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The Methuselah Family Of G Protein Coupled Receptors, Meghna V. Patel

Wayne State University Dissertations

G protein-coupled receptors (GPCRs) are one of the largest class of transmembrane signaling proteins that regulate essential developmental and physiological processes in a cell. GPCR success is illustrated by their abundance across both invertebrate and vertebrate genomes. Phylogenetic analyses show that GPCR families have undergone a lot of gene gain and loss during insect evolution. In Drosophila melanogaster, the fifteen Methuselah/Methuselah-like (Mth/Mthl) genes are in fact an insect specific family of GPCRs. In our study, we conducted a phylogenetic analysis using receptor sequences from five Drosophila species and two related insects, including Tribolium and Anopheles to examine the evolution of …

Cationic Amphiphilic Drug-Induced Autophagosome Accumulation Is Due To Autophagosome Sequestration Within Vimentin Intermediate Filament Networks Resulting In Prolonged Autophagosome Half-Life, Miriam Devorah Kleinman

Wayne State University Dissertations

Accumulations of autophagosomes and non-esterified cholesterol are

observed in several cell lines derived from lysosomal storage diseases,

including Niemann Pick Type C (NPC). The relationship between

autophagosome accumulation and lysosomal non-esterified cholesterol is

unclear. Exposure of murine hepatoma 1c1c7 cultures to the cationic

amphiphilic drugs (CADs) U18666A, imipramine and clozapine caused

lysosomal non-esterified cholesterol and autophagosome accumulation.

Measurement of LC3-II conversion in the presence of lysosomal inhibitors

bafilomycin A1 and NH4Cl, degradation of long-lived proteins, and

colocalization of GFP-LC3 and LAMP1 indicated an increase in

autophagosome synthesis without compensatory increase in clearance.

Autophagosome synthesis was blocked using 3-MA to monitor …

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

Dioecious Plants: Evolution And Sex Ratio And Asepen Decline, Jordan P. Sinclair

Wayne State University Dissertations

Although dioecious species are rare in nature, the sexual system appears in a diverse number of families and across all life forms and global locations. We looked at the population dynamics of natural populations to determine why many dioecious populations display biased sex ratios. We also looked at the role incestuous matings, seed and pollen dispersal patterns, and compensation play in the evolution of this sexual system using two theoretical models we developed. Finally, we studied aspen populations in the Midwest to determine how climate variables affect growth and decline. We found many dioecious species display male biased ratios and …

Prevalence And Physiological Significance Of Gene Looping In Saccharomyces Cerevisiae, Banupriya Mukundan

Wayne State University Dissertations

My Ph.D. dissertation work is focused on studying the role of promoter-bound transcription initiation factors involved in gene looping. In this study we showed that the RNAP II subunit Rpb4 has a significant effect on termination of transcription. Gene looping is disrupted in the absence of Rpb4. Rpb4 shows a strong physical interaction with the Mediator subunit Srb5. Mediator subunit Srb5 crosslinked to the 5' and 3' ends of INO1 and CHA1 genes and is required for proper termination of transcription of these genes. Srb5 affected termination of transcription through its interaction with the CF1 complex. Srb5 interaction with the …

Determinants Of Cns Adult Neurogenesis Are Sex, Hormones, Mouse Strain, Age, And Brain Region, Carrie Lynn Tatar

Wayne State University Dissertations

Multiple sclerosis is a sexually dimorphic (SD) disease that causes oligodendrocyte death but SD of glial cells is poorly studied. Here, we analyze SD of neural progenitors in 6-8wk and 6-8mo normal C57BL/6, SJL/J and BALB/c mice in the subventricular zone (SVZ), dorsolateral horn (DLC), corpus callosum (CC), and parenchyma. With a short 2 h BrdU pulse, no gender and strain differences are present at 6-8wk. At 6-8mo, the number of BrdU+ cells decreases 2-fold in both sexes, strains and regions indicating a common aging mechanism regulates BrdU incorporation. Strikingly, 2X more BrdU+ cells are found in all brain regions …

Biophysical And Biochemical Factors In The Cellular Microenvironment; Effects On Cell Migration And Invasion, Shalini Menon

Wayne State University Dissertations

Cellular migration is a vital process central to many physiological events including development, immune surveillance and wound healing. However, migration and invasion are not unique to normal physiology, they are also key determinants in the progression of disease states such as cancer. Given the significance of migration it is important that we understand how the process is regulated intracellularly and the various stimuli that can promote it. Even though the role of biochemical factors in mediating migration has been studied extensively, the role of biophysical factors in modulating migration and invasion is less appreciation. The biochemical and biophysical components of …