Brock University Digital Repository 

• Investigating Neuromodulatory Mechanisms of Cotransmitter Proctolin in Drosophila Neuromuscular Junction

  Jung, Jae Hwan; Department of Biological Sciences

  Proctolin is a neuropeptide that induces or increases muscle contraction in nearly all arthropods. In the fruit fly, Drosophila melanogaster, proctolin is released onto skeletal muscles as a cotransmitter with the excitatory neurotransmitter, L-glutamate (Glu). This thesis examines mechanisms of action through which proctolin modulates contractions of Drosophila muscles. Chapter 1 includes a literature review of neuromodulation, cotransmitters, neurohormones and effects of proctolin, and it gives a rationale for the scientific questions addressed in subsequent chapters. Previous work showed that increasing neural activity reduces the threshold and EC50 values for proctolin’s ability to increase nerve-evoked contractions. Chapter 2 provides evidence that this activity-dependence cannot be attributed solely to an increase in Glu release with increasing neural activity. Proctolin potentiates contractions elicited by directly applying Glu to larval muscles but does not consistently shift EC50 values. Effects of proctolin and Glu on contraction are supra-additive but do not appear to be synergistic. Chapter 3 demonstrates that proctolin increases calcium-induced fluorescence in muscle cytoplasm by itself and enhances calcium signals elicited by Glu. The effect of proctolin is blocked by nifedipine, an inhibitor of voltage-gated, L-type calcium channels in the plasma membrane, suggesting a role for calcium influx. Proctolin failed to increase calcium-induced fluorescence changes induced by caffeine in calcium-free saline, suggesting that proctolin may not act directly on ryanodine receptors (RyRs) that release calcium from the sarcoplasmic reticulum (SR) into the cytosol. Chapter 4 examines a hypothesis in which activating the proctolin receptor inhibits calmodulin, since calcium-calmodulin complexes are reported to inhibit RyRs at high calcium concentrations, limiting calcium release from the SR. A calmodulin inhibitor, W7, mimicks some but not all effects of proctolin, suggesting that although calmodulin inhibition may contribute to proctolin’s effects, other mechanisms must be involved. Data are presented implicating the possible involvement of protein kinase C (PKC), the cAMP-dependent protein kinase (PKA) and the plasma membrane calcium ATPase (PMCA), which normally removes calcium from the cytosol. This thesis adds to our understanding of how cotransmission of proctolin with Glu modulates muscle performance in Drosophila, and it suggests an experimental framework for investigating effects of cotransmitters generally.
• Training in Trauma-Informed Positive Behaviour Support for Direct Support Professionals of Adults with Intellectual and Developmental Disabilities

  Bulten, Emily; Center for Applied Disability Studies

  People with disabilities are vulnerable to experiencing trauma due to a complex interaction of systemic and individual factors (McGilvery, 2018), urging for supports that promote safety and control, such as Trauma-Informed Care (TIC) and Positive Behaviour Support (PBS). Behavioural Skills Training (BST) is a competency-based training procedure used to teach a wide selection of professionals work-related skills (Gormley et al., 2019). This study evaluated a multicomponent training package consisting of didactic and activity-based training plus BST implemented with 12 direct support professionals recruited from a community-based organization supporting adults with intellectual and developmental disabilities. A pre-post- follow-up design was used to determine the effectiveness of didactic and activity-based training on knowledge and application of TIC and PBS. BST was used to increase skills related to trauma-informed PBS for a subset of six participants using a multiple probe within-participants single-case experimental design (Ledford & Gast, 2018). The three skills trained were providing opportunities for choice, multiple stimulus without replacement, and paired item preference assessments. Training resulted in increased knowledge and application of PBS and TIC on post- tests and at follow-up. BST was effective in training all skills to mastery, while maintenance and generalization were evident for most skills four to five weeks after training. Implications of the findings, strengths and limitations of the study, and future steps are discussed.
• Magnetism, half-metallicity and electrical transport properties of V- and Cr-doped semiconductor SnTe: A theoretical study

  Bose, SK; Liu, Y; Kudrnovský, J (American Institute of Physics, 2013-12)

  This work presents results for the electronic structure, magnetic properties, and electrical resistivity of the semiconductor SnTe doped with 3d transition metals V and Cr. From the standpoint of potential application in spintronics, we look for half-metallic states and analyze their properties in both rock salt and zinc blende structures using ab initio electronic structure methods. In both cases, it is the Sn-sublattice that is doped with the transition metals, as has been the case with experiments performed so far. We find four half-metallic compounds at their optimized cell volumes. Results of exchange interactions and the Curie temperature are presented and analyzed for all the relevant cases. Resistivity calculation based on Kubo-Greenwood formalism shows that the resistivities of these alloys due to transition metal doping of the Sn-sublattice may vary, in most cases, from typical liquid metal or metallic glass value to 2–3 times higher. 25% V-doping of the Sn-sublattice in the rock salt structure gives a very high resistivity, which can be traced to high values of the lattice parameter resulting in drastically reduced hopping or diffusivity of the states at the Fermi level.
• Electrode effects in dielectric spectroscopy measurements on (Nb+In) co-doped TiO2

  Crandles, D.A.; Yee, S.M.M.; Savinov, M.; Nuzhnyy, D.A.; Petzelt, J.; Kamba, S.; Prokes, J. (AIP Publishing, 2016-04-20)

  Recently, several papers reported the discovery of giant permittivity and low dielectric loss in (Nb,In) co-doped TiO2. A series of tests was performed which included the measurement of the frequency dependence of the dielectric permittivity and alternating current (ac) conductivity of co-doped (Nb,In)TiO2 as a function of electrode type, sample thickness, and temperature. The data suggest that the measurements are strongly affected by the electrodes. The consistency between four-contact van der Pauw direct current conductivity measurements and bulk conductivity values extracted from two-contact ac conductivity measurements suggest that the values of colossal permittivity are, at least in part, a result of Schottky barrier depletion widths that depend on electrode type and temperature.
• The Observation of Highly Ordered Domains in Membranes with Cholesterol

  Armstrong, Clare L.; Marquardt, Drew; Dies, Hannah; Kučerka, Norbert; Yamani, Zahra; Harroun, Thad A.; Katsaras, John; Shi, An-Chang; Rheinstädter, Maikel C. (PLoS, 2013-06)

  Rafts, or functional domains, are transient nano- or mesoscopic structures in the exoplasmic leaflet of the plasma membrane, and are thought to be essential for many cellular processes. Using neutron diffraction and computer modelling, we present evidence for the existence of highly ordered lipid domains in the cholesterol-rich (32.5 mol%) liquid-ordered () phase of dipalmitoylphosphatidylcholine membranes. The liquid ordered phase in one-component lipid membranes has previously been thought to be a homogeneous phase. The presence of highly ordered lipid domains embedded in a disordered lipid matrix implies non-uniform distribution of cholesterol between the two phases. The experimental results are in excellent agreement with recent computer simulations of DPPC/cholesterol complexes [Meinhardt, Vink and Schmid (2013). Proc Natl Acad Sci USA 110(12): 4476–4481], which reported the existence of nanometer size domains in a liquid disordered lipid environment.

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