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
While it is known that a large fraction of vertebrate genes are under the control of a gene regulatory network (GRN) forming a clock with circadian periodicity, shorter period oscillatory genes like the Hairy-enhancer-of split (Hes) genes are discussed mostly in connection with the embryonic process of somitogenesis. They form the core of the somitogenesis-clock, which orchestrates the periodic separation of somites from the presomitic mesoderm (PSM). The formation of sharp boundaries between the blocks of many cells works only when the oscillators in the cells forming the boundary are synchronized. It has been shown experimentally that Delta-Notch (D/N) signaling is responsible for this synchronization. This process has to happen rather fast as a cell experiences at most five oscillations from its 'birth' to its incorporation into a somite. Computer simulations describing synchronized oscillators with classical modes of D/N-interaction have difficulties to achieve synchronization in an appropriate time. One approach to solving this problem of modeling fast synchronization in the PSM was the consideration of cell movements. Here we show that fast synchronization of Hes-type oscillators can be achieved without cell movements by including D/N cis-inhibition, wherein the mutual interaction of DELTA and NOTCH in the same cell leads to a titration of ligand against receptor so that only one sort of molecule prevails. Consequently, the symmetry between sender and receiver is partially broken and one cell becomes preferentially sender or receiver at a given moment, which leads to faster entrainment of oscillators. Although not yet confirmed by experiment, the proposed mechanism of enhanced synchronization of mesenchymal cells in the PSM would be a new distinct developmental mechanism employing D/N cis-inhibition. Consequently, the way in which Delta-Notch signaling was modeled so far should be carefully reconsidered.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196275 | PMC |
http://dx.doi.org/10.1371/journal.pcbi.1003843 | DOI Listing |
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