Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item INVESTIGATION OF LAMIN A PROCESSING AND REGULATION(2017) Wu, Di; Cao, Kan; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Lamin A is a major component of the lamina, which creates a dynamic network underneath the nuclear envelope. Mutations in the lamin A gene (LMNA) cause severe genetic disorders. One of the most striking cases is Hutchinson-Gilford progeria syndrome (HGPS). It is caused by a lamin A mutant protein named progerin. Due to the abnormal retaining of a permanent C-terminal farnesyl tail, progerin gradually accumulates on the nuclear membrane, resulting in abnormal nuclear morphology during interphase and perturbing a diversity of signaling and transcriptional events. To better understand lamin A gene’s function and regulation, I studied lamin A from three aspects in my dissertation, including its post-translational processing, post-transcriptional degradation, and transcriptional regulation. For post-translational processing, I examined the potential effects of cytoplasmic progerin based on a previous observation that membrane-associated progerin forms visible cytoplasmic aggregates in mitosis. After removal of the nuclear localization signal, I find that both LAΔNLS and PGΔNLS mutants are farnesylated in the cytosol and associated with a sub-domain of the ER via their farnesyl tails. While the farnesylation on LAΔNLS can be gradually removed by Zempste24, PGΔNLS remains permanently farnesylated and aggregated in the cytosol. Moreover, both ΔNLS mutants dominantly affect emerin’s nuclear localization. Previously, the accumulation of progerin has led to the speculation that progerin is more stable than the wild type lamin A. However, the low solubility of lamin proteins renders traditional immunoprecipitation-dependent methods ineffective for comparing the relative stabilities of mutant and wild type lamins. Therefore, to investigate the post-translational degradation of lamin A, I employed a novel platform based on viral 2A peptide-mediated co-translational cleavage to infer differences in lamin stability. My results support the notion that progerin is more stable than lamin A. In addition, treatment of FTI reduces progerin relative stability to the level of wild type lamin A. Last but not the least, I investigated the function of LMNA first intron in order to better understand the transcription regulation of lamin A. My results show that a highly conserved region within LMNA first intron is essential for the expression repression of lamin A in HL60 cells. This process is fulfilled by the interaction between this conserved region and transcription factor Sp1. Taken together, my results reveal new insights into biogenesis, protein interaction and transcription regulation of lamin A.Item An Investigation of Exclamatives in English and Japanese: Syntax and Sentence Processing(2006-08-24) Ono, Hajime; Lasnik, Howard; Linguistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation is a case study of the syntax of the left periphery, using exclamatives in English and Japanese. In the first part, I discuss exclamatives in Japanese in detail by focusing on the properties of the exclamative wh-phrases and particles that function as licensors for wh-phrases in exclamatives. We argue that licensing exclamatives involves at least three functional heads: Finite, Focus, and Mood. Especially, the necessity of the Mood head differentiates exclamatives from interrogatives. On the other hand, we claim that having these three functional projections does not type the clause as exclamative, and show that the presence of a wh-phrase of a distinct form is in fact a crucial part of the clause-typing for exclamation. This conclusion supports the claim that clause type should not be directly encoded into syntax as an independent functional category. The second part of dissertation deals with English exclamatives. We show that sluicing is available in English exclamatives, suggesting that focus is playing a role for the availability of sluicing, assuming that both interrogatives and exclamatives involve focus. Another conclusion about English exclamatives is that exclamative wh-clauses are licensed, not by selection, but by being c-commanded by a factive operator or a factive predicate. This goes against the traditional observation; our conclusion is empirically justified based on the observation that it is possible to license exclamative wh-clauses by a non-local licensor. We argue that this property is similar to what has been observed for the aggressively non-D-linked wh-phrases, accounting for the distribution and behavior of those non-standard wh-phrases. Finally, we investigate how Japanese exclamatives are processed by native speakers of Japanese with an on-line self-paced reading study and two off-line sentence fragment completion studies on the processing of wh-exclamative sentences in Japanese. These studies investigate the real-time formation of sentential structures with higher functional categories, and show that the parser immediately engages to build syntactic structures with discourse-oriented higher functional projections before coming across the head, favoring the incremental processing model.