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: 3098
Function: getPubMedXML
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
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
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
C-type natriuretic peptide (CNP) activation of guanylyl cyclase (GC)-B, also known as NPR2, stimulates cGMP synthesis and bone elongation. CNP activation requires the phosphorylation of multiple GC-B residues and dephosphorylation inactivates the receptor. GC-B knockin mice, expressing a glutamate-substituted, "pseudophosphorylated," form of GC-B, exhibit increased CNP-dependent GC activity. Since mutations that constitutively activate GC-B in the absence of CNP result in low bone mineral density in humans, we determined the skeletal phenotype of 9-week old male GC-B mice. Unexpectedly, GC-B mice have significantly greater tibial and L5 vertebral trabecular bone volume fraction, tibial trabecular number, and tibial bone mineral density. Cortical cross-sectional area, cortical thickness, periosteal diameter and cortical cross-sectional moment of inertia were also significantly increased in GC-B tibiae. Three-point bending measurements demonstrated that the mutant tibias and femurs had greater ultimate load, stiffness, energy to ultimate load, and energy to failure. No differences in microhardness indicated similar bone quality at the tissue level between the mutant and wildtype bones. Procollagen 1 N-terminal propeptide and osteocalcin were elevated in serum, and osteoblast number per bone perimeter and osteoid width per bone perimeter were elevated in tibias from the mutant mice. In contrast to mutations that constitutively activate GC-B, we report that mutations that enhance GC-B activity only in the presence of its natural ligand, increase bone mass, bone strength, and the number of active osteoblasts at the bone surface.
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Source |
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http://dx.doi.org/10.1016/j.bone.2020.115320 | DOI Listing |
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