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Filename: drivers/Session_files_driver.php
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Function: require_once
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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Function: str_replace
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Loss-of-function mutations in the nonconventional myosin Vb (Myo5b) result in microvillus inclusion disease (MVID) and massive secretory diarrhea that often begins at birth. Myo5b mutations disrupt the apical recycling endosome (ARE) and membrane traffic, resulting in reduced surface expression of apical membrane proteins. ARE disruption also results in constitutive phosphoinositide-dependent kinase 1 gain of function. In MVID, decreased surface expression of apical anion channels involved in Cl extrusion, such as cystic fibrosis transmembrane conductance regulator (CFTR), should reduce fluid secretion into the intestinal lumen. But the opposite phenotype is observed. To explain this contradiction and the onset of diarrhea, we hypothesized that signaling effects downstream from Myo5b loss of function synergize with higher levels of glucocorticoids to activate PKA and CFTR. Data from intestinal cell lines, human MVID, and Myo5b KO mouse intestine revealed changes in the subcellular redistribution of PKA activity to the apical pole, increased CFTR phosphorylation, and establishment of apical cAMP gradients in Myo5b-defective cells exposed to physiological levels of glucocorticoids. These cells also displayed net secretory fluid fluxes and transepithelial currents mainly from PKA-dependent Cl secretion. We conclude that Myo5b defects result in PKA stimulation that activates residual channels on the surface when intestinal epithelia are exposed to glucocorticoids at birth.
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http://dx.doi.org/10.1091/mbc.E18-07-0415 | DOI Listing |
J Int Med Res
December 2024
Department of Pediatrics, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabi.
Objective: Duchenne muscular dystrophy (DMD) is a rare X-linked neurodegenerative disorder caused by mutations in the gene. This study examined the efficacy and safety of ataluren, the first oral treatment for DMD with nonsense mutations (nmDMD), in patients in the Middle East.
Methods: This retrospective longitudinal study assessed the outcomes of seven boys with nmDMD who received treatment with ataluren and follow-up at a single center since 2016.
Plant Physiol
December 2024
Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan.
The directional and sequential flow of cytokinin in plants is organized by a complex network of transporters. Genes involved in several aspects of cytokinin transport have been characterized; however, much of the elaborate system remains elusive. In this study, we used a transient expression system in tobacco (Nicotiana benthamiana) leaves to screen Arabidopsis (Arabidopsis thaliana) transporter genes and isolated ATP-BINDING CASSETTE TRANSPORTER C4 (ABCC4).
View Article and Find Full Text PDFJCI Insight
December 2024
Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, NIH, Bethesda, United States of America.
African American (AA) women are disproportionally affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) contributing to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair Natural Killer cells (NKs). As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK dysfunction related to obesity and hyperlipidemia in AA women from under-resourced neighborhoods.
View Article and Find Full Text PDFChaos
December 2024
Department of Physics and Astronomy, Northwestern University, Evanston, Illinois 60208, USA.
In the classical control of network systems, the control actions on a node are determined as a function of the states of all nodes in the network. Motivated by applications where the global state cannot be reconstructed in real time due to limitations in the collection, communication, and processing of data, here we introduce a control approach in which the control actions can be computed as a function of the states of the nodes within a limited state information neighborhood. The trade-off between the control performance and the size of this neighborhood is primarily determined by the condition number of the controllability Gramian.
View Article and Find Full Text PDFMol Biol Cell
December 2024
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.
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