published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

Heart failure (HF) is a prevalent disease in society which is associated with decreased cardiac output. This thesis describes the proteomic analysis of cardiac tissue obtained from HF patients and a transgenic animal model of HF. Initial experiments optimized one proteomic technology, 2-dimensional gel electrophoresis (2-DE), to maximize the number of proteins which could be observed / resolved from human cardiac tissue. Protein abundance changes in cardiac tissue between normal patients and those with a diagnosis of ischemic cardiomyopathy were determined by performing 2-DE and identifying proteins by mass spectrometry. HF patients had a reduced abundance of proteins involved in energy production and the sarcomere. Sarcomeres contain the myofilament subproteome consisting of thick and thin filaments with the thick filaments primarily myosin. Thick and thin filament undergo Ca2+ induced ATP hydrolysis to form crossbridge cycles, resulting in muscle contraction. An assembly chaperone for myosin, UNC-45B, was found to be increased in HF patients. Western blot analysis confirmed that the abundance of UNC-45B was increased in different etiologies of heart failure. Follow up physiological measurements demonstrated that UNC-45B is most likely a protein necessary for transcriptional control of the α-isoform of myosin heavy chain. In a second proteomics study, abundance changes occurring in a pacing induced model of HF in wild-type (WT) and transgenic (TG) rabbits with increased expression of the α-isoform of myosin heavy chain were examined. WT and TG rabbits had a different response in their myofilament and intermediate filament abundance changes following induction of HF. TG rabbits had a decreased abundance of heat shock proteins and non-sarcomeric associated desmin. As well, TG rabbits had an increased ratio of actin:myosin heavy chain and UNC-45B suggesting an altered ratio of thick to thin filaments. In conclusion, an altered abundance of contractile proteins, regulated in part by UNC-45B, may be one cause of the contractile dysfunction which occurs in HF. / Thesis (Ph.D, Physiology) -- Queen's University, 2007-12-21 09:19:45.172

No description available.

Graduation date: 1993

The experiments described in this thesis examined post-extinction recovery phenomena following classical conditioning in the rabbit. The first series of experiments examined the rate of reacquisition to the original conditioned stimulus (CS) and to a cross-modal CS following various amounts of extinction. In both the rabbit nictitating membrane (NM) preparation and rabbit heart rate (HR) conditioning, there was a graded reduction in the rate of reacquisition as a direct function of the number of extinction trials. In the rabbit NM preparation, there was also a graded reduction in the rate of acquisition to a cross-modal stimulus (CSB, e.g., light). However, concurrent recovery of responding to the original, extinguished stimulus (CSA, e.g., tone) during training with a novel, cross-modal stimulus (CSB, e.g., light), appeared uniformly robust even following extensive extinction. The second series of experiments examined the conditions necessary for concurrent recovery to occur in the rabbit NM preparation. The introduction of CSB-US pairings resulted in strong recovery of responding to CSA, while the reintroduction of the US alone failed to result in any discernable reinstatement of responding to CSA. Concurrent recovery was specific to the trained and extinguished CSA, with virtually no generalized responding to a novel cross-modal test stimulus (CSC). However, pretraining with CSB-US pairings significantly reduced the amount of recovery to CSA during subsequent CSB???US pairings. The third series of experiments revealed that concurrent recovery was specific to the extinguished stimulus (CSA) with only moderate generalization to other familiar but untrained stimuli in the same modality as CSA. Together these results indicate that concurrent recovery is not primarily the result of the unmasking of the original CSA-US association. Rather, concurrent recovery appears to be at least partially the result of learning-dependent generalization. However, in order for responding to CSB, to generalize to CSA, CSA must have been paired with the same US which is subsequently paired with CSB. Thus, the CSA-US association must be partially intact for concurrent recovery to occur. A layered network model with multiple hidden units is able to simulate rapid reacquisition, facilitated cross-modal acquisition and concurrent recovery.

ix, 131 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1974)--University of Adelaide, Dept. of Zoology, 1974

ix, 131 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1974)--University of Adelaide, Dept. of Zoology, 1974

The experiments described in this thesis examined post-extinction recovery phenomena following classical conditioning in the rabbit. The first series of experiments examined the rate of reacquisition to the original conditioned stimulus (CS) and to a cross-modal CS following various amounts of extinction. In both the rabbit nictitating membrane (NM) preparation and rabbit heart rate (HR) conditioning, there was a graded reduction in the rate of reacquisition as a direct function of the number of extinction trials. In the rabbit NM preparation, there was also a graded reduction in the rate of acquisition to a cross-modal stimulus (CSB, e.g., light). However, concurrent recovery of responding to the original, extinguished stimulus (CSA, e.g., tone) during training with a novel, cross-modal stimulus (CSB, e.g., light), appeared uniformly robust even following extensive extinction. The second series of experiments examined the conditions necessary for concurrent recovery to occur in the rabbit NM preparation. The introduction of CSB-US pairings resulted in strong recovery of responding to CSA, while the reintroduction of the US alone failed to result in any discernable reinstatement of responding to CSA. Concurrent recovery was specific to the trained and extinguished CSA, with virtually no generalized responding to a novel cross-modal test stimulus (CSC). However, pretraining with CSB-US pairings significantly reduced the amount of recovery to CSA during subsequent CSB???US pairings. The third series of experiments revealed that concurrent recovery was specific to the extinguished stimulus (CSA) with only moderate generalization to other familiar but untrained stimuli in the same modality as CSA. Together these results indicate that concurrent recovery is not primarily the result of the unmasking of the original CSA-US association. Rather, concurrent recovery appears to be at least partially the result of learning-dependent generalization. However, in order for responding to CSB, to generalize to CSA, CSA must have been paired with the same US which is subsequently paired with CSB. Thus, the CSA-US association must be partially intact for concurrent recovery to occur. A layered network model with multiple hidden units is able to simulate rapid reacquisition, facilitated cross-modal acquisition and concurrent recovery.

The experiments described in this thesis examined post-extinction recovery phenomena following classical conditioning in the rabbit. The first series of experiments examined the rate of reacquisition to the original conditioned stimulus (CS) and to a cross-modal CS following various amounts of extinction. In both the rabbit nictitating membrane (NM) preparation and rabbit heart rate (HR) conditioning, there was a graded reduction in the rate of reacquisition as a direct function of the number of extinction trials. In the rabbit NM preparation, there was also a graded reduction in the rate of acquisition to a cross-modal stimulus (CSB, e.g., light). However, concurrent recovery of responding to the original, extinguished stimulus (CSA, e.g., tone) during training with a novel, cross-modal stimulus (CSB, e.g., light), appeared uniformly robust even following extensive extinction. The second series of experiments examined the conditions necessary for concurrent recovery to occur in the rabbit NM preparation. The introduction of CSB-US pairings resulted in strong recovery of responding to CSA, while the reintroduction of the US alone failed to result in any discernable reinstatement of responding to CSA. Concurrent recovery was specific to the trained and extinguished CSA, with virtually no generalized responding to a novel cross-modal test stimulus (CSC). However, pretraining with CSB-US pairings significantly reduced the amount of recovery to CSA during subsequent CSB???US pairings. The third series of experiments revealed that concurrent recovery was specific to the extinguished stimulus (CSA) with only moderate generalization to other familiar but untrained stimuli in the same modality as CSA. Together these results indicate that concurrent recovery is not primarily the result of the unmasking of the original CSA-US association. Rather, concurrent recovery appears to be at least partially the result of learning-dependent generalization. However, in order for responding to CSB, to generalize to CSA, CSA must have been paired with the same US which is subsequently paired with CSB. Thus, the CSA-US association must be partially intact for concurrent recovery to occur. A layered network model with multiple hidden units is able to simulate rapid reacquisition, facilitated cross-modal acquisition and concurrent recovery.