Biochemistry Commons^™

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings …

Axonal Transport And Life Cycle Of Mitochondria In Parkinson's Disease Model, Hyun Sung

Open Access Dissertations

In neurons, normal distribution and selective removal of mitochondria are essential for preserving compartmentalized cellular function. Parkin, an E3 ubiquitin ligase associated with familial Parkinson’s disease, has been implicated in mitochondrial dynamics and removal. However, it is not clear how Parkin plays a role in mitochondrial turnover in vivo, and whether the mature neurons possess a compartmentalized Parkin-dependent mitochondrial life cycle. Using the live Drosophila nervous system, here, I investigate the involvement of Parkin in mitochondrial dynamics; organelle distribution, morphology and removal. Parkin deficient animals displayed less number of axonal mitochondria without disturbing organelle motility behaviors, morphology and metabolic state. …

Characterization Of Cu-Rich Aggregates In Neurogenic Niches Of The Rodent Brain By X-Ray Fluorescence Microscopy, Brendan T. Sullivan

Open Access Dissertations

Copper is an essential element in the brain playing several critical roles ranging from neurotransmitter synthesis to ATP production. As Cu is typically present in micromolar concentrations and has a spatially capricious distribution in the brain, determining concentrations has historically been challenging. X-ray fluorescence microscopy (XRF) offers excellent spatial resolution (down to 30~nm) and detection limits (sub parts per million), making it an excellent tool for analyzing metal distributions in the brain. Using XRF, it is demonstrated that Cu-rich aggregates with concentrations in the hundreds of millimolar are present in the subventricular zone of rats and mice. As the subventricular …

Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu

Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in …

Examining The Role Of Atrx In Astrocytes, Haley Mcconkey

Electronic Thesis and Dissertation Repository

Astrocytes perform many homeostatic roles in the brain while supplying metabolites to neurons and mediating synaptic transmission. The current study explored a possible role of the Atrx gene in astrocytes. Hypomorphic mutations in this gene cause the ATR-X intellectual disability syndrome. Deletion of Atrx in the forebrain leads to an apparent increase in reactive astrocytes, potentially caused by the high level of neuroprogenitor cell death. To avoid such non cell-autonomous effects on astrocytes, we generated mice with inducible conditional inactivation of Atrx in astrocytes. Preliminary analysis two weeks following induction of Atrx gene deletion revealed variably lower expression of Connexin …

Enzyme Analysis Of Oxidatively Modified Proteins Post-Tbi, Brittany Rice

Online Theses and Dissertations

The brain is one of the most important organs in the body. It functions as a control center by regulating and coordinating actions and reactions, which is facilitated via signal transduction pathways. Its function is primarily dependent upon sufficient supply of glucose for energy metabolism. The dysfunction of the brain resulting from an external force is known as traumatic brain injury (TBI). Symptoms range from physical to psychological and effects can be mild, moderate, or severe depending on the extent of injury. TBI is associated with oxidative damage, the overproduction of reactive oxygen/nitrogen species. Reduced energy metabolism is a consequence …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …