Browsing by Subject "circadian rhythm"
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Item Elucidating the Functions of the Sialylation Pathway in Drosophila melanogaster(2012-10-19) Carnahan, MindySialylation is an important carbohydrate modification of glycoconjugates, which introduces sialic acids (SA). The relatively large nine-carbon, negatively charged sugars are typically located at the termini of carbohydrate chains. SA's are often required for functionally important molecular and cellular interactions including virus-host interactions, tumor progression and malignancy, immune system development and function, and nervous system development and function. However, the study of sialylation in vertebrates, including man, encounters serious obstacles associated with the complexity of vertebrates' biology and limitations of available experimental approaches. Drosophila is a useful model system with many advantages including quick generation time, a large number of progeny, simplified glycosylation and neurophysiology, and ease of genetic manipulations. The primary focus of this thesis is on the functions of Drosophila melanogaster CMP sialic acid synthetase (DmCSAS) and sialyltransferase (DSiaT) in the central nervous system (CNS). A combination of genetic, immunostaining, and neurobiology approaches were used to characterize the functions of DmCSAS and DSiaT in Drosophila. This investigation revealed the expression of DmCSAS and suggested that it plays an important role in a specialized and developmentally regulated process in the nervous system of Drosophila. Further experiments examined sub-cellular localization of DmCSAS revealing that this protein has a complex mostly Golgi-associated distribution within the cell in vivo. I discovered a novel link between Drosophila sialylation and circadian rhythm regulation. I also characterized the electrophysiological phenotypes of DmCSAS mutants and compared them to the corresponding defects associated with DSiaT mutations. My experiments also revealed that the relationship between DmCSAS and DSiaT are more complex than originally thought; these genes may have independent functions while also participating in the same pathway. Taken together, these results elucidate the sialylation pathway in Drosophila and shed more light on the role of sialylation in the nervous system. My experiments provide a unique evolutionary perspective on the sialylation pathway in animals and suggest that the neural function of SA in Drosophila can be conserved in vertebrates, including humans.Item Estimation of circadian parameters and investigation in cyanobacteria via semiparametric varying coefficient periodic models(2009-05-15) Liu, YingxueThis dissertation includes three components. Component 1 provides an estima- tion procedure for circadian parameters in cyanobacteria. Component 2 explores the relationship between baseline and amplitude by model selection under the framework of smoothing spline. Component 3 investigates properties of hypothesis testing. The following three paragraphs briefly summarize these three components, respectively. Varying coefficient models are frequently used in statistical modeling. We pro- pose a semiparametric varying coefficient periodic model which is suitable to study periodic patterns. This model has ample applications in the study of the cyanobac- teria circadian clock. To achieve the desired flexibility, the model we consider may not be globally identifiable. We propose to perform local approximations by kernel based methods and focus on estimating one solution that is biologically meaningful. Asymptotic properties are developed. Simulations show that the gain by our proce- dure over the commonly used method is substantial. The methodology is illustrated by an application to a cyanobacteria dataset. Smoothing spline can be implemented, but a direct application with the penalty selected by the generalized cross-validation often leads to non-convergence outcomes. We propose an adjusted cross-validation instead, which resolves the difficulties. Biol- ogists believe that the amplitude function of the periodic component is proportional to the baseline function. To verify this belief, we propose a full model without any assumptions regarding such a relationship, and two reduced models with the ratio of baseline and amplitude to be a constant and a quadratic function of time, respectively. We use model selection techniques, Akaike information criterion (AIC) and Schwarz Bayesian information criterion (BIC), to determine the optimal model. Simulations show that AIC and BIC select the correct model with high probabilities. Application to cyanobacteria data shows that the full model is the best model. To investigate the same problem in component 2 by a formal hypothesis testing procedure, we develop kernel based methods. In order to construct the test statistic, we derive the global degree of freedom for the residual sum of squares. Simulations show that the proposed tests perform well. We apply the proposed procedures to the data and conclude that the baseline and amplitude functions share no linear or quadratic relationship.Item The light mutant oscillator (LMO); a novel circadian oscillator in Neurospora crassa(2009-05-15) Huang, HeCircadian clocks are present in most eukaryotes and some prokaryotes and control rhythms in behavior, physiology and gene expression. One well-characterized circadian clock is that of Neurospora crassa. In addition to the well-described N. crassa FRQ/WCC oscillator, several lines of evidence have implied the presence of other oscillators which may have important functions in the N. crassa circadian clock system. However, the molecular details are only known for the core FRQ/WCC oscillator. The light mutant oscillator (LMO) was identified by two mutations (LM-1 and LM-2) and shown to control developmental rhythms in constant light (LL), conditions in which the FRQ/WCC oscillator is not functional. The objective of this project was to determine whether the developmental rhythms driven by the LMO are circadian, whether the components of the LMO communicate with components of the FRQ/WCC oscillator, and to begin to define the molecular nature of the LMO. First, the conditions for growth of the LM-1 mutant strain that reveals the best circadian rhythm of development in LL were found. Second, the LMO was determined to display the three properties required of a circadian oscillator. Third, the LMO was shown to function independently of the FRQ/WCC oscillator to control developmental rhythms in LL. However, evidence suggests that the FRQ/WCC oscillator and the LMO communicate with each other. Finally, using Cleaved Amplified Polymorphic Sequence (CAPS) markers, the LM-1 mutation was genetically mapped to the right arm of linkage group I within a 1069 kb region. Together, these results provide a start towards understanding of the complexity of oscillators that form a circadian clock in organisms.