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Function: _error_handler
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Filename: controllers/Detail.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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Function: _error_handler
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Filename: controllers/Detail.php
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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: formatAIDetailSummary
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Filename: controllers/Detail.php
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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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Ras-related protein 1 (Rap1) is a major convergence point of the platelet-signaling pathways that result in talin-1 binding to the integrin β cytoplasmic domain and consequent integrin activation, platelet aggregation, and effective hemostasis. The nature of the connection between Rap1 and talin-1 in integrin activation is an important remaining gap in our understanding of this process. Previous work identified a low-affinity Rap1-binding site in the talin-1 F0 domain that makes a small contribution to integrin activation in platelets. We recently identified an additional Rap1-binding site in the talin-1 F1 domain that makes a greater contribution than F0 in model systems. Here we generated mice bearing point mutations, which block Rap1 binding without affecting talin-1 expression, in either the talin-1 F1 domain (R118E) alone, which were viable, or in both the F0 and F1 domains (R35E,R118E), which were embryonic lethal. Loss of the Rap1-talin-1 F1 interaction in platelets markedly decreases talin-1-mediated activation of platelet β1- and β3-integrins. Integrin activation and platelet aggregation in mice whose platelets express only talin-1(R35E, R118E) are even more impaired, resembling the defect seen in platelets lacking both Rap1a and Rap1b. Although Rap1 is important in thrombopoiesis, platelet secretion, and surface exposure of phosphatidylserine, loss of the Rap1-talin-1 interaction in talin-1(R35E, R118E) platelets had little effect on these processes. These findings show that talin-1 is the principal direct effector of Rap1 GTPases that regulates platelet integrin activation in hemostasis.
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http://dx.doi.org/10.1182/blood.2020005348 | DOI Listing |
Exp Ther Med
February 2025
Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China.
The aim of the present study was to explore the role of ovarian cancer G protein-coupled receptor 1 (OGR1) in osteoclast differentiation and activity induced by extracellular acid. The impact of extracellular acidification on osteoclasts was investigated. Briefly, osteoclasts were generated from RAW 264.
View Article and Find Full Text PDFBrain Behav Immun Health
February 2025
Department of Neuroscience, The Ohio State University Wexner Medical Center, USA.
Chronic stress increases the incidence of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Repeated Social Defeat (RSD) in mice recapitulates several key physiological, immune, and behavioral changes evident after chronic stress in humans. For instance, neurons in the prefrontal cortex, amygdala, and hippocampus are involved in the interpretation of and response to fear and threatful stimuli after RSD.
View Article and Find Full Text PDFTherap Adv Gastroenterol
December 2024
Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou 510080, China.
Background: Early biologic intervention after diagnosis has shown improved clinical and endoscopic outcomes in patients with Crohn's disease (CD), while very little is known about the effectiveness of early versus late administration of Ustekinumab (UST).
Objectives: We aimed to compare early versus late UST use in managing CD and identify potential predictors associated with clinical and endoscopic outcomes.
Design: This was a retrospective observational study.
J Transl Med
December 2024
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, 510080, P. R. China.
Background: Renal CD8 tissue-resident memory T (T) cells display prolonged survival and activity in lupus nephritis (LN), exacerbating renal pathology. NLRP3 regulates the T cell response. This study explored the impact of NLRP3 inflammasome activity on the regulatory functions of T cells in LN.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Materials Science and Engineering, Korea University, Seoul, Republic of Korea.
The native extracellular matrix is continuously remodeled to form complex interconnected network structures that reversibly regulate stem cell behaviors. Both regulation and understanding of its intricate dynamicity can help to modulate numerous cell behaviors. However, neither of these has yet been achieved due to the lack of designing and modeling such complex structures with dynamic controllability.
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