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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Delineating The Role Of Mir-124 For The Activation Of Neuronal Program, Ya-Lin Lu
Delineating The Role Of Mir-124 For The Activation Of Neuronal Program, Ya-Lin Lu
Arts & Sciences Electronic Theses and Dissertations
The ectopic expression of two brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), can robustly and efficiently reprogram human skin fibroblasts into neurons. The miRNAs act as repressors of non-neuronal genes in fibroblasts for the induction of the neuronal program. This process is analogous to neurogenesis in vivo when the expression of miR-9/9* and miR-124 represses anti-neurogenic genes such as REST or NRSF (neuron-restrictive silencer factor/repressor element-1 silencing transcription factor). Although we have some mechanistic insights into how miR-9/9*-124 drives fate conversion by acting as negative regulators of gene expression, little remained understood of the role of miRNAs as positive regulators …
Notch-Mediated Regulation Of Atrial Arrhythmogenesis, Catherine Lipovsky
Notch-Mediated Regulation Of Atrial Arrhythmogenesis, Catherine Lipovsky
Arts & Sciences Electronic Theses and Dissertations
Abnormalities in electrical impulse generation and/or propagation that affect the heartճ normal rhythm are extremely common. Clinically, cardiac arrhythmias are prevalent worldwide, yet the molecular mechanisms underlying their pathology remain largely unknown. Current treatments for arrhythmias primarily target symptoms rather than the underlying cause and these treatments have limited efficacy. The most common risk factor for developing an arrhythmia is a previous cardiac injury; however, the mechanisms underlying this are not well described. My thesis work has demonstrated that the Notch signaling pathway, which is crucial for cardiac patterning and development and is normally quiescent in adult cardiomyocytes (CMs), is …
Post-Lysosomal Cholesterol Trafficking: Novel Tools And Insights, Mckenna Rae Feltes
Post-Lysosomal Cholesterol Trafficking: Novel Tools And Insights, Mckenna Rae Feltes
Arts & Sciences Electronic Theses and Dissertations
Cholesterol is an essential mammalian lipid. It is a major component of cellular membranes, a precursor molecule for the synthesis of hormones and bile acids, and a regulator of protein function. Although cholesterol is synthesized, de novo, in the endoplasmic reticulum, cells principally meet cholesterol requirements through uptake of lipoprotein particles. Lipoprotein-derived cholesterol is transported to the lysosome where it is transferred from the soluble lysosomal protein, NPC2, to limiting-lysosomal membrane protein NPC1. Cholesterol is then re-distributed to other cellular membranes in order to fulfill organellar cholesterol requirements; however, the cellular machineries involved in coordinating this distribution are poorly characterized. …