Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
Line Number: 71
Backtrace:
File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
Line: 252
Function: insertAPISummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: 8192
Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
Line Number: 8919
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 258
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 259
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 259
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 994
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3134
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Multivalency represents a critical parameter in cell biology responsible for the overall avidity of low-affinity interactions and the triggering of cellular events. Functions such as catalytic activity, cellular uptake, or localization are frequently linked to the oligomeric state of a protein. This study explores the impact of multivalency on the import and routing of peptides into cells. Specifically, cationic import sequences such as decaarginine, decalysine, and the HIV Tat peptide (GRKKRRQRRRAP, residues 48-59) as well as the nuclear localization sequence from SV40 large T-antigen were assembled into defined peptide oligomers by fusing them to the tetramerization domain of human p53 (residues 325-355, hp53(tet) domain). The resulting tetravalent peptides typically displayed between 10- and 100-fold enhancements in cellular import and intracellular routing properties in relation to their monomeric homologues. These peptides were not toxic to cells. Flow cytometry results and transfection assays indicated that tetravalent decaarginyl peptides (10R-p53(tet) and NLS-10R-p53(tet)) were the peptides most efficiently routed into cells. Their mechanism of import was subsequently examined on unfixed, viable cells using a combination of metabolic inhibitors, flow cytometry, and microscopy techniques. These studies revealed that tetravalent arginine-rich peptides bind to heparan sulfate on the cell surface, are internalized at 37 degrees C, but not at 4 degrees C, via a clathrin-mediated pathway, and accumulate into endosome-like acidic compartments. A fraction of these tetravalent peptides access the cytosol and accumulate in the nucleus of cells. This study concludes that the oligomerization of proteins harboring arginine-rich peptide chains may profoundly influence their ability to enter and be routed into cells.
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Source |
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http://dx.doi.org/10.1021/bi051338e | DOI Listing |
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