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Full-Text Articles in Animal Experimentation and Research

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien Dec 2023

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien

Dissertations & Theses (Open Access)

Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …


Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw May 2023

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia Aug 2022

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …