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||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F20434207%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F20434207%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 20434207 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 20434207"/>
|
||
<input type="hidden" name="email-subject-hash" value="ece03de78bf56694cb84e36c20f3720bc5e1c60b1c77b9175cdb3d749c46b264"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="20434207">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(10)00382-X"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=20434207&db=pubmed&nlmid=0413066"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="20434207"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/20434207/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=20434207&db=pubmed&nlmid=0413066"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="20434207"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/20434207/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/20434207/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="20434207" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F20434207%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="u7yVOUJoR4qXpZJA7kysJbF8hpeWBlNmLUi0rKcKrFdrjqPqKDbudjbMPtW8uWlG"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
</div><div class="content"><div class="format-container"><span class="option-label">
|
||
Format
|
||
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Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation
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Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation
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Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation.
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Extracellular signals regulate protein translation in many cell functions. A key advantage of control at the translational level is the opportunity to regulate protein synthesis within specific cellular subregions. However, little is known about mechanisms that may link extracellular cues to translation with spatial precision. Here, we show that a transmembrane receptor, DCC, forms a binding complex containing multiple translation components, including eukaryotic initiation factors, ribosomal large and small subunits, and monosomes. In neuronal axons and dendrites DCC colocalizes in particles with translation machinery, and newly synthesized protein. The extracellular ligand netrin promoted DCC-mediated translation and disassociation of translation components. The functional and physical association of a cell surface receptor with the translation machinery leads to a generalizable model for localization and extracellular regulation of protein synthesis, based on a transmembrane translation regulation complex.
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<p> Figure 1. DCC colocalizes with translational components </p>
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<div class="figure-caption-contents"><p> (A-H) Immunofluorescence. (A-D) Cultured commissural axons. DCC (red)… </p></div>
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<strong class="figure-label">
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Figure 1. DCC colocalizes with translational components
|
||
</strong>
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<div class="figure-caption-contents">(A-H) Immunofluorescence. (A-D) Cultured commissural axons. DCC (red) and ribosomal protein S6 (green) appeared in puncta within the growth cone, with a subset of puncta overlapping (yellow). Panels B-D are enlargement of boxes from A, showing filopodial tips, with a central growth cone area in the inset. Arrowheads: examples of colocalized puncta, notably at filopodial tips. (E-H) Cultured hippocampal dendrites. Labeling for DCC (blue), eIF4E (green), and the postsynaptic marker PSD-95 was seen in puncta at synapses (arrowheads). Nuclear DAPI staining is shown in purple. (I-V) Electron microscopy, showing double immunogold labeling for endogenous DCC (15 nm gold particles in panels I-S; 10 nm particles in T-V) and ribosomal protein S6 (5 nm particles). Some variation in particle size is caused by silver enhancement. (I-S) Cultured commissural axons. Panels I-O show distal part of growth cone near the base of the filopodia; P and Q show axon shaft, oriented vertically; R shows filopodium, with distal end toward upper left. (T-V) Cultured hippocampal neuron synapse, diagrammed in panel V. White arrowheads: examples of clustered particles. Black arrows: outer boundary of the cell. Boxes show enlargement of clustered particles. Scale bar: 70 nm in J, R and P; 15 nm in T. See also Figure S1.</div>
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<p> Figure 2. Tandem mass spectrometry screen identifying… </p>
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<strong class="figure-label">
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<p> Figure 2. Tandem mass spectrometry screen identifying translational components coprecipitated with DCC </p>
|
||
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<div class="figure-caption-contents"><p> (A) Tandem mass… </p></div>
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<strong class="figure-label">
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Figure 2. Tandem mass spectrometry screen identifying translational components coprecipitated with DCC
|
||
</strong>
|
||
|
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|
||
|
||
<div class="figure-caption-contents">(A) Tandem mass spectrometry identification of proteins following immunoprecipitation with anti-DCC antibody. Proteins listed showed specific coprecipitation from 293-net cells transfected with DCC, versus vector control. Ribosomal proteins are highlighted in dark orange, and initiation factors in light orange. Grey indicates proteins previously shown to interact directly with DCC (although other known interaction partners such as Nck, Src and Fyn were not seen here, presumably reflecting detection limits in this screen). Accession numbers: UniProtKB/Swiss-Prot data base. (B) Most of the candidate translational components from the mass spectrometry screen were tested by Western blot, and in every case tested were confirmed to show co-immunoprecipitation with DCC. See also Figure S2.</div>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b80/2881594/bd1c9634afe7/nihms-196478-f0003.gif"
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<p> Figure 3. DCC receptor physically associates with… </p>
|
||
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<strong class="figure-label">
|
||
<p> Figure 3. DCC receptor physically associates with translation machinery </p>
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Ribosome sedimentation from netrin-expressing 293-net… </p></div>
|
||
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<strong class="figure-label">
|
||
Figure 3. DCC receptor physically associates with translation machinery
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Ribosome sedimentation from netrin-expressing 293-net cells transfected with full length DCC. DCC cosedimented in 40S, 60S and 80S fractions (red box) but not prominently in the polysome fraction. Control proteins were distributed as expected from previous studies: S6 in 40S, 80S and polysomal fractions; L5 in 60S, 80S and polysomal fractions; eIF4E primarily in the 40S fraction; and eIF2α in all four fractions. (B) DCC association with translation machinery, with all proteins expressed at endogenous levels in developing spinal cord. Left panel: DCC cosedimented in 40S, 60S and 80S fractions. Other markers such as eIF4E distributed as expected in spinal cord (not shown). Upper right panel: translational components co-immunoprecipitated with DCC. Lower right panel: DCC co-immunoprecipitated with eIF4E. (C) DCC-Δcyto mutant lacking a cytoplasmic domain did not co-precipitate ribosomal marker L5. myc-tagged mCdGAP was a negative control. See also Figure S3.</div>
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|
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|
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<strong class="figure-label">
|
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<p> Figure 4. Effects of DCC and netrin… </p>
|
||
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|
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|
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<strong class="figure-label">
|
||
<p> Figure 4. Effects of DCC and netrin on translation </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> (A) Full length DCC mediated netrin… </p></div>
|
||
|
||
|
||
|
||
|
||
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|
||
|
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<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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|
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<strong class="figure-label">
|
||
Figure 4. Effects of DCC and netrin on translation
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) Full length DCC mediated netrin promotion of translation. 293 cells were transfected with DCC constructs, together with a reporter plasmid for cap-dependent translation (Figure S4A). Reporter translation was normalized to a cap-independent internal control, and is compared in netrin-expressing 293-net cells (+) versus 100% in control cells (–). DCC lacking a cytoplasmic domain (DCC-Δcyto) showed no effect on translation. n=3 experiments; error bars, SEM. Without netrin, full length DCC promoted translation slightly in some experiments, although to a much lesser degree than with netrin (data not shown). (B) Netrin reduced the association of DCC with translation components. Western analysis showed reduced coprecipitation of markers of the ribosomal large subunit (L5), small subunit (S4X) and initiation factor eIF4E with exogenous DCC in netrin-expressing 293-net cells (+), compared with control 293 cells (–). An association above background remained, however, in the presence of netrin (see Figure S4H). (C) DCC cytoplasmic domain (DCC<sub>cyto</sub>) inhibited translation. Purified recombinant DCC<sub>cyto</sub> (100 ng, 200 ng, and 500 ng) or GST control protein was added to a rabbit reticulocyte lysate translation system. (D) Ribosome sedimentation profiles of reticulocyte lysates following incubation with purified recombinant DCC<sub>cyto</sub> (right) or GST control (left). DCC<sub>cyto</sub> cosedimented with 40S, 60S and 80S fractions. DCC<sub>cyto</sub> decreased the polysome fraction and increased the 80S fraction, implying that a step after 80S ribosome assembly was inhibited and became rate limiting in this assay, although earlier steps may also be affected. Ribosomal proteins distributed as expected: S23 in 40S, 80S and polysome fractions; L5 in 60S, 80S and polysome fractions. See also Figure S4.</div>
|
||
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<p> Figure 5. Involvement of the DCC P1… </p>
|
||
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<strong class="figure-label">
|
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<p> Figure 5. Involvement of the DCC P1 domain and ribosomal protein L5 </p>
|
||
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|
||
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|
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<div class="figure-caption-contents"><p> (A) DCC cytoplasmic… </p></div>
|
||
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<strong class="figure-label">
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Figure 5. Involvement of the DCC P1 domain and ribosomal protein L5
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A) DCC cytoplasmic domain contains three conserved motifs: P1, P2 and P3. A nested series of deletions were made, and an internal deletion of the P1 motif. (B) DCC promotion of translation was prevented by P1 deletion (DCC-ΔP1), and partially reduced by P3 deletion (DCC-ΔP3). The assay was as in Figure 4A, with cap-dependent reporter translation normalized to a cap-independent control. n=3 experiments; error bars, SEM. (C-I) Physical and functional interactions with ribosomal protein L5. (C) Far Western dot blot quantitation of direct binding of purified recombinant DCC cytoplasmic domain to purified recombinant L5. Ribosomal protein L13a and GST provide controls. Ponceau stain shows similar loading. n=4 experiments; error bars, SEM. (D, E) Western analysis of endogenous L5 co-immunopreciptation with DCC, showing L5 associated with all mutants in the nested deletion series except DCC-Δcyto, and not with DCC-ΔP1. (F-H) Immunofluorescence of DCC (red) and GFP-L5 (green) co-transfected into 293 cells, showing colocalization in neurite-like extensions, notably at the tips (arrowheads). (I) Functional interaction between ribosomal protein L5 and DCC<sub>cyto</sub>. The inhibitory effect of DCC<sub>cyto</sub> in a reticulocyte lysate (see Figure 4C) was rescued in a dose-dependent manner by recombinant L5 (100 ng, 200 ng, and 500 ng). GST control at the same concentrations did not rescue. L5 alone (200 ng and 500 ng) had no noticeable effect. Column 5 is a duplicate of column 4 to clarify control value. (J-P) Effect of DCC-ΔP1 as a dominant inhibitory mutant on commissural axon pathfinding in developing spinal cord. Chick spinal cords at E3.5 (HH 23) were electroporated and analyzed 36 hr later, compared with controls electroporated on the contralateral side of the same spinal cord. (J) Illustration of spinal cord open book preparations, with imaged area in box. (K) Diagram of axon trajectories seen in panel N: axons grow toward the midline floor plate (arrowheads), cross it, then turn and grow anteriorly (arrow). (L, M) Control plasmids expressing GFP and RFP; equivalent axon numbers, growth rates and patterns were seen for both tracers after 18 or 36 hours. (N, O) Axons electroporated with DCC-ΔP1 (right side, red) compared to GFP control (left side, green) showed greater numbers remaining at locations midway toward the floorplate (red; examples indicated by arrowheads), and fewer had reached or crossed the floor plate compared with control (green; examples indicated by arrows). Panel O shows enlargement of boxed area. (P) Quantitation of axons reaching the midline after electroporation with control or DCC-ΔP1 mutant construct. A total of 530 axons were analyzed in seven experiments; error bars, SEM. Scale bar in N, 100 μm. FP, floor plate. See also Figure S5.</div>
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<p> Figure 6. DCC colocalizes with newly synthesized… </p>
|
||
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<p> Figure 6. DCC colocalizes with newly synthesized protein </p>
|
||
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<div class="figure-caption-contents"><p> (A, B) Localization of DCC (green) and… </p></div>
|
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|
||
Figure 6. DCC colocalizes with newly synthesized protein
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents">(A, B) Localization of DCC (green) and AHA labeled sites of newly synthesized protein (red) in cultured commissural axon growth cone. Panel B shows enlargement of boxes in A. Arrowheads show examples of overlapping puncta (yellow) notably at filopodial tips. (C) DCC (green) and AHA (red) labeling in cultured hippocampal neuron dendrite. Arrowheads indicate overlap. (D) Quantitation of AHA labeling in DCC puncta at filopodial tips. AHA was added for 20 min; then cycloheximide (CHX) for 20 min; then 200 ng/ml netrin-1 for 10 min. Netrin induced an increase in labeling that was blocked by cycloheximide. Panels A-C were in the presence of netrin-1. Scale bars: 5 μm in panel A; 1 μm in B and C. See also Figure S6.</div>
|
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<p> Figure 7. Models for interaction of DCC… </p>
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<p> Figure 7. Models for interaction of DCC with translational machinery </p>
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<div class="figure-caption-contents"><p> (A) In the model illustrated,… </p></div>
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Figure 7. Models for interaction of DCC with translational machinery
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<div class="figure-caption-contents">(A) In the model illustrated, full length DCC associates with translation initiation machinery, including 40S, 60S and 80S ribosomes and eIFs. Signaling by DCC within this complex is enhanced by netrin, and promotes formation of actively elongating polysomes which are no longer associated with DCC. Polysomes may nevertheless tend to remain locally within micron scale structures such as a filopodial tip or synaptic spine, and this may be facilitated by their known interaction with the cytoskeleton. Transduction of a signal across the membrane by DCC and other receptors is believed to be mediated by dimerization or higher-order clustering. In the absence of netrin, spontaneous dimerization and signaling by DCC may promote some translation, although at a lower level than with netrin. Signaling by some DCC molecules in the cell would not preclude the coexistence of other DCC molecules that remain in a complex with translation initiation machinery. In addition to DCC and translation initiation machinery, the complex is proposed also to include signal transduction proteins, and DCC may regulate more than one step of initiation. (B) No prominent association with translation components or functional effect on translation was seen with DCC mutants lacking the cytoplasmic domain (DCC-Δcyto) or lacking the 20 amino acid P1 motif (DCC-ΔP1), showing a requirement of these regions for physical and functional interactions with translation machinery. (C) The DCC cytoplasmic domain by itself, DCC<sub>cyto</sub>, cosedimented with 40S, 60S and 80S ribosomes, and inhibited protein synthesis in a cell-free system, showing that this region is sufficient for physical and functional interactions with translational machinery. DCC<sub>cyto</sub> is proposed to act here as an interfering mutant, occupying downstream components but lacking an extracellular domain necessary for positive signaling. Although the diagrams are not to a precise scale, receptor length and ribosome diameter are approximately in proportion: the eukaryotic ribosome is ~20-30 nm across (Spahn et al., 2001); each Ig domain (oval) and FNIII domain (small square) is ~4 nm long; the intracellular domain of DCC (rectangle) is approximately 25% of the protein sequence as illustrated here in proportion with the extracellular length to account for potential folding, or in more extended conformation it could be up to 100 nm long.</div>
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data-ga-label="Amino Acid Motifs">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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role="button"
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data-search-term=""Amino Acid Motifs"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Amino Acid Motifs"[MeSH]"
|
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Animals"
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tabindex="0"
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|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Animals
|
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</button><div id="keyword-actions-mesh-terms-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Animals"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Animals"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Animals">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Animals"
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Animals"[MeSH]"
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data-ga-category="search"
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data-ga-label=""Animals"[MeSH]"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Axons / metabolism"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Axons / metabolism
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</button><div id="keyword-actions-mesh-terms-2"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Axons / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Axons%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Axons%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Axons/metabolism"[MeSH]"
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Axons"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Axons/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Axons/metabolism"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Cells, Cultured"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Cells, Cultured
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</button><div id="keyword-actions-mesh-terms-3"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Cells, Cultured"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Cells%2C+Cultured%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Cells%2C+Cultured%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Cells, Cultured"[MeSH]"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Cells%2C+Cultured"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Cells, Cultured"[MeSH]"
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data-ga-category="search"
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data-ga-label=""Cells, Cultured"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Chick Embryo"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Chick Embryo
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</button><div id="keyword-actions-mesh-terms-4"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Chick Embryo"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Chick+Embryo%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Chick+Embryo%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Chick Embryo"[MeSH]"
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data-ga-label="Chick Embryo">
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Chick+Embryo"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Chick Embryo"[MeSH]"
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data-ga-category="search"
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data-ga-label=""Chick Embryo"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Dendrites / metabolism"
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tabindex="0"
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data-pinger-ignore>
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Dendrites / metabolism
|
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</button><div id="keyword-actions-mesh-terms-5"
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hidden
|
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aria-label="Dropdown menu for keyword Dendrites / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Dendrites%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Dendrites/metabolism"[MeSH]"
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Search in PubMed
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Search in MeSH
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data-search-term=""Dendrites/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Dendrites/metabolism"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Hippocampus / cytology"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-6"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Hippocampus / cytology
|
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</button><div id="keyword-actions-mesh-terms-6"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Hippocampus / cytology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Hippocampus%2Fcytology%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Hippocampus%2Fcytology%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hippocampus/cytology"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Hippocampus"
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Hippocampus/cytology"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Hippocampus / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-7"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Hippocampus / metabolism
|
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</button><div id="keyword-actions-mesh-terms-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Hippocampus / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Hippocampus%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Hippocampus%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Hippocampus/metabolism"[MeSH]"
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data-ga-action="mesh_term"
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data-ga-label="Hippocampus / metabolism">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Hippocampus"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Hippocampus / metabolism">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Hippocampus/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Hippocampus/metabolism"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Humans"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-8"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Humans
|
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</button><div id="keyword-actions-mesh-terms-8"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Humans">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Humans"
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data-ga-category="search_mesh"
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data-ga-label="Humans">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Humans"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Mice"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-9"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Mice
|
||
</button><div id="keyword-actions-mesh-terms-9"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Mice"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Mice"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Mice">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Mice"
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data-ga-category="search_mesh"
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data-ga-label="Mice">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Mice"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Mice"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Nerve Growth Factors / metabolism"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-10"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Nerve Growth Factors / metabolism
|
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</button><div id="keyword-actions-mesh-terms-10"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Nerve Growth Factors / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Nerve+Growth+Factors%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Nerve+Growth+Factors%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Nerve Growth Factors/metabolism"[MeSH]"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Nerve+Growth+Factors"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Nerve Growth Factors/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Nerve Growth Factors/metabolism"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Netrin-1"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-11"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Netrin-1
|
||
</button><div id="keyword-actions-mesh-terms-11"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Netrin-1"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Netrin-1%22%5BMeSH%5D&sort=date&sort_order=desc"
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|
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<div id="substances" class="substances keywords-section">
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Substances
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Nerve Growth Factors
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Receptors, Cell Surface
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ribosomal protein L5
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Netrin-1
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</div>
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|
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<div id="related-links" class="related-links">
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<h2 class="title">
|
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Related information
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</h2>
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<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=20434207"
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Cited in Books
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Gene
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MedGen
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MedGen (Bookshelf cited)
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</a></li><li><a title="OMIM (cited) Links" href="https://www.ncbi.nlm.nih.gov/omim?linkname=pubmed_omim_cited&from_uid=20434207"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=20434207&ordinalpos=1&linkpos=5">
|
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OMIM (cited)
|
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</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=20434207"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=20434207&ordinalpos=1&linkpos=6">
|
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Protein (RefSeq)
|
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</a></li></ul>
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</div>
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<div id="grants" class="grants">
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<h2 class="title">
|
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Grants and funding
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</h2>
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<div id="linkout" class="linkout">
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<h2 class="title">
|
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LinkOut - more resources
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</h2>
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|
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<ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a
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href="https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(10)00382-X"
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