+publisher:"University of Illinois – Urbana-Champaign" +contributor:("Ceman, Stephanie S.")

University of Illinois – Urbana-Champaign

1. Kim, Miri. Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10.

Degree: PhD, 0323, 2014, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/46927

► The work presented in this dissertation focuses primarily on the role of FMRP, the fragile X mental retardation protein and its role in translational regulation.… (more)

▼ The work presented in this dissertation focuses primarily on the role of FMRP, the fragile X mental retardation protein and its role in translational regulation. More specifically, I began my studies trying to understand the role of FMRP in the nucleus. This work is novel and interesting because the nuclear role of FMRP has not been widely studied. FMRP is an RNA binding protein that is important for normal neuronal development and maturation as well as proper cognitive development as the lack of FMRP results in fragile X syndrome (FXS). I next move out of the nucleus and study the role of FMRP and translation in the cytoplasm. This work elaborates on a novel FMRP associated protein, putative RNA helicase MOV10 Chapter 1 begins with an introduction to fragile X syndrome as well as a current literature review of the fragile X field. I introduce the history of fragile X syndrome and the characteristics of the syndrome as well as introducing the key player: FMRP. FMRP is an interesting protein because it has several RNA binding domains as well as several post translational modifications. Despite all that is currently known about FMRP, there is still a large gap in understanding about how these modifications act as guides for specific RNA targeting and binding. My first project outlined in Chapter 2 focuses on the role of FMRP in the nucleus. FMRP contains both a Nuclear Localization Sequence (NLS) as well as a Nuclear Export Sequence (NES), however how FMRP enters the nucleus is unclear because of its non-canonical NLS. I demonstrate that FMRP enters the nucleus and that it requires Tap/Nxf1 for efficient export from the nucleus. Additionally, I use the Xenopus laevis oocyte system to demonstrate that FMRP is indeed present along nascent mRNA transcripts suggesting that FMRP enters the nucleus and can target newly transcribed RNAs. Next, in Chapter 3, I focus on a novel FMRP associated protein, MOV10. MOV10 is a putative RNA helicase that associates with FMRP. I demonstrate that MOV10 and FMRP associate in a salt and RNA dependent manner and that the two proteins exist in tissue in similarly sized granules suggesting a cellular interaction. We also determined that FMRP requires MOV10 to recruit a number of brain specific mRNAs and that both FMRP and MOV10 bind G quadruplex structures specifically. Using iClip, we identified MOV10 specific mRNA targets as well as identifying binding sites of MOV10. We also found that Ago2 binding sites influenced the fate of MOV10 clip targets, suggesting a role of MOV10 acting as a facilitator or inhibitor of miRNA mediated regulation depending on proximity to Ago2 binding sites. Chapter 4 develops a novel single molecule study directed towards understanding how MOV10 behaves as a helicase. I generated mRNA constructs to study G quadruplex forming RNA sequences at the single molecule level and establish that sc1and sc1 mutant RNAs behave different in salt solutions. In addition to studying sc1 and sc1 model RNAs, I expanded the study to encompass hASH1, a… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Chen%2C%20Jie%22%29&pagesize-30">Chen, Jie (committee member), Champaign%22%20%2Bcontributor%3A%28%22Stubbs%2C%20Lisa%20J.%22%29&pagesize-30">Stubbs, Lisa J. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Myong%2C%20Su-A%22%29&pagesize-30">Myong, Su-A (committee member).

Subjects/Keywords: Fragile X Syndrome; MOV10; RNA Binding Protein; RNA Helicase; Translation Regulation

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APA (6^th Edition):

Kim, M. (2014). Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/46927

Chicago Manual of Style (16^th Edition):

Kim, Miri. “Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/46927.

MLA Handbook (7^th Edition):

Kim, Miri. “Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10.” 2014. Web. 14 Apr 2021.

Vancouver:

Kim M. Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/46927.

Council of Science Editors:

Kim M. Nuclear binding and translation regulation by FMRP through novel associated protein and putative RNA helicase MOV10. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/46927

University of Illinois – Urbana-Champaign

2. Matt, Stephanie Marie. Epigenetic regulation of neuroinflammation in the aged mouse brain.

Degree: PhD, Neuroscience, 2018, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/101119

► As the average lifespan continues to rise, there is a significant increase in the number of people suffering from age-related chronic inflammatory diseases such as… (more)

▼ As the average lifespan continues to rise, there is a significant increase in the number of people suffering from age-related chronic inflammatory diseases such as autoimmune disorders, cancer, and neurodegenerative diseases. Therefore, there is a greater need to understand the factors that contribute to quality of life in the elderly. Growing evidence indicates that the immune system plays a critical role in regulating the progression of brain aging. However, an important question remains of whether inflammatory pathways become hyperactivated with age, or whether deficient immune responses, which fail to cope with age-related deterioration, may contribute to disease. Microglia, the resident immune cells of the brain, are key players in regulating neuroinflammation. They function as the primary immune surveillance, provide the first host defense by secreting factors such as cytokines and chemokines, and carry out specific central nervous system functions such as synaptic pruning and secretion of neurotrophic factors. Of note, microglia are also long-lived within the brain and have a limited turnover, suggesting that they are a likely target for epigenetic regulation. In order to determine possible causes and targets for interventions to promote healthy aging, the current dissertation explored the role of epigenetic regulation in microglia as well as potential pharmacological and dietary interventions that could be beneficial for chronic age-related neuroinflammation. This dissertation was divided into three major sections. In Chapter 2, we determined that aged mice had decreased methylation of the Il1b gene promoter in primary microglia basally or following systemic lipopolysaccharide (LPS) that is associated with increased Il1b mRNA, intracellular IL-1β production, as well as prolonged sickness behavior. We also determined changes in epigenetic regulator gene expression with both age and LPS. Furthermore, we found that inhibiting DNA methylation increased Il1b gene expression and decreased DNA methylation of BV2 and primary microglial cells similar to microglia from aged mice. In Chapter 3, we investigated whether inhibiting DNA methylation in the brain of adult mice would alter sickness behavior, DNA methylation of the Il1b promoter and expression of inflammatory genes in microglia similar to aged mice. However, we found that inhibiting DNA methylation and injecting LPS in the brain of adult mice produced faster recovery of burrowing behavior compared to mice treated only with LPS. Genes of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e. the sensome) were also differentially expressed by inhibiting DNA methylation alone or in combination with LPS. Lastly, DNA methylation of Il1b proximal promoter was changed by inhibiting DNA methylation alone or in combination with LPS, and these changes persisted 48 hours after LPS treatment. In Chapter 4, we investigated whether injections of butyrate or increases in butyrate through a highly fermentable diet could affect… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Johnson%2C%20Rodney%20W.%22%29&pagesize-30">Johnson, Rodney W. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Johnson%2C%20Rodney%20W.%22%29&pagesize-30">Johnson, Rodney W. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Steelman%2C%20Andrew%20J.%22%29&pagesize-30">Steelman, Andrew J. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Uddin%2C%20Monica%22%29&pagesize-30">Uddin, Monica (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member).

Subjects/Keywords: Neuroinflammation; Epigenetics; DNA Methylation; Aging; Microglia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Matt, S. M. (2018). Epigenetic regulation of neuroinflammation in the aged mouse brain. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101119

Chicago Manual of Style (16^th Edition):

Matt, Stephanie Marie. “Epigenetic regulation of neuroinflammation in the aged mouse brain.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/101119.

MLA Handbook (7^th Edition):

Matt, Stephanie Marie. “Epigenetic regulation of neuroinflammation in the aged mouse brain.” 2018. Web. 14 Apr 2021.

Vancouver:

Matt SM. Epigenetic regulation of neuroinflammation in the aged mouse brain. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/101119.

Council of Science Editors:

Matt SM. Epigenetic regulation of neuroinflammation in the aged mouse brain. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101119

University of Illinois – Urbana-Champaign

3. Chu, James L. Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus.

Degree: PhD, Cell and Developmental Biology, 2018, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/101126

► Circadian rhythms in mammals, such as metabolism, hormone release, and the sleep/wake cycle, are orchestrated by the suprachiasmatic nucleus (SCN) located in the hypothalamus. Mass… (more)

▼ Circadian rhythms in mammals, such as metabolism, hormone release, and the sleep/wake cycle, are orchestrated by the suprachiasmatic nucleus (SCN) located in the hypothalamus. Mass spectrometry peptidomics of the SCN identified the small peptide cerebellin-short (SGSAKBSAIRSTN) consisting of 15 amino acids, which is released from the SCN in circadian fashion. Cerebellin-short is the C-terminus truncated form of the 16 amino acid cerebellin peptide highly enriched in the cerebellum. The distribution of cerebellin-short in the SCN and the functional implications of its circadian release, however, are unknown. Here we showed that the precursor of cerebellin-short, Cbln1, is expressed in the SCN with daily oscillations in mRNA level. The level of Cbln1 process intermediate also oscillates around the day. Immunofluorescence revealed that a portion of both AVP- and VIP- positive cells in the SCN are also positive for cerebellin-short. Cbln1 on the other hand localized immediately dorsal to the SCN along the 3rd ventricle. Cbln1 also showed strong localization to the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the median eminence. No Cbln1 or process intermediate were observed in GFAP-positive astrocytes. Crude synaptosome fractionations of the SCN revealed that the processing intermediate, but not Cbln1, is enriched at the synapse. Exogenous application of cerebellin-short at midday and early night phase advance the spontaneous firing rhythm of SCN neurons. These results suggest that Cbln1 is actively processed into cerebellin-short at the synapses throughout the SCN, and is likely involved in the intrinsic circadian time keeping mechanism. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Gillette%2C%20Martha%20U.%22%29&pagesize-30">Gillette, Martha U. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Stubbs%2C%20Lisa%20J.%22%29&pagesize-30">Stubbs, Lisa J. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (committee member).

Subjects/Keywords: Circadian; Rat; Suprachiasmatic Nucleus: SCN; peptide; Mass Spectrometry Imaging; Long Term Potentiation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chu, J. L. (2018). Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101126

Chicago Manual of Style (16^th Edition):

Chu, James L. “Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/101126.

MLA Handbook (7^th Edition):

Chu, James L. “Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus.” 2018. Web. 14 Apr 2021.

Vancouver:

Chu JL. Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/101126.

Council of Science Editors:

Chu JL. Characterizing cerebellin-short, a novel circadian peptide, in the rat suprachiasmatic nucleus. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101126

University of Illinois – Urbana-Champaign

4. Iyer, Rajashekar. miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons.

Degree: PhD, Cell and Developmental Biology, 2018, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/101315

► The wiring of the nervous system is an intricate process of self-organization, of unparalleled complexity in the natural world. To get a sense of the… (more)

▼ The wiring of the nervous system is an intricate process of self-organization, of unparalleled complexity in the natural world. To get a sense of the scope of the requirement, imagine all the billions of phones and computers connected by wires to form the internet. Imagine if these wires branch out and divide, avoiding inimical landscapes and waters, to reach the right servers and computers, which turn had to send out wires to meet yet other servers and so on, till you have the internet of today. Now imagine that instead of a few billion computers, you had eighty-six billion neurons. Instead of men laying down the wiring on pre-programmed routes, the wires had to grow on their own. And instead of the lands and seas of Earth, you had to achieve all this in the space of a single human skull. This is the self-organization challenge of the axons and dendrites of the brain. Developing dendrites encounter a variety of stimuli that direct their growth and final architecture. Cellular substrates respond to these stimuli, integrating extrinsic information to direct dendritic growth. Of interest in this process are microRNAs, small noncoding RNAs around 22 nucleotides long, which can reversibly repress local translation in dendrites. By responding to external cues sensed by dendritic filopodia, they participate in the key decision-making processes in developing dendrites: where and how to grow. This study focuses on the role of miR-125b, a brain abundant microRNA, for its role in the dynamics and structure of filopodia in developing dendrites. We inhibited miR- 125b’s activity in cultured hippocampal neurons during the early stages of development as filopodia explore their microenvironment. We show that miR-125b function is critical for maintaining the structural features of filopodia, and that inhibiting its function changes the distribution of the type of protrusions emerging from dendritic shafts. Inhibiting miR-125b increases dendritic expression and localization of the GluN2A subunit of the NMDA receptor, and we show that dendritic GluN2A is correlated with maintaining filopodial morphology. Using Spatial Light Interference Microscopy (SLIM), we show that miR-125b function contributes to maintaining the dynamicity of filopodia. We propose that miR-125b is critical in maintaining the filopodial phenotype early in dendrite development, thus contributing to dendritogenesis and spinogenesis. Through its regulation of GluN2A, miR-125b shapes neuronal response to the synaptotrophic factor glutamate. These high-resolution analyses reveal fresh insights into the process by which neurons integrate multiple external signals to establish the correct connections. Such insights are critical to understanding the implicated role of miR125b in various neurological disorders like Fragile X Syndrome and Alzheimer’s disease. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Gillette%2C%20Martha%20U.%22%29&pagesize-30">Gillette, Martha U. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Brieher%2C%20William%20M.%22%29&pagesize-30">Brieher, William M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (committee member).

Subjects/Keywords: Filopodia; MicroRNA

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Iyer, R. (2018). miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101315

Chicago Manual of Style (16^th Edition):

Iyer, Rajashekar. “miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/101315.

MLA Handbook (7^th Edition):

Iyer, Rajashekar. “miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons.” 2018. Web. 14 Apr 2021.

Vancouver:

Iyer R. miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/101315.

Council of Science Editors:

Iyer R. miR-125b toggles dynamics and structure of dendritic filopodia in developing hippocampal neurons. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101315

University of Illinois – Urbana-Champaign

5. Magis, Andrew. Next-generation sequencing analysis and RNA editing in human brain and glioma.

Degree: PhD, 0319, 2014, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/46939

► RNA sequencing (RNA-seq) is one of the most common technologies in use today for the analysis of gene expression and transcriptome variation in biological samples… (more)

▼ RNA sequencing (RNA-seq) is one of the most common technologies in use today for the analysis of gene expression and transcriptome variation in biological samples (Zhong Wang et al. 2009). As of 2011, the NCBI Sequence Read Archive (SRA) surpassed 100 terabases of sequence data, comprising nearly 40,000 RNA and 260,000 DNA sequencing projects. In 2013 the SRA comprises over 500 terabases, with a projected doubling time of 22.3 months. The explosive growth of next-generation sequence data now exceeds the growth rate of storage capacity (Kodama et al. 2012). Researchers’ ability to process and analyze this data depends upon bioinformatics tools that are accurate, easy to use, and fast—especially when multiple data sets are available for processing and additional analysis beyond standard mapping is required. To address these issues I have developed SNAP-RNA, a new RNA-seq alignment and analysis pipeline designed for datasets involving hundreds or thousands of RNA-seq libraries, while maintaining high alignment accuracy. SNAP-RNA is capable of natively reading from FASTQ, gzipped FASTQ, SAM, and BAM formats, and directly writing to BAM and sorted BAM formats for immediate visualization, without any need for external software packages such as SAMtools (Heng Li et al. 2009). Quality filtering of input reads is incorporated directly into the alignment process. SNAP-RNA can automatically identify and report contaminants or viral/bacterial infections in samples, and gene read counts suitable for downstream analysis with popular statistical programs such as DESeq (Anders and Huber 2010), edgeR (Robinson et al. 2010), or baySeq (Hardcastle and Kelly 2010) are automatically generated with no running time penalty. Finally, SNAP-RNA automatically identifies intra- and inter-chromosomal gene fusions with high accuracy, reporting the results automatically, while maintaining speeds competitive with the fastest available aligners. I demonstrate the capabilities of SNAP-RNA through the analysis of nearly 1300 high-quality RNA-seq samples from several different cancer types derived from The Cancer Genome Atlas, using recently published studies as my benchmarks. Recent developments in next-generation sequencing have revealed unprecedented levels of RNA editing of expressed transcripts, the majority of which occur in the brain. Alterations in transcript editing levels are increasing being linked to pathology in human cancer. Using a novel RNA editing analysis pipeline enabled by SNAP-RNA I have characterized changes in A-to-I editing percentages in nearly 400 glioblastoma and astrocytoma primary tumor, normal brain, and cell line samples. This study represents the first global view of differential editing across multiple brain regions and low- and high-grade astrocytoma. I identify relationships between expression of the editing enzymes ADAR, ADARB1, and ADARB2 and editing profiles in both healthy and diseased states of the brain. Furthermore, I identify many differentially edited bases across normal brain and gliomas that have not… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Price%2C%20Nathan%20D.%22%29&pagesize-30">Price, Nathan D. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Price%2C%20Nathan%20D.%22%29&pagesize-30">Price, Nathan D. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Sinha%2C%20Saurabh%22%29&pagesize-30">Sinha, Saurabh (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ma%2C%20Jian%22%29&pagesize-30">Ma, Jian (committee member).

Subjects/Keywords: RNA sequencing; next-generation sequencing; microarray; transcriptomics; Illumina; single end; paired end; alignment; Tophat; Bowtie; Burrows-Wheeler; classification; top-scoring pair; top-scoring triplet; relative expression; RNA editing; adenosine deaminase, RNA-specific (ADAR); adenosine deaminase; Glioma; glioblastoma; astrocytoma

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Magis, A. (2014). Next-generation sequencing analysis and RNA editing in human brain and glioma. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/46939

Chicago Manual of Style (16^th Edition):

Magis, Andrew. “Next-generation sequencing analysis and RNA editing in human brain and glioma.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/46939.

MLA Handbook (7^th Edition):

Magis, Andrew. “Next-generation sequencing analysis and RNA editing in human brain and glioma.” 2014. Web. 14 Apr 2021.

Vancouver:

Magis A. Next-generation sequencing analysis and RNA editing in human brain and glioma. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/46939.

Council of Science Editors:

Magis A. Next-generation sequencing analysis and RNA editing in human brain and glioma. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/46939

University of Illinois – Urbana-Champaign

6. Guzman Sanchez, Irisbel. Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells.

Degree: PhD, Biochemistry, 2015, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/78610

► Protein-RNA interactions and protein folding are critical subjects in biochemistry, because of their significance during the formation of active complexes and signaling pathways. Regardless of… (more)

▼ Protein-RNA interactions and protein folding are critical subjects in biochemistry, because of their significance during the formation of active complexes and signaling pathways. Regardless of the substantial amount of studies in the fields of protein-RNA interactions and protein folding, little is known about the stability and kinetics of these in the cell. This doctoral dissertation aims to advance the understanding of protein-RNA interactions and protein folding inside cells through comparative in vitro studies, utilizing U1A-SL2 RNA complex and PGK/VlsE proteins as model systems, respectively. For the protein-RNA studies, dynamics experiments of one positive charged mutant of the spliceosomal U1A protein, the golden model for the RNA Recognition Motif (RRM), reveled a conformational transition for the protein only. Also, U1A-SL2 RNA dissociation kinetics studies with U1A positive charged mutants supported the previously proposed two-step dissociation pathway and demonstrated the importance of positive charge residues. The U1A-SL2 was also investigated in macromolecular crowded buffers were its binding affinity increased. It was also studied inside mammalian cells were it localized in the nucleus and its binding affinity decreased. For the protein folding studies, the extracellular VlsE antigen was found to be destabilized inside mammalian cells opposed to the intracellular PGK enzyme. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Gruebele%2C%20Martin%22%29&pagesize-30">Gruebele, Martin (advisor), Champaign%22%20%2Bcontributor%3A%28%22Martin%20Gruebele%22%29&pagesize-30">Martin Gruebele (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Gennis%2C%20Robert%22%29&pagesize-30">Gennis, Robert (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ha%2C%20Taekjip%22%29&pagesize-30">Ha, Taekjip (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member).

Subjects/Keywords: Protein-RNA interactions; protein folding; fluorescence; fluorescence resonance energy transfer (FRET); fast relaxation imagining (FREI); temperature jump

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Guzman Sanchez, I. (2015). Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/78610

Chicago Manual of Style (16^th Edition):

Guzman Sanchez, Irisbel. “Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/78610.

MLA Handbook (7^th Edition):

Guzman Sanchez, Irisbel. “Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells.” 2015. Web. 14 Apr 2021.

Vancouver:

Guzman Sanchez I. Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/78610.

Council of Science Editors:

Guzman Sanchez I. Kinetics and thermodynamics of protein-RNA interactions and protein folding in vitro and in cells. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/78610

University of Illinois – Urbana-Champaign

7. Maki, Agatha. Analyzing peptide release using mass spectrometry.

Degree: PhD, 0323, 2014, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/49662

► Neuropeptides are cell-to-cell signaling molecules that act as neurotransmitters, neuromodulators and hormones that impact a large variety of neuronal processes. The term neuropeptide refers to… (more)

▼ Neuropeptides are cell-to-cell signaling molecules that act as neurotransmitters, neuromodulators and hormones that impact a large variety of neuronal processes. The term neuropeptide refers to bioactive peptides made in neuron, stored in vesicles, and released into the extracellular space. While many peptides can be detected in a tissue homogenate, these will include processing intermediates and even protein degradation products. It is of great interest in the field of peptidomics to focus on functional characterization of proteins products such as cell-to-cell signaling peptides that are released from specific neuronal tissues, whether a brain region or specific cell. A variety of analytical techniques have emerged over the years to analyze neuropeptide release, and these methods have enabled scientists to characterize thousands of brain peptides. The focus of this research was on using various sampling approaches coupled to matrix-assisted laser desorption/ionization-mass spectrometry (MALDI MS) to analyze neuropeptide release from rodent brains. Chapter 2 is a general overview of the current state of analytical methods used to characterize neuropeptide release from cells to animals. Chapter 3 highlights two methods demonstrating neuropeptide release in a mouse model of fragile X syndrome. Sampling techniques using synaptoneurosomes and ex vivo brain slices were used to show a neuropeptide release deficit in Fmr1 KO mice. Chapter 4 highlights an approach utilizing in vivo microdialysis coupled to offline MALDI MS. This method was used to characterize extracellular peptide release from the hippocampus of rats in response to saline or morphine injection coupled with a spontaneous alternation task. In particular, fibrinopeptide A, a peptide derived from the fibrinogen α-chain, was significantly upregulated in rats exposed to morphine and spontaneous alternation testing. The functional consequence of fibronopeptide A release is still under investigation. The advancement of such analytical approaches to characterize neuropeptide release from a variety of samples ranging from cells to animals enables new discovery efforts for understanding the physiological and behavioral role of unknown peptides. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Gillette%2C%20Martha%20U.%22%29&pagesize-30">Gillette, Martha U. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Galvez%2C%20Roberto%22%29&pagesize-30">Galvez, Roberto (committee member).

Subjects/Keywords: Peptides; Neuropeptides; Peptide Release; Mass Spectrometry; Fragile X Syndrome; Synaptoneurosomes; Brain Slices; Rab3A; Dense-Core Vesicles; Morphine; In Vivo Microdialysis; Hippocampus; Fibrinogen; Fibrinogen-α Chain Peptides; Fibrinopeptide A.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maki, A. (2014). Analyzing peptide release using mass spectrometry. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/49662

Chicago Manual of Style (16^th Edition):

Maki, Agatha. “Analyzing peptide release using mass spectrometry.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/49662.

MLA Handbook (7^th Edition):

Maki, Agatha. “Analyzing peptide release using mass spectrometry.” 2014. Web. 14 Apr 2021.

Vancouver:

Maki A. Analyzing peptide release using mass spectrometry. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/49662.

Council of Science Editors:

Maki A. Analyzing peptide release using mass spectrometry. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/49662

University of Illinois – Urbana-Champaign

8. Miller, Claire. An insulin-like peptide regulates size and adult stem cells in planarians.

Degree: PhD, 0323, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/29421

► Animal growth depends on nutritional intake during development. In many animals, nutritional status is uncoupled from moderation of adult stature after adult size is achieved.… (more)

▼ Animal growth depends on nutritional intake during development. In many animals, nutritional status is uncoupled from moderation of adult stature after adult size is achieved. However, some long-lived animals continue to regulate adult size and fertility in a nutrition-dependent manner. For example, the regenerating flatworm Schmidtea mediterranea becomes smaller, or degrows, during periods of starvation. These animals provide an opportunity to readily observe adult stem cell population dynamics in response to nutritional cues. We explore the role of insulin signaling in S. mediterranea. We disrupt insulin signaling via RNA interference and show that animals, despite eating, degrow similarly to starved animals. Utilizing in situ hybridization and immunofluorescence, we assess cellular changes in proliferative populations including the planarian adult stem cell population (neoblasts) and the germline. Both impaired insulin signaling and nutritional deprivation correlate with decreased neoblast proliferation. Additionally, insulin signaling plays a role in supporting spermatogenesis that is distinct from the effects of starvation. In sum, we demonstrate that insulin signaling is responsible for regulation of adult animal size and tissue homeostasis in an organism with plastic adult size. Importantly, insulin signaling continues to affect stem cell and germline populations in a mature organism. Furthermore, we show that adult organisms can differentially regulate specific cell populations as a result of environmental challenges. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Newmark%2C%20Phillip%20A.%22%29&pagesize-30">Newmark, Phillip A. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Newmark%2C%20Phillip%20A.%22%29&pagesize-30">Newmark, Phillip A. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Raetzman%2C%20Lori%20T.%22%29&pagesize-30">Raetzman, Lori T. (committee member).

Subjects/Keywords: Planarians; Insulin; Adult Stem Cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Miller, C. (2012). An insulin-like peptide regulates size and adult stem cells in planarians. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/29421

Chicago Manual of Style (16^th Edition):

Miller, Claire. “An insulin-like peptide regulates size and adult stem cells in planarians.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/29421.

MLA Handbook (7^th Edition):

Miller, Claire. “An insulin-like peptide regulates size and adult stem cells in planarians.” 2012. Web. 14 Apr 2021.

Vancouver:

Miller C. An insulin-like peptide regulates size and adult stem cells in planarians. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/29421.

Council of Science Editors:

Miller C. An insulin-like peptide regulates size and adult stem cells in planarians. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/29421

9. Betancourt, Mariana Aparicio. Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments.

Degree: PhD, Neuroscience, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/99328

► At the intersection of clinical neuroscience and communication sciences and disorders, this dissertation provides a compilation of studies aimed at examining contextual influences on children's… (more)

▼ At the intersection of clinical neuroscience and communication sciences and disorders, this dissertation provides a compilation of studies aimed at examining contextual influences on children's communication development and the implications of this work for children with neurodevelopmental communication impairments. As discussed in Chapter 1, the present work is grounded in dynamic systems theory of development and a distributed model of communication, which together emphasize development as a context-dependent dynamic multilevel system that unfolds over time and is shaped by a multitude of factors. Neurodevelopmental communication impairments such as speech sound disorder, language disorder, and autism spectrum disorder affect approximately 1.5 - 16% of children, and are associated with academic, socioemotional, and behavioral difficulties. The work in Chapter 2 directly examines a common form of environmental support for children with neurodevelopmental communication impairments, speech-language therapy. More specifically, it assesses the effectiveness of a multimodal, integrated speech-language intervention in facilitating multisyllabic productions in six children 2-4 years of age with various neurodevelopmental disabilities. It uses single-case and within-subject experimental designs to understand individual trajectories and shape clinical practice. As a complement to the behavioral intervention, Chapter 3 of this thesis explores the novel use of noninvasive biosensors to measure electrical conductance across the skin during speech-language and occupational therapy as a potential support for communication in eight children, ages 2-11, with neurodevelopmental disabilities. Skin conductance is mediated by sympathetic cholinergic sudomotor nerve fibers and has been used extensively in the study of psychological states and processes. However, traditionally its use has been limited to highly controlled laboratory settings, whereas the use of such technology within the context of daily activities remains a major challenge. Next, as a means to examine a broader range of environmental influences, Chapter 4 uses a longitudinal monozygotic (MZ) twin difference method, a genetically sensitive design, to examine four candidate nonshared environmental influences on children's language development: birthweight, breastfeeding, and home reading exposure and parenting (M age = 7). This study aims to identify nonshared environmental effects on later language development, at mean ages 10 (n = 115 pairs) and 12 years (n = 108 pairs), across two assessment contexts: standardized testing and narrative language sampling. Finally, Chapter 5 concludes this dissertation by highlighting the need to study a broader range of contextual factors influencing communication development and its associated mechanisms, incorporate diverse and complementary methodologies, and develop effective communication supports for children with neurodevelopmental communication impairments. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22DeThorne%2C%20Laura%22%29&pagesize-30">DeThorne, Laura (advisor), Champaign%22%20%2Bcontributor%3A%28%22DeThorne%2C%20Laura%22%29&pagesize-30">DeThorne, Laura (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Federmeier%2C%20Kara%22%29&pagesize-30">Federmeier, Kara (committee member), Champaign%22%20%2Bcontributor%3A%28%22Petrill%2C%20Stephen%20A.%22%29&pagesize-30">Petrill, Stephen A. (committee member).

Subjects/Keywords: communication development; neurodevelopmental communication impairments; single-case design; electrodermal activity; monozygotic twin difference method; quantile regression

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Betancourt, M. A. (2017). Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99328

Chicago Manual of Style (16^th Edition):

Betancourt, Mariana Aparicio. “Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/99328.

MLA Handbook (7^th Edition):

Betancourt, Mariana Aparicio. “Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments.” 2017. Web. 14 Apr 2021.

Vancouver:

Betancourt MA. Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/99328.

Council of Science Editors:

Betancourt MA. Environmental influences on communication development: Implications for children with neurodevelopmental communication impairments. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99328

University of Illinois – Urbana-Champaign

10. Thomas, Alvin G. Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration.

Degree: PhD, Cell and Developmental Biology, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/90910

► The larvae of Xenopus laevis can naturally regenerate a lost lens from the outer cornea epithelium after it is triggered to do so by signals… (more)

▼ The larvae of Xenopus laevis can naturally regenerate a lost lens from the outer cornea epithelium after it is triggered to do so by signals from the neural retina. The signals have been widely studied, and FGFs are reported to play a key role in causing the cornea to transform into a lens. However, the factors that make the cornea itself competent to respond to these signals are unknown. Understanding the factors that underlie regeneration competency is the key to granting otherwise ordinary tissues the ability to regenerate, including in our own bodies. Thus, the focus of this work has been on the cornea, in order to unravel the signaling schemes that operate within it. The Retinoic Acid (RA) signaling pathway is a major cellular signaling pathway involved in development, organogenesis, and regeneration. It was strongly implicated in the regeneration of the lens in another model system, the newt, where retinal signals trigger the dorsal region of the iris to differentiate and give rise to a lens. Antagonism of RA signaling was shown to inhibit lens regeneration, demonstrating its necessity. We investigated whether the same was true in Xenopus. We inhibited RA signaling using inhibitors of RA synthesizing enzymes, and of the RAR nuclear receptors. In all cases we found there to be no effect on regeneration. We validated that the drug treatments were meaningful by observing, via qPCR, a decrease in the expression cyp26a1, a well-established marker of RA signaling. We also examined the expression of multiple RA signaling pathway members both in control corneas and in corneas harvested in the first 4 days following lentectomy. In both these normal and regenerating tissues we found the expression of cyp26 genes, which encode the RA metabolizing enzyme CYP26. In light of this finding, we assessed whether CYP26 was necessary for supporting lens regeneration. In contrast to the experiment described above, exogenous addition of an antagonist of CYP26 greatly inhibited lens regeneration. Likewise, a synthetic retinoid that activates RA signaling without being metabolized by CYP26 also inhibited regeneration, as did excess exogenous RA. In all treatments, we observed profound upregulation of the RA signaling marker cyp26a1. Taken together, we demonstrated that the action of CYP26 is necessary for lens regeneration, which implies a necessity to attenuate RA signaling by metabolism in order for lens regeneration to occur in Xenopus. This represents a species-specific difference in the signaling schemes that underlie lens regeneration, and a previously undescribed role for CYP26 in regeneration. Using immunohistochemistry and a whole-cornea mounting technique, we observed the widespread expression of RALDH and CYP26 enzymes within the corneal layers under a confocal microscope. We next investigated the possible mechanistic roles of CYP26 that could explain its necessity in lens regeneration. We assessed whether RA signaling regulated cell proliferation in the cornea by quantifying changes in cell division following… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Henry%2C%20Jonathan%20J.%22%29&pagesize-30">Henry, Jonathan J. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Brieher%2C%20William%20M.%22%29&pagesize-30">Brieher, William M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Chen%2C%20Jie%22%29&pagesize-30">Chen, Jie (committee member), Champaign%22%20%2Bcontributor%3A%28%22Raetzman%2C%20Lori%20T.%22%29&pagesize-30">Raetzman, Lori T. (committee member).

Subjects/Keywords: Xenopus; regeneration; cornea; CYP26

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomas, A. G. (2016). Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/90910

Chicago Manual of Style (16^th Edition):

Thomas, Alvin G. “Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/90910.

MLA Handbook (7^th Edition):

Thomas, Alvin G. “Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration.” 2016. Web. 14 Apr 2021.

Vancouver:

Thomas AG. Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/90910.

Council of Science Editors:

Thomas AG. Investigating the role of CYP26 and retinoic acid signaling regulation in vertebrate cornea and lens regeneration. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/90910

University of Illinois – Urbana-Champaign

11. Belagodu, Amogh P. Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model.

Degree: PhD, Neuroscience, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/97769

► Fragile X Syndrome (FXS) is the most common form of inherited mental retardation affecting 1:3600 males and 1:8000 females (Cornish et al., 2008). The primary… (more)

▼ Fragile X Syndrome (FXS) is the most common form of inherited mental retardation affecting 1:3600 males and 1:8000 females (Cornish et al., 2008). The primary cause is a silencing of the FMR1 gene, via increased CGG trinucleotide repeats, which encodes for the Fragile X Mental Retardation Protein (FMRP) (Santoro et al., 2012). The current prevailing theory for the molecular mechanism mediating FXS molecular, physical, and behavioral phenotypes is centered around dysregulation of down-stream products of the metabotropic glutamate receptor (mGluR) (mGluR Theory) (Bear et al., 2004). However recent clinical trials using mGluR inhibitors have all failed, attributing to various factors such as a need for optimized dosage, developmental time for intervention, better metrics for human studies, and most prominently complexity of the mGluR pathway (Scharf et al., 2015). With this ubiquitous failure of mGluR inhibitors, new thrusts have been initiated to determine which of the downstream components of the mGluR pathway is leading to and causing FXS phenotypes. In the pursuit of isolating and determining potential causes/therapeutic targets for intervention, the current dissertation explored the role of vascular endothelial growth factor A (VEGF-A), a downstream component of mGluR. This dissertation will outline a series of studies where we demonstrate that VEGF-A is elevated in adult FXS mice and that modulation of this elevated VEGF-A can attenuate many FXS abnormalities. In Chapter 2, we obtain developmental expression profiles of the VEGF Family of molecules and their Receptors to help understand where this dysregulation occurs and how it manifests throughout development. Next, Chapter 3 we found that through blocking VEGF-A, Synapsin-1 levels (a presynaptic marker) were reduced to wildtype (WT) levels and resulted in a rescue of physical and behavioral FXS phenotypes (Belagodu et al., 2017). Chapter 4 explored and characterized ultrasonic vocalization (USV) abnormalities in FXS mice to find more human relevant behavioral metrics to assess potential therapeutic interventions (Belagodu et al., 2016). Utilizing these studies, Chapter 5 assessed the extent to which blocking VEGF-A can rescue many FXS behavioral abnormalities, such as USV production profiles and behavioral measures of locomotion, anxiety, and stereotypy. Finally, to determine which of the VEGF Receptors are driving the beneficial effects of blocking VEGF-A, Chapter 6 utilized VEGF Receptor specific blockers to assess similar molecular and behavioral properties examined following blocking of VEGF-A. Overall these studies will help to provide further insight into which of the downstream components of the mGluR pathway are playing a role in FXS. In particular these studies will establish which of the VEGF Family and Receptors are driving FXS abnormalities and thus may serve as a viable target for future FXS therapeutics. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Galvez%20%2C%20Roberto%22%29&pagesize-30">Galvez , Roberto (advisor), Champaign%22%20%2Bcontributor%3A%28%22Galvez%20%2C%20Roberto%22%29&pagesize-30">Galvez , Roberto (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Wickesberg%2C%20Robert%22%29&pagesize-30">Wickesberg, Robert (committee member), Champaign%22%20%2Bcontributor%3A%28%22Llano%2C%20Daniel%22%29&pagesize-30">Llano, Daniel (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member).

Subjects/Keywords: Fragile X Syndrome (FXS); Fragile X Mental Retardation Protein (FMRP); Vascular endothelial growth factor (VEGF); Autism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Belagodu, A. P. (2017). Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/97769

Chicago Manual of Style (16^th Edition):

Belagodu, Amogh P. “Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/97769.

MLA Handbook (7^th Edition):

Belagodu, Amogh P. “Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model.” 2017. Web. 14 Apr 2021.

Vancouver:

Belagodu AP. Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/97769.

Council of Science Editors:

Belagodu AP. Analysis of the expression and effects of vascular endothelial growth factor family of molecules on Fragile X Syndrome abnormalities in a mouse model. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/97769

University of Illinois – Urbana-Champaign

12. Bhate, Amruta. Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration.

Degree: PhD, Biochemistry, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/99467

► Analysis of metazoan genomes has led to the extraordinary observation that mammals contain only ~25000 protein-coding genes. Therefore, post-transcriptional gene regulatory mechanisms (PTGRMs) are thought… (more)

▼ Analysis of metazoan genomes has led to the extraordinary observation that mammals contain only ~25000 protein-coding genes. Therefore, post-transcriptional gene regulatory mechanisms (PTGRMs) are thought to be crucial for generating the diverse proteome required to support their high cellular complexity. Alternative splicing (AS), the most common PTGRM, is a process by which the exons of a pre-mRNA are spliced into different arrangements to produce structurally and functionally distinct mature mRNAs thereby contributing to the transcriptome complexity. Regulated AS events are known to play a determinative role in the brain, heart and skeletal muscle development; however, regulation of splicing or its function in hepatic growth and maturation is not well understood. The mammalian liver is a major metabolic organ responsible for a variety of functions and has an exceptional capacity for regeneration. Liver undergoes dramatic transitions with regards to structure and function during postnatal development and during regeneration implying that intricate regulatory mechanisms must control these processes. Signaling and transcriptional networks that regulate postnatal liver development are extensively studied, but the role of post-transcriptional mechanisms is poorly explored. My goal thus was to identify conserved AS networks in postnatal liver development and establish relationships between these splicing changes and their putative regulators, RNA Binding proteins, in normal liver maturation and regeneration. In the second chapter of the thesis, I studied the changes occurring in the liver transcriptome during postnatal periods of development. To characterize the conserved AS program during mammalian liver maturation, high throughput RNA-seq of mouse livers at E18 (embryonic day 18), P14 (postnatal day 14), P28 and P90 was performed. We observed ~5000 genes change in mRNA abundance, ~530 genes change in AS and ~200 genes change in alternative polyadenylation with minimal overlap among these categories. This indicates that postnatal liver maturation is accomplished by three separate modes of regulatory mechanisms. Analysis of AS at intervening timepoints (E16, E18, P0, P2, P7, P14, P28 and P90) showed that postnatal shift in AS is temporally coordinated and subsets of AS events follow distinct patterns of splicing change grouped as early (E16-P2), late (P14-P90) or biphasic (E18-P7 and P7-P90). As the liver is actively going through the process of maturation, we wanted to understand whether the changes occurring in the transcriptome are a result of the maturing parenchyma or due to a cell population change occurring in the liver. Comparison of AS in purified hepatocytes (Hep), major cell type of the liver, and the other cell types, non-parenchymal cells (NPCs) showed that a majority of AS are cell-type specific with most being Hep-specific. These AS transitions are evolutionarily conserved in mice and humans. RNA binding proteins (RBPs) play pivotal roles in regulating splicing transitions by binding near the… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Kalsotra%2C%20Auinash%22%29&pagesize-30">Kalsotra, Auinash (advisor), Champaign%22%20%2Bcontributor%3A%28%22Kalsotra%2C%20Auinash%22%29&pagesize-30">Kalsotra, Auinash (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Martinis%2C%20Susan%22%29&pagesize-30">Martinis, Susan (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Zhang%2C%20Kai%22%29&pagesize-30">Zhang, Kai (committee member).

Subjects/Keywords: Alternative splicing; Ribonucleic acid (RNA); Epithelial Splicing Regulatory Protein 2 (ESRP2); Liver development; Liver maturation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bhate, A. (2017). Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99467

Chicago Manual of Style (16^th Edition):

Bhate, Amruta. “Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/99467.

MLA Handbook (7^th Edition):

Bhate, Amruta. “Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration.” 2017. Web. 14 Apr 2021.

Vancouver:

Bhate A. Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/99467.

Council of Science Editors:

Bhate A. Identification of a conserved alternative mRNA splicing program that supports hepatic growth and maturation during development and regeneration. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99467

University of Illinois – Urbana-Champaign

13. Zong, Xinying. Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression.

Degree: PhD, Cell and Developmental Biology, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/97563

► Recent advances in transcriptome analysis have revealed that a large proportion of the mammalian genome is transcribed. Thousands of these transcripts are classified as long… (more)

▼ Recent advances in transcriptome analysis have revealed that a large proportion of the mammalian genome is transcribed. Thousands of these transcripts are classified as long non-coding RNAs (lncRNAs), with size larger than 200 nucleotides, but very few have been functionally characterized. Here, I detail a journey of the discovery and analysis of lncRNAs in gene expression control and cell cycle progression, beginning from the characterization of a mutual regulation between lncRNA MALAT1 and its natural antisense transcript TALAM1, followed by the identification and functional characterization of lncRNAs involved in cell cycle progression. The mutual regulation between MALAT1 and TALAM1 presents a novel feed-forward positive regulatory loop at the MALAT1 locus where MALAT1 positively regulates the transcription and stability of TALAM1, and TALAM1 in turn promotes the processing and maturation events of MALAT1 which are essential to maintain the high cellular levels of MALAT1. In the characterization of functional lncRNAs in cell cycle progression, I focus on an S phase-upregulated lncRNA, termed S7, and demonstrate that it plays crucial roles in cell cycle progression and tumorigenicity, through regulating the expression of genes in the cellular proliferation network including the Hippo signaling pathway. Altogether, these studies support a model whereby pervasive lncRNA transcripts, previously regarded as transcriptional byproducts, function through diverse mechanisms as critical regulators of gene expression and the vital cell cycle processes. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Prasanth%2C%20K.V.%22%29&pagesize-30">Prasanth, K.V. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Chen%2C%20Jie%22%29&pagesize-30">Chen, Jie (committee member), Champaign%22%20%2Bcontributor%3A%28%22Schuler%2C%20Mary%20A.%22%29&pagesize-30">Schuler, Mary A. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Katzenellenbogen%2C%20Benita%20S.%22%29&pagesize-30">Katzenellenbogen, Benita S. (committee member).

Subjects/Keywords: Long noncoding RNA; Metastasis associated lung adenocarcinoma transcript 1 (MALAT1); Cell cycle; Natural antisense transcript

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zong, X. (2017). Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/97563

Chicago Manual of Style (16^th Edition):

Zong, Xinying. “Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/97563.

MLA Handbook (7^th Edition):

Zong, Xinying. “Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression.” 2017. Web. 14 Apr 2021.

Vancouver:

Zong X. Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/97563.

Council of Science Editors:

Zong X. Discovery and analysis of long noncoding RNAs in gene expression control and cell cycle progression. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/97563

University of Illinois – Urbana-Champaign

14. Qavi, Abraham. The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators.

Degree: PhD, 0335, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/34548

► With the sequencing of the human genome effectively complete, the development of high throughput and rapid biomarker assays has become a major focus of research… (more)

▼ With the sequencing of the human genome effectively complete, the development of high throughput and rapid biomarker assays has become a major focus of research as the biomedical community seeks to translate genomic insight into clinical improvements in patient care. One class of molecules that has attracted considerable attention is microRNAs (miRNAs). miRNAs are 19-24 nucleotide, short post-transcriptional regulators, involved in a number of cellular processes including proliferation, apoptosis, and development. They are also implicated in a variety of diseases, such as cancer, neurodegenerative disorders, and diabetes. Despite their importance in a variety of cellular functions as well as their potential for disease diagnostics, miRNAs are incredibly difficult to detect. Their short length makes it difficult to attach any label (fluorescent or radioactive) without introducing a signal bias to the measurement. Additionally, traditional PCR-based methods for RNA detection cannot be utilized, as the primers themselves are often the lengths of the miRNAs. To further complicate matters, miRNAs act in highly complex fashion. A single gene can be regulated by multiple miRNAs, and a single miRNA can regulate multiple genes. In order to fully understand the role miRNAs play, as well as utilize their potential as informative biomarkers, a multiplexed analysis is necessary. We have developed a sensing platform based on arrays of silicon photonic microring resonators that is highly amenable for the quantitative, multiplexed detection of nucleic acids, in particular, miRNAs. We begin by demonstrating a label-free method for the quantitative, multiplexed detection of miRNAs. We further extend this technique by utilizing S9.6, an unique antibody against DNA:RNA heteroduplexes, that significantly improves both our sensitivity and specificity without the introduction of a signal bias. Furthermore, we present an incredibly simple but elegant, method for distinguish single-nucleotide polymorphisms based on isothermal desorption. This not only offers potential applications for screening genomic SNPs, but more importantly, provides a framework to begin to distinguish closely related miRNAs. Future work will focus on the development of new amplification schemes to further increase the sensitivity of the microring resonator platform towards miRNAs, as well as applying this work towards a variety of interesting biological systems and clinical situations. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Bailey%2C%20Ryan%20C.%22%29&pagesize-30">Bailey, Ryan C. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Bailey%2C%20Ryan%20C.%22%29&pagesize-30">Bailey, Ryan C. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Suslick%2C%20Kenneth%20S.%22%29&pagesize-30">Suslick, Kenneth S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (committee member).

Subjects/Keywords: Sensors; microRibonucleic acid (microRNA); Photonic Resonators; Biosensors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Qavi, A. (2012). The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/34548

Chicago Manual of Style (16^th Edition):

Qavi, Abraham. “The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/34548.

MLA Handbook (7^th Edition):

Qavi, Abraham. “The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators.” 2012. Web. 14 Apr 2021.

Vancouver:

Qavi A. The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/34548.

Council of Science Editors:

Qavi A. The development of new sensing methodologies for nucleic acids using arrays of silicon photonic microring resonators. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/34548

University of Illinois – Urbana-Champaign

15. Lin, Ya-Chi. MicroRNA gene expression in the zebra finch brain.

Degree: PhD, 4094, 2013, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/42462

► Songbirds such as zebra finches communicate via learned vocalizations (songs) and studies have shown that experiencing song playback triggers complex genomic responses in the zebra… (more)

▼ Songbirds such as zebra finches communicate via learned vocalizations (songs) and studies have shown that experiencing song playback triggers complex genomic responses in the zebra finch auditory forebrain. MicroRNAs (miRNAs or miRs) are important regulators of gene expression which may coordinate complex biological processes through post-transcriptional mechanisms. This dissertation aims to explore the potential roles of miRs in the genomic response to song. This study began with a bioinformatic analysis of published microarray data and qPCR analysis of a specific conserved miR (miR-124) in zebra finch auditory forebrain, elements of which contributed to the primary paper describing the zebra finch genome (Warren et al. 2010). These preliminary studies are described in the Introduction to this thesis. Chapter 2 then presents a full de novo characterization of miRs in the songbird brain and demonstrates that song exposure has effects on several. This has now been published as Gunaratne, Lin et al. 2011 (co-first authors). A significant outcome of Chapter 2 was the identification of a novel sex-linked miR, miR-2954. Chapter 3 describes the tissue, cellular and subcellular distribution of miR-2954 and localizes it to subsets of cells in the brain. An antisense inhibitor of miR-2954 was then applied to a zebra finch cell line followed by RNA-seq analysis to test the hypothesis that changes in miR-2954 levels lead to changes in the network of genes expressed. The results confirm this hypothesis and suggest that the initial song-induced decline in miR-2954 expression described in Chapter 2 may help reprogram gene expression networks to support the metabolic changes associated with song habituation (Dong et al., 2009). This thesis research helps better understand the transcriptome of songbird brain and establishes novel roles for microRNAs in song perception, discrimination and memory. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Clayton%2C%20David%20F.%22%29&pagesize-30">Clayton, David F. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Schuler%2C%20Mary%20A.%22%29&pagesize-30">Schuler, Mary A. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Clayton%2C%20David%20F.%22%29&pagesize-30">Clayton, David F. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Robinson%2C%20Gene%20E.%22%29&pagesize-30">Robinson, Gene E. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Prasanth%2C%20Kannanganattu%20V.%22%29&pagesize-30">Prasanth, Kannanganattu V. (committee member).

Subjects/Keywords: MicroRNA; Zebra Finch; Brain; Cell Line; RNA-seq; Genomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lin, Y. (2013). MicroRNA gene expression in the zebra finch brain. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/42462

Chicago Manual of Style (16^th Edition):

Lin, Ya-Chi. “MicroRNA gene expression in the zebra finch brain.” 2013. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/42462.

MLA Handbook (7^th Edition):

Lin, Ya-Chi. “MicroRNA gene expression in the zebra finch brain.” 2013. Web. 14 Apr 2021.

Vancouver:

Lin Y. MicroRNA gene expression in the zebra finch brain. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2013. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/42462.

Council of Science Editors:

Lin Y. MicroRNA gene expression in the zebra finch brain. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2013. Available from: http://hdl.handle.net/2142/42462

University of Illinois – Urbana-Champaign

16. Soto, Carolina. Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma.

Degree: PhD, 0323, 2013, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/42476

► Over the past few decades, our knowledge of tumor immunology and the role antitumor immune responses play in tumor recognition and eradication has greatly increased… (more)

▼ Over the past few decades, our knowledge of tumor immunology and the role antitumor immune responses play in tumor recognition and eradication has greatly increased and led to immunotherapies being investigated as a promising strategy for cancer treatment. Current clinical studies with various immunotherapies have shown promising results, including therapy with adoptive cell transfer (ACT) of T lymphocytes. T cell immunotherapy is highly attractive because T cells have the ability to selectively recognize and destroy malignant neoplastic cells. Although a promising approach, one of the limitations encountered clinically is the difficulty isolating and expanding tumor-specific T lymphocytes from patients. This limitation may be circumvented by genetically engineering T lymphocytes to express antigen-specific T cell receptors (TCR). The goal of this work was to investigate adoptive T cell therapy using primary T lymphocytes modified to express genetically engineered T cell receptors against murine melanoma and glioma. In chapter 2, a new SIYRYYGL (SIY) peptide-expressing murine glioma cell line (GL261-SIY) was generated as a model to investigate strategies to improve adoptive T cell therapy for brain tumors. Our findings demonstrated successful development of this new cell line as determined by surface expression of SIY antigen and effective peptide presentation to T cells in vitro resulting in T cell activation and induction of cytotoxic T cell activity. In vivo, T cell infiltration of brain tumors and long-term survival benefits with adoptive transfer of transgenic and TCR-modified T cells was examined. In chapter 3, ACT of MHC class I-redirected CD4+ helper T cells was evaluated in a subcutaneous murine melanoma tumor model. TCRs specific for MHC class I-restricted antigens were introduced into CD4+ cells to assess whether high affinity TCRs, in the nanomolar affinity range, could provide an enhanced antitumor response compared to micromolar affinity wild type TCRs. Our study revealed improved survival and long-term immunity with CD4+ T cells expressing high affinity MHC class I-restricted TCRs. T cell therapy with CD4+ T cells (alone or in combination with CD8+ T cells) for the treatment of murine glioma and melanoma resulted in development of graft-versus-host disease (GVHD) in some mice. In chapter 4, mice affected by GVHD were studied in detail. Clinical signs, physical GVHD presentation, and GVHD-associated histopathology were dissected to better understand the mechanisms and factors involved in the in vivo interactions between the transferred T cell populations and the affected host tissue. Overall, this work examined adoptive therapy with ex vivo activated T cells expressing wild type or high affinity genetically engineered TCRs for the treatment of established tumors in mice, as well as GVHD development secondary to T cell therapy. The findings in these collective studies demonstrate that immunotherapy with CD8+ and CD4+ T cells expressing gene-modified TCRs is a distinct strategy to optimally exploit… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Roy%2C%20Edward%20J.%22%29&pagesize-30">Roy, Edward J. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Roy%2C%20Edward%20J.%22%29&pagesize-30">Roy, Edward J. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Kranz%2C%20David%20M.%22%29&pagesize-30">Kranz, David M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Olivero%2C%20William%20C.%22%29&pagesize-30">Olivero, William C. (committee member).

Subjects/Keywords: Cancer Immunotherapy; Tumor Targeting; T cell receptors (TCR); T cell; Melanoma; Adoptive Cell Therapy; Glioma

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Soto, C. (2013). Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/42476

Chicago Manual of Style (16^th Edition):

Soto, Carolina. “Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma.” 2013. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/42476.

MLA Handbook (7^th Edition):

Soto, Carolina. “Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma.” 2013. Web. 14 Apr 2021.

Vancouver:

Soto C. Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2013. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/42476.

Council of Science Editors:

Soto C. Adoptive cell therapy using primary T lymphocytes with genetically engineered T cell receptors against melanoma and glioma. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2013. Available from: http://hdl.handle.net/2142/42476

University of Illinois – Urbana-Champaign

17. Thomas, Diana L. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.

Degree: PhD, 0323, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18568

► Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific… (more)

▼ Adoptive immunotherapy and oncolytic virotherapy are two promising strategies for treating primary and metastatic malignant brain tumors. We demonstrate the ability of adoptively transferred tumor-specific T cells to rapidly mediate the clearance of established brain tumors in several mouse models. Similar to the clinical situation, tumor recurrences are frequent and result from immune editing of tumors. T cells can eliminate antigen-expressing tumor cells but are not effective against antigen loss variant (ALV) cancer cells that multiply and repopulate a tumor. We show that the level of tumor antigen present affects the success of adoptive T cell therapy. When high levels of antigen are present, tumor stromal cells such as microglia and macrophages present tumor peptide on their surface. As a result, T cells directly eliminate cancer cells and cross-presenting stromal cells and indirectly eliminate ALV cells. We were able to show the first direct evidence of tumor antigen cross-presentation by CD11b+ stromal cells in the brain using soluble, high-affinity T cell receptor monomers. Strategies that target brain tumor stroma or increase antigen shedding from tumor cells leading to increased crosspresentation by stromal cells may improve the clinical success of T cell adoptive therapies. We evaluated one potential strategy to complement adoptive T cell therapy by characterizing the oncolytic effects of myxoma virus (MYXV) in a syngeneic mouse brain tumor model of metastatic melanoma. MYXV is a rabbit poxvirus with strict species tropism for European rabbits. MYXV can also infect mouse and human cancer cell lines due to signaling defects in innate antiviral mechanisms and hyperphosphorylation of Akt. MYXV kills B16.SIY melanoma cells in vitro, and intratumoral injection of virus leads to robust, selective and transient infection of the tumor. We observed that virus treatment recruits innate immune cells iii to the tumor, induces TNFα and IFNβ production in the brain, and results in limited oncolytic effects in vivo. To overcome this, we evaluated the safety and efficacy of co-administering 2C T cells, MYXV, and neutralizing antibodies against IFNβ. Mice that received the triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Based on these findings, methods to enhance viral replication in the tumor and limit immune clearance of the virus will be pursued. We conclude that myxoma virus should be further explored as a vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Roy%2C%20Edward%20J.%22%29&pagesize-30">Roy, Edward J. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Roy%2C%20Edward%20J.%22%29&pagesize-30">Roy, Edward J. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Kranz%2C%20David%20M.%22%29&pagesize-30">Kranz, David M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22MacNeill%2C%20Amy%20L.%22%29&pagesize-30">MacNeill, Amy L. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22George%2C%20Julia%20M.%22%29&pagesize-30">George, Julia M. (committee member).

Subjects/Keywords: brain tumors; immunotherapy; oncolytic virotherapy; Melanoma; Adoptive T Cell Therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomas, D. L. (2011). Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18568

Chicago Manual of Style (16^th Edition):

Thomas, Diana L. “Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/18568.

MLA Handbook (7^th Edition):

Thomas, Diana L. “Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors.” 2011. Web. 14 Apr 2021.

Vancouver:

Thomas DL. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/18568.

Council of Science Editors:

Thomas DL. Evaluation of Adoptive T Cell Therapy and Oncolytic Virotherapy for Treatment of Brain Tumors. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18568

University of Illinois – Urbana-Champaign

18. Sun, Chia-Yun. Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations.

Degree: PhD, 4094, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18617

► Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is critical for development of the vertebrate musculature and vasculature, however its precise molecular function is unknown.… (more)

▼ Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) is critical for development of the vertebrate musculature and vasculature, however its precise molecular function is unknown. Because of its location 125 kb proximal to the FSHD1A lesion, a deletion in a subtelomeric macrosatellite DNA repeat array, it has been considered a candidate for mediating FSHD pathophysiology. This study investigates FRG1???s function to provide insight into FRG1???s role in vertebrate muscle development. First, we focus on the subcellular localization of FRG1 and identified FRG1 as a dynamic nuclear, cytoplamic, and sarcomeric protein. During myoblast differentiation, FRG1???s subcellular distribution changed dramatically with FRG1 eventually associating with the matured Z-discs. The Z-disc localization is confirmed in mouse myofibers, suggesting FRG1 may have a muscle-specific function involved in sarcomere maintenance or signaling. The nuclear fraction of the endogenous FRG1 is localized in nucleoli, Cajal bodies, and actively transcribed chromatin associated with nascent RNA transcripts, supporting a function in RNA biogenesis. Furthermore, we show that FRG1 interacts specifically with RNA in vitro, associates with mRNA in vivo, and directly interacts with the TAP mRNA export receptor. FRG1 also exists in a cytoplasmic pool that is dependent on an intact actin cytoskeleton for its localization and we demonstrate FRG1 itself is an actin binding protein. These data provide the first biochemical activities for human FRG1 and indicate that FRG1 dynamically shuttles between the nucleus and cytoplasm and is involved in aspects of RNA biogenesis, potentially including mRNA transport and localization. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Jones%2C%20Peter%20L.%22%29&pagesize-30">Jones, Peter L. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Bellini%2C%20Michel%22%29&pagesize-30">Bellini, Michel (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Jones%2C%20Peter%20L.%22%29&pagesize-30">Jones, Peter L. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Brieher%2C%20William%20M.%22%29&pagesize-30">Brieher, William M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Nardulli%2C%20Ann%20M.%22%29&pagesize-30">Nardulli, Ann M. (committee member).

Subjects/Keywords: FSHD region gene 1 (FRG1); RNA biogenesis; mRNA transport; Actin; Z-disc; Myogenesis; Facioscapulohumeral muscular dystrophy (FSHD); Muscular dystrophy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sun, C. (2011). Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18617

Chicago Manual of Style (16^th Edition):

Sun, Chia-Yun. “Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/18617.

MLA Handbook (7^th Edition):

Sun, Chia-Yun. “Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations.” 2011. Web. 14 Apr 2021.

Vancouver:

Sun C. Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/18617.

Council of Science Editors:

Sun C. Human FRG1 is an Actin-Bundling and a RNA-Associated Protein with Distinct Subcellular Localizations. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18617

University of Illinois – Urbana-Champaign

19. Shah, Samit M. Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse.

Degree: PhD, 0323, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18622

► Profound sensorineural hearing loss affects nearly 700,000 people in the United States and cannot be treated with hearing aids. Many listeners receive cochlear implants that… (more)

▼ Profound sensorineural hearing loss affects nearly 700,000 people in the United States and cannot be treated with hearing aids. Many listeners receive cochlear implants that can restore hearing by directly stimulating spiral ganglion neurons with electrodes implanted in the inner ear. However, the success of cochlear implants in older patients is limited by the reduced availability of surviving neurons that can be targeted with electrical stimulation, the distance between the implanted electrode array and the neuron cell bodies, and the formation of scar tissue at the interface between the remaining nerve fibers and the implanted electrodes. An approach to improving the performance of cochlear implants is to stimulate and guide neurite outgrowth from spiral ganglion neurons toward electrodes to form private channels of communication between the cochlear implant and the targeted neuronal populations. To date, there has been little investigation into the roles of Wnt proteins signaling through their Frizzled receptors in neuro-regeneration in the adult inner ear despite their involvement in axon guidance, dendrite morphogenesis, and synapse formation throughout the developing nervous system. In Chapter II, I show the differential expression of several Frizzled receptors in the spiral ganglion neurons of the adult mouse cochlea in an apical-to-basal gradient, as well as the expression of Frizzled 9 protein in growth cones of regenerating neurites in vitro. Then, in Chapter III, I demonstrate that the activation of canonical Wnt signaling by lithium modulates growth cone mediated neurite outgrowth from adult spiral ganglion neurons by altering the neuronal cytoskeleton. This dissertation research demonstrates that Frizzled-Wnt signaling represents a potential regenerative pathway for the restoration of neuronal connections in the adult inner ear after injury. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Feng%2C%20Albert%20S.%22%29&pagesize-30">Feng, Albert S. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Feng%2C%20Albert%20S.%22%29&pagesize-30">Feng, Albert S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Kemper%2C%20Byron%20W.%22%29&pagesize-30">Kemper, Byron W. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Kollmar%2C%20Richard%22%29&pagesize-30">Kollmar, Richard (committee member), Champaign%22%20%2Bcontributor%3A%28%22Raetzman%2C%20Lori%20T.%22%29&pagesize-30">Raetzman, Lori T. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member).

Subjects/Keywords: Cochlea; wingless-related mouse mammary tumor virus integration site (Wnt); Spiral Ganglion; Neurons; Regeneration; Growth Cone; Frizzled (Fzd); Cell Surface Receptors; Cochlear Implant; In-Situ Hybridization; Catenin; glycogen synthase kinase (GSK); Lithium; Auditory; Hair Cell; adenomatous polyposis coli (APC); MAP-1B; Kinase; Intracellular

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shah, S. M. (2011). Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18622

Chicago Manual of Style (16^th Edition):

Shah, Samit M. “Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/18622.

MLA Handbook (7^th Edition):

Shah, Samit M. “Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse.” 2011. Web. 14 Apr 2021.

Vancouver:

Shah SM. Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/18622.

Council of Science Editors:

Shah SM. Wnt Signaling in Growth Cone Mediated Neurite Outgrowth from Spiral Ganglion Neurons in the Adult Mouse. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18622

University of Illinois – Urbana-Champaign

20. Mustroph, Martina. Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.

Degree: PhD, 0323, 2015, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/72960

► Treatments for drug abuse and addiction remain largely ineffective. Recent studies in both the human and rodent literature suggest that exercise-based interventions for drug addiction… (more)

▼ Treatments for drug abuse and addiction remain largely ineffective. Recent studies in both the human and rodent literature suggest that exercise-based interventions for drug addiction have positive outcomes. Exercise has many effects in the brain. The mechanism by which exercise achieves positive outcomes relevant to drug abuse and addiction is not known. One idea is that exercise extends plasticity to the brain that helps to weaken drug-context associations underlying drug abuse and addiction. It is known that exercise increases hippocampal neurogenesis. However, recently, conflicting reports have been published showing hippocampal neurogenesis to either be involved in or not contributory to learning and memory, and so the role of hippocampal neurogenesis in weakening learned drug-context associations remains unclear. The goal of my dissertation is to identify and evaluate select potential mechanisms causally related to accelerated extinction of conditioned place preference (CPP) for cocaine from exercise in male C57BL/6J mice. Since the conditioned place preference paradigm represents the major behavioral assay I employ in the proposed experiments, Chapter 1 presents a review of the relevant conditioned place preference literature. Chapter 2 examines the hypothesis that timing of exercise relative to conditioning has opposing effects on cocaine CPP in male C57BL/6J mice, and that exercise induces hippocampal neurogenesis. The main findings were that wheel running accelerated extinction of CPP when running occurred entirely after drug conditioning, whereas running delayed extinction when administered before conditioning, and that running approximately doubled adult hippocampal neurogenesis. Chapter 3 assesses the relative contribution of running versus enrichment to the neurogenic and pro-cognitive effects of an enriched environment in male C57BL/6J mice. The main finding was that an enriched environment devoid of running wheels did not significantly up-regulate hippocampal neurogenesis or improve behavioral performance on a spatial learning task, although running approximately doubled adult hippocampal neurogenesis. The finding that only running bestowed significant neurogenic and behavioral effects leaves open the possibility environmental enrichment promotes other types of neural plasticity that may make it a suitable substitute for running as an intervention in other domains. Therefore, Chapter 4 investigates the possibility that environmental enrichment, like running, can accelerate extinction of CPP. Results suggest that environmental enrichment does not effectively accelerate extinction of CPP, nor does it significantly increase hippocampal neurogenesis. Chapter 5 directly tests the hypothesis that new neurons from running are necessary for accelerated extinction of cocaine CPP from running. Chapter 6 attempts to answer the question of whether there are neuropeptides that are differentially induced in runners versus sedentary C57BL/6J mice in the amygdala and hippocampus after exposure to a drug-associated… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Rhodes%2C%20Justin%20S.%22%29&pagesize-30">Rhodes, Justin S. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Rhodes%2C%20Justin%20S.%22%29&pagesize-30">Rhodes, Justin S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Gulley%2C%20Joshua%20M.%22%29&pagesize-30">Gulley, Joshua M. (committee member).

Subjects/Keywords: cocaine; conditioned place preference; exercise; hippocampal neurogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mustroph, M. (2015). Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/72960

Chicago Manual of Style (16^th Edition):

Mustroph, Martina. “Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.” 2015. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/72960.

MLA Handbook (7^th Edition):

Mustroph, Martina. “Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice.” 2015. Web. 14 Apr 2021.

Vancouver:

Mustroph M. Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2015. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/72960.

Council of Science Editors:

Mustroph M. Effects of physical exercise and exercise-induced adult hippocampal neurogenesis on conditioned place preference for cocaine in mice. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2015. Available from: http://hdl.handle.net/2142/72960

University of Illinois – Urbana-Champaign

21. Scavuzzo, Claire. Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling.

Degree: PhD, 0323, 2014, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/50428

► Our motto “Use it and boost it” suggests that stimulating experiences enhance neural functioning. Previous work has shown that cognition is enhanced by mental and… (more)

Subjects/Keywords: hippocampus; striatum; place learning; response learning; multiple memory systems; glycogen synthase kinase 3 beta

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Scavuzzo, C. (2014). Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/50428

Chicago Manual of Style (16^th Edition):

Scavuzzo, Claire. “Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling.” 2014. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/50428.

MLA Handbook (7^th Edition):

Scavuzzo, Claire. “Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling.” 2014. Web. 14 Apr 2021.

Vancouver:

Scavuzzo C. Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2014. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/50428.

Council of Science Editors:

Scavuzzo C. Use it and boost it: cognitive and physical activities modulate cognition via BDNF-TrkB signaling. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2014. Available from: http://hdl.handle.net/2142/50428

University of Illinois – Urbana-Champaign

22. Weng, Ning. Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome.

Degree: PhD, 4094, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/32022

► Fragile X Syndrome (FXS) is the leading cause of inherited mental retardation, and the most common identified genetic cause of autism. Lack of production of… (more)

▼ Fragile X Syndrome (FXS) is the leading cause of inherited mental retardation, and the most common identified genetic cause of autism. Lack of production of the Fragile X Mental Retardation Protein (FMRP) leads to changes in dendritic morphology and resultant cognitive and behavioral manifestations characteristic of individuals with FXS. FMRP is an RNA-binding protein that is believed to regulate the translation of a large number of other proteins, leading to a complex and variable set of symptoms in FXS. In a mouse model of FXS, we previously observed delayed initiation of synaptically localized protein synthesis in response to neurotransmitter stimulation, as compared to wild-type mice. We now likewise have observed delayed early-phase phosphorylation of extracellular-signal regulated kinase (ERK), a nodal point for cell signaling cascades, in both neurons and thymocytes of fmr-1 KO mice. We further reported that early-phase kinetics of ERK activation in lymphocytes from human peripheral blood is delayed in a cohort of individuals with FXS, relative to normal controls, suggesting a potential biomarker to measure metabolic status of disease for individuals with FXS. Furthermore, dysregulated phosphatases, especially Protein phosphatase 2A (PP2A) may account for the delay in ERK activation. FXS and immune dysregulation is an emerging area in FXS research. We hypothesize that immune cells from FXS patients may have different gene expression and protein profiles. We first analyzed genome-wide microarray data from FXS lymphoblastoid cell, and found several immune gene sets are differentially expressed in FXS patients. We further reported that the cytokine profiles and cytokines activation profiles are dysregulated in FXS patients. These results could be used as potential cellular markers for FXS patients. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Cox%2C%20Charles%20L.%22%29&pagesize-30">Cox, Charles L. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Kemper%2C%20Byron%20W.%22%29&pagesize-30">Kemper, Byron W. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Cox%2C%20Charles%20L.%22%29&pagesize-30">Cox, Charles L. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Newmark%2C%20Phillip%20A.%22%29&pagesize-30">Newmark, Phillip A. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Pilas%2C%20Barbara%22%29&pagesize-30">Pilas, Barbara (committee member).

Subjects/Keywords: Fragile X Syndrome; extracellular-signal regulated kinase; extracellular-signal regulated kinase (ERK); Mitogen-activated protein kinases (MAPK); biomarker; cytokine profiles; flow cytometry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Weng, N. (2012). Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/32022

Chicago Manual of Style (16^th Edition):

Weng, Ning. “Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/32022.

MLA Handbook (7^th Edition):

Weng, Ning. “Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome.” 2012. Web. 14 Apr 2021.

Vancouver:

Weng N. Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/32022.

Council of Science Editors:

Weng N. Dysregulated ERK signal pathway and immune profiles in Fragile X Syndrome. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/32022

University of Illinois – Urbana-Champaign

23. Aldridge, Georgina. When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation.

Degree: PhD, 0323, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/29550

► Fragile X Syndrome (FXS) is the leading inherited cause of mental retardation, and the most common identified genetic cause of autism. Although many phenotypes have… (more)

▼ Fragile X Syndrome (FXS) is the leading inherited cause of mental retardation, and the most common identified genetic cause of autism. Although many phenotypes have been associated with the disorder, arguably the most well-studied and interesting is a pattern of dendritic spine “dysgenesis”, found in patients and animal models of the disorder. Specifically, dendritic spines, thorn-like protrusions associated with synapses, appear “immature”: often exhibiting abnormal length and shape, and found in higher than typical density in many brain regions. The phenotype described is consistent with the hypothesis that deficient synaptic pruning results in the observed spine phenotype. However, directly testing this hypothesis is not possible using traditional methods because the history and fate of particular spines is unknown. Through the use of repeated in vivo imaging using 2-photon microscopy I was able to track the fate of individual spines over different periods of development on layer V dendritic tufts. Spine turnover, including both the formation of new spines and the elimination of existing spines, is enhanced in the Fmr1 knockout (KO) animals compared with wildtype (WT) controls. Furthermore, the increased population of transient spines in the KO mice are not sensitive to modulation by sensory experience, such as by chessboard whisker trimming. Newly formed and eliminated spines were found to be more immature appearing compared to stable spines, suggesting that these spines could contribute to the abnormal spine profile described in Fragile X. However, multiple experiments showed KO spines from the layer V dendritic tufts do not display the spine phenotype previously described for this region of neocortex. Instead, my analysis of spine morphology and dynamics in this region suggests that morphology and size are strong predictors of instability, but that in the KO mouse, there is some dysregulation of this relationship. Using lithium, a model pharmacological treatment for Fragile X, I was able to demonstrate that the dynamic, in vivo spine phenotype can be modulated in both WT and KO mice. Lithium caused increased turnover of spines, and may specifically lead to more elimination of spines in the Fmr1 KO in some contexts, potentially explaining the phenotypic rescue described for this drug in the literature. Finally, in order to test whether the spine phenotype could be modified in adult animals, I used recombinant adeno-associated viral vector (rAAV) to induce reexpression of FMRP in the brain. Analysis by Golgi staining showed that expression of FMRP altered the spine phenotype towards a profile resembling the phenotype in WT animals injected with control vector. Together, these findings support a dynamic model of the dendritic spine phenotype that is responsive to the current environment and context, rather than being subject to developmental constraints. This novel dynamic spine phenotype observed in Fragile X mice, including an increased population of labile dendritic spines and abnormal responsiveness to… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Greenough%2C%20William%20T.%22%29&pagesize-30">Greenough, William T. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Greenough%2C%20William%20T.%22%29&pagesize-30">Greenough, William T. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Juraska%2C%20Janice%20M.%22%29&pagesize-30">Juraska, Janice M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Korol%2C%20Donna%20L.%22%29&pagesize-30">Korol, Donna L. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member).

Subjects/Keywords: Fragile X Syndrome; dendritic spines; development; 2-photon; multiphoton; lithium; Gene Therapy; viral vector; Fragile X Mental Retardation Protein (FMRP); synapse; mouse model

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Aldridge, G. (2012). When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/29550

Chicago Manual of Style (16^th Edition):

Aldridge, Georgina. “When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/29550.

MLA Handbook (7^th Edition):

Aldridge, Georgina. “When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation.” 2012. Web. 14 Apr 2021.

Vancouver:

Aldridge G. When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/29550.

Council of Science Editors:

Aldridge G. When good synapses go bad: dendritic spine dysgenesis in a mouse model of Fragile X mental retardation. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/29550

University of Illinois – Urbana-Champaign

24. Caetano-Anolles, Derek. Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor.

Degree: PhD, Cell and Developmental Biology, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/90857

► Neurogenesis, and the processes through which neural stem cells and progenitor cells differentiate into neurons, occurs most actively during embryonic development, although neural differentiation continues… (more)

▼ Neurogenesis, and the processes through which neural stem cells and progenitor cells differentiate into neurons, occurs most actively during embryonic development, although neural differentiation continues at lower levels in certain brain regions well into adulthood. A vast regulatory network involving many known and conserved transcription factors regulates these functions. We have identified a novel zinc finger transcription factor (TF), ZNF286A, which is conserved in all eutherians and marsupials and provide evidence that this novel TF plays a role in regulation of mammalian neurogenesis. ZNF286 occurs as a unique gene in most species. However, we demonstrate evidence that a gene duplication event in very recent primate history created a human-specific duplicate of ZNF286A, called ZNF286B. ZNF286B arose as part of a larger duplication in human chromosome 17, approximately 600,000 kb in length, that also includes many surrounding genes. Concomitant with (or shortly after) duplication, a processed and incomplete FOXO3B pseudo-gene was inserted into the ZNF286B genomic sequence and a DNA segment, encompassing a coding exon and regulatory sequences present in the ancestral ZNF286A gene, was deleted. As a result, ZNF286B encodes a protein with significant structural and expression differences relative to the ancestral gene. Most strikingly, the exon deleted in ZNF286B codes for the chromatin-interacting KRAB-domains that are present in the ZNF286A gene; in this respect the new human paralog resembles a natural KRAB-less alternative isoform that we demonstrate to be expressed naturally from the parental ZNF286A gene. Using ChIP and siRNA knockdown, we show that ZNF286A protein binds to DNA at or near genes involved in the networks controlling the differentiation of neurons and the formation of axons during neurogenesis, and that both ZNF286A and ZNF286B directly regulate expression of many of those same genes. The pattern of DNA binding closely parallels binding of well-known neuronal differentiation factor, REST, in the same cell lines; siRNA results suggest that ZNF286 proteins act antagonistically to REST during development. We show that the mouse gene, Zfp286, is expressed at high levels in the developing nervous system and that both mouse and human genes and proteins are up-regulated transiently over the course of neurogenic differentiation in vitro, consistent with the predicted biological role. We hypothesize that the duplication event that gave rise to ZNF286B allowed for independent regulation of the KRAB-less isoform of the ZNF286 protein, permitting this ancient mammalian gene to take on novel functions in the adult human brain. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Stubbs%2C%20Lisa%20J.%22%29&pagesize-30">Stubbs, Lisa J. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Stubbs%2C%20Lisa%20J.%22%29&pagesize-30">Stubbs, Lisa J. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Mizzen%2C%20Craig%20A.%22%29&pagesize-30">Mizzen, Craig A. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Rodriguez-Zas%2C%20Sandra%22%29&pagesize-30">Rodriguez-Zas, Sandra (committee member).

Subjects/Keywords: KRAB-ZNF; recently evolved paralogs; neurogenesis; transcription factors

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Caetano-Anolles, D. (2016). Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/90857

Chicago Manual of Style (16^th Edition):

Caetano-Anolles, Derek. “Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/90857.

MLA Handbook (7^th Edition):

Caetano-Anolles, Derek. “Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor.” 2016. Web. 14 Apr 2021.

Vancouver:

Caetano-Anolles D. Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/90857.

Council of Science Editors:

Caetano-Anolles D. Gene duplication and alternative splicing play a role in modulating the functions of the ZNF286A transcription factor. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/90857

25. Winograd, Claudia. Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally.

Degree: PhD, 0323, 2013, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/44333

► Fragile X syndrome (FXS) is a genetic disease caused by absent expression of the normal fragile X protein FMRP, presenting with a constellation of features… (more)

▼ Fragile X syndrome (FXS) is a genetic disease caused by absent expression of the normal fragile X protein FMRP, presenting with a constellation of features including intellectual disability, connective tissue abnormalities, and impaired vocalization (speech and language). FMRP is an RNA-binding protein, and animal models of FXS present with abnormalities in protein translation. This work will address the roles of FMRP in the development of a neural circuit for vocalization, and in protein translation regulation via the microRNA (miRNA) pathway. Humans are vocal learners, meaning we must hear normal adult vocalization during a critical period in development in order to learn this vocalization properly. Because FXS has both impaired learning and atypical vocalization, it is conceivable that these two features are linked by impaired vocal learning. Our hypothesis is that FMRP is necessary for normal vocal learning. An established model for vocal learning, and thereby ideal for studying the vocal abnormalities of FXS in order to deduce the molecular role of FMRP in vocal learning, is the songbird zebra finch Taeniopygia guttata. In this dissertation I present work that shows expression of the zebra finch FMRP in brain regions critical for normal song learning. Furthermore, I show that this expression is variable across development, supporting the argument for a role of FMRP in song learning. Moreover, I show that this variable expression is not due to singing activity alone. Finally, I present preliminary work developing a genetic tool with which to generate a zebra finch model of FXS. In order to study more thoroughly the role of FMRP in neural development, I will then shift focus to the role of this protein in protein translation regulation via the miRNA pathway. miRNAs are small, genomically-encoded RNAs that regulate translation of target mRNAs, generally by translation suppression of these target mRNAs. It is unknown how miRNAs are regulated in neurons both spatially and temporally. Studies in our and our colleagues’ labs have shown association of FMRP with protein and RNA members of the miRNA pathway. Furthermore, phosphorylated FMRP (P-FMRP) has a suppressive role in protein translation and is present in neuronal dendritic transport granules. Our lab has observed an increased association of P-Fmrp with precursors to miRNAs (pre-miRs) along with a decreased association with Dicer, the rate-limiting enzyme in miRNA biogenesis from pre-miRs, both in comparison with FMRP. Our hypothesis is that P-FMRP transports pre-miRs to dendritic spines, protecting them from Dicer until a specific neural signal indicates necessity for continuation of the miRNA pathway, thereby assisting in spatio-temporal regulation of the miRNA pathway. In contribution to the development of this FMRP-miRNA regulation hypothesis, this dissertation presents data on association of FMRP with other proteins in the miRNA pathway. Notably, some of these associations are affected by phosphorylation status of FMRP. … Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Clayton%2C%20David%20F.%22%29&pagesize-30">Clayton, David F. (committee member), Champaign%22%20%2Bcontributor%3A%28%22George%2C%20Julia%20M.%22%29&pagesize-30">George, Julia M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22DeThorne%2C%20Laura%20S.%22%29&pagesize-30">DeThorne, Laura S. (committee member).

Subjects/Keywords: Fragile X Mental Retardation Protein (FMRP); Fragile X Syndrome; zebra finch; songbird; RA nucleus; song learning; microRNA (miRNA); protein translation regulation; synaptic protein translation

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APA (6^th Edition):

Winograd, C. (2013). Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/44333

Chicago Manual of Style (16^th Edition):

Winograd, Claudia. “Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally.” 2013. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/44333.

MLA Handbook (7^th Edition):

Winograd, Claudia. “Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally.” 2013. Web. 14 Apr 2021.

Vancouver:

Winograd C. Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2013. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/44333.

Council of Science Editors:

Winograd C. Neuronal FMRP: facilitating learning in a critical brain network for zebra finch song acquisition and regulating synaptic miRNAs spatio-temporally. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2013. Available from: http://hdl.handle.net/2142/44333

26. Chang, Li-Hsin. Deep vertebrate roots for mammalian krab zinc-finger transcription factors.

Degree: PhD, Cell and Developmental Biology, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/98278

► KRAB-associated C2H2 zinc-finger (KRAB-ZNF) proteins are the products of a rapidly evolving gene family that traces back to early tetrapods, but which has expanded dramatically… (more)

▼ KRAB-associated C2H2 zinc-finger (KRAB-ZNF) proteins are the products of a rapidly evolving gene family that traces back to early tetrapods, but which has expanded dramatically to generate an unprecedented level of species-specific diversity. While most attention has been focused on the more recently evolved primate KRAB-ZNF genes, the vertebrate roots of the KRAB-ZNF families have remained mysterious. We recently mined ZNF loci from seven sequenced genomes (opossum, chicken, zebra finch, lizard, frog, mouse, and human genome) and found hundreds of KRAB-ZNF proteins in every species we examined, but only three human genes were found with clear orthologs in non-mammalian vertebrates. These three genes, ZNF777, ZNF282, and ZNF783, are members of an ancient familial cluster and encode proteins with similar domain structures. These three genes, members of an ancient familial cluster, encode a noncanonical KRAB domain that is similar to an ancient domain which is prevalent in non-mammalian species. In contrast to the mammalian KRAB, which is thought to function as a potent repressor, this ancient domain serves as a transcriptional activator. Our evolutionary analysis confirmed the ancient provenance of this activating KRAB and revealed the independent expansion of KRAB-ZNFs in every vertebrate lineage. This finding led us to ask the question: what are the functions of these ancient family members and why, of such a large and diverse family group, were these three genes conserved so fastidiously over hundreds of millions of years? In chapter 2, I report the regulatory function of ZNF777, combining chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) with siRNA knockdown experiments to determine genome-wide binding sites, a distinct binding motif, and predicted targets for the protein in human BeWo choriocarcinoma cells. Genes neighboring ZNF777 binding sites can be either up- or down- regulated, suggesting a complex regulatory role. Our studies revealed that some of this complexity is due to the generation of HUB-containing and HUB-minus isoforms, which are predicted to have different regulatory activities. Based on these experiments, we hypothesize that ZNF777 regulates pathways best known for their roles in neurogenesis and axon pathfinding, but also recently shown to play critical roles in placental development. Since ZNF777 is also expressed in embryonic brain, we sought to further investigate the functional role of this ancient gene in neuron development. In chapter 3, I show that mouse Zfp777 is expressed in neuronal stem cells (NSC) cultured from early mouse embryos, with a pattern that changes over the course of neuron differentiation in vitro. Using the NSC platform, I characterized the binding landscape of Zfp777 in undifferentiated NSC. To circumvent the roadblock posed by the lack of a ChIP-grade antibody for the mouse protein, I exploited the CRISPR-Cas9 technique to tag the endogenous Zfp777 protein with FLAG epitopes. Our results revealed a novel Zfp777 binding motif that… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Stubbs%2C%20Lisa%20J.%22%29&pagesize-30">Stubbs, Lisa J. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Mizzen%2C%20Craig%20A.%22%29&pagesize-30">Mizzen, Craig A. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Bell%2C%20Alison%20M.%22%29&pagesize-30">Bell, Alison M. (committee member).

Subjects/Keywords: ZNF777; Zfp777

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APA (6^th Edition):

Chang, L. (2017). Deep vertebrate roots for mammalian krab zinc-finger transcription factors. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/98278

Chicago Manual of Style (16^th Edition):

Chang, Li-Hsin. “Deep vertebrate roots for mammalian krab zinc-finger transcription factors.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/98278.

MLA Handbook (7^th Edition):

Chang, Li-Hsin. “Deep vertebrate roots for mammalian krab zinc-finger transcription factors.” 2017. Web. 14 Apr 2021.

Vancouver:

Chang L. Deep vertebrate roots for mammalian krab zinc-finger transcription factors. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/98278.

Council of Science Editors:

Chang L. Deep vertebrate roots for mammalian krab zinc-finger transcription factors. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/98278

27. Masoud, Farzaneh. Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells.

Degree: PhD, 4094, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/31131

► Establishment of the disease endometriosis requires the attachment and invasion of endometrial fragments into the peritoneal lining of the peritoneal cavity. For proper attachment and… (more)

▼ Establishment of the disease endometriosis requires the attachment and invasion of endometrial fragments into the peritoneal lining of the peritoneal cavity. For proper attachment and invasion to occur, the endometrial cells and mesothelial cells that line the surface of the peritoneum must interact. Previous studies by Witz et al. have shown that endometrial fragments can attach to mesothelial cells, but the mechanism by which these endometrial cells are able to invade through the mesothelial layer into the underlying peritoneum is not clear (Witz et al 1999, 2000, 2001). Mesothelial cells normally display an epithelial–like morphology, but in response to injury or inflammation they undergo epithelial to mesenchymal transition (EMT). As mesothelial cells undergo EMT, they lose expression of E-cadherin and cytokeratins, exhibit a fibroblast-like phenotype, and become more migratory and invasive. This transition results in the formation of gaps in the mesothelium and could allow attached endometrial cells to invade into the underlying peritoneum. Recent studies have reported the up-regulation of extracellular matrix metalloproteinase inducer, (EMMPRIN) as cancer cells undergo EMT (Abraham et al 2008). The goal of my research proposal is to determine whether secreted factors from uterine epithelial cells of endometrial fragments can cause epithelial to mesenchymal transition of mesothelial cells. In this study we utilized a human mesothelial cell line, LP-9, to examine the effect of EMMPRIN, and other uterine epithelial cell factors such as IL-1β, and TGF-β1 on EMT by monitoring changes in expression of N-cadherin, MMPs, cytokeratins, vimentin, and transcription factors twist and snail. Change in rate of migration was also assessed using the in vitro cell wounding assay. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Nowak%2C%20Romana%20A.%22%29&pagesize-30">Nowak, Romana A. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Bellini%2C%20Michel%22%29&pagesize-30">Bellini, Michel (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Cameron%2C%20Jo%20Ann%22%29&pagesize-30">Cameron, Jo Ann (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Kemper%2C%20Byron%20W.%22%29&pagesize-30">Kemper, Byron W. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Nowak%2C%20Romana%20A.%22%29&pagesize-30">Nowak, Romana A. (committee member).

Subjects/Keywords: epithelial to mesenchymal transition (EMT); Mesothelial cells; Cytokines; Human Uterine Epithelial Cell Culture (HES); extracellular matrix metalloproteinase inducer (EMMPRIN)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Masoud, F. (2012). Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/31131

Chicago Manual of Style (16^th Edition):

Masoud, Farzaneh. “Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/31131.

MLA Handbook (7^th Edition):

Masoud, Farzaneh. “Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells.” 2012. Web. 14 Apr 2021.

Vancouver:

Masoud F. Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/31131.

Council of Science Editors:

Masoud F. Induction of epithelial to mesenchymal transition in mesothelial cells by secreted factors from uterine epithelial cells. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/31131

28. Dezwaan, Diane C. Biochemical analysis of proteins in the telomere maintenance pathway.

Degree: PhD, 4094, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/18345

► Eukaryotic linear chromosomes culminate in nucleoprotein structures designated telomeres. The terminal telomeric DNA consists of tandem repeats of a G-rich motif that is established and… (more)

▼ Eukaryotic linear chromosomes culminate in nucleoprotein structures designated telomeres. The terminal telomeric DNA consists of tandem repeats of a G-rich motif that is established and maintained by the action of the specialized reverse transcriptase called telomerase. In addition to the function of telomerase, the telomere environment requires an efficient means to assemble and disassemble a multitude of structures to operate correctly and to help achieve cellular homeostasis. Distinct protein assemblies are nucleated at telomeric DNA to both guard the ends from damage and lengthen the DNA after replication. In yeast, Cdc13 recruits either Stn1-Ten1 to form a protective cap or the telomerase holoenzyme to extend the DNA. I have established an in vitro yeast telomere system in which Stn1-Ten1-unextendable or telomerase-extendable states can be observed. Notably, the yeast Hsp90 chaperone Hsp82 mediates the switch between the telomere capping and extending structures by modulating the DNA binding activity of Cdc13. The telomere length and telomerase telomere occupancy also appear to be yeast Hsp90 dependent. Taken together, my data show that the Hsp82 chaperone facilitates telomere DNA maintenance by promoting transitions between two operative complexes and by reducing the potential for binding events that would otherwise block the assembly of downstream structures. The first telomerase cofactor identified was the budding yeast protein Est1, which is conserved through humans. While it is evident that Est1 is required for telomere DNA maintenance, understanding its mechanistic contributions to telomerase regulation has been limited. In vitro, the primary effect of Est1 is to activate telomerase-mediated DNA extension. Although Est1 displayed specific DNA and RNA binding, neither activity iii contributed significantly to telomerase stimulation. Rather Est1 mediated telomerase upregulation through direct contacts with the reverse transcriptase subunit. My studies provide insights into the molecular events used to control the enzymatic activity of the telomerase holoenzyme. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Freeman%2C%20Brian%20C.%22%29&pagesize-30">Freeman, Brian C. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Belmont%2C%20Andrew%20S.%22%29&pagesize-30">Belmont, Andrew S. (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Nardulli%2C%20Ann%20M.%22%29&pagesize-30">Nardulli, Ann M. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Gillette%2C%20Martha%20U.%22%29&pagesize-30">Gillette, Martha U. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Freeman%2C%20Brian%20C.%22%29&pagesize-30">Freeman, Brian C. (committee member).

Subjects/Keywords: Telomere; Telomerase; Chaperone; Cellular dynamics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dezwaan, D. C. (2011). Biochemical analysis of proteins in the telomere maintenance pathway. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/18345

Chicago Manual of Style (16^th Edition):

Dezwaan, Diane C. “Biochemical analysis of proteins in the telomere maintenance pathway.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/18345.

MLA Handbook (7^th Edition):

Dezwaan, Diane C. “Biochemical analysis of proteins in the telomere maintenance pathway.” 2011. Web. 14 Apr 2021.

Vancouver:

Dezwaan DC. Biochemical analysis of proteins in the telomere maintenance pathway. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/18345.

Council of Science Editors:

Dezwaan DC. Biochemical analysis of proteins in the telomere maintenance pathway. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/18345

University of Illinois – Urbana-Champaign

29. Cheever, Anne E. Microrna-mediated regulation and the fragile X family of proteins.

Degree: PhD, 4094, 2010, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/14560

► The main purpose of this work is to understand how two members of the fragile X family of RNA binding proteins, fragile X mental retardation… (more)

▼ The main purpose of this work is to understand how two members of the fragile X family of RNA binding proteins, fragile X mental retardation protein (FMRP) and FXR1P, are regulated by post-translational modifications and microRNAs (miRNAs), respectively. Both proteins play key roles in normal development and function. The absence of FMRP leads to the cognitive defects seen in Fragile X syndrome, the leading cause of hereditary mental retardation, while loss of FXR1P expression in mice is fatal after birth, likely due to cardiac and muscle abnormalities. Small, genomically encoded miRNAs are involved in almost every biological process, specifically in the regulation of mRNA translation. Although their biogenesis is relatively well defined, it is still unclear how they are recruited to their mRNA targets. FMRP and its autosomal paralogs, FXR1P and FXR2P, in addition to the single Drosophila ortholog, dFmrp, associate physically and functionally with the miRNA pathway. Constitutively phosphorylated FMRP (P-FMRP) is found associated with stalled untranslating polyribosomes and translation of at least one mRNA is downregulated when FMRP is phosphorylated. We hypothesized that translational regulation by P-FMRP is accomplished through association with the miRNA pathway. Accordingly, we developed a phospho-specific antibody to P-FMRP and showed that P-FMRP associates with increased amounts of precursor miRNAs (pre-miRNA) compared to total FMRP. Furthermore, P-FMRP does not associate with Dicer or Dicer containing complexes in co-immunoprecipitation experiments or in an in vitro capture assay using a P-FMRP peptide sequence bound to agarose beads. These data show that Dicer containing complexes bind FMRP at amino acids 496-503 and that phosphorylation disrupts this association with a consequent increase in association with pre-miRNAs. In sum, we propose that in addition to regulating translation, phosphorylation of FMRP regulates its association with the miRNA pathway by modulating association with Dicer. We present a new model for the effect of phosphorylation on FMRP function, where phosphorylation of FMRP inhibits Dicer binding, leading to the accumulation of precursor miRNAs and possibly a paucity of activating miRNAs. FMRP’s autosomal paralog, FXR1P, plays an important role in normal muscle development, has been implicated in fascioscapulohumeral muscular dystrophy (FSHD) and its absence or misregulation has been shown to cause cardiac abnormalities in mice and zebrafish. To examine miRNA-mediated regulation of FMRP and FXR1P, we studied their expression in a conditional Dicer knockdown cell line, DT40. We found that FXR1P, but not FMRP, increases upon Dicer knockdown and consequent absence of miRNAs suggesting that FXR1P is regulated by miRNAs, while FMRP is not. Expression of a luciferase reporter bearing the FXR1 3’UTR was significantly increased in the absence of miRNAs, confirming miRNA-mediated regulation of FXR1P. We identified one of the regulatory regions by removing an 8-nucleotide miRNA… Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Chen%2C%20Jie%22%29&pagesize-30">Chen, Jie (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Bellini%2C%20Michel%22%29&pagesize-30">Bellini, Michel (committee member), Champaign%22%20%2Bcontributor%3A%28%22Schuler%2C%20Mary%20A.%22%29&pagesize-30">Schuler, Mary A. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Prasanth%2C%20Kannanganattu%20V.%22%29&pagesize-30">Prasanth, Kannanganattu V. (committee member).

Subjects/Keywords: Fragile X Syndrome; Fragile X Mental Retardation Protein (FMRP); FXR1P; microRNAs; translation regulation; phosphorylation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cheever, A. E. (2010). Microrna-mediated regulation and the fragile X family of proteins. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/14560

Chicago Manual of Style (16^th Edition):

Cheever, Anne E. “Microrna-mediated regulation and the fragile X family of proteins.” 2010. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/14560.

MLA Handbook (7^th Edition):

Cheever, Anne E. “Microrna-mediated regulation and the fragile X family of proteins.” 2010. Web. 14 Apr 2021.

Vancouver:

Cheever AE. Microrna-mediated regulation and the fragile X family of proteins. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2010. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/14560.

Council of Science Editors:

Cheever AE. Microrna-mediated regulation and the fragile X family of proteins. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2010. Available from: http://hdl.handle.net/2142/14560

University of Illinois – Urbana-Champaign

30. Amaya, Kensey R. Small molecule profiling and imaging of the zebra finch song system.

Degree: PhD, 4094, 2010, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/15549

► The ability of songbirds to communicate though learned vocalization and the discovery of discreet interconnected ???song nuclei??? involved in vocal learning has made them a… (more)

▼ The ability of songbirds to communicate though learned vocalization and the discovery of discreet interconnected ???song nuclei??? involved in vocal learning has made them a valuable model to study the neuronal mechanisms behind learning and memory. This dissertation focuses on studying small molecules (i.e. lipids and metabolites) in the zebra finch song system, a songbird. I will use analytical tools and methods to detect and image the spatial distribution of small molecules (e.g. lipids) across the song system. In addition I will investigate changes in small molecules in the auditory lobule, a brain region involved in interpreting and processing auditory inputs, in response to song stimulation. Applying advances in Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) small molecules (e.g. fatty acids) are detected and high spatial resolution images (2.3 ??m) are generated, forming 11.5 megapixel chemical images using a sagittal brain section collected from an adult male zebra finch. ToF-SIMS analysis reveals a heterogeneous distribution of small molecules across the brain section corresponding to different anatomical structures, including two song nuclei that are important in song-motor control. Expanding upon the ToF-SIMS results I increase the number of identifiable small molecules; and expand the number of brain regions to include all of the major song nuclei in the zebra finch brain. Using ToF-SIMS and applying multivate statistical methods (e.g. principle component analysis) I show chemical differences between functionally distinct and tissue specific brain areas; as well as at different developmental stages in the male songbird brain. Metabolites are a diverse group of small molecules that act as end products and intermediates in biochemical pathways such as signaling molecules (i.e. dopamine), amino acids (i.e. glutamate) and in energy metabolism (i.e. glucose). Metabolomic studies focusing on the auditory lobule, a brain region involved in the acquisition, processing, and interpreting of auditory inputs, exhibited unique metabolomic profiles between birds exposed to novel song exposure, habituation song, and silence. Biochemical pathways involved in sugar metabolism (e.g. glycolysis), RNA synthesis, and GHB metabolism exhibit overall changes upon novel song stimulation compared to silent control birds. Integrating genomic data and metabolomic data suggests other biochemical pathways are responding to song stimulation. This dissertation reveals the heterogeneous distribution of small molecules across the major song nuclei in the zebra finch brain and at different developmental stages and the metabolomic response to song. These experiments serve as a stating point to study the role lipids play in the development of the song system and learning and memory. It also serves as a starting point to conduct more rigorous metabolomic studies and integrating metabolomic, genomic, and proteomic information to better study song response in the zebra finch brain. Advisors/Committee Members: Champaign%22%20%2Bcontributor%3A%28%22Clayton%2C%20David%20F.%22%29&pagesize-30">Clayton, David F. (advisor), Champaign%22%20%2Bcontributor%3A%28%22Cameron%2C%20Jo%20Ann%22%29&pagesize-30">Cameron, Jo Ann (Committee Chair), Champaign%22%20%2Bcontributor%3A%28%22Clayton%2C%20David%20F.%22%29&pagesize-30">Clayton, David F. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Sweedler%2C%20Jonathan%20V.%22%29&pagesize-30">Sweedler, Jonathan V. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Ceman%2C%20Stephanie%20S.%22%29&pagesize-30">Ceman, Stephanie S. (committee member), Champaign%22%20%2Bcontributor%3A%28%22Bellini%2C%20Michel%22%29&pagesize-30">Bellini, Michel (committee member).

Subjects/Keywords: ToF-SIMS; metabolomics; songbird; brain

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Amaya, K. R. (2010). Small molecule profiling and imaging of the zebra finch song system. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/15549

Chicago Manual of Style (16^th Edition):

Amaya, Kensey R. “Small molecule profiling and imaging of the zebra finch song system.” 2010. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 14, 2021. http://hdl.handle.net/2142/15549.

MLA Handbook (7^th Edition):

Amaya, Kensey R. “Small molecule profiling and imaging of the zebra finch song system.” 2010. Web. 14 Apr 2021.

Vancouver:

Amaya KR. Small molecule profiling and imaging of the zebra finch song system. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2010. [cited 2021 Apr 14]. Available from: http://hdl.handle.net/2142/15549.

Council of Science Editors:

Amaya KR. Small molecule profiling and imaging of the zebra finch song system. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2010. Available from: http://hdl.handle.net/2142/15549

Open Access Theses and Dissertations