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The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson Dec 2020

The Effects Of Maternal Delta-9-Tetrahydrocannabinol And Cannabidiol Exposure On Fetal Heart Development In Mice, Gregory Robinson

Electronic Thesis and Dissertation Repository

Up to 22.6% of pregnant women consume cannabis during pregnancy despite the uncertainty of teratogenicity of the main ingredients in cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). This study tested the hypothesis that gestational THC and CBD exposure leads to heart abnormalities. Daily, oral THC exposure induced heart abnormalities in 68% of offspring with three main phenotypes including thickened semilunar valves, ventricular myocardial hypertrophy and hypoplastic coronary arteries in fetuses, and postnatal cardiac dysfunction. Altered gene expression of key cardiogenic regulators, increased proliferation, and reduced epicardial epithelial-to-mesenchymal-transition were demonstrated implicating potential mechanisms responsible for these abnormalities. Also, maternal CBD exposure resulted …


Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz Nov 2020

Deciphering The Ck2-Dependent Phosphoproteome And Its Integration With Regulatory Ptm Networks, Teresa Nunez De Villavicencio Diaz

Electronic Thesis and Dissertation Repository

Protein functions are regulated by the post-translational addition of covalent modifications on certain amino acids. Depending on their distance within the 3-dimensional structure, addition/removal of individual post translational modifications (PTMs) can be impacted by others. This PTM interplay constitutes an essential regulatory mechanism that interconnects the molecular networks in the cell. Protein CK2, a clinically relevant acidophilic Ser/Thr kinase, may be responsible for 10-20% of the human phosphoproteome. Such estimates agree with the number of known substrates, which continues to expand. Furthermore, the demonstration that CK2 participates in hierarchical phosphorylation and has similar sequence determinants to caspases suggest extensive PTM …


Development Of Water-Soluble Polyesters For Tissue Engineering Applications, Trent Gordon Nov 2020

Development Of Water-Soluble Polyesters For Tissue Engineering Applications, Trent Gordon

Electronic Thesis and Dissertation Repository

The development of tunable polymers has become increasingly important for both tissue engineering and drug delivery. This thesis investigates the development of water-soluble polyesters that contain both natural and synthetic components. These polymers offer tunable chemical structures, as well as functional groups for the conjugation of crosslinking moieties or cell signaling molecules. The first series of polymers was synthesized from poly(ethylene glycol) (PEG) and aspartic acid (Asp) via a titanium catalyzed transesterification method to provide polymers with molar masses of 12 kg/mol. After deprotection, the pendent functional groups of Asp were reacted with methacrylic, maleic, and itaconic anhydride to introduce …


Analysis Of Oxidatively Damaged Proteins By Mass Spectrometry, Vincent Saullo Feb 2020

Analysis Of Oxidatively Damaged Proteins By Mass Spectrometry, Vincent Saullo

Electronic Thesis and Dissertation Repository

As humans age, exposure to oxidative stress may induce protein degradation or aggregation; both resulting in loss of protein function. Protein oxidative damage remains a dominant pathology in many common ailments. To combat these pathologies, scientists must understand the nature of oxidative modifications and their effects on protein structure and dynamics. This work employs a range of mass spectrometry (MS) methods to characterize and analyze the effects of oxidative damage on the model protein myoglobin (Mb). Mb was oxidized using tert-butyl hydroperoxide, and the resulting modifications were characterized by top-down and bottom-up MS workflows. Hydrogen/deuterium exchange MS indicated elevated structural …