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Subject: Bone marrow-derived cells fuse with normal and transformed intestinal stem cells -- Rizvi et al. 103 (16): 6321 -- Proceedings of the National Academy of Sciences
Date: Sat, 13 May 2006 13:12:52 +0200
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<TD></TD></TR></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE><STRONG=
><FONT=20
color=3D#a70716 size=3D-2>BIOLOGICAL SCIENCES / MEDICAL=20
SCIENCES</FONT></STRONG><BR><STRONG><FONT size=3D+2>Bone marrow-derived =
cells fuse=20
with normal and transformed intestinal stem cells </FONT></STRONG>
<P><STRONG></NOBR><NOBR>Adnan Z. Rizvi<SUP>*</SUP></NOBR>, <NOBR>John R. =

Swain<SUP><IMG alt=3D{dagger} =
src=3D"http://www.pnas.org/math/dagger.gif"=20
border=3D0></SUP></NOBR>, <NOBR>Paige S. Davies<SUP><IMG alt=3D{dagger}=20
src=3D"http://www.pnas.org/math/dagger.gif" border=3D0></SUP></NOBR>, =
<NOBR>Alexis=20
S. Bailey<SUP><IMG alt=3D{ddagger} =
src=3D"http://www.pnas.org/math/Dagger.gif"=20
border=3D0></SUP></NOBR>, <NOBR>Adria D. Decker<SUP><IMG alt=3D=A7=20
src=3D"http://www.pnas.org/math/sect.gif" border=3D0></SUP></NOBR>, =
<NOBR>Holger=20
Willenbring<SUP><IMG alt=3D=A7 src=3D"http://www.pnas.org/math/sect.gif" =

border=3D0></SUP></NOBR>, <NOBR>Markus Grompe<SUP><IMG alt=3D=A7=20
src=3D"http://www.pnas.org/math/sect.gif" =
border=3D0></SUP><SUP>,=B6</SUP></NOBR>,=20
<NOBR>William H. Fleming<SUP><IMG alt=3D{ddagger}=20
src=3D"http://www.pnas.org/math/Dagger.gif" =
border=3D0></SUP><SUP>,=B6</SUP></NOBR>,=20
and <NOBR>Melissa H. Wong<SUP><IMG alt=3D{dagger}=20
src=3D"http://www.pnas.org/math/dagger.gif"=20
border=3D0></SUP><SUP>,=B6</SUP><SUP>,||</SUP><SUP>,**</SUP></NOBR> =
</STRONG>
<P>*Departments of Surgery, <SUP><IMG alt=3D{dagger}=20
src=3D"http://www.pnas.org/math/dagger.gif" =
border=3D0></SUP>Dermatology, **Cell and=20
Developmental Biology, and <SUP><IMG alt=3D=A7=20
src=3D"http://www.pnas.org/math/sect.gif" border=3D0></SUP>Molecular and =
Medical=20
Genetics, <SUP><IMG alt=3D{ddagger} =
src=3D"http://www.pnas.org/math/Dagger.gif"=20
border=3D0></SUP>Center for Hematologic Malignancies, Division of =
Hematology and=20
Medical Oncology, and <SUP>=B6</SUP>Oregon Cancer Institute, Oregon Stem =
Cell=20
Center, Oregon Health &amp; Science University, 3181 Southwest Sam =
Jackson Park=20
Road, Portland, OR 97239=20
<P>Edited by Suzanne Cory, The Walter and Eliza Hall Institute of =
Medical=20
Research, Melbourne, Australia, and approved March 3, 2006 (received for =
review=20
October 5, 2005)
<P>
<P><!-- ABS -->Transplanted adult bone marrow-derived cells (BMDCs) have =

been<SUP> </SUP>shown to adopt the phenotype and function of several=20
nonhematopoietic<SUP> </SUP>cell lineages and promote tumorigenesis. =
Beyond its=20
cancer enhancing<SUP> </SUP>potential, cell fusion has recently emerged =
as an=20
explanation<SUP> </SUP>of how BMDCs regenerate diseased heptocytes, =
contribute=20
to Purkinje<SUP> </SUP>neurons and skeletal and cardiac muscle cells, =
and=20
participate<SUP> </SUP>in skin and heart regeneration. Although bone=20
marrow-derived<SUP> </SUP>epithelial cells also have been observed in =
the=20
intestine, fusion<SUP> </SUP>as a mechanism has not been investigated. =
Here, we=20
show that<SUP> </SUP>transplanted BMDCs fuse with both normal and =
neoplastic=20
intestinal<SUP> </SUP>epithelium. Long-term repopulation by =
donor-derived cells=20
was<SUP> </SUP>detected in all principal intestinal epithelial lineages=20
including<SUP> </SUP>enterocytes, goblet cells, Paneth cells, and=20
enteroendocrine<SUP> </SUP>cells, suggesting that the fusion partners of =
the=20
BMDCs are<SUP> </SUP>long-lived intestinal progenitors or stem cells. =
Fusion of=20
BMDCs<SUP> </SUP>with neoplastic epithelium did not result in tumor=20
initiation.<SUP> </SUP>Our findings suggest an unexpected role for BMDCs =
in both=20
regeneration<SUP> </SUP>and tumorigenesis of the intestine.<SUP> </SUP>
<P>
<P><FONT size=3D-1>intestine | tumorigenesis | cell fusion | tissue=20
regeneration</FONT>
<P>
<HR align=3Dleft width=3D"50%" noShade SIZE=3D1>
<!-- FN --><A name=3D""><!-- null --></A>Freely available online through =
the PNAS=20
open access option.<SUP> </SUP>
<P><A name=3D""><!-- null --></A>Author contributions: A.Z.R., W.H.F., =
and M.H.W.=20
designed research;<SUP> </SUP>A.Z.R., J.R.S., P.S.D., A.S.B., A.D.D., =
and M.H.W.=20
performed<SUP> </SUP>research; J.R.S., H.W., M.G., W.H.F., and M.H.W.=20
contributed<SUP> </SUP>new reagents/analytic tools; J.R.S., P.S.D., =
A.S.B.,=20
M.G., W.H.F.,<SUP> </SUP>and M.H.W. analyzed data; and A.Z.R., P.S.D., =
H.W., and=20
M.H.W.<SUP> </SUP>wrote the paper.<SUP> </SUP>
<P><A name=3D""><!-- null --></A>Conflict of interest statement: No =
conflicts=20
declared.<SUP> </SUP>
<P><A name=3D""><!-- null --></A>This paper was submitted directly =
(Track II) to=20
the PNAS office.<SUP> </SUP>
<P><A name=3DCOR1><!-- null --></A><SUP>||</SUP>To whom correspondence =
should be=20
addressed. E-mail: <SPAN id=3Dem0>wongme{at}ohsu.edu</SPAN>
<SCRIPT type=3Dtext/javascript><!--=0A=
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document.getElementById("em0").innerHTML =3D '<a href=3D"mailto:' + u + =
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<P>=A9 2006 by <A href=3D"http://www.pnas.org/misc/terms.shtml">The =
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/*=0A=
=0A=
Cross-Browser XMLHttpRequest v1.2=0A=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=0A=
=0A=
Emulate Gecko 'XMLHttpRequest()' functionality in IE and Opera. Opera =
requires=0A=
the Sun Java Runtime Environment <http://www.java.com/>.=0A=
=0A=
by Andrew Gregory=0A=
http://www.scss.com.au/family/andrew/webdesign/xmlhttprequest/=0A=
=0A=
This work is licensed under the Creative Commons Attribution License. To =
view a=0A=
copy of this license, visit =
http://creativecommons.org/licenses/by-sa/2.5/ or=0A=
send a letter to Creative Commons, 559 Nathan Abbott Way, Stanford, =
California=0A=
94305, USA.=0A=
=0A=
Attribution: Leave my name and web address in this script intact.=0A=
=0A=
Not Supported in Opera=0A=
----------------------=0A=
* user/password authentication=0A=
* responseXML data member=0A=
=0A=
Not Fully Supported in Opera=0A=
----------------------------=0A=
* async requests=0A=
* abort()=0A=
* getAllResponseHeaders(), getAllResponseHeader(header)=0A=
=0A=
*/=0A=
// IE support=0A=
if (window.ActiveXObject && !window.XMLHttpRequest) {=0A=
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      'Msxml2.XMLHTTP',=0A=
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      } catch (e) {=0A=
      }=0A=
    }=0A=
    return null;=0A=
  };=0A=
}=0A=
// Gecko support=0A=
/* ;-) */=0A=
// Opera support=0A=
if (window.opera && !window.XMLHttpRequest) {=0A=
  window.XMLHttpRequest =3D function() {=0A=
    this.readyState =3D 0; // =
0=3Duninitialized,1=3Dloading,2=3Dloaded,3=3Dinteractive,4=3Dcomplete=0A=
    this.status =3D 0; // HTTP status codes=0A=
    this.statusText =3D '';=0A=
    this._headers =3D [];=0A=
    this._aborted =3D false;=0A=
    this._async =3D true;=0A=
    this._defaultCharset =3D 'ISO-8859-1';=0A=
    this._getCharset =3D function() {=0A=
      var charset =3D _defaultCharset;=0A=
      var contentType =3D =
this.getResponseHeader('Content-type').toUpperCase();=0A=
      val =3D contentType.indexOf('CHARSET=3D');=0A=
      if (val !=3D -1) {=0A=
        charset =3D contentType.substring(val);=0A=
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        charset =3D charset.substring(0, val);=0A=
      }=0A=
      val =3D charset.indexOf(',');=0A=
      if (val !=3D -1) {=0A=
        charset =3D charset.substring(0, val);=0A=
      }=0A=
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    this.abort =3D function() {=0A=
      this._aborted =3D true;=0A=
    };=0A=
    this.getAllResponseHeaders =3D function() {=0A=
      return this.getAllResponseHeader('*');=0A=
    };=0A=
    this.getAllResponseHeader =3D function(header) {=0A=
      var ret =3D '';=0A=
      for (var i =3D 0; i < this._headers.length; i++) {=0A=
        if (header =3D=3D '*' || this._headers[i].h =3D=3D header) {=0A=
          ret +=3D this._headers[i].h + ': ' + this._headers[i].v + '\n';=0A=
        }=0A=
      }=0A=
      return ret;=0A=
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      if (i !=3D -1) {=0A=
        ret =3D ret.substring(0, i);=0A=
      }=0A=
      return ret;=0A=
    };=0A=
    this.setRequestHeader =3D function(header, value) {=0A=
      this._headers[this._headers.length] =3D {h:header, v:value};=0A=
    };=0A=
    this.open =3D function(method, url, async, user, password) {=0A=
      this.method =3D method;=0A=
      this.url =3D url;=0A=
      this._async =3D true;=0A=
      this._aborted =3D false;=0A=
      this._headers =3D [];=0A=
      if (arguments.length >=3D 3) {=0A=
        this._async =3D async;=0A=
      }=0A=
      if (arguments.length > 3) {=0A=
        opera.postError('XMLHttpRequest.open() - user/password not =
supported');=0A=
      }=0A=
      this.readyState =3D 1;=0A=
      if (this.onreadystatechange) {=0A=
        this.onreadystatechange();=0A=
      }=0A=
    };=0A=
    this.send =3D function(data) {=0A=
      if (!navigator.javaEnabled()) {=0A=
        alert("XMLHttpRequest.send() - Java must be installed and =
enabled.");=0A=
        return;=0A=
      }=0A=
      if (this._async) {=0A=
        setTimeout(this._sendasync, 0, this, data);=0A=
        // this is not really asynchronous and won't execute until the =
current=0A=
        // execution context ends=0A=
      } else {=0A=
        this._sendsync(data);=0A=
      }=0A=
    }=0A=
    this._sendasync =3D function(req, data) {=0A=
      if (!req._aborted) {=0A=
        req._sendsync(data);=0A=
      }=0A=
    };=0A=
    this._sendsync =3D function(data) {=0A=
      this.readyState =3D 2;=0A=
      if (this.onreadystatechange) {=0A=
        this.onreadystatechange();=0A=
      }=0A=
      // open connection=0A=
      var url =3D new java.net.URL(new =
java.net.URL(window.location.href), this.url);=0A=
      var conn =3D url.openConnection();=0A=
      for (var i =3D 0; i < this._headers.length; i++) {=0A=
        conn.setRequestProperty(this._headers[i].h, this._headers[i].v);=0A=
      }=0A=
      this._headers =3D [];=0A=
      if (this.method =3D=3D 'POST') {=0A=
        // POST data=0A=
        conn.setDoOutput(true);=0A=
        var wr =3D new =
java.io.OutputStreamWriter(conn.getOutputStream(), this._getCharset());=0A=
        wr.write(data);=0A=
        wr.flush();=0A=
        wr.close();=0A=
      }=0A=
      // read response headers=0A=
      // NOTE: the getHeaderField() methods always return nulls for me :(=0A=
      var gotContentEncoding =3D false;=0A=
      var gotContentLength =3D false;=0A=
      var gotContentType =3D false;=0A=
      var gotDate =3D false;=0A=
      var gotExpiration =3D false;=0A=
      var gotLastModified =3D false;=0A=
      for (var i =3D 0; ; i++) {=0A=
        var hdrName =3D conn.getHeaderFieldKey(i);=0A=
        var hdrValue =3D conn.getHeaderField(i);=0A=
        if (hdrName =3D=3D null && hdrValue =3D=3D null) {=0A=
          break;=0A=
        }=0A=
        if (hdrName !=3D null) {=0A=
          this._headers[this._headers.length] =3D {h:hdrName, =
v:hdrValue};=0A=
          switch (hdrName.toLowerCase()) {=0A=
            case 'content-encoding': gotContentEncoding =3D true; break;=0A=
            case 'content-length'  : gotContentLength   =3D true; break;=0A=
            case 'content-type'    : gotContentType     =3D true; break;=0A=
            case 'date'            : gotDate            =3D true; break;=0A=
            case 'expires'         : gotExpiration      =3D true; break;=0A=
            case 'last-modified'   : gotLastModified    =3D true; break;=0A=
          }=0A=
        }=0A=
      }=0A=
      // try to fill in any missing header information=0A=
      var val;=0A=
      val =3D conn.getContentEncoding();=0A=
      if (val !=3D null && !gotContentEncoding) =
this._headers[this._headers.length] =3D {h:'Content-encoding', v:val};=0A=
      val =3D conn.getContentLength();=0A=
      if (val !=3D -1 && !gotContentLength) =
this._headers[this._headers.length] =3D {h:'Content-length', v:val};=0A=
      val =3D conn.getContentType();=0A=
      if (val !=3D null && !gotContentType) =
this._headers[this._headers.length] =3D {h:'Content-type', v:val};=0A=
      val =3D conn.getDate();=0A=
      if (val !=3D 0 && !gotDate) this._headers[this._headers.length] =
=3D {h:'Date', v:(new Date(val)).toUTCString()};=0A=
      val =3D conn.getExpiration();=0A=
      if (val !=3D 0 && !gotExpiration) =
this._headers[this._headers.length] =3D {h:'Expires', v:(new =
Date(val)).toUTCString()};=0A=
      val =3D conn.getLastModified();=0A=
      if (val !=3D 0 && !gotLastModified) =
this._headers[this._headers.length] =3D {h:'Last-modified', v:(new =
Date(val)).toUTCString()};=0A=
      // read response data=0A=
      var reqdata =3D '';=0A=
      var stream =3D conn.getInputStream();=0A=
      if (stream) {=0A=
        var reader =3D new java.io.BufferedReader(new =
java.io.InputStreamReader(stream, this._getCharset()));=0A=
        var line;=0A=
        while ((line =3D reader.readLine()) !=3D null) {=0A=
          if (this.readyState =3D=3D 2) {=0A=
            this.readyState =3D 3;=0A=
            if (this.onreadystatechange) {=0A=
              this.onreadystatechange();=0A=
            }=0A=
          }=0A=
          reqdata +=3D line + '\n';=0A=
        }=0A=
        reader.close();=0A=
        this.status =3D 200;=0A=
        this.statusText =3D 'OK';=0A=
        this.responseText =3D reqdata;=0A=
        this.readyState =3D 4;=0A=
        if (this.onreadystatechange) {=0A=
          this.onreadystatechange();=0A=
        }=0A=
        if (this.onload) {=0A=
          this.onload();=0A=
        }=0A=
      } else {=0A=
        // error=0A=
        this.status =3D 404;=0A=
        this.statusText =3D 'Not Found';=0A=
        this.responseText =3D '';=0A=
        this.readyState =3D 4;=0A=
        if (this.onreadystatechange) {=0A=
          this.onreadystatechange();=0A=
        }=0A=
        if (this.onerror) {=0A=
          this.onerror();=0A=
        }=0A=
      }=0A=
    };=0A=
  };=0A=
}=0A=
// ActiveXObject emulation=0A=
if (!window.ActiveXObject && window.XMLHttpRequest) {=0A=
  window.ActiveXObject =3D function(type) {=0A=
    switch (type.toLowerCase()) {=0A=
      case 'microsoft.xmlhttp':=0A=
      case 'msxml2.xmlhttp':=0A=
      case 'msxml2.xmlhttp.3.0':=0A=
      case 'msxml2.xmlhttp.4.0':=0A=
      case 'msxml2.xmlhttp.5.0':=0A=
        return new XMLHttpRequest();=0A=
    }=0A=
    return null;=0A=
  };=0A=
}=0A=

------=_NextPart_000_0000_01C6768E.F0FCF0E0
Content-Type: application/octet-stream
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.pnas.org/javascript/ajax/utility.js

/************************************************************************=
*****=0A=
 * javascript/ajax/utility.js=0A=
 *=0A=
 * Utility functions for working with XMLHttpRequest data.=0A=
 *=0A=
 * Copyright 2006 Board of Trustees of the Leland Stanford Junior =
University.=0A=
 =
*************************************************************************=
***/=0A=
=0A=
/*=0A=
 * Copy XML nodes into an HTMLElement. This effectively=0A=
 * clones XML markup which uses XHTML naming conventions=0A=
 * into an HTML DOM.=0A=
 */=0A=
function copy_xml_to_html(src, dst) {=0A=
  if (src.nodeType =3D=3D 1) { /* Node.ELEMENT_NODE */=0A=
    var e =3D document.createElement(src.nodeName);=0A=
    for (var i =3D 0; i < src.childNodes.length; i++) {=0A=
	  copy_xml_to_html(src.childNodes[i], e);=0A=
    }=0A=
    for (var i =3D 0; i < src.attributes.length; i++) {=0A=
      var n =3D src.attributes[i].name;=0A=
      var v =3D unescape_xml_string(src.attributes[i].value);      =0A=
      e.setAttribute(n, v);=0A=
      if (n =3D=3D "class") {=0A=
        e.className =3D v;=0A=
      }=0A=
      else if (n =3D=3D "style") {=0A=
        set_css_style(v, e, "");=0A=
      }=0A=
    }=0A=
    dst.appendChild(e);=0A=
  }=0A=
  else if (src.nodeType =3D=3D 3) { /* Node.TEXT_NODE */=0A=
    dst.appendChild(document.createTextNode(src.nodeValue));=0A=
  }=0A=
}=0A=
=0A=
/* =0A=
 * It is unclear that this is the right thing to be calling=0A=
 * from copy_xml_to_html, but it appears that Safari decides=0A=
 * to convert &amp; to the NCR &#35;, and then encodes that=0A=
 * NCR to &%26%2338;.  So, I'm going to treat the DOM Attr=0A=
 * value as a plain string, and run our XML string input=0A=
 * through the decoding routine below.=0A=
 */=0A=
function unescape_xml_string(s) {=0A=
  return s.replace(/&apos;/g, "'")=0A=
          .replace(/&#39;/g,  "'")=0A=
          .replace(/&quot;/g, "\"")=0A=
          .replace(/&#34;/g,  "\"")=0A=
          .replace(/&gt;/g,   ">")=0A=
          .replace(/&#62;/g,  ">")=0A=
          .replace(/&lt;/g,   "<")=0A=
          .replace(/&#60;/g,  "<")=0A=
          .replace(/&amp;/g,  "&")=0A=
          .replace(/&#38;/g,  "&");=0A=
}=0A=
=0A=
/*=0A=
 * Parse set of CSS rules and apply them to an element.=0A=
 * This is quite horrifying, but I'm unable to determine=0A=
 * how else to handle this with IE 6.  FireFox and other=0A=
 * sane browsers let you simply set the style attribute=0A=
 * or use e.style.setProperty(rule, value, priority),=0A=
 * IE 6 appears to have neither of these capabilities..=0A=
 */=0A=
function set_css_style(css, e, priority) {=0A=
  var rules =3D css.split(";");=0A=
  for (var i =3D 0; i < rules.length; i++) {=0A=
    var nvpair =3D rules[i].split(":");=0A=
    if (nvpair.length =3D=3D 2) {=0A=
      try {=0A=
        var name  =3D nvpair[0]; /* style attribute */=0A=
        var value =3D nvpair[1]; /* attribute value */=0A=
  =0A=
        /*=0A=
         * For each possible style attribute, set the=0A=
         * appropriate style property in the element.=0A=
         */=0A=
        if (name =3D=3D "background") {=0A=
           e.style.background =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-attachment") {=0A=
          e.style.backgroundAttachment =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-color") {=0A=
          e.style.backgroundColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-image") {=0A=
          e.style.backgroundImage =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-position") {=0A=
          e.style.backgroundPosition =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-position-x") {=0A=
          e.style.backgroundPositionX =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-position-y") {=0A=
          e.style.backgroundPositionY =3D value;=0A=
        }=0A=
        else if (name =3D=3D "background-repeat") {=0A=
          e.style.backgroundRepeat =3D value;=0A=
        }=0A=
        else if (name =3D=3D "behavior") {=0A=
          e.style.behavior =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border") {=0A=
          e.style.border =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-bottom") {=0A=
          e.style.borderBottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-bottom-color") {=0A=
          e.style.borderBottomColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-bottom-style") {=0A=
          e.style.borderBottomStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-bottom-width") {=0A=
          e.style.borderBottomWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-collapse") {=0A=
          e.style.borderCollapse =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-color") {=0A=
          e.style.borderColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-left") {=0A=
          e.style.borderLeft =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-left-color") {=0A=
          e.style.borderLeftColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-left-style") {=0A=
          e.style.borderLeftStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-left-width") {=0A=
          e.style.borderLeftWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-right") {=0A=
          e.style.borderRight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-right-color") {=0A=
          e.style.borderRightColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-right-style") {=0A=
          e.style.borderRightStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-right-width") {=0A=
          e.style.borderRightWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-style") {=0A=
          e.style.borderStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-top") {=0A=
          e.style.borderTop =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-top-color") {=0A=
          e.style.borderTopColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-top-style") {=0A=
          e.style.borderTopStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-top-width") {=0A=
          e.style.borderTopWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "border-width") {=0A=
          e.style.borderWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "bottom") {=0A=
          e.style.bottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "clear") {=0A=
          e.style.clear =3D value;=0A=
        }=0A=
        else if (name =3D=3D "clip") {=0A=
          e.style.clip =3D value;=0A=
        }=0A=
        else if (name =3D=3D "color") {=0A=
          e.style.color =3D value;=0A=
        }=0A=
        else if (name =3D=3D "cssText") {=0A=
          e.style.Sets =3D value;=0A=
        }=0A=
        else if (name =3D=3D "cursor") {=0A=
          e.style.cursor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "direction") {=0A=
          e.style.direction =3D value;=0A=
        }=0A=
        else if (name =3D=3D "display") {=0A=
          e.style.display =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font") {=0A=
          e.style.font =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font-family") {=0A=
          e.style.fontFamily =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font-size") {=0A=
          e.style.fontSize =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font-style") {=0A=
          e.style.fontStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font-variant") {=0A=
          e.style.fontVariant =3D value;=0A=
        }=0A=
        else if (name =3D=3D "font-weight") {=0A=
          e.style.fontWeight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "height") {=0A=
          e.style.height =3D value;=0A=
        }=0A=
        else if (name =3D=3D "ime-mode") {=0A=
          e.style.imeMode =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-flow") {=0A=
          e.style.layoutFlow =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-grid") {=0A=
          e.style.layoutGrid =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-grid-char") {=0A=
          e.style.layoutGridChar =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-grid-line") {=0A=
          e.style.layoutGridLine =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-grid-mode") {=0A=
          e.style.layoutGridMode =3D value;=0A=
        }=0A=
        else if (name =3D=3D "layout-grid-type") {=0A=
          e.style.layoutGridType =3D value;=0A=
        }=0A=
        else if (name =3D=3D "left") {=0A=
          e.style.left =3D value;=0A=
        }=0A=
        else if (name =3D=3D "letter-spacing") {=0A=
          e.style.letterSpacing =3D value;=0A=
        }=0A=
        else if (name =3D=3D "line-break") {=0A=
          e.style.lineBreak =3D value;=0A=
        }=0A=
        else if (name =3D=3D "line-height") {=0A=
          e.style.lineHeight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "list-style") {=0A=
          e.style.listStyle =3D value;=0A=
        }=0A=
        else if (name =3D=3D "list-style-image") {=0A=
          e.style.listStyleImage =3D value;=0A=
        }=0A=
        else if (name =3D=3D "list-style-position") {=0A=
          e.style.listStylePosition =3D value;=0A=
        }=0A=
        else if (name =3D=3D "list-style-type") {=0A=
          e.style.listStyleType =3D value;=0A=
        }=0A=
        else if (name =3D=3D "margin") {=0A=
          e.style.margin =3D value;=0A=
        }=0A=
        else if (name =3D=3D "margin-bottom") {=0A=
          e.style.marginBottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "margin-left") {=0A=
          e.style.marginLeft =3D value;=0A=
        }=0A=
        else if (name =3D=3D "margin-right") {=0A=
          e.style.marginRight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "margin-top") {=0A=
          e.style.marginTop =3D value;=0A=
        }=0A=
        else if (name =3D=3D "min-height") {=0A=
          e.style.minHeight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "overflow") {=0A=
          e.style.overflow =3D value;=0A=
        }=0A=
        else if (name =3D=3D "overflow-x") {=0A=
          e.style.overflowX =3D value;=0A=
        }=0A=
        else if (name =3D=3D "overflow-y") {=0A=
          e.style.overflowY =3D value;=0A=
        }=0A=
        else if (name =3D=3D "padding") {=0A=
          e.style.padding =3D value;=0A=
        }=0A=
        else if (name =3D=3D "padding-bottom") {=0A=
          e.style.paddingBottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "padding-left") {=0A=
          e.style.paddingLeft =3D value;=0A=
        }=0A=
        else if (name =3D=3D "padding-right") {=0A=
          e.style.paddingRight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "padding-top") {=0A=
          e.style.paddingTop =3D value;=0A=
        }=0A=
        else if (name =3D=3D "page-break-after") {=0A=
          e.style.pageBreakAfter =3D value;=0A=
        }=0A=
        else if (name =3D=3D "page-break-before") {=0A=
          e.style.pageBreakBefore =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelBottom") {=0A=
          e.style.pixelBottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelHeight") {=0A=
          e.style.pixelHeight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelLeft") {=0A=
          e.style.pixelLeft =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelRight") {=0A=
          e.style.pixelRight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelTop") {=0A=
          e.style.pixelTop =3D value;=0A=
        }=0A=
        else if (name =3D=3D "pixelWidth") {=0A=
          e.style.pixelWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posBottom") {=0A=
          e.style.posBottom =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posHeight") {=0A=
          e.style.posHeight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "position") {=0A=
          e.style.position =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posLeft") {=0A=
          e.style.posLeft =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posRight") {=0A=
          e.style.posRight =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posTop") {=0A=
          e.style.posTop =3D value;=0A=
        }=0A=
        else if (name =3D=3D "posWidth") {=0A=
          e.style.posWidth =3D value;=0A=
        }=0A=
        else if (name =3D=3D "right") {=0A=
          e.style.right =3D value;=0A=
        }=0A=
        else if (name =3D=3D "ruby-align") {=0A=
          e.style.rubyAlign =3D value;=0A=
        }=0A=
        else if (name =3D=3D "ruby-overhang") {=0A=
          e.style.rubyOverhang =3D value;=0A=
        }=0A=
        else if (name =3D=3D "ruby-position") {=0A=
          e.style.rubyPosition =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-3dlight-color") {=0A=
          e.style.scrollbar3dLightColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-arrow-color") {=0A=
          e.style.scrollbarArrowColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-base-color") {=0A=
          e.style.scrollbarBaseColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-darkshadow-color") {=0A=
          e.style.scrollbarDarkShadowColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-face-color") {=0A=
          e.style.scrollbarFaceColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-highlight-color") {=0A=
          e.style.scrollbarHighlightColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-shadow-color") {=0A=
          e.style.scrollbarShadowColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "scrollbar-track-color") {=0A=
          e.style.scrollbarTrackColor =3D value;=0A=
        }=0A=
        else if (name =3D=3D "float") {=0A=
          e.style.styleFloat =3D value;=0A=
        }=0A=
        else if (name =3D=3D "table-layout") {=0A=
          e.style.tableLayout =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-align") {=0A=
          e.style.textAlign =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-align-last") {=0A=
          e.style.textAlignLast =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-autospace") {=0A=
          e.style.textAutospace =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-decoration") {=0A=
          e.style.textDecoration =3D value;=0A=
        }=0A=
        else if (name =3D=3D "textDecorationBlink") {=0A=
          e.style.textDecorationBlink =3D value;=0A=
        }=0A=
        else if (name =3D=3D "textDecorationLineThrough") {=0A=
          e.style.textDecorationLineThrough =3D value;=0A=
        }=0A=
        else if (name =3D=3D "textDecorationNone") {=0A=
          e.style.textDecorationNone =3D value;=0A=
        }=0A=
        else if (name =3D=3D "textDecorationOverline") {=0A=
          e.style.textDecorationOverline =3D value;=0A=
        }=0A=
        else if (name =3D=3D "textDecorationUnderline") {=0A=
          e.style.textDecorationUnderline =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-indent") {=0A=
          e.style.textIndent =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-justify") {=0A=
          e.style.textJustify =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-kashida-space") {=0A=
          e.style.textKashidaSpace =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-overflow") {=0A=
          e.style.textOverflow =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-transform") {=0A=
          e.style.textTransform =3D value;=0A=
        }=0A=
        else if (name =3D=3D "text-underline-position") {=0A=
          e.style.textUnderlinePosition =3D value;=0A=
        }=0A=
        else if (name =3D=3D "top") {=0A=
          e.style.top =3D value;=0A=
        }=0A=
        else if (name =3D=3D "unicode-bidi") {=0A=
          e.style.unicodeBidi =3D value;=0A=
        }=0A=
        else if (name =3D=3D "vertical-align") {=0A=
          e.style.verticalAlign =3D value;=0A=
        }=0A=
        else if (name =3D=3D "visibility") {=0A=
          e.style.visibility =3D value;=0A=
        }=0A=
        else if (name =3D=3D "white-space") {=0A=
          e.style.whiteSpace =3D value;=0A=
        }=0A=
        else if (name =3D=3D "width") {=0A=
          e.style.width =3D value;=0A=
        }=0A=
        else if (name =3D=3D "word-break") {=0A=
          e.style.wordBreak =3D value;=0A=
        }=0A=
        else if (name =3D=3D "word-spacing") {=0A=
          e.style.wordSpacing =3D value;=0A=
        }=0A=
        else if (name =3D=3D "word-wrap") {=0A=
          e.style.wordWrap =3D value;=0A=
        }=0A=
        else if (name =3D=3D "writing-mode") {=0A=
          e.style.writingMode =3D value;=0A=
        }=0A=
        else if (name =3D=3D "z-index") {=0A=
          e.style.zIndex =3D value;=0A=
        }=0A=
        else if (name =3D=3D "zoom") {=0A=
          e.style.zoom =3D value;=0A=
        }=0A=
      }=0A=
      catch (e) {=0A=
        /* ignore error on attempt to set e.style.[property] */=0A=
      }=0A=
    }=0A=
  }=0A=
}=0A=

------=_NextPart_000_0000_01C6768E.F0FCF0E0
Content-Type: application/octet-stream
Content-Transfer-Encoding: quoted-printable
Content-Location: http://www.pnas.org/javascript/entrez/callback.js

/************************************************************************=
*****=0A=
 * javascript/entrez/callback.js=0A=
 *=0A=
 * Entrez Linking callback to populate content box.=0A=
 *=0A=
 * Copyright 2006 Board of Trustees of the Leland Stanford Junior =
University.=0A=
 =
*************************************************************************=
***/=0A=
=0A=
/*=0A=
 * Execute callback to fill content box with Entrez Linking information.=0A=
 */=0A=
function entrez_callback(pmid, callback_url) {=0A=
  /*=0A=
   * MSIE 5.5 and below have issues with the JavaScript=0A=
   * used for Entrez Linking. For now we have to disable=0A=
   * the callback until we can track down a proper fix=0A=
   * (or everybody sanely upgrades to version 6 or 7!).=0A=
   */=0A=
  if (navigator) {=0A=
    var appname =3D navigator.appName;=0A=
    if (appname =3D=3D "Microsoft Internet Explorer") {=0A=
      var userAgent =3D navigator["userAgent"];=0A=
      var s =3D "MSIE ";=0A=
      var n =3D -1;      =0A=
      if ((n =3D userAgent.indexOf(s)) !=3D -1) {=0A=
        var v =3D parseFloat(userAgent.substring(n+s.length));=0A=
        if (v < 6) {=0A=
          return;=0A=
        }=0A=
      }=0A=
    }=0A=
  }=0A=
=0A=
  /*=0A=
   * Acquire table row element to update, initiate callback=0A=
   * to update table with Entrez Links.=0A=
   */=0A=
  var tr =3D document.getElementById('entrez_callback_'+pmid);=0A=
  if (!tr) {=0A=
    return;=0A=
  }=0A=
  var req =3D new XMLHttpRequest();=0A=
  if (!req) {=0A=
    return;=0A=
  }=0A=
  req.onreadystatechange =3D function() {=0A=
    if (req.readyState =3D=3D 4 && (req.status =3D=3D 200 || req.status =
=3D=3D 304)) {=0A=
      var src =3D req.responseXML.documentElement;=0A=
      var dst =3D document.createDocumentFragment();=0A=
      for (var i =3D 0; i < src.childNodes.length; i++) {=0A=
      	copy_xml_to_html(src.childNodes[i], dst);=0A=
      }=0A=
      var tbl =3D tr.parentNode;=0A=
      tbl.replaceChild(dst, tr);=0A=
    }=0A=
  }=0A=
  req.open('GET', callback_url, true);=0A=
  req.send(null);=0A=
}=0A=

------=_NextPart_000_0000_01C6768E.F0FCF0E0--

