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Subject: Tumour stem cells: Rooting out resistance : Article : Nature Reviews Cancer
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<DIV class=3Dpage-heading>
<H1 class=3Dpage-header>Research Highlight</H1></DIV>
<DIV class=3Dbox>
<P id=3Dcite><SPAN class=3Djournalname>Nature Reviews Cancer</SPAN> =
<SPAN=20
class=3Djournalnumber>6</SPAN>, <SPAN class=3Dcite-pages>904-905</SPAN> =
<SPAN=20
class=3Dcite-month-year>(December 2006)</SPAN><SPAN class=3Ddivider> | =
</SPAN><SPAN=20
class=3Dcite-doi><SPAN class=3Ddoi><ABBR=20
title=3D"Digital Object =
Identifier">doi</ABBR>:10.1038/nrc2031</SPAN></SPAN></P>
<P id=3Derrorcor></P>
<H2 id=3Datl><SPAN class=3Dtopic>Tumour stem cells: </SPAN>Rooting out=20
resistance</H2>
<P id=3Daug>Nicola McCarthy</P>
<DIV id=3Darticlebody>
<P class=3Dnorm><A=20
href=3D"http://www.cancer.gov/cancertopics/types/brain">Glioblastomas</A>=
 are=20
aggressive brain tumours that rapidly become resistant to radiotherapy. =
Jeremy=20
Rich and colleagues now show that glioma stem cells are the root of this =

problem.</P>
<DIV class=3Dimage-legend><IMG alt=3D"Tumour stem cellsRooting out =
resistance"=20
src=3D"http://www.nature.com/nrc/journal/v6/n12/images/nrc2031-i1.jpg"></=
DIV>
<P class=3Dnorm>Glioblastomas present as diffuse tumours that invade =
normal brain=20
tissue, and patients who are diagnosed with this disease have a median =
survival=20
of less than 12 months.Glioblastomas recur after treatment with =
radiation, but=20
often as focal masses, suggesting that only a small proportion of cells =
are=20
responsible for recurrence. Both normal brain stem cells and brain =
tumour stem=20
cells have recently been characterized, and cells that express prominin =
1 (also=20
known as <A=20
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=3Dgene&amp;cmd=3D=
Retrieve&amp;dopt=3Dfull_report&amp;list_uids=3D8842">CD133</A>)=20
are enriched for cells that show stem-cell-like characteristics.</P>
<P class=3Dnorm>Rich and colleagues asked whether the glioma =
subpopulation of=20
CD133<SUP>+</SUP> cells is involved in the development of =
radioresistance. A=20
fourfold enrichment of the CD133<SUP>+</SUP> cell population from human =
explants=20
is evident after treatment with ionizing radiation <SPAN class=3Di>in=20
vitro</SPAN>, and the authors showed that radiation does not induce =
CD133=20
expression in CD133<SUP>-</SUP> cells. In addition, increasing the =
percentage of=20
CD133<SUP>+</SUP> cells in a defined number of glioblastoma tumour cells =

decreases the time taken for the tumours to grow in the frontal lobes of =

immuno-compromised mice, indicating the enrichment of tumorigenic stem=20
cells.</P>
<P class=3Dnorm>So, are CD133<SUP>+</SUP> glioma stem cells more =
resistant to=20
radiotherapy? <SPAN class=3Di>In vitro</SPAN> colony-formation assays =
after the=20
irradiation of either CD133<SUP>-</SUP> or CD133<SUP>+</SUP> cells from =
the same=20
patient or xenograft confirmed that more CD133<SUP>+</SUP> cells survive =
this=20
treatment. Moreover, viable CD133<SUP>+</SUP> cells from irradiated =
xenografts=20
formed secondary tumours in mice with the same kinetics as =
CD133<SUP>+</SUP>=20
cells that had not been irradiated, indicating that 2 Gy of radiation =
does not=20
reduce the tumour-forming capacity of these cells.</P>
<P class=3Dnorm>Why can these cells survive radiation treatment? The =
authors=20
analysed DNA-damage checkpoints in both the CD133<SUP>-</SUP> and=20
CD133<SUP>+</SUP> cell populations, and found that CD133<SUP>+</SUP> =
cells show=20
greater activation (levels of phosphorylation) of DNA-damage checkpoint =
proteins=20
such as ataxia telangiectasia mutated (<A=20
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=3Dgene&amp;cmd=3D=
Retrieve&amp;dopt=3Dfull_report&amp;list_uids=3D472">ATM</A>)=20
and <A=20
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=3Dgene&amp;cmd=3D=
Retrieve&amp;dopt=3Dfull_report&amp;list_uids=3D5884">RAD17</A>.=20
Although both cell populations sustain the same level of DNA damage =
(shown by=20
analysing DNA double-strand breaks using the comet assay) in response to =

irradiation, the repair of these breaks occurs 4=969 times more rapidly =
in=20
CD133<SUP>+</SUP> cells. The pre-treatment of CD133<SUP>+</SUP> cells =
with an=20
inhibitor of the DNA-damage checkpoint kinases <A=20
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=3Dgene&amp;cmd=3D=
Retrieve&amp;dopt=3Dfull_report&amp;list_uids=3D1111">CHK1</A>=20
and <A=20
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=3Dgene&amp;cmd=3D=
Retrieve&amp;dopt=3Dfull_report&amp;list_uids=3D11200">CHK2</A>=20
reduced the survival of these cells after irradiation <SPAN class=3Di>in =

vitro</SPAN>.</P>
<P class=3Dnorm>Drugs that target the DNA-damage checkpoint are in =
pre-clinical=20
and clinical trials, and these results suggest that their use might =
improve the=20
outcome for patients with glioblastoma and potentially other solid=20
tumours.</P></DIV>
<DIV id=3Dreferences-links><A class=3Dbacktotop=20
href=3D"http://www.nature.com/nrc/journal/v6/n12/full/nrc2031.html#top">T=
op<SPAN=20
class=3Dhidden> of page</SPAN></A>
<H3 class=3Dsectitle1>References and links</H3>
<H5>ORIGINAL RESEARCH PAPER</H5>
<OL class=3Dreferences>
  <LI id=3DB1>
  <P class=3Ddetails>Bao, S. <I>et al</I>. <SPAN class=3Datl>Glioma stem =
cells=20
  promote radioresistance by preferential activation of the DNA damage=20
  response</SPAN>. <SPAN class=3Djtl>Nature</SPAN> <SPAN =
class=3Dcite-month-year>18=20
  October 2006</SPAN> (doi: 10.1038/nature05236)</P>
  <UL class=3Darticle-views>
    <LI class=3D"ref-nature first"><A title=3D"Article on Article - "=20
    =
href=3D"http://www.nature.com/doifinder/10.1038/nature05236">Article</A><=
/LI>
    <LI class=3Dref-medline><A title=3D"Article on PubMed - "=20
    =
href=3D"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=3Dnpg&amp;c=
md=3DRetrieve&amp;db=3DPubMed&amp;list_uids=3D17051156&amp;dopt=3DAbstrac=
t">PubMed</A></LI>
    <LI class=3Dref-isi><A title=3D"Article on ISI - "=20
    =
href=3D"http://links.isiglobalnet2.com/gateway/Gateway.cgi?&amp;GWVersion=
=3D2&amp;SrcAuth=3DNature&amp;SrcApp=3DNature&amp;DestLinkType=3DFullReco=
rd&amp;KeyUT=3D000242581100060&amp;DestApp=3DWOS_CPL">ISI</A></LI>
    <LI class=3Dref-coi><A title=3D"Article on ChemPort - "=20
    =
href=3D"http://chemport.cas.org/cgi-bin/sdcgi?APP=3Dftslink&amp;action=3D=
reflink&amp;origin=3Dnpg&amp;version=3D1.0&amp;coi=3D1:CAS:528:DC%2BD28Xh=
t1OntbzP&amp;pissn=3D1474-175X&amp;pyear=3D2006&amp;md5=3D7fd3c817628c238=
5367ea9f10238dd88">ChemPort</A></LI></UL></LI></OL></DIV>
<DIV class=3Dno-header><A class=3Dbacktotop=20
href=3D"http://www.nature.com/nrc/journal/v6/n12/full/nrc2031.html#top">T=
op<SPAN=20
class=3Dhidden> of page</SPAN></A></DIV><!-- generated by Nature-branded =
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<DIV id=3Dmore-like-this>
<H3>MORE ARTICLES LIKE THIS</H3>
<P class=3Dexplain>These links to content published by NPG are =
automatically=20
generated.</P>
<DIV class=3Dwrapper>
<H4 class=3Darea>NEWS AND VIEWS</H4><A class=3Darticle=20
href=3D"http://www.nature.com/doifinder/10.1038/nbt0207-193">Targeting =
brain-tumor=20
stem cells</A>
<P class=3Djournal>Nature Biotechnology <SPAN>News and Views (01 Feb=20
2007)</SPAN></P><A class=3Darticle=20
href=3D"http://www.nature.com/doifinder/10.1038/nbt0207-193">Targeting =
brain-tumor=20
stem cells</A>
<P class=3Djournal>Nature Biotechnology <SPAN>News and Views (01 Feb=20
2007)</SPAN></P><A class=3Darticle=20
href=3D"http://www.nature.com/doifinder/10.1038/ncb0203-102">ATMachine</A=
>
<P class=3Djournal>Nature Cell Biology <SPAN>News and Views (01 Feb=20
2003)</SPAN></P></DIV></DIV>
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Content-Type: text/css;
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Content-Transfer-Encoding: quoted-printable
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------=_NextPart_000_0000_01C8B60A.07827EE0
Content-Type: text/css;
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Content-Transfer-Encoding: quoted-printable
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------=_NextPart_000_0000_01C8B60A.07827EE0
Content-Type: text/css;
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Content-Transfer-Encoding: 7bit
Content-Location: http://www.nature.com/reviews/style/layout.css

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#extranav {
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------=_NextPart_000_0000_01C8B60A.07827EE0
Content-Type: text/css;
	charset="iso-8859-1"
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.nature.com/common/style/main.css

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}
#head-er .accessibility-login {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 5px; =
PADDING-TOP: 4px; TEXT-ALIGN: right
}
#head-er .accessibility-login A.nature-link {
	FLOAT: left; FONT: bold 160%/80% Garamond, serif; WIDTH: 4.9em; COLOR: =
#b1062e; MARGIN-RIGHT: 20px; TEXT-ALIGN: left; TEXT-DECORATION: none
}
* HTML #head-er .accessibility-login A.nature-link:hover {
	BACKGROUND: none transparent scroll repeat 0% 0%
}
#head-er .accessibility-login A.nature-link:hover {
	BACKGROUND: =
url(/common/includes/header/images/nature.com.underline.gif) no-repeat =
left bottom
}
#head-er .accessibility-login IMG.nature-logo {
	BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; FLOAT: left; =
BORDER-BOTTOM-WIDTH: 0px; MARGIN: 1px 20px 0px 0px; WIDTH: 82px! =
important; HEIGHT: 11px; BORDER-RIGHT-WIDTH: 0px
}
#head-er .accessibility-login .jumplinks {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FLOAT: left; PADDING-BOTTOM: =
0px; MARGIN: 0px; WIDTH: 45%; PADDING-TOP: 0px; LIST-STYLE-TYPE: none; =
TEXT-ALIGN: left
}
#head-er .accessibility-login .jumplinks LI {
	DISPLAY: inline; PADDING-LEFT: 15px
}
#head-er .accessibility-login .jumplinks LI.first {
	PADDING-LEFT: 0px
}
#head-er .accessibility-login .jumplinks A {
	PADDING-LEFT: 10px; BACKGROUND: =
url(/common/images/icons/b1062e/arrow_down.gif) no-repeat left center; =
COLOR: #000; TEXT-DECORATION: none
}
#head-er .accessibility-login .jumplinks A:hover {
	TEXT-DECORATION: underline
}
#head-er DIV.logon {
=09
}
#head-er .logon .onlyformacie {
	FONT-SIZE: 3px
}
#head-er .logon .onlyformacie {
	DISPLAY: none
}
#head-er .logon A.login {
	PADDING-RIGHT: 15px; PADDING-LEFT: 0px; FONT-WEIGHT: bold; BACKGROUND: =
url(/common/includes/header/images/logon.gif) no-repeat right center; =
PADDING-BOTTOM: 0px; TEXT-TRANSFORM: uppercase; COLOR: #b1062e; =
PADDING-TOP: 0px; LETTER-SPACING: -0.1em; TEXT-DECORATION: none
}
#head-er .logon A.login:hover {
	BACKGROUND: url(/common/includes/header/images/logon_over.gif) =
no-repeat right center; TEXT-DECORATION: underline
}
#head-er .logon A.login:active {
	BACKGROUND: url(/common/includes/header/images/logon.gif) no-repeat =
right center
}
#head-er .logon A.logoff {
	PADDING-RIGHT: 15px; PADDING-LEFT: 15px; FONT-WEIGHT: bold; BACKGROUND: =
url(/common/includes/header/images/logoff.gif) no-repeat right center; =
PADDING-BOTTOM: 0px; TEXT-TRANSFORM: uppercase; COLOR: #b1062e; =
PADDING-TOP: 0px; LETTER-SPACING: -0.1em; TEXT-DECORATION: none
}
#head-er .logon P {
	MARGIN: 0px
}
#head-er .logon .user {
	FONT-WEIGHT: bold
}
#head-er .logon .inst {
	FONT-WEIGHT: bold
}
#head-er .image-user-services-wrap {
	FLOAT: left; WIDTH: 100%; BACKGROUND-COLOR: #d6335c
}
#head-er .image-user-services {
	BORDER-BOTTOM: transparent 1px solid
}
* HTML #head-er .image-user-services {
	BORDER-BOTTOM-WIDTH: 0px
}
#head-er .image-user-services IMG.journal-header {
	BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; FLOAT: left; =
BORDER-BOTTOM-WIDTH: 0px; MARGIN: 0px; WIDTH: 344px; HEIGHT: 74px; =
BORDER-RIGHT-WIDTH: 0px
}
#head-er .user-services {
	FLOAT: right
}
#head-er .div1.user-services {
	WIDTH: 12.35em! important
}
#head-er .div2.user-services {
	WIDTH: 8.7em! important
}
#head-er .user-services UL {
	BORDER-RIGHT: #fff 0px solid; PADDING-RIGHT: 0px; BORDER-TOP: #fff 1px =
solid; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 22px 0px 21px; =
BORDER-LEFT: #fff 1px solid; PADDING-TOP: 0px; BORDER-BOTTOM: #fff 0px =
solid; LIST-STYLE-TYPE: none; TEXT-ALIGN: right
}
#head-er .user-services UL.list1 {
	BORDER-RIGHT: #fff 1px solid
}
#head-er .user-services LI {
	BORDER-BOTTOM: #fff 1px solid
}
#head-er .user-services A {
	PADDING-RIGHT: 13px; DISPLAY: block; PADDING-LEFT: 0px; BACKGROUND: =
url(/common/images/icons/fff/arrow_s.gif) #767474 no-repeat right =
center; PADDING-BOTTOM: 1px; TEXT-TRANSFORM: uppercase; COLOR: #fff; =
PADDING-TOP: 1px; TEXT-DECORATION: none
}
#head-er .user-services A:hover {
	BACKGROUND: url(/common/images/icons/fff/arrow_s.gif) #000 no-repeat =
right center
}
#head-er .publications-search-wrap {
	BACKGROUND: #000
}
* HTML #head-er .publications-search {
	PADDING-BOTTOM: 3px; PADDING-TOP: 3px
}
#head-er .publications-search {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 4px; =
PADDING-TOP: 4px
}
* HTML #head-er .publications {
	MARGIN: 6px 0px 0px
}
#head-er .publications {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FLOAT: left; PADDING-BOTTOM: =
0px; MARGIN: 4px 0px 0px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none
}
#head-er .publications LI {
	DISPLAY: inline; MARGIN-LEFT: 10px
}
#head-er .publications LI.first {
	MARGIN-LEFT: 0px
}
#head-er .publications A {
	PADDING-RIGHT: 15px; BACKGROUND: =
url(/common/images/icons/fff/arrow_s.gif) no-repeat right center; =
TEXT-TRANSFORM: uppercase; COLOR: #fff; TEXT-DECORATION: none
}
#head-er .publications A:hover {
	TEXT-DECORATION: underline
}
#head-er .search {
	TEXT-ALIGN: right
}
#head-er .search FORM {
	DISPLAY: inline; MARGIN: 0px
}
#head-er .search FORM A {
	PADDING-RIGHT: 14px; BACKGROUND: =
url(/common/images/icons/fff/arrow_s.gif) no-repeat right center; =
TEXT-TRANSFORM: uppercase; COLOR: #fff; TEXT-DECORATION: none
}
#head-er .search FORM A:hover {
	TEXT-DECORATION: underline
}
#head-er #searchtext {
	WIDTH: 10em
}
#head-er .publications-search LABEL {
	TEXT-TRANSFORM: uppercase; COLOR: #fff
}
#head-er INPUT {
	FONT-SIZE: 100%
}
#head-er SELECT {
	FONT-SIZE: 100%
}
#head-er .publications-search INPUT.button {
	PADDING-RIGHT: 3px; PADDING-LEFT: 3px; FONT-WEIGHT: bold; BACKGROUND: =
#eaeaea; PADDING-BOTTOM: 0px; COLOR: #000; PADDING-TOP: 0px
}
#head-er .accessibility-login {
	PADDING-RIGHT: 1%; PADDING-LEFT: 1%
}
#head-er .image-user-services {
	PADDING-RIGHT: 1%; PADDING-LEFT: 1%
}
#head-er .publications-search {
	PADDING-RIGHT: 1%; PADDING-LEFT: 1%
}
.header-leaderboard-wrap {
	PADDING-RIGHT: 1%; PADDING-LEFT: 1%; BACKGROUND: =
url(/common/includes/header/images/bg_leaderboard.gif) no-repeat 50% =
0px; OVERFLOW: hidden
}
.header-leaderboard {
	MAX-HEIGHT: 105px; TEXT-ALIGN: center
}
* HTML .header-leaderboard IMG {
	BORDER-BOTTOM-WIDTH: 1px
}
* HTML .header-leaderboard ilayer {
	BORDER-BOTTOM-WIDTH: 1px
}
* HTML .header-leaderboard IFRAME {
	BORDER-BOTTOM-WIDTH: 1px
}
* HTML .header-leaderboard EMBED {
	BORDER-BOTTOM-WIDTH: 1px
}
.header-leaderboard IMG {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
BORDER-LEFT-WIDTH: 0px; MIN-HEIGHT: 90px; MAX-WIDTH: 728px; =
PADDING-BOTTOM: 0px; PADDING-TOP: 0px; BORDER-BOTTOM: #fff 1px solid; =
HEIGHT: 90px; BORDER-RIGHT-WIDTH: 0px
}
.header-leaderboard ilayer {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
BORDER-LEFT-WIDTH: 0px; MIN-HEIGHT: 90px; MAX-WIDTH: 728px; =
PADDING-BOTTOM: 0px; PADDING-TOP: 0px; BORDER-BOTTOM: #fff 1px solid; =
HEIGHT: 90px; BORDER-RIGHT-WIDTH: 0px
}
.header-leaderboard IFRAME {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
BORDER-LEFT-WIDTH: 0px; MIN-HEIGHT: 90px; MAX-WIDTH: 728px; =
PADDING-BOTTOM: 0px; PADDING-TOP: 0px; BORDER-BOTTOM: #fff 1px solid; =
HEIGHT: 90px; BORDER-RIGHT-WIDTH: 0px
}
.header-leaderboard EMBED {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
BORDER-LEFT-WIDTH: 0px; MIN-HEIGHT: 90px; MAX-WIDTH: 728px; =
PADDING-BOTTOM: 0px; PADDING-TOP: 0px; BORDER-BOTTOM: #fff 1px solid; =
HEIGHT: 90px; BORDER-RIGHT-WIDTH: 0px
}
.header-leaderboard TABLE {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
BORDER-LEFT-WIDTH: 0px; MAX-WIDTH: 728px; PADDING-BOTTOM: 0px; =
MARGIN-LEFT: auto; WIDTH: 100%; MARGIN-RIGHT: auto; PADDING-TOP: 0px; =
BORDER-BOTTOM: #fff 1px solid; BORDER-RIGHT-WIDTH: 0px
}
* HTML .header-leaderboard TABLE IMG {
	HEIGHT: auto
}
#constrain {
	MARGIN-TOP: 14px
}
#global-subject-areas {
	BORDER-RIGHT: #ebebeb 1px solid; BORDER-TOP: #ebebeb 1px solid; =
BACKGROUND: #ebebeb; MARGIN: 0px 0px 20px; BORDER-LEFT: #ebebeb 1px =
solid; BORDER-BOTTOM: #ebebeb 1px solid
}
#global-subject-areas ABBR {
	BORDER-TOP-WIDTH: 0px; BORDER-LEFT-WIDTH: 0px; BORDER-BOTTOM-WIDTH: =
0px; BORDER-RIGHT-WIDTH: 0px; TEXT-DECORATION: none
}
#global-subject-areas A:link {
	FONT-WEIGHT: bold; COLOR: #9d0006; TEXT-DECORATION: none
}
#global-subject-areas A:visited {
	FONT-WEIGHT: bold; COLOR: #9d0006; TEXT-DECORATION: none
}
#global-subject-areas A:hover {
	TEXT-DECORATION: underline
}
#global-subject-areas H2 {
	PADDING-RIGHT: 10px; PADDING-LEFT: 10px; FONT-SIZE: 110%; BACKGROUND: =
#b1062e; PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: =
5px; BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H3 {
	PADDING-RIGHT: 10px; PADDING-LEFT: 10px; FONT-SIZE: 110%; BACKGROUND: =
#b1062e; PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: =
5px; BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H4 {
	PADDING-RIGHT: 10px; PADDING-LEFT: 10px; FONT-SIZE: 110%; BACKGROUND: =
#b1062e; PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: =
5px; BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H5 {
	PADDING-RIGHT: 10px; PADDING-LEFT: 10px; FONT-SIZE: 110%; BACKGROUND: =
#b1062e; PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: =
5px; BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H3.view {
	PADDING-RIGHT: 17px; PADDING-LEFT: 17px; FONT-SIZE: 100%; BACKGROUND: =
url(/common/images/bg.7x1.b1062e.gif) #fff repeat-y left top; =
PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #9d0006; PADDING-TOP: 5px; =
BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H4.view {
	PADDING-RIGHT: 17px; PADDING-LEFT: 17px; FONT-SIZE: 100%; BACKGROUND: =
url(/common/images/bg.7x1.b1062e.gif) #fff repeat-y left top; =
PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #9d0006; PADDING-TOP: 5px; =
BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas H5.view {
	PADDING-RIGHT: 17px; PADDING-LEFT: 17px; FONT-SIZE: 100%; BACKGROUND: =
url(/common/images/bg.7x1.b1062e.gif) #fff repeat-y left top; =
PADDING-BOTTOM: 5px; MARGIN: 0px; COLOR: #9d0006; PADDING-TOP: 5px; =
BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas UL {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; FONT-SIZE: 100%; PADDING-BOTTOM: =
0px; MARGIN: 0px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none
}
#global-subject-areas UL UL {
	FONT-SIZE: 100%
}
#global-subject-areas UL LI {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 5px; =
LINE-HEIGHT: 150%; PADDING-TOP: 5px; BORDER-BOTTOM: #fff 1px solid
}
#global-subject-areas UL LI LI {
	PADDING-RIGHT: 0px; PADDING-LEFT: 5px; BORDER-BOTTOM-WIDTH: 0px; =
PADDING-BOTTOM: 0px; PADDING-TOP: 0px
}
#global-subject-areas UL LI H4 {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
FONT-WEIGHT: normal; BORDER-LEFT-WIDTH: 0px; FONT-SIZE: 100%; =
BACKGROUND: none transparent scroll repeat 0% 0%; BORDER-BOTTOM-WIDTH: =
0px; PADDING-BOTTOM: 0px; MARGIN: 0px; COLOR: #666; PADDING-TOP: 0px; =
FONT-STYLE: italic; BORDER-RIGHT-WIDTH: 0px
}
#global-subject-areas UL LI H5 {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
FONT-WEIGHT: normal; BORDER-LEFT-WIDTH: 0px; FONT-SIZE: 100%; =
BACKGROUND: none transparent scroll repeat 0% 0%; BORDER-BOTTOM-WIDTH: =
0px; PADDING-BOTTOM: 0px; MARGIN: 0px; COLOR: #666; PADDING-TOP: 0px; =
FONT-STYLE: italic; BORDER-RIGHT-WIDTH: 0px
}
#global-subject-areas UL LI H6 {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
FONT-WEIGHT: normal; BORDER-LEFT-WIDTH: 0px; FONT-SIZE: 100%; =
BACKGROUND: none transparent scroll repeat 0% 0%; BORDER-BOTTOM-WIDTH: =
0px; PADDING-BOTTOM: 0px; MARGIN: 0px; COLOR: #666; PADDING-TOP: 0px; =
FONT-STYLE: italic; BORDER-RIGHT-WIDTH: 0px
}
MAP.journal-nav {
	DISPLAY: block; MARGIN-BOTTOM: 20px
}
MAP.journal-nav UL {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: =
0px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none; TEXT-ALIGN: left
}
MAP.journal-nav UL LI {
	MARGIN: 0px; BORDER-BOTTOM: #fff 1px solid; BACKGROUND-COLOR: #eaeaea
}
MAP.journal-nav UL LI.grouped {
	BORDER-BOTTOM: #eaeaea 1px solid
}
* HTML MAP.journal-nav UL LI A {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 3px; =
PADDING-TOP: 2px
}
* HTML MAP.journal-nav UL LI A:visited {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; PADDING-BOTTOM: 3px; =
PADDING-TOP: 2px
}
MAP.journal-nav UL LI A {
	PADDING-RIGHT: 5px; DISPLAY: block; PADDING-LEFT: 5px; FONT-WEIGHT: =
bold; FONT-SIZE: 80%; PADDING-BOTTOM: 4px; MARGIN: 0px; COLOR: #000; =
PADDING-TOP: 4px; TEXT-DECORATION: none
}
MAP.journal-nav UL LI A:visited {
	PADDING-RIGHT: 5px; DISPLAY: block; PADDING-LEFT: 5px; FONT-WEIGHT: =
bold; FONT-SIZE: 80%; PADDING-BOTTOM: 4px; MARGIN: 0px; COLOR: #000; =
PADDING-TOP: 4px; TEXT-DECORATION: none
}
MAP.journal-nav UL LI A:hover {
	COLOR: #fff; BACKGROUND-COLOR: #c00; TEXT-DECORATION: none
}
MAP.journal-nav UL LI A.on {
	COLOR: #fff; BACKGROUND-COLOR: #c00
}
MAP.journal-nav UL LI A.on:visited {
	COLOR: #fff; BACKGROUND-COLOR: #c00
}
MAP.journal-nav UL LI A.submission {
	PADDING-LEFT: 20px! important; BACKGROUND: =
url(/common/images/online_submissions.gif) no-repeat left center
}
MAP.journal-nav UL LI UL.subnav {
	BORDER-TOP-WIDTH: 0px; PADDING-RIGHT: 0px; PADDING-LEFT: 0px; =
PADDING-BOTTOM: 0px; MARGIN: 0px; PADDING-TOP: 0px; LIST-STYLE-TYPE: =
none; TEXT-ALIGN: left
}
MAP.journal-nav UL LI UL.subnav LI {
	BACKGROUND: url(/common/images/nav_dots2.gif) #fafafa no-repeat 11px =
5px; BORDER-BOTTOM-WIDTH: 0px; MARGIN: 0px
}
MAP.journal-nav UL LI UL.subnav LI.on {
	BACKGROUND: url(/common/images/nav_dots1.gif) #c00 no-repeat 11px 5px; =
BORDER-BOTTOM: #fafafa 1px solid
}
* HTML MAP.journal-nav UL LI UL.subnav A {
	PADDING-RIGHT: 10px! important; PADDING-LEFT: 20px! important; =
PADDING-BOTTOM: 2px! important; PADDING-TOP: 2px! important
}
MAP.journal-nav UL LI UL.subnav A:link {
	PADDING-RIGHT: 10px; DISPLAY: block; PADDING-LEFT: 20px; FONT-WEIGHT: =
normal; FONT-SIZE: 70%; PADDING-BOTTOM: 2px; MARGIN: 0px; COLOR: #000; =
PADDING-TOP: 2px; TEXT-DECORATION: none
}
MAP.journal-nav UL LI UL.subnav A:visited {
	PADDING-RIGHT: 10px; DISPLAY: block; PADDING-LEFT: 20px; FONT-WEIGHT: =
normal; FONT-SIZE: 70%; PADDING-BOTTOM: 2px; MARGIN: 0px; COLOR: #000; =
PADDING-TOP: 2px; TEXT-DECORATION: none
}
MAP.journal-nav UL LI UL.subnav A:hover {
	BACKGROUND: url(/common/images/nav_dots1.gif) #fab934 no-repeat 11px =
5px; COLOR: #fff; TEXT-DECORATION: none
}
MAP.journal-nav UL LI UL.subnav A.on {
	COLOR: #fff
}
MAP.journal-nav UL LI UL.subnav A.on:visited {
	COLOR: #fff
}
#journalnav MAP.supplementary UL A {
	FONT-WEIGHT: normal; FONT-SIZE: 70%
}
#journalnav MAP.supplementary UL A:visited {
	FONT-WEIGHT: normal; FONT-SIZE: 70%
}
H2.society-resources {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; FONT-WEIGHT: bold; FONT-SIZE: =
80%; PADDING-BOTTOM: 2px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: 2px; =
BACKGROUND-COLOR: #fab934
}
UL.society-resources {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px =
0px 20px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none; TEXT-ALIGN: left
}
UL.society-resources LI {
	MARGIN: 0px; BACKGROUND-COLOR: #eaeaea
}
UL.society-resources A {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.society-resources A:visited {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.society-resources A:hover {
	COLOR: #fff; BACKGROUND-COLOR: #fab934; TEXT-DECORATION: none
}
DIV.society-logo {
	MARGIN-BOTTOM: 20px; TEXT-ALIGN: center
}
DIV.society-logo IMG {
	WIDTH: 100%
}
H2.npg-resources {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; FONT-WEIGHT: bold; FONT-SIZE: =
80%; PADDING-BOTTOM: 2px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: 2px; =
BACKGROUND-COLOR: #b1062e
}
UL.npg-resources {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px =
0px 20px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none; TEXT-ALIGN: left
}
UL.npg-resources LI {
	MARGIN: 0px; BORDER-BOTTOM: #fff 1px solid; BACKGROUND-COLOR: #eaeaea
}
UL.npg-resources A {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.npg-resources A:visited {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.npg-resources A:hover {
	COLOR: #fff; BACKGROUND-COLOR: #b1062e; TEXT-DECORATION: none
}
H2.npg-subjects {
	PADDING-RIGHT: 5px; PADDING-LEFT: 5px; FONT-WEIGHT: bold; FONT-SIZE: =
80%; PADDING-BOTTOM: 2px; MARGIN: 0px; COLOR: #fff; PADDING-TOP: 2px; =
BACKGROUND-COLOR: #c03
}
UL.npg-subjects {
	PADDING-RIGHT: 0px; PADDING-LEFT: 0px; PADDING-BOTTOM: 0px; MARGIN: 0px =
0px 20px; PADDING-TOP: 0px; LIST-STYLE-TYPE: none; TEXT-ALIGN: left
}
UL.npg-subjects LI {
	MARGIN: 0px; BORDER-BOTTOM: #fff 1px solid; BACKGROUND-COLOR: #eaeaea
}
UL.npg-subjects A {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.npg-subjects A:visited {
	PADDING-RIGHT: 5px! important; DISPLAY: block; PADDING-LEFT: 5px! =
important; FONT-SIZE: 70%; PADDING-BOTTOM: 3px! important; MARGIN: 0px; =
COLOR: #000; PADDING-TOP: 3px! important; TEXT-DECORATION: none
}
UL.npg-subjects A:hover {
	COLOR: #fff; BACKGROUND-COLOR: #c03; TEXT-DECORATION: none
}
UL.npg-subjects A.npgsubject-browseall:link {
	COLOR: #c03
}
UL.npg-subjects A.npgsubject-browseall:visited {
	COLOR: #c03
}
UL.npg-subjects A.npgsubject-browseall:hover {
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}
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}
* HTML #foot-er #footer-copyright .footer-constrain {
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------=_NextPart_000_0000_01C8B60A.07827EE0
Content-Type: text/css;
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Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.nature.com/reviews/style/group.css

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BODY {
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 * $Date: 2007-09-16 23:42:06 -0400 (Sun, 16 Sep 2007) $=0A=
 * $Rev: 3353 $=0A=
 */=0A=
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------=_NextPart_000_0000_01C8B60A.07827EE0
Content-Type: application/octet-stream
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.nature.com/common/scripts/global.js

(function($) {
	$(document).ready(function () {

		// enables dropdown ads to display whilst maintaining .user-services =
visibility aat small resolutions
		// yes, it involves browser detection, and yes, that is truly =
horrible.
		if (jQuery.browser.mozilla) {
	=09
			var dropdownAd =3D false;
	=09
			// for each descendant of .leaderboard that isn't a <script>, =
determine if it's taller than standard leaderboard height
			$("#hdr .leaderboard *:not(script):not(.padder)").each(function() {
				if($(this).height() > 90) {
					dropdownAd =3D true;
				}
			});
	=09
			if (dropdownAd) {
				$("#hdr .leaderboard").css("overflow","visible");
				$("#hdr .leaderboard .padder").css("overflow","visible");
				$("#hdr .leaderboard").hover(function() {
					$("#hdr .leaderboard").css("overflow","visible");
					$("#hdr .leaderboard .padder").css("overflow","visible");
				},function() {
					$("#hdr .leaderboard").css("overflow","hidden");
					$("#hdr .leaderboard .padder").css("overflow","hidden");
				});		=09
			}
		}
	=09
	});
}) (jQuery);
------=_NextPart_000_0000_01C8B60A.07827EE0--

