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    <title>Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages - PubMed</title>

  
  
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      </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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">
      
      <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: 12421970 - PubMed</span>
        <input type="hidden" name="email-subject" value="1 selected item: 12421970"/>
        <input type="hidden" name="email-subject-hash" value="77b18c2fb5cbff591d16efd25fb3a4f12ac376b1b2e65b701eef1aec7e5a79df"/>
      </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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">

  

  <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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
        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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">

      

      <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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">

      <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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
      </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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">

      

      <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="MVBresKotPoz1UaF9KjrZWQh3vqqhJMy3IlwRidK3qb3VlgvM3Wtt4mVBz8CakkS">

      <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="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
      </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="12421970">
    <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://journals.aai.org/jimmunol/article-lookup/doi/10.4049/jimmunol.169.10.5874"
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         ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=7898&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=12421970&amp;db=pubmed&amp;nlmid=2985117R"
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    <div class="short-view">
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        Full text links
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      Previous studies have shown that engagement of Toll-like receptors (TLR) 2 and 4 can induce macrophages to express a variety of proinflammatory cytokines. We have recently demonstrated that TLR2 agonists poorly induce a subset of TLR4-inducible proinflammatory genes (e.g., inducible protein (IP)-10, inducible NO synthase (iNOS), monocyte chemoattractant protein-5, IL-12p40), due in part to differential activation of IFN-beta production and phosphorylation of the transcription factor STAT1. TLR4, but not TLR2, agonists can induce IFN-beta expression via a mechanism that requires the adapter protein Toll-IL-1R domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 (MyD88) adapter-like (Mal), but not the adapter protein MyD88. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes results, in part, from their failure to induce the expression of IFN-beta. In this study, we show that IL-6 expression is also preferentially induced by activation of TLR4. TLR4-dependent induction of IL-6 expression did require Toll-IL-1R domain-containing adapter protein (TIRAP)/MyD88 adapter-like (Mal), but unlike iNOS and IP-10, it did not require the expression of IFN-beta. Although exogenous IFN-beta and IFN-gamma could synergize with TLR2 agonists to restore high levels of iNOS expression and NO production, these IFNs could not synergize with TLR2 agonists to induce high levels of IL-6. Similarly, neutralizing anti-IFN Abs could block iNOS gene expression in LPS-stimulated murine macrophages, whereas these Abs had little effect on IL-6 gene expression in these cells. Together, these studies demonstrate that IL-6, like iNOS and IP-10, is differentially expressed in macrophages stimulated via TLR2 vs TLR4, although these differences appear to arise from distinct signaling mechanisms.
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        MeSH terms
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        Substances
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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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               data-search-term="&quot;Bacterial Proteins&quot;[nm]"
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      Carrier Proteins
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