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- Title
- Molecular pathology of FHV-1 infection within feline cornea, conjunctiva, lacrimal gland, nictitans gland, trigeminal-ganglion and ciliary ganglion
- Creator
- Jacobi, Susan
- Date
- 2008
- Collection
- Electronic Theses & Dissertations
- Title
- The role of parkin in the recovery of central dopamine neurons from acute neurotoxicant exposure
- Creator
- Benskey, Matthew John
- Date
- 2013
- Collection
- Electronic Theses & Dissertations
- Description
-
Parkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to...
Show moreParkinson Disease (PD) pathology is associated with the selective degeneration of nigrostriatal dopamine (NSDA) neurons, while the tuberoinfundibular DA (TIDA) neurons of the hypothalamus remain intact. The same pattern of selective degeneration has been observed following exposure to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyradine (MPTP), a mitochondrial complex I inhibitor which recapitulates many of the molecular pathologies associated with PD. The purpose of this dissertation is to identify early molecular events that underlie TIDA neuron recovery from toxicant exposure and adapt these mechanisms in an attempt to rescue NSDA neurons from toxicity. NSDA neurons show loss of axon terminal DA concentrations following acute (20mg/kg; s.c.) and chronic (10 x 20mg/kg; s.c. over 35 days) MPTP administration and exhibit cell death following chronic MPTP administration. In contrast, TIDA neurons show no loss of axon terminal DA concentrations or cell death following acute or chronic MPTP exposure. The recovery of TIDA neurons is independent of extrinsic factors such as decreased toxicant exposure or hormonal activation. TIDA neuron recovery is associated with an increase in the PD-associated proteins, parkin and ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1) within the arcuate nucleus (ARC) 24 h following MPTP. Additionally, parkin protein concentrations remain elevated in the ARC for up to 22 days following chronic MPTP administration. In contrast, the susceptibility of NSDA neurons is associated with decreased expression of both parkin and UCH-L1. The high correlation between the presence of the parkin protein and the recovery of DA neurons from MPTP toxicity is consistent with a role of parkin in DA neuron survival. In order to determine if parkin is necessary and sufficient in the recovery of TIDA neurons following MPTP, recombinant adeno-associated viral (rAAV) vectors containing parkin shRNA or a scrambled shRNA were created. Mice received stereotaxic ARC injections of rAAV containing either parkin shRNA or scrambled shRNA (250nl/side; 3.5x1013vg/ml), or remained naïve to surgery, and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four h post-MPTP, TIDA neurons were able to recover axon terminal DA concentrations following MPTP in control and scrambled shRNA treated animals. However, axon terminal DA was significantly reduced 24 hr following MPTP exposure following knockdown of parkin in TIDA neurons. To determine if parkin overexpression would protect NSDA neurons from MPTP toxicity, mice received unilateral stereotaxic injection of rAAV containing parkin into the substantia nigra (SN) (500nl; 3.4x1013vg/ml) and were administered a single injection of MPTP (20mg/kg; s.c.) 30 days following rAAV surgery. Twenty-four hours post-MPTP, parkin overexpression was unable to rescue MPTP-induced loss of DA in the striatum (ST), but did rescue MPTP-induced loss of tyrosine hydroxylase (TH) in the SN and ST. These findings are consistent with the following conclusions: 1) TIDA neuronal recovery from acute MPTP exposure is independent of extrinsic factors and is mediated by an intrinsic ability to increase expression of neuroprotective proteins, 2) The ability of TIDA neurons to up-regulate parkin is at least partially responsible for recovery of axon terminal DA following MPTP, 3) toxicant-induced loss of parkin contributes to MPTP toxicity within NSDA neurons.
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- Title
- Signal transduction pathways involved in the upregulation of cyclooxygenase-2 by 2,2',4,4'-tetrachlorobiphenyl
- Creator
- Bezdecny, Steven Arthur
- Date
- 2006
- Collection
- Electronic Theses & Dissertations
- Title
- Molecular identification of pathogens in ancient skeletal remains from Butrint and Diaporit Albania
- Creator
- Mutolo, Michael Joseph
- Date
- 2006
- Collection
- Electronic Theses & Dissertations
- Title
- Immunomagnetic separation and rapid electrochemical detection strategies for microbial pathogens
- Creator
- Setterington, Emma B.
- Date
- 2010
- Collection
- Electronic Theses & Dissertations
- Description
-
Biodefense, food safety, and water quality require the means to efficiently screen large volumes of samples for low concentrations of microbial pathogens. Rapid, sensitive, and field-ready detection methods are essential, but must also include a means to specifically extract and concentrate the target pathogen from a complex matrix. This thesis outlines three proof-of-concept approaches for rapid electrochemical detection of microbial pathogens, each beginning with immunomagnetic separation ...
Show moreBiodefense, food safety, and water quality require the means to efficiently screen large volumes of samples for low concentrations of microbial pathogens. Rapid, sensitive, and field-ready detection methods are essential, but must also include a means to specifically extract and concentrate the target pathogen from a complex matrix. This thesis outlines three proof-of-concept approaches for rapid electrochemical detection of microbial pathogens, each beginning with immunomagnetic separation (IMS) of the target organism. Additionally, the development of an improved IMS methodology and its use in an electrochemical detection method are described.In the first approach, target cells were detected directly by means of their ability to impede electrical current.Bacillus cereus (as a surrogate forB. anthracis ) andE. coli O157:H7 were detected from pure culture with limits of 40 CFU/ml and 6 CFU/ml, respectively, in 65 min. In the second approach, Bovine Viral Diarrhea Virus (BVDV) from bovine serum samples was detected by means of an electroactive label, in 80 min. In the third approach,E. coli O157:H7 cells were electroactively labeled, magnetically positioned, and detected from pure culture with a limit of 70 CFU/ml (corresponding to 7 CFU present on the sensor) in 70 min.Finally, an improved IMS methodology was developed forE. coli O157:H7 using two magnetic nanoparticle (MNP) types, and its specificity was initially evaluated againstE. coli O55:H7 andShigella boydii . The method, optimized in terms of antibody concentration, MNP concentration, and conjugation conditions, required only 35 min and yielded antibody-conjugated MNPs that were stable for up to 60 days.
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