9~ .fi!!<!Jk.,w wat~Jf.: 47ch.QSC COl'OSlwciftc ~ls. 29 'Chose hcterosp~cHic (1;:1115:.

room

ihe same pop:ulmi.oas as ~lIiIeS)flill'-

00 Fie:ma~eCOIU:JIitiOD1 !!lSI)

fUlilmOOI

of o
o

to ~witdil fram dmosing. deep waterm ,r)~oo5in.g betefoo:pe~fh:~lJIs;in SIll,al~o!i\r water (j,S) •. "B~I
[li~'!Ie:~Oplmlerntrate o!1i' di ]llma~e"~ ,ollfspring I I[fimm PJr;e S. bo.mbijroJl$ Ipa'1:ril1l9i~) ,i3!!ii'l !~!J!r:!m:Qf!Q'f thi!U'Iili~{!ie(~ pmpe!l5~1!yW s:~,dIl 'fil'om dlO6sirt!,l CD!III"ipectfic t!lUS n:1IIdeilp watt!r to (.hoO'Slmg he'te,~osp~~niC ,U;I([s: 'in si'l:;allow wmr (18', Eacllilp~~m:rep:~$~1ilti1ID!~9II€l!1i! of tw.otldpole.cS frlHlil .t! !ill/wrn re~,kilte; 1l'm1l'

:r'emal;epmpensity (oospecifijrca~llsm

Cl

o
Q

,US). D,afllllallie jttH!:fd (by ,addnl~1 sma'll~ l~andollll~"lu~s mtile ,oliigin.,iil dilliii .along ~he x axis ['or p~e.sellltlltiOlll anly). I~h Iparne'! .Q.,4i·M IIJ' ~ OA ,(1,6(1,8 sh~~,the ros'~lits; i1! 1!il~!lPi!~afl'!~ric :SP~f~ of P~opefilSilY orrer:na!E!' tIO $\'I.~'drl ~r;eI~e!1Oe Irrnitl~ :l'ain'k·ooder (orll'~itiiOI1l8ilila[~i5 that i5 1m:;'(JJlcslrr.gly m:.:t:Iy .to sw.,lttlJ: '.. 1IiI,rn:5eIUtii:ve to _t~ier~ (;lin Iwea51~q,llJa]i'e'!l l~e!Jrressi~n (d,lsl1ed~ nn~ ..arl~ :;h~WIi! f~ 'illuSlr.ati:Of!1 '~f!~~Y.· Sp~JU!1!~nl waflk (~~I~tiO:iil ~()emdElf!tt SVL.S:Jl~nrt",oo~t 'So 9 NOVEMBER .2007 VOL 318 SCIIENCE. WII\lW.sdenaemag,,()1'9

w~ro 1115 r~,~u~€:S.rl!llr ~adn o~'the: 1;1: fem.a~~

o
P~j)e9Sit:lOr
.~ncre.~

re!!llI<!i!e ~o S-iM1~Cl11 Pi'E~er·er!ce 1~1y to S1.V~M ...

h~!Ilg,~,

REPORTS

x/-

=4.JO..P = O,oo.a),Marecho~oo ·of s: mt~JtiplkQ~re!il!l~es did not dlff~1' :si.gn~fi~11Iy

bC'lili!.iCeIl wfL~~-depll~ t!liealmf1I1ll (x ,1 - 0.28, P ()i.(i{]li],. 11~1IlS,bccausc' mulr.r.pi.lt::aw(l :fema.le.~do ~otbm~£,~t 'by hyb:n'<i.iziilifj. wi.lih IIDtli/)iji'Oits

1. II. II.

IR!!~l!ren~e:!;a!lidNett,!:, : (![I~. ~. A. Orr., 5.pe,UWM [Si~~!J!lr ~~~, oijrul'H!l~~~md, .MIL> ~OOilJ'.

s..

~laJ~I3!!l, 4), Ihera.ct 1~Ih8'n.l.hcy ii;:liIo.q!lCilmspeci fie p 1fI.18i~Ll:ili ~.ga!m!~!\i '>V8!D.t'f hw~l .flli)lppo:rtS Iill~ ~)'poll)~sll~t ~Ioo~ in !1fi,,'lIt~ dilOiic~ ~m!:l'r;iI c<volve O!l]y when. 11.)t~ridl!rl~li'm L'l: fOte!t~01iny

.s.

or

adaptive. ~n doopo'Walci,tri1ils, sym!p9lrie s.. b(MiibJjivJlo~ c~hos(l:ool~,ooHi.c C9.I!Is.signi:fic::.mlly more arlen,

1~lIiIa[l. dicll .a]l\]pame f~l1Il1tl.e:s, (Wi:k~Olil
l1(ul1~3l

~_11JI. OOW!IFtIi., ~ II HyIM.id .Zl1fi.!"!S! ,~.I'MI the f~~!t#~.!li!l'I'l' H ~oI!:IJ, R, ~1 ifIa~rI!iOn.\ Ed. '~OdOfd UIIl1l. IPrf!~s.. N~ iilil~t, '99J}., w\ ~~'9. 1 ~. M •.Alildti:!~'I1J1" ~XiiI!T,t 5ekd./M U'liif!luWJ1 lImv.IP'ri!~~ N~mi}lI. N.~.1994t 4. J. l.iImbJ ~. C. .Avi~e. Pro, .. Niltf.. AfIlId, .S·d" l.t£A. 831, 2.~·26U ~6),. s, II- Wf~, ,kJjfm. Be.fiaV. !~8" 1\ (~'iH~llL s, ~L.B_ ljl21!!iIM, EI., I( Su~fival1..1 lLaI]il~ fwt i!lt j,.fNgc
fL'tlt 515, ,126 (2oiilll},

2~Q\ M. A. NMf. Nrir,w~ ;3:1!!i,,6 [1'9~SI. l:l,G. ~, iOOlll: ~t I'll". N'lU1tr:t1 3f1:l'. ~89' tl! 991l. ~'2. M. R. ~filedr 0, M . .A. F.. N'oor. A.!\!iu. Jil'ell:.. ~""L E"I!llI!.:S'f:5r .. l4.~~·~' (20(1~t ~;!, J. M, ~~~ f~ •.!V!t,t. mg, f!f!!f. <::1. ~.~S·~1?73l', l.tS;, C IBnten, h. L (~ili!.l',~. ~af~; AlGtf,~J, lI!I!il 6Z1 f 25, K. S. Pi@l1nI9\. (..uI.. l'».t J {)tg. (mi..s,t .Mil~ (2003J. ~;6\ R.. I.e:~'liin$,E~llffiM in 'O'!~ing fll!l!i{;Q,!W.!lMIl.:
(2,OJ):l)_

'''I

:i!ppllOxim~lto:n:
~ ~~ 'fhe

2'5~f!iP

-2 ..~. ~ P S

O,Oll•. ~

IleOO[-Q5r«ifi.cs when h)'bri:diza~i'ion\l!'ms Iilot fm:'TIJiabilC (i.e.,h~ deep water) :!>IJgg,es:lS Ihat ~h.~vi.m:sd1!Eltrnin,i~ unize :iliy.'br.kli:?lllj£m Ilm\!'c evolved. un sy.lIl1)atmy~ Sue1'a di:Ff~~ncm;:belwoon a noplltiJ and Si}'I.b'np311)' :i!mro:'pG~~~d if~I,L}(;tl(Uil faV(l!fS.'l!1i~l1ng ~~arv!'OJfS
IDIIli;M p:mili'it)lle !rqlrOOu(lDive i!iQ~1M.i{il!] ~hll.l(i~!~ .~ eies ".I, .2', 19-2'1). 1'1ilUS, <zyIw(p1J!!ric fo.mEl~es hiilVC 3pparenUy eval'iiied. IJIl)i(::ELbj~·~~:y lillOdirydu:~r to digool1J:limlllloll ~ainsl htlt.erosped:fi,cs, dcp€'lild~o.g (jIll. dil!cfilm}SS COIIS(l!{)lICIJ.Ce!> ofIl'1bridiiza~'ocm. l1~ffiilldi~ ~m~ d1<UII.clllIaiIDVC s\'l!dtd~DS
nJD

raCi~ 1!llila!1 ~Yll.~c fem<l~e" di~iln!nat!,)tW ~~h~t

S. blJJlJb!fi:D1~:~

7. f. Vt!{!Il.tl!, nl., IIlfJ~U1., Mi ~2!l10'll. ,8. M, L. AJfI(I~d,trla,mlUJlI ~mNlmJ'rJn (!mJ ,i!'litl.Irllrfi:l.~· «Mimi Uriliv.. f'Irt~, Qo1.il''I}N. i9!m. 9. M. O. j!lMiI!!I15, M. f1'ellii~,BJ'al. R~. (am!!. ffi[fJJ. :51)... n~ u??1). 26,~ ~O. I. le~i U,~.5:a!JE~t W4r,~.gIOcl, sei f1999}, u. If. WI@ma: :5, '" 5.IIlIIt~r, fietuh.~~l_ ,fWii H, 26 U9Q'9:i. U. s. (Moon, ]1. Sf]lI![I,A. il~lllrli!nk:1llJ1.~l!I. (lIlT. BJ'ol.I.6., R~~l~ U~Q:6), u. P. W..:5aLtI~r,'Op~ia:1:9815, 324 1l9SS)I .. li~. ~.~,. eRr!~~ M. tl. Si1r'Nl!'i~J~f~'III.fnJ;]. 0$ f~r. 56. M :l.a:40(200n H. M.A. SjllnlJi,ljCm, C A, :5<I~.lmil!!' 4 CI~~id:, f\l~(. 5aIl ()i~ $«, Jlttrt. ~.t, l!:~?~. t(~99.u, H_ 1:1. r, F'lltoe!!1!E!F, ~ptJ.r,atag1t:(J j:'IJ •. :If!2: (;19751 1:1. III W, PI,!nmng. ,fV:oJ,. JlU }. ~_ fVJJ/' 46,. UDI~
(19Q2).

f~~Q(ari'lii'1i '(P,nm!lton UI~iI!<. r~~, ~ f,'rinte;OOn, NJ;. ·li?6:OO. ~7. N- l\. ,Mor~n, Am. )Vat .~9, Q?~). 23,. ~.. lit \llW!Ii., frot. Mt j Org. f~. Ml,BS3 (2!!1'IBL 2:!.t I Illl!!mln 0, fi'~emfllig. flo, M~J:tlfl, (, l~kifHl<ill. ,M. M(Gil!l" III S(~1t G. lilll ifii:!FlIlruii, J{ f1iililffiulil!... '~~. I!l!lmifn~, M 1ii1l!:l1~1lIm. A.. SOOn'iiFt:. <lI!!!I A. Rt~e:1 '~r Iii!) <100 Ilelcd' <Il<'!iist<llKe; II). IPiiffll~~,ii. ~OOJ, Jl ~1fIi1l. C. (iierJ~rd~ i JI!. ~'!le, iii. OIl!~tJ!1. [ .. le~!!lII-RW;i~\ ~. 5erveli!itl: S, !)U~t~.C, Kiigl'Ih ~iM;IlI!;, W~ji;~~ i!)~ ~men!~, .~m-!l !bi!'~tali! ~!ii!'l:H:.iE!~iIf Alrizonii" Ctiklli~i!ki1, tm.i Ilie<n[o" ~nfl Tws, 'fm'perlillt~ 1iii~wall l~a~ Strppil.ri.'i!IlI I;i)i N1Sf:glr2l1rt

r~dt.ar

Sr;I:rrJe

?n.

[;jIfB--D!i~.ji!566, SUPiptli,rti!lgl On'h!!Mal~ri..l ·wm.w..!l!:k!iililEIfrIa!iiI.~~~Dfiln!nlliulti3.11i!ll5&5.2~6~mCl rI',n{!,n.al~:!iI1:!I M!!ttl!l!!~ fig. ~5,:I.

.AIIdl~~:1iloo~2
f!,~er:elllC'!l~; <:i Jw~ tro!!l1; .:r:~t!P~l\r! '9 O~m~~r 2001 1!0, U:il~dm~"U.!l6l)~S

1,8. :!lee wpp!lfitin!l rrnteriB'l en Scl'&ICl1 OnIiBt. 19. J. ~mt!ill1d:)',;!m. mM. 74, 312 U!MIO~.

[~l!IliI!e :m~-clit(}Ic~bellfflflC!rOOtjjmbl)lJ.~

I~D

~i\l~I[[y~~in~ ;lid ~fu:iiJ'l J~liz.OO ~'ry~ridimlion' in 1~llab wherel'l)1:nrids mayllO'l.w ~1@Rler ]],tll.tSs: (8, 14').1J~ aditt!iOOl,jJic.."C ~ulls S't\~~ I'low by'OOd_s Imy IMmtsli in Ibe face 0'1' a gml~~ pall~m. selection !:i.wMIlls1.!lrnltlii. ("~Il{f~ of I aJJ]i';. wliKm.I.wybrii'l am di'lfaNOrOO,. Sb'loolilalil, ShOldd: [iw:lt1(}~e d.tff~VPllntt{n of blllil8!\lDOfS ill syI'l'1pitnl)' 1~li1aJD. [li~llYd~ li1)'bri~~iliOJll. (L~L. l~i!lJl:tbrc~iI1J$nO (1. 19-2l~ Cilj:PQcle.d, s lWIVlb{fivtl5 b,wiles .k> In SYli1!ptluty;, blln·oo~;Hlk'ip<!i~,dl~lI.i.ml1e inst ~ Aall'rlillil "'It 1.. Kaljlil l,amllllelil$" L 4 Cllal!ldia CIiI'IIl'ilr:Mfii~.,~' Al:fiiled ILill!IIiIm'eJn~.l ~. (.alfS'~~,lPierl:k;.1 $.2 ~c~~~ciflcs\'WiI1C1~ ~.Ybridization is: coot~y, U, Daitiidl Ktl!d1~1. brl·Pder [H\~,p'f!'!!l!r. l1iJi!ll!il'!gJ!!IC~Ii'l',!I~Pt how(;lver~, .f~j:uaat~1>acuJt!ltive~.y ~l:ybllidm.z.{; when f i~.i3 beneficta], by~ri.dl.7.;atiOmlll!lff":Y persist ON.AplJlY,Ii1lI@~ 111 P.Dl'IV iSi 8!!!karyotk lesion IbYip;'l'SS polymell3 s.e tIillmt l1e1ps orl::l~n~S!iiIIlSm S!l!l"!rNe Ie)[~wre ~ ~QCa~.~:y thkl .1i1Ccof <I. g[.()I:Hl~ plat~m Q f ooil'lrn. to 1I1lUlri3,vid~eI: (l!I1IJ) lradiiatioo'r and! blili1ll0'Helills toi gailllllr,e5i5ti311ii0! .aQ;lil1l!51t 1Iil[~Iatif'I·~ed (hemo:thmlpy. :I~ f(lr:ceEl:l~I!it. Th~ ~!~~ra~ ofh.;'bl'id!i: .in syJlmn'!l~ allOw; l(elJllii to repiJi(Me acress ml<9Bi-linlk I~~ionll ~dlll!j; 1,.2.dIDGpG) Ici!j~imadd:1lW; ~Pt:-(6) and LN1~lIi!ilI~ ~~Olve8eemtl!!,gly ~m,':!ergml,e liCin!b~ ment inw.!edl a~-s}11~~ymiime dlim!l1!r!l1.. pr!!8en.~!II:mljlmnal~.lImd Jjechelll1icalaJm .. I~is: ('Iif hOi'll p~m·t1Ioopies ~!{jGF We. i !solil~n Qtl!:ib~ted, to 1'IlI!isl~sinl]late clwlice. ,oonta11i1~g [IN!A.11iIe ,dam'a!lI~1 DNA. 1!>boone! 'il'la:J!l ~1iI .IilN!A.bindill'lg rim~rm:d~M1idi"~ 'transfer re,,"res 1h~ cOl~silmint;s:o:n fetll1Ja~~ choi,~\Oli' ;ron:led OQ!i'lIIi~ __ . !HI .C.I~ ,.."" "".. I],a ...,.:~. --f-m'~11 DN~ .il "'"-il'lw o31_. ... ~li\Il (00. (If._·.<!·,,,,,_.1 4t(--_- ~''''"'..If·;-:. 1!!!~14]1 C" ell !!'I@ ,"'_. JI-"'''''''Iii. ~'e: WIi!!~1l! i.l!i!j! 1'", ... y~ '!.J'Y- tJ!!J@III_CIilIj.i!..Ii!!;j1 ,~~oi;- ~'''''Itrd~- ;-,f.",~",_ .... ~ _4'1'rT1!:1 ~ruiQUl. by male$ (4-7), HQw~'\I'rn:, Kacll:~~ative Foc '1ID!i! 3'dG Ilfth@, Pt,6<i, 1hi~ S!~p'i~ilocom;j:llilshoo by;:! Wa~'i!I<riek OOsie:pairro dap .aJil~: l]odlMlicaUV is aooptive ~yb.ridiz3t~mi'l.poDflnii~t~ly ~'xpl2.il1JsIlhe 'l\fOOel!it and a~~!!!I'ilt@o.In (·entraslJ;, bjp~ of'lile S'd(j ,of IDe' P't"G,G ]~ l.ess effideltrl: .and Iprll:lfIlliSLOOl!!i~mr d:CTP IflL3lr!;;'stlim.{)'C of hybrids d~lit~ the pfi1;dict[{iJllll alild dAmP as i! res!iJt (If tiliJe [~e,Siefl:oo of the I'ilc'gld PI: IC!wss.-lililk. (JIlU .a:na:l1ftii~: IrlltVEli1l15~heSiE!it f sifIlr'l!lffil[o1Il o 1!m.8!~ '~~nfl;!ll!C¢fi'iI~f'lt $h(I!~I'ld~VI~I~~aUy ¢li'1Iii~n,:3!h~ ffiatuJ~e:\i. tliJat Blllarmte Pol1jJ1tie' Irep~(ate at:roi5'!l. :51tJr10n:gtJt d1istGil1i~ DNA IIe:sloru!l;. lile ... ··di· .l;i'.. - (If)_ ,_~. ..J .• ,~-,~) il}'IJiIi1!. _.t':a _ Or!. _

s.

Bypsl:s,S 01 DINA. Lesions Gieneraled Dur.ing Alot'iic:,an'C 8'r Treatment with C,iSlplal'tiin by DIINIA IPoIYlmera:s,le' 11
1.2t

Gener<llly. wheliley,erfiw'e$s: ·Iis r·eY,eo:s:oo. iu differe-nt habi~a.ls,fllC!]native s:'I?ilil:chesilil. 111Jtilt~ 11dl:reekingdoIJIS of life possess speciai~ y~ mmUy DiNA ~oiymrn'alles U, .1), img hcho.vtoU' m~ i..wol Vtl ~f f~:l'l'Iaie... routinely . n~SIe; '~'it:iiCl; s1i1arn~\fUU~high.:fi.del it)! C:)lpcrtlC~CL'l diffei1lmthabilalJ> ~I canl. a;$S~:S e:iwimi:'imOOl:!i~Cl!i~ l~h[]!.~liably ~rudi,t'l~ ,(i1I- DNApolyttt'i:~~ IlIillt:i basic l:liUeloolndyllra'I~[~r SIl!'ins: filllllesS (2,6, 27). ElOO;;:U~S6 lhelltooss OO!l~ '~l$o1il~[ln~illiL d 1jj.~ri.!1:~~l~hwld-~i!k~i!Ii"U¢l!:t~. M ~!:t~ setllU'e!'ireS ofnwe dl0~(:e may .often depe!ldcm 1~lIileremillles:' .own 'ph~lolypem the lim!bl.Uil·h~ %m'ich,Coellier I[\:ir Inlegr~~ ~1~i'!,S:der!;o!! (C1~, l1,!l~9 WIMch 'their olfsp:!1illllg develop CW, 12. .2;8)1 Ma;jmiliOll~ Un[l;'ernity, 11).813:77 Munich, 6;!rI'n.m¥,~lGene Olm@Fin tile DIli.pilllillle'llt !lit CJITiWlil-try .. 1lHi .8ioch!!rml~. C1Oiti'1ll1Xt-clcph,lcltmt f(mml~ Itla.ttl clmic€: may be Ll:Hl!.!lrigl Mi3:cm;lia:J1lS.lllIni!Jf!~, 11)-8!l!3", -~IIiii(h, GI!mUlilf. C10mlWmll {9-i2)...Ex,l.ain.iIDlg jf~~ vatl3t1£min, '~na:nJ3dt{]lm~ i:s in~~nl, ~.m'C: f~.Nm. ,dlrl!t.~ rlla!a~~1y aflw me g~OnlC (!If se)!IlJ<l!.]5~looti(l!~ ~nd, ullin~~l)'. spccialian.

Ii~e ~l~iail ])J\~ dlllt1kx b~ncllDml.g smf::!.1:;e is jl1Tl.c~dI 'by a iIfOlYil~llIsc,,~~alM domMn. {PA.D !l1S:O~iii.OIM. '''littlc~i'i,g'G:ii'' for iirk~ rolGl in. romiPl!lI~l'lbin.dii.~g) r~ili!i'ldOO'l~y.~~.Y~lfamily j])Olym:~~~s: (1). .DNApo!.ymi~r:,L"'~ '11 (Pol 11) in
j.

elll!kmyo:lesis ab1e ~.ore;p~ica~e ~1~roUi.GhUvimJllooo ,eycloolllt!l!'le wrimldine diil!llefS (CPDs)

('iI-6). o:r cispl.u:lnll"iootJIoed l,2~{G~), <liddliWlS (~n"GGsl' (7) fllntu~dl tn. !I.~ypica:l 9nlli\':=UtCGrdlc:ri!lpy wild~,iJsplamil~1 (S).~lBl e of :meb. ·el'm'l"~.iJlllk.. . i~pe:l1Ii~tl\<"II'I!y di~rlruk bocal!Nll ~l;!O a4jaroN .emng

ba..~s ~ ..siml!I!aM(I!U.!;;~yiliurJ~~.ed. To, rev~~dle

!1H,ch3Hksmfo:;

1IJ1I1~~riy I

l!i~def$lood lwiom

967

REPORTS
H-- 1:""""", &a .~ l1Illd Illhe ,(,i-p;!loop~l1);~e is O!1~ ..;!i;O A. ~ cl~Ol!!:iSltOO ... Ie ....~""--(g (iW!lpil~-e:s wi(l~ for n~Cliro~dy~fr:a~rer, exp!~~!~h'i!gw~ylillie fil~ i~OOlW:~n!ildiNlP ~rldl lVl'O diIT'Cl'erit ~,6~bp lel!:l~ s!~l) of lesion ~:rp1lSS is: l1elativdy ,effilCic'nt. 1;iI,lmes:OOOlnj~ll'lg 3, sjle~ecm,c iPit~G. Qimealedi COrredposj'lkilflillig Of ~ffiledCT,Pm, .he .3'dG ,I'" I~Ot~ di:rr~i~1l'J.hp prii:i'n<lrs: (el'l mild CP1). . . li"'iliDlS, '1" es'OO!'il, sy~ul~S:~S:fJl!n~""_.,1 1M. 3J U "'_ "-':1 ,IJL=PlmU 1nt~ ~ks[ Ol]i',!U,aiil!! 3rna~,Y1_OO_ [M,turo(! II.\W dif~[woon the ]'OH gr~pof dCTfan,d! 1:Ii1~ femnl oo.m-p .1~ - - ifi- A. and C,, :and lE'ig_- 2:A) '-1 OOol(oon~ of Pa~ ~. ,8J[ Ph~J~1 ils w~n as Illy - - -' - ~ is}., '-' - . -b •- 8!': -}'P<l!-" '~le~t
(If

:-. b~IDt 0 -~.",[~~ P.!L ---y, -\1i._re .1;; •. 1" y~~ Pol 11 as m.:~

5,'dG of diel~~

is Ole .1'imI ~!lpai-!'OO b&<;e.

eI

im ~,~ ,::1.~rn.mli~C~I~i'n. n~ir slrU:C~ w~ A ~IUTioo. 11'1(1; ~~weru (lJibool'l'oo by oo~a:yS"!ai!lizinSP'Q~ll widlllle: DNA Ite.IiU,PIBtc"p1ii·nlCr ,OOUSIJUiIll_CD CPI.. hi ood'l. OOl!il~ 1:iI,le:>:es,he :Pin~GG Qfloss.:~hd!:is weB del'lmoo,iu, t 1~N1(\l C~~I~del~Uy, and I:fiIkl' bssss .ihnllimg lllii'l Plr-OGI¢S!i~.ll a", :pooutiol1QilW ail. ;'I -9np- ;ul!i:l\il:

d~rew!~lh.wd 3.1 ,<l.~-

hyd~liJ;g'blc i!Ult~~ll(!:mJ w;M!~ (61} 84). PhJ~' I··.. __ ._c___ i~ '111 .:!i.roc . ,~ __ IfL ~ .. ~.i 10 _'U;;_\lI.Lill __e ' .. " .·Ie , _-e!;J,!~_

'PliI"~

e>

ribonlJdoos;idl:!Ifi~II'o:~I:llil'es:OO:In elllla1i~g tile camlyttc (lenlCr (.10), We I~{:-XII cr,l-'Sm~l:izcdl P.b] ill 'I~(!dter widl thG'lJ;!mplilllD-pr.irm;lf 'OOllStittCt C'P2 in. which Ill(\!

Agah~cfysl:Ol:tS\1i.rere Qbtai!]edl\!i"iU~ (W'O dl~ffc!''' eJ.m o(nnp:~e)!_es: i!lil the~SYlilm;e;lriic 1111it {(;mill~ pr£!X .~b and .2b) delr;M:lllinoo ~t l-.3 A resQ~lJI~icm, (Co:mpl~ Ib) (fig . .3,. to. :ruruft, :9), l'he obnailloo. !!trucrul1b~, '\loillit~ol~ v.~if)I ~milar, [plfiOvi(i(l .un.are· si~~l il~~(1 li1he ~incl k!:sio!i'l b:ypa~ s~ (5i1dG ~10I'I,~~()n1). Bioo,!~J~'1icany. w~ '~51~N'OO I~hal bypa,_<t$ ,of the 3'00 ·IzyPoI 11[1 ls: e.fli-ci~lIlt .u'K! 1l1'osIfl.y error .1J're.c. {fl.g. 30. B~~ ofdJ1e S'd.G, ho\!IfC\I\~~~S slower and Ipmn]~s:mI()M fm {leTI? aud -dlATP {P~g. 3,D), mn tile SId(] ,e~oog:alkm CD:Ifllpl('lx, i:h(;l' ]~clJG (I·f t!ml~lcu~ru[ll]:l!ifL'" \\f.'l1-.on-

W~~~l ~~el 00 oo~'Il ollt~r {Fig. Iu). Th~ fi~l co:mp~~ (Fi~. l, A 00 .1)) (3'dO clQ!l~aOO~step) CQ;Jillains Il'he :Pi~~G~cSi,on ~ru:lh:llly SiltUltoo,h~ I~~~e ctive site, wHI'I lite 3'dO of lhe lesion, a f-omaillll.g II SlaJlllOOirl W.a~mn..crick base [pair 'wiil1~. l~iIl~ i.ll0auni'lng deIP (Fig,. [C), IrI.:'PliflStmoo,g a 'nlod(l~ !for tlt(;'l c:ffiei~lu b-ypi1[t(! {)if 1!I~(l 3'dO (lief 111(;: I~om. TI]~ ~lIdeOlfl]pl~ 5:how~ihe Pl-GO
~eskmQllIlsiidk: Iilile ru::IDVC ~e l!IIIITOllll·o:f!lre DNA blinding rim. (Pig, I D. :2A), \\'C, SU~l tlml: i1~~s oj)iIJ11p'~~,r:escn~bles the ·'p~.'IlIl:gatixm" sune. nn, ltI<Qd~ ~llImllre-s, d~e' l:empllatcpnrnnCli oo:nnplex.is 1l(]tl!lldli~. tl! wide; DNA. IiJhtdillgnm. ~~wu~m liBel OIipposingllt'l!l:mb ru)d PAD dO:IfI)fIin." (f'i:g" l;\} 111l1:st~ ~ri'~ I~pd dlCSlructU1~ (11,[ tire apol€!1_ZYlllCl (9) simre ~~e Sil!]l(l space g;~i'l'illld shnnar 111ilit oo~1dltrncnslolls. A C1:ml~ 1!iI1~1Th oil'dro 3idG clongarnonoompic:lt WIIIDl. I~ 1

rc1o'CaL~ i!iMU 1)1[llimpOOil!ai1lc:l~angc& ~M>'3lrd lit£: D~. (flig; :S~.~~ d_udoop 306-:Hl;{~g ...]D)'OOtl~L~ 1l.1:G :mod iJNAbil.okbrme:.Loop 3:S3-36)move:s ~O\\iar<cl; 1~lilellnifi~rrgroove, ,a:IIld, fl'Kheel~l~ of dge PA.D' ! di{)IfJa'~1iI s'bilb by 4l A tuwaroJ1Il.e DNA. b~_ck~ bone. TILe~ wori1:lntltt[ml ofdDe DNAlllrom, 'Ih.e Pile" e-kMlg:atiOIll, imto the 3~dGeI0llg8Jlkm si:3&c (Fi& 2. B and C).~ :aoCQI.~allliOO_ b-y SJit'IfIiII.footkmsoftilif: I!Wr!.llfl~oa:ntl P.A:D dO:linains,~larI!i'i{lOl t{D Id~~ ~ailm :and ling(lr d'ou'lain .. (jig; 82). ni'J .DNA COI~IaQ1!8 'l I~Otl1e FA.!) don~ilin a!:es!tl:f~dby {l!l;l1;oosel)otir (fig. :::3), ,In i1e 1)~~ekmgatL!lm, wmp lex: {.Pi~ 2A)Jd~e PH',Ji(ilcsion i,spos:i~iQIti;,'lclJ Q,utsii,OO ~~~ ac~,iv~:si:IJil8Jl\d1i11c: J'dG ofthelcs:iol:'l~.s held 6 A away rrom 1iIl('l: dCTIP ('3ldG·06 ••'04Jr>.1fI.~-d("n'J
apOt1ilrynl'l':

ne~h.tlmb

d:Om~1i1'il rnl1Me8

·t:¢C*~r:;~~

~.I

HQJ'.I!ZOI

-llll,t.I(;'I,t!'

dCTP is fOStuionLld ~!l. I:Iin~ 3,ctiv'C: slIDe Illii.~.;,lb'j()I1~Qf 1111111" t~I~~.~liltg, ~" T'\.'lKI ~ '~le!al ions ate see!]~n i!~ea_\:i~ijve si~e,~i!i@l_ecl by ~~~l1; alalytLcIlU.y ,essoofi alresi.du:es ASp:lDl, c ASp~S5 ruw -Ghll~sc; (Fi,g. 2A). Tille .l'O~ ~mlliP\ which was nmeted ~mQIli&m struClmie beesase dlii: j!iI,rirrtiler r~IIDCi!! ::I. did~oxy Ill11i'iit'iIiI1M~, is ~ooalnd -:8,5 A ~tWa,y from th(':dCTP~ 'ri-pllMiphl,te: illi'ttt
:Slin.dle
~~f'lJil!lJ

~I -iirll!l:i~' TdG~"S1(1

l1'J.! 'I~I

1.;!~1

~,

ni

'5"

aG

e~UOlJ·

1~IMOO iq i,iifiltb!(l;

00, p.,tlltfij:ml~iitl~r~IOiflWlliO:[I, ni!l8i.1l1mlicn~IS 5l!1bsnai!niaUy cl~nsOO w]n~n the

l~lJ'I'I1!phlle"pdme, ,cml'l~le:ll. imlates into Inhe 3'dG e~ang<itiolil.stale (I"'~S,2 , n end q, He'lIe, the ]/dG (I!,fdtc:tesio~. cSi~bl~shcs: !fI SD3:lfIdrurlW::llt'>OI~rI.ck b~ra:irwirt1a 1i11.~'pro-orJmt~arudJdCT' (Fi~. [C), Aqg7 ooowimu~ Itllilc dCTP'!.;. 'rII~pI\'fispl\'llUl: .MI'dl ~~cb (m tl:tr::~e m~,jd~ E!~ l!I~is oomplex, lire diitooce be1i'wQen 'he PUI!li!!\re 3'OH ~uclcoJ'lhn'e

Ftig. 1. Pol.llstrudtl!lmE! 'il'lihlrrllillY Cl(J~~ex with 1iei.olil,l1ollltallfliny DNA.. (AI Inile

3~dG elollQatimii

,(-om!l~ the rl~~ti'l!l (mllg,enrW ~~.shawn with ~he lplatimlm aJnom-aloul'I eleolJmnl dBlil'>ity :OOl1Ifrlur-e~1t a 10 e, 'Th~ ~ri!m~al~dloor!\~late!5tra!ild~,o;f 'lhl'l DNA (broW!'l~alii!dl the; Wats~!IH::rh:k H~~@:utd~di dlcr~ (rIl\il;ge'lilt.-d ar'el d'epkwdl as ~,1limli. lIh~ two mlffillioll1$ are ShOWIiI'ilS: 9[011,:11' :li:plne;res. Uj~ V~iew ef the l,:Z.d(G,pCi) ,clSiplatinl lesl:J:1iI SllIlperim;pO!Se!c: with 'ille sim.l!lla1!ed ialillfUe<aled ,oom,pollil!:"iJIlI1U deDls.ity malP' 'oo!1tJ:n~:~~ 1,0 ~,tg!l!'la (,C)'i!lh~(!!~l~;c i!I(ilsidilll~ ,at .aJc:tiill~ m~.'l7~ ()iM~.f'I'ls 1 :lhe:dcrF fm' !+bof!dtlg witfitht3'dmx~U!lilli'iirt~ rDf 1ihE! ;~esff'Dlili. 1l!I)1.5dtE!lIrlalti:cs of l~rme5Ifi·DNA CDili'itGictts ~ Il!p:rresemin~ the pre· ,~tDn!!aijoo.,3'dG ;m.l1IgtmM., and5,'dG, '~liIgMiiOI1J comple}C.. ImrKl:~ i!t~iI"ogelil-bol'tds are~i!ll!rl~L:d,tedby ~Ud H!il~s.DNlAc()f!,bm 1Mththl'l s;~m:~=r~~~ OU)~~(iJi:~~ glf~ W!m: ~()!!!!".
~I~~

9 NOVEMBER .2007

VOL 318

SCIIENCE.

w#w.sdenaemag.,()1'9

REPORTS
Ccickba$~;l!~ to iilli:e piht!.~!!' de ~~. The i!liOOl~tng d!NTP' staeks ,O:illop ofU~~s base 'pair. 'ooLwee!iidi~ @x0Cydic C(())-NH:l ali~i~ogm",p f ~'.]"P, ,.;I _lie ,-,\\1>J' - -,+~.-'~," , -,- 0,' 0_ \l!t-~_ _ <my ll- N€.kO··' ca,~!:.I!.!,!!y_ oxJ1loo ,f ne 5'dG of I~~e nlO'i,IIed.into, th,e,ruct~'I;Ie si~t\. tiU, d~e S'l:I!G. i:n lht'll Sln:octU!re', the mOOe~edlpi'i:Unli:.W b .3'OHis 7.S: A a:'Wny frollm the d.ATP; a diisUlIl,oe l~iIlIe oross..:~ililk~n!l';'(·b.'utd tnDh~ 3'.ci[Gfuroc.s th~ f !:llaypcrpei,tdi!oo~,aJr mlau,\'e to '~il~e~noorn~t'I,!l, d.1Jlrt .fu:! s:igiliflcailJl~~laJI~@, compared. ' I'.rilllil IID]IC d,K£1P (F:i!} ):13)" On1)1 ,OO'I~ H:..bon.d iSi: ~"l~n~,hed! flP.i1 don~liornoorlii;it!~~:K (5 A),lpm¥idil1ig:1l
,j

r:al~~elbr i1i~ .s1Q\Vl)f ~dl :1!;t~~5 ¥I~p. [ri! OOlHplc4oi lb, U1e5'dG is even 9SJ..aw'ayrro:nl Ih~ Ililho:s:plmte, and no ~ydmil,cn bond, is fnm:led 10 theiit{lQ:~ning dAT,P fiB.g. SS ~ I1'111S, lIiIe :!<im:l,g~tl ~brnadri1~moo. between InI~e hvo H patpoodieu.1:ady ·omLmI,OOh~~I~ ~~1~ Ihe pn.til~r ~lmJid al~ Inh~ dAl1P' IO~~~r. S~:ch .ru'I H;oo!ld .~<; 'OiIl1~y ~sibl~ \7I'id!l dA]ll~CI dCf.P, "~IMch e_'''Iilair!8 d:le Pll'Onl!5cui'ly far dCTP' ou'K! dATP dllllri.l'li,g tIl!e SCQOlildbypllS;'S: !it!!p.. Tuo'~ taii~ flll~ilinell' !ill,Ppon for this I~YPOidffiesi!i" Ifrim~r
cX:hmsion stud~c:!! we;repcrfornu'lii:l wi,dl PII·GG eOfl]:aini:ulg ~ftI!Ipl.:r~oo.md 6~(I':lll:'I1Iiflil)C}l'aidlirl~m.-

Irllillllc,(lGlifit:
!rQl,;!tI'!i11il

mOitlQ!I!!

p~~(1"iphaoo: (~.Z-TlPl wllicbical1Jn{lt fOrifl:i dJie cri6cOil H-ooud. A!!J,~di(;:~, bypa._~ (If UilL'l· 5i' dO ~.vidl dZW t", indeedredlliood r( fig. S6)'. \ve ~ tlIve CQ;ll~lm.e·medilil m,ooe~ (I nlO'wl?D~ll cH'ecl~ by:pass o,f :Pl~,<:iG~csi.>rn~s[dC!lllilc lire l.iLllllHed r,as:ol~niollJl ("<~ AJI Sind. beSili.lil.& :iill Itl.illd.
~~ets

IF'ig. 2. The 3'dl,ji ,eI)ongaliion IprOCef>5af'

,~O~'1

llineml imii-5:iliiild ~~e dCirnP i'llre s!iMn 'ml' tile pre"elOlmlg<l:ti,on mmple,)J .. P'h,e~~ , ~tgd~ tII",!!)n til!! dNWs dl'ilo~~~~, Ute clNmflis ul1,paiooa. (I), D:e1iliil@tJ1 ~ oflhE!! l'9\'iio,1IU ~llIthe p~e-el.a:llIg:atio!~ Ciom· I~OO'X ((yanll~l!pefPosi~o!1~:dl I!\Iiim th~ 1~e5lo~ifll the 3'diG eWliIgat10lll $tare 1~linaglHlm]'. '~Cl:rr,d~a;rrily,.th.efilllgillr d~· ilnd lfiiiiig!ifita) i!ir~ viewed illl a simpt~6eci. ~orm!.. Wamm(rick b~~ liI~iringr~'IIllIlv:esile il!HIJA tc ~C;Sll.1liCf! W@ 3'DI11 c;fth@ Illfim~~ fur l~ucle®pI1Ji~k .alttl.~I!::CJ:III the a;p!l1mp'JiJat~ of t~e dl~rJf. {C) The I)MA.u,evllll~ oomme pre~~kll"1:gati~1II state il'l'b1l 'Ih~ :ffiirst el.lmgartiOIi!. ~'tPI~, r'Onni!llg ill WatsDWI·Okk Ib,,~ pill .. , Tlhisa'l~~ns; 'I:!i!~ 3,;DH W' the ,jJnmer f'Of 11!!",'d.eotidyt traUis-fel[. lihe l~rotlElinof the p:re-e~ol1g.m{l:lil'lDmpte<X is !Omitted for cllaJrilf, i'lili1dtlire. Ipreo,reill'l ItJf the 3~,d:G el.o:liIgmi:l1i1 51:ate is de,pideid ~In 'gray., The D,fIIIA.n:lole~Ultes are mlQlf cededas iIrI Fig., 213.
liI!l!i'!i!1l :hi1!$ ~II! m(J~e(ulle~ '~al'i

(A)

Th~ cat~~¥bk :r,esndues:. the

tI\<lt cf,yS;l!l]pa.ok:in.glh~s In~~t ~nfl~jcllilee (If l!l~ ~tIUCl!,!!liell1lmp,t!l (rCiam ID1!~aCliv¢ ~il~l. Tlliil ~\'iIlzym~bU!ilcl!f:l !]j'~U~ifI:lplat~·prirl!!!Cr OOlll!ptex iD1o~prodltCti... yin d~e '"p:re..elol1lgatimll'·' d st<J1!:e,which is :iJuI eqlli.I'ibril!L1iu 'W:~th,lheprodu(:..
l!~ilIt llliIe dNTPs arc iboUII.d

live _3jd.Clclo(l1ig~tion smte (.Ill We suppose, rum. preslJlIl1ahly m,~ Idly i!;'l'idHl!ngcd.illl. die iM:([veslt~, [f a dINlflP is bQtI]'Id, aM able toililJ,eract \-vid~ 1iliI.~ OO!:I1lt1!ialing ha'\!1;, ~. $1ai~~ laie prim~r-;,l~atl)law Gq~iHt1riUiJ!'l
I:orwardll

dle 3'dO el(l:Jllpliolil' .!iltli!re;.

:ilir!

'W~llch

omHtoo gild '!h~ t'lN~,

mlcloolldyilraJI'l'lif'1Ct oooms. 1m ~e second step of leslou b:ypass, tiIIleprl~llre_r ]:eJJ1jlpl!at(,': i1'11iOVCS fnmrafdi, !i""~truI one H~born'ld! apparull~lybch1lgdt{; minlwum1l OOf!;tIlliim1:00I. to pU.n thL'llt~pla:lEp:rr:irn'l)-' er MlllpIl,el>l.'cYw!iruJ the i!!OOll'llimg dNtp ~n oWer OO'l'Ittt)\v ihe S'dO 1.t1!1!(:lt,'O'licl)I'IIram.."n~if, 11.1iis ~a:p.pens "l~U1\fh redllwdl efficicJ~CY OlHd a.~C~f,acy" ll1e proposed. ImUltiml cs~~would be: ';lI"eo~~Il~ tiCflUy qu_i~e disl'inctfrollll lh-ediNTP~irect£idl hn.~ dlJili:.'d 11:1. (libsel\.redin high.tklclily ~~ymcrasilS (3) and could be a spGci fle 8&p~atkm for mpUcaJtlQ:il'I o:l' lI:ail'apliltes oOlOOla.:~ing iwlin;:lla!ldc~

,of Ptol 1m !(~, eloiiig!Q.tlo!ilIOOl'lilpl~): iiSShoW!il l!il: ,gray" (lInd the p;¢ililll!lr'-llldt\e:m~:te S!iram:tare dlepi~ O1I!S s!TIlm '~tinriOMd. 1iIiIiel le5:tOO ,illllldilhe' dNTP dire depicted .a:s. !>Ikks ~n ,ijOli:ir'. (8) TIl,e:l':a,t;lytic I~@sidl!!@s W!!li!t~!:!r:Mth 1!Iii@mi!tia!lic'lI!s IlICl.!fiidi 'l(J! IdllP .are~lhmYm.The nud,eoilide IDIliIiD!i ollie H~oomOi wilithe .5'de:sl)lxY~Il1linijli!,e f thei lesnonc. If 01 o JI\ll!!(I[@wdlli WlSl:lrtiO!ili ,stu~:s; ~~posit~th:~ 3'i(i, of tilile l6iO'~ IIllinga ~~uo!rleS(!ffil1·liibeled l3ilintl r lihe5'dGi
Cli ~m~p~~c dsp$a:ljn I~e:sknl twSIO(!!) 'or MllhiWt 1~1e:s~Jon ~[ee:)I. The· ~f:Illl1Pll!JsOOin 'ei'li!lm e;(p!riIinIilIi1I is: 11lI1m:edl .ilIt 'ttte 'top O'f ~liIe Lalme;.The m!lllr~m (MJI U!PJitlS8Iilt anlnseJi'li(lO [I;pp.ositl:!ile 3;'6 '(14m@r)' alnd the S'G (Ume;rr)" (0) NlJdeotid:ern'semon 5rud~~ op,p!)!§liteltie: Ir~~oolii~'IG, U5img lie .5ame l~ellOOtlf! {oar!dl!1lic~s .!IS ~!II (O.~h .aJn'y:~fUooi!'t' I~abeled !.41in er IIiI)!\bridfllf,d'i:ol dli8me~ 1[I:f:iJA tEmplatE wiih e~!h,err a ~:te ~pe:::irk d5fl1aiti:n les;ion '~t~liOfl) Of w~iflcl!.wt ~~~Of! fv~l

!Fig. 3. The 5'dGI ,eTong.mon p~1i

lA,

l~ylbridi2!ed

'loan, lamer IQIilJAtemp~te eijher with

liHIin!'flji;

IIBIIfIj

~·ccoc~oc~~.r:cT:

5"~r~

969'

REPORTS
IF1g. 4" S,tr!!!!Ci'W!rli!4b~dl PQint rn!!!~nl ~\fl!i!lg 73: '~:A}' S'eqUl!IiI(eilll~igln Inenitt of S: alfBviS'Ge. h:L!Imlfln .lInd .mOUSie .~o~ fI, IDP.[)lI., :nldl human Po~ 1 ~b@Wi!1gl ~~m:R13 'is C'@!lSi~l'LI'~ iflPl)'~ TJ hClmcioQrs. 5emliloory .~njIJdtur'e ,e1emeOOiiltre'itI rOO:']IiI9i~e fur (il: l~ie1b:.and I'IU'iGWS If:Or Ii m,mds;. (I) ~NA .~El'lJUflllce!> 1~5iOOri:):~ p!'imlil~ l~ooli!s1o!i! stto~ijiesa!i!dr@1' 'fI!lill !Cl)!Stami!iii~1JiI of ~htlii'~s!'tt b:\!'PaJ$ :Site:p (CP:t)dlild ~~eSietllllldl hypas.~ ~p !((P2l The SlirteS (If tile 1~~s1(1!u~ i!l!dkaJl;i;!,d '11 red', «(), 'ifi!1ll~dil!,pel!i1d~!1tt ,riml!!re::dli!'IiIs1'ofil :ntadiE!S;M,~1il Pam ~. (ti)' allild IP·ol 1'I1R73L ()t)~using thE! .sa:rneilIe!mpialteand primer stwand5 1lISE!:d for aystam~ijolf'l but ~(llIttl'lill ~!iespedfii'c dspl&iuJ leSiioml. (m)i 'ifime9l:ie,pellfld:entt l~riliTiler exlE'IiI81DnI.!i1:udie:s,wnll porn 11.<l'ill' <llliId IPool TJ R7:;1L (1I1l1 with 'tiile:s:a:metemlPlate gIld primer sHoilnds as ln4( Il!Uit Ciislte-Sipetific ,~s:plam Ire~l:Irn.. .
1

.t... ,yPgl",.. "'~:!.."'1

~l",!
!!·L'<\'I1""l. iI:I'~

____,

~I

F~--~----~~',

:!]

~~--~----_~

!I"

1i'!I'

ilIroflif

1I1.1t!

i!!!Io

I"'W

~u

... 1ilIi

«!

:il,.

'"

'IJ"'1IIi7

U '"

lI!! '"

I" · l!:t.C!I!! ..

"'" O!II

m'th

5, r m'G:GA'l!G:lG T dJIT~

c.M:~JM::'IZ'CGG:'i:J!le'jllC1l'

3 ·(2.cCT-AC:'Il~'l\C'l'l:'il1'

5~

IQ!p.QQA!IlQAIC: T 1IIr.i'

~i!!!kl~km_~ (12. 13). 111imp:mpt;D8oo~:~olll,m'lism M.gll!.es d'l~ Po~,"1 se.1ect'l OCMd d1\7IPs :umt by silBpe b1ll1 by hyamigon, 'oonJdi cmw,~cltlclltru:hy, which ls OOlfls.is:lent 'WIlUa. ~re'!;'io!ilS, hiocl~c...alil:kat observalii.ons (14),
To I~~ Oli' 11m:

g~i:n1 ~'uj'lher .in~.gblintQ the bioch.6f1l11~~ bWIlli~$.ii'il);aotiolll 'l,1I!'J{,'l all1a.~y.zoo a :si~l'l-

9. )1. 'TI~In(ll(l !l1 Ifl" oMllli C!.111 8, 411 (:~oo1i. iLD. A. Iii, IDillocia, 1r4. 0. GriRdr:e!l',C:'~1. J~e, li~WifriArili\i; 1ii'e.5. 3], 4·129 (2003). U. II. J, li:t1thwdl, '6. ~k,'l!l1l~fb, t lW~ ~1.j!8'~ ;::a:Ba4 (itOiirr). 12. ItL }il~,IIt!«I, M. tWi!I!lllmgtoli\i S. l'Iratasi:l,II.. Wr.1lI:.a~III. t~- th~rL~:;!5!7,'J,47 ~OOIl~_ H. M. t W~llI'I mg'liflJl. t PI'~~ilil\, S. P!'jllr'i!sl1\ C>'!!llltn. ~.li? (~CjD,

·mtlp3ir., (llllll)ejjJii5d.ef(jrn)IW'I1g5gi~meI'o9lih.,.t «tPS"l ,~r.H! S;PB64,61. Viilil'lW<!iJern rmH~!I;»n. ifoli!dSd!:rGI~mi5l:her! IlndllStri~, ~!ldl N~I!fu,M.iil .graiefulll!l~ ~ EI.lI ~,!:, 'Gu~e Tl'!li~i~ OIndiM~g~il)lr,e!I~llp, ((U.lSiQX!JWJ!i). (iIIlI'dlmale;~arll!! slliUltUne< 'faCOOf:! hare bem ~J»Sl~!&iI ~(] tlJe. f'i'ilI~~ IrMta lB2i'it wlllil!!r ,:j~I\lDl ~.~~ 2RIli~'~tMl ,
N

~r!td

IlIj' &JllliPNm lJIM!ln ~n~fat@dl ff"J~1 ·l!).NA

2MJ(.

litll! 'lU.~Ill~

·[!OCI!rl!!

00 OOI'III~~f'I!Ifilllilfl(kil. IlIllf!r~ll!i,

dil'WXid Il'1!,Ji~ttlill. (lfPQ1lil" .Arg73 ~~fi~ 1{I;.1(;llv,lMjj) and st<iM~ize Ilhe dNWro~r lllliIe Ie.'l~o!l bypass

steps. 'llle~midilijunl gN'IJIl stacks 01] tilP ot I~~~ebase nlOlic~)" ~i1eil1.{lQ]fllillg dN'TP (l.J)1 of
\l,!hicbi5i1.'LIiI~allt: tor !he CiQIiroCI pasi~ioli'li.ll~l of l~iI'mdNTP'@Ftig . .3B). Arg73 IS h~gh~yool!L~f",oo IUl~OI~g Pol 111 b{Jm,olo£}l b~tIH)1alllQ:ng ,ot~~~r

iL.4. M,t Wl[fiilmf!!Jllflll. 5,.A Hleli!Jllliiil!.E. T. Koo~ l. f"r.ill:1i~Hl, :5. P.r~~_(j~I!. I!t!i. Cej'i!, 8i~. ~3\ saoi' ~2iOOI91l, 1~. IE.,iIi,.1!,t~~r. R. t::. Q~~i<lm~, F. ![)iederi~!il. ~~ Olem. m.r- .1f4. ~2~mO fl@Il~U. 16_ M,. t W;l!llfri mg'l'llifi, it it.. ~~i'I!i[)rn, s" h'~t.as[], t, ii'r~~~111, .f!!oc. l'la!:l_M>!ld, Sri. .u:S.JI. 9'1.~09.:1 '[;HlOO)" j[j!. WI:! tma.iIt tlili!, ~o!IU alllle 1f'K·.iIl b!!amL1A~ ~it SiM5S Ligmt.
S~um! MI~ngt!ill SWil:i!ttilafiiDa~ iD!~2 ~.
[ifiN}jl@ffl,

SUP'pi],rtiil!iJ Oill'~iti@Mil,tE!1'i1l;;d Wli.iii\.!:~k!Ifl(l!t'I\li~I,~~(mVtQmill!rnlir:ulll!31a~a'5,2196"1~OC:l fi11!' •. s.1l'!)S'9 mill€! tl..

f!!e']eFefl!Qe~1

Y~fliU'ilily m)(}lym",~~

ArgiJ 10 I.eU.CI!l.'C (flg. S8) androlmd ~:tmt Po~. I1R'7J.L (:Po I 'I]"') stm Ciiln~~,1,.~t'e mKi~1l1~gOOl

(F~g. 4.A)!.

We !m~te($

~~hfatrOO III.ildiilL'lorn f'oc;Lll1t[{IJ~fr,

flrilOO~.

2.~ ]Wlif :liOO·;.: auepltd 1!O,'O(kit~ 10,1l12:&lsdau.ll.1l4il.2!42.

~:OOji'

~c~np~.lIies (Fig. 4C,11"), al~ru.cru,ghmile ~iYIw..1'u,~ 28~iOl1l elll:ick:ncy~s S-UbS~ool1i!lUy redlUOOO. Po·~. 'lR13L is ,ab!(l to ~rfbrm, ~1h~i1mst b:ypascs step ~1Q'i,~'~Y1n~fi'IIpari~ll ..l.I'idii d:m 'W1iId.•ry~~rnr.ymFl!,l; i
(P~ 4D.~1"')".nbe~., the ~~(I:m;[f>1~p ·of'l~~m~ bypass is slro!.~gi.y c~nl1promi&eclL The same bloCilLendlOlllp1'llperrli'e!i are observed with CPI) ~esnmls (fL:g. :87), sbowing that the fiuncliol~1 or

GNIAT!-ILi ke Strat:e!gy' fori IPolryk,e'tide C,blain Initialion

LiaJl'iI!;Itai 'Gi~ lI..2~Jood Gedll!i~li.~'" IBD,Wcail'ilg;"WiLli'iim ,H. 'Geli'Mick,." ten'stil1lil IhikiIilUl~SOI1l,;~ IDane1L Smrudl.1,$t ID.alw~d H. :Shel'imal1li~·~i4·~t bi.och el!l'ilkal~ strr ate<gyriDr c;haillllinm:llioni is: de.licri be~ for 'the ~Ga.d~lngmo d:l!ll.e of ·the po~yI(eijd @ s,yn.tlhase ofcll!Uadn A" ,alii an:t)ca 1'iI~e!i lead de!llfwed hll:1'I'i! thiema,rinlE!! 'Clla ~ oilaJdelliil.l m ~.~y,a m,~~wl;(1' •.A. 'OOliitriill. ONS·~'I~md N~.cetyltr'~!ils:r~,asre (GNA:iIi) Id~rnlg:hii' b~i!'!IIi'5, bifunmC!!'Ilg! G 'ti@'Ul:rooxylas@lS~(ie:tyttr.an $~e;riSieact!iflliity .• both I.!IflpreC@cilllllltE,1liCllillie GNAT sup@rfaliTilily • .A "lIfA f IO!a,d~~IfI'9~m~!dcmailil. ~alll~l~s;triril ef iliflacla,ptillf a111maiirJ, thill' GNAJ (jom~iin~ tl!n;~allflacvl WllJ:u:iie<r protE!rlil, ~l WiiiJ,'5d's.'Se~fledll~ioth!!liJfIh:,tllllY', I'e!i!ea~ililgl that 0111 d'l:IITliCllifl~lIiJoiMifl!\l homolog), tal GINAV (GINAT.) c,]1t.aJL~!!5 dlec01lroo~.yld.tio:!fI ,of m!BiIoI!~~.·coen:zyme A {lfllilll~ol'lyl-CoA) to i!l1(ie'tyl.·CoA .. 1!]i),d dil1E!'Jlt S':jiuiel:yl. tr.a:l1IsJer from a'Ci~·<()A to l.oa:d an a.dija[ellit:u~ ralmriem p~fltejn oom:allill (A:(PJ. ,Moreo'll',~rr,. the N1-t@lIilililill'la:~dJd\ppt~ ~ailil was :shown til faCilitate ,a1C1e1¥"igrorl!lpl:raliisfer. Grr.\Is:ta~ :5tmdlllllTe!l o,f IGfI\I':AfIL ~Iie! s:o[~dl at 1.'9511Ii1giSi~ !(~ig!an.d"free foril'l'i!)gfld~.7511ngstmlTllil ~,~!..(1)JIi. ,oomple~, shcwililg ,dilrtililct :Sl!b~1!tam'bl!mili@lsfcr acyl..(oA anlli holo-ACl?l b1lfld'iilflg~~d@lir!gandi siK¥dir~(j m'i:daQ@IiI!s,is e'xperilll1m1S; ,Ilieltionmateci that h'frs,1iielliIl!-389 .altd th!l'@(l:lflin;e.3ISS., ail the (clt¥ErgeoCl! aF the CoAiimdl ACiP tunlile!~, parlidpatll:in lliDillo:rJ}'l.·CoA. (llecilrlbrn;yiMioovllIt 11I0t1111, lI!;Qlli¥·gfiOUIp 'tfilllilsfe'r. DeC!lrOOx.~iti.Qm I!lrlet:Eae'l: .a.c~.gmllp tr,am'fe;r,. ~e.:Jdlirngto ilCietyl·.AC~L <Ill. the br cUiua.cinA. milterr lImn.

w.

II 13 L..

@GI'IC:i:'8nyreql:1~i:'Cdi 1'()'1)i:i'

ror

the 1iiCP:~iruattOi~. Pm Il!IliIexli',~tM

~il[l)lZ~([

1~lIiIro'j[jii.hilll:i'lli>lIiInJtlcrufill"\HD~k. (16). ..

11~~~

crys13Uog,fapld.edy

comp~exes, lOge~er willi. the bfucllC!J"!~cat datl,

f!1OVDe 41, sle~~ ,.L(:ture of ~:le~esim~ ~;W<'!.!SS I;)lrooess.. 1l1isildo:l'lil:lilDionmay lead to 11f,"" ci~ 1iii:1~lindelri),!;,!I~;i".e~s· I~:O' esc.!I.r.e 'nm1ilslesi:Ol~rep" able liC3tlQn. i~.o:rrd(\'l' Itl) O\i'G:I'l.~OIl'm: tlJil'Dtoil"mistlUfil)~iI~, dSP:~:ui![lc~!l~.'O'IlIl@~y.
R~fl!i',~Iil:i!:~:!l <inC! NOtell ll. 'iI'~IIg', rum, l'\l'l-irI.. !S'i'WfJ. &((11\, ]3, 2.~ (2003), 2;. E. C. FIM~dI>!lJ>!J, R" Wag~er, M·, lIliloo~:iiIl\,$'ciMCf ~~9~,

m~

w.

1~2:~' WOO~" 3. T. 1'\.S1i~itl.. j.. iJ'irJ/, 'Irm.Z7'~, 173:'S (j,'~99~.

4, (,rI!;!~i!!l<!11i ~11:i!~~ NWfte399', 'j'iI)Q

W}~~l

S,. 11,. 1::, J~llfl~ml.(, M. ~o!lI!Jr<tLid, :5- ~r~~~ll. ~. Prat;~~, sr;im.r;e 2;1l~,- ,l6~(1l"~" ~. i1;,.ILJllm:M1l~i, ·S. i'l'aK.:i~h;L P,r:1k~s", 5!."IMr~' :ZI!:il:, :lOiJli 1. ~t. [;I, Jilhlerttll<l, C. ~. !jr~~1l"J\, It lehman fI" J. 'O'(jJmnllf, (!I'Imeri!lg ·6:5, 9n9 42005:1. a:, 01. W<!nIL S. 11,U~rd\, ~.Re~ ~9 .Di.f~ 4., 307 ~;2:0DS,L

UL9,"'.

,.t

I.'lltclmy 1iI~i.liktbo1Ut~ \Vi~~.3. brooo. ~lrum of bi(ll~ical activi~i~ M~ltiR!!M;lio!'!<3!1 l'l'liCYu'!es c;)JjJly~e froSt.1:IflUlillldi ~~l(l~lic pallw{ays 00 VOL 318

.a.~smnb~c:511ru.olll!l:r:'iIJUy

OOUlru: po~yke1iid:e syn111imses I(PKSs) ~ I~~ 'bio~Y'nlllil~~i~m~o11~n~. ~~a~

dnV(l,l'!lc
SClC:·

assemMe sI}of1'~lnilin IIcyl..(JoJJ. 'btJildJll~ll: blocks iilfllO Qomp~ll"xpol.)'k(lt'ldc IPl'ndm::ll>, by n:ne !>IcPlJif dnailil iI~[lil'[]ioli'l, f(l!!~01WCd, by mu]"'i~J~ steps o:f e~~il~ !1:long,alion ,:MId, proce$:~I~g.. Polykelid~ . chai!1!~loo~a;liO'~l ~ps am. cat<1iDy-.I!oo by i~len-

S'J.(I;!ilr!lcJ;i;,hil~ ~<I!I are !win!a:rl<'!Uy

C'OIll;tKlsool:Jif

9'70

9 NOVEMBER .2007

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
fiI:lislicm!ly and slfl.1:ctl1il'mly disDiI:'~l!i.Iish.edl mm. 'duo:.!PiKE; lIi1f1d: EAS AT .G0011!llins thalfl~IKti<nln as S"l1liCy~li"iiili'I5fur.Me.s., mc' a mvaleiill c:M!ymiCiil'lte"~ m~d:latt'J.1lifld 1be1clJJ€llo thl:l ,w~l~y<!.m~3S('l wp~r.family (13-16)" T1:vus, .acyllfiUi~f~r Iro :!IfI.ACP ~<lfw.yzoo by .<l! "l~~i'lis. n1l!ooi!.!~.e"llia..~~ aijl Ihi.ol :smt!ip~:~~lg ~rI Vln~~d!~nte~ ~"cchara~ci.zoo 'KSIt. ,cOJl'li'its (1ird\orl1!!~!\c'"~.orn-o~~ Iij'Clcl1! for GNAT en.~mes., (iI',!J,U!JIs:,,dd1 do:rrmills of ~l~e Il~IinJmnsii e1>i:tel'llSlm~ , T:a,illf'I!Icsli;g.mc d1e:ll~WtOid rKS dmiinilli.t~" EIJIion I)l!IUOe:ss, we dmnedl and. o,vcrexp~ nnoollllc" A klorliimg flIcY]I~mllSfelllill,se dOlrtlain fmgUfill1S of (:llrA cl~CJ:lI<jng ~~~~ N4~rll1iimai~ (AT :!L) II!.ISGS au :~u;y~~CGA suh.'iln'tttl to load an adjaooot ACIP' doma~iIl. (J'i.:CP·,]., T~lIy.dlii'l moollll..tin, AR.GNAT~-ACPI... Se"~irral. ,~presATn., oo~tr:li!l~ ig: au (1.-cam(li'l:yl~~L'lda~I-C('lAj ~con c~'S~,~elgWI1l~ m:3d~ro ililc!.w~ Iltolil 1I!IfrQiJ:l ~n:l'!th~· s~~h~ fur dlain ~))((:(ln8t(D11!!, ~d acyl oon1pOn:(.'1.~~ nwu'iiQ'~ ()01f!lbLnallion~ ~f'i!j;.2A. ~ Il~t5lCr is r(d~O""""e~ Iil¥ d~'{yi~(t'O!~ [:):'/ 01J m~ f:i.~. Sol, A ~B~ Co!iL~als C(Du:t!U!'1!in~ ·'jKSo., d,(D'l1.1iI1nwLtJ~in dle loading IlIDdlUle(! ; 2), ACP.l wcregen.erili1ed, ii!l1 IroIo :rm!l11 ~!)' (loex~ A]~cn:tatiV\e:~y. in llliIe l?iecU....lll.ldliiOO eryd100nay,cin, p~iml1 with iI,P:l.ssl'l1id CI:MCOOj~~gpllosp:lloJml' PK.s, :2Ii Irnl~climg 1n:e,t11ybrn.1)lon:li'lIc.oCoAdCcru:~ Ic~h.ciuyl lnmsfemse (S1jp" ~lmn .lJtt.cilliJ!l 5ltjhliJ~s bo-xy~3SI.l:i:l!CIS eu !l~..tylaJBd, a.cyl,-CaA be(.17); \."I~tLliIO:i!U tbillll plAo;;mi~ E.~·eMJ'it.i'h~cali :pmd.u~MA(:rl. iml. 'UI.e:apo fi)itn:t AU iX'I!l19hClS fofL'l acyl trnlil'lf~r Iil:y ATIn.. {3" 4)c Cli!!t,:}CuQf! A. a m;)fill~ ,eYa:Jfl(lba(;;!~f'~~·~~ttlb~ I laclci,~@: tIDiI.): AA domin welil'l ~dij[y ~~~ood :~ lloil!!!blJc poiYiPOptides,. but I[iKISC including AR. olHc f'-mm L !l1(}jil8Cuta.is a mi'll00." IXllykelide mlom,oo.s.oil:tlOll"pefJ~ide nili~ufill ~roollcl: wlllll po- 'CAR~NATl and AR·GNAT~!..t.l\CP'dlmdl! suhIM1~,;!!;IJ~~pmlifl:'mtllveand cyl4J~ox,icm:::H,vily !>n,..rian,ydecrea..~ sOlllbi~ilY.,and [~lee.".cired ag:Olll!Sl 001011', rcuml ..,3m:llbre:ilS.t~ca1ilcef'-deri \;,00, AR dOm3il~\,laS llaotobroill.cdi in so.t!JIlhk (mill, lJ~n nl1~,(5~ 1l~('l mCelt~ Ld.m~tmCalkmfl1ld pmr~ lmtielt !lny ool~dilioo$ ~1.'lil"lM." SoIUJ.ljiiUty W1lS l~i<1l1 ,el1W:aCt~.tilmof[he fuJi1lil)'l1inhd.c[Ja'd~W'1l'y :moo,:uril:jJ]ly ~-er: for d.te:AR-GN'ATI.-A:ClEl fill!' ~i,] A (6)~\I'~~ ,an. ilf)liplcal ffJ;1{jimlg (holo) lul-dolllain U~H f:or 1~!Iil~,~po oo!.!!!]~~iU'1I (fig, S:IA), SMlmestjng dun rih~-p'1!oSpllOJ/D,atlU:}· nlooule.,[r! whL-ch ml~YOw: A:CPi~ I~Mb!ed lyp" tea!. PiKE dOlMOliM. Sinil1ar loarllllig :r:mxkile;s also d.1.C'1ue'p;Pant)' OCIIl of ACPl (lflo~n)smalbllrnes the ( oo::ur in I.IL~biOO)lI~drletlCpatllway5 for pederil~ (7), All dOJ:11<11n. U!c 63.J.!kD A]l..(jNATeA:CD?t its strw~mllI ;\IIlalogs mm8itruid:c and.lh.eQ,ooe;ril~ polypopnid;~ism(I:iQ.o.l'a~:rio (fLg_ SlC), (8),m:'fN!ovirosoin ..A (~), andrh:lzoxi~. (10), ~m, To. a,~s ln1iJeil1liln.ffljO:llbehavlor of dm OlLlrA l~iIiI~ nallll'lll pl'r:ldliLIcl biosYII,,!llmll.c ;!'lJ,\lillll c11.1lS~llts, gfii'l.®I~rl:lliLiII.w'e ~100.llh('; 3~ al1.dibolo fm1l1S of 1~1h~chaulrI.illi~liMiOiI!lli:tJ>dllllies 1I1~ 5tr:uctu~ ,a.c!i 11111 U1¢ CI1DiA IDd(lma!nl~ (AR.(iNAT l-A(:.P1W and r-.l·temli~,II-ISij~iJimlno @c[doo,gi<llll O,rlnlkJww,~ d:idonuun (ON'AT'l~A:C.P'J wid} ndJ~ollllbelcd fUIIClio!l [adal~ler (AR) domain. ~10\! p~-SCI1ll in, ~y~"C(1iA:s ~u:KI. alliLll~dJ ~rotdn ri1diQlil~linlll Omd3Jfb'r Qlulamide]. ill ¥ari8bl~i"!crl£1h,~h~1«:r rcgi\oI~,GNAT.·!...8!~dI ACP!.(fig. l), De p:re.-(ACP)-pl~sa1lll(uliflryfluoce:!ish'!l OOI:i:lruOS (e.g" :~e!IQrodrrelllSe~dlll:IYdmlrure, ;lind Cl1o:yt m(lucla...e), As~ntillily ac:td, :)fdfldl!ilSC.~ (FASs), PKSsCllIn.~l~ S chain ~)1In:rnNiio:rn~y .[1. d~N.jI'l,8'~ivn lJo.11I,d~m!" ~alno9. ~i::IiQltPi"l~.y:ll.l~~i~eh:!li~ i[intiatl{!u, i~ d:imcdrlmcl.io:ll(lf

1~llirec~~~l'a~ ,dklililiiiJ).,_;kelos)lIiJithiiSili (KS)\. ~CY~~J.liSfe~ (An .u~d ~Ic<i.m.erp:mteh~

acy~ ~r~!' i!~ ~~rn~e of a c.o~'<i.~ern~~i:ile~- by $]!):S-pt;!iIYiiCli"yI,:mii,te :~el ~Icdmrhgi~~~ U~e

!l"ie:d!kulil '00 Itlie e!~!lle ,(1

n. GNATs

@fe~lech-

(PA.GE) {Fig. 2 B}. Thehnlo fl:l".iil!t:1S of 'oo!ltii.b~ Iriidoo,niTIiln,ilinCi didbnl!lin iflOOrporat!JciI! tllite r.acil!i~ labe~, whereas 'uJ~.e apo fl'Mnli!>were net la'beled, llild.icalil:l& Irn<lJ1i~t:I1]oes.umifi:c..1Ikm afdn.e acy~,~

foom. CoA

'10

~G:

"!P"Pa.nlarnn

(J/f

ACP;

iI1tillS,

d~e

N ~nt'i1in~l ,d~n13i.1';of CllIrA ca!alyz~ a.eyl tai3d-, m,~,,;mm oo'ditLQ!l!l.ltP~~t~5.~ Illot mq!.l~'d. b~ of ra.d:iclabetin-s ·of !I~e!lip;! roml~ ,<li~so'~I!d1~_~ ti~aI: 100cilifrlg does Il.a! proceed. 1~m.ro1Jghfi (lovnleml[ crnzyane .iltn.'irn~ediatC;,!,Xililicb is t1o:nSi.is~tMI1 wi~1IiI

Ii~e dil'lecl~\dt:r 1!1!:Jc.tmniSl11l esta!lbH.'liled for o~mr (iNAT ram.li:y l!lu~1.1I1I1bt:~ (3., J1).lhiQis ]111. (;M~~L ee Ule '·'C<'1!lrIonical'· ilKS ~oadirng m~
!.lIe;, lWi:~t;cl

(DlEBS) AT l-AC"P.l (3), i~WI~dl a @\f<l~.entlfnU:lllilooimeis obsa:ved forl'hc.~ rOfiln (fj:g. 28:). "Wile ahmty ,of Inlne GNKI'.eA:CiUlt (liolo) djdQJWII~n 1:(11 load all ac,;'I group dCl!lm~strntoo: 1ID1md.te ea~alyti.c: machirnmy [101' ch~n il~ilia~mn ~.dOO widll~ th~ GNiATI. dolt!lail~ ~lIldn(ltW~dlilll the AR dO(nla~.!lt,~1iiibiChi8;MS(lsli!PW'Ort~tru ll!y thi!! rild I!fljm~ seIedoo I'nl!l.t1lnI01'Is wid~hl GNA.T:IL.
ilIfi'iOOl.ed!'he hmdifilg, bcl1<1vior of AR ..GNAT1L~ ACPt both, ~~lcis (f~.il.S2)'lli!CI In b.I:JS (fLS. S~'. H,owe'!,oiC~;dlM!im::reased level ofacyl ..glOOp loadiirnlg activilly by I~h(l AR,-(_"iNAT I!.mA.CPll.. (110110) lhld!on.tall.n (F.ig,. :maud :!lg,83) S"uM~1S tlwtt AR is ,,~!.Ui~d! fQr ~ffic:i~liIII1Ic;{l. Inran:llf~.

by 6-doo...:.yr;ryd.lll)wlioo

B ~rHa1al)¢

URet:pectl:ld!~y.oolh IMrnlmayi-CoA and iJootyHJoA rUilICliiQ;f~e.d as Sl.!:ool!nlesror tbe AR"GNAT!IL ~ A{PL (holo) Ui.dolmut~l, wi.li,'lsbru~ilrcmcioocy
(rig. 52.)\ To fll!.lflhcr~lWeSIJ.~ lI.w CmA .AkaIA'fm_A'L"fa, 1rid000aJin (;OI~IS. wa anllly.mdi I~OO pmuer;: 1I.'lI.t..~lI.~ Qov.all1Jl!1Iily 1dl1:~ to tile PPMI.
aml

(If ACr;n..Wcintem~d ~ni!,!5.,'iclla!L:gesOl1 AR·GNATl~ACfilL i11r 'in; .as ~yl-goo1l!p IrnllSfllf

an 'Qifl~llil~ GN.AT!;-ooollllill,~t:lg l'Qad au acetyl. gfO.1Jp Qmo lire PKS~mblylhw(6-.I0)1 b~t ~eme~~t~~
ril(l(hde.s.
Wil!S

O!:!;sIJ!WIl.'M rem.d!'l'W.~~!C~m". GNAT :Iis II SlJpertmnily of .N~M:yirUm1f1SfCil:ase Il:m1.,ymn::sthm: call11Yilio acy,l, lrl<Uli5&rio a prima.y am:ilae and [u:Iilcl:ion Ull.c1!~vm:s~patl.'l\l,Iays ~11J !pmka1iYot~:M1'IdJ CI.lkflty<lte.$,ifldooiug, a,tlUbiQ1:ic IresjSlfl!lI~, gelne .m,g,~~3iit]l\md! ocm;one ~mthe:b '(n -''''i, ')'P!~ '!k' roA~ -~"'A.,i~ f ::>~lil.. -', }711 T -"n ..y; :Vro'_~~'LC""'!Y!. ~l.!'!'i,awy~:u"C GNAT~:h<ive ~<J!le bhidi!1l£ silesriJ:r Ule acyi dOH{)1' and <lccqJIOl:" .woolmtes ru'ldca1a:lyze direct
~[jf,~Sriim~~.~ 11lS~llltl!, U'niIi'ElIg~!I' !!If ll'Ii~IiIj"~~, lrrrn I\J1Jcir, MI A MliI..I!I9, U'W\.~ID!i!pilrtrm@n~ 0'1 M~.5d·rtilChl!'lllls~li)'; IlJnUooB:il~

Qr

or

t\!il~h~g;ll'" ,An~ liirbuf; /",1 ,<t8l!(l9. lli!'l 3[1I1:partnnMI'~ I[M~r(ij1 (~rnr~'Iry" UlmW,ff,~l)' MkMgI~ru, IIll!lbOl", fiU iii' A 48!1.09;, U5A. *,Depafllfflerrlcd ~hmtim'f. IlJni';'el'5i~ IDf Michi· gan, /lin II! AfbQ!",eM.! ~:611)9. U~l\.~Dep<!r!lf!1enlt M Mi'(fCob~ogy ~ndl hllfl'1~~logv. ~riJ~er(ity Ql llidl!igan~ lWif\rbor; MI, o1i81lJil9, ,US/'" ~epal1lliflllmt (Ii e..;ologi~l_ Sd~nll!~ Purd:IlII!' IJI rii\i\~'[;5j":t¥, iM!st I!AliI.!fe"ttl!\ IN 4,79(17. l.F£A. l;CrilP~ Irns~IDliDm or OWmigfl<IIJ4!I!', U~NI!\r.iil"1of (alif;Qmi<! at :'l;an 1lHi!g1l. La

!Io1la,

(A

92a.93, USA.

'·The\i~ ~'U~hors"QI~I.ribu~edqlJ~il'l' to' thi'~I!IDP:. e f~o' w11'!!llFlil Wfr[,~pm~!i!~ ~1!lI ~ . .a~dr~'I1~,E"!l!l~it daijfd~@\I!!'I'!kaf!.«!lu. m.H.SJ;Ja!'lE!t~m1ifli!@um.ich.,ed~ W-:S;.)

filfj. ·IIL. ~ilI~,1iial:i(jlnmo(:J'ijl~WJrh.lllflili;.g GINAlii. and ~omp(jIliIfiC!S [pr,edu:ceiJ by the PKS Ipatiuiili~. AllG,NAif"L." 'Mn.taJining riimdu~s: are p:li'eldi.md '10cilitalyze the loading [!if a.1iI alCieli'flglroup.18 ~all!ls.e ,d~t~e' l1i~i~similarity ,of ~oo~i'iIi1. oonarnid~. gf!:d~hoo.~d~rim ,ooly oo~a~idil: Ais mowfl I!Irmly~ '~miJ:!!I~,

,,,sm~

97"

REPORTS
bYit5ing ~~e.i.ii;;iwd A£Pi, a'll !;he hllr<il!bs:acyg~ gfo1ll'p ~Pltt (Fi,g. 2C).&idsed ACPtalllcl: l~iI)\',psj IHlige·s~:cdl A RAJ NA]'l ~ACP.l S:ijImrp~,es were 0::a'l'll~ed by Fm.mleur IU~II:ljt~;fti.mlllioilJ ~loli1On ~ilOC Iii:m.'> ,~ul'iOlil1i~ (rnCR..JM"R)and, illlfi'!lM. ml!lltlphOl(in disni:1llion. (]R~irp.D) ~~h.(Ir ~'ii:

AA,,(lI\V\,TlII.~ACWlIl •• Wedl.~il.td.

i~cis ~c6t}'~-

.~ iM._~ ~ ~labl~lIll1ro ..:-"l''l' b· 'M"'3Iila1g~, i~~ s~ . ~cs. ~..~ as .';1 ,!_

.;1<;.' 1;;,0 ..

V 61). fi~l,~h~ (Fg, plI~~(lpa!'i:t~in,yl:Mi(lIlI A

~·'.I

l!fyps.!nzd ' igeste(]." A!Iil1.iGNATl~AOh. ..

l...

1[iI:y~llWlmilg

u1e

J _-'I' c~ ·~11 Jo'I;,t'l'1 oom.'Sp;[bri.lm~,.::Mi:r ,_,,\ II.

Irn!Cion.ll(I3M~ S~l or KMi,fflIIii~ for ,::W~lyl~l1Oqp 1li':lI!\c~r~rw~~ill1.lilar fQral;:~IJ'~.C!:aA <1!!m ~h1i!~yl·CoAsub~nm~~ In oon.rllfasl, tffite~. (fUl..' 53.·.··.).· ,aHld.~.~'
,'.'fLlle O .. ~

group l!!'ai:lsferd~ of AR·GNAT:I.. -AL'Pt (h'Olo) .by lIISing 1[1~'~:aootyl"("oA and [2~ ~~C]m:;llo:ni~' JCoA subiSnmtei>.n.e ~. andlKM Vi1i.liI.!.e!l were d.c.lri.vccl .by 111lCiliLWriilil l.heiil.u!m:w.o~eculaf a.c;ji~ It:lI!irI('ln~rrrnJ~e a sml'~ oJ aelA-CoA COO1Cl!l11at

~lfomrDati~iW~ clmn:gli: 'llfial le~ lID effucli\.<e bi'nding o:fiillie ACP;II. PPaiU<imi Wi I!le OJ.clive site (k2 ~n fiS, S7). Ta]k;en '!:o'gelh.e~' willa. the

n~~,

(84771\) ACP]_ ~Jt1IlIItBntproDe~1fl(1.9]" No.1mbl,Y, rut bod~ n1rSl.lbnyl.CoA and aootyl.CoA $1i.bSIr.al.:es,

Beeausa preiv~QI.il~lydcscfil.bm1 GNAT enz-yll'tLlS 'c:alalyzt'l '!i'a:rI(!1)LS N-'M(I(wkallomma.cliloms, OIn:ly .aTil :lC~lyl gfOtlip \'Vao;: .c:J'eU!lCitoo on I]l~ PPl3!Ult am~.of AFt ..iNATII.-ACPI. (.h.(llo) (Fi1l. 2,Ciill'l~ { f'i~ S3), 'Of ACIP'l, (I~ono) (Pug, 2ll' and I~~. S4A). n~, Ole CurA GNATl looding!noo~:de' COlJ:aiyzes borili d'ecru;box:,laljOl~ aud.iil.Cy'~ ~Ir.u.\;,>fur of cail'boxYl-=acy),.coA !iu'bslmrI!c:s.nese mutarev,cal G~"IiI.4I.CPI. (~.~9gn .. a ~iilfH)ir;;filnCli,Q:Iil~hri II GNA1,'~t}!Tpepolypeplid.c., cc.~=l!!,.~'l ~::zmm H wdl as ,SJdlivt'l:ugmmDL:;!l:om all ofih!lf ehsrac~NAT~ ('-A'~9l I~er:jz~ f'K.$ loading nndul~ .til l.v:hlcll. 1lliI~ :ley~ IC~n. ~~1'Ilj,'\'~1 3iJI! <»II !rL?: l~nllSltr and ,&'~.xy~ali(lri <lfi')~Iy-~. by AR (I-1U} a.-: :lUll~ sepam:!e d0011i!iins:(1'. 4). fll!lJrer all~iy;,,;i!!;:bybiQb~ Ck iIQ3,'~:n 8 .ACP!. (4'IIt~~, p:lf0i11;w~oe~iq)l.lidi chl"Olil~~ogrnljh,y (Hr)LC)~lilcl FHCR "MS dClillOfIlulIi'n.u-:d. dUll llill (lQI1!>lJruOts D m1n (lQ:ll3inli"U,g 'G}'IUi;.Tn..{GNAT!.. GNATt·I\i.Cpt,:i!IIld, AR..GNA'f ..:.A.CPL,) ~pnd decatOOKyJoo(m of !~ m.l:3ib:lflyl(;oA, ~~~!yln'!lakilil;Y!.-CoA.,and .•. 1!lllllonyl~:n·!il.o,III' AC~ 10 ~uQ~ra:t~ ,.w!1<1yl-CoA, :POOfJ'm.~y"C1JA (~g;. Cik't11M7' SS). ~cl! oo~y,l-ACPlib (flg. S4B). iL!eSpoot~"'d.y. Nexl:, k'ItehiC pM!lIllclll't'S rO:I"d'eca..rboi"'YI~ ~-JI!~' "C!"L.,@j ~ ~I Hon ''Were :une..'lS.urodi by H1PLCfur nudOOlyl<:"oA ami :lllell~yhna.lalily~.(-:"OA. and ltJ:y rad$oa.~'Ia)' for r 1 ,j_l'~C~llilll~fi!!lyl-ACP:L S lj). cTI~e steady{laifuile Sla~ rulat~.(lI;$indk3~di IIIlM. IfIl8ilooyl-CoA is lI.ffi fi~f~rrOO :!ru:b5ImI~. 'n'l'" ~tal)'ili(: r_ OOIn!>tamt If, \~: •i ...j' ts ~"Gi.} :~or mawny 'I"........ was ~i.O 0 S-~., W I~L'C"~., J'l"" 3bQlIIt sixfo:l!r;!, Dud. ~9""r{llc:ID liliiilertl'lll]H lhase 'ii'~lltles for Ined:lylnmlOl~I£Malld :lIllllouy~.~ ':igl. 2. (A) l~re~iol1J rnnllilru:m. for (1I.II"A. imtiatioo modl!lle. (I) .S!I!IOOl!Jrr.a:te~oa~m!lgl (a;r:m,"Ill!:! Ilmlo) ' of AC'~. lucspec~i.vc~y Sil:l'D:~lady,.dlCi calal,ytic eif~ .. GNAil'l"ACPL,A!R:"GNA"IJ"K"ACPm.,all!d: DEBS ATJI,"ACPt• Pwt~in~ t14]' ¢f.IJ W~ inrobl'itW w'tIh ·9,0 ,~(QA fldeu!:y, /t,r:l!L/KM (wh01'C;KM is dl!; Micllall'Hs!sub.s.llrra.w,irl 50' mM tII\oolp$. pH UJl1 aft room temJ!l@ratlililfe •. ihe S:OS~P~GE gel iml'3g;8li for (O~UfIflas.sl:e! Illue Mllllu:on~m$"tant), :r():I" rl'lalonyl.-C1)A ,'jiM -5.25 !!ita'ining (mil') .amiil umr,adiogl'<lJilhry 6:mt;t:o.ru ,a:re 5Il10!l11nl flO FileR ml8J~sPectrum ~(lefij stiCIlWiingl the ACiJ' .. ~l~r'l s~.I:>\~~~ht~ ~utd~~!bl" ~1(,I ~oo"'k~1!l,~ S!ef~ClOO'tar~~~n~ P!i!ptidl'l' 'rro:!in th~ 't~i",·dt\\1~ed ,(h~I~O) .lUNjNAJl4\iOllh)ad~d :wt1h maJlooi~",Go:A.. and oo~d h~'I:!!:lf ~i~m tlrose va~ ·Qf Il1I:~!!)1n1@1.oIlJ~~ PIIIrtlidl RMPIO sp@CUUI1ITl ~IiiQIWl' !!hON11if!Q the' IPPaliit ejecliiD111 prorllLict w1i~n ~ loo~I"CllenWlliJ l~ililmJI jI'c@t:yl CgA, m~.d :!I!1lkl!ll}''tI~.i\:CPIL,!leSl~dwty. 'gm~. m'l2" mI\18s1ch,nge IJatilin. ~D) 1~lriI!ilBl meR !mlM5: ~emr<l showing (holm! ACP~.-SHI (ierf), ,amid ~hclO) \V1t11l elesr evki.enlceoor a rela1ively .m[),jal A(IPIk.-iNH2 bight) looo~d 'Wilh alllet;¢·CoA. 1i~e Irni~rmin~llHnstlg! of A(IF\. was n:~movedl, 10.1,lM vnolo) docmiltl!i)J"yllaiti.m~j SIGp calfllyzed. hy GNAT:IL• "Wi: AClPl~::a-!: [or ~lt5 ~ O1olo)' ACPL·NHlll~liIdl :2 ~. AR-GINAl-A:C'P,- were' in.euibated with SiO ~atety~ Slfl!l.gt1ir1 to mCa.;lum thera1,(': of ar;yi to.ading by ali: lI"OOir:Jll tem~eratl.lirefo:rr 310 min •.

b'fl(cl:ylllmup tmru;ft.TiwSS -78~lbld slower d~on Ih~ k"i'Jjmr d'ooamOOx,yhllkl:1il of nl.Olo:nY~' eoA~ ~;Ihlt& 1.llila:~.dl:lmu:boo:yl8i&iQ.1fl acely~" and group IIlramISf(lrallC :separ:Moo. by .91£lo~v ["dOl.lIlalt!

dooaJlOOx.'Y~aYo:nkiJli.)ti:c dam, 1(I~.es('j resullS (lflua~ li[Jall d}.\'it.I:t1okin:rl-Co.A.d:e<::aJho.~yla:Diouprooodes aootyl-grouplml1;sfl'lortoACPIi. Om:1i:l), 1.1Mdlt!ion 1Il!1~PiP~''1J~. ~M ~r~t!yI.lCGA or' m8J~(l':iJy~-CoA 3 [Qf ~1 ~srtr ~ 80-10 90-rQI~l()!\~.. Ii'l;m ihe KIJnIof rnalo'nyl·CoA ~r d~x)l'Ia!lion .~ ~;;: depem:lent on d'le m'atioofli'ate··cm~lllS (Ie. to k(, ilfl ~g" S7),

r_... . . ..~

em

[Pig. ::J. ,(A), .;tro~Wre ofG'NA:1Iil.wmiiiill. (I) Subs'1iIfartewnifje~ rih ifiliode[~, 1~)lill.adtl.C!o'I!oredi caroon,g OfiilcetyJ..(M l~helll~lall!ed~ .a'n~' .PPan:i!.arm o~ holo··

AUll l!o['g~!ilg,i:'=(~I~~d~), ~~idY1(l!'Si~9', 1

HwM, lh~~5s,a~~ ArgfMaoo~ shO'il!fl 9 NOVEMBER .2007 VOL 318

,ith~oMe~dl~1rocb.lIim!!, siha'WirngiMe:li:amon Ilif Hii!:~a~alildllilr~~iS'withthill~1!er !::aribo!l:yl '!:)fgCI~l~~!:)A. ((I1~~i!1g1i5td~fI,ti~i3!l ttJthM in (e:~I.

SCIIENCE. WI!\lW.sdenaemag,,()1'9

(gmee,ifj'(cllOred CilJOOIiIS). '~f~1Sgrreo· di~,g!Famcf ilillloo'e'ing mul1±S: wem1aid w11~n

9'7:2

REPORTS
wh~il~ CurA GNATI, ti1.'tii~d ~ 8U~~ar fes~dll!ilaaDtivijty. We S)'llU.mIzOO <1; CWA ACPI..:~PiPallllln<llog bear:i~g ,I !terrnhml NH(!iu, f,looe (If fUltl~e (holo) ACPl...sH (ruft}U' to Hlie !ll\'.i»iii,~ Oillii~C' lil:'ialt'lmel) and tt'lSIM,it for in
1!m'3n.~:i'ln~I.-wro!il~ ti1tl1.!!lfLiil'· cali!i~~OO by AR-

wet~'d

GNAT1 ..-ACPI:. (a:P'o) ~, ~~.cis~C!lrA (liol.o) AC[!lI.,-NH.~ (1~,oi,~iOO'red l;!yFlfrrCR-M:5). A c(I!i"!l.I"en:tem !!1!.i!:en'iil 8Iand1!;!'id wa~ 'SllIPllllioo by 100wlev~l.s of ACPl.tSH~n, dUl A!C'PeNH2

Si!I~r~lIt~ily(n, J2'j. In C~A GN.i\T.L.ts~kld.ivil)' for CoAo¥et ACP.l is ~!Ii!pafl&l by d]~l(lSpl'l!i.ll~b.imHl1g ~O!!'lp (resid'ue!: 327 to 332) m:iI :~ Art!'" rocogiddon of Ihe J!1'.ho~aate.. ~!I!S!.eraf rth~ li'COO~in.il~iQj1r~res exir;1S in F~1vt 111 GNAT ~rJ8ii!L'Wy I:IiIi!lillntt dla!t.Ul'i~ .31 ,aetl-ACP &111;]1' mi~tro: (12). Corn~,7i'id:l llte~!n:m~ dern.~t:yCor'dJilieM !iloc~~O'tic:ie1 d~ib'

as'-

IF'" \~ :~~

':I ..... '-[1 ff .. .;I''_' 0lI.1_. jll. -8, NI) , ._.IS 1ID .' 'd'-._ ... : ~.- p;m-. ,;:oQ <Iii! Th_X;~ [106ed l<l! slll!Jb.itilre a!1JCf1.Q~<i•.~<!iriion mla:!~oo<l1e Qf I&e dccruM:x:)iliiilkrnl'eilc~ioo. We :fiu!l11lerpropose l!im~ Illile jS{le\ll~eljc rntil1>fi.'U:ofnl1, ,[Cely:~ ~rol1J:"'

for' !he PPa:!ltatml 'wm\~k~ra:E'!tW fu)diCllliv,e ·of Il.lullip~e ccufonflattm1S. ~rI~aps as a ~tI~l, of tile
pltSe~oo of boIilil idle 1'I13llOl~yl"CaA. S~~!llld dn.c: lD(}[y~.ctl.A. d~yJalion, . . I?ro.duct irn !:be
Clrry.i:llat

foom a.oot,I.-CQA l{D,I\iCP.I_~ Ou:i~o) is ~ml,Y"loo by djro~~:ul.3ekof the dl:l,pIDtfll],.'\IIedi thio1lat~ af A('r'l.. upon a.eelyl .•CoA. ~t d'I.C:jUfl~tiofil ,o;fil:iJ~ GNAT:L Co-A- and .ACf!l;~bir1d~!fIgru!ule1~,The bij!rnoo A;'I4M tresid:y~III the~eof n~eACP:ILbilndJing~lII.nlilelmI.lY faciHtmc' b:i~dj~g ofdte deprolUl!la!loo.d~i(l!. of fiDe o.ooopl'or PfaHl W'"IJlIf of Aep't_,. De N"~Iii~:imd AR dm:l1laill'l,,,,,"11ich, was st:rubl~izelCiby the f'P.;lt.lf1 ann of.ACP ... rI~y .also aiNuNliJa d(l.lr'l{l'l[Jll[g {lIJJOl!(!.) A_(·P'.. ItoGN'ATL• AR L'li1I~~1yoohnvea COIll~tl,{l!] lfuncuorll ~rrlGiNAT:L-

f'~amli-oin (Wig. ,2:0)1 Ulrel:r ~ll~il'£lrroi~l, the aCllivil:y of Cil.oo~f:liOlllll E:cai ACP sy"d~asc or E..fIlD (201. [~ro.~h'::l.«00 !~h~signi:fieant Ic~l. of
:m~yaloodJ[~g 10.1'1 A('fl-SH: (Fig..:m)1 ellllly :lJ I~Q~~an~l!Irliloracet;fI-NH~CPL \!laO:; d~1i3el.oo< II!l! addi(ion, 8~mple a!ky~ ,a!lTI!nes ~e.~.,ctl~yIcne! di,majine ~CiI, blill,ylnunc) l¥e~'eilJeSteclJ is s.slrnles for a~tyl"grroIJlPlrmnS"fer 'by CuI"A GN .. l, bun no .N~cety~UlIjt.,>rl!rn.~oo.tiVllty 'was delootiCdmr any of 1II1~mn.TIm_til., die N-a('cty.lhlL:!lr~f:L~3Ci.'ivi!y '!!IP~~ly1I!oociatcd wil.l~GNAT m~ ~s;:a:lmMt cglDp~~ly ;alJtl1ltlu;too in 1lE!~ CrurA AR. ..GNAT:I..~

No<

f1a\l' I~~rn

dtln'Si~y \l,lS,q oos~oo

in

u~e ~~(!tld luulI~l~ ~i6Il.\v~d~igrnlal~

IDm~cP~

A:r

mn'lil:mg[l;ilrl!l~l.llli1l s~'cham ,of'ro'L~~d1 ~ .' t'mn.s ·Olil~ VilUU (Dr ~e pula!!i\~ ACPH:AJitmdin~ lUIDll~l (,FIg,. ,le and ~iS. S~).and a series of wal.er

OOl~I:atil!l!ing ~'t!OOt!le.s ba~ed ·em

served
seq.llLCIWe,

~~iS [1i~hly

con-

ACPl.cliain initiilltioll mooule,. To advance onr tIInder:s!fl'lildl!iJL~g olf GNATl fmlcinonillll.d toicfierntifj [:Ictive s:i~,e rcsLducs,\,re deile£ll~ilJ.odl! thecrysml stm01tm::S off du:: ~Lscd
CurA.apo GNATL ~:tgaUl.d!.•fro~) dOlMUlil and. of
1!1iI~CO~sp(UiI.dil!;g

Co.J\ (tilil¢ 32)!,Ol',jAJ:u.(Ci1wA~idli!~ 2]9 Ito 439) :bas ij~e mAl" superf.amHy riOld.ooi_il,g
{!Ilf!l oCl!llm'l.
(I!

GNATo_ cWil1l added malooy~.-

nllos.tly mat~fl'm.l~cl ~ shettl'llrulkcd hy ltc:H.oes: (Pig" 3A) (U. } 1), mud is Illoot ShXli!8iIi to serotOf~Ln N~OL)1;}'~lrans:rcmse (~t miWl SQlilflrre dL'lVia:!lon ='1.9 Amr i; 6i} Cfl~ !iIOms) ('21).
1Il'll'l ()Jslfll
8tli1ilCliJ~ (llf

molectllcs ~'ii~em~;[ngtcodile [protein, (!lit.cri.ol" tf1J~ dJ,C'a~I!i:~~~I. nclbr:W~Qll'd .A.CP~bI'Mirng 'l11i!liillcl ([Wttl.a~ ~U'l;vidldw ~~~yt-gml!lpaOtl~tnf $i:h;,iml.olll!l~r GNATs. is WeU-rliI.'ll.dlrnt inkil:lgd'l It) !llii!L;l folly I.l:XWnOOdi PPa:nt ,!l!!i'Jn ofl.tQl,o-ACIIP'1. 1(",:15 A),1l!IlCllikdy funm IUle AC.Pl PPa1!llam1'b'jrn:!imlg slte . ,313), lhe two ll!lllThncl. nlcela~ s eenservedf .,jllS1:. as nmn.y o:IIDn:r(lNA1" IluUl· i~.y I:llcmlyu:s l:lKl,\\'C'lmllCiI:wo' bindiii1@ siru-s S.-m~1'd. t .Oy .fl!mfftl1[}jl1JattC mcsiidlle {fig, :3B and f~ 59} ,~ .semdl~ full' 'P<1t~li1l1 calallrc~i.dlIllMl fo... ~~yl{1tion d and :fol!.!ud Hi.~~ iU~d TII(t~:'l at !lI~ejll!RctiOOl ofnhc bil.'o tll!llillOis (f~. S9 and fIg. 3C}. ne...'>C £c'siciJes are ;~y ~.tl!:tonoo .Oy I bonds of His: . Tyr' 19 and of h:::·n oonl'l to t~(\':Affi'g4li14 iiLdcc~~3!i". U A

Based, orlldle

stltldi:esCCescribcd

above-.d1.1::

IlM:;ch9JltW!~:r:II FC!I.Irn AR.oNATI.",ACI?l,.is p~ Q pasoo IroirINolv~ II seri~ll of aeYt.CoA.-mJ!~lml. prot~in~l!Otcin, and IProt'(ilLmc-',P'P.anl ann imLnt..tc,. ti(UIL" (Fig. 4 and fig. S7)dw !iIlOOi~l.(i 1I1~ dis~inD· t~",ebLrllllnctw.l!i~:l dooafbo!!!.yI!L..~S".acel}'llfl!JlSfern...1fC !lD"l'UV~ty. It .~ Hkc~.y 1~~~1]1 therpresen~l.v o un~ recognized GNATmcmbc:.I's win. be flJllIn:d 'Will.
lII[1e:XPC:ODed b.ioobcmic~Ipr.~mc'!> or that previ .. G)":11l!l!Y [d.~li1lifLed! Ilmt"ChlS will IJ~ grou~ \lIi'.illhUIiI. trl:lisd,arg~fl!lilllU1y" flo;.,®(mnpl.e. l!:hearyM:.en(lOOM

!Jj.~yrm;1llo[iJyl~. d~~~.yl(i;.~ (4) ~~ .!t()l been IDe subjeol, of sLmctl:!:i.iLt .umiysis" bl!l_tcom~rnl:ivell!llllino :00],(1 :SC-lC!l,~!CI'lCC' 'ElI~~~ysis I[lOW p.micilS '~:Ham QOO1lnil~5\ tbe GN AT scaffoldL It

~'ilur o·lib~se

ffic'lhllil"£s..tre' inVMiant

;lIMI~g

hl. ~m\po:lilrull O'UlOOlllilf:0 fthc:clure.uaf \\I'O~.~s dfl(,; re.a~izatiorn IltalGNATn.. -oontalm~.rugmooru~oo

i!llIl';n(J1 UrnloomlnO:ifl amongpmviouNfy ehm:ao-

C\l'id~l't-'Y in,~ghlL~hUn IImrtl~K1aonlQf~11.i8 dislal'lCdYe me.illber of OiII~gc lind U:llJfqui_pt'Oh::h~

Oi!.lrA GNAT1• pID-

trulWily. "n1!l(D' 'u.!umcls IlDJiI!qpposile faces of the pmt:e.LiuI cOlIV~e~JiI; a, ~iiliiOfl (l~ll.dillg i~O la~1!acHv~ SilC5 offi':h(lfoologQl!ls GNATs (Fig:. 3:B~.

b~".dillg sil~ for d~~ffan~. :L1Dll$,of ~~~(;QA and ACP~.!S11ibsiml:~ "PO'diE~ng!JioA~~e t>'\!Q ~Y!._!.s. we OOMedgys~"! Qr GNAT._, with lllll!llony~£'oA (mbl>e Sl), New e'-lec~ron dl:1~l~y~ o~Clin, QIIly Olile ~.~nn.el~ ~h.e(!ol\"Muldlumg HU'llJ,e~,(fig. SS). l1y;l/ooatjo:n 0t lnibis ~llft]l((il and the nll.ld.e ofCQA bil'tding,in, wb1cllthe IDItlc~colid'e:~.ksim.a !S1!IfaC(l d~illlm~d tire
:I.l!Diln£~s:,~
lIiIiIIl:;

P.&"illlll!ib:ly;' 'nhme

(;I'NAl ~~ ...ett'ilrumingPKS loo.dirn~lml{]!dtI!lIM ;(iI1g, 89l t'-o IrLMttile~l.¢ ·C)f Hb~8!l.~D.,t5i5 .: ~);I(: ast sa)~.HJS,9A, HJg~ •.a!"adl~JSSV v_npoo· Icillls:foli' dc.cfl1ilDoxyl,Me I.l!Ld a.ce~y~,IDiaIlSfl;,uase a~ti'll'it.y{MlD'l.c SI). ~<Jimoxyl!rui(m was, s~ly iI~~airnOO ' . Inons, al eiillet: site" Spcciflcal. lYI '1:&00: i I ili1.d Tlu:"~!i varioolS mfftJ!tloo.iu ,a~

ron~~ IW.I.llLlml pi'OO'i!.I.OI. b~d~eli(. g~ifI~diilSl~, iil.1fIdi are \li,~U..!Mq1WC5en:led wi~l;lhiooclerial

gcnOHl.e sequ.~uces, This 1n;~Hc .S"LrnlcgyIfi~us re.~CHlS an adrliulio:mli~ widely IIIIsed. chmn imli~

lef~t ~.OO·rtird rOOlilcliO\Ulllf1l..tal f~..d~rbo:-:>[:f:iat~ol1 'IQ~y[~QI\ ,,!!dim fl'ila"tlvl;,'ly In~est !CI!<iI!l.ges to KM V<:H"~!I!el>. In CQ;~trn;s!::, SlJ.!bS'I:Yllt~!onsilt H~1ItI ruxil, T1in)iSlrndii {)I'Ily :~l!Xl~;

Qf matml!)"I·Coi\ to

eli"ecls;ol~ooclyl"!fi'1U1p tm''iSfJCrflC.i~~myj,~n:l:Oll"
sDra~in:g IdmldteS~
~c:n-III1.\'S

d!)nolpllay

oolnCflJ~
AC',"

tiati,m pr:ooess rUI'~~I1.'lbly o!' ~.m~~n hi'oIogically a~iVil SInaI! u'IOh"culh*l .. At ,81QO]Ilpara!live Il}wl~ the Chr:A GI\~AI' I..lws a :;iglil~.flcantly slQv,"C[ S-.;w~yl~!1;. .. !bm'>e <1c!ivU,y tW!!m. tIIile '~IJ;wQmYC:~!1 'KS ATl• HowfW~U'./!n 1lioju.1lcilla Wl<!iSJ; :ffitati'il\o]y O sJow groW!lh. rnliC in ~he ~:min,e envimnmre:HI; 1M> we~I.<IS in 'C!i.dlJL.Ii~ (i.e., dmJb'J:rng l]g'llC of-~, [Idays)
(23) aud a <:(I,~ndinglylmvproom::uQ;Il. of

P-Prullt !1m. GNJtoods~I~I.o iiIrIB ~1!I1i1l~I,a~Ot::llili.$IMt

with

~Cl.~

of otIDi~f

!~~.l~fS

Qfih.¢ GNAT

i!"l1, dl@ P~lt1 am'rS i;.l,f a«t~I-CQA

role ilIl. accly.I.-gro:!Ilp 'lruimlk:r. Based CJf:l ~1;ag~L'l8is fJ&"I!l~tsand

OflJ !linodB~-

(ilid

compared wiilh yi~~di)oil othLlii microb~31oorUlm.l procll!I~~ I[e'"g", ¢!)1bJi9!nyci~ v.t.a UlC [lEES aglyC"(}"~in.l,I3r!l~ diOllteby tbcal(}.{:'()poly¥WI'a e?r!Jlrol~ (j4)]!.ll~us, Ii~e O!1IfOOln, A PK:S ~ribIylil~c! ~~asl;.'Volvo:i lJ~d~' ,mv:lu]11I1eul oollStrniinls Iud m;ganisllli.c: i~ tI'laJl.rel1OO1i~ i:'OOuooCi. I.lffLi::::i.ency. nc \!,;Iod:. dSllCribod. [11 l'Il~51~rt ~m'Vioo~ CI~'lJfe:vit!!oooo: f~fa:lil i:l!Ulr:oooo&i~lnd h~fll.~CUJ)il.aJ
ail

c~dml

ApeI'

iI!Ilili~ bic.m:a.o;s

cl~~x}lIa!li;l(So.t1Q('lt!i'~.lrnil;;;:r@;i'l,1SL'l

~I~

flilf

th.e

"'!f()poo~d m~dh!'!!iliSfl'! olf th~ ClJrA AR",rJNAll"JI,.(PL IdIl!'!~ ffi~i,ijg,tio!1mQdilloo, M!!lo!ryl,~.t!. ~fli~ th!i: rCM-bllilrnmgl tllllllnel '~Wh~TIemnll1e:~ of thee GNA:r:L~'on18iilil kl!ark b'~ue regmnJ d'fId. GNlAlL. tfltllyzes decailba~IffiCW'l 'loacety~(aA.. The A1lt dSiiafiril'~~igiht rDwe! Imrde) d]m~ the PP.mt: arm of AilCPL (1f!l!~~Mdr,c!~l') l!iirolh~ACP WnM~ (y~~~:ww!I!r:!el)for s!Jlibs~~~ .amyl"g~IO'I;lp 1!l~a~ll'lf viii. u'a!i!·sth'io~ri~~!I)!iI.
IFig.4.

ClIrA GNAT sea f'lhId,. which S~bSt!1iflli,.Wty b.moo,e~ dtechemiCllI!'eZlClaOnin'ii'enlOry of Ilhis we~l"kl'lo!Wnp:n:1ilein superr~l'I1Iily. Tln.C:1'W.cd'lOd of PKS clmil~i;lIi'Iit~9ti.olil, descri'bed h~'re c:nahtes m:allm,~...coAlO g~e 3'.c~ Ih~ oo~~ pllll!£:lil'SOr ~o oodli1trlia!~1il :m.d t!xtcnd d'l~ camli1'1 ehaln (Jif' cl!!!:<lcin A. MOreQ!W!f, ·tzyviirtuill Qflihe~a:mr.'i!' ~ of ,ace!Mevcrsl!ll; propi~laOO wf!$fi.'lr '10 ACP;n.

973

REPORTS
1.13,4:2. GMO;~4n (to o.!H,S.l'a lid O~:2~Q9 I'm ],L;H L,G" 'Ii! 2809 t~003~~. ~!l!ppo:Jr!~i!ll!of<!rn Eli LllI~ ~1r<lJ;j!!il'1Ii ~ellorn;!i!i"" Ire 6.!'MJ'l l~. V, ,r~~r.S;,~'fI!1'r, N- 6<111>, ~(i?M~ 3U. H:51;! (~oo6). '~[;}bQri!~"'E!: I\I;~~.~ ¥~~!D r~iliLJ'at 'i~A~'[l~~ PJW!~1ifJ~Ilil[oe~' (~I'S) i~n.ppmrlem IJ)i tile! rillf-I NtMillrn:f'1 H- ll" t.a'~\ C·y, Killil, I, II. M:lt~\s, E. (aJiiI!, c... I!'JiiMl~, ~_ tIl(,j,~_ .ArM. ScI. U5,At. lG3, Ull'<l, R'OO61. ,IMrlllitl! Ge.il!!ral ,rlli!di(lll Scle\rll1~~ (G1l.I(Ji alild II4i1~IIiMl n.. [ ~, Q,oo~\lI !JJ ,al" fiir)(jjfJ/J--Hstty ~:l'. l"lM U'99S). t, '~i1!1@r irl!!llltil!1;! '~l.i\l,Use uj' tli!! A!~ ~\ili~ !l!Ip'rooHi~d Iby Ih.~' [)1l~rIJl!l!lnl; o'f Ell~IW. We '1h~1l~ (ur~~ao ,:too le. P. (. ITlol,~I!:!,~lrI,~,r.'m", I'3l'M11'1.mmrzy 0\115, 1.21S6 (2iQllI&t 19. Si~lif,II~~lr ~ilbreiiiati,oll!' '[Qrthe ilmilMl Qad 1['~,5,id!Jitl~, Ih<l' Uillil:l:~~n Rllfie<ilfth <lInl M<imgfflltlll ojIf Sladiver~ity '[l::,M!'iI!!.Bl~ r,IH'eiI ~tI1it:liti!l1l Jor permiil5,ian ,~11IIIiIS~iSl;an!ie: <IrE <15 r!lillo~= 1\, Ala: C. C!i'5: .1), JIi!:p; C. (i,II.l: iF. Pile,; <lJI!!JI il! ~~ my ~(I~h.lCli(!1JI;~r t~, (~r q(;int'pr'!:I~!.Kiiflg ~, 6ly~ iii" lHiit.; ~ U~ t(, !.y5,; IL, !J;:us ~ ~ ~, !\In; p. f"IlI; q'<!~l!!ect~ri!ll'!1. ((lilia4iII~te~· ~ltm ~tr~drnIPi!' 'f·i!(t~~ Il",,~ (I,. G~N; II'{, ~Jl9,; S:, ~~; i~Thr; ~'. \I'~t !i'll, Tr~ an!lli' Y, 1'yr. heM D'I!jlMit!Ili'~!IIN! I'l'llooin !}:li12l Eldin!! {1l.!oW.i:r,~~bu:][m') ~D". R H" ~,Il'I'~IM .!/ ,tll~ (I~_BrDA 3:, ~.~ (111961. \1ottln aUoe:5si~m,,~00e~ .2f1£E~rnd ,2:fl:EF•. 21- A. 8:•.H1~Njl> [). c, K~r!lfl\,IF.,Olfdia.. Mi!!t! 3,•. 23 o.m}. ~2. It til. Vim \\IOlgoffl!l'r" ]1,C~rdi, SfIlUflMl't' 1.4, 1425 ~~!OO6t SUP\p!lIlrtiugl On'Ui Dl!!Mi'llt.l!!riOil 23. ]I,V. kCissi. .til. A, Fi_i)btllL~, H. 0. )(00, W. iii, uiffilIrd;" is, C. ~BI08llil. '1". Fang; A. Y. CIIlt!II. ri A. S~llm!lf1r" ARI1.II" &!111~ ,1l':iO!he.ol1'. 76, ];9~, 1200ii!~. U. :So Simi!"'- .I'Ii. 'Wilk!ll\WOl1i. A, P::,Iooli. :Pt"'fj. ,~
(I, IE.

C.'l fIiI!,

Ii'! k'i11i@lik dl1la,II~i1IH. u~ rOf' ITICft.\M!j lOOlu[i:t:ll1 d!8ii51illl(li!. T~Ii~ wmt M~ W~l>&rI!e!l ~)' NIHI ~rcal!lt~

4" '1'" ]1. Htiel1i" P. I[ KoGti1l1l1kJ.iHl~,J, 8QdoriOIl. :176, 114 U,9::l41 5,. P. \i'E1:tff~r'l'irn~ld et ~~ Mat, PhamJ(i(,(JL 5,':!, ~~ n.991~t G.L> (~1Ii) ,et tiL 1- ~w- f'md- :6:7. U5~ t2@D>'!l'. t, j. rT\i@~ i'UiC. Mltl. Mad. s.:~, USA. '~'. 111000 (2.002}. 11:. ,~. It1itl ,i!JJ' d,~ Pi"K JlfaUAtfl'il 5tl'. U,s.A,10~ 'Jl6,m'
~2.(04), 9. "!1" ~lrr:l~M-l!ft{f/ fi/,. (he,ma~d:J~mi'. 12,0& {2(10.6j. 10. t IP; P.l'It[da-til.al1il'lt',l, c, HerlllW'k;, ~mBiclJi'fm r a,,4!~

R~fl!li@IU,!!~ .auf! ND~!!i ll. ('. ~sangl ~,r .tll" .fflrJIM7!1l0,1. ~Dlt! 1[1')'99'), 2~.Y. XIJ~,L 211MI II'!. \\I', tlu, ~ H. :)Il@i'ft'lall, h(J(, lrt(Jll. .ACM,. SU. btS'A. 9'5.• Ill,n, (1999), 3.~, Iii", (),. Call1il', C. t::liI!Ilila. BicxOOrJ1'SlI)' 39, :iLQSl4, (2{100)" t

.a

ilr

u.s,

ce.~

~JJ1;;Jt 5~[ur1::l9, 8l t2,OOOl 12:. ,fit W. \t~I:lJin9 ~1 ",t, N.rn. ,B.i'a.:'hem,8l'tip~.4n." ~DIJ!j,l

(2:001t Ill. f. ~.a.

I)"

c. ~lei!t II. 8. ~i(~a!1<,

Mnll!. Re~; ~r~\i'lJ'$. :1!l!2

J. Appl. ~_yc'Ol '9, 195 (1,"7)" :!~.W. M'I1I~, P. B.ru!1!:ier" P.F. ~m(J.~,1:. ,BOSiI!!,!, BIQ~'dm,~, !!¥~,14, 561 U?9ID. ~s. we tI~nIi: fl.!.. ir)" !3!!Jr~.illIIlcr ~I!i!l eql!i'l$!ii~J!Ipn<!5!!1ilttS
Ui~~@ ~1'J>IIT·DF(K}anaf,llIr u~ pamti!lneip.~ 1I~r1'ng' ,~ t!rlft'l,irn:l'l. m~, lit ,G" Mattil!!!!W!l, '!or 1iIM!' ~nal1f-!~
(w C!)M2I1II1(! IPi';)ln1allli:,llj[~ltr~lWk!r~~e~poo$pllo~

.m!.W,,9!Iefil:l!ma~,ijry1~Omill!liIlifuW.31ml$S5,2fflOi\OCl rlliIl@f'i.als ElfIe IlIilttlOd~

Figs. S:1 ll[l:l!9

T~ble~ S:l.tQ' S~

.a~'~

!i!.ererelf!Ce~

is Ji~1 :2007; M)~pi~d 10 OIi'tI'bEt'2G~:1 l!En 126J'!;dl!Jl~& l'Il>1~79Q:

A Bi'func'lio'nal Bacterial Protein ILiolks IGDI D'i.sp'I,8!c:,e'lme'nt: te [Rab1 A,ctiivII'I:ion

~aJb gU'!ii!li O~;ii!~bI~lPh!!'Jt5iPh:atal$~ (GWPaS!~) fegijla~,i'i \II~'Siid!i1! tr,aft1k:kifilgj ijli~1!! kal~tk~t.1h: by Irilll\,i"~f$ib.\y ii!ss{ld~lJliliigli!!ii)1ij lipid m~~bi'!iil!li~. lfi!g~' Riib G1f'Pl1!~ .,,~ mgllMaJil'ied i!li,the crt05~ru Ib:y 1~liiiidiill!:l tQ GDP-.disS!(jdMi,Dfi hl!hl'itDlr (GD'I~', nls b~U~dliillt :;pedi:!!lm.dlliif>O't~lfiiS"IiM! f~~~fii,dW

bmh L fltleltllJopJli/a efft:otarsmlO tl'mcfm,l foOf i~~'!CU(leptj4~g Robl .. onlroUed secfe~Ol:y",esIcle Q tmusport dwing inffi'Ul'!Cl1.oI1l,
A.lltiJmnl.!ri1~ mel'!lIIltinlOOI Gil' host ccl~.R.ab~. ~o 1i1~('J LeV mq,uif(ld SidM (ltJ,21~ IDllil.~bb~·GBf

3~iv'!~y of S:tdM i,1IPa" Ui!1II~kcl)i' 00 ms~[I:sib.l£: to

Cow1~llli::\: ~pM!'mit:lg~"'~"t. b~~(; R;JIbl ~TIlU5l'~ &m G[)[ bemre !]Ii.!ch:.·,o\~d'o ,e..xob1!Lqg~ CalilOOCI!JJt The L. PJreum()pl~i!a g,Clilonro does loot clwOOe any ,abvkrus. .fRA.~, bCUlfloiQ£s'lIil8l00t[~

released

Rib GifPa:s,>e!;oo,f,ore IRab arnVaitlioiii bY~IU'.ail;Osinle diplnciSph,a~i!!anesii'ie 5'-trip!~m:splilate' (GDP-IliJiP) fi!ilCrnlng,e ftmrors '~G,raF~." 111!ere" e found tliNilt Sic:nM fro!ll11 .L8f}if),aella w pne,rJmophira lcould dict 1315 both GIEF[lllIIdl GI[)ll)-di!lip.taJ~lern,e;nt factor (GIDlP)f,or iR:;ab3l. Rabl r,~~ea:s{1dl 'ffimml GlOW W<I!Ii insIM1:!!dl iinto liposo.n1Il'!.l memlbr.'lImles. ,[lPH'i M!~ IUSied <l1!li1li1!>1:ra[e 'f,or S~!d.M-lrilledii1ltied <lIS Ili1l,1d~C!tl.dE! X(hg.litg~ il)l)Iriil1ril hlClrot .()(1iU ~Iiilf~ctioli!. rflOlltritm~nt O'f Raliil trl' .t.egi"J'l.ell(]"~lli1ti1!~liilil'lg ~ va'!:IJ!:t)k!'sd!lll1l~ndl!!ld ~I:!i! thilll 'G,DF amViity I):fSidM. Th~s, GDIF ,i1!nd GEFa~it:y ~aJlll~~IP·r,c!iI'Ioted by a smngl@promin. 3!!lid GDF ac:tivij,'ty !:an oo(ilfd~n,am ~bl IlN:mJiJitmeM' m1liOml~'~ GlOh'b'OlliiF!dl POlCl.
ffCIllfl'ii

di!;pl.1i;(e GOI

mggcr om dnssooi.i!l1iOOl from Ra:ht.lIms, .\"'" tesliOO. wh.etlmr S;~dM !I1n.d/rn: LidA. had Gnp
a(;l~i\li:i~)' t(fw1m1lnl~.e GIL)!!'

Rr:llb ~I-Gli}] oon,,;I~, Because

:p~[~ttentilil]iy ~ind')rrenylatoo ItaaJ, Pffll.eiM (24),aud lb30wa 1~t1~ enzyn1la([\l11iI!.icb[~elY fill Ra,i), ~renyla1 L'OIl,.SaociuJfV!I,I):ces (,'el'l,ml-Slae w,as usc'" for the prodlutcijo1:l of P.uelly~.med hex8,~ bis~iQ!L[I~(Hl%l.Ia~ ~~tlj:tliar.l .. 1tab~ B (SeRab~.) and FLAG 43.gg.00 hmmlJll.GDl2 ~Sc(im2) (.~;g, d~,{)Cil@'lilt to :l1eqli,d.~ Dl-dlt.~plao~umt faGliQffl SI.l' Doulb,t~ prreu{ylal:iO:l'lofjrl1irifiooSillhbl G was .BS.,i.C:.l£.t.fa.. millie. k.}I.~g.'.• OO .lN.!i'~. I..... I.'.l.~em ram ...._ . ~ ..h.• ...,.~ oolllin:uu~dI.{2j), .:md pliuli.fw(l S!:Ri'l.b ~ ;tHd &GIDr2 ,(G.rrFs) (J J., 14) .. :PRJ\-I (tbe hon.un.h(UllQ!og OO:WJild organ~II~II~~~.lmtYQuc~~~IS' IS regul*d -by !.Ii,!; ~!J@!dy eenserved Rilb S~l. o:rV~3) f>!'ci~l:rt..J.'e'll: disoocl<ilil::m e!~clooO'l~lO!i~ rgm~ed, a heie!lCldlu1erk: 1:] wn~~ex, family QrSln~n guan\QSlu~ triphoS{p,Im;l:ases '!!'Yhelll Scrtab ~.scGD12 was: hlLCu1:mted WiOl b;ei!d,~ rtab prol~iuilS [rom, o(l:D:~~m:ll:q)~entsi1l !protein (ar,Pasos) (J). R~'l:)p:roie;itilSi\'OtiVllted, by~liJat~ w[nh. ODI::'activny di~te ]JOlIU a 'GEf UJ), 'liile i!llm'IQb~~~dre\l{m.lbilmllt SidiM. 00" UM" ScIDtab~: S~rI~ d,tph,ospbata-gWiIlOi$]1l1C 5'~Lr.ipl~o~,:hillil.e idcn1iityand. fU;llolioo of olilcrp:mldrl!S w~,lThl OOl[y btrlllll'd. to S1dM;~oaredi ltiead5ibul ool to (]OF {GD'P ..~"T!P)~c'ha![I.gc: ftl.Ctms (G1EFS'), ~. asro· LidA.-coa.mc;l !beads Q:Ii 'lill(Olltoa, ooillirol acti'!.!'ilyh;riI;$i\elm~rn'I~ ~hfisi:iv.a ~lli~ with m1Jlllmru:tLl8 by U1H1laG$ oftw'O ~ydf(l<. (fig:,. lA). SCGiII)~2 didlm()~ 'C\lpuQ'Cipil~ wiilll nHlhl!llmulI.rail:hog~..ltJgion(;4l,fl {)I,1t11JJ'lU:1: ~1~.c ' . ·TIi11 ... ' .. ' .... ~ . -'.1' .. _'f'C_~"",,,. _!,clF pMJ(:j' ~lajbli$h~ <i.r¢pticaIi9l~ 'iI';Ol.C~Qle ,).,rullii!"i !;l_!.Q Ii:·' .. P:~'.r' groqp!l, '-'CQ¥'U~!i! -[kil'" ·~"A,jl JJ tl:'· SLi;iM·ho!':!!~~ cR<ibl, whiQh i!idic..~th<!ttl S "'v.i." C ~e!Twi!~s (2-6).hw.clivarod ClDf':R<ibs .a;ue e~~ :ai~"oo~ !~ro;Plwg.es byrecmiti~~g !TI<liIe;riat 1Wo~]1 dLsp~~ fum] Ilheoo!wple1'l. Nm~p:re.!~ywled(lD]Uil.ehost oel! e!ii.dQP~llSrJilic reij,Cl)il'mln (ER), (.uj.-i~). i!lIiOlcledOOU ~m,':lii~lesmcli nutinIOli~nedl;i !~,the free hU~1J.1iIil Ra,b·JI p1.lrifiedllhm:l E._~I~eJiahiaroli l1;lc,OOomllna: Imns~oc~es: ,<I lru:gc, oo!,],ort of ,ef'. C~cRab~) wru;. ooulildl'e!flllalily by :!:l:tdM:~ LiclAcyilorol by GI),P'4is..'lOd.mti()ninhi'bi~:or {G[ll) mld, coo.tM. ~ (Fig,. V\:) (2(}), Thus, the RaM. ·GIEF ~'retor~ii1 ... i'nlln IIle 1Ki6t(!~II.(;J'toIDl byun~ (7-/1]" ,Go.I. b:i~.d:ing POO'\milrllS !!poi1~9nOOUS S.~dM ~~hubilUciG]Jf~iJvhy ru;'j(it pooilllalM. GDf·GTf e:..chail:g.cou .ilt?ihp:roIRiiilS, 3it-d~I~h(l;re-. of ilS .Dutl.JCIi~.p:mfi'l. y~ rv ~i:on ~ ~j~. fore,lhclr iii'la,ppmprtl3Ulacti'll'a!liotI (12). di~liofii 01i' the' St:bM-$cGDJ2 e<i!it'iI~le)oi (T4SS), {J9). T\vo .of d!J~lrnJiils1ocaledp:mleii.'i\i, ~elI. :":la.ll~rI!aliain ~abl lD.eli\l~ry (1:1' Ril'b OTPfu~!Il R'i~it~ ,of :acl~- SidM ,([WA) ~.Li~, dW:i!1g $eRaM 1rr!1Ildiill.\!'!lIIe~ liM I;;ill{!ing ""0', "'~~~,U ~1.,-- re,i!ll! Ia~O'f(L en··d""'s nllC!lellI~ ,-' ..f -. .... vi:l!!:ionin'llolVle5 Illlileirrelease from '001, :iJj !prooess W,i:l,i!l mu;cl.oo ~<li'!he GD~-(Fee fi::nl11 of Rib·]. ~..::v ~ ,._le Key ~I"!.l'l B!OCOlY!l!e SidM di.ssoo:r.a:ledRab~fmJ;u (:lU! U1ruJ!M fER), (0, C1(llgt ve-siclelr!l~:xJrt,C21, 2:f'). (fig. ~A}, we~~cdl lJIibe;Uner SidM cCiol:l~d. SidM wasn~ bd:'1e recrultmettl:QfRtibllO IDll[parlDl£rII ai 1!,ij~(Illi.3f lliatagiY ~llI!l11.Mi(l'ooualogil',Mlis ca.~~tym ,exlO1iI9J~g!l'arGDP 3gain~l rudlio~a~Ie,d, dlG:.L~:ria.,ella..o()MtaBI~inf,; VltOl!101)e (LeV) sud had IJImi:\!',~rr.il!j')ilJlm:i;[ of f.t~llin~. Ba~ton. ~A. C(~~i'1l:1, u&A. (lEF aCJt:ivtly SfL'Cillca.RyIrm3m. Rm ~(217. 11).111 ry-~JG1P·l~ [gruEln.tl'illic: 5'-O{l·'.lhjonripl~~Ii'l, zHlJt'foi,rd Hughe.s li\edk~[ imijwt~, Tuft~ UIlIWfJijify 5,[1'10"'[ V:il~ !imfae~-lm[!l'101h]tizcd $irnM :JIx!. LidA. oouM a. Il!Olt'li1ydmlyzaM~ GTP 31l3ilog] in. :SeRa!:)1 :~m. of llIIedi:dme. l[lostOR'. ,Mil 02111 USA. ~l1!ple", \~~l SOClD~2-. ~:~the <l~".ce Q·f SidM, 'Vo whom wrr~~~IiI~Ii!U: $holil!ld b~ .ndtessed. iE-m~!I.~ ooU~bo~ to ~~l~~ER-d~"'M ~icl~ d~"f!den( m~.lcliv.u,edl.~bl (20)\ which SIllS:~~ d~M ScRa'b,]-ScGm2. showed only m~nim.al sp<m.mfalph.i~bern@~l!!ft~"ed'u

or

<~g.

boo.

.<.

, ,-,~.

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
W.~QiJ!_<;

[':l')tl

i!l1l~o SeRm ~. Howc'\!er, th,{; ·(if [y~.lSS]GT' ~JiICOiJi!ilmted inJto, ScRab ~ ilfloon(ple:.: Wilh SoGml (Fig .. lI!:)rwas ooilsi.stGflilly lCi~Vb'" Olm. that Oblmlf'il\L~d for Ee!Ra.b] {fi~ tC), B~~:lctu"'~ .bh (j1Pa,.~ a..~;:,u~ wW~ I~~ 1~~1tQ!:l¢ by :n~·ofd)~i:Jt (;-lemllil1~~ p.!'I.'1'1)'~ iGf01:!ps WI.vivo ~5.;6, 14,.2'6-211), lI1!e laC'l: ·gf;:jjlipid: ~l]a)(erCl1JlI:i:llg the in ViimGD:P=['I'"3dS)CITP:"" cocclwlgc s.4.lI!Idl'cs. tfi~.~. Ill13Y 'L'!.,XpliLtiIDl BJ' ~hc at .. ItOO.Jared. aclivmio:J1l off ~roIly~Med S:c:.Rabl. COIn? gi~l'I!~ wil.h ,niDI'),. w~ ftrl.!!!IilG dIal!.SidM"fUiOlOO~cl
(iI:f

addiuM

[V)iS.S]G'J'.p

sl'G1fP ~ptake~flg. ]B).. IilI CO]~tra~~ 1:;jJ~ioo lf Sc~bl iQr~PC v~(j~~ ~~dlon~J' Q in ~e pre'letlGC ·of~. S!ldM and (l1P~r-S {Pig. ef SLtlIM ~ed:w !.he !'apldh:1;cm;,~im~

pri~Uii!g.l1w8, Wg!;'~i~loo ilo ~pd~g~iono;j

Oir

aJ'I1ii!l!tl:lflt

SitdM COJFitrib~tiJ!,g ~CI ooch ofOl.~e<K:tivities:. ~,:E).\VitI'lOi:t·~. {Ir'1"dS, ol!ln,y 111 :fra.ctLcn o fScRab I :Pl!lrified SidlM vari.mltl> 'with, N" or C~oo'l'nliiml was itfltegrated inm PC '\Iesrc~es. IInti fenmlncd _nc.."i!liou!! (F~g;.2A end :flg. S3) 'Were aUlll.ym:!. 00, ~lI!In,Cl1i:iy SidlM,. which :slllow:cd. dlat ilU\lloo~idc:: fm 'Ole!k mil~ty illlCllilICl. wid'! EcRabII. 1[)c,1l.'lli~HS ,~ch:\\ng~ wag Iffiquil\Lld. (·0 3.UOW r~I~Me of i!lNooodimg illitti.1103eid~Ito 316 allih~ NI2nl1lIl'll","~ u'i¢tl:!lt'iran~~ooulj;dSc:R:'lbl by SidM ~r~ iiUloOO:l- Or ~idJ,:i~, 545110. 647 at ~lliii';C ~m~irit:b<: disi'IlijplM

[y-~~.S]GTP i.l1co:~rr.-u:iQrn.u~t.o ScRi'lb~ i!i1 tiM): ~~IiI~L:l (Dr pllooptl,a~idJ1·I.OOCklul1!~ (fC), H!KJ6L')Jt!:~
wa.; n'Qorelllar~ fOlWIli!fI~ ~1Il<1:lgecrl ir1J thJ;): !.Ibs~~oo of ~'il)idl V't'Si.cJ),es{f~,g"]:D}. 'llI~'us, :s:o:Rabl <LCliva~ I~.ton ~ :SiaM. waslo;inctica!lly CllIhliUlUedi in the !;lirescn,m: of a I~PJliI biiayer,presulf.liably beeanse 1~llimI1:lU:aycrprovided. a.1,~ydr{ophJlbie m[v:iroll~m.t imt(l wh~ (jm-:r~Ll: $cR~] ool:ll'dooinc(l~ lromd try Sid[M;

Ncxl.w'e 'pe;rf()!lliiOO vesiele noill;illse1'lper~

:~.lOOlil~r~rote;i!lil a.<>SOciHlio:ll\V[·Ul ~~[~ SOille-5 during lll.c~d:ilf~rel!ll Sl~ of InaciootidJe ~x:clml],gc:: •. rniUlcuwtLQ'll of!' SidiM ,!!,Iith HI mol\sc' C)!!.~
im£liUs 10

,~ St:lblbl·-S~D'I"]: 'OOIN~I~. !W&~ \VII;~ UCJli\ l7l.a~added! 110PC H!»sor'lm; liM: pJiCireln ~i.fim·~y ~rlteroc~:edl \'II:~lh w~ieles ellriched in (i1P'''i~:S~SC:Rab I. (lFi~.1 F). McmbmJ1ilC""-bonm:l ScR.:ab~1 OOIIiwtcclland released by S:idM W~ lim 3J'!1i3i~la'ble bi1itcll OOWlMilma!irl1ac~pUlI}l Slil:cb as l~t:'I UdiA. Th~ SidM ..nOOi~I)~dRab~!lW-",:rulioUiIJfflt ~ ~n Inhc~fureoodivi.dLXI ill;~o li!hffiL;l sti$~ (~ 'GDilrel~e rromRat!,~ ~l]pa!]red bymcrll" hl'i1ine ir:lsel1Uial] Qf&idM~ooll1ll~d .[tab l, (H) C<IIJI·, ysis ofliluc~£()tidce~c~alflgein Rilib~j, and (~ii) relc85C ofacliv.:illIldi bbl by SidMInSl~IQ~i'iI "kf'!Nrul~1:I'!I .Iigand blil'ld!lng l~oGn'~R.abl.Alleu.Jnaliv'L:;i~, Sik!M oooll1J hi3J'i.!'~i!ll(Il[~U,y~l~t.u:,~ Qle; d1U!l~i<1tioIlQfScOm by ~]!r:.cil'lg 11l!1cll,'tIlide esel .. ullge il1l Slc.R!!'bl\\l[JiJi3e l'.1<!1I.!lud.1!o SoG[)I., dn.ereby gelll~lil:,gm'-c'lmQl:cd ScJtilib.1 IiIilm: is relieasoo. by ScGDrn.

~~oo.

00'!~1m..~ ~~rt!em.ts Cil!!talrliiri!~ amino aCLds 31'l Ill' 54S b OlmdEcRa'bIM en:iei.entl!y asrnn~le~g."tih. SmM. Si:mi 1m-resullS WIJre o,llta~ni:1d inpuU..d.<n\fIJl stl1dies rlJ.l,!>ifil~EcRabl (S2£Nl) (fig. 2A). a GDP" .
l.ookOO nlUHUll,(19). llu,:L'l,. theee:ilural i~io:li'l af SL"dli"M oo:lJ1minrirq:g 3mWloacicill n710 54:Sm~

bil!J.dWn~ rSi~vari<linl3: o

00 Ee:RaM (Fi~ 2B~~!l

~q,!Ji'lIOO fOf&:R~'li;Il ~~[Jdi~ 8~~ila!l'ly, 'We {Ou~dI 1IIla:~ a!~~y SkIM"'3riar!l~ OCHbl:EliullIing mn:iIDlO acid. residu'CS 3~.'l to 545 ;IL'lID" ci~~"t>diith ScRnb i. (fl.g .. 2Cl ScG.DU did not w pr!.:.~i p:rn8!w wilffil ScHabl om aae beads and re.. m~edifil the i>:llp~fjlial:all~. {Pig. .2JC) •. ccmsi~li::!ifll
wid:l!I:!! ~dusiOf.l

1lm11~ liliIo onlfl'tpl~

or S~I:~:aM;

bCU.1lfi~ ItO. SidM v:i!naUJI1<:,

cess of ScRab~ -&:c:rDI2 n.'V(::a~.oo

dl.!a.ttTCCW1rlD.~

TIle diiSJ:!cwc.ry of both ,GEF lind GD.F 1:1.0· liv.ifY,vr[h.fll'l Ole srul12po!,~pthl~ dl1ltll \V,as S,l]r~

[E~~II

,tIWlllil

/;,.;1

"el
11)1 i2j)

To~de.llliry ilbe GEFoom,\l!m. SidMwri('ulU> with N~ or C·tennillim~lrUnCi'ltri(miil.Wt~ mmlyzr.xl ro~' [heir a'biUroy to l:l1IflCluu~' inool:po'mtiOln: of (y}i.'JSj(JIPinto EcRnb.l. OIl~;YSitfM fmgn:mnlS OOii!:aull~ng lfihe ciliture .l1ctgioll. roq;I!lJrnd. for.Rab l bin.dirnlll (re:s!c:lruL.'S 3~."I to 545)1 $~'1PWOOOff acti,..ily ~qWv;tl~n.t to fiU[[-wl1lgth SidM {Fig_ 2]))1, L:il·ewfue,(J!!l~.yihoS\l Sicl:MJ v~ria~ns, tlw [had aEP ad~vitytQwardEclll.lbl ca~a;lyzOO1(]DP[y~]~S]:GTIP ,e:xc~~an.gc whcnim-.c!J.Iooted w.~I~h. ScRab] -ScG1Df:l, "Ivi:dil. C(ffichmc:ies ooillpamble to· ftlU-~milglh SMM (fig .. kE) .. 11m$, GOI. dJRplacmlil!int,. .RaM. bh~dillig~ and JUic1.eolu~e exchange aCl~iv:~ty ~.wil~ 'ilie ~:n~ o(llJ1lt3i ~wom within SidM {fig.2JI.). . 'we IIIso Chil.rnCli~cli .~ SJiJM v~rirnn con~ SiSI:hffig of (ua1y amino ru;:·icilll.¥.lidues, 11 to 54.5. 3 PII!lri.:~OOIl:ooJ!I:Ilbil.1WX~ SkiMP 1'7-545·) i.'.jf[jehm.tly 00l!1nd. te i.1iI]lmIo'b~.~.tzedn()'"l'l'pre!ilyl~i.ll:d. gtlLllAriliiQIl:(;l S-lfif<'LI1Ilfeimse

00

4(11

00

Ul!

~,

30

,!Q

ISQ

TIme [min]

iirmeimiin]

D
1::'"

~ ..... 4

I:aM12
'~

3·
•
+*.
''Ii' .~.

IF
iSiaM!
G'I'\~~

,0.2
'~u
~

~ PC y";~
:1

'GT:PyS SldM

+ •

..

.~

z: III

@I:
,0

1~I~il~;;~LJ
5 1() 1$ :Olo

EJliIMl1 UScG;DJ2ll C~-!l'Q]

!iiil

+ '.

11 ,..,.'.111

ISCGDlt2il

[;ilfA!

I f.!te'lEI,tljJ'"""!!l

(GS'f)-i~i.'IMOO.Ec:Rab] (F~ .. :lAy, :Simi~cly, SidM(3! 7-:54:5) W<lS~[~il!bk: or djsrod3Ihg.Sc(jD)~2 rro:nl ~.J,m~ a!~dl displ~yedl ScRab.~~billldJIhl,g atCi:lvHy cOllll:pa;l.Il)~etCi that orful I"lel:'l,gth SJ,dM (fl,g. :3:13). Fw:themilIOfe. SidM(3 ~17-545)affic:km.dy callar-yz~d GDP[y_!l6S}Gl'P exchange in botihBcRab 1 (Fig. 3C) i!lIndSe:Rab~-80(10J2 ffi~.3:0.),. Thu,q. the C~[lIraJ
f¢gt,u~ Qf

3,1710 545wa6 suffidC\!lll to. !'Woola~f:n~e(l;ctivitt'eS !Fig. :1.•. Rilbl arn'll'atiilllill by SidM in1;'(lhi"~ (liDi di!)pl<UiEl'il'llllllilti!llllIdl memlIrralne' inilillrtiOOO~ S(;Ralbl... ,tA) ofGD:1 displa~nel1l, R<ibl 'MM:~llg,O'In4 nu.c!e!F $cRab\!ll. pull ..dQwna~¥ :sho1li!$ ac.ti'l.l'ity by :stdM burt: IPiot UcllA, IBie<ad:.ollililmobil.iZedl $~dM o.rr UdlA. ou tide ,e;x:dmlge. 1l.!!,!(1oo~,d ro~tr~!~ beads: V!I~r,~fif!cl.!ba'OOdl ith, Sd:abl1!d5cGt'II2 w ~t:o, f!~l)Of ~d!tabl (b~ ~ l~aif!€!I~lla!i!d .Bodl SidM rand Ud/\. cfi'ici~lil, lfuemclBd. li!!Jrorein~ on~e Ibe1Jds '~bei!lnd~OIF th ~ 5l11il!l!!lmlilatllliil: ~m (linD(Ji1Indi! Wer,e dl~,cted byimliniilli.ob~Dt til iilalv:s.~ widl Ra.bl1i:i1cl! lCiiCaHzed. In tim CYIJ)i1Ia.i>nllic Slir;.. II!I~in" "U:vtbCid¥ iiI.gailiist GIIDII:t!or R:a1lmlJJlt (Bal!il!!!1 01For .ilI Iy_3!iSJG1W il'ilco:~lPol'a:tion ellperillilile!li[f, 'W2 IJ~~!!I faooafllil(l LeV (2{)~ 3tJ).. Ni3\Ji@;"iiI1ne~&.~.QifI~y SKIM ;! p!IIf!tll SfdM and '~!tl'r40 I~m:ot :S,(Ra'b'1ll",SCGDI2 (B) OI"ZO J:!mol. EidRabl (0,. [y,?I:iS)GTP 'in:oo~ticn {IF ~nd!].gi1ill.QiM~ ,·1l-:SS]!GiPllil(.IOI'pOfJiltiOIJiI by SidM U~61J11IiIoll w~ ~Ilif~ fOr Ih~ ~iU'n.¢ijl WM de1E(tllid .~. ~he iUTe1li!leil'l r~diMrtMityever time .. (I) b r Raibl ~o LeVs (~g. ~) (10. 11). .Because' S:ldM illlm ill m!ll~r' exr:es.'Sf Sdl;aD!l-S.Ci~'DI2 !():O pmol)i!lI ial[ulerated!illltltE! pri~el1l(e of pllm!5plil .. lid~dnrlfillle o diSSo!JlClatool Ul,e:Sc..:R.a!l):~ -SicGDr2COlillplex in v1tro '(PO I~po.s~ts. 1!1~WIWS; ai~~!!!dt~df-m:h:an:g~ :~wdJi~ '~li!'the: ab!;€!Ii!()@ Q'f PCves1;cl!e:s. ·aJ'~ShD!n\f! with (Rg. ~iA)I we <:Wood wh.etl:ter GDFoot'ivaty aJ~ alnmtJ.~r s~i!lleilil th.einSll:it.. I) IfJr'Greilli <lli50~a:timll with IPC Ve5j!dIJ~ dUriillll~: nucl.eeil:ide '!;'Xdllil.IiIQ,Iil $:cRabl· •. Sc;ij,DJ2 w1I!5lrilcuba.ted!wIilIP( tiip05lC1m;esfrii the p:lfie'SenUie or .allilseril,clf! &1 .SidM 01' IG:'liP1!'-.5; (as ml1d~cated). I.oWti-d SidM I~OIru'g('l~ d~€:eytop:18sllil:ic :POOlllD~'ll:!(lS(l~~s w~r'~ :iepgf'!}~dlf'~(l!i!'! 5iohtbl!e ~J'Otl'liM Iby~y(ros~"gi!'i.!d~e'm '~rirl!!:gi1!tio!,!,!'!~d l!i1If01iefl!ilsi!1!' t'h!i: GDI.,roo'l!lrnd .ho,'i!. cc~~,Rabl, !ilnd\v1t~~rn,~r th.~ lack .of ON acti'li'~tyil~LidA mJi'e'(!\('liiflled,O~is ~rroot(1!i' \!ie..~ide~1I.8dio:nwe~e de"l:eded by illil1mol1:oblet an!1liL~s. (F), AmIL~llaf LWd!',.a~~mjiMiGllllI'I!i:tlil PC wsid£!'5 [oom ~iliglgRa'b] OOOllpt~oo I[)~ (lD]' 'fI~uS; I~revi.oll~~' ~nc:uMte.d with Sc:R.a.hrl-5tGIIlII::t!.irnthe Inel'>elilce ,or <libr.enlce of 5;d~,a:lildl 11,'i,"W1'oS (:a~ l!1!d)kalm,d). 'r;AJ t(;l ,~;r;)mp~~ at ~!lSl: wro· rflp€titiO!il,s, wel'CSwdi Wi~~!ef illC: !~l!!irellne!f!( f(!lf S,ldM

'TIlma: I~mllill!

S/ig:M

CO:~l~s~Wig lUirli~Q

<itid

re.sijues

975

REPORTS
dunl!ii,g Ra1l}l ffl~~t~l¥~UIo LeV's oould ~e by~ ,:-.~,1 "",i ~w·~ _ole -_ pa..<i.S!,;;O.II':J 'l·,:l" :'. tI-_·· p~l1oe .. - Q ,flJl,_,kPr'>'IIAN)_ .,' " J!1 _~'\.ii!jU" ~~ (fig. 85). a Rah] nnlUmt in wbic.1~ ASflJ (N} ~

~,Iooes A~ {D) atresi.dl'lC! M ru1<i,IIl!atshares all fC:il11.1re!';,deseribed. tb.r Wnd.l:ype Rabll'Mn lh;at~s ILIrnabl,eto b:i[lldi om OJ), 1l}~ IM.fN 8ubs.tihu~(m ~ri,Ra'b] dtd. ItOlitll~~f~fi'i \v:Jllh.LidA bindirng;a~ GST-[taM {D44N) al~d (jST~:Rab Wp'llrijfied from E ,cdliwereooun.d eqwaJ~y by l!ieoo.nl'bl!m!l~.lidA
(Fig, 4A), WIl£n COS~I celils p:1'Odlt!cimlg~l~ fl'l1o:rescen~ p:I'Olein, (GFp]"'~~clRmh l (DMN) wer:eit~ifuctil.:.':d \!O'illl ,C,., pJU!IIl1Jop]ifia {Fig.. 4, B, and: C1 G'fiP~abl flJ44Nl, \m~,el'flei~lIIdy n-K~lII!Iimd, l~oLCV~~ (Hltmlllimg wi!d.-fY:Dt!l (4J4 =* 8%], but !~ot C 1!1til~ ly,~ lV ~~liol~ .. d~~ti'il'~ rr4SSl ~lrai!~ LpOJ, (] 2m .3%), wh~(;h imdiQ1t~l l~iI"l G!fP~ ,Ilabl (D44N) recrui1mcl](' wru; de'pcllidel~t on a
fulliO~kl':n:1ll DO~fo[Cill1IIrrnlS[pOl't(t(.

walY~'l~w Qf om all.d memillm:~l of Rilbl froJIii d-e cyt_"~ilsti'iic 'j)Qo! req Ii!i~wdld~e ,GDF <iefi.vi'I!),of :SidM, 1ihe~n.iiJJbml:yor LiM. I~:OexlmCl~ .Rah~. frrnn GDm indl&cated Iii biernrollY belWt}Cfl
F'~g. 3. TI~e ~IilIDrrfll rE~~.QftI of SldM

d!i~ hiirQ L. J)ilel'{/J/.opkila eft~to:U5" lP~!'Il<iMy Ill, e~!iWie Ow Rab]~!lIiiled ~o U'Le.LC'V\:Va!> oovivmed. ~y Si~ bdmeLl'laSsoc:dlltioil. wimilil

UclA. whi(lh!lJSSis-4Sii~

Ilooum:u.ilmin'!l, QrC.il'ivaIM,

suftfiici~m1i:forGOI d!i.~pltJ(-mrmlilt, Rilbl balrild~riIlg, and GEW: acmrity .. 'tA}' lm:Si't:iM('3U-:54J.5) by GST·RalllI:I:-,oo_1
bead; OOltJl!l,t ~- G1Sili-batlrnci !jontro~

i~

mt!fiI~i~oo,t s.iIi!llJ~lng p,~dp~tatij,(l~ OIf

beads:.

.Ili!!il@

rnarnk'€d vdth

i!!il

gs'I~risk

l: t}}Jtlil~l~lf)tJkil(J blatl'ld \!!lith 1~~,d"ff,!iiilmi(lb'iU~~d[d~ ) 1,\l\lfi1iim~ ~1iIU1IDE!rs indicj!fie iim~moadd A.,~;.dM" wh~d~ 'WD:5 dcfooli.ve fQl"th.c recn:Jji~lJlC::fU r,eSfdl!le'l) Of' IlIIIK!lta!tecii mIlItr-ol bea.dl5, Q'~ l;vndJ.t}:J~Rab] (2'0.21) •.sha:wl1L1rom. coloh d 11.~ d) ~ calizatiol'ltvil.hCr:Pf";Rabl.(044lKfi), (!H ;t W%), a:n d P~Il~ . (Iii!. t_~ 001)_~. wo;ilUi)~'~'
Hlis

:sh£lWS,aproteillioi 2:5 kD (oorrl~o:lilrllingl to,iltte haI!: pfioteilil 1~S1) ,(jre~-n:!\aml1gl wit!!l! the ilUillWJOdy. (8) S(G'bllll!! ~spla(;~. iJiient tina Sd~ail\ll rn-,indilii'9 ~ :5idM (31'1-54JS~I. :5(R.abl-S((ii[ll2 was: irnnm-

C:
'13

...0. riG' Sic:lM .. '" $:dIM 1:1~5!J') .0' + SlIM ~'a 11.&'15) .... <1 &:RIIb~

-0
..

SidM(1-<liSO} -0 ""SldM(317-545j, .... ,.j.SidM

-I'

ooSidM

1),15- smllOI:S'cGCH

~: 2
I~
'C'(i

S~dlM·iliid~~~u
WM;

~~ill]l~[ll

(lr GF'P-

1111 .iju

e 511!pt!:rnatauot (1i!IIiIOOl!!lld) were

'1 S ~:C'1i5 lfIm.!il1 l[m~liI]

Rilbl(D44.l\~

by :n.JdA.:a!> delet~on o·fbmlll ;s/tUill and rt.(/Ailil L. plletiilU'O,rJhna ahrogaled lreoru:inucllt of OFP ..[tab I {D44N) to Lev" (1,1 ±7"-li!). Thus, LtdA ~illdh"2,i:lD. vIvo was :~rl.clOOJ oonOT~fro~ .Rallt, wk[ch ex:pilan.fl'l
mooj!}lted.

detected

a:nd,I~1SidM'lUil'~,4~) !h~ G'~Fac6ili\jlij,

by' ~tmml!lliloolm: an .. l~sis:. (C

El:IRabl ~10 pmij (0' Or SdR;abl~5~G012 (1;25 iJll1lIdIi},(D) werein~ubaitierll wiilifil SidM van,mlli; (3 p,tmlm), ,rnd.l!lpt3ke lliet.ean'l!med CNJ!!r ltim~. A!figllne. pal"b r~IfI'-e5iMt;rt least tIIilIl~itiPlil$. ,<,!,
~L

:5, ~IO '~5 Time [nrl11lI1

IQf

21),

~Iilis S.!I:utly (liI~ml:!8'f5:~lfujltun@ "'min:Da~d reSitiJ'ue:s). '(lRiglh~) Summ-dl'1 of the ID;pell'im!E!n"tr:5Qwn below ~ ilil (8m i9indiGlting plIirnive (.+) or .liIeg:m.r,e (=) o!rtmQil@s" Th!i!' 'OrIDtli'aJl reg:i:0!11 l~~e!ill g,m']f!i(J; al::ki l~esidlJleJiU7 .a!l1d 545 (~haded b~lIe) lIV.asfoun.d to Ibe 'e:si5eliltjal'rm all 'inllolilitiro· artilJitjf5: of Sl:I'M. (Blalil cI C:~I Nll-~ of EdR:abl ~B) QrSdRab:l·ScGDI12, (0 Iby oooo-imm.abilJzeiJ SiaM Var1iljlillt:i•. PMellrns baulildl to 'th~ ~d50r I1IililbocNJili'ld ~'IiIthe wpema.taiil.tw'ere de:t\e(t@ti by ~mfluJ!Ii!IlI:dtlt analyjs (usinQl FlLAG· ~1Pe!difiii!: or Rillbi1ll3i-Si!ilemic al'ltioo.dy~l. The' larae lril1I"I~ll:EdllM~an astErisk. shaM,a :2,& 1.-k!~' InatEin (rosH@a(tin.~1 MIn ~!1! a.fiItibCldly [C)CI!lIllSPClfildiftl!'l1 110 the Ibali] prme~IIIS~'dMI~396-,64'ln. (D a.md! E) [y_3~]:GlP 'inlm:~pOtrratiolill i'll1tn (IIJ) ~!c!l)iab:l m~~efij .:2:0 pmdl. (ri~hO 10 PJlll(l(] ~'f ~i~~1 )ciR!1!ih1ll""SdiOI2 1(10 ;Plll1ol) by SioM vanam (:2: p'.mdl.~. Rabl . •md S1dM Wlri'!l1I.1lsW'efe rill:'l!Ii~ated~arildl [IllIpU!ke b~ :RaI~'l protiifil$ WM· dd~!iI1~noo as ·tIll!!! iIliU~@ ~1iI ~io<adilViilll' lowr1iim.e. ~B,) ttl ~E) IrepIrresel!iltat \east ~a repi1iiljool'iJ.

lFig. Z. DO:IiII .. int 1m Schemlaltic r~p~mtgt1ioo

'of SidM .. ,00' (Leffl Sid'M valiaf'!lb ij~d '~

.A,
(11-:20'11)1II
C::=:::::::iil:~~

(~-{t,1 a:-~I
t1HM35} (114!jiO}

'~S'16 ,~~~~~oo;IIS95

', .,',~~,'~
'&._
'~"".,

[y-~5S]IG1P bylllilM.

!protelnllVoBS

'"t,t "iSl

.~.

""~"'...
,

,-

MIA

N'/A,

N'IA
NJ:A.
+
l'

~/A
NIA,

,4Mi

(11.s4S} :SiidM (202~1} (a17~7} ,~~7)1 (~;:n -@:Il,~

("61I*17Ji

~:

I 545

INltA

""
eli-

,+
IWA

'"
.... +.
¥

,t

+,
-t'

... ...

""

+
N\fA

*' +
N/A.

...
+

NIiA

1""'11.

j,546·G41}

NIA

N/A Ill/A, NtIJl, NIM.,

,!iiH

- .~ SIJiIM{l~) ,-+~1M -+~~mi~~

Il'!tl,9l!lM ."" '" lili(il!M(1 ~o~

'. SildM{~liI.7'·B<I'71

.... , 'f. 8Iil1Mt!U :iI'~"l .... -to SklM"396~iI'l .... I· 1Sk!M:["i411 ~;ii')

-.

no SldMI

I!

lliKI SId""

- .~S[dl;l(h~.5)
-"",S!dM

- *~!dIiAI~!)I~~!!oI'I7) _, + Si'dM(3;17"B471
.~. ,~:8id"'l'1-,!ijl!l~

100Gb':

13
~
1ft
A

0.75'

e< EQ'

:2

0.5

0
11ll!

:2(1

<l(l!

a'

01----.,..--,..----1
,g, .iltil

lIime, ~lIf'Ilrn~1

40 1'lm:tl, [m[iiI]l

·40

TIme l,m'ln.1

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS

[I:

LIlA ·!;.II-~~~;:...;~

~#

!
~.

li? M •. s:.. :511!1iln.~1lI"ll. f!. !~~ blfrK.t Immlill ..~~; .3~09 ~.l99SJ. I 18 •. L 6. iill\;lli!, (I,. S. lIiarlill P. ~. ~{i'OO~ty, 11:. G. ~g,jl'tiOIll" C.. fI, R-~J'. ·Cell Sri: '1:14.~:6~7 (2100:11
li;~, S;,

~ili!iill.1C. R. ~-O)',ilifOOit ,Miff~Wi

0:992), 11', (lli!~1'ier ~~.m'" N.cr:l!J'r.f' 3,!i3, 769 (:1:991). ~9,.C, NLlllrl'i!lf, HI, W. ~~d!~n',. li M<lne50m,I. Mei~~IillI" 111. IE. Bi~tl~ j, (ell' BioI. 12:!i,. ,2.2:5 tl ~94t ~(I. G, M. ~!'I.~l;. ! O!err~ ~I P. VI;I9e!I. !1,. Iii. ~I;io;:rg,..~ .•. •. 2:8,

~.(I.. 1i1. ,f!1~~hl~r. ~. It. ~~~.r'!I' .Q~. (,gfli!, 47 (lOQ~l 21, r, rJ,till'i!li! f!1 "L Nm. [€II ,s.i\ri! II, '~11[21006)_ 2'2. 1iI_ ~M~.f .t,r ai" / •. C8i'j Blat, 115. 3:1 (1991). 2:~. E. j, 'Tr~iI<!le. J. Ire.B{lUIDf!:, ~. ~l1oirr~1JI;.~ar. C,,~, !)~. '111,. IE. Btl[irJI~): C!'!t!i'BloA U9, 749 t!l9'92t 2:'1 .. O. P)\1i"I>!lMO il'l m". £MOO j,:l:'5, 1I3 ~:il:OOIt), ,:5. MiltElli,jI~ilfIiI me'lfl!ldj ~Hi' ~~<lil.ab1.eil!~5IIpp.mfl'l;[l !Il'~teri<ll 1.l[l5deM~ QI1I!i~~_ ~15.S:,li.rak:i, K ~lblJd,~ T. :Sa~:;,t~ Y, 1il<It~ T~h~ Mol. (ell B.fDL. 1:11. 1L~3S~1'i911'. 2:7. MLiSII~•.M. KaW8I:a. '1', Va~1!11 ~!Mol. OMim. ,:;l67. 9.2211 J

r-

15, 312 (;1:007]1,

v,

r.

[Fig. 4. UclA !tan r1mtilrit 6Dh_e RaI~1(ID44lN) WUl lIhe: ab5etKI!!: of Si~M. W lilA UllliI bind Rallill('Dc44Jm" B;inding lOW LidA.to bf!la:d·ilil1lmooi~ijl)ed 'Gist· RaM or 'GSi·tR.abl«(W4N)bMt IlIIolL GST wal~ detellirnined IbV :SD~I)!'ai(!)ifal~id~ ~oodJoph!)(~i!!. !1!Ji!d '((j(lID~S'ie· stliuring, 'U'h~figumr,~r'~~!i!j] MIl r~Ii'~(I!i!s. '~B~ ,Rii!(n!!ltmem: of GfP-Rabl (044 N1j![iUlnlilg LPfj8r.JmflphflrJn·ulfnrt T[an~ltern~ylJlraJI:I5fieded 005;1 (Ial[is ,
Iprodudlll!J (j;;p.lA:<lbl(fJ44M were infeCted '~()r 30 mifliilS ilild~«lrted. (!ell!5If11ere ~"~ea .. llilal staineal fm hlltra~E!lhdar ,baderia (leffO. (Middle], 'GFiP·Rab:ilIn~44f11J). [rig~liIt) merg;ed ~UIiI!iligl')$: With ba.cter'B (,d)alild IGIRIl·!l:albillmM4IN) {g'e!!n() .• AnuWil lliidiGtim, th(!b~ilDom of the U:V m.afjlliifti:etllthreerold im theinSl!!\1:$ o·ff eaoo p<llilili. Scale' b.al~, !5 !Jm f.ll!liltras.u V!l8!S eqfllll~ty dl.all;ged. by l~rle8ir I!dJIlI~1m;m1. (0 tQ.l!lal1tifi1mtiOJIl Il~ I~B'II~oWim.gl 'Nt !1'l!auilmemt of IGFP!.Rab:Uo.44N~I~ii'Ithe :absemce of SldM reqllliir,~ LidlOi..1ihe 'graph Ir@p:oo~e;m poc!red IiJtart:! (m@lln :I: SO) Iiirom 'rO!;jf fldi!!I~@ndiefit 'el'!p@nl'l!l~ms. ¥"'" 0101001 (Stooellilfs. t 1ie:S,t).

Mf(\ro~fqj. 30S f2(03). ]!I,. '" Wii!ll}:II, R" ll. Erti'r:n;3ll.; W., A. M~~~~, J•. ~.iol ,(l'IflIi'I. .. :!71, lj]·~3ji!(19%1 32. Mo tlirul:k (, ~I!Hn'a,lIi'IGtri, L ~~ ill ltd! (Jllf!aydiillJIKII1IWrli ~mf r'M@winQ tliHl' m:aili'lli!uftp1;: ,", 8~tzl):, 11. tiJmlliblKhl, M. IBerriirrnn, E. (f6l~~. KA .. SlIealliiul, Z. ~]. 'T, 1l'Ii:I!)IVIIlI'r, Jt E"Jl.~mingiflr:,..'" ~i~lIn~1I, <100 , '5:MoholMli!di far (ri~~ UI'II1I1Je~a!1!l :stienti!k i!il!¥ice; "rod .iI'\. !,!I~mPil~N~ F!;( "f1)~!ii!llg r~!!!II~' Ji~ 'l'f{![i( wassilpportelil Of tile' !ilIII'IIl,rotl Hwg!ni!~MediGllI!.lfIrtj~ll!i!! i!ii~ b:!f N<~I.i!Jrna I 1'n.~tiJIl! iii! l)I:3bi!l.~!l aitld iiirl~i!~':lwi!~i'ld tilIliI~1@!l' OI~~!\(!s. NIH, D~rjjlfl 9r~ ~I. P:lOO:K:34928,RlR:1 3,:1.

~a:,

1s a How~F1II 1iI1I~1l!!.5.Mildi~ili. ilMlltut@ tlw@ili~iltl(i!,.

SUllhPD,rt;iflg) Orn'~ifle Ma,tlefillal.

Wi.~W',~~~rni!gl,g~Ql,@I~oln~~lll!rull!lM91211I)!!:],
~Ierf<l~
illl~ .Me~l!o!:I~

16, ~Il:~ til. 'l'lI1)_ ~mlgt. p/J,e,MfmJplltla tlUdA showed deiayed Rab~ H. 'Ii. SDI.d!ii.tll, D\, ShalH~o. ,A,. a, S'o!jSlrtJp, S. 1ft I?r'e'~@r. oocruimn.lelilli «nnparod. with. \vikl.ilYffi1'3.LCVs (20), Millffe 3'6·9., n\ (19·94l. skiM ]Si3: frotdn tlK1lt ~1a.~ooml~G.bFamd!GD!f iL5. U .. SiIIB r~, DI,I!iI;'~Dilill. S, fr.. Hl!If'~r,UOldJff '~,2S, ®S6 (il',O(lIJ), iH.cllivily to'!Narcli <I R3b GfPa5~. 'fh,L'iI.UDi.ql!l.~a'bi~.J i~y S:tdM to Unk of)! dispIacea1!iOO'I. IloRab,~ 16, ,",1\, FI~rwi!.:.,. f$g, ~. n~,1.31,) ~l9{m. ·of a.ClmiVaUOIl expliJii~!Sbow ~e~nJnl.w.clll)o.l!ar. pil'lhogm 1", ,PIM!l,rnlil,l;/.ril'a can ,eilici\l'mly exploirl host
~f'

!lab I. abou~: ,!ihclCV. ]ndoodl

V:aclJ'(D~CSoOOllillm.~

U •.

f!..

,B. ID'irac·S'\i@J~~rLip. T. SUtilW,ilI!,. 5,

!l;,. Pf!ln1e:r.,

(M'.BO}.

~i9!',S;1 l>!! '5i~

Tabie $1.
1lIi!~~f·~mw.;

1.11AlJsI~t 2.007; ilW!pI.tdl 9< OCl!o'bH .roa.7 i'IiIbli~lIed 'D~'im:i! U Oct.tlt:ier ilOO~; 1IO,112~"'!!:!l~~, n~n21 lUI~t!J!!e~.il.inl~rm~,lM 'O\I~~
~ij !i!lllli$

~per,.

cell Rllbl ~1 h~ the presence arGD:1 tI'latnm,u,,mlly i:1]Ie:rrf~ widl 'dllispt:'OOCSs ..The disCGvcry of ~tl,l GBF 2Ill'd. (iOF acDv.iry willllh:~SidM raises d~~h~mri!¥l1lil~g po~Mlily d:ta.t~karyolkGE:f P-I:\lo. ~cim,.!~-Y' po&..~ Si!"l~~~".rolli~!esto medJ~ lim;:n~a bmt!~e dcl:hl\~~'Y .tnt;! a.cliv.u:l\!l!~ ~b G'fPase'S

Rhleb A,Cliv,8tes mT'OIR by Antaglolnizling IiIs IEndo'gen'o'us IOllhlibiitiol:r"F'KB,P3:8

Ma~:l!· AnlfJflI£! L[u,4 .X.ia OYlillll :51M!'1II~~'IQillililling ~. W,al!l,g' •.~

or

d.l.lIrig~glinlrncell!:!lil!I"
liI@fl!r'e!In:!t@!§OIndi

ves!,;lel.rnl~rort
Not@~

X'i'alocfhlilrl l.aiii. :l!,[3 ,Dorlgmul YOII!l[iffrffiil.1II1LilL!l.Z VIIJI.Jiiin!l!lll~ l

il. til...;!~;rIil~ H.Md:lrll'f@,. fflY_ fi,~oi;j~.

2;. ~. c. lFilmswDi1h 1J~" iIlmr. Iilaill ..A(tM/,. Sft (jI, :S:AlIl.l3 .• ,N &196 (llWI!J. 3,. r. CnavrieJ. R. !ii, Jt.l!r!~!'!, HI, f. H~L!!ril !t sr~~~,
~"'.Z,!:qia~

~,mon.

{:t!ll fjf.ot~. 10]

A._ R. Kh.O:!f'aV,'·F.3rr i!'i' !!i" Plot. Nail. Mad, Sli, Cl.5.A. 86, 6264 Ol991!). s, tit l?>Ilt~r, P. C!l1!iiFl!!r. E,. A. NIg!l\ M,. ~Fti~! ,.CdJ Sci 1Q2., :857 (:;[992'). .
... (I,

f~1l'16~

~~"! U'~~·o:i·,

r,

~IMII..a. 'M,A.

iI.!illile!ll:.J. llNi. (hem. 267. 3.'90:1'0

fiu,,: mamm!il!lijafil t,uge~ of ,rdiPQImycin~ 1n;iIOR., 'ii'lill (e,ntr~~ l~eg,l!Ilattir' ef (!~~~ groWlii. 1'15art.i!lity is f,e!1~latecl ~ R:heil", iii IHas-Uke Sf!iilalll'!1IUgIliOtS<iill'l~ b'ffiphi:i:Si~··hata'Se (GWase),. ~~ r~"ljl{iI1I!!:eto g:rowth fatror sitliiilllyruattiiO!il a.lildlll!I~Jtrif~nt g,'l,I,CI~tabU!t.¥. W@s'h~w ti1!l!t Rhi@b f@Qulliatm:s ,nIli,iJiORthroliigh IFKBP38, al m:emiilIll!iF of thieFK50,6.,blndil1g p:mte~1fI (fKBP) family tllhiiltts !itn.!ctlll!liCl~ly r,@'i.ab:!dto, Fl{ii!~:t2:. FKBP3S blinds tel I1I1TiOIR: .alrld i111mbjUl "it! .;lIClfiirityi !Ii,i'! lliIIIiiI miller ~']l1IIlmaJr totflat o*~ile IFKIB:P12-rn,p.'I'Rilycirn, ,ooml1'l.ex. ,frlji"l!ib, inlbilraru ,diill!d~lIWii~1iI FIK\8:P3::B .and preve'rnts itIiiil:5SJllCia.tio:n with IflilTOIR im ill 'g~no:!>ilil@ .Si r "~rilpl!DlllllpllllaU! (GTP)-dependent 1I!IiI.I! rmer. OUlrfiin:riilng!l SlllIggm 'th\'!,t FIKB:P:3~ i~.0:11'1 'BndCl~elnOliS. mnhiibitor ICiIf 1iI'iI10~ IIiIh{l'~einhibitcH')l' adirilyi5 alfillf.1lgollilized I~Y Rliieiil,inl re!>~illl~!! 'to 'gf(lwl:hfadol~ ",tjmlil~~atllllni3ind n!l!Itrieillt ..a\l'a~~1Iibmty.

U.9·92:1 1'. T. :5.il~ki el ai.,). Dir~t (mm,i!6S, 2'1133~U~!JIJ. It T, :5~!dal,ii.~ .l. l!iieriE!fer. S;. It- Ndfer, i'tlQ.r_ ~. Cd/4,
~~S 11993]1, 9. 0, i,.J~IIii,flle;1 ~t•.t, slo.!, CI$rrI,~6:[1\ 13~4:'i (1~~3}, 10 •. fit ~. G~rell> ). '::.lalln~r, C M. (~i!f!II!~, i?, i. N'IM!!k:, :Ml50' J. H, ;)J'lS (199~, n..s:. ArilU, A. Kikudll Y. H~tii. M. ,ISOIilI!l'~iJ, Y. 'T.~kiI~,.).{ji,I!J~

{hem. 2J6~, UOO7 ~1990J.,

1:2: .. 5.. It!l·~1'fli:r .I\, 61, ()ir~~"-Sw~I!UIJ, T. Sri!iilli!l;i. • ~.~ri. ~Jro, 1':0507 {!!'99~1',

J.B..ioI ..

iI~rn,~polljJ;e: '10 variOl.l:!;c:m,\I'irQmmllntil~. ,cues, iI}, Chil.dJi~g s:ln.mil.l:ta.tLo:n.by growtl~ factars, eba.tt:lgM il:l li'iu.m(lji~'!em~dill.oEll!, and ]lll1.ctuatklilLlI tn.f:!lnflW levd~ O. 2). mTOcR c~i~ilSits. :!,.lciO'~ir(; fi,jI~c· liouin d~eco!!re:vl ·of ~W(l disli!lC( mrultiQlroleJ!'!

I.,l.re.!11Ol!~1I.:OO'~.'i~.__ ~.'-' .!".-.•..Ofra. ip.'-.~H.'~.i~mro. ...R._' tS lI.sennecliueonmepmlem~m'!aSC: d~a~ c<lHIroIls a wid(l S1~eeu:\un ofce·UI.WJru: e\'ren~

OOll'1Jl'iexes wl'!'!1edi mTORcCJlup1ex ~{nlTORC l), m~ mJOR CGIlPlC~ 2 ~nt'fORQ) .~~~ :~paal1l~n. lill .ooll1lp;l~ wIth F'iKBP]2 (<In. :F.K:5iOO~btuidirng .~ re..tiu), spcci:rL:cn~lyinti(lrrcre!l willlil. lwTORc] fllllm~ llO1ll, 8:11'1(1. Cl)IH;tMJll)i!lt~ly. il1i.l~ibilSren..gtWwnl~ (4., 5).

nemajm 1tlp,!>lroatn :~glil]amrs ofll!1:i"-ORC~! aile me TSC] and TSC2 l~lI!~~Of"~llIp~i;(ln;. ll~c two TSC ~!U!CU!'lS Ibml a C(lf:l~!·e;.;; thaI disp~a~

977

REPORTS
it ' ,'a!i'i~_ --~ ,- - ItI,lJil- _~", 'liO.-'haiiil --~ ,~--

~!roll3i!l «lAP)actirvil.)!
!lllil<J;~~GT.Pru;e

' C..... f"se}r.i - c - -- ,g "Iiwt:iim ' ~,""_T "'" Itowa!id .~eb,a ~,.~qke

o'D1n:er SIliUIl], GT~ i:ns gl.Ianilbe m111£:~coticOObiliflru~g!i1i1,~: it~sa'Cli\leiniu;Gr.iP~ lJoulild ftm:nantl inaclivc [1'1 dl~ gl1al,'(!lril.toG!dipllos1~ll3re (GDP)":OOUlld formn (9), 11.t¢ TSC1-TSC2 CQ~Jflp~eJ( ill1ulM~~ Ille i!Urin.~~crr!Pas~aC~\fiJly ~ (lif Rhcb mcl\ UWl'>, !1.~.at~v~ly IresulalesRjqeb
l~iIlIeaoniv~rty of Rlheb, is dlic.ttlklGliby iiilmcltolll, COOlvcrse~y. 11loctivlliioUI Intle:TSC~~ TSC:2 OOI'U\P~CX re!>ti.I~,1S~Jll OOOllIrl'aulmjo:n of arp~ MMm.1. R!IJ'u}b, \Vhilch acti,vaJtL'lS I1nIIDOCI (10, .I i).
I~~L';p():plid_)'[
1!(!;ll5 Ithe 3$..f"KBPg,) b~l!ongs I~l) pr,olyl d!i1lm"ng: iOOl~~G'I.flC (!Pfla$) fcallrnily ·of FKBPs. ItOOl'iI!~!IIiJ a !l~.sjo:njref~md '(SJlflOkIDIO\'l{[I

{6-8ll-lle

dependemt~~Q8phOllr}4alia.ill ii~'i ood~ :S:&J( and 4:E·BPlwl !tol'of ~tracelll!!l!ol.r slgn!iil-regul~ed kinase (ERiK) ~.at 2: (Fig, 2C). l1~is c,:lie-c:I, on mTORJC~, .aeitivil~y !i,p'p!'i'ali'Cldi tnbe SpeciifaC, be·

catb.~~a dii'ti'eilCilill FKBP38...spcci~ic siRNA, oH·

gObu;tdoottd~ 1~Ii!KI~i.o~.i3J ~1I'II,li'laI'~IT~[ (flg~ $3), hil a~iliM ttl Inh~,~mhl'ul.o~rI,~'~lllili uflORC] ::l.e. '~vily I!llild~ lUloo'l'la1 :QmWit:1'! oonditi!(:l!.l.'5" docm..'_~ ,<IDl!!!mam::e of FK8P3R at-m.rOO1.l:cedl: Uterat~ ·of

rnTOJtCl itl'iacti~~1.'!ion i. ~ptll!).~ ~o 8~!'Wii or W aJll!ti'iO acid 'vatioo (:jig. S4,), \-'!I't~lchindicatedllllL91til1e cted eells were '~ess SerlSilivc ~o ~l!,Vd~roo(or or i~lJtriel~tiimillltio:rl. The pafilis! re5,P'O!'ire -oF mIDRCl 'nochang&s: iI~ seruml m:W,
nn.un~IM Qo:mdiut~Qn'.l'! may :11M.l1l fm~JI, lb'h,~IiI.ml!a~n.l!i'i_gfKBP)8 :in 'll!l~c~ns) A.t~iWIlMi,\I~I:y.il~, lil'iBy
m([~ca'[L:l

or

meiha.f]~sms 1!h~Ures!:!:~ !~TOltCI.

Ute

~i'll~~

Oir

FKI1P3~,.I[!l.dgpend~l Co-i~eolive-

lFK.BP33

FKBp·(' dOH'IOiil!T!. iIDla!! i"hi~lhly i~Lai~& ~o' fKBPI2 (12~, .FKBP38 n~so ~ru5 a, liIOlH!>= :~nelil:bm.rl~edQn.IDil~, at lhc'!;'cl)' C tttll1l:ifnu'>, \?o'i11kih.
is t1J111jqlllc91tlCllg

~",idrl. GT.P~y..s" a t'IOllhydml.yzabill: Gfp mla1.og, ~UanJlll~rile c~1",O-(j~.d,~iolri.rph;o.~lmle),exh,V1CJJ.u~.d: :mt1.dlhigher bil~rling allli'inuly tmvru'd fKB.r38 l~lmn,did (Jn~1.Jnd ,o:rtllilt~cl!!R:ll~~b (fiis- lC)l ~n cells overcl-il:lni:-ssi !ll!!: f'KIl'jPJ8, i.!ml!linS'ltDllYlmed pl~oop:lil(myladoDi watSliliI'ge~y pfC\I\~nte.d: for .~~. dU~"'II1Slre'ilinllf!iugcllii oif nrTORCI ,hit'" clllaJinlg ll'bo:::J.somalp:rolcin S~ kinase ('S6K)1 rlboOOlrnl~,S6 pmtdn. {S6)Jand '~le~ikaliYo~icillilllloocm. f'3cmr 4E.-"':b~li'Id!Lng pr{.)llliill I (4 E-m!P 1) {:F~g..2.A,

lro(jl).ln~~ fnrll!u'gelDng ~t, IlilJil.OC:h'(,m.dn,il V 3, ll1fJ ee Wr:; i~!lllBd FKHP38:i~3, yt)a;ll'WO.11)'i'IiJnd ~Iil d~gm:Il~. 10 id~lify Rlt~.il~,te~n~ PIlOWijn.<: (frg. 8!.), {,IS). The' 'p;uICl1lti!l1immel,ion be:h?!reen .llhcb.EL"Ili.J .FlKUP38im U'I1Iill1t1llil::lilililil cclls was eonfim:.oo: by OQUtll~ulllnoprc.clp:uUition of CliLdogeU'OllS Ithcbwill~ FK.B:P38ool'nl Ihuinan el,n'Dlj'ofilk kid,~ I[lCY (,HE]Q,9.3) oelt lIysal~ (F~g".1A). .Vrnth.en'l'l:oro:, 1;iI!Wi~~ lIIDa~ly ~p~Strl I1':)canfui:nrrmt .Rlneb ~J1dfKBf3~iru~1OO ,~~d:l ~~ (ltl~1t m. l,lI'I,ili viuro Illirnd~,g ~ (.Ftg, .I.B). TI1Ci~c~(D ru'lcb \\I.'UI1 PKm3P38.appe;I.nOO 10 ~ d.epelLoomt em iasImclood& Ml1dh~g s.l31f~. ~<Jil1SC [~b lmrlcd

aU dlCFr.:J3P

pr04:t'rim

811d

is

,2

or

F1gl. 1. G."d!1!~!i!dl1;m: h~lbn!}~(:)rI Rh!l'.b r.mh IF~IP3,a.. (/0 Cohil'iml~!il.(lpredprrtai~Ofll of FiKBP38 ~tIil !)f RhElb. Llf.'ates bom HtClK2:~~ (j~~srrereill'llmullJop;nmpitMI with ,~mtiood:yto FKBP38 (lanEl'S2: <lml 4J or ,oon.iI!ol 19Gi I~~arn~sland 3), IItlCIBP~3 '~llop} amd IFtlneib (OOucrm)il1iIDe p-:r-eclpltarte5 were' detected, by iml!lili;!l!iIoblottil1l!!,. (I) I[lJt~e(,1b!:li!dliW! b~iil! 9 Rh~b ai!i!d ,rlKl!!!P3i~ m""'O, Histh:lliJil(l4aggedl Rli!eb '~is" Rheb')' w\\t!i ~rlci.lw~:~1 with gh.ulta,tlirioo'i! .S'·tri1i11sfe ra51! (GST) or G5T~Mgrged fKSIFl38 '~GS:if~fKP3S') iliDlLowed by !precipi1!'ailiiclli!Jwn:th ,gllJltathionE! ,ileBidls-The p~ecipita~ werr,l!! imm~Mh1otteL'ilf'0I' ,Hi51.Jlheb ~lbo*m)I. G5T;aIUlcl (DJ'~IF:K!B,PS;B'(blp)\ (Il:) GTP~d1~erLl.:ll!nt b~,di~.,gl o,r IRh@lb with fKiB!P3S. Uiltrea~d H:iiS'lRhl!b Q.tIlilel) GlP,"¥·S-looded HiivRh:eb (Lallile 2), and GOP·ilSa1oolti 1Hil~'"1tRhllb ij~tlJn.E! 3)1 wewe .aUil'ltJ!J.Ibattedll'llii:tiII G51·:FKIB!t?3sraUCM'm lily predpllmtiim with gll1lItathiolfNl 'lbeadIsi. llfrle IpreCipltates wBreimllltlllnlJllraUedl 'I'or GSi.fKEl'F'38 anu MliS·!R_h@It!,
1 ~I

A
Rapa
~~ ~g,Rl!!$!}

CIJjI ~$8

IslJ;;:NI!,

'f. 'f.

,-

_.

,-,
.jo,

_'

. .,

.~'

~~

'I-'-'i!' .~ '"

--',f'=+'
HA~ ~~i'!
,I\kl

P,S6:K:(T'3ii9~ii-'

.......' =rEI~~~'''''~'
!!iiii!i!!I!!'

P-S6"~~1~1
f'.,.1JfS.IW1·(n1I<!G~, p.,AA%~1~) :II

....

~'_.~!!iiiiIiII!L""'J"

I~ir

~Q

and I1:g. Sl~,~f!,CQ:!Jlimo;D. !FKBrJ8 QverpoodUl;lrl!;H~ ~ad lr!o~teotJb!e effecto;¥! ~hQspllQryl<!.tiQn (lit
I!lIro~i~~dllase ~ .i\kl: (F:~ :2A)'.TIrc h11ilibhrn-y eWect oil" f,KB'38QII, In1U,RC'lactbtity was 1:e"!1l::rsOO. if Rh(~b W'<IS~prus5t,-d, which ~~dJflt
ot,-

-if'

+
-

*•

'.

~+ -,+-+,~

~,

mlUi.gQl~izesfiKrrMs. Siimub.i ell!)~iS of FKBPlS ovrupmd\1ciiilll ((II !litIT(fR:C~a(.'tivi~y we~~«I. whe!QJ celilsdlilPriV\edQf.a1~lino ;:a}i;;i~ were 'eN:p;i:P.wd til arnil!ilO ad& {PUg.2B a!iidfis. 82), ~I] "ens: Irtn:iSie:lfi.t~m.iliSreciteci WUU1. FKBP38~ specific snmJllillwrferilfig,RNA (si.RNA.) o[[8pnlll.~ clcO'I!icms, dteaiOOUitn.~ offKl3:PJ8 wore: re.d~ct by -B0'l'/1l) CFig, 2(;)6 AOOOIl1iI,pan,yin~ Ihe dcc~ ahmldanro QfFKBP.38:M1Safiiin.erua.~ ~niliiTURRheb IOel,pa!1_!"!u!'IfII! -of Pha~[f!1acOi[Q;g). U!ilh>I!:~it.1 ~ Pit~swrg'if! S;~IfJOGi.,of Medldne, E135,7 IBi(lfl'!ednc:al Sd\e'I'lCJ~ rr'(!I\lier•. 200 ~!llUlrop,SIr~l!\t, fi:tt~blJll~, fA 1rS2D, USJt ~'~~rll1l!!nt mI ~I!;uro~¥" Ul'1iw I:>ltyQr PittsiKJr-grn :5d"1ool m rI!i!lilidnO!;, IlITtslJiu~h, PII. 1S,2U U!lJ!.ID@p>l:rtIill'~liit of (@U,I~iDlll!iJ!I'. Sdloo~ ~ Ba~k MediCili Sdi!Iil(IIl, Swthi~fI ,ri'6'd:i'[i'll Uni· ven;ity, G,wngili"u '5l0l515, (hiin;"

~1::'£IF'1 A'IlI

~ OO:T~l!o!' -~.~P,3gl mToRC~'

+,t ~ "'" '"

-+

+'+

'"

'" ...

--------

P"l~' Iicl~}

Q.f l!lIiIiI''GR( l ,am1.ffity b-!{ FK!BP38. HEK29c30elbwere transfiooed wlll hem!a9!QI.utttlill1l (HA)-tagged, :5:<H<l..(lll!glw"iih ('Ii') Qrwfth(!t!it H .Flagrtilg;Qeti ~heb and lHA~~g,e,d' RKSP3tJ: iMirV'!dk~I~d;.(A) a Elea ,0'1' IFI<lB!F'38 orlirusliillfufi·£tilliliulMed phasp~o:nJJilatioo. CeII~5;idlere Cl)I~lededi after Ibe~'ngl depmr,~ IOf seruP'l'i!:OO\~~~~1fOii 16 lilOm$: anL'il.,atM I with :tOOl tiM fin~wUI'II Iror 3!f!l1milil .. {B;~I rur&~:of: fK!EI!~.36 ,onQ1min:(l iad~rnl!'~mdl l~hQspl1tlrylaticf!. (i~~ 1I!'@r,eokcted i'!ft~r .b€ing (freprnroocf ,a!!'Ilinoaddsmrl hOOifend o
lfiig. 2,. lnihibitioo
J

~dI)9.e!i!(I~$1y ~,r,~~dl !~m~ ~.h~)!"W~Oi~!J!J!CI'J"i!i:d fromJ J.J~~~9lJ cell ~Ysat~,\!!!~idl.i1!!iltibodr"y 1!I!1!'WR aJf!.d t;). ac-ssayedlor activity tcw.ard r'~(liIiIbilil:ant 'G!5iI'~E-1BIi'1 [i11I!1ii'E! 1~fm!I1;Ce (*) or a'~2!~u)e H of the ma'i:(ailed f 'Vo whom wrr~~~IiI~Ii!U: $holil!ldb~ .ndtessed, tE·m~!I,~ ,a,geilllt!l. P1hO!ilillOi~la,tjonlwa,s: ,deteCilie!dl by fm,liIiIllIinQ~IilIMtil:l.:g I.t'l~lng :antitbod)f to p!nQ!SIPIn~IE·BtPl0'31f46)1,. ,il.!I!d qU(!~t!1:floo by dWMm(rtryJiUJO!i!'i thl!i@ll! i!i!d~~ndl!Hi!t ~~ri!iniN!tS (ttli~).' jOO!i@$U'Ij~r, eharm.pilit.edi.!

tliten~liH.!!JIbated wirthililTlinoilc:~:ds;hll[ 30 Illflin. Rillptlm,y('iml'~2rO aM) \!MIS ad:ded ter~fiI'li! imd~~ilted samp~e!i 30 mil'll Il:Dekl.~etheadctl~ionl of ilili'll!llill! clrr am~nHl,a.dd"l. ([) IEff,e!Ct of IrKIB:t?38 dep&etii:oml on mllORCl am:vUty, I'fIEIK293 ~~ll5li\1ll)rJl1; tfa:fls;~lElm,d wilt! RKBP3:8Fspoocific (l!a'"IiI'(l! .2) (lr'~o!'ib~~ (1oi!ii!1l) l1l) siRINA. Q!lI;s ~ litlll¥5tOO and li~ffi 60 litoors <I:nhi1ritll'tmo1lllisi"-emoo. l~eillld~(o1It:ed protefns. (right :pillrle:~~Jand their pho~lilQ~lai:ioo Uef!t: paRel$) were det-edoo byimmlumo~l.ol1]lliIg, (ID) ~1iI !Abo kin!al5e <l!!>5-i3iY' mTORC1. ·or

9'78

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()I''q

REPORTS
ofFKUP38" ,ijJ~lidl sYg~~!S ~!.h<it ra:pari;'iyclmi. ~uca1 i!t~<!'Ct wilhF'KBPJSandi ~t~Ol!-1i'ncrease ~~ ill. ArnP38il~1ib:~ed, kkl~l!Se ru:ttvny aflllTOJl 'hjlliit01ij!'actlvity 1~,Q~!l,!iHdmTOR:C] ilil a dos:e~~pcllrleilin llmfn.lI.erirn viilm, (Fig. 20 Coilmmma~recl,~llltkm :1lt.~lecldil{( .I?iKBP38 and :~g.SS]" and the ~~ool.Qfmaxinl iI11~jbitim~1 ~il.k:ldl wililil dte oOlinprmuH.'1i of: IwTlORC I, in· wa..q :sim:ularr !IO IUoal ioouooClitJ.y IUne FKElP12cl'ocIirn,gmTOR illOOl~ '!he G~ p~'-ima.!llld ~~or:; bul: :~OI ri('l!Q:J'. a !.!!lifIiq1!.l~ cCli~:'Ip(!n~l:n lm/lORO CJif capanuryci I~ OOtl~p~~1(. (Fi~.:m~ .A~!h.oughi ~pa~nycilll<1iJa'~~ ~;lid!flO ,~£fOOl (II!'! ki I~g~::l!cliv:ily {f1;s. 3A)1 wi'lidH1 ~~~~ UW'fiKBP3B l~ll1 a,r ~nTOR, it>ll!!~:l'!e!f~ed dlei!~hi'~iI:(I:ry effect niTORCI ~u'lr!{)1 !~roRC2. ]0 ad:$[I!or!.~he

is a !~egativ;e re,gula1or ,of mllORCl.

iy" '!ltiie ~.bQ<v;e rli!ld:~Ifi.~5 cl~O!ic~led.w

FKBr3S

a~a:~iOl1 or fKBP'")swilh

iJi:l1fOR:C~~~~

Rh~b asoocial.'I'S wid~ n~:m.Rl!I~m1!.l.~1~ a.i\e~.m~. (amilrlP mdq ~. I~El2:]9~.)1iliIa!I.O'\!'~D'la.~\wil.h %7 '~Im F.KB!PI.2~yom. bill.cl~'1,B(FM)do-lEun (a:nniln at::kt"l: 2'(1)15 Kl2114), (1,6) W~ I~~U,!O: ~bil~ty

Ill· oo~@'i.da!IOO by nulri~tro:!'td.OOIOl'iSj b~use :ijlie MSOOimiool1 was:~nc~. in oeUs d'ejmwCl of ailil~1l0~idl!;.

-lftis;.;mi'iOR ,(1007~'2.191~,

'............

GI;II' GlI'" G;()p G1VP ·CUi Rlwb RIIib W RlM:b fN.b

I~.. <I

tll~~jJ~a.~ianiOlf! WM !~ooi1lired dUlJl~!$b FIWP38. ludoodl, a l~o;lnb:iil1lIDl peJJ~idleoontaif~inil;lmuinC! a~Lrl~ H,1607to 2J 91 of mnTORinlCf'il;CllJlcl. dircctJ)y wid} F'KBP38ima. an ~!Ii1'!{~~ro,8I.'>S3:Y (Fig,. 3B~) 0tiJ, .. lil~fl ()idwrl~a11lcll,.mo dime I. inlr~.clion \~ di.:'j[~If\d bet:\~ 'RlliI~':9!U1d l~lIlIisfKl3:"P3S bLlWillilg (FJ(]3) oollmmll o:f mllOR (f~ &6)~D~l!~rOfl ;,trI<uysisof lFKBP'"38 fU,Qrtl!tefre",earOOJd1.~t ilsf'lKB~P.lC .domiiJ:lill. a rcgLon hi!JWy s~nlfLar 10 If:KBPI2. wms sllltT:~cil!nmfur mlUR bim:liing, whcch sngg.eslCd dila~. FIrBf'3Smay bind. wm1URina lJ1jl8ilill1er SlIm!! lUi t~, 'nhat of 1l.1fl IFKB'll.rap8![j)'YC~n. O(lJII1plL1X ,(fig,. S7n),. 10 ~upp:1J:t or d:lis, ,,\ilL:) Il;U,lirld! dial
dIlL:;FKBP ~2·.rnyclne(i!m,p~~e\II1'111!f!!~r@d.wililb FKBP3Bihr mTOR lbinding in vilro·(~S. S8)1 ruld. rnpamwcinrerlllloed tile ffiso:::im!lial of !fKBI?3,S, widllnTOR :llilcc'tlls '(fig. 3C). ncilill.CmcU.on. Gil' FKBP38 'w:Lnh. u~ FJm d dGJ:I'!I.aJiIi'I 0:1' m'TOR. <lI~~d ttl b('lffi,gt]~ruti1ld! b'y Rheb 1"1"1. !3!cmr~d~nt I:ru;,mrl~[. be~ dte iIDlH~m.c~fiilll,!;l~ !l!1l;;l!If~c~~d Id~~ \ lYy p~~~ of

__

,_lHi&-mm~1001:-2~'9Jl) eS,'I':.tFlKElPae:

--,_,
S IS

-oof IFig. 3. Control. of til:emllrat.tiOO batw.eem IFKIB'P38 and mTOR by IlTheb.. '(A)I AsliOdiiamn of ftcBl?38 vri!h IliIillITIRC1. IH~I<2i!J:;J: ,~~~~ weme d~rNM o!~il:rililirlO a(id~: tor:l hoolr anrlthminrubat,edWir~1iI amiJilo ,ad'l1!iiIm 301Ulilill!. ~.~~f~ p.!iOOp"ItlOO·watlii ii!n.1iioo~ym IFKe!P3a~:~~i:l!'ltrd 19:6'.ii!!i!,dlP:!'fldptM~~ t11~dfur tlile oom;"llilents of mliO:RCl ilnd mm.R.(2. (B,) Th.e R<B1P38 ~in;l;iilil~1 dOrmJallilmlil III1TOR. ~ombiJliant IHis;. IrnI"I'OR(19(r)l~1.91} IDr His-1m!:! d1OOl1am'of m'JiQR W3:S 'mcma,ted witlil IG$1CI: GSJ -fiKBP38fcUom lily

Gm?'"oolliud Rll.dJ 'OOl~)j,!Ol.S abolisllCd by~h.c pl'leSlof ~e srulle anIDUlill of urP~OOl!rnd .mlcb (fig. 3D). 111Ci dlssocitliolli of FKB!I?38 r:ro:nnd,K;
CROO

by IWlf~ci~Jta!o!ll. ith, gl~hioo!§: beads. ilih~Pf~o1W1itau:sw~~ tmmuooolokd fOlf GSi ~booom.la!ne11',GS,T~ w

<II

F.1:rn dQ:il.'iaif~o:fm'TOO.
~l~ bindin;gln

:Rhoo, winlch ~rocru

was also acoomj)3lJilioo

~lff!dt11l

~'K:BJ.l9;e ill'Iottollrl" lanes :2 .il'IliIa;3), Hi~"llrlTOR (:I.'967~1911'.ilaldl Hls-fRiB ,~qp, ItIrte'Sl. to 3) •. Asteri$k d\(!ru(rhl!~ ~neal>m:l(l,WIiII~redlmt ofRKBP3s:. (10 Eiifect of ra.p;!Im,ycil'l Ol7llilililE!~80ciall:itan .m' FKBP'.38 with mTOJiI. ,1H ~IC293 ,c@lls;~JJr€Sisililg bm~, myc"iiilii'OCllR.and HA"-,rK8;P3 a· VilB~~~md :w1'1ih20 IiIM tollpamyclfl 0aa1@~2arl~ 4) or drllJgve;~id.e (!BInes 1. iI rnd 3)hm:1 1001111".Ly.s;lle!Swere' pr,oo,itlted witlili Bll1itibOO(y IDIIIlIYC ei!limpE1. HlA-IFKIBP38 <lInd liI1Y'C'"i!1Imn [Iillilile preriplmtell ~re de~ecJtedll~·imml1lnllll~at;j1il9. (10) !:iifectOif Rtu~:b otlillhe ilill:erartiibn I!)f !FrKIBP38'wi.m mTOIt ~Cl'!!if'lblil1a:ilt HiIS<4rniWR(1967'~,2:!91) ~!1d IGST·FKBP38 vm~ f!il(!.d)J~ mg~ ~rin ~he .abselilce '~~aTIe 4) or ~5efl,~' '(Jf G.DP,&J<:iffed IHi~il.heb ~ne: S~ Ol~ G1P.IJlI~(jied llits~R:heb (lafie 6). Fol.I!awed by preCJ1pit-.moIilWI1~g~u,tlr:m~Dnebe'H~.Trhe peipita:te:s were imJifilllllllloblotted for 1G$1_ftQBIP38 'lib~b:mrd .• IHi~".m'W.RJ'19'~'7:"'_:U91) fuIp. b~IP'bands), g'l1!d His·l~heb (rop. I.~·ef Ib!1!!iI~>,

11!I"1~mclli.o11l 'wi' ..R:ii!mb~mt.i.lrJe:rod wilh fKBP]~ binding to rn1:0R B~ru;;:;e RD'ir;ib acl!iiv~y is regulaJed by ,groWlh. factor .ilK!, Illllm:elJ!:wmJ.tiolliS {(I. .17, l,{fl~ we c1'lamiru.x!: 'W~'»Z~ln,erlhcll cOl1IfCi~led t'MIC lm~~,~ l

IiQl~OOI.\¥OOIl,
3.

cn(!ogt1~.Q'~sfKPrP.3,S. faldmTOO

;UIII.

.grocwl:lllr.l!Jctor~ alldfQunri~lro-d~p!lim:rOOI.

ll'Dallif11(\i.

[f'ig. 4. Qlm~Ul'Igi~~a~fI

o:f R(IB~a

wit! mTOR '~Rh.ebilil 1~~llflse ttl, ~l1Illrn ~miml!tallim ,allldl ootriil!1~ a.va1labtffil;y;. HIBK291 M iOOUs W~ tra!i!s~doo vtitlll ~ontr(jQ ~,~ il'Ir ~1ile~liIdi,i3JtHIRheb mutams; anD inrulJl.ated :fa 2:41 hm.ll'li... '~I Effie« of <1mi'm ilddl m.n~ di,ti:Iln:5, oiii the i*racno!l of FK1W36wt11~ IliIiimA:. Ge'l~sw~, ,rne~1 cf a:millDiitOIds '[M) f'or 1 Il10111'' (:-l {ollowedl by lreMiditiom of' ·amlncn:n::ids. 'for :;1.(1In'D~iIiI {+'Ji. (B) lmliled Qf~~ruml~oiIfidiiitiO!l1S, (lrnitlt~~lIlt~fac'tiofl (!f WiKiB,f3::;t,with IIiIiI1rOR.. (eI.lI:s were !l~m.1IIlId'eIB, l~riv~ (O.5~lQ' ~rl!lii'l'!)for '16 I~OiI)Jr.s:.rol" l~ol!'lietil by' t,ii!d'tmmtMth 20~to serum for :03_, - + - + 30 loon ,(+): or no trieililIfllelilt 'HI. LysillIDes l~~~~~~~~ '(ilnpl!ft) Wl':!r,~ I':m~dpitatoo with glntiiro~.)I' tel ,~~!,!¥! qp' I FKJB!~3S. The: p.res~liI,oe: ,of ernltDg;etLOuS -~~-~ ~B~::;tp mfOR; ..i!lnd ootojic<lHy exp~eslioo Frl:hebil'1lthf! prec.lpiJtarte$Wtli$ deteotedl by. imllililliilcl::ilGitliJlig. lilIpu! .
1

ifIiIDb

'il!'~~IIi'·I:=::=========-..::

iiii--

.ni

FIm!P3:8 jiill~mdedl. wiill'D. ml"ORun. ceUsde~'i,I~. of <!..m.hID ~iQSi' @Jld d'le !n1~~~Q$! ·WM.~~ wl~] <1.!l1j!l{l.~ .~. ~ (Pi,g,4A). Ove!'" e1'lllm.(m of '!!.':ll!rJ,4ype ,ru,lcb also rccIuced,dtc h~iemctLon ·(If fli:::UP3S with IillTOlt in cellsdepriwcllof .8!m.llill"lOacids, and lim ~t:il:m.cli{lllli "I!i';t1S ftfii'i.h~r dilwin.i.$hecl wh~m.a.l11l.1~OO add..!;;were re!<loood AOOO!llJ'i[llUlyi11lgdlCa.rflll~np .a.c,ld~indn'C(M.!. ~~e .~i1. i.il~ il!lle~IiQ!ii.Qff'KB.P~lil wttijj !T!iJTORwars alii h~e~ !!II the biliidiing ofrulie'o with FKBPJ8, which suggested IhalR:he'b ~,~ velblied .FKIIP.38rro:~ul}:il'l'din,g to n~TOIl in re", SPOi~se 1~.>u,runiill"lOoold ,~8!i~miHl:ll. .R~~h i:nll!ltanl", .• il1Jlch.l.d:iiii~ imacli'illL'! 9nc:t~, Q64.l~ in. whicl1. llDucilifl~ifG.;1l!looi}(> ililiJitamiiUiii~ ill

""

.. +.

_fli{Elpa;jI

-Is~
iIIi"ITOR:
R1a,£I:-Rrn!!!'1i:I1

residue M~ ~h,'i,1Q i!~6ve!line~r.lS. SJOIN m1d DOOK (in \?;!!ilicit a5parngiue rep~aces serine· al

:=========:::;;~P'ilEi mTOiiil
i-_".;:::;..,;::;;...._'!"'""_~;.,;:~;;;.,,;;?
f;!i'!g>ft!ldC,

residue .20 and Iysu~e is subs1iill!:!~ f'Oraspartk: acta. art residue 60~ !Ire defocl:iw for- it'!1lClealid'e hillldiiuiIil. Wht01~ nm.d(MSd~(l: 'i'nltil:alll!> .~ru:gel:yU~lilltm£i~i.!ii\~ du~ GAP':lI.Cl:vV!ily oOif~llile SCUl'SC2 to T ,000j~P:]IlN (J9,.JO}.h1 c«ll~ ,~'pres~rirlg 1!11~ Q64.t ml!laIIr~, IUlei!lternc~iom 0$1<0.1'138 W'iIth.mTOR. w.as 'oo!'li~y de!oolable, fegarolcss ·(lfllle O\'VOlnwiH~y

979'

REPORTS
ijlf;m:'!:iwio ~cidt5'. wl~'l m:he i!.II~liQiI!. gfd~ gj[~ p~d: Rlleb !'!~b!at widi FKBP38 Wars slroJ,g {F'i~, 4A !lnd iIii~. $9). ~il~ tilis, the 'latle1iilltt:r~
3.cIi.Oii'l Wrul

.. ,- . ~... 'pre..'lS_Q~

,mrtiian:~ sc6t~'iie to OOillin.o, oo1d:£tarvi!i~

W[tI'l

IniOJ~, ooiiisi~ill

{1,poo.1!Qw lfii1dii:lg

IIMlt the

Q64Lrn1tl~ru1t [L'ta:jm'l~ a.II1i!.~;rudlil..~IPO:M~ d'le:GAt to. ~.eliviry Qf 1l~L'!l Tscm rrSC2 00l1.1p~ (..lljolLfn comI!m.~ i!!1 iC~11s~~;I~S lfih~ SZON m!!dat11,iiRl!e Rll~,~wa5 bo!.l~d ~o FKBP3B·,. af:l\l. tile :il!1remcHO!~ (!I,r f1K8:P18MtI~, l'b"IIDJl 'W!IS sln:mg end Im:gely llIlse'iIilSitiveto eham'lg,esin amjlrlo acid, ooltditlons:. TIl~oo!liel'VRti.oru'l ind.icate 11m( 1~1\"e!I(l Rhe'b

prev.e:I'I!OO by ~rul'iil~p1etiQi1 QrOVe.~f\\t'I.li.t····· . Ell -i~. llfi 4~:)· S'._Wl_iM!}'. if, "b.:i Q...L~ ¥i'C' li'i._Qe~ \._8\Il:!I" ove£C->lptre.»sioJil.of acU·ve, Rh~ mllIan.~. (Q64I:..) Of i!li1active Rhe"1i:ImllLtan]S; !CS20N ~nd ])601<) tro11· d.er:o::! Illileii.ttCii'aCliOifl of fKIlP38 with m"[OR. ilib<;i1!mritiv!l to dtan~ in :Sb'i:'llfil OOG1t1J~lio:M.\vMch Si!I~ lih,t liliiL'iil!:r~~oil! \va"lI14'gMh'!'oo Illy ~b in 1~I~ro ~1tl!t:I ,oonditi{ii!l~ U!e abi.lity oooo~dI! and ~!lhibit mTOR.acLivily in file OOSC1'Ce of:r.1P1l.lil]~lll cstJl'i~ishes FKIlP38 as on ald.QgCnms imlhibi[m of mliORLlnd:cr mni·

~,. A. Gararr.n o!IJ' mI,. Nl~l. C:i!l'l :n, 14!i,' (2]003). 7, It loolti. )f" u T. Xu, It:' L. (i!1l1I1), !1Ir!1Ie'~ ikr,. ::I!1, 1829 (~rllJ.!w, 51 57'8 Qj)OI~, ~, "'.~, Mp!!l'!!I, E T~~I"!~~ (~~. 5)9~ 16, UI;G, (:211)04)_ :Hi\ fie, i!L ,MMm~mg. IL. (_ (.aill~~, l'rmdl: il'Jorliem, ScJ_ ;l,Il. $~~ ~2:00.3J, fl. y,. U,M. N, (lIflrillltlt1, lK. iMkL IK. t GlJall,rf~di: i1i.rxlie;n, Si:i. ,29" ,B-2: ;'l:004l ~ G.l'i~l!er. T. VI'3t!I~r. r; larl1t. f.f.ElS lett, ,~26.U ~l 99B1. :n. Fc. t:clli(!il el aL ~I,I'OJ,. ~!4.2&1a, (~()Q5.l ll<l,. M_ '5~~lr~,roe,1(. l Nl<!byiHI1:a, I'/.(JI,. Cell ~fQl_ !l\, ~a:~(lO~L as, M~t~;j~~l!lld IrIi!rttHl!I!! ~OO' ~"all~D'ti! .~~ !lljJj»J1:iil:~ m:aterial en 5!ltMO!! Omll:rl~ ]6,. )!" i1i~g, Y,.lI~l,~, Ort~!,fl!ga,. ~. )f.ill!i@.~io7i2i, ~ A!ilIK~. IGtN.fIIDJ, ~S. 7~ Gl:QOS~. :l?" ;(" lQmq,~, Orii1,c,Vif(l~, ¥. ~io" ],i1/m.!dD" i" .8iQJ, (ilr,f[f.Il, 2:60.. 234n (20.051 ~a,.Ill. 1OOli;ii:iQ, J. l. ~~, F. J. ~Wilrlllnvit .(},rI.~~ :!:!5\ 65 7 (2006). 'li 9', ]!I•. P.. liaDanull'~Jr, tl 01_, j: B.YJt Uledi. 27e, :li!~1121
U" (:2003)_ 2:11 y,. U, K.. In!lnl. 1(, l ISrnJt MtlA ,('iIlll. B:i'ilt :M,,~96:; (2(J()4.). F:, Edlicill ft oJ.,}. BI"ilt ~ffl. :21li:ai, :1.4%1. I[;!Oill6l. ~:2" W·~tba~~ I<. f\la!0""~mlill. ..'iI.. GWIl\, F. Jilrn,mill~ t;: N. 'S>!lf!enlb!:1lI> ~IMI ~, [1i!~llliw p1ltiIDiitt ~!I!i! re~QeIIll~; !!)- A!~Iru!!l!~F rQf$Y~~l~n~,!!'!d );'.Ii!!H~lll!t~~ l!'!F,tDtiC.al pea;iii mg I)l'tlfIi~l!1amJliC~,. Su pJ!'!lnt!!I boj g~~nt~U, YJl. trflm tlii!! ll'5;. n~jj~rlm;~i\t 'm~ [l1i!J1~ii!:~ (Il'i'SlX!i\ltll·OO.l.ooQ:I',I <l1Ii! W 'il'J. '~Fmlifl 1W!!!t1Gi1i (1!In!r,~r s:ud~Ly ~1l:;:(l.<O]":iIl9-,,'rIM) ~I1dl N i Ii (GM().Il8:e.~2').

a '1', .ZIil~[)~1et uL..~1.

t200Jt

Mock dl'41l ,a1fl:ri11'1}~lci~peJtode:l~I. r~l1ibUi(lllC)f ill$ il~'f3()ni{l1li br.'iWOO.l!l FKBP'38!liJ]~ ~f[OR, wliWh :Sll!~~ tHalll 1I1l1:iwlo acid oom~.11M!3[tr,.'l

no aeid er .serum, :!l;tar\I'i'itii(m tlrl~s·m,TOR iillhdiblito. 1OO1lil~d.ilil1'41lffen::s wilih.I'IlTORC n .~ITiL!nctkm iml.:l 1t1.'lIm(~J ~~Iill;hu't{D' Ill,:,"tt. (lf~Iil~FlKBP] 2i"r.1{p:3!Hl,ycin
oon1ple.'I(
a-

dirm!il's:

control l~heil'U.~racdQl!~

:~nllQ~ ll:uilJ!J.I~ PJ1Cb., '1Ii11L': c'lfoC"i

·or FKBP:38

I[J~l00;

roWUw~

:fiC.t\lr:sC)f~TiI!i!ilo

"WiIU~

acid avai~~b;lNlYr Rlleb, p:"-""Vol'tiLil: IlillIe imU~c(i(l,1,!

of FKBP.3 8.\!Vi~nlmTOR.i~
llilllHl'lCf;

aGT.Podcpellldl::m

of DOOK 011 dlCimllcmctiOl1 of FKBPl8. wilhmIDR was !iulnil~ ~t o.f S21QN. I~O HQ'"~vilr~ d~iru: lIS failrulm 1.0 bind IrueliWl!d-e
and .a.lQI\;v (lX:PII~i.OIil ~Cvtl~.(J 9)1 Ihl:): D60K ml,iI!m:t~in:t·eraot,6dwiU~ FKBP] 8, 11U.ore ~ifil(Jllgly 'l.luaI~ dicll\\~.~d·lyl)eRheb, <lim theilHmCli(m was i nsenstil'i'YIi::to dllmJ:ges in ~m~no acidlcmtditions. 1iIlis, observ,attOl,~~OOc:us:d~mdl~ Asp to lys (DI I!;oK)I suhsili~lIIti:olTh t posiit~m~ GO oQn~ to W~cb a a ~i.~1]lN affitnuty for FKBP"3:8 1tJU'~. ~.n~~ lIS aClliO:lilto I~ mTOR flll,ilm FKB:P3it faCl l~h1I1LIlt;;; DOOR:. :rI1l,jj!~t bil~& 8<1:E'(!1It;g'Y fKElP38 I~O Ibu~,-does nO( disp:1ace i.t:lmm nlIDR i.~llemctiQl~

'~~~i.dh.lcadslo

[1lI1ID1tC a(]tivilli.orn.. I.

'dlc .ac"llioo ofRffilCib on IlJil'OR is OOfiL.o;i~;'um~ ith ~vidLWIoo Iftiia:~.aclilve Rlwb w ,~i:.~ l~~ wilb mTO'R Itl~3I~ doosdle; ~n:1CIi'!,!L':l fornn (6). ln ;ldditi~1:lJ tl)~fllORjIl'K!E3;P38 :~~ "W~jbBcI~2 llnd G!lcinoorin (14,. 21), Ii! is d]1.IS posSib~e I~bmRhein' ulo1yili!50colurol BCt·2dqioem:le~ op!JptiOsismd: ~:ru!cim::ucilll.(t~t1 'IroDlscr.i:1J)u.ma, throughl FIrnP3,S.
1f!I{iI!!refl~@!O (2:000),

lltili; IIlmmlli.'>Ialftl1r'

zr,

n~

;amid Nmll'.i

Sglll'~lrti!!!lI1 Ornl~i!!J!!fII!!~ril"l
Wli,]h'I',!i~i~.r.l:.!!ma®,~~~~o~nell",ruW3,l~!S.~,~971jllJ(l Malami'll.!; ~I\d ,MEtliO;ili~, frlJ~.5:1 l!!I ~~ i(;~r@r@rnc~s, s 1rnl'l' 201l1l'~ .:ttil~p1J!!d ]!A Si!p1.lJ!lfiilbi!'1 .m!!l1 liJ.1l26MJ8~(!' lU ~.3:'),9

1. I). IE .M~nim. ,M. N. Hall, Curt. G,pm. C'rll i!lilJj.,. III,1:5;8 •

suggeau> dmt l1lIe t)andlf~g of F.KBPJ8 wD ma.e'b 3.l1.dd1Ql wilJ~ mIDR. ru:e 1il00~1ULI:JiI<lIl,y ~tmi.ve.;, (J~ls d-epuiwdofooltiiinl also ~l,'001 t~reao;;cd 1l1IUlllaoetlOIil, IbeI~WCml.FK:BPj;!l; <1!flid. m"f"0.R lhat

2. :5. W~I\.\j()ll!Iev-r. ~, lQe":<\Ii~" ~, NI. ~Il. (ell :J2.:4. ,4l1,

(OOii!Q).

3- Il~~'lih

~l

<'il,. Mal, (~N'J@, ilfi7 (OO~).,

~. R H~f'"~ ai", Ce.1I ott

s,

P_ IHI.i{im ~~ .t:lJ" Wl

no, U7 (2002~" no, ::11'13 (2()!lI2).

:Ma,gIn eti cR eson ance S plelc:troscolPV :Ident:iifie:s; INeulral1 IPlrlollgelniilor C:ell:sl in the Lii·ve Hlumian Brain
ILouis N. M.ilIIilWlUS, !!.~XllIIe1J!1ililg Zhallil§l,:t 1t'oilil)i !LV RiI plilael~, D. Hialz.@~:lUi! S'" 1il000wd5mitlil. IMi'I~kE.W\CIQlS-hull}' IFriltz. H~Ii'IIn..~ liiellene 18elil~einri5lie.,.;l!'~Petalr M. Dli,-,Iriic,:'i' '(},lriigl@rii Emiko~iO'PO~,.~"' IM'i~IIIIHI M!areti,6-Sav ... tiC:U~
:i!

W~iflliiftcali(Jn and ~ki.m1gurn. vivo" CI,J!~i.)~ ~ l!tmnc~uissiQn, :~Ol.l~og~11Y, stngl~llOto:lil ~o:lH"'

Plll~ed, liOl,uogrn(phy :scamn:i,llI,g, mId IW3,!lJIlCt[c I:c.ooml!tll}¢ JnllI,g,i!llg (Mml;[) flore bein~ ,e.."ifillili!lloo,

lI'heid~li!tilkaJtion 'of 1l~!,!Iirral.$'~el:ll.allildlprrog€li!lioor 'cells (.NPU]I by iii! .~

i~part~iilt im.~U:"!lt!1c!fll:5 fo(r dia~Ii!O's<ti~"liIJLi:lglli!~s!tk• iJlJildtth~ra~~l!lftic .
1!!Im:! IPNJWUI IiIlJdelllW Illlllgllletk Iff-Sonoma:! :S[l!lecIrOiSmpy

brgi!il

imaging could I~!l\le

~,,·hfadves.imd !1l~©rt;rgre ,,_r.r; ~1O!tO1ppHecliror Ull; dctec~io:J:l {lfe~ooge!l.o"!J.IsNrcs: J~:l theh,tl!l1mm braln, 'VC~~dll,no1Dn, nl~),cl·l.c r,coormn~e ~.~ Oro'.'OOpy {I H~MRS)I to O''i,II~rQ(mlO lite abo'\'lll~nl~~,~ tiolilli1and WdCloot NPQ-;im.~l~leUv.o ~l1i111a111 brain.
PfI)tOrl llIIIi.d~ mEl!£lfneli(llllliSo:!l:1tlllce ~~coo.&., ¢Off)' (iIH~NM~)I.~;; ~I:I wid~!.y I;ll~ f4l!r;11I

i:owam~\isgoo~{5-i}, 'Illaeiril tCltliB1lQllogies~ulre l'>.!'fCs: to ~,prul~&d. ex viv()i with lf3.dJoc:!hl~led ~gi;nts or ~p~l]ll!lRlllfil'li£nd!~ ImI1l oxidI~-ba5e<1

We d~crib~ a IIfIII etaJbol.!c biomCirker fuof the: deteWlo.!Ii l! ~dl QU!!liltifU(,lItk~1lI of NPCs. ~~ the Ihum.Mi1 bfiil]l1Iin vI,vo. We
pYmj!li~S~'s..

00 idelilmfyalfld charaa:eli1iii:e ,a biolllilarkerin wi~khl NPCs (Ire !enrr~d1ed and Ide:m1o.n.straredl its U5ie:fI_5: iI. r1ffi;l'!'rleme' for mOlilitor1ln~ neulmgenesiiis:.. Io de:ted ~CJII'I! mmentirril,tiOI'l) of NPGi illil 'Vivo, 'we de'!le~oped a .r.ign.1Il pmces&il:JlQi meth,od th!iI1:. en[lti~.led ~1iIf1 1iliS.~ G),f magliletic rf'.!l'lln.ilIIilCe spectmf5G!.C'lPJ forr ~h,e alil'..I~~n~ om ~he INIP( blol!n'.illrker 11'11ath the b Imdeililt bTainlalildllifil!~ hiilPpocallil1iPllliS OI~ ilive 1:i11!li1ilil1il1ii5. (J!ur fnlfldift!J5 thlil:S OI~i!I ttlil~IIJ)Q!5csilbility lof 'illillll€:~tigalri"'~tb~ 'millE!o:f' N Pls gllild lliIl~lJmg~n~$l~ iii! ,;11 Md~ va~i~tyllif hJ!jliflanl brr,aiin dl~ordter~

vilro d~~~t!tg'l (D!rl(D~l!.,~]~1tI1'!ti~ fblo"WlThnl~~1lQ olites ,<ll1idi the id£liIilifk.dim!l .of Im].;!io"'~'Ull (lcml'" pGU1fN.iS:p.m.sel1lin !body fluidlS mt rtiSSIlIe!>LI1 vlW
(8).'H':NMR crnatdcmHIY'~nelaoo.~i~esdfial .~ s~ci flo for m(Tl!.iMillJi [such as N~.oeinY~.9SIP~ate (N.AA)] or g;Ha [such iL~ lel\ifi~i"C1: {C&a.o) :.md. iTI!yoin.ooilno:l {I~.I)],al~dllt~~ 'OOI1~l!.iiw.~ha!'$

~e.OOU1U IlUMlW.1iI1i1. l.i!m ~.]. lin .t<l. I!;S ~~e.!lb.·.H~ l)'pes, The abLlily ·of NPCs to J'lrodL~e lte~, ..' r.:I. a~. mod, li.godenrlrocyte-sin, vii[J'OMldi in d nylrl gct1.Gr3le "I~W "ll!.IDrol'b.'l, 11~ U~uroIlS are' ~r:odwcM m",I) 1~(Ii!lr:,ll!l.tCm, and pmv:i.voi'aii%'S iIiIlc prospoc'll of: Ill'lliil~~Jj~g 'dl£m. to gmrl~J.orc.c~!ls(NPc...). \\''lli1nd~ m.~id2i1~1~~~ hiwon£'IPaI; n.crve 'li!>goodlai~.ocI. 0$ !n,'i~.IOnrum~Dgj.cai campill['!:alldilm KI,lb':\I"@nmrula:ii.:lDtne(J-4}l\.iiPOl .di~".~ .00' 1I:m'"i!ll.t~a U. 2t4Jn~ 1i'e3~.i2a;liO:i1I Qf dlu,',l ~~~ d~e abi~ity LO s~l:f-renew;;l;lfldl also I~O c~r;aGive ~H1i<'!1 ·ofNP'Cs wooil!d b~~fllrm~l a!~ ge!l!ernoo 11~OOy I!~a;~ ~l gi.v.e ri..se 00 !'lmJM!re ceU de".c~"melu I;)f m~ll!oos: lhat \:l:ooldl ermb.1e I!le~r
reo

-;~. T

bGe:rn! UR~d

3.~ ~Habl~

IiL(l!Ii~

(Df !!he .~

~SU MIl S~!!Iln)' Illtlook.5rolll~ H!iroOO~~N'l' 1.17'911, tlS/t ·IlFOO~;r'l@n ha!f~n\ll. l.ilOOra~(H)', Upton. N'{ lilJ~191. U 5J!" "3C,dldl Spri~ Harbor lalJiIlfJl~ Cald ~il"i[i lH<lr"bOr;. NIl(

J1.l{~", USA. ~T!J' whl!Uil ·~(lrFeifJmJjIWl~El ~moul~di be OIllId'rrned. ['liIIlail: en]k~Off.S::lhted~(G.EJ; lfIlrn~ li:liC"l<l,Y~@ifi!Q~es.I!I.~!~r~b, ed!u, diu\. , ).

'9'80

9 NOVEMBER .2007

VOL 318

SCIIENCE. WII\lW.sdenaemag,,()1'9

REPORTS
c~l il~ .~iJi.~SQ!~I~d ~'ro~ ~pt~ Howe~,'H~NMR COi!~no1 0 ~800 ~CI .mal~ 0 rnenalOOliles iIl1.lhrc O~lMflisms.; itllS~e.1.d!,iilS oo:~ lillie,. ·~H~MRS. 1JS(i(l to pro'!,1~deinrm:iiuniiln. is aool1~,idlJ.'l; ibilcmoolnc: .slmlls:of a ti.~t1e in vivo (9)1 n~ two IOC~lIn.l.ql~~Scnr.lllpl~m~IT~.~.ch, · oll.ter wh¢l'l :pI.W.~!()~ical (}rpalh{li1ogica~ ~ :!i:~
~!tdit:ig

i!lV'~~led (if lZ). Th~. ~ d~i.dOO to ~~h ~. ··Nru">· i:li c ·1;;'''' ·I;.--!it·, US_.i[~IIC!I_"''1M.·1!l!-l1id'~Of_ J-'-'~ec _.,,..,a._JY__e8 ,g n p. _ ..Ii'. <1_. dlCUI tfll,exp:loil Ibe ~~~fo"'I'I<!ili{m oooul dlese ItlIl'lillIlxilite!l for delec.tiwag; ~WCS ~n ~he live btnlin ustlng IH~Ml:S. To kl-Gn~ify tnnlql!ll'l r~h'n):;)lurn. thil: !>ipeo· Ir~{l!p:uc fr-cJ!fil~ of NPO;;\;.,,~ (:(lI11p.lU'oo Ilih~
c_

IB

with Idae SPOOIrn oif oollmo:1 iUlellMns.~yles, and .Qt~gOO.elldrocyt.'fS (~ lA.). iII11e NPC ~emra a:G:m,OOInrated. [IJ lILIi~{qlli'lipmiti,l~, IilCluJ:dill;g_8i If!iD:lil~ i!il(ti1ll pe:.ak .. IM. Ih~ f~ll.tm.cy {l!f L2B [ilillt~ ~. mini(il~(~pl.tiI)~wlliii~h\''i.I!b~ It\iilO'OS~L~d ilil onh.~ !t~l cell lr~ (Fis:.~.A)I, QI!!<lH.~ificali:o!.]Cif Ihe seil"Cled 8i~~ <Implitu'tie cO!r!~!TI1edl!i!al'NPU wem stron~ly cm.i.ched h~1'~jbe ].2~pml hio" m:arl«:.'II: S00Jl'iI Pl1I'rod 10 oUter cell. l,pes,\\!il1ereas, 8 as C';:(,pectcdl, M (2.1l~ p,P-ltnl) was :pmmUiilila1ill N
1

U.fJ·-NMIt ~ ~rNpc~liion~'eiJ1ib~illic ~'!:)ou.'SC bJ'aWi t~'m!e 'Cill~tt'l,l<J!!ed~.!W-fOsP~~~ iii vilt:Q (13)

m.i1ellmi:b" ::U1dCllO O.22p;p,llfiI) ii~ a.~,.1llil (F~g, 18). SnilliU ::UI~nts ·t'J;f NAt\. !lW ('11,(1. '\\L:;~:;II~
O~\5~¥,!<,~.d ill NrC's, mQsl~~~~yrot~~uli!~dt¢ p~~nee Qf!lel!OOr!~ ~l!~dI.a.,;;lroCYC~OIlI!1I1iilledi p.m,gcnilcm;ill tlte I~Cl!IlIiO:f>phere!'l.Tilile 1.'28:"pPIll1 b.iO:lill'BII'li:iCIi'·was dl;:tcctoo, to 9, lesser deg:n:.'C, in our oligoolm.df!Oq)'ll!l propacmiOOl.pcril9.(lS dille to d,1e

~I

QW~g)CIdam;l~y:tas

~~A~ I,,,:JN .
.,.
.

NAA

• ,

~:

pr¢s~ncl1: of ol.~gOOlmdmc:ytt:l progl1linjtor cells {OfCs;. also ~~ IFrg, ID) wi!d~Llll 1lI~L:; :pt'iltrna:ly ~lIi~t~~ aHM~oo, n~ .amp~i·lJ;td(l,of;b1ml.28:-;~p:m Sligllah:m !.'he iH~I"~tI.'m~b .. ,!!!!a,\; propm11onill. rro I!~e w1lIloor of NPCsIru:c'nfti:r~11liiysjs (F~ ~. C)i

j
,

dlis: lillleru:'oon:eliat1.(m il'l'liicared, dla( it is p!1I85ib:I£~rto qJJmnt~~IJ(h,t:iya(!OOltnl for 1NlP'Cs. based em tbe 3mmUl~of;[Jm ],2&"'\Ppnl I.H-NMR sUgimt To fOOll~~amll'lC: Ule sp~lIiC:lty ofdle ~. ,2H\v:tij~ the ~!lOllics oiF embryo:n~c stem. ,oe1ls (ESCs) .. CQ1]S .of the :I!rur follid.e>--deriv(l(l spheme rulut1'e5 (SiPCS]1 (l4).QfCs, am,d. ol.lmrlypcs Oif cells (hal llfiIay be Pi'l...~IU~iiI . 1I1f1(,; bmL1iI, such as maoopllIag.~'i~ fi}'m,pilooylm;, arn.d.mucrogJj3. 1]~iIli ~.i.:8-p,Pl'lIl. biomllrker l~~ , ~C){'lt~ 1.1111 'ES:C~, :SPCs, ain:dl OPO.a~. !.'l]gf1iflcanily lower levels Il~ III the NPC-sru)d. W.\l.5 Incru:' or bc-!o~",' Ih!;;: de~!ilCliQn~iI~l~1 ind;l.C re.sljl'll.iJ, n~roEo'IJBgcs, T b~l~llJ:OOcyICSi,fIIl(l :Il~kmg~ lie (F'lg..IQ.), .\\!'e' a~s:opcrfiQ[ll1,OO expi.:.1i~uenl'i \V,illl {llll~twOO i:l¢U!l'Q~lLllJi'CS dLliJi""OO.f'l:\.1ul'lbrainsaf
imal!Lsgl,lnic mioo eNjfn...")S1uggmllln, ff1u(!~a(l>l1l1 protdn (Off) !JJm;~llr d!~c~f!lrol of I~esli!~ .g~1lll r RPll1l bL(liHljUIkct, ..~~ o(l~d OJUSO(lJplC p!U.fi~e o;F N1Pcs
Ith~IH-"'~MR $poc~

~' ,

~!_-~,~,

.
151

..

\1" .. '~~15ail

R~~ '1
0,1<1

+. 1~
.~ ,I)

0" ... -...,...·

Il'

CI.g

....... Q"~

....... 'i!1iI5

...... --.--

~~~

rOl' INlP!!: ,1~1(111'

re,gYi!aro !)' elemcars U.3).N~dn~GfiP !lWI'Qspl~~1iWW~ disooci~lcd ~md cel'ls we~ oorl.ed. om iI~e basis ·of OW !.';~lPressr.ol~I,e-ve!]s by :lllCflIlS @f I1l!loruscc~"aetiiv~loooG~1 sommg{~ig" 8:1)" N'.Ii'C:l

ernrichcdO;-W-eN@IL.:'%i!ll!,

o~n pOpt~:l3.rimil.~ C(Ul-

IF'ig. L :uJi:e-l.2:a·pplllll,b~om:ameN' idel!itiimes NIPCs. (A.) :Spmflil~ P[O~:~e:s of (lJI:hoodlU!ilI!:a~ (;e~litWe;:N PO,. 11iI,~-uro~oIig,[uf.fln:droqrle:s;. i'ilndlillsll!it'i~. 1]'().lltedllin~!'loo:t:llii!e~ne 1.28-ppm Nf'(peak,. NAA (;:um12 PPIiIiI) . • GI!lld One 1(:1.23 R~m)\ l\ioolM!:~alli$ dimom Lact~ d~!Jj'~l@1S (JU3: IWn:lt51~W'a i'!~~ not of @q,UilJ~cal~. ~B) 8:i1Irg~liDh!i.!ilow '~Wll1itific:lrtioo of Itue1.28-:IJPrnJ ~iorlil\i!.rb!r (Jt;op.t NAA (lniddle},i! ru:l Cho '~~QtmDm'I (2 ..5 :x l:O~ ~e~isear:h, iI'l ::: 3 e.BmiiUlilel1lt::'l ~Brr gm:IlIPi. Idooein mp~'icaJ~ .5ii!lirilllp~e:§ err eJo:lPrimBl'lt) .. fSI, liIeurolil"l" 0,. ~

btlll00hi.!PJlII$m' l~L'l of IIt~ ]~28:ilpm billmmr d,1<l:!li (:ifP"!'IepJve~l~ did (flg,Sl). T~«h~f:i lJ~ese eJ;peri~l~W~S iWldtwle U'!!olt lJ~eilil'orcetl!s of dil'-elienl origin. {bul: caol~ wiill ~UIDJ ~(lllia!) clollnessdlel .2:3"W1il hio:rl~mk.er. d'Wlt amollg nile: panL;\1 oftestOO oens, NPO;IIft\r(l; the Ihj!1lh~~. le~!cl. of dIe biO:ilJ~dmr; ami. Ih~ m~i.h~'lit~mioollic di~f[\]'i,lfijlia!~l:,{:!'roll.. [lor ee~1s wilihol!it. ~rogel~iti;)r

pmpert~ ~pl1l..~ i1Ilelbicunuk.cr.

[f
1.1!1il!

cells, Ihe Q~l~cd~dro~S" A; ~~:es. (C) Quaiiuifi:catlon W@ L2S.PlJm hiomruk~r sh~$, (aITfLatio,1I! l1~~h@ OO!.rei,<Ji!es with IU~,epro.genjik)'r ,sl<l:!. levels oflliis bionm.rkcr should. deCli'e!l5e as cells llilumoor of Nfl\C"i .Mldlth.e l.28-iPpm s~gn\i!l \i!mpL~tmf~ ,(n;; .~ e~perrirn11l1'l~per datil palm. don~ itllllIiipti;rnte S.al'll1ipl.e5 er e.xperimen:~I. I~D) ijU<lITftiiflcaliJ1on ,m: the 1,,281Pprilil biorna rker iilil pfolijiferating cells: NP(:s,.. ~$C~. di tll.'mil~ia1~in, vitro orin 'vlV'01whCili.'lru,~ du::. ]£;\'1.-:-1.s: p dJillcreiil.~i~'tI OL'lII~shoulld. $P(s. OflCs.•.~~'~rop$lag~;(!W!»,. T Iyn\~hQ*.~ ('Ii(),"i1!~d1 m,kl!'(lg~ia(l!!!!~') ~:1x:llf ~ch,.~ ""•. ~)l[1i1~riments of I!he hiorrrualitems ~ iiliCma!\~,WG eUlMuvi:l!IOO rn.~i!i:m[\pl.\o£'lm!~I:m.d~r 1i!i1!!F r,oilip,. (io:lfie ililm,~]e.alte Siiliil'ii~k!'5p;er expmrnJi!fit) •. FocatlfigllrSs,qwmific.atirDiiii g ilWiiS dCilfie wiIti fhi:! coruJ.iliofi~ IU~,;li1 :!lro~]O<t.e:th.cJr nCl!!oo!f!aJl ~. S.!lIl·U!l[l]ernllllliletl1o~ bar g,~alp~~fE!iWlres!e1'1ll: lit ::1= •. S~M; "', .1'1' -e 10,0.5; ....., P -e mea 1; -, .P' <: O,O[lI]L Deta.i[:ed asl:roc)'t[(;d~ ~nii<i!ftm] llHd <lJ~l;!P'&dIilllei!1'1H:_ l ~tWsu1;(S ~~ ~ro'VildMi!:! the S:l)llPportirli~~:II!IiW!,~ l~amri!QL

~ir

p.rese~lce

or IDle 128~ppm b:lom~r or

or

no

REPORTS
SilIPi~ by .;l. d~f~"S¢ i!~ L28·Wii1 ¥1!1i~~ tll!;l a!iiip~iludewhen !~~l~\~ lhiealecli wid.l ooruilmin,a'lll ~j:lllihitorof f.j].lmy acid syutIJ~C5is 'I?'i~,. nUI!~er C~C! inareasedl alFler seNcm'~~s ofmj,~.~ 2:£),'1-0, ml1h€teX!l"l~;llilae wh.etltcr tile ~.2S'fl,lliln d . l~i,!{91iQ:i1fi.!} 21\.). We itCi1U oom~arod Idu:, SflOO~iI".1 rumrll:1lrKCr clOm:ailk'> lip~!dls,. W~ anaily:zecli IIDlu.'l { (I,f ullJ3 i~(lhilwdJ fm~:~ the ltlnJlJ'I!I!l,~ hm~n 1'I.t IH-NMR :~cU13of N'PC~ ®xtmct:e:dJwll1la ~nIJliryolili.c d,1!j' W (E] 2'). wlmn IlfI~l)JI'l)~1Ti~i'i 2; Cil!ilo:rti!r~!~l181f16ln1~U,lJ'ie, 111¢1,28·wrn lD~o· was n~!linl,Y~~lllt iu tlle cl:ll~~nn Ii;!~i'!c", mId :U ~~ daJ' (P30),wJ1~!i! 1tIO~1 Il~ (lj,f Ihe cells in libe brain l~aV'e III!)eadll dif~ fcn:mliatcciL Tltc l~~s onl~e ] .,:2~ipan b:L:i:nnmrlmT A. 'were sf(gll!~fiillm.tly rern!l.coo, whcIl'l.ms IdlC h:vcls of biOlimLlitms of rlilfcrenti8ro~ eaHs 'W"Cre slwn~l1~ C3linly cl~vallW, in d:i~p!Mnnill.a~ adult IDf:lIifl, as ClO~1IOO to llul): ~n:II;u1l(lniebrail~ (Pill.. B). Z ~. lliliXl ()Il(al1~iJn~ vJill~~ n~~~e,lic ~ gi~ts (If di!e <adll!~t brnil!l!~ C"!mcl~i~ !~e· L28~ ~lMR~~ti!<!.. "ill1.l,e levels o·f (he ~ .2B··j}pm biaJrtl~er ~~, "ii1!'he~ Oie 1C\reils (lif ll~ i~'etllImUl'L]l)ion.l!l:rk.er NAA and~:ytic bio(F'~g.2G).htdood,

specific fR~lyOCoidspoolll'a, mostCiosel)! wHlhdJ.e speClm ·of salllm.tecli :fill1llyaclds (S.FAs), wc1~ as.

hotio:!l, \l\lh!i.cl~ i5 ~~]\le ·ofa lii!id !~~ttiooUte it o~rer~l)ppoo\'\"U~ wnie ofdw

so

Pffi,lttlittc 9.cidi, ru1ld. (lfmOil.IT~iWlUl'ated fat~yacids ~MUFAs:)\ W~~:1Ill (il~~ieacid (Rg. 2ii). The .-.)clmof ...... """"' . - r:Uf'i'a:i!t~ (NJFM~ '}I 5Jl'I1--. ,.•••lUllt"""Jr:aleCIl. 'J. . - ~..- . 5u<;h all ~~:lid.\[I!Jlic acid, ·\"'~~ich fl.~!~"U~ til. ihe

1Ji)'

!;iI'pm Ihlon:mrker.

We C{}ll1l\p-3llOOtlw:

'H~ NMiR

ilheadldl IfDKlIJSe l~ippooal'D1p1l1S .,\'V!rrlcre G01illin;[lo:USllc:ullU.gooc:sis

sp!Xlrn. ofoe~lisisci~atoofrom

c
~:
'a
·110

DII

1D11

C!
H

1~*(iSp~a~. and rmm. liI~c ·cortc;:.!,. wh~[('l rnl(\tI!.tfO. gi(,'IIfI~is ~ ~1lI1:.d~~i!C~oo. 2, .I Sl A ~ig.jJir.~lt~ly (1, ~i~~~falOOlJinl grlh~ l2~·p:p~'Il bi()m~~rwas (]J:bserved. u~.lh.cad.ui~lliIi(wpOCii.!r~IH!lS I:!S oon.lpiID!d

.,5· iiIJ· .ti

(I,

1"" ....
I )gj

E~
n.

the QO~lCX (.fiS. 2CJ. :pl'Ovi,dmngadditLQrurl evidence dlfi1th~ :pre-sooceon~lel ..2S.Wm bloI~"O'

ell'!!

iUll8iri:.cr C(Drn:eilates: with Lln.c' pUClienoc QfNfCs~ We l~iEle[l.3JtflflIYLoo. \l,ih~CJtcll.!lll15i.lS in 1lI.~~J.e,mo;; of I!~(; L2S..;ppl.'ll biomwk,~U' vo:mre:la:l.~..vJi~.h.~namic

"'F'J1I

dlilng~ kI ad[!l~i:1\>I;,'Umgl;H~;~.NcuW(r!~~$,ili i~iile adlllJl !NlTI!fimUan ~j~_)1j)pm IR scPBitlVC ~o it w:lde mI1ge oil' stl'lft1(lli, tnch.tdhng clectm'Ooom~ 'IIulsi'l'le s'Ilook !~CS), (1'6-2'.1). \¥e !:Ippik:d ReS. i~:O arliUlt m:t-ct': .;lLmdJ .a.'>f.I3.<;,'>CtI oe~I~Ufm<u:i{m 11..~~ii1g
brurtlOdooxYiI!.IIiclitllltl: (.BuI.U)irnloorpom~ioonrn d1£l S[[fu.@l'3I:Li!.I~aififilrn(l (ifr lilmm.'1I!l1le gym'" and measlut~dl levels O:f ItilU'l ~.28·iPp:ltI b~<utla~,~' usiing I H.NM"R. fhe Hlllm:ber of.Bro,lJ~illnlJllll!roreaclh~ cells\'!oras s.gni;!i:c.m~ly :tl!l~e.din. .E.c~U'Cm.ed. as oomp~dI to coliL.I sha:nl"lOpcmt.:cd, 21uimals,

E.

H·NMR IS dm'Ug11t !:o ar:1ire froln macw-nn1o.te.. clhl~ and t!,lG f:aI!~y acyl dto'tlrn1s ofimacyl~~y.ccn.dG:;!l :ai~.cl101w.;·!~1 ~~ren;: fOOp~cl! In rf!&C:.;.iloi!l~iIi.g iJilobi~e ~~pidc~ tb~ CYIOl::d~ iif~d '!Jli~tri(:led :~tn. il~ Hp'id mie~lum5 near n~.e~~aslll<l ~1ellilb:r.\!~
(22). :Prola~ (ibe.ll~c1!i~shifi Q{ln1!llil.'tth:mspoclllO&'

~Uf'

demo:ifl_i:ng tha·e;tlJtlCuvcm::s:so:f rIlmprocooure (Fig. 2D). tho 1~1.s ofdlCI,2Silflpiml btm:rutrker im IliJ(l j1l1fi:-i'Pil'mliQU (.1!rO~rI8 fi1Om. th.eMp~liI(ll!I1.'l \l,'(;l1'f.1: ~1.'l!O :si;gu.mcalilt~y flil~~dI :l~r :ECS (Fig.. 20). TQ,_gell!&r.Qt~I!"!leS\.Ii:swhh~l'e c~'Ullncl: N.rt-'s ~nd~",unl. dCN~Jop1I11.g!!md. adliU rud/limll 'bt:ii!iiu, the d,~~~ei:hatU!l;l :~lftl:O{I!n:t of ru .2S1?pnl. bio,rllad::c; ooll\C:lil~ ·w.~lhr:mtlrogoooo1silInd. oogg,.cst I~'la!~liflng(lSi!I~. nCinng.cm~ esnbe 3MlY-LM c illl;~ing the I "2:8·Prn~ blt]nmt:~f asa \l1fiJ~iCloof¢~rI~ for NPC$" \Ve :me1:lt !ID1!!~~llodlia.mclCri~e dW1Wk~d till!e 1~<l(!lIre of drel.2S·p'plll Mm'mul.er.A. specific
o~~~~lill~es~ndle

"fPC. '~OI.plr

I _...._
11..15· 1."!~::W

WIll'(; 1,M!IO:1l)

~.

.. 1#01#0 , ..

fir ~""'. -U, ~lll .~ 1.!li'D ~ C!~I~J'II'iJ"i~,

~~A/~~c
~

11,:11' ·I·~ UI

~a.!tVNI~

U! U,i:j U ~I UI ~~~IiIiYII Uw"nJ

uu

U 1.2 1 t

~o

~SNl'Ilj!"'~

0: m'2_~ln.~~.

OfUKl

Iflig. 2. A:nwaIY:Slics. 'Ilfth!! ~edfkity .and mc~ecufuJf' IlGmplldti'anl of 'the INI~Cbi:Jl!iIiiiillm~Eru~ngl ~·ifil1MR (A) .. OU,!i!!!1Itltr:katRoo ~IPC,. f!,Elurolilal. (NAA). af!~g6al. (ChQ) bk~!IrIa;~l!wsd!.!prill!gif! ¥iltt;g diffi"llfi:lIilt!i1oo{lli!. • .aN!!, '1. ,gf .aria :5 dlarvs (0) af'tl! r lii£!lli!roSJjhertl pk'till gl (1 x 1O~ ,rellis'lper time paint,. 1J' ~ 3 1~:Ilp4!rim~t5 per limE!' p[Jint., dooe iIllt:l1i;plicate ~ m~Ie:s. I~!rr e~perim.mfj'. ptl!rlfilffBe pant dimE! im1:lripti~ ~tlilimp~~·llelre:Mpefirlililelllt) •. u::)'Q!!IantJ1fi~iOnllfif the NP( biomalilkerin thE! ,diS1!ioCiartedladutt m.OOl!le' [D:ntex ((,DO h]ppoiarinpUJ~ (IHII (:11x gr6 lle~lli!per grellJp •.n:; 3, ,experimenb1 p!fi)f Igmup" d~l'Iei!il triplkam ~f:lilpt~ ~r ~rhl~n6. (D) ~(S ~!iI~f'~~~ oo'hlu~ fI!!!!irlllDw IB~dU· ~iff imnn 1IiIllOlrfli:lw:v!!cells 1m ~ ..3 eJ(perimem~; f"<, 0,:(1) ~ndtll.Ell ",:8"ippm biollliltlrl!leir 1m ;:;.. 3 e~'er~lmellirtl'i; P <: 0,05) ]111the mOl.lse :ilipIP0C<lllilpus. (EJ The ill.:2S:-Plpmlllilia:r;n<lllbr diminiishes :whlle 'hal ]mc:r,ea~ tlp(m bltod:a(je 'of fa.tty !1!,dd sYll.thilil'.sb withl otl\liYI~!linl (CW ~}(~ri!i!i!~!'Its: Ii!~~ gl[jQ!Jjlp. d!O'Il~ tlil! tnp~]alrte~mjJles Pli!f e')\p~liln1ie'Rt, P <; 1~),OI)1). (f) ,5fAs a 11(1 II!JF.A! aJrl! m'CI[,e abliiliiidillrltin N PCs th:liii lllfi M <I"llroq'te:o; I~'~:; ]b)•. I~GJThe :m.:2S·PP'1lI'11 Ilbioma ril(er' .beIJOr1!£IS t:ci alr:h lomafll.rnllil (((I~D)I[lnd 1'101 m.~hanlol (M~O:O) fra,roorl. It ~'\ll!!i~~i3!P.~ SFAs ~f!id~llIFAs I~g,th!'lrtbanIPU.FAs, with

b1Qfi!1~rkwsl~ W:hc['~tnaroi!lhamc!ll~i3!tiIlsat

U2 aJnd 1F'30(1 ~.1O~ ,oolills,~~tim~ po'in1i. n ""3, 'e:l(p.!lnrnenLS

(8) QIlI'al'lttific-atiOIIll

IDf

NIP.c, n;etlIlronall (NM.) <llndl g~\il.I.(ml)

and

S3!l1fltill F:v.l;l. :IA~ "fl~e !l,{!lfu~ (lW Illi'!~ 1.a8·Wm biomafkelw oorrespO!~d8 to ti~'icls \?',las alslO

copy of NPC's si.IDWed. tbat. dtere\:I,13S a.J~ooul.'~jt1,g ,aliFlu:rrOIi dw::l ..28·PJ1lrli~.Ibknnarkcr at (l8 Will. a.') Wo"i!.I!I.d be: ~"pootm fo:, 9J .rally ae:id ()Oli'll:ai:llllflg I~n~~h:yl J,) groups Om ~!Iii('l ~]1~ :m!ocl.1J~~(fig. (.CfI

I~~

""

~.

9 NOVEMBER .2007

VOL 318

SCIIENCE.

w#w.sdenaemag .. l!'9 <

REPORTS
i .3,- i!ol.4-pptr~r:a~ge,. did! liliol QV~l;;Jip(Fig. 2(0), U~,~g gas dt!'(u),i!(iIJ:l,grnpl*". ~\reMll!Igffiil to· 5ep~e and qllliUl~:iity speciflC fRt~y acidS inl N.P,cs .md: (lo ..:qw.ed.l.€ilm Ii) ihese fatli1Jlai 11f1. ash:oo~, Them was 0\'Ii bi.~l~ oonocitu::;r~iQiflo:fSFAs· :.mdlMTIFAs
1~~aUl.Oif

t2S.-pp.m bl.Q!i'iat:ke!'i5.~la~ llkel:y <i !w:~Wile of lilli&i lilarli!~du'CIe :SlfAs<liiiClJor MUf'As.

We 1fIext addressed. tlilepon~~biHty of:' I.!lS.iI,g ~he

wh~!'e di.v:i.di!,i;1i: Nrc'S aile undet~cHt~le (Fig.. l). ~ 'iIJ'itad~~iornilFourier biisf'O!TI1 5i~!iiail ~r-OO~!'ig
W.as limable~;o,disling:lllishIhel.28"~}I'n blm,1;ID~~ er .~~ ltih:e lilippooa1iD1PW: rro:mooc1k.Wf!l'Jlu,d ~O:~ (F~~,3A,.~i1S~IS), mQ:,~likc~y d.u:e, to 0 k,w NI?C ~r!y imliheat!tI~1 :rnJI. ffiI[~n'lpl[l.S" 1l1G:milihm, \V.~ d~\i~I~8i.rnlO~ ~1!l~itt:\I'~ ;sugn.tat"iPrOO~I'Ig algoridlJnl~ll olld:~r ~o :i~1a:ll:; dIe: ~i~ ·orlhe :L28~pp:!Tl biOl:n~ r~n~ !\'!}!se w~nl~~!'Hlle :i~ ·dle. vivo ~H~MR.S ~ocua.Wc uscd! s~ng.1Il1ar value dooQmposiJtiQ;f~ (SVD),. wltrich [pcooilS in~proved detoo~iQ:m :lI11 ~ow !>i.gn31.-to"\1fIol~'>f: and. alklws rnlios ~l.I!ll'ruS!i)h.vtiofil ()~ !>ii;gfilaJ(;"OI.l!lptlilt'lll:!l (m~) dlal: ~ d~ ooon:i); :il1t(ldl~il1!. a ~iv~11l f~l!t~l!ey donm:aill {23-2j)i Bac~dlOil SVD ~igrliUl proo~

PUFAs Ln. N~P('·~. un b

~a1.i!~1 3l>1rl)C)!\~~

1'>l"PC 'biomark:er ft1r 'iill va.vo bmillil ~l'lMl:ginS. Using l'i 9.4·T micro, MRJ (mMIU) ~nucr, we obtalnoo. ad!lllllll'at 5paclra of 'd~.e:h~~poeamll'u.!k\ wlu.lrl'l 00dM~nQi!Jtl. NfC~~td~

(Fi~ 2:F}l.,o,~l.ber'QI!.u'1~~1i! ~sg(lSllll4it d~

and 1~lt~:~ri~tal~~~

G,III

~I»~J
,~

CI\NU'

~U~
:8t!1U:!"u:: iI'r~",~,PID"it
iWi

[5,0'1
~,III

iq~g, M ·d¢1..'e:lo~d <JflI :a~ri!il~~'!1!' Utat e!!~M~ deteG~io:nor~~e ~.2Srpplw ·b:i.ollrmmJ!r in ihe acltill rat lilippoomnpt:Is~u vi!;lO (fig, .1A, rod!pc;:1:k],. A'bsllllllllC qjl!lanu:lIrullioo of I~~£ ] .28:..ppm b~ mamror ~.1iCiJ~i~voo by e:slilma:nilil!)!; d.Wl3mpHmd\'l
of lillIo ] .28;~ppm ~U!l.l.al" whe~~]3.tiV'\'l ql!,l1lin-

;3.0
2.0'
1

1.Il1·1

ti ft~ji!i)1I1 w;t£ adllir;;",,~ iltty .~tigl~~wic all1~lysis wUIl !he c~line (01') svg.nal anlJ.ll.ilYde ao; 11
dem:m~i~i!i!or:.Eotilil qllllrnllifi:co<uti.o:n. ~n;cllod'i mire

I) ',",' _li-d---'~

'Il

esl."I.'blished as reliab,1.eindic.:lt'On!i Qifiil gJven (lOIl~ {lrnllra~iOlil ofll1embt.:dilC (26):. A large diITefiClilCe: w,as obst\~ WllCi:'llhc llbso:l~qj!lOOlildes; Om'l!: LiS-fpm h~01Jruat~ ~re oom~.OOtw~u InI~
hippocrunpal andoortical ~~tr~ 1iIl~ 'lML'I<paml-

k.JJcd Ib:}f,uie rn~(mlelric 'q]IlI,MtlllcaliO!J!,\'l.rIDljdh OO!].~ f.1OO dillll (tie bippocarnpllil \:1.[&5 hi~ll.y elmoihlt'li m. ~h.el 28"W11fI b:kmmkcr as OOlllpar:ed to 101C' ~. (f'!~g.3A). ~ <lIl00 IliIi".:u~~m~terl fL:s; i:moo,the 1~fI.oor" N tic1i!l. ~t\IiIi~sp:liu:;re Ilhe adillhm1. hmlill. lind ill.~f j6(;1~ ..i!I!Il ~qya~ vfllh,lIl'U'~O.r sal!lre 1111(·0Ii~e()01!l.liro1 I ri£;ln h,cm:tsJ.~ILerc"~H--I\(RS dam WCU'e obtained! :rm both h~il1isplm-e-s from vQ(II;,els ofl'he &lme!
sii,zc,. ~nQro(lQ;f~ Iililc injcctedm't:ali (fl£. 3~;). Both. Fowief lrlllilSroml {iiiL9CI1,and. SVD'·based sU..gmlaii ~n~, (oowl!edpaa'ks) d~~yd0t<ooliMJ. 1l11~L2fl.p~al1l bOC'.la:nillker: In. Idae ~lmofdl¢ ~l(p~~[llal. $~t~oof]!a!~fdllig I\~ (Fil&l, :lB.).

i.·,·.' . ~u

IE)

!j

..
~

~. .U '1;11

~CS>t,

'"

J~

1':",
iii
!I'

-=. u Ii

(liJ~'

Both the direol qUiOlJIUicarl;~O!~ lnd. the !ro_ttm¥l~tdC' < mmlys'ls delllo:1tsnmll',}.;:j UlQi ~gC Slgmli!i1inllll: helf.tl~ spl~I;."!f:ewidlthe :i~~j'C\ltedi NPCs WflS :llli:l:lie !1I~ml.3S tililm~ler tlJ'lailldw in lfilfi.~ Q~;il.di"!1l ~ giGn oftllc oorn.wl. O(}Fitica! hcmisphrnu (Fig. 3.BJ. ru.fil'h~mlo:ro,.to detcC:it1lail1.~. in Idmdell~Y
.(If
~1:Jq.t:'ll1(tu!!,,~

NPCl

1rnl. VIV(I, "'~ l~d

ilduli

,~.,

t~cs+· -:."..,." ~"!N. 11,- ,~!!l (g~'!Ji'-;ll ,~.FPI1\ ~Ii! ~.n.(I) .~m!a,gifllgl Q·f

IF'ig. 3,. Id'limtith;atien of :fIr:I,i?y inl the· luat brainl h1l'L1'i\l,o, uiS11ngt mMlRl ·fPedms.mpy.
,_ ,Ac-~-c-li~ r.!I~-,,,"I~Iii- g ~~!!ill l.ii--. --,-II _!,' __ .r ii!:1i!1,! __ .L~ el'l",I;II]~f!OOS IMIFlF~_'!~'m:}~.!!fiie t"IaJ~1ilI.! aw __ .:n.- mp;pO(i!!fIi!IP_S .•(L,lIPP~':I~llfl~1il:I'~_ 0,.;),. ~_)',Ilg

~lJ,porta m~liS, the 1.:2s,.PPIirl bliOlirliarker '~r'OO)'i5evidel1tden 5VO-oosoo .sig,lfia~ prooessngi:s iI!I~rrf{jnilllE!d I(mb:i:liecl pee:~) bnrt !II(!It whremI'Clll!lrie,' 'tralil$fOl'ml 15:dOIil~ ~;IIiI5!~. 1111 l)ol1\e:.:. ·lhel.2J8."ppiI1 bliOm\i!r~er its the Iif!'ct detOOOOdlby e11h~r d~ a!1~IIy~is. (Clfti~ a5t~nst!iand 1~~l$,ootT€lam. Bilr ~Jri!ph~s;h(IW ill IJOOIUit!e 'GtlJp) illl1d nllatiw (botmd qlll\lllrntiifi~ii1i!:l1 of ~i'I!!1..2,a·llPm biOll!lfnll<err ,(0 ,~ 4 '~)1PEirill!lelilts~ Po:: OJ]5.). ~EI) ~m:a.girilgief tr.arupLarnte<dl NP'C5.Vro:)i)el:5. e ~Ii!lcedlin t~e: .!.f,ealof INIP( :ttl' .ammrta IlIt '(NT~5 x: '].rnr·INIPC~ in '5i!1lI~o~ M ' s;mUJlf!@) Slili!1,e:~niettic\f'! (S,T; 5, ~~, III!! ~e NT se,. the: 1..281~p:m hicl'!'iatb::r hc:!) i~obse:rved 1MIi~ b~1h and FV'!JJriIHuan5.rOfl1lll .lind .SVD~ba~dI s!Jglliill p:wliie!l81ilil~~. 1111iI Sf :mel',. 110 ~ig lIIilffiooll1ltI.i28';PPIilii ~ig,IiIilI~.is ~ille observedl. Balf graphs; :!!how <l1b'sol.urire (tap'" ill nl:ll re~aii;re (tileililDllI'1I]qJl!IDLntirn:ca,tiOIllof' ~llIe l.:28-PPIllil b:'ini!l~eu '~fl".5 ~.,~~'h~1~MS; p.;: Oi~5", :@di IDl !!!rngi!i!g OIf~1",d'Qg~!i!oo~,~pCs·gr~f ~r:s;, VQ¥~'l:s; . p~~.d .aJlCJi!9 " ~ ~he M~poc.ampus; incOlWil\Dl~KS-)and IECS-trea,tet'i (ECS.it) adult r.a,tsl~O. tQi!!aifitil'6~itlOi!i afilhel.2SJ.~l!lIm

mi.;:;; ~~h EC~tP'i\rQ days al\er Uie im<libile!liil. 'Ml lujecwd BrdU ~olilie~ dividi!lg '".ells a!Ld aJlQ~ llyzcd Iiile ECS~liItea~:ed and. s!!mnl~pet@h.->d centoo~:ilniitlalsdM~ umH d~)'. Quniuiliica~i(m (i!,f lIw
1.:28.-PliPili'ii.:Ci: si;gi~lal.runpHUIld'e ra!lioSi ~ildu: i~!h ~!Jli'l SllQ\Wcla. slgliiilka.nt ine:rea;se ,u;fdl(j 1.28-,piiI.'i b~01:1N!ttqi!i1.ECS~.tLW rnl;ga.~ oOill\~dI 1.0 :Shan'Hjper.:l!!OOool~trols {P1g. 3iC). To val:id<l:te 'ii1espeo!roscoIlLc f]rndin~. weql:l:llndfied Itle ~1II1I~ber rBmU~iIl111111!1I'KlI~.eaclii\lle cells indte o hi~~pns of 111m.!>lU:Iii~a;nima.1s (F~ 3D), A S!l.gtmi:fiGal~ll ~1.'lrn'Ca.~ilJJ1i'I the mli~r of BmUm:'iit.'lu:lnl)roa(l~i",~o('l]l~ii~ !E':C8-l~l<JJfk~ Ml oom,.· ~d! tQSI~'!W-Glperated COOllf6~~ derrtl)rnslf;ali~

Ibio.lililar'ker·l[tO.~ :;;; 4 e,)I,~erim~liI:h;. <: OJJS]ailildl the n.l!lmiberof Bm1r-imnilllIllCl!mE1,a~ P (ells 1li1f111elrilel:1.tate Igy.r,~$o:~ th~saml!l ,anim'Qll[U)i~, n == 4 e·!(:p~rim~~\; P <; rQI01Jllil:!d~(gt~ 1~I!1ool~orr·~~gJti:oo~e,;). c

li~a;u, ~ ,expeclerJ,OCS

u~c~ed NrC I)~H~

REPORTS
Mo!'OO'¥\1lt~ili)'U!.e1i!C:3"~~~d .u~i!lli1L5"we IbLlilld: a~aliQ!fI ~ilNCen lIDieliiyliw 'Of E3fd1U~ inll'l1i,'lJIl<Ire."lCtive eells Imd dIe I .28"PiJIl,1£~' sigua~. ru'lll,pll~lI~m1io in dl~ hi~.~InJm!'oil" mile ®iU'IlL~ animal. (Fig,. 3E). Ti],~dler; !ltege illlm,l~:ldica~(l;d~at IJ.[.MRS, calli bt:l ~ugM. kJdn~~ .:rnd! rnt'liZa~ dmlils.~ in iIiiI('idtn~ity of~nq'!)l~ N'fQ, .imJ. v1w, We then ~!'OO~ \l,~"d'll1;ud~llIlifi~liOln or e!]dogoerlou5 NPOs i!~ 1!1~e hlH~Wl bmin. Brni.li)! I, H"MRS was ·~rtlfo,,'IlIOO OlnhCilldliY <l:d'lJ~ts.
I!ia'l.

!lliljw dir~~liCe: ~h"'Ge:n the hiiPfi'I;)Cafilp!.l'land

U1e ooi1e:x wh~ 1!il5~ft!g eithiW aboolJ1!ile or r.it!olreme CjIll<linli:fI.c:niM of.'~hel ,:2:B:lPPlll bioHiI<Irnrer; indic,,9.tl1ilg IlliIm iOO'I1I1 can be appl led to lildJiroclJly iOO'asure NfC dmiiS:i,tyin, 'dlcl~unj~ bLP~'lrnf' pm, No dlW~roIiI("Gin I])~ .h~'i,l\~1 f9~ ~.:281lP'lJi'lj o

~~O!U)!~'i ~i{,J.!Jifia!'~@.t .i~l1Ilelive bu.riilj~d dMl,m5lra:~e.dUleII!!Se or,ile IIblQ~urkeT rQ.I'ide!m~f}'if:i.g

NfCs in '~'I~e ~~R1inOO bmifl. The: 'I\~C bi~ '~ire mcmrkcf ,coUlM be re."Idil.y dClllctedl in v~tro wilili ~H:.NMR~ lht:i:~ilS deti.'JmiQn8l~ l.owOOi1iCentmllims 1m. Ih{: 1U""'!llbmil~ willlu. IR.:M]tSrnqlliuruJ dl~

bi(ml~r
kip~mpi

Wa.~a,bll~OO ~)~
1j,~~

Ule ~~ftta!l(:I riglr~

d.tW;~top'rm.tl'(Il ·of

1t~'~AinOO,~.odrn~(lID'.a:ror

InJsin® ill 3"T MR] scaltmcr

rum, SV])~l:med

sigl'lal

,'r:ooessill'lg (,F~ 4A).. .Ama, C1IlptmrnlEutal. vo:tt1:~, wa.~ p~ac&l alOln.s I!h('l ~milglln, ofd.t¢hip;pocam~ [~~, whi:l~:!I COOIID] voOl«il ·of 11!~ s;'In~ c",nhalfi¢ imcllllliied ~y~l!d Wlli~ ~l;'l!u~r 100fd~~~si!alr;~ ~I~~oorte~ (Fi~ 4A). Tle Fouri,l'it ~m!1,,<;lbm1 die! iIIIQt, reveal thal .28~Wlnbkln'llliUl'kcr (ln$)~)h~ any oHilc'voxcls {fng" 4A} Howcver, the SV.Dc.
b:llm(]): IfLrl8Ilj'Wiis (colored, peaks:) c:lcail:y dmeclOO, l~iIle ~ ..2S.p,P'lll Ibiolfl'lill~]!uifil tDl(!l ~appoe3!mpal spoclta i.ndical:irnlg I]I;n this mi.l'lt1lodtllogy can be 1!!t:ilOO~o~.i,)rntify ,1tl~d!o,g~n(!!lL."NPCs il~ Inlle hUJ1lilI~ brotn (FIg., 4A), For c'Wh pers(m. we fOlJlnciJ: n
j

COIllp3nOO (F~s:,41\), F~I~U:· !llgre,.w~l~ ~ ..e~w!agOOtile l~ft hippoc.aal1[pM ·of dle !llillw£':pe:Ollk,: ailllie, <I. 3'~'l1On!lhpcrioodclJming w~~ich,dl~t:'CWa!l UQ!nUlijOfdh!ln~e ~n II1~eir dni~,y :roU~ililC. 110diili;'lli"CiilOe Will> ahj~ervcdl frl the L28·

ppm. btm1i'il2Dmr ~fl~l 4lBj .. f:t11lrJIlly. \!"'e3Jna~)'Z.oo Ul,e; ;'I.g~.ndarod (\1113.1ilg~; in Ullil L2:S.ppm lIm~o· !ll!Lrk.er dlJlfil!l!g lllll~~ (hw~lo~;mg~u~by i,.l!I<l~i!l~

poople ,of v.aryinla; ages: prooo'Q!eoo~~ts,..dQ1~.

NlnlS,iUilCl :od'lJlts,. (~mIl1Lificali.olll of Ihe ~.281~pln b:i.omruiter revealed II. decrease in. th:e, ll.2~r.mll sigl:aal IUvaplitudc (f'j,g. ~Cl wlrui'ch ·is COOltp1i:~i.blc wtfih,dalll. ~ililoiiINtrnlBi:ug .a:g,e·li'Cil3tcd~'lC ~Il Jnl:llllmgl1l:[I~~im anmllals 1(2711111 ur wnrt" ' IP;.tL): id:~rltufi~ a ~!f(l_lloopic o 'oommnker ofNI.1Q;,Cfu:vCl~ped II, nKI~odailogy llJ

~"t¥'V~CI I!~OO s\!!~J,erior!o the tr:adi~i:o!ml1yI~OO FiOumertrnJ1L5ramn Rnd can. Inowbe 1lpp lied, in a. 'vrn"iely of imn~jn~ selmin:gs wbt're lowlev.e~s of [I 'pi! nicllllar IflJet9ooHro; p,rocillde :ilS r,e]ialb~e,rn,w.mlumiu vivo. 'Ot!i:r .11M.l11S !ill~~ ~,lm:~.IUn!:!' NPC lJiOO1:3![j;('lr, n:l~Gtli~~d by a U8-ppn~ 5pQ~I,ra~ peak, ~s a OOnilp~e\(. !:tIi-'.Hii;lr~ (If ~~lur:M,l}dl a:ndlor !IiI'IIOo!l(}U!~ll!~~U:a!!oo . <l!cid.~ .!lJlt,f!rel<iitoo C(li!ITIPQ~!'!d:lJ. f~ .uy ll1e func!ion!l'~!lieo1eVllI1.Cje of jhese filiOlcclilles for lI~e eO:I1Im~o,f p:roIW~'rnrjQll .am:!. dillH;~l'Cntia~'iQn Qif NfCsreJfl..m:llIs (0 b~cllllc::l'it:!lill:oo. F1.I1i.~ly, CW" d~~a,(m h'i!D:'l'!iiilm prpvi~in. 'l/iw imnagjng ~vid~[loo fer iNi~im I!I.~B~umm hi~po~m:. 'll1:1~If]IfIcl!~UI!}'S ~ppO[t Inhe n!,Qm(.'f{n.~ &tldel11orn;trnling
delllllte .gyrus (1, ], 2~

s.V[).~)a~d si~,al pr~~.ing

[Fig. 4.
rr\I

1"C:s

r~too human
(It)

,~defllti~OOI

of :hip-

,A,

~ds, a~ [~Iaoed aloog tloo, [~ippo;. ~1tI~RS,

(ampl!JSancllil1he~
~JiI ,th~ hiRlJoca!lfl,~

[~~mpUlS.·ffi~ WW, mil,£!

'ilte \¥e' also demOlllslmlioo. 1I~s:~ Il!!lIlmi.I"~Id~£ pr:es£Roe 'QfdlC: N,pe bjmll!u'k:er .in im ~hc ~jp'pOC3l,npt1S dmitliilican.y decrt'a.'>CS \\!i!~~
age" A.II11~1lI II d(lC~ in it~Uffl@,Cllesls iIl~be~UI n:lporl~iill. agL1rIgl'llanooals. ~~lj¢ ~ d~ 1iin:>ldkn rOOm ~~~Iivilllg I]~~ml!nbndl'l lmal indi~r.:; a docrea8e in NPCs wnng '~rnl!'ll de~l(l,~m.C!'!:!:f!mn : cl[i]dhoodID am..lthood. More genIQmily,. Iilifu

cooti!Wlm.l!~: !,lem.llOg00es:~ in

L2S,ppm

bi:om,ilIrker

tim'

'~rll1'd~]s evid:en.twllilelll :$Vi~ased sig!i1I!'!I. P]iQ"

u!s$:ing is p'effiO![mi!d
l~lHrit IliIot: wllilen Fournier ~l'l'Insr~ is d:;ilne. In the' rortex"lhe 1.2Sfp:I'III!JiiOIlIIIIiluker 15 net ~I by' ~tlile~' data O1!I1'aty.s1:s. l(Oil!.

biOllW],;'U ,00Il be 9P1'Jlicd tOlrnck [lild rul8~.Y"'ifl: mn.dogcilOlW or Irnruwpl8!iltedl NPCs" 10 nlOi~i~1,jr noo~rtt....n.<; i1l1. 3widn: r3itlfill'l ofi:rUimrulmmrologl.cal a:nd J'ilsycl~iaIJri:(';disom~ .iI:'iI:!. to '('f'O!'r!lluall'l I!lm effiei~II1CYof dleGl~ulti(; i_f\fCl~liO:[lfl~

I)roo asteri:lks and

CDffi:.

(Ired:PMk~oon'(date. ~,u

'(t<ip), iinjj f~~~ i_II qu'iln1ii:cilliion of the' ll!j;.~IIi!mmarm;{CiF>;, (orte-X; lH, ~eft 11I~l!lpo. IGdI1!ljm; R;HI, niglitli: hipplo"

gr;~p~~s:how absQiluoo

,am.

mill ~JtI, iUIi 'l.o

2,§ ,O!'_(I

(:~

~il '~AU.!~PPfDl I

1111 ~_O lllli

4. Iil. i1:. I~j~ ttSomg. 5.~- CJ]!a~iIH). s, L MTig. F- !iI.Ga~. ,~_ ~ .. fJhtttMWiil JW1~J 4<1, .3W ~OO1II)l 2,. '13,l Mf~\, I~ '5'llfl!il\ Ail111rl. II7tii'. MM!M!1'( :2:11,22.J (200SL ::I, III. ~ oCllniS et Ill.; S.rii!'lI'~·1S" 1243 ~(J!iJ71. l 4.. 5:,. A. ~Lii1lli1il1ffi. tit .s.. Wilflili'4!m.o Pl!JjiM rIM:!:. R. .~'oc Lomro:r.l s~~. 3:6,1• .l.;'i6.~ 120(16)" i!i 5" p, cr~dlet~ d "~.,, C~!illmst ~.rIiti Ma.!. 1.t;lll'ly.i'i1'9',lil!i

~fe~!i!I~$!!!I~d

IN~tes

~rt:~~
11lM,

.'

01101 ,afllj[ P ,_,;: 0.05;

~I.

((!mpl!l>; n

= 5, ,~"

0;:;

~~t:"

'iB) 'Qwl'lttilml,lioo of th!e :m,~l;I1PPffl' Iifil!al~~fin, .~~ idillit h~·

i I
( :!I

__ i!:il'

;J:,::;
~.(i, .

~.[
2.~1

mo-

,e!,

lifIIIiU'1

tim.e ~ == 4 people. P'=:. I(JI.1~n Th@ same' 1!l!!:!F

[~h! wl'l'r,eilll1dig;e,dl 9(]1 day.s iii.paFt (0 QUilIllIlrnir.·
(gtJOliI

;hi'ppocam.pl!I!~ over

~i u "',
·tlC'

4,0 ~

.~H! .~

.2~1 'q,~ 1..0 ~.~

~~

CI

~I

O~~i't'!'Ji\!1!l

lai'm(! L2B1iPflil

00

liJiCilllllinkerin '!he' hUl1Il1InJ Ihi~~1!1$ de-

loomg

....
ji,

Vii~iUinl

mit; amatt ag:E! gm~; (n. := 3, peci~ [~~U !~rooPi po <: O.OOi).

oo~rrt, am

~ooleSi'

:i ~
,1£:11:1

,~

ii~

1:

1b4",,1 ~,."b,,~41r-1J~_. 11;.'10 1'i!-11~ !ID~; pt:II,g.J'lIiIiiI~

6. ~,IiI,C!'Ii!'l~. ai" Mila. ~ CQmIi1tD'!. ~4,l:.M? ~~(!O;ll•. 7. !i. s- AIh3~,. W. !..i'i!, 1- ~, F.r.aiil~,~lReL':. .~ .1J~it<!S 1, .t<l] (2006)1. a, M. Irt jjj~;fII" Afl'iIi'led.l1 M>!l'~fjJru, .~,sli,2:29 1[6007). 9', It ~~, !j. Ellum6AIMt. Roc ~2'S. 5·U~O.O:]jIMI!W Amtl. lOI IiI.Sleil!IIUl ,i!'~ m" J. fielll(J/. S'd 2160.,1]2 l2mm. n, A, Stel'!g!:q eI'aJ., ~tr~ R~an. 1\1ed. !ii2_, 229 [200{~. ~,2, W,I!. ~a,r<l)'<lm\ J.~IN@~mg 15:, 46:.~t2000.}. n, J. L. ~jg~~"v, ~~~~. ~ $, Oivi1!1'Ig. !,'I, ~~~rl1i!i!.;,v, G_ [rni~IOPIJiii. J (oi!mp! ~f!iJld 41'!9'. ]U ~2~tI), :U, .. 1. LlIligDlIi:Ji! at otl~~ CIZI{ t;l!lt!! .60" :lUll t2il1D7l I5. It fl',. 8hill~1 P't(j(. N:mol Airtl\iot '1:d.. jHJIJ.][o3, :12St<1 (200"'. :~6\, H. V.Hf>iOil~, G. K:eI'!l!perm~nI~. it GJ~. Nut. f',. lVe.~,i" j!~ :260U 99911, ll'il"G. K'Ii:!1~ll'llfil1i1!1l!l~ (j" IKwl~lIt If, I'll, ~~. lIfa.rtrlfi leli6, HI. olI?3 ~;;;,1. III. ~!\I;fn~~, V~"fI~o!G!r]. G- El1Ii~!opQ."'. N«. Nurl !!'I. .~tt(i,. ~d. i!l.s,JiiOl, a:B~ (;2o.Oq.), ][9'. l L.. Wi'lFlM!r-~~~tillil1. S. i)Ufili:li11. U(p~arnplllll' iII!ti. It 23;9 (2006J, 20.. 'T'. M. M;ad'ml to,! ,~t~ ,Blo!, P~.i'ii!lilsy 4~. :HJ4~, ~2(JOOl. ~.1L l" 0. Pereraft ml',.J. ~If(}!id. 27, 48:94 (2IOO7), 2'2, M. IL, $pli!ri~l!!l1i'IR.:Zi~tI~Ji" l M!JU~r, ;5, I. (h~~~ Arim 8l4i!rliem. l!!78.. &7 (l!:9iS9t

~200;1

~u~n.

'9'84

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
2],.

24. ,a'.k :2lS-" 2;'. ,23,

~"

!to EI.a~khuij~~, R.. ~ Bffif!~, O.!tanl Om:IOIU[1,}. M~,~. '5S~ (:1.:9,81). !l. CovilS5i1il1 eel aI'~): ,M'~'n. ~.IOi!I. fllooJ.3. 9:7 'l19'17). W'.. SI~iGiI, N.5~oo~re(1~ Y. S~~Il. t I,i'M!~!TUI~'. ~ Il~[i !ill,!ji.gj, I. ~~~It§~ :l~5\, 00 (..looJl, ~. 0i:I!1.i!1~1!,'{\" r.:~~~G" ,S;C111mtt~!Ie~k;ffi. 5!!M, <'loot ,(';Ij,fo1ll1. ss, ;;,2:ro, (2!lDQ, ii., G, t::llillf~ ,It Di~k~in1lll~·)!fi~n'. f. H. ,tj,~I!, J. ,~l]jjrGl5d 16, 2027 (Jl9%~. F" S.E.likio$on .e',f,:rl" Na~ M'ed:.4. 13 H (].991l~. W~~mlk: !1I. Zilm ii~: K l)eciX~ Ifi .e~r:t 'te;:hl~~iJl.
8it!iQJl..:;!~, ,~j,$ill!!lJrn{!:'

~,.tl.IIH9ijrl1F,t 'Sp!:~lr~5l)Ow.

EI.'fg~5t-er .

for

InMRJ!~!iNnw; It (;ml.ogn:ll{l'~~rope ~dtlll'!!,~ s, !;~rk.'l ~T I'II<Jrnin(lll]liall ullttml:!, ~',·IiI,F~rk 'ril'r illMlJe 00 ECS; ,~nd ,A. S!~rr,it,. ]1, Mi., EiJl(ql'lilt J. 5, Tf11mm~r. ~, Sti>\iTC!po~l!l(l" 'm.~ J. I~!i!'~~i ~!:!F 11e!P!U diWJU;i!!n5:. l!1ii W~~ ~~ ~!!W~I1~ il:I' t~ Na~~~~ 1!~1i'!~~J:: ~W~~~~ '~f 1)1~i!lflfE~ .:lM SUll~ (r;JlIr4lil5) ~Irami:i; !l21IN$015675-l am~ 51«)8 NI5!J~,~l(6), 1..1:5., IIlrn~ Mi!idic1!IlJi:e5M[~h (jJf,BiU [)AI!'Il!)~1l1'OIl'],O':l'§,41 ..M•."!),I; ~I!!! Ua,t1mf'lllll.!rlrtl!w iii ~ ' [)i~tl!l:~~ ~~,!iIffitI!:i~.l!tiit@ j(j~I1Ii!)' Qtl~IN!!i!!1(grAm alld 'Bjl~O!i!~2n-16) !l!..tMU; IMIN[)'~ !!Jill'It ~1,,~S~27064; NAJR'SJll);the 5er'Oip:11~lImjlil~iillnl:~Ill!lHilf~nil'l l'~yrnw~i~1l,; the H!I)~ r:(lr ll!:pre~ij~riI F~'1l:ti~~I: n_m.e

,fl1l!~m ~~IW'atioo (~IEJ; ~n~' ~[lilltlll'~I!U! IElli~!W ltS" ~ r,~mtF!j'jlP'M{i,"06~J (iii ,S,); NSF <9rillil ((HIS 1S2ol:6!; .mllllillii: iOU~~~ r4iIWl lteieilr"ln ~rarrt NC!01!ll.4lc06-1,,af

OO:mU',OO, Sgp,~,rth!gOrnl~i~M!lI~!"i",l
'W!o1W\~,i\i!l! ,

LU'3ll':I5I!,'5,~ffl~I).;\!:IO

fIlal81.als ;Bnc
SOl!.~ T,e<.tI figll. 5.1 llCl :5.~

~.

16 ]I.! II" 21007; ilUJI!pledl1!2 'Oc!lIber :tWO,' :l!ltl1~6J'S~ien~e,U4 J!l!5l

Sex-Linked G'Bn'Blic IuriIIU'B'nICIB' en

IC,BsleDe'lermliilnalion
1!h~ m~lst1~1)i)~~~llt;

inl 81 Termite
~I

$lIociill~sful and d~tfl!l~ ttl~nii~ 'Spooles:a~lh~lli1: wilJ;i g: nymph ,~$tl:l andl ~!lil iHI~I~Sibl:ywt~!:i.t~swork~f' (:g:s,~, 'ilihe ~~rtif d~~ltiil'm,I'.H'itgllbifYr,cgt!1o!li' se~if<M'i!ii!:ll 'lhe5!fii ~tfiiS its: witiel.yar:c~p;te(iro be !i1J1lcrt.y @liIivirol1me\rlta'l~.y ,tietYn~lrJ!d.We IPr,!;Sent !e''ilid:eme tl1:at g!rlO'type aiso innlle;liI~eslffiris pifO(I~. Off~ril1g from f~r diffm:! at (roSSleS o~ nynl]lh", an:dlMJ!mkEr·dE,llwdse:rollldiary Ireprodl!lc1N~inmlidl!ll'lls hfld!>1rloogly dine r,mtiatled c11Is'te11l1ildisex,l!8itifo~ de'5pb! ;un~roili'll'rI retl:rirl'g, !bOO ditiO!Iil'>.Wh~5e diJlaJ f~~a:lilX·[ililked" 0I1U\l-tcJfCJllSl-MO,.:,allel.e mM~L or fi\le po.s8iibb:!'!!ienmypes;. (llille wti$ I~~~al, 'two re~uttel!ll'inl WO/i~e~5i!'.IliIdMO re:s'tdJ.e!l!l1 iii! i~"eu li!ymphisor renrvii[;onlnrlelilta Uy d~rlin~liIed, wr:JIf'ioIelrrs. •. (atS~ 'i'SmlJ$ CO!liltro'l~d bO'Ih ~yeJlIvirOll'lm:l!'!nit and by a: I)omp~ex g:l!'!n~tlk i:lii liierim'lil(.e ~Irrlil.
cl~!e;~d b.y l!he;:dJ~ft\~nt!a'ul(n'!of colo· . _lily :lneI!IDor.:s~1O ,e~dler NiProduct~ve Of stm~~ !lldlvicfu.El15 (1).. KUl sdJootion liliIoory PU(\"

.S

jfjde~nd(,111, mlrel8Jtedli'mlwl1~, ool{HlY 1.0 IPro:Jfl.~O{e i:l.gs prOO1iI(lnion. ISMfl ~1J1;' ~at~.'v~O! ,00i~ :liIJd laif;!oo 0)'50 !!lni,,!1~W'O~~L';~ lIDu'Il1 ltile IijIlJillik oolon)' i!O ide~~l t':jJwjl!tl!1!lTJ;~t<li~aBlld: p~~i(;~nfy I1I!1!<e!lCCSnde\1'iC;lop1menlail o bir~liOl!l Cfii~. ll, 'fhe .sc''l:.andl cast~: of d~iml.,imlSlar oUspril'lg \i\'C:I'e rlGtclllrlilne<i.3S weue :mrv.iv.aJlrnles.. [11, [he a'bsence of a il1l:al~ r,~modl~:cli.ve.R. 8p(jnHJ.i.~ fcrml!e.!l c~nl. ~Pfod:u(;~ ~p.arihlJin(l,gml!.llic,an}' \l'i~ ID.h£lyt(l!k.Q~ ~,1[ItO:!Illi.N:~8, ~'IiJHtng in ~OIfiO"Lyg(!!1J$ fL;;~mle !'lymllPb Oifl'Spri~g (lS-20)..'fI:1i~fdore. 'WJ;l~1¥o el!!!!mi!f!ed !iliIe~vcio;p~'!lc!l:1 of ·~rtJl>eQo,genclic oIJs,prilJgfmlll si~1.1Je~p8iren,ts]onypes fN and f[:;;. M1oo-.g :rt'U;lli.cat:es of a pru'ilicu:lnr pair 1}'jpC, g:ardl~

(!!Cia]:i'~'i,

:S~d.l iiil

.~j!Sm~

~,":RiWs, ...

.;l!re

dicl'i dmlcm:c'wsilllS inooooo.diffhnlllCrn;

fi:mn 'mlvlmllil1llieilJIHIlly Ul gene 'e:l!:p:l'CSSioofrom a l~ol~~~ml~'1l!:}m:L':J (J"l); a pmdlk;,1ioo sUfpoiiloo iry ¢!w,pirical 8h!ldi~ ·of ilIymt:ten.opUlI':a!ll.~i1!l~UID5~t~

de~e!I1li11i!Jiatt'On .~r~ym~no;plerolll.qlll.e~n i.mrl Wou fr:oJnd~ d'~ilnol:cdh:mi£·s ,of RetiClllilermes CIlS~es 1IiI~ ioocn dOCUI'III.tllmxi, (6-U), theseaue 8t/e.roW.iIJ. Wecl"OSSoo dlel'l1, (i.e" fNI'liN.I:Nnm., ma~oo ~:CCp4:t()f1S m."llI~til1gf.i:o:m hykLdiizatiCt.1:l, '1Iu:~.)'it~ fE..an!'E, fEm'N) as dcscdibOO (7).Each pair W<1lS [l1,fL(lcdwith :50 fmulilte wor:~el'S firollil an ;II;OU5 l?ia.rtJjQ~I1tl£'em~S (a5&.'U1.'l~ frOOu.c'~iM of fel:n3~.eo.n:"ip:[(ng). fiiild dimorpht'C q!JIe~:fi. ~m IM)lmifiil.'eS, dle :q:lfOdlllcIiiVlL): and \>,iQ[k(lr casllCS .;]!~ ~)1XJ4!I~~~ ~. be d~rafiill~cl! ¢Ullirely b':y e:l(mlii~ n: nym:ph sle fllctQ£S~ [.)nn_Uy l:iherauOlle:!l (1'.2-/). N:: nymp:hoidi Tennr~cs <l'n.'LIt!~ia;: [oopil;,lt'a~'are Q, ~lIOOC~a~, fonn of Clookltro.ach (1.5). :~n:>80%or ~,e51. a A.: ,al,ate !l.'i[IJrmca!liOJ1l(:uil~l!IfS.carlyi[l d~ve!Ofllllent (Fig,.~J 11m V'~t t!lmjonty of of[~ri.rtg (OOU~r~ll!iiale:.aa-d
~ll!'lI~) ~lIIt~r l(Ii~ rii,lfi!.¢t!l):lI1l1Uy8i~nl!~,ifln;,'\rt;rs:ibl'y wim~.§$.ll W'QE1l1~FpaIiliIW<l.y 116<), Nrel'!l~~\!¢'~y,oolil;le offspdng devdop M.ng blllasOllDcli en(et

(b~.

;iIiiL , ..

wa~iS) {4, 5), All.h(:ll!lgh,~~~i{:

olI~r.it:t!!l casre1illHdi sex mtlcs wtl:rre sitmil:llill; n:;iof wiJ:e.tiliJerlJit~y \'~o1!uhIT'(}cl! or in1L1iU I~mlioos, N~t~lI1i(:.S :may ari8~ fmm In!h~ ~·Y~:ipj~M Vi), No ~rJi~ IlQlllt diff~r~.m.lolflg (l1[~l'lring ;liI!l@forlhe W'OT~~ ~aU~w,,"_y ,md!~. ~~i",~ly~ lYr~ C~i{~ fQIIlI!ld.WiUl fl~lL'f's e;.,~tl test ,[fN!'I1N. p .. 0.3 0 {II .. 7)~fE!luiE, p- n.:! I. (n '-4); fEn:1N; lonnool ~~lnp'lilOtds(wid~ wl.ngblllds)ruacl1ctllato:lcls l? - 0.5#1 (rl - 7)],. widl.lhc" e::rocptlon ,of fNiunE (widwlII.t, w~ngbtrJds)!(Ag.ll" al~mJgIl (1' (Ull), 'W~}.cro [ of 5 :replicates: had! 511gl~t~y fUlldi:L\lIm].~y 's1l'!ailc. tll£ruf;'ore~ :rotaiilldl~a'bll;[~y to ~"anyooCOilJU'; f'Cni~cin some ~cs~ Il!l\()ffi fmllFll~ 'work.fr:;;~ ,mJ~dl.Ou~hdroo' ~8Ilmm. 'MIS; ' WI;; ~$olatoo.fD:pnph!l anti wcn:ik(';1}l :[inl'ml Silmilar I~O the other 4 1~~lC3!t(l;S W = (t~, llipol1 (I ~R'!Id!ll.(:I.i.ve :indJv~dll!lI;$; pnxll!l.eingrtlI111l1~ (r) ~l(ciOL~km nfOa~ rl'll'lrftil~e '\,'\IIMI~ke.w~ ~rJit!llfl)' amI([ m.'lj~ {m) l'I}'ltiph\l,itii<l {N),::tOO ,~~nQ;i& {.B) l1~tO~, l,;\(,~ poOioo Q!.!IF ,dala rijr oonl~!'ll115

'\u~e;rs,

Oil

wilhdl'e (tiber ~@~t:Ilen~. ,A'll oisprln@ of p.ru:ttiien.QgCu.tili:1N and. fE w.eii!e f!.':Unai~e, andm:rrali1S'1 aill diiff~iatedlill.to Il)'I'I1Ipll'l (~, 00% ru~ 9()!ifii" rt'SpQa!liV'dy~ Q"i& 2]1, III.

NI

NI

HI

(1,.

i!m.elIi1YlwphallpaIlWilI,y, which !eadS~o the al~ (primruy n:prodrn:Hve) Cast'C.h;1 tbe albs~llc:e of I~[timq,l.1~n amltoo kii~ &O:linCiiiMliv:i.dlUl.ls (lem1ed
Wllool£nJ.ell)

rula.iliiliflM, j!;li\!~rti.t~ cmi:m).C~~niC8 (13l [m~ireed)~r!~wid:!ln the coiro'!), is: 19U;JSOO1I~Ii.'!Qni~

laikitl

OV,Ll:iij

d~C1: m~~

tlJlF r~i1Cltol~

w:wmk9r.
E: erg;aftD d:

whil~

E.

~UaJlll!ifal H~~~\llry L.abcr,a,t.cfJ (nlrl!9~ Ilf$Li!!'MiOO', IIl~JI1lki IJI nil.!1l!t~i~~, MilO" ,11l"'r;ill~i:n(ll.i8,5n, J~p~n, ~'IlI!IlIa:lliioolFad n G~I1i!!'~ru:'o;I :500~1.In~d:s liI'bm.r;aMI,ry, School of mm~'.3l SG~1OC11l'S" IlJnL'I'ersrty of ~m~.~, S)'dn~)'; INet~ SQU~1;r W,ales :':!O(l6, .. l\ustr,iI~iI.

a:JiIW\!i!;~lfItiJka1ecttaSioffilllmol!tsw iii,eQteifiit i'iJiI'Ii~liiciids of Ii! r'9Mtit(is, wliiich Niy rtprodiil:Ql'~ifiil!liie a'bSimw 'Vo whom WFI'Ii.'~~IiI~Ii![i,' $holil!ld b~ .ndtessed, lE-m~!I.~ ,ohhe q,l!Ie~nallld\l'ior Iking. Worker~ lindler-gil] :s,btiOlilia rt mlllB <lifter' 'IIYS,Sc:~mel1l.are dieri'l.!'M froml W4i!11ll1dl Ws. ~!tade@!!TI(Ii.lbr.a~i,a~ EligamidlSgj'~re (rom all WOflo:i~ s,1g~.e5art~ Wi'

fiig. 1. Caste devela(pm:erlMll l~o;m1lYS o,f Re'iJ(uli're,rmes ~~p'. (13).'III:HlIIiI~tesal[e diploid! (Inti .hem~mletaboW(m5; Il!aINae' IDf' 'l'G~hSlfrXricllra!N ,e'l'l1e utltleworJi:Er Ipa~bwa.y:., w,hich i:llIdi:viduals. IliemalllI mill i~l!r~!b~y wi!i!gi~e:s~ Qr!h~ ny!i!'lpm\ Ipath~ay, l~gdii!i!!iI ~o"e g;l!lllil!~(lIrm, A@ws if!dh:a!IJ~flIIIot'l$; d'ottoo

REPORTS
al'l'~pil!g &un dill~x!pai~ diygrgwi!~ C;lS~e,~di ~t<J!~os.rN!!1.N had ii-I :il'atio .of fcn:iEl~e \'1;I"QJ:lm 'k) n'iit'ile 'lM)clters [48.4 ± ~,. 7%: 47. '7 ± 1.5% {mW1 ±: SEM)].fN~nEhad: a. ..,1 : ~ ~atio offuit'1alc" ill)i'mphs, to ifl:1alc warJf.!e~ (4:5,.9 ± ~. :9112~1 ... eli!, 4o/~)"rEniN had! 3. -1: 1: ~ nu!io of
CQ:!'il!<i!S~

~.

Ow data I'lt...g~~c6c 'ii~Qdel f~ring ~ slll· .gte X-I:hdoodl locus, duhbed '~!'-'QJ*er (wk), wid.l

OOIls~tooil

i.iVilblhe..~ [i~iCllon'j;,. R:. spewk'(.'ii

'1,~cipie!i!tcoIQ~ie!S COlltlii~ed ,.... .tko

qli!~.!.ki"g

two alleles,. A and B ,Fig ..4) [se." dbrer:mfo1Jlarlion in R. S{!tlrnttti'lf appears: Iiliuoolvc an XV system, .RS fOl.IIJ:Id i~(ldrnr :R.I~imnefiru~idaeaU.d T~rmi~idDe (.IJ'I 1'9)]1•. 11~~ n10dtli ~!ilm:Mmo idlntl!.lillltlof
'L!iIflv:imiJll]tn~nl.i!l1 :s!iI'l1l)1~ip:~!!Ir:6d1lJy

It'olE!t'lk:: \voli'ik~ ~G rfua;[~ wo:~)~ (3 rn .Oil;; 4'(D%~ 35;.8·;t. d;. 7%: :3. l" 9 ± [,4%),Fqlla.!ly,. rll:3il~ l!'iytt;tl~'l~l!;I

~p:~.cti':",L'l
~~k''\.Kl

illdiv:id .... ~ OFlSpcin,g\t1illl

g.elng~y~

",md
..

e~rs and s:oldielfS ,d:erivOOi .frJ">Ol'l1ll ~illle woOcloor line (fig,. I), bllin iOO 1IlI!f1'I\P11S (19). On d:1C i.1'nI~.er hand, I? ~rmr.tJ> (!jfllcen.-qUGOO imcijpiCilllI: oo~Jln.ies COil~ I3n.i1Gd nY1m,ph~ :m!'!. wod:i3r.l (/9)1 H IP!li!Wnl:!l:ed ffllm our ~I':um~nl~ sII:I'O!<viltgilinvil'(:lllilD~nl3! mooifi~ti.Ci!~(If nyJ~lp'll.!l,~!l~lW~,bl 1I'1tl: I!'el~led

fEnlI~ lmel ill. ~l :] !I :Isplil ,of 1.!U fO!Y!' oilfsPl~"S: I~y~, with~ :!ll~~h~ias 'Orln1,)l]"Ilpl~ O\f>ef. wo:rk!()lj'S b
(33.0::1: 5.8% fenmle mymphs: :29,.7':1: :5.2% m!aU~ Irlymp1its: 19;8.:!I: 4.5% :fCrl13b WO:i~CI'!>: ]7.4 ± 4.1 % mH~w~). '\\~ sa"l,"s~n~iea.n: di!furm()~ {P -c

wk''''y develo'p -h~tOW>O~rs:; Qrrl'>~I!i!.s:~d:! gcnm!t11es l!?k"'Aamcili wl!i1; dcvclol) into 1IlI)'1npil!S

(JtOO'] )~Iil [h~ ;O!mp:tin.g C3£!e: and !l~. nllio:.ll lor 3n~ sb:p-air'!.'l'~ C~!tlJpari:OOI~'i belW~~ pair tYi~ by Fis~efs ~t !.eSl wid'lBo"f~!lO:!fIioo!TOOtf{l!l. The mean !ruIMV'al mne (Fig. 3) of n~, off= spring was s;ig~ilicmn~y lo.wlo.1rd~g.n ~aal: Qir fN, fNmliN,ID'Nm.E, and fEmE. The mm:an sITI"IIlwl I~lil of fEm.N olT~ni~g \WS ~!Q'"l.l.ur than :a.Uu:c:at'nl~UllSWl ff,!lJdroug;h. uet sigttlil~~I.ly.~aJ~~
(!f'r I~Vo\l:l of ~
PjI' WQ~L;l~OOrO:U(lh:J).I.dii!lg

A~le~e Bis !m:rnozygOl!ls le,tb81 .Bec...:me hl8'lfof dn.c: olf~rnng plt'lduoodpardl~'L{)~n~tiMI~y .by ,~~tr::Ii,cl!ii amnIV~~~ d:'l~ 'will btl: ~ W';afille-;. Ihi:s is .• oorn.o;'ii!S~rnt\7I'il.b i1~ )ligniflcaoLly ~(fw¢r ~!!IF!.'ivai~ ~i1l OIffH OII."PrilJ!~ {Fi~. 3.). S.iInilarl:rjon'!~· q~r (!If fEa~'lNoff\Wri,q~ are' p";ldie~ed l~ik iI'I'I!'iiliMe,~~~idh. i~: in rug- ...."Cn'len~ w:lth,d1.e lower
:5I1.1N.iv·!li1 role of d·lCSe p!a:iNsrolati:'I'e~orNln:fN', fNl1mE .: f (i.,mE, and fN. WYl'fli!lb.gmlot.y~s, Iili~ ~~as~ie~bo1d~g wbjet'!~. ro

pll~ftI!Onal. n~ooific:<"tlOIil, \~oo

wepla.ood

l~;jj[~

O1:ooolmted fmo£t~r!i!igmo:.~i~y. BecallSe .~~ 'il'aedl~I~pe.ilf.OO, o:n~ylWi'Col.y, it .r.s Wl,gililly ~.mHkcly 1~lIilm.w<Drkcrsremo'll\ed partictlixtr m<;.t(.'S. lIte scm" !lidvity of ~£nl1ile eggs 10 ,e.x:pcrim:clIlml oond,~r l~rOl:iSillfrY ClC,11lin '!1m [\(lla~i.v~I)'low S":U!"II!¥811 may 00 d!J1.e~o \~.
rallia~l1l:Mm.e siJ(. l!rolIlnlen~S (:s48%) {in Our daU!oo!~mldi!o! Il1I!~ I'IYp.cl!dl~$. !ljl~l 00r'" ~nhC':!1}rnl~h and, woller caste derenl.1iiumt.io!~ is

thcIlQgm~tLcam~y p~~ fN !l~ridflg (wk"A) in dre prrescrn:le of a l'Iul!te and fbn~:ille nYl'Wphoad pair'; 24% de\fcil,o~in.to fen:m!e"""Mtm, d~e~rest hna faJilKlle n~mplls (/ 7). S!l:r.gh~c\1mli.OI1iSill o['sprin~ d r:a~ios predicted ~ I~b::~m:!d.el (as sOOilirn, fig:. 2)

nest ~aw!~ food'll\!illll!] onewoodl sonroo. AU ofr:'1pring hll.\'C ll1IIe~tefIlial for mr.~~ dcvel:op:lil:lCllt into aB9Ics ,or ioootcHa,btn liI~~l reilfullu.fl.iS gJ)ooh~im:lh,tidua:ls tlllOOU' dleiln:l1l!l1erme of p:la~mJl'iIOftLlS~clI b"y :lllllR:dt!i~Ii\!\(;; ~rn:!.i'i{idlials_ TiIlI(ll $~r~ti'lt~adW!lt~ag.('l ,t),f'!:Ii(l: dL'>Fi~: .R. "q}(tJ"(lltll!>'g~~tuc ~~ml'l1ay b~ ~]h:l"~~:dll'l'hlkliti:cUli of se.lfis1il reproductiou by Q£!:"Spring, Il~:i~~ billy dur:illllg ,oo~ollyd'C\iie~armlc:nLTIle olf~ri~

R. jlavipes. quoon-kins: OO~iJ!'Iil:es,con~aJned If!e8[t~sib~e~111l11oors Ofllll)'1IfI]pilSl (O.?'! ± 0,.:28, n -17), W'h,Cl.ruru: ql1Cein~cs:s Qolomi.es, (w:i:lli11. ItcOIenics) ·OQj'llI:ai[b1M I~y ItymiP1:t5 (:550 ± 8.6, rI ... 3) (2'1 ). The lI:!irti~lOO .~ ;patlili\W-Y .Sl1iovmiil. r~@:" 1 iL.. iiIiI~l.ighi~kiI. ~l<'l!VlL'lLf~~",~diitlflil ,a. rrI~r !ilalmway r ~ 02, 13, 21). S~ci~ wilh a li!l~r p;i!Dhw~~

b.a._~1(2'2) .~

'ph~nlOrnJ)l.

ii~O!i£tlCe fmlll'!l.

produced in: !t ,iiipitUl!U;S @OOiKting ·ooknajes rue p.HtI!rllllb:ly I.m!iblc IDO develop i!lllo ."!:~. 3.t\Id. Illll!lar propett<irlY I~O dl}¥~IOll ~"'ii:O se.lfih'iDI ilOO!e:ill~.c.s is
relruli.ve1yb.v; R. :fipl1..rotI1,'!; ny~I!l."'Iil;':Q!Ilrl'C; -12 ~y,~ilI~ a ~Jligl.e[Q:li)ll Ito~!l~e liIjIfI·mj1oo.i&, W~a!eol5 wor~Ci!'S lll;lCJiuh:e ~!() w' 4!0 da~ lind t!8.'O

du.eo:nly

I:DCnv,troifillJerll

(12-.14) (rig. 2). If

1i11mOl1Ul~ l;ITCC1i5il~ llliIe cggs;\1I,[crc~:liS~blc fur l~iI)mdifferti1:li1 easte ralli.fiS,. we sltmuld sec: sirnUl!ar m'l.;M~i'l.liii'IS 3j11.0I'Iig -oifspri!llg of i'NmN'a.11Id! fNnliE~ and 111$10 of ftlmlB .a:IIl.d fEmiN.. Similarly. paremal c«w.'I: are liillll.ik~~y~~eo,f IiilLl; highl)' diWe~'!liu~cd caste !<lItkls o~ oiWsprihg ~];\Vcel~ CNI1I1N ~aI:Jd, fE:1I.1N anel lJel\Wticll. fNmE .iU.1d:

1~lIldJunli:wC!~,illi)Qirn.lprew [~nn!mUlca .u:wk, (ld,l~I~i. wi.l!l,l ~rr~'C~ .!').!fI. ~\IOO: and $~, 01'·;11 ~ oombanOl.li()!] of ille5C §rr@flJ'. \Vc: <1100dC1iet1~,rincd a s1n1~1ill: blilt less 11at~1;lOJiliOU lln.ode~. tJJal, filS the 001"11 ofF'l~ 2: am:! :3 (fLg. S I,).

I'Em,!;.

In{)~,tsto· bcocm](:l a;garulds (.2'1)..Thc'ovo~utto!Ji of ale ~o!iCIlU)'ultfluel1cedcaste d~(i;;m~in_alkm, m1f1 1i'1HUil'llOrohavc faci:lilm:cedia'ICl'('85oo We poodfct ~'lat ofm's,prii~g ii~ o(llil.ieci:tr.~iilg ~l'iI. ool.ollli~w~n iI:m wammi:> {L(l..w,0Ax wk~ '"--t o()kli~Y size and ooologieal d:a11l1~naJ1l00., , [fl.,&'fvil1lgg~netl.cally I(a.~O~M. Ilg Ci:'1IVI~'Li~1B+ l'loift).ll~ 111m ~"'lliltd131 ~ffiI(,;~iI1iOOrn! ~nd/o:r I'l)~M:lilcll!I[1J1M~oom~:tn~ \\V!'}rn.ersl,Wb'tl'l: advanl'n.· ki!lflgd~e~.e:rga!n~dflQot~li'IiCl'! £lnould! d~'IIelop; and fEnllE, qllJ;le!t~!OO, Of k;iIJl~·fE nla1h~gJS s:holllhl gw'Wl,. Ihe A1ille'~e WOlJldlin:wd\;: !he l~op:!JI~ali,OJIl. rcs.tih 1I1w!Oriwrs~mel :gen.gl;w~o irlyn!~lS I(Flg. 4) .. ill ~!~.Allele A.~"'tou:1kI,l.e'ad ttl ,colO:l!liesproducing II rl:nlD~C hu8.S lU'I1Qflig oimes,. due 10 ~jj% (Df ~:ndepeudent QQ!ouy C>Ol.nPOSiDioo s;ltldieswcrc m:ilcs be:ii:tg 'Mllgicss 'WOrloors, $nch a hk"lS oo.ul.d f'aV{)!I:liI'mii,Wrl&OII, (]irB. c~vh.ieh.WQ'"ukl,~ am. alate s~';[aJmjobias j:~l\wfdlmll~,dI(te~.o ;:::500/G) of f~:J:LaI~ withhl co.:lbl~h~$beJlIl,g\V;I~~.~ WQtk.411 ern, Event~.i.!ny, p;!"inu!!),~l'rod,~I'Ve i!1dividl:!<1~
UfO
IIJi ,!Ii

IE
fNID1lJN

T
b

.~

T
lOll:!

,iii

,Ii!

...

'fEmN 'fE.mE
(II

O!.---'-r----,,__----o------l

f.NIE

pr,o'port~ons of 100ffsp;r~iJ1lg ,ca:ste a.nlds!e:x

0.25

0.5
1

10]5

(n"4~

~i"1

W!mN 'f,Nm'EEmNI n:mE

'~~,I (41
~S)
1>'111

IF'Eg_ 2~ 1F'~opartij!cms of II. sp(!rurusflerllla~e <llli1dImle, 1i1,~ph <lndwmker ciff:sprill1lg from sib:. experimenta!~ 1~~f!ri!1!g b\'ia,tm~ If'ifty!!'!(lJ~rs raiS!~~g£gs fwQm l~rthe!i!Qge!ilmk fem~~' !i!'Y!l!1i~h\"1id'tS.(fN)!i!!ild ~r!latlJids (lE~,ali1d1 the 'fiol!llr ~O:!isnbl.e' l!:lm.S5e.5: illTlorngfNl.. ·~E.IiI'Il8lernYlil'liphoids 1~ni1N), anti mle '!\I[!jEiWili5 1~1iI'iI1~1 ~.e'•• fiNIIiIiIIN.• ~~IIiI'I~.fBmN, f,UnE.~ orms:~rin,g!'ilij:!~1"! od!edarrClIS!1i,~plica.te ,oololi1,;~fall' earn mlClft)f p tyPE!!(se~utll .Sarnpt,E!! ·~il~.(m.H111lI!@rs '~f oJf.sp:rill'91 pr,~dI~.!!:ooJa~~s:hOWf!Iat: 1h~ ng'ht
9 NOVEMBER .2007 VOL 318

Fig. 3. .S1!!~l ~a,~s of OfifSPI'li'J,gl00 ilie third illilstlr (liTiIfJtln~·.. SE:ilI' i1 ,expilrirl'mliltl~ trMilmEliI'ltl'i. . litart'e:s :welre determlli1.edf·o·r mill!>! lieptka.tes pr,eseJl!I!:d i!ll, Pig,. ~,Mt!1'!i11Sthl1lt Ib~f ih!'il ~!l!~:e ~'r I[i.e.~a O[ l~) ,i\iir'E! not s~grni:flicamliV difreri!lilt (rl!l'l(ey'~ H@I te,>t.. p> (1.115); n "".Inllllil'ilb~r of rept~~s; I~~~ it!1~at~!1!t

SCIIENCE. WI!\lW.sdenaemag,,()1'9

REPORTS
d"
'IJi.-' ~."A!L , ...i!o'

'wABY
li1,ympl1.01il

wk,Ay
r:f
,e-rgar[old

~r'~I( '!!'!

wkM
~WOfl!er

IW~y

il WOf~ai w/fAy
d'
wo;rk,er

wk~Y r:! wCr:l':)Elf

~kM!: rlkAB
~~bj[jl ~'WoffliU'

wkAA
~,nymp~1

!WkAY'
rf waIl!:er

w.~,
~~ph

:n .Siee s~(lfIOrUfl'JIlnlatl!IIi::lL
~::HJIl3J.

'Y~rl::,~?961~ pp,OO-l12 ~I!I 5t,/mrl? oruIlfH!', :11:3.,'f iflaya!l'lil. Q, li<itO!l!l1£!,,~I, IfiIl1hrilil, £llfO.\llQl: .S'd. 6 .• 2$3
($pMI,~'r~\.I'\I!Jlagj N~

114 J. K~~b.,S,' Km~lIli1tZ1~ i'~t ~ 6.•.M2 (20041. •. :lS" N. L.<J /.ai' ... ,i!!itll. t&ll,~, ::;,6.~ QOOI7l, e ~6,. M. l{ig3s11i. T.l\be. i!ll B~JiI'e~1y. /Iii f~~k,al Pef:t.pooi~" 1.1I_be'. 5. II. llie~~, .1It !ili~sh~ [;dI:l,

IPll2li'(Y.), A/10ill, ('. Oo~ll'Il\, L.. Kf!lL@f, 5lirMti!1' 30," l~OI (2004t ji]." 11. fI, \i\DIJiy.. 11). 111,GO~doo, PI"" liIall. AtMli'I: 5": KA. 'iI'9, 6~oa(20021 U, !;I., t TlhQ~~, AlI!m~ l'il~; u4i, ~p.l!. ~@. <1" U;~n), ][;1, ¥. RIOO51Fl. l,p,T.emN1.i!!\:iBI&.mJon, SIl(iatf~, SJl'fi~.r~~•. ((QIog)I'. AI!t~, Ill...:, lil~Lt ~~, 1i!i'!J,MII~ {1'J~r Emile fl!,(ild!!!iIlk. &rdoodli:. N:~Uiil!rI~~~ :lOO!:!}. JI11I.. 95-:.110., •

HI .. /iI.

u.

r.

w/(D6
~ lalh~

wkB'V rJ I1piii1p:l;i

wtAB
~~mEit

cr~

wkBy

19. I{, i'lt.ilt:l'llllr<\ M. F.ilJjlil!OOtllo (IQ:l:iI. Wffl~!I 5'«, ~':1.~2S, It (:2004~. 20. Y. H~a~'li. r.I ,Mfy<ilil, 0.. !(j ~d'e, :Soc:roJ.Jiol'09.l'

4,e.a·~9

IF1g. 4. Onil"locus"twli"a\~~t~m(ldel ,(!If :~e!i!~afff,OOii'!f!gl C~~ dmrmillhl!ilion in R. sperams" 'This lIiIU}(JeI.liit:5tlil1e data hom Figll. 2. and 3.11h:e lo~us,. debbsd worklKl(~)"is X;.i~irnlj:ed, and 11M h!ftJ'ilIll!~m$, .A
:RJnd 1:1. ~m'a!Ie'$inl1~MiIil!1 two ,oopii~ Clf A hQ.lJe QJ ~h gleJU'ty,pe; f~m'ale5il1li1eli'itin!1 ,a ICopy ofbm:h .Pi and B hav'~!ii w~k~~ g!i!liIotyp~ (th~ IB,allele is d'om~rn!i!n:t), Mal~ , a !)cpy ~f A h>a'l,il~(i wc!I'iK:er g!!lfl~pE!'; llilili! ~~S irnlt(ml:tirnQI a WililY ,Oif B: 1iIi1¥eill rnym:!ilIiI, gelflo:typ!!.l1he ernot;i1ile i~[efuaIL Genoty:pe 1!iIil!lt:lliles l~ht1!l:Iot¥pe! ul'lde,~e;q)eri'liliu~liIra~ r~rim1i (Mdiitiml(> (lrl1!.,inl thi3~bsence' of r,~r,odum;\le Im::lJ~d~.i!ls),:I'~Ul:~ pjj\~S€N!!~~ !1~rool!!m;\1,@ llildivi~ua~s. th,t! IiIvm,~hl g~fl~typ@' llIlil!y b@ ~mgd]fiooirlWi:! (If worlolerpltertnl:yJ:!;e' as il resul:lt off emvim:lilr1l!!'!n1ial mmuli !Note: R. ~~Il~ :rlYlIiIllIlilo.icl and ,ergtlitold Ifemales p:roallce hOO'1lo~goo!i. f'ermr:ale:s, by ~a l'iIiIi1ellilqger:le;I8:" c;ru~ytthg 3.001~;Il!atLQ;1iI a:fA and .B: <'l~~er~\:vw!cl! ~I!OdMoowurk~rg of bodl se:x~. o~ornlpeti!lilg 1!1il~ with ornly ()Il:e ~ il!~da]![)~~~ dIe .;lU~I,~ mg.
t~(a, spread
I'Il'!ifl'!!r,~IU!@~, ;allld Nm@'.!i;

(2'OO~zi, C E, L{j~~\ 8,

I,_ ifhiiiiW.!,

N, l 9~1~rn,I!II\iJ'!~r,lIIIDaI. Ill!\!,

:2,:t 'G_ j,

(1'.;1, 'i!lJ9' (~003,}fJirlllil\p!liiIfl!.

O. Ki~~. rI.!. lLo, it It. (:~M{!r. J :tliot

fllrJI.U, Mil 1[~Doo:I. 2,3" 1'1. Mi)1aliil, ItL Ifliru1~I~l. O.

rnll;OO,

!ntomo!:Si:j',

7., 3Q~

~:<l. ~,luljk:.~ tl'i91i.

~20041.

G!A111_~f

:2S, H. K. 1'ie>e.Wi:.

J. :S~~~ell!'Itr.ii""~"'>e.

331 1101 !:l9001 f~~ f,01', lI,'l" ,3:5,/"

10 f~.alio:!ll. BOClUlse an fE·<llways l:la5

1~!IIle ()~Il!my L'Onrmte lIInder Ullltl:l'ai (lOlKtitioll~ (w!:th ~iItI!e kit~g. l1!iE,. o:r linN). !cUliR[ l!/Rul

.3.

win 111Jl be lli'!Oduood ~y fE p8U1!hl!lO'li:'lOgCIDl~~, Hmvecl,~r; ff:..,king Of;·fffi:mN om,s!>t':S, ~.f '~Iil~yoo(fi!lr, ilH reslll~t lA 2~(ij() .lettlial.n/L~[l, 'tim w il!drv.t1:lI'Ilage ·of 'ihe: B ~nie~t;l(Le. .• p:~C:lMI'iI ,nf fl;!lla1e w:o:rni",m) IJ!"CSIlI!lIIwly o!~llw~iS;i!s tMs ~{)tcn1br:lOO!S!. A:ld,\OlJJ/g'h. SOJrllClCn:n.1tes Il.lil;)' ~~iiI:'!i'e~p ~oI~~f I~lhcir @l)m)miC ilu~oo, eo the X. and Y cl'Imm:o$OillJ~Jl (24). R. ~pr2.J'tiliIS app~il) h18iVe :at n:i!i:lSt :2 (lut or:2 ]~lap~(lkll} sex d~mnli):SOll'leS {.H')I nUio<i1, the p~uce of lil'k Ol:l a *~~I;I~!o:;$ddl1:1T(}~lomrne Ulay belinpoort.!!ll Theory' 'pre<!k:~ dutt se~~Hl1keclllQCi ee 1»Of!: e:ffld~llt at hmt)Ort~~'lg a gM04:1pe.s
1~I~ei"QptilattQn fr.olJl. .~pr,eviol!s~y w7'!l!i.mlly nlQ,'[lIF ~lOli'ifh;~.coplnlf:t'llUlliiI 'to i1,~mlP~m'\,.S(l1>l.-OO:fildj!iollat

QlJlttils. J. IE.Str~5Srnan. i!IIosdifICil' 4!8. 165, (19')1'131. ~. !J. ~. WIlIftl~r, Am. Wri!~ ~8,B (l:91l'6J. ~. II. H./C:'wier, 1P. p..;!!tril!l~ ,fll'lI!I!tJiQfl (!J/!W(lW.j'm«'t Ci:1.1M~fS(JQ~fJi.~lII Unri"'. PI'e~. ~ew 'I\~rfi:. :Ul!o~ ,6•. U. W~iIrI!l!f., II. lliii!lhEfl!,llil!f. lrtt.t'!mo/, '~IiI, n, :I!25
I)" C.

atI\ [9m. 2. 11,. S~~e,r, f. llloo{. 8.1D.1, 91l. 1 ")li

~.o_ Wil:sDrl.1h1!11~.~adet!~~

~~ll::nai!'. ca.lifb:f'kl,~, {l19l8l!).

26, ~ tiMl;nt K Maru 1:0, W. Q, ~. IHiJ9l1es.. 1'(,. Int C~I!J.!:iElf. ~ SW!m\. ~, .~Ilaf~f • tli!! Bl!'lia;dot' .:il~ G!!iiuitle~jjl Sild<il. 1~!!ul.!J, Lab,at !lie lIn~rsiljl (lIr SydIfl~ fii\! dI~(Ij 1S[~i'Ii~ ~IJPPill'il@d Il» &ill1ts~l'I-Ald' "or !ldtlillli!k ItflstiiWl ~6146, l? !I7 [l!U3, a nell :!L9~7'QOO~'rillI11 tll!l! ~p,il1l :5tKi:\\:1)' f,CrlQI~ I"rtltml~illm ~I :Sd~lK!i: 'L't.lll ilOO

.am

Oil(J;",1KI al)~~f'aL~!li! .f.!!~~!'f~hip (~I,U"

IR~ear:lh

(JljlIII!d~ !!~~td!l)(tor!il

SUIil'il'D,rt1n~ Om/he Material.

_

_ (:!~lI!lnnulV3,],Mi55'2Nt~'SJl)Cl

,. 0. hYFl'f~E1 eI (ll~ Nll!ttre 43,!t, u~al~:llOOS!. e. S. lih!lln~ C.ahlli'l.1L Illllll!r. lVilrlJre 42)11, Ml~ (20:0.3:). 9. G. ~. J~liilil. . Iii. IFt~lli,l, ) 'Gadl~lI, a,.A.. f,il\i1f!5o.n" I). l.arfiblie, f.f/JiC" Natl • .4(&1, s;a: ,US.A, 99'.eJS? U~(ln,

(1986).

:l:l)

)JJ 1M! 2007; ,iI;[~ll>t.ed 9 OctCl.'!!i1 2001 lillU2.6,!'St~ce-l146"!:U

(i!:ptt~nllm,as w'(mkl '~I!h!L'l case dMng ~:rl''II~t(m of I~mmA allele {25J AII(,lI~':! , and BIfi3'V¢:I11 A (i!~ibt;l ,~IT~lil~ cao1~ 5e1\. Alle'le A reslillits In Sl-'!IDlwlclh1~al'e InYiluphs when :hmnnzYSOllls!, ~~",. ~uJt !resll~Is'in, !wmJilcWQol;lIlems as a si;oglk: oopy;w/tV. 0U.e~e .B
R'lStltnsii~ lIni8le .~i1QlYffi'lie iWi:i1jfhs" 11~Y. bl.lt frnnillie 'Workct'S', ~f~ik!'~ .. r@j113~.e and lImll~!lIMes eaeml .rumy t1iitC i1n~ll1l I~~, ,;,Iltiebl i.'Il~OO an I~f! (i!rr~iiilg; OI.fltJa~otipo.~ul.e~~ ~sdiifii1i in.wil~gl~ 'WOrkers. ]rr.booOOlirnS wIthi!!! Ole coliCiny .a;ppe<i'fS i!O be reql1iired to, pr.odtloerlilnillle,aliil.tes:.~t :Us 1Il!e occ-rn;i(}lnl~~rodlllC:liLGnby wa~keli8{as erptoidS) l~kni!d~Q\!IS ,C)'c:le lo ool!lI:i!lfllll£..;.TIIC c.....istmno(\'l of 11m iH:lV{lt.lllli~]llC:~C:ic:!>: with c~/iclS ndfor wQ,3i!~rn ofrnlly Qllt'!: :!lex: 03) suOOe$l$: dli3t ~l1eliCOlUyi!afha.~!~e~ Il1ymP!l and wOt:k~f ca~a dere\l!!~li!l.ttio!~rllay mot ~e limiled [0 R.sIHiJ"OlJ'rs,

Mnleml'D,nic FUlncliolnJ 011: 'the Dorsoiale.rsil Pr',ef.,ontall IColrte.x In 'Conlflicl-llnduced Beha,viioirallAdljlUlstmBnt

Our (1JI\Timv~ aJb]~iti1~~iii PE:rlai'mm'~t~5k;s. Cireln~rl!elil(i!d by e>:;~ri~iii~~d ~(jmpetiti'DfiJoolilfllli:t ~~iii btehmDral, (hok~·., To il1I'etermine tne filruili of the in!ib:inOi' ,e1rng[il.date loortex Q\CO' an~ dI(if$jJm.ral~ prefNlllltll[oofiteli:(I[)ILlPFC)in the mnllicl:d:etection·~~rnutiiolli p:roQei'ls, e (oomctedl mm~'menl!aryle5iomr w and sii~g:~e-ceUIr1ec:curling srtruJdres, mO!IiIIo1e:y5 that were lrre8ol~!lIgl B I(Onf~'ict b.e'i1weermiwo Iml!lles:.W'e ,ol:n~er'II'ed ~IPl >oonmct."imluia:!dlll1l~hllMm,am a.djlll!>lDrmernt ~hl!t'l: 1~~si~,ed .. frl:eJ' l:esiiDI1I!'lwiri1lirin tl:re MC but dislll.~pe'all'ed afffer l.esion~ withinl ~file DlP~(. ,[~the !lillIPK." ,a~~ was lli1iii}dl!ll~tm!dl 11111 ~omJe'celb: by 'm e '(llllrr:el1:tm~mrn: I~e!lel ,and' ~Il!'!'ther !l~~15by ~Il!\!!)onlffi~id: @ii:.1~~~'~ illi the' previOl.ls 1rl'a,I,Wi~e fllSl!.ltts shol!\l ~hM th~ DU'FC.. bliH mot th@"ACe, is ,e:!;s@,ftllfal '(lfHte< camlttJj411d!il:loo b!;!hilil'll1ooCl,l ~ @d~:~!Tt!IDt ,atlti s!J;~g,mt!lil"t ent:ooJnQI and mlalfl1iEmall!oo ofl'liomaJm:on, aJbWlt ,experienced (Dmltu is; m.e,dia~dllby the O:L~Fc.

;able

T
__

·he WiSOOl1.~'n.·CanI. Smlllilil~ T~ (WCST) (.1).•.. \V1~1Cb as .oo~n usoo ooUll.n~l)r.(u h

a~~s!l~1:, !s

rl~p~lK'llQ~~~] lasli;: to ·ex<Jimhle

a S;gl!l:.

~J~c 1~lm!'l~l1!5

of On;)

oooUim"lJitdllt'loo hehlViotllll a~jl!lSLll'lill1t.ll~ dIe WCST, dt~ ro1tlvall.tru:~!l!m:ll i~ fruqu:cnl.,chalil~ aile !l,<Dl J!I!oo,md tllC~tbre' I1H~8g~oc~ faoe a C crn~f1ie! Of (l(Ullpetttioo 'OO!l,1\ree!~ Illhep;aI!Q!~~al

REPORTS
~lMooh~:g. n:i1~IPa~c~~ \lJ!lhh prefilj!l!!ol!loorleK d;~l.\l!$ twicatly shQw imfll!re,d perfO;ml<JJice Oill. Inlae WCSTiiliridi othiilill' tnsks in ~:vlilich( 'line}' slmul\d,i~~\le ·OOl1mO~, betrwcel1 ~1ilia;1 mk"l)! (illrrt."1pOi~u!! {2-4). We; Irniil!i.':d 16 m11Ae9QU!'l ~lOl1Ik~.~ to p""rt'Qr:n, a d~analo;g,of,al(lWC:S'f (fi~, SI and :5:2) (5~.7).. fOQrlli!Cll.t~t'!y~ I~~i:v~ ~:ilal~l'lll a~imtio!l~~io:~ to 'Ih~prim'lcipal ~!.!I'lcu.i!; wilt~~il'l tile l!lLPfC,Iil:uf'(Jther ! m!()i!lkeys receivoo bihneml ~csiol1l!l1U ~lIe slllill:lli ~iliQn wi~,l'hl' the AGe, ru,1d,si"l. OOl~' rn(l(~eys m'l1aid'lcd as: unopomrnloo oomm.ls (Pig:, ~Q J[ldle two 1:t'm~njJ1il.g rllrnl~YS fMl .~. M2), .. singl.e-oo.Uacliviry wa_tI; I~OO flU'Jfll U1(llDt!PfC ~!~~h tri:aJ~ tillL.'l I'f'!:o!]k~,~we~ ro~!JinW i~O select wh~DlrlOOi;! gut ·of U~e different ~l iOO!l~s :~mHollied a s:a1fllPle." ,oocord:~ng ladle cl.lJi'irel~lly
Irch~vanA malClitLI1,g ru~C!, 'um.dcIiOOle oftl.:vo dif= fcroll! Ic't,'Uis of{\OJ1IiIl~et low OOiitl1ktoocli h£g;h oOIil~lkt III I~!!t:; .igb.-Mnf:liC!. CQlldJ~Uon~dl~ samh [[IlL'; Imtci:lLl:d (Inn Q!f '!he: I~~ lft~~ in cC)~r .m~ :!!i(l',"L;ir 1~~5tt~!'I1 1!Iii ~Ii),a~~:Wio\'\'i~~r~,u~ i did nol 'nmtch dleremii!:~l!Ii ns t!!~H.~!rt'\ln:in dti~er eelcr (]!ir sh,~ (fiS. SI). ,'h!::l1e['O:re,. 111~emO:I1b:ys had .(Fi, _ g.,,'~~' Th-,:mdi __ ~ e

ihll1ilOmlset .nld IniaeliUSl. sereen slG'\:vei~m high~onljUct ui8ils .. ALlu:ce· WRy mil9~.ys~ f vruirulre (KIN'OVA) 1[".i:W!if1tkeyl' o l~r"~~-!<I!Ibj:ecl. fatloi) if( "(lolfl~1icf' (liQ.\,v/hugh· \,jI:h.i!l'i.~li!lbj~.t fitcl.or) lor ~',~!JP" {coI'III!J'(lVDlWC/ ACr~ ~hJ\,t¢e!l-.slllbj~t f'aelo.)]1 apf~i~d1 t(i. an~ nOO11l).~~ STS i~~ ,~ bii..~ slID\?irOO~'1at O~ere .~ II ~~~3ni~CEl.'Ilt m<l!~n. eff~ orCQ<Jl~fCl (F , 2:SI> " 509, p-« ~ x ~'O...,(f;!-),!rul theilillcmctkm between dn.c:oolil~ict and g.t'OtiP :foo.l'Olr:!li waslilol siignrif~. cam (f:i, 2S~ =1 :9,. P = OJ 5) (.il WhBil'l \:v.c: used
10001c1iI, W8I!I (Jllily

tnJiid~ was C<l1.cu1J.tood!as !Jie~p!'ooi3!1

DeI;WOOn d~e ~I

~"'~i

f _~. (L i"",,,..,

B~;cl1ian ~ '~~h {S~\ s_ 6C.

,ofUli.e·1:lmne

lul~O!~ QfoCI!]Oicl ~d .i!.t~jmv~ ~\l:ioml o"i~ d!!C!.i,jT:iSI<l]i0e8 \vltereoo!]r1ict .~ yet agruln. Qmseq,[J:en~ly, ~f:I ,cmer 1m ~litiIr,e Wll£dle11 I.nili1lk~s· petfnm:mm.1c Ilf'\\l'limllfro"lll[ixl wh.ein, failed widlqeauxl. hjgb,.oolil:~ricl sitlJmio:ru:,

m nbsc~~rU

g-IS

aiflL'; a~r:l!s.~d 'a,~WllS!;Iii~O~) WU)trli1lllliZLid fur !laCll ~lI,)Jflkey~I!IlO ~S'l1ifi£<'lr!l ·diif~ f~nce was !'OOOf! .~~. the' rn<1..Q1liludeo f Ute STS modui~ilIlion (Lie" 1In.edi.lfcreuce la~ SfS ootween hlgb- mll~ ~J)\!,k-00I1t1i~l, oilill~) bCtWCi;.11 ~COC!ll= tro:l and AIT' gI!OI1,Pi'i(1M'" R.3,P - 05, t t~)
valillL'l

.ooflfli~llirial<:l~hill.r6lIo~d~ow-{(li~mN manit (LH 1ciiL'l) \l,.;:nl~ l!:hal 1m! 11,~1!1-i7,\nflfljj~~<: Hlatlb!lowedi ~l!~_~ ;mflia~ !.'!'i<1J~" ~HH l!!i'Valis).. OBly cor~ ..o roC!~:Irii.ds: lni1al were IPreoodL~dI by oorroaliltilllls w~oolt'>Ldcred iI~I:1IIJS analysis, ob~eiVed thaI!:, iifll. bodiI the oontrro~,3J:d A(:C gro1)lp~, IllimSIS ·of ~lI'I~ooe(lmlUJ1(1! in .HH. maicim1.!b'l '1!,1~" s;i!Jli~ClW~ly~t~fdn,1JI~ llliIaot (ilf UjJ~ ~olld !ci~ il~lH p:;l!i:!1!~~; I~~~~i¥r. 1'10 ~~ch Siipi:A~!u dil'~!l'ce ~l\?f(ll;)!l HH 0l1K! lfl .pairilllgS, was soon in dle !l]lPfC grcmp. .A dlr:t'lCC= w,~y A.NOV1iI. 1["rw.Oil'1!ley" x "pre'viollS cmdlLl:1t'"

\l!~OOI'li!l,pW'ib'tl

Ih~nIQUI~!l'

~havi(l!l'urn.

~~igt'll,.

"'I(:

()rOO""\1~lll~Jm~lrn:ltll[\d.

DlPFCgm!llIPll

{l7,m!; =

O_til. P = Q4~ l1~es(;l~~t"lin.di~ ~hal. 1]115 ul(ldJ,lillMigl~ (!IF SIS by thC:II:!JtrtCnt ,0000Ili~~ !L}'i.!'L';;l WiL'! not dirferen! between con.liJ1o~, and ~esioo
grl)1Ip:!>,
~ll1IClIn

(HHIlLH.) X "gmI!lP'l fI:I1!pHedto the STS s\lowed. a s~.~ifli~~url ain c~Thl;;~1 f ~lro'il'i.(lUi!l(!(l!illmCl m o (F~.:256 = ~:'41 l? = (U)M)a!!'Qc:I n.oilli1~~l'aClil~n bfit~L')<if! I:'I1I{:II.l!i!!ey and p:f¢ViOU¥-oC'OJ,'i~l~~I: f;i{l~orn or a~liimw.Q.Ilumkcy, pre,vi:Ol!..~dl iC!!. <!!nJdi group rnCill.U:S. tP )- OJlS), H()~!ll'e'!i'er.; IDlere\!i'll\! II sig~

~'lc oo:mpelti,timl l.x:~eOl,l two ~~ I~fll~i;[l nll!lllwhiugrules (~Je".• mllml:hiH\g hyaolor andl'.l13lCilnng 'by shape) 10 SdOCl U.tewrgcl ~m
I~:O' ~·eEo~ \'C:

Tillie (lOll ffiI oca~~ypoIl1esiis (&-J(}'JI posil?> Ih181 Ole <D:f (\O:Iilltlict and lfihc ~llStI!inlg adjll~' nle;f~t ~ifI. conool :sillYl)lDdi ~1.!IJ~t in.oollilil.Q®d .: 11CSO.

nilflcrun (F~. :156 - 3.14. P - (10.3)1 i.lJ1te.l'IlClillll. bctW'CCiIl tlne:pre;viar~!:iOlltldel: MI!(!llgr~p filOt.ol"S. A fo!].ow4lpposl.lmc I£:sl. (T1l!~Y ~r) :S1iIO\l,IOO

\Ve ~.1l3Iled! !JJlcpossiblerolc' ot the At.CC and DU'FC In, Ollfljn~.ct~l"Illlmed belllo1\rioml .. c:i,~ jl!l.lslInocB1SOycQllI:pming .be fOSt<Dp::r:aII'ivc! be~,avitn o~ :i~lCi\iilk£:ys bil.fftera~, ~.cs!Olll~ i~ilinl \lo'idru w d~~A:C(; {ACt: glUl.!lp)IOii ,DLPFC rOLP.FCgroup) (Fig:.IC) \1l'i.d~ ih~ belttaa.riol' (lril1:t~tl:l.'101DIreys
(~oJilI.,ol!llOO'!.Ip). TIl", ~(jl!lIlillgl~()1l$ w~re ,a.'S] l~le!1ded h~ ~1e ACC ~.!d DlLPf-C lcs!o:ngrol.l!,ps (7) O~gs, 58 ,mldl 59)1. .AU gro{~ps, sl.IIoccss;nqlly pet:ronm{l,9u: ~VCS1' 3n;1~.og, .as ~".kl~dl by idmar abi~:~Heslo lliH8.k:e 1II1lme:ro:IilS s\!"1!tmel;l belwOOflJmatehiill~ ~I~s per ~t)1I ~9;95\vitdl.e$' .~·&tt~y s~~m:'liill 1iliI!'l Mill,. I!IE(I!~ .~n)ll,!l{l <i$ ,~n~r~d h:l 9\6 (lIfId; ~l!6ffW~ldl~ !~the ACe <It!dI •. DLPFC gmlUPS, r~rlvdy), For angrtHJps,\i)i,re obse['\'Qdi d'laldL.e level of cOIil~i.cll}e!weelll. u'Datchl!1l,g Rides:~IlIll!lJeiIl.cedlihe t ~lQjjlk:c:ltsl bocba\ilor ~n ernm:m1.as \Vlc:tl ,as in. subSBqUetltlri

1~liIc :~G;w-oo[lfl.i.ct 'OOI1.cliti.on, Ole stillUP.Le nwe1n¢d (!!i~ (t!:f O~e OO'5t it~n~imoo~~ ooIO:n"arndshape, and it ,dild net :ll.liIIJCh.d'!ellltJ~e!" t\'VG L~l~le~ns;b~ e~ther color or shape; til!!!>" d~ere 'was 1fI0 001]= met bel:wcel:l 11l8toiullig n1iles. The Io\,!", fmd high.tlQl'lni.OIl'riil~s w~m ~.Il~crllrninlgt~~ mnlliila dom order, 'fria~ ~\!Cl:~lS. alil.d. ~H'; fl]ooibaek \wro slmil,a.il1l, ~'l!,gh- tmdIIQn....~ol1niOi ecm,dJi~ioos (Iii~, S ~Iam,d! S2),

,A
Lo~mGffi Hig;~flict
I(l..) iri;:d's 1.1 0"1) IlliaJs I.

fll .iildj'!U~1lmJeIil~in c,al'ltnJ!~ IlH.!PF>C~ ami Aiec 9rQIJps. ,~ The R1e.l1lli1 l1lorillll1ll~d SliS !If! I~t)w"c~~rti!l ~L) tlnd Inigim·~(ll'Ijijd (H~ ~mia~~ (ellflror hIm ~lIIdf;U1!lte ~il:M).. (1)'lIhe mOO11ll dllenmc~ifl STS, wI! l~pectW the !:ilKmd bB~ of 1i'lIi'lWrnLl5 ILH tria~ 5ieqllerlCe~ Dianmrlm ir:u1icalri:!

Fig'• 1. Ccnflkt4lf1dyo~ 1~lh1MQr"

thl'il data fi!i(lflf!l i!ildiVidl!l'al mOiIfl~~~. ~I!:) B:lad~ shaldililQJ~ slhC1tY the ~1fIl

telllded! Le~omwnil!ill'i1

1IiI.e DIJl~(

B
CO!"1llrol.9fO!l!!J)

U~ft:1i '~lfAC[ m'ghtJ.

EJ
0
0

[J:IbPfC

g!1OYJ;l

AOCgroop

M1 ~OO~

ak
ItOCnif.i\@U!l Ittla~~ \~

.0.03· -

W~t!IiI ~.
.~~.U1~OO!.Rltllj'

[CYUlf1.cl thai,
i)~'!~cl

::;elootlollJW<IS s!o\:I,rOO by (he presoore of comJHcl

~(Jognil.q...~ l1i.rajn Ma:p~!lg libmor.!to'l)/, RU;:EN Brafnl S6~mll!! !I'istiMJt@II' \q<lII'i~1 Soiil:<irn<l. 3S,l·Ol:98~ },ap,m •. ~'oil!J!lHlm@n;t !lif 1[~~~rimE!l1lt.ll 1~1ji(hi:ilillg~, lliftof'd IJnlw,r!!ii:I'I'. futol\liI, OX:i :mo.. Ult::. jGr(ld!1.il:1i~ ~-~hod ~c:i~IilQe imdi EIlginf~ri:rug. •. S,aii:.aJllllaLI'~n,.~mlityl' 1 Sarlarma 33SHllS;:Q, )OIp:arl, . .

ACe, and DLPFC Sro.u~,.

or

'Vo whom wrr~~~IiI~Ii!U: $holil!ldb~ .ndtessed, lE-m~!I.~ Ira~nad.@mtliN;ilI.!i~en.je.

'9'88

9 NOVEMBER .2007

VOL 318

SCIIENCE. WI!\lW.sdenaemag.()1'9

REPORTS
1~IIlia!l ~er>C\li"a$ a .!j!,giii:nCa:iJlt ijffe~oo d belw~~ ~lIlieciOl~ool ",lid DLPPC g;roU_P8 (p< 'O,.IQ<S)b!!!i i~o:I: bctwee~ Id~.e Qonurol m'Kl; Au::.' ,gIDllIij?S (P );(l9). 'V'i.lilileu \'\Ie used onlyQ;'lu~!livemged, {~~ scs:,ious} va!lrtefu:u eooh, Ut~.<lItk:ey. there "'laS ~, :!!i.g~ r.iiJ.C3l1td]ulffibrolK:ei", dIG m!lf,>ilrIiwd'e of IlI~tlsrs rnl1oo!itM&o1:l ~"(t, I~i~ djff~~nC,i~ ill ST,s I:l~n\','>b'!:ilil HH~iJldI LA: ~ls) Ix~!$~, d~~ ~OO1lm~i;ll'ld IleSI}'b!iJ1 l'£Ii b:!tweal Int~(lQ.1flIJ,(i~!!in(l Ace tro~i!l (.l'~..6... 0.0:3,. P - 0.5). .Figurel.B, slwlws I~~le~n~ :STS u1ltod'!llJmiQ.1flif~1 d~('laoolro~ Ace, and DLPF(; grotlip:s.as wellasin 1iIiI~ l,.!,i'O 3ddiliO:Ii'I:!it :wI()I'Il:i~Y'~:('W.ii1il.(iYltlffl..ol1sj rl!l1l00i~ iih¢

'ooh,vee!'idi~ 1l\... 'O CotifllCl tec'vels t;,;lli~.e l!Il~ .eye pos~tiOl.l tvaslix;ed <U!'!d 'before i9~emmlkey had il\[u:i<Lted ~m:>I11UJlm:lleSJloOl15e~ ne exru:npleccU SEiown i[l 1F1S. :2slmwcdl higher' activinl€sin the Io\"'~ilfliol tnriilllll; dlllnng 'Om s."l'iiuplepcr.ioo, reo garoli!l:S$ aW the dil"iill:':l!llm 0 f Ifiim!l'pc()Il}~I:I,g nm,rnlllr
~~Ii<:~"

rIO!'each oOIfl!lle S<W1.'ti .!liliitlpl~ C:o"dj~o~". ](Wa5a!oo hid~ deln fro(Jl1IJ InlU~lrel~vru]~,lm~e, OOMUse dleootiv:lmy w,as ~lIi~~eril~,11:;i,w..mlJlf1'ici c:(iiildilrlOIlSi i~ive
~!~

aDtivi~i~'i \~er,e h~liiigiBi~f1icl

of Ifhcre1Jevag,n n:ti~e (~g.SiS), \\/h!;1ll \'l,i'@. :aWUild ..:1 two.'way ANOVA

fiDel'"
;w::

fCOjfj,.

Th~ :aeli.\!'~ry ,d!m~I'!$IilC;L'l

OLPF'C ~ps

(tim'" 2M"

r "" O,02.,o!!@'laU~

,::lIIlm

hiSh-o(mfliol

lciaL5 \Vall n:(lt

re~al~

~tw~

t{l~liIo.

lin, an~

~I1;p~eidentti!,\OOCM!se

oonsiislCnt~y oo~-d. f.or eaeh f.lfd~.~LI:uree sam~ pIes usedi[l low.oo:tlillicl OOl!lCiIllDious, and. lower

I~i~h~!!'.. a!:i~roies\'o'Cre

(lIf 146 ~oo ~]L'5, W~r01!.!n.dOl{!( 12 C~ng .(Ws.'%) a~d 30 cel!Ls: (21%) 5ho~~ted a s~gp!~fica!!1! (? '< ~l05) Iillah'a,,effcct OfC(DI~f1~lilfldn.e' !>M'I'D~~e and decisimlpcrioos., ~i'l,llely., Oillly I~.'WO {sa:mple
"IDlI]e") ta, Lh'¢ 3;effyl,!!Y in C~eIEn8Jhl

Fli.g.

sw.g;1e-,~n IIlOO0000di,~~ ~u.&yeMI and M2.) .. Th~ ~

WC~iIllHs: show ~~:,Jl,iln int!lcl '~1Orl!key8 ~!]d allsil;l llilllaolilkeys W~]iIl l,csiollllS wid~in the ACe. Ibe STS was :lm:~.'IlI'IIt~edby Ilillle c0I1Hi.aI: expe~ li:lf.':lil>CJOOitll da!!i:prevto'l1IS lIial b[lld~aI dlls m.odI~ liLlli1i!~Qn ·w:asimpai.r~d :;!fm!r lesiens "viifil~ill the: DlLWC. ~:a~il'hgC)'8i~~·ro IhM !fiI~~'t:(n~Ali(l~.il1dlll~ be1~1l!'!,IIO:I<l:t>1djl!!!l.tI'lW!ll ww; impaired ilirl ille [)lfPC ; ~esim~ ~1,(DI1Ip,\?{ecl<plorodi ~~e UI~.de[lying n.euu;al I;ilfOOCSSCoS Iby rooordl~n!m sifi\gl.e-edl ru:ti:wtyim, lhe DLPFC of two IllO[lk~,!!i ~I amelM2). :l3ol'h, !~uo:ltk.ey'S ,slJlJ)C\':SI'lf~Uy per.rtmm~ !he alD.i!log (fig. S2) ¢¥aiI \ViiJtffil ~m m:J:ditl(DI~~Il();{I~[re.. ~nt\.lltof~y~ filt;'Ilmn" anti d:l~'Y~rutd !1'10~ ~~aJl U) c1rnl1£l(.':S ~f!g~e' rolc'I'IH~ IRlle :per day (7). FOr 00111. nu:nlkcys.iI~c 8TS W'aS 3tgJM~l1cal1l1y Sro,\\VCf ~n Jdg'llF(lo:nfJict Im1s U,l aU dilroe response direc~ I~im'oll (£1:& S3A)"end IDlm ~lS.in HB m:aL~ W2L.1l ffiglliliQll1Jlly !ra_~'iJr 'i11<:1ulila:!. of Hi Imriru,o:; in all Id!rne ~I!l~ d!r&'li.io:ll~{f:ig:,Sll3)c We· ri!rUJIII~ dta! d\'l)i])UifC 0011artiv:ily £ilif~ fl;rea. ~e!'WCe:n. l'ow~ Ilud hfgh"(lOJllnicl. n~<ll:s h~ I~~estunple ~ridl decis:1.on, pio.':iOO!~ (1.1). lil1commst IKl d~elcsIQll stlJlldiy;~n, !!IiJe~~Q.mingsind; (7) (r~ becasse dilJc~"1illSililuptcs weIeOOl:'li.\ds4.l.m~ly

r'~restiiiiitedl comJirt

a,

D],I)I~(

~Il ~~1[y

'!!ilimed~1II the pliev100S mi1!l (A, and B) AdMtie'!l~1!I UI trials: (bl.U~)alildi ~!I! Hi"!

~n~

A,
13'-1.

........ 'lW!I~ ' tJll

lIP~.'oni,
.... ."""" IFIHIImai~s

trials ~in'l() aresliimNTIl f(lf 'two (e11J; ~E$lLlfu; ,illie :sihOWlilI f()i!' OOll' mil i!1!I'(I\,) !1!lldfur1he lolieu cemw '{Bll 'ilih~1lfI;e<.'in ,adiM'ties ,i3i~a'ij!ll~ed !1rtsa;mPI~ mSI~ Only .a~ Uill

mo.~

10000ctma'l5li1at 'en! p:1I'e-

wes:r

,oodeid l~~ CD:JiII~ mah we~!! Il:l:itl!~. lih@f1 1fiiIlOOi ~h'O!.'ll tile- £iglfiliIliCllIIil!ll! llewl. of ,i!I(~ ti'lli~' !~m&en:ce! iIII me' f()';[ljtioo pe~;()d I~~~ HHI arvd mi mills (b1lil, 1l'Ifudth, S!S 1fI!S).

B:
7

IP<I.Ml111
10

•
f

iILI•sed

:sn

+--- ........ -------i:I

:S4)1 Ilhe mOt)k~y~ CCf!<11dl{ll;lfWII1~e oor~.flt\';t. lc;vet

in

Ole;

hligh. and

~m;q"-(lQllmC[

irla,1s (fig.

..1.1

(l!f the i:rial as. soon a.'! 1iI1~ $lI.tl'iiP~.e~Wl(lip~noo; Tilldll design ~d~Q'W~ Y!S to CQ;~lp.;are ijLe Oldvi~ DlPK noll anmy IiEpr,e~eriI~~d oo~id. 'liE! il~t'p@ri.wnrulJ!!S 1_ ~PS1) l~iwgl"am shaM am1iitie.s~1iI row· IFig.
~~

SUifik:;;:OO

______ ..'. .r "

Coler

L.' .s~4I1ei

flXatl'.a1lil S'WI:I~eonset

~~uon _

,ii,

SimJ)te IOIl!$!e't

:2:.

ClJ!Jf,ellUtly

L~.

SMpaI

Shape

COIClI'She;pe. ~ ~

IRUIe
DireebClI'I

u.)~<!~

HrtilJ..oolfifUct (H) ~liials

~~

R.iJ1t

IOOliIiThld:(bIIaddallld high-(!onfli:ctt '(mj)! mi~1s '~iIl wldth" SiS m~. fad'll IOOtulllTmslilmlt.! atilNitIiiElSil1l low-ilIlilal llitigJn,·cQlliliict. 'Irii'al.';, tIIlat r&Jliied 'line ap,IPH~tfoo of '~(lSii!!!ile mab:hi:lf!gl Iri!l~fl]fidi n:!Spoo~in tJii!l!'SlI:IiIII! dii1~Je(:tion. L~'t !illiidl Iriglh1i: wrti ~l

.'

RifU

I~r'ilk'm l~illt@si!1d1h:at:@ Sii! Ililjple ~Ii!i!

on!5irt and Ute OOllet aftest item!5, l~e~d'llBly ..S1!lml!l15preJiente~ inl leaoo ,conflict ioo!'!d!tioo'i'lI~~ ShQ1iiifiJ
i:lIOOW

0----

1~lbil'1lwidth. 20 m.s). ;hr gluap!it5 .aJ!

imd'Mdlulll PST

hn~~<l1II15i

Ibo~m Sh()w~hil!m~fI ~cti'\l'il.y if'! lie :~mpt'i!' l[;iermd. On~['Y 'OOrrect

1!ilia1l5 wNt!ii!ildm:led. Ue reoordiilil91

'h '111
00---Simc!!J,'S.

air~

COIi~~ed

Ib~h ,dli!''SaIl g!!ild~n'l!1!l banks t'if ~h~,rif!~l)al.