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||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</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%2F20097765%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%2F20097765%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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
</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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
|
||
|
||
<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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
<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: 20097765 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 20097765"/>
|
||
<input type="hidden" name="email-subject-hash" value="f7010ede2f1fae6d9719e6f91a72cbe832972c730c852e0681153def3d7028af"/>
|
||
</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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
|
||
|
||
<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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
|
||
|
||
<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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
<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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
|
||
|
||
<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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y">
|
||
|
||
<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="20097765">
|
||
<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/S0021-9258(19)40567-X"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=20097765&db=pubmed&nlmid=2985121R"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="20097765"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.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/20097765/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=20097765&db=pubmed&nlmid=2985121R"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="20097765"
|
||
><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="/20097765/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/20097765/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="20097765" 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%2F20097765%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="lrzseyOXr7kHiz8AmYaoStP0hJkx0XBECejxRohj1I7bc0eqZhNqmBlEPN2JTy9Y"><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"
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Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids
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><sup class="key">1</sup> Institute for Clinical Chemistry, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland.</li>
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Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids
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HSAN1 is an inherited neuropathy found to be associated with several missense mutations in the SPTLC1 subunit of serine palmitoyltransferase (SPT). SPT catalyzes the condensation of serine and palmitoyl-CoA, the initial step in the de novo synthesis of sphingolipids. Here we show that the HSAN1 mutations induce a shift in the substrate specificity of SPT, which leads to the formation of the two atypical deoxy-sphingoid bases (DSBs) 1-deoxy-sphinganine and 1-deoxymethyl-sphinganine. Both metabolites lack the C(1) hydroxyl group of sphinganine and can therefore neither be converted to complex sphingolipids nor degraded. Consequently, they accumulate in the cell, as demonstrated in HEK293 cells overexpressing mutant SPTLC1 and lymphoblasts of HSAN1 patients. Elevated DSB levels were also found in the plasma of HSAN1 patients and confirmed in three groups of HSAN1 patients with different SPTLC1 mutations. The DSBs show pronounced neurotoxic effects on neurite formation in cultured sensory neurons. The neurotoxicity co-occurs with a disturbed neurofilament structure in neurites when cultured in the presence of DSBs. Based on these observations, we conclude that HSAN1 is caused by a gain of function mutation, which results in the formation of two atypical and neurotoxic sphingolipid metabolites.
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data-image-alt="FIGURE 1."
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||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/a46874b105f8/zbc0161010370001.gif"
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||
alt="FIGURE 1." />
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<strong class="figure-label">
|
||
<p> FIGURE 1. </p>
|
||
</strong>
|
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|
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|
||
|
||
<div class="figure-caption-contents"><i> A </i> , <i> de novo </i> sphingolipid…</div>
|
||
|
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|
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|
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|
||
</div>
|
||
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|
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|
||
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||
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||
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<strong class="figure-label">
|
||
<p> FIGURE 1. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , <i> de novo </i> sphingolipid synthesis pathway. <i> De novo </i> ceramide synthesis involves several…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
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<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
|
||
FIGURE 1.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i>A</i>, <i>de novo</i> sphingolipid synthesis pathway. <i>De novo</i> ceramide synthesis involves several steps. SPT catalyzes the initial conjugation of palmitoyl-CoA with <sc>l</sc>-serine to form 3-keto-sphinganine, which is subsequently reduced to SA. SA is acetylated by ceramide synthase (<i>CerS</i>) and desaturated by ceramide desaturase (<i>DES</i>) to form ceramide. The degradation pathway starts with the deacetylation of ceramide by ceramidase. The formed SO is then phosphorylated by SO-kinase and finally degraded to hexadecenal and phosphoethanolamine by the action of the sphingosine-1-phospate lyase (<i>SO1P lyase</i>). <i>B</i>, HEK293 cells expressing the SPT-C133W mutant generate an unknown metabolite. HEK293 cells were transfected with either wild-type SPTLC1 or the SPTLC1-C133W mutant. <i>De novo</i> synthesis was blocked with FB1 for 24 h. This causes an accumulation of sphinganine but also of other potential SPT products. The accumulated sphingoid bases were extracted and analyzed by HPLC. We observed a significant accumulation of SA in HEK<sub>L1</sub> cells (<i>black</i>). SA accumulation was lower in HEK<sub>C133W</sub> cells (<i>gray</i>), which reflects the reduced activity of the mutant. In parallel, we observed the appearance of a second, unknown peak (<i>arrow</i>). This peak appeared only in the presence of FB1 and was increased in cells expressing the C133W mutant. It was absent when SPT activity was blocked with myriocin. <i>int. STD</i>, internal standard.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
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data-slide-index="1"
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||
data-label-slug="figure-2">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/8274e0890682/zbc0161010370002.jpg"
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itemprop="contentUrl"
|
||
aria-describedby="figure-caption-1"
|
||
role="button"
|
||
data-image-width="512"
|
||
data-image-height="302"
|
||
data-image-alt="FIGURE 2."
|
||
data-pmc-id="PMC2856995"
|
||
data-figure-id="F2">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-1"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/156049d177d6/zbc0161010370002.gif"
|
||
alt="FIGURE 2." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="512">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="302">
|
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|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 2. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , products of the…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 2. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , products of the SPT reaction using serine, alanine, or glycine as…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 2.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i>A</i>, products of the SPT reaction using serine, alanine, or glycine as substrates. The conjugation of palmitoyl-CoA with alanine and glycine leads to the formation of the two DSBs: m18:0 and m17:0. <i>B</i>, chemical structure of the DSBs. An abbreviated nomenclature for sphingoid bases is used in this work. The numbers of hydroxyls are designated by <i>m</i> (for mono-) and <i>d</i> (for di-) followed by the number of carbons. The second number indicates the double bonds. For example, d18:0 stands for sphinganine, and d18:1 stands for sphingosine. All shown metabolites were also found in the <i>N</i>-acetylated form. <i>C</i>, accumulation of m18:0 and m17:0 in HEK<sub>C133W</sub> cells after supplementing the culture medium with alanine or glycine. HEK<sub>C133W</sub> cells were cultured using either standard medium (−) or medium that was supplemented with 10 m<sc>m</sc> alanine (+<i>ala</i>) or 10 m<sc>m</sc> glycine (+<i>gly</i>). <i>De novo</i> synthesis was blocked with FB1 for 24 h, and the accumulated lipids were analyzed by LC-MS. <i>D</i>, accumulation of DSB in HEK cells expressing mutant forms of SPT. HEK<sub>empty</sub>, HEK<sub>L1</sub>, HEK<sub>C133W</sub>, and HEK<sub>C133Y</sub> cells were treated with FB1 for 24 h, and the extracted lipids were quantified by LC-MS. <i>Error bars</i> in <i>C</i> and <i>D</i> indicate S.E. <i>p</i> values ≤ 0.01 were labeled with **.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
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|
||
data-slide-index="2"
|
||
data-label-slug="figure-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/48fac176cf71/zbc0161010370003.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-2"
|
||
role="button"
|
||
data-image-width="513"
|
||
data-image-height="298"
|
||
data-image-alt="FIGURE 3."
|
||
data-pmc-id="PMC2856995"
|
||
data-figure-id="F3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-2"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/85a8fe3bed6a/zbc0161010370003.gif"
|
||
alt="FIGURE 3." />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="513">
|
||
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|
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|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 3. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Accumulation of DSBs in EBV-transformed… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 3. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Accumulation of DSBs in EBV-transformed lymphoblasts of HSAN1 patients. </b> <i> A </i> , the <i> de… </i></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 3.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Accumulation of DSBs in EBV-transformed lymphoblasts of HSAN1 patients.</b> <i>A</i>, the <i>de novo</i> synthesis of DSBs was compared between EBV-transformed lymphoblasts from 12 HSAN1 patients (all C133W carriers) and six healthy controls. Lymphoblasts were cultured for 24 h in the presence of FB1, and lipids were extracted, base-hydrolyzed, and analyzed by LC-MS. SO was not detected in the lymphoblasts. <i>B</i>, sphingoid base levels in total lipid extracts of lymphoblasts from HSAN1 patients and healthy controls. Total cellular lipids were extracted and subjected to acid/base hydrolysis. The resulting free sphingoid bases were analyzed by LC-MS. No significant differences were seen in the total amounts of SA or SO, whereas the concentration of m17:0, m17:1, m18:0, and m18:1 was significantly higher in the HSAN1 lymphoblasts when compared with control cells. In <i>A</i> and <i>B</i>, <i>p</i> values ≤ 0.05 were labeled with *.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
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|
||
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|
||
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|
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|
||
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|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/19d7d5450b3f/zbc0161010370004.jpg"
|
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|
||
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|
||
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|
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|
||
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|
||
data-image-alt="FIGURE 4."
|
||
data-pmc-id="PMC2856995"
|
||
data-figure-id="F4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/701e17a94709/zbc0161010370004.gif"
|
||
alt="FIGURE 4." />
|
||
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|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="477">
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|
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|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> DSB plasma levels in HSAN1… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 4. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> DSB plasma levels in HSAN1 patients and healthy controls. </b> <i> A </i> , total plasma…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 4.
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>DSB plasma levels in HSAN1 patients and healthy controls.</b> <i>A</i>, total plasma lipids from seven HSAN1 patients (C133W carriers) and three unrelated healthy controls were extracted and subjected to acid and base hydrolysis. <i>P1–7</i>, plasma of HSAN1 patients; <i>C1–7</i>, control plasma. <i>B</i>, the m17 sphingoid bases were only detected in the plasma of HSAN1 patients. No m17 bases were found in control plasma. The symbols are: −, not affected; +, mildly affected, ++, moderately affected, +++, severely affected. <i>C</i>, comparison of m18:0 and m18:1 levels in affected (<i>P1–10</i>) and unaffected members (<i>C1–10</i>) of a C133Y family. All C133Y carriers showed significantly higher m18:0 and m18:1 levels when compared with family members who do not carry the mutation. No m17 sphingoid bases were detected in the plasma of the C133Y patients. <i>D</i>, m18:0 and m18:1 sphingoid bases were also significantly elevated in three carriers of a V144D mutation (<i>P1–3</i>) when compared with four non-carriers (<i>C1–4</i>). No m17 sphingoid bases were detected in the V144D carriers. <i>Error bars</i> indicate S.E.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
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<figure class="figure-item "
|
||
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|
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|
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|
||
data-label-slug="figure-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/94959e473c1f/zbc0161010370005.jpg"
|
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|
||
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|
||
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|
||
data-image-width="512"
|
||
data-image-height="482"
|
||
data-image-alt="FIGURE 5."
|
||
data-pmc-id="PMC2856995"
|
||
data-figure-id="F5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9807/2856995/22b317049e3f/zbc0161010370005.gif"
|
||
alt="FIGURE 5." />
|
||
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|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="512">
|
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|
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|
||
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|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , effect of SA,…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> FIGURE 5. </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><i> A </i> , effect of SA, m18:0, and m17:0 on cultured DRG neurons. Dissociated…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
FIGURE 5.
|
||
</strong>
|
||
|
||
|
||
|
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<div class="figure-caption-contents"><i>A</i>, effect of SA, m18:0, and m17:0 on cultured DRG neurons. Dissociated sensory neurons were grown for 12 h in control medium before the lipids were added for another 24 h. The addition of SA (1 μ<sc>m</sc>) had no effect on neurite number and length when compared with controls (<i>cntr</i> = BSA without lipids). In the presence of m18:0 (1 μ<sc>m</sc>), the cells showed a greatly reduced number of neurites. The addition of m17:0 (1 μ<sc>m</sc>) showed a similar but less pronounced effect. <i>B</i>, quantitative analysis of the formed neurites in the presence of SA, m18:0, and m17:0. The presence of SA had no significant effect on neurite outgrowth, whereas the presence of m18:0 clearly reduced the number of neurites in a dose-dependent manner. A similar effect was observed for m17:0 whereby the presence of m17:0 mainly affected cells with two and more neurites. <i>C</i>, effect of m18:0 on neurite formation in cultured motoneurons. Like sensory neurons, we observed a significant reduction of neurite numbers in the presence of m18:0. However, this reduction was less pronounced at higher m18:0 concentrations in motoneurons than in sensory neurons. <i>Error bars</i> in <i>B</i> and <i>C</i> indicate S.E., and <i>p</i> values ≤ 0.01 were labeled with **. <i>D</i>, distribution of neurite lengths in the presence of SA and deoxy-SA (m18:0) in sensory neurons. The distribution of neurite length was plotted as the percentage of neurons with neurites longer than a given length (<i>y</i> axis) <i>versus</i> neurite length (<i>x</i> axis) as introduced by Chang <i>et al.</i> (21). The length was measured as total neurite length elaborated per neuron. Neurons were cultured for 12 h prior to the addition of the lipids (<i>dashed line</i>). The presence of SA (1 and 0.5 μ<sc>m</sc>, <i>blue</i>) showed no reduction in the length of the formed neurites when compared with the control (BSA alone, <i>dotted line</i>). The presence of m18:0 significantly reduced neurite length in a dose-dependent manner (<i>red lines</i>). No difference to the control was seen with 0.1 μ<sc>m</sc> m18:0. In the presence of 0.5 and 1 μ<sc>m</sc> m18:0, we observed a significant shortening of the neurites in a dose-dependent manner. At the highest m18:0 concentrations tested (1 μ<sc>m</sc>), the neurites were even shorter than at the time the lipids were added (<i>dashed line</i>, neurite length prior to the addition of the lipids). <i>E</i>, the presence of m18:0 induced neurite retraction. Cells were cultured for 24 h prior to the addition of the lipids (<i>dashed line</i>). In the presence of SA (1 μ<sc>m</sc>, <i>blue line</i>), the neurites continued growing, although the growth rate was a little diminished in comparison with the control (<i>dotted line</i>). In contrast, the addition of m18:0 (1 μ<sc>m</sc>, <i>red line</i>) induced a significant retraction of the formed neurites. <i>F</i>, this effect was confirmed by immune fluorescence microscopy of sensory neurons that were cultured in the presence of SA or m18:0 (1 μ<sc>m</sc> each, 24 h). The SA-treated cells looked healthy and showed a clear co-localization of actin (<i>red</i>) and neurofilament (<i>green</i>) over the whole length of the neurite (<i>left panel</i>). In contrast, m18:0-treated neurons showed a disruption of the neurite structure with a retraction of neurofilament and a disturbed actin-neurofilament interaction (<i>right panel</i>). <i>B</i>, cell body; <i>N</i>, neurite; <i>C</i>, growth cone.</div>
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<span class="docsum-journal-citation short-journal-citation">FEBS J. 2013.</span>
|
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<span class="citation-part">PMID: <span class="docsum-pmid">23879641</span></span>
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Juvenile-onset <em>PSAT1</em>-related neuropathy: A milder phenotype of serine deficiency disorder.
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<div class="docsum-citation full-citation">
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<span class="docsum-authors full-authors">Shen Y, Peng Y, Huang P, Zheng Y, Li S, Jiang K, Zhou M, Deng J, Zhu M, Hong D.</span>
|
||
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||
|
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<span class="docsum-authors short-authors">Shen Y, et al.</span>
|
||
<span class="docsum-journal-citation full-journal-citation">Front Genet. 2022 Aug 16;13:949038. doi: 10.3389/fgene.2022.949038. eCollection 2022.</span>
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<span class="docsum-journal-citation short-journal-citation">Front Genet. 2022.</span>
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<div class="docsum-citation full-citation">
|
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<span class="docsum-authors full-authors">Takahashi-Umebayashi M, Pineau L, Hannich T, Zumbuehl A, Doval DA, Matile S, Heinis C, Turcatti G, Loewith R, Roux A, Reymond L, Johnsson K, Riezman H.</span>
|
||
|
||
|
||
|
||
<span class="docsum-authors short-authors">Takahashi-Umebayashi M, et al.</span>
|
||
<span class="docsum-journal-citation full-journal-citation">Chimia (Aarau). 2011;65(11):849-52. doi: 10.2533/chimia.2011.849.</span>
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<span class="docsum-journal-citation short-journal-citation">Chimia (Aarau). 2011.</span>
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Auer-Grumbach M., Mauko B., Auer-Grumbach P., Pieber T. R. (2006) Neuromolecular. Med. 8, 147–158
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Dawkins J. L., Hulme D. J., Brahmbhatt S. B., Auer-Grumbach M., Nicholson G. A. (2001) Nat. Genet. 27, 309–312
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Bejaoui K., Wu C., Scheffler M. D., Haan G., Ashby P., Wu L., de Jong P., Brown R. H., Jr. (2001) Nat. Genet. 27, 261–262
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Hanada K., Hara T., Fukasawa M., Yamaji A., Umeda M., Nishijima M. (1998) J. Biol. Chem. 273, 33787–33794
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Models, Biological
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Mutation
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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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Neurites / metabolism
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Neurons / metabolism
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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 major"
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Neurotoxins / metabolism*
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Serine C-Palmitoyltransferase / genetics*
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href="/?term=%22Serine+C-Palmitoyltransferase%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
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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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Substrate Specificity
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</div>
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<div id="substances" class="substances keywords-section">
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<h2 class="title">
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Substances
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</h2>
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<ul class="keywords-list"><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 Fumonisins"
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Fumonisins
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aria-label="Dropdown menu for keyword Fumonisins"><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=%22Fumonisins%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in MeSH
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data-search-term=""Fumonisins"[nm]"
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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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Lipids
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aria-label="Dropdown menu for keyword Lipids"><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=%22Lipids%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Lipids%22%5Bnm%5D&sort=date&sort_order=desc"
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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 Neurotoxins"
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tabindex="0"
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aria-expanded="false"
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Neurotoxins
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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 Neurotoxins"><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=%22Neurotoxins%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Neurotoxins%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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data-search-term=""Neurotoxins"[nm]"
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data-ga-category="search"
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data-ga-label=""Neurotoxins"[nm]"
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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 Sphingolipids"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
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Sphingolipids
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</button><div id="keyword-actions-substances-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 Sphingolipids"><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=%22Sphingolipids%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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data-search-term=""Sphingolipids"[nm]"
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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=""Sphingolipids"[nm]"
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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 fumonisin B1"
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tabindex="0"
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aria-controls="keyword-actions-substances-4"
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aria-expanded="false"
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data-pinger-ignore>
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fumonisin B1
|
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</button><div id="keyword-actions-substances-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 fumonisin B1"><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=%22fumonisin+B1%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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data-search-term=""fumonisin B1"[nm]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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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 SPTLC1 protein, human"
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aria-expanded="false"
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data-pinger-ignore>
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SPTLC1 protein, human
|
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</button><div id="keyword-actions-substances-5"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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data-href="/?term=%22SPTLC1+protein%2C+human%22%5Bnm%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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