Medicine and Health Sciences Commons^™

Classification And Effect Of Correctors On Sitosterolemia-Associated Mutants In Abcg8, Brittney Poole

Theses and Dissertations--Medical Sciences

Objective: To classify mutants of ABCG8 identified in subjects with clinically confirmed Sitosterolemia, a rare form of Familial Hypercholesterolemia distinguished by the accumulation of phytosterols in plasma and tissues and determine the effects of correctors and/or regulators of proteostasis on maturation of the ABCG5/ABCG8 sterol transporter.

Methods: Disease-causing missense mutants within the cytosolic domain of ABCG8 were generated through site-directed mutagenesis. Normal and mutant proteins were expressed in human hepatocytes. Cellular proteins were prepared, and maturation was assessed by SDS-PAGE and immunoblotting. Formation of the higher molecular weight, mature form of glycoproteins was used as a bioassay for trafficking the …

Establishment And Verification Of A Sars Cov2 Antibody Detection Assay Comparing Venous And Mitra Samples, Stephen C. Mayer

Theses and Dissertations--Medical Sciences

During the COVID-19 pandemic in 2020, the need for highly-specific, wide-spread, and rapid serological testing surged. In this study, we showed very strong positive correlation between venous blood collection and Mitra home sampling kits for the detection of anti- spike IgGs using an in-house ELISA protocol (based on a protocol from Mt. Sinai). This study demonstrates the utility of using at-home, patient-centric testing to enhance the sero-surveillance methods currently in place for viral tracking and monitoring.

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Mammalian Target Of Rapamycin Cell Signaling Pathway In Phosphatase And Tensin Homolog Induced Kinase 1 Knockout Rat Model Of Familial Parkinson's Disease, Martha Helena Mortell

Theses and Dissertations--Medical Sciences

More than 10 million people are living with Parkinson’s disease (PD), one million of which are people in the United States. PD is the second most common age-related neurodegenerative disorder, after Alzheimer’s disease, and is characterized by the accumulation of a-synuclein aggregates and the degeneration of dopaminergic neurons. The loss of endogenous dopamine in PD brain accounts for the motor decline presented clinically in PD patients. Etiological factors of PD include oxidative damage and inflammation, although the detailed mechanisms remain unknown. Risk factors for PD include gender, age, environmental factors, and gene mutations.

The current thesis research employed phosphatase and …

Apoe Genotype And Sex Modulate Ketogenic Diet Enhancements To Metabolism And Gut Microbiome In Young Mice, Andrew T. Yackzan

Theses and Dissertations--Medical Sciences

The apolipoprotein ε (APOE) allele in humans has been associated with risk for development of Alzheimer’s disease (AD). There are predominately three variations of the allele – ε2 (E2), ε3 (E3), and ε4 (E4) – with E4 contributing the greatest risk of AD development. Recent research has unveiled evidence of neurometabolic and neurovascular deficits in E4 carriers present decades before the onset of dementia; it is believed these chronic defects play a major role in the development of AD, thus making them a potential target for preventative intervention. The purpose of this study was to examine the effect of a …

Trem2: Gene Expression And Role In Alzheimer’S Disease, Henry Snider

Theses and Dissertations--Medical Sciences

Genetic mutations in the TREM2 gene are highly correlated with risk of Alzheimer’s disease, but alternative splicing patterns of TREM2 transcripts have not been fully described. Characterization of TREM2 alternative splicing will be of significant use to the scientific community as the field of Alzheimer’s disease research progresses. The goal of this study was to fully describe splicing patterns in TREM2, as different splicing isoforms of genes can alter express and/or function of the final protein. Human blood and anterior cingulate cortex brain tissue from 61 individual donors was processed and used for PCR and quantitative PCR as well as …