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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Investigation of Regulatory and Functional Diversification of Arabidopsis thaliana Shikimate Kinase Duplicates

Buranyi, Stephen 24 June 2014 (has links)
Two Arabidopsis thaliana shikimate kinases, AtSK1 and AtSK2, were previously identified as having arisen from a duplication event 40-60 million years ago and are both believed to function in the shikimate pathway. We investigated the homologs have acquired divergent regulatory or functional roles since duplication. AtSK1 demonstrates different transcript levels than AtSK2 during heat shock and in floral tissues as determined by RT-PCR. Mining of publically available microarray datasets identified HSF1 and MYB family transcription factors as possible regulators of AtSK1 under these conditions. Heat shock response did not appear to be affected by either sk1 or sk2 knockouts in assays measuring thermotolerance and ROS production. Floral morphology appears normal during floral stages corresponding with AtSK1 transcript induction however, pollen viability is reduced by 20% in sk1 knockouts as measured by FDA staining. Thus, this work has identified instances of differential regulation and function between two recently duplicated shikimate kinases.
2

ED-A Fibronectin: A Storage Site for Latent TGFB-1 in the Myofibroblast Matrix?

Chau, Grace 24 July 2012 (has links)
Fibrosis, a major cause of organ failure, has no effective therapy available. Responsible for fibrosis are myofibroblasts. Mechanical stress, TGF myofibroblast differentiation, however the exact link remains elusive. I hypothesize that ED-A FN stores the latent TGF -1 in the ECM by interacting with the latent TGF -1 binding protein (LTBP-1), and that matrix stiffness is a regulator of ED-A FN and LTBP-1. Using co-IP and ED-A domain antagonists, ED-A FN and LTBP-1 associated in the ECM of human dermal fibroblasts (HDFs). The effects of the 11th_ED-A_12th recombinant FN peptide was most prominent in blocking LTBP-1 incorporation in the ECM. HDFs seeded on collagen- coated substrates, showed an increase in expression and organization for both proteins with matrix stiffness. In conclusion, the ED-A domain may require the aid of heparin linkages flanking the 12th domain of FN to bind to LTBP-1 in the ECM.
3

The Role of Mechanical Stress in Regulating Integrin Recruitment to Latent TGF-β1

Kwon, YongGyun 20 November 2012 (has links)
Fibrosis is characterized by excessive extracellular matrix (ECM) production and contraction of myofibroblasts that differentiate from fibroblasts under the action of pro-fibrotic cytokine TGF-β1 and mechanical stress. Myofibroblasts liberate active TGF-β1 by integrin-mediated pulling on the latency-associated protein pro-peptide (LAP) which is stored together with the latent TGFβ1-binding protein-1 (LTBP-1) in the ECM. I hypothesized that the binding affinity/strength of LAP binding integrins, in particular of integrin αvβ3, is regulated by the mechanical stress arising from the contractile fibroblast cytoskeleton and the stiff ECM. To test this hypothesis, different methods were employed to investigate mechanically-regulated integrin αvβ3 recruitment to LAP in the physiological context of fibroblasts. The main findings of my thesis work are that (a) fibroblasts use αvβ3 integrin to bind to LAP; (b) αvβ3 integrin is capable of transmitting considerable cell force to LAP; and (c) mechanical stress increases the recruitment of αvβ3 integrin to LAP.
4

ED-A Fibronectin: A Storage Site for Latent TGFB-1 in the Myofibroblast Matrix?

Chau, Grace 24 July 2012 (has links)
Fibrosis, a major cause of organ failure, has no effective therapy available. Responsible for fibrosis are myofibroblasts. Mechanical stress, TGF myofibroblast differentiation, however the exact link remains elusive. I hypothesize that ED-A FN stores the latent TGF -1 in the ECM by interacting with the latent TGF -1 binding protein (LTBP-1), and that matrix stiffness is a regulator of ED-A FN and LTBP-1. Using co-IP and ED-A domain antagonists, ED-A FN and LTBP-1 associated in the ECM of human dermal fibroblasts (HDFs). The effects of the 11th_ED-A_12th recombinant FN peptide was most prominent in blocking LTBP-1 incorporation in the ECM. HDFs seeded on collagen- coated substrates, showed an increase in expression and organization for both proteins with matrix stiffness. In conclusion, the ED-A domain may require the aid of heparin linkages flanking the 12th domain of FN to bind to LTBP-1 in the ECM.
5

The Role of Mechanical Stress in Regulating Integrin Recruitment to Latent TGF-β1

Kwon, YongGyun 20 November 2012 (has links)
Fibrosis is characterized by excessive extracellular matrix (ECM) production and contraction of myofibroblasts that differentiate from fibroblasts under the action of pro-fibrotic cytokine TGF-β1 and mechanical stress. Myofibroblasts liberate active TGF-β1 by integrin-mediated pulling on the latency-associated protein pro-peptide (LAP) which is stored together with the latent TGFβ1-binding protein-1 (LTBP-1) in the ECM. I hypothesized that the binding affinity/strength of LAP binding integrins, in particular of integrin αvβ3, is regulated by the mechanical stress arising from the contractile fibroblast cytoskeleton and the stiff ECM. To test this hypothesis, different methods were employed to investigate mechanically-regulated integrin αvβ3 recruitment to LAP in the physiological context of fibroblasts. The main findings of my thesis work are that (a) fibroblasts use αvβ3 integrin to bind to LAP; (b) αvβ3 integrin is capable of transmitting considerable cell force to LAP; and (c) mechanical stress increases the recruitment of αvβ3 integrin to LAP.
6

Investigation of Regulatory and Functional Diversification of Arabidopsis thaliana Shikimate Kinase Duplicates

Buranyi, Stephen 24 June 2014 (has links)
Two Arabidopsis thaliana shikimate kinases, AtSK1 and AtSK2, were previously identified as having arisen from a duplication event 40-60 million years ago and are both believed to function in the shikimate pathway. We investigated the homologs have acquired divergent regulatory or functional roles since duplication. AtSK1 demonstrates different transcript levels than AtSK2 during heat shock and in floral tissues as determined by RT-PCR. Mining of publically available microarray datasets identified HSF1 and MYB family transcription factors as possible regulators of AtSK1 under these conditions. Heat shock response did not appear to be affected by either sk1 or sk2 knockouts in assays measuring thermotolerance and ROS production. Floral morphology appears normal during floral stages corresponding with AtSK1 transcript induction however, pollen viability is reduced by 20% in sk1 knockouts as measured by FDA staining. Thus, this work has identified instances of differential regulation and function between two recently duplicated shikimate kinases.
7

Auditory Sensitivity and Defence Strategy in Insects

ter Hofstede, Hannah Marie 28 September 2009 (has links)
Predation pressure is a powerful agent of natural selection and is responsible for the evolution of various antipredator defence strategies in animals. Sensory thresholds for predator detection could play an important role in the evolution of defence strategies. I tested the hypothesis that the ability of animals to detect predators is correlated with defence strategy, with the prediction that animals with poor predator detection abilities rely more on preventative (primary) defence strategies than animals with low predator detection thresholds. Bats and their insect prey were used as a simple study system for these experiments due to the reliance on a single modality (hearing) for both predator and prey detection. Many insects have ears tuned to the ultrasonic echolocation calls of bats and can use this predator cue to initiate evasive action, but variation in auditory thresholds exists among species. In moths, a group in which the only known function of hearing is predator detection, a clear relationship was found between auditory thresholds for predatory ultrasound and a risky behaviour, nocturnal flight time. A more complicated situation exists when the sensory system serves more than one purpose, as with the ears of orthopteran insects used for both predator detection and mate localization. Some gleaning bats use calling song as a cue to locate these insects as prey, and both primary (reduced calling) and secondary (song cessation in response to ultrasound) defences have been identified in orthopterans. The auditory interneurons considered the “bat-detectors” in katydids and crickets most likely have context dependent functions in several groups, as a predator-detector in flight and mate-detector on the ground. The relationship between reliance on primary over secondary defence and auditory sensitivity in these insects appears to be influenced by the nature of the calling song of the species and their mating strategy.
8

The F-box protein FSN-1 Functions in an SCF-like Ubiquitin Ligase Complex to Regulate Synapse Formation

Liao, Edward Hai Dhow 31 July 2008 (has links)
The chemical synapse is an asymmetric structure consisting of presynaptic and postsynaptic terminals in direct apposition to each other. Synapses function to mediate the transmission of signals between neurons and their targets. The formation of synapses is a tightly regulated process requiring the interaction of many genes and molecular pathways. I am interested in identifying genes and signaling pathways that are required for proper synapse formation. Using the GABAergic neuromuscular junctions of C. elegans as a model system, I have identified fsn-1 (F-box synaptic protein), a gene required for the control of synaptic growth. fsn-1 mutants exhibit a synaptic defect characterized by both synaptic over differentiation and under differentiation. FSN-1 is an F-box protein with a SPRY (SPla and RYanodine receptor) domain that functions cell-autonomously in neurons to regulate synaptic growth. I have shown that it functions in an E3 ubiquitin ligase-like complex with the RING-H2 finger protein RPM-1 (Regulator of presynaptic morphology), SKR-1 and Cullin. The composition of this complex is similar to SCF (Skp1, Cullin, F-box) E3 ubiquitin ligases. We hypothesize that this complex controls synapse formation by down regulating synapse promoting factors through an ubiquitin mediated process. We have identified two receptor tyrosine kinases that genetically interact with fsn-1, the Anaplastic Lymphoma Kinase homolog SCD-2 (Suppressor of Constitutive Dauer) and the C. elegans insulin receptor DAF-2 (abnormal DAuer Formation). Loss of function mutations in scd-2 or daf-2 partially suppress the synaptic differentiation defects of fsn-1 mutants, suggesting that they participate in signaling pathways whose activities are normally inhibited by FSN-1 during synapse formation. Unlike FSN-1 that functions in GABAergic neurons, I found that SCD-2 and DAF-2 have cell non-autonomous functions at GABAergic neuromuscular junctions. SCD-2 is required in the nervous system in the RID interneuron where it could modulate synapse formation through ligands present on the motoneuron cell surface. The DAF-2/insulin pathway functions in postsynaptic muscle cells to regulate FSN-1 dependent presynaptic growth likely through a retrograde or feedback mechanism. I propose a model where FSN-1 regulates synapse formation by attenuating signals that converge upon the presynaptic terminal to stimulate or inhibit synaptic growth.
9

The Role of Discoidin Domain Receptor 1 (Ddr1) on Macrophages in Adhesion and Cytokine Production

Britto, Karen Elma 15 December 2010 (has links)
Atherosclerosis is an inflammatory disease of the cardiovascular system. Discoidin domain receptor 1 is a receptor tyrosine kinase that binds collagens. Previous work in our lab has shown that deleting DDR1 in a mouse model results in attenuation of atherosclerosis, with fewer macrophages in the plaque. The aim of this study was to determine what changes in macrophage behaviour due to the lack of DDR1 was attenuating plaque development. In order to carry out experiments, primary mouse peritoneal macrophages were used. DDR1-deficient macrophages adhered significantly less to type IV collagen and fibronectin compared to DDR1-expressing cells. In addition, when plated on type IV collagen and fibronectin, DDR1-deficient macrophages produced decreased levels of MCP-1 protein, a cytokine known to be important in plaque development, particularly in leukocyte recruitment to plaque. These results suggest that DDR1 is an important mediator in macrophage adhesion to matrix and macrophage cytokine production
10

Predicting Kinase Substrates using Conservation of Local Motif Density

Lai, Chi-Wai Andy 12 December 2011 (has links)
Short linear motifs (SLM) play critical roles in cell signaling and are associated with important biochemical events such as phosphorylation, glycosylation, and other post translational modifications. The primary aim of this thesis is to develop a new computational method (“ConDens”) to predict kinase substrates by assessing the evolution of phosphorylation SLM’s in a novel manner. This method could predict yeast Cdc28 kinase substrates that were not confidently detected by several other prediction methods published in literature and was demonstrated to be generalizable to other kinases. Genome-wide predictions experiments with this method also revealed potentially interesting novel substrates of Mec1, Prk1, PKA, and CKII.

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