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Full-Text Articles in Medicine and Health Sciences
Investigation Of A Novel Mitophagy Regulatory Pathway And Chemical Inducer, Jane E. Craig
Investigation Of A Novel Mitophagy Regulatory Pathway And Chemical Inducer, Jane E. Craig
Theses and Dissertations (ETD)
Mitochondria are vital organelles that coordinate cellular energy homeostasis and also have important roles in cell death. Therefore, the removal of damaged or excessive mitochondria through autophagy, a process called mitophagy, is critical for maintaining proper cellular function. Much of the research elucidating the mechanism and regulation of autophagy was performed in yeast cells, so there is still a lot of mystery surrounding how mitophagy is promoted and regulated in mammals in general and in different tissues. The most well understood mechanism involved in mitophagy is the PINK1-PARKN pathway. However, studies often rely on severe mitochondrial damage using CCCP that …
Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest
Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest
Theses and Dissertations (ETD)
While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. …
Selective Targeting Of Cyp3a5 Through Chemical And Genetic Approaches, William C. Wright
Selective Targeting Of Cyp3a5 Through Chemical And Genetic Approaches, William C. Wright
Theses and Dissertations (ETD)
Cytochrome P450 enzymes function to catalyze a wide range of reactions important for various biological processes. In humans, the CYP3A subfamily is particularly critical for drug response. Within this family are CYP3A4 and CYP3A5, which collectively metabolize greater than half of all currently prescribed drugs. These promiscuous enzymes can bind a broad and structurally diverse array of compounds, in turn leading to an increased risk of their modulation via small molecules. In the case of CYP3A5, which is over-expressed in some cancers, this leads to chemoresistance. Such aberrant expression and corresponding drug resistance merit a need to selectively target CYP3A5. …