Severity: Warning
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Filename: drivers/Session_files_driver.php
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File: /var/www/html/index.php
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Function: require_once
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Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)
Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
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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
Line: 249
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
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Filename: models/Detail_model.php
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File: /var/www/html/application/models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Function: require_once
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
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Function: formatAIDetailSummary
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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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Filename: controllers/Detail.php
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Line: 256
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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File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Line: 259
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Line: 260
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File: /var/www/html/index.php
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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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File: /var/www/html/application/controllers/Detail.php
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The venom peptide maurocalcin (MCa) is atypical among toxins because of its ability to rapidly translocate into cells and potently activate the intracellular calcium channel type 1 ryanodine receptor (RyR1). Therefore, MCa is potentially subjected to posttranslational modifications within recipient cells. Here, we report that MCa Thr(26) belongs to a consensus PKA phosphorylation site and can be phosphorylated by PKA both in vitro and after cell penetration in cellulo. Unexpectedly, phosphorylation converts MCa from positive to negative RyR1 allosteric modulator. Thr(26) phosphorylation leads to charge neutralization of Arg(24), a residue crucial for MCa agonist activity. The functional effect of Thr(26) phosphorylation is partially mimicked by aspartyl mutation. This represents the first case, to our knowledge, of both ex situ posttranslational modification and pharmacological reprogramming of a small natural cystine-rich peptide by target cells. So far, phosphorylated MCa is the first specific negative allosteric modulator of RyR1, to our knowledge, and represents a lead compound for further development of phosphatase-resistant analogs.
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http://dx.doi.org/10.1073/pnas.1517342113 | DOI Listing |
J Nanobiotechnology
December 2024
Cancer Stem Cells and Fibroinflammatory Microenvironment Group, Instituto de Investigaciones Biomédicas (IIBm) Sols-Morreale CSIC-UAM, 28029, Madrid, Spain.
Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis.
View Article and Find Full Text PDFRedox Biol
December 2024
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China; Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, 430030, PR China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:
Background: Oxidative stress and microglial activation are critical pathomechanisms in ischemic white matter injury. Microglia, as resident immune cells in the brain, are the main cells undergoing oxidative stress response. However, the role and molecular mechanism of oxidative stress in microglia have not been clearly elucidated during white matter ischemia.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Rheumatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
Gouty arthritis is characterized by an acute inflammatory response triggered by monosodium urate (MSU) crystals deposited in the joints and periarticular tissues. Current treatments bring little effects owing to serious side effects, necessitating the exploration of new and safer therapeutic options. Macrophages play a critical role in the initiation, progression, and resolution of acute gout, with the cellular profiles closely linked to their activation and polarization.
View Article and Find Full Text PDFJ Neurosci Res
December 2024
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, School of Medical Science, Centre for Brain Research, University of Auckland, Auckland, New Zealand.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder traditionally characterized by the selective loss of medium spiny neurons in the basal ganglia. However, it has become apparent that white matter injury and oligodendrocyte dysfunction precede the degeneration of medium spiny neurons, garnering interest as a key pathogenic mechanism of HD. Oligodendrocytes are glial cells found within the central nervous system involved in the production of myelin and the myelination of axons.
View Article and Find Full Text PDFCancer Gene Ther
December 2024
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Angiosarcomas are a group of vascular cancers that form malignant blood vessels. These malignancies are seemingly inflamed primarily due to their pathognomonic nature, which consists of irregular endothelium and tortuous blood channels. PIK3CA mutations are oncogenic and disrupt the PI3K pathway.
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