Digital Commons Network^™

Determining The Effects Of Mistranslating Transfer Rna Variants On Drosophila Melanogaster, Joshua R. Isaacson

Electronic Thesis and Dissertation Repository

Transfer RNAs (tRNAs) play a central role in translation as adaptor molecules between mRNA and protein. Variant tRNAs can cause the misincorporation of an amino acid into a growing polypeptide. Mistranslating tRNA variants are surprisingly common in humans but the effects of mistranslating tRNA variants on eukaryotic biology are poorly understood. My thesis aimed to create a model of tRNA-induced mistranslation using the fruit fly Drosophila melanogaster and characterize the effects of mistranslating tRNA variants on eukaryotic biology.

I first integrated a gene encoding a serine tRNA variant that induced proline-to-serine (P>S) mistranslation into the fly genome. Proteins isolated …

Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah

Electronic Thesis and Dissertation Repository

Myogenesis is defined as the formation of skeletal muscle tissue during embryonic development and involves a multitude of cellular signalling pathways. Among these include the Sonic hedgehog (Shh) signalling pathway which must be deactivated for differentiation into muscle cells to occur. However, less is known regarding the pathways operation during cell differentiation and whether Suppressor of Fused (SUFU), the protein inhibitor of Shh signalling, plays a role. To address this, mouse C2C12 myoblast cells were utilized as a model and differentiated into muscle cells to identify the presence of SUFU during this time. Experiments in qRT-PCR show a decrease in …

Investigating Task-Free Functional Connectivity Patterns In Newborns Using Functional Near-Infrared Spectroscopy, Homa Vahidi

Electronic Thesis and Dissertation Repository

Robust functional connectivity in sensorimotor resting-state network (RSN) has been linked to positive neurodevelopmental outcomes in neonates. In the current study, we aimed to map the developmental trajectory of sensorimotor RSN in awake neonates using functional near-infrared spectroscopy (fNIRS). We acquired fNIRS resting-state data from 41 healthy newborns (17 females, gestational age range=36+0 to 42+1 weeks) within the first 48 hours after birth. At the group level, we observed robust positive connectivity in numerous channel-pairs across the sensorimotor network, especially in the left hemisphere. Next, we examined the relationship between functional connectivity, gestational age and postnatal age, while controlling for …

Examining The Relationships Between Socio-Cognitive Factors And Neural Synchrony During Movie Watching Across Development, Kathleen M. Lyons

Electronic Thesis and Dissertation Repository

While different cognitive abilities mature, the conscious experiences of children likely become richer and more elaborate. A challenge in investigating relationships between cognitive development and real-world experiences is having measures that assess naturalistic processing. Movie watching offers a solution, since following the plot of a film requires cognitive processes that are similar to real-world experiences. When different adults watch the same film, their brain activity begins to align (known as neural synchrony). The strength of this alignment has been shown to reflect the degree to which different individuals are having a similar experience of the movie. While this phenomenon has …

Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes

Electronic Thesis and Dissertation Repository

Pathogenic variants in the human PRR12 (Proline Rich 12) gene are associated with PRR12-related Neuroocular Syndrome. However, little is known about the gene/protein function. The zebrafish was utilized to address this, as its attributes place it as a premier model to study genes involved in human development and disease. In situ hybridization and RT-PCR of embryos and larvae, and qRT-PCR of adult tissues revealed the spatial and temporal distributions of the prr12 paralogues: prr12a and prr12b. Both paralogues were detected from the maternal and zygotic transcriptomes in a global and diffuse expression pattern, and there was enrichment …

The Role Of Xenopus Laevis Reck In Ecm Remodeling And Tissue Patterning, Jessica Willson

Electronic Thesis and Dissertation Repository

Proper cell-cell and cell-extracellular matrix (ECM) interactions are vital for cell migration and patterning of the vertebrate embryo. Matrix metalloproteinases (MMPs) and their inhibitors, reversion-inducing cysteine-rich proteins with Kazal motifs (RECK) and tissue inhibitors of metalloproteinases (TIMPs), are all differentially expressed during embryogenesis to regulate such ECM remodeling events and cell interactions. While TIMPs are a family of 4 secreted proteins that share overlapping substrate specificities of MMPs, RECK is unique in that it is a membrane-anchored MMP inhibitor that is embryonic lethal in mice. I used Xenopus laevis as a model organism to investigate the role of RECK as …

How Does The Brain Represent Digits? Investigating The Neural Correlates Of Symbolic Number Representation Using Fmri-Adaptation, Celia Goffin

Electronic Thesis and Dissertation Repository

How does the brain represent numerical symbols (e.g., Arabic digits)? Activity in left parietal regions correlates with symbolic number processing. Research with functional resonance imaging adaptation (fMRI-A) indicates that the intraparietal sulcus (IPS) exhibits a rebound (increase in activation) effect when a repeatedly presented number is followed by a new number. Importantly, this rebound effect is modulated by numerical ratio as well as the difference between presented numbers (distance). This ratio-dependent rebound effect could reflect a link between symbolic numerical representation and an approximate number system (ANS). In this doctoral dissertation, fMRI-A is used to investigate mechanisms underlying symbolic number …

The Origins And Development Of Visual Categorization, Laura Cabral

Electronic Thesis and Dissertation Repository

Forming categories is a core part of human cognition, allowing us to make quickly make inferences about our environment. This thesis investigated some of the major theoretical interpretations surrounding the neural basis of visual category development. In adults, there are category-selective regions (e.g. in ventral temporal cortex) and networks (which include regions outside traditional visual regions—e.g. the amygdala) that support visual categorization. While there has been extensive behavioural work investigating visual categorization in infants, the neural sequence of development remains poorly understood. Based on behavioral experiments, one view holds that infants are initially using subcortical structures to recognize faces. Indeed, …

Partial Characterization Of Putative Cyp86a Genes From Soybean, Trish Tully

Electronic Thesis and Dissertation Repository

Soybean (Glycine max [L.] Merr.) is a globally cultivated crop that is important to the sustainability of many industries. However, like all plants, optimal cultivation of soybean is threatened by detrimental environmental factors. For example, high yield of soybean is threatened by soil-borne pathogens like Phytophthora sojae. Resistance against P. sojae was previously positively correlated with aliphatic suberin deposition in soybean. As such, a deeper understanding of the biosynthesis of suberin may assist in engineering a resistant form of soybean, based on enhanced suberin content. In soybean, the ω-OH fatty acid monomers are predominant and most strongly correlated …

A Comprehensive Catalog Of Post-Translational Modifications Of Drosophila Melanogaster Hox Protein, Sex Combs Reduced, Anirban Banerjee

Electronic Thesis and Dissertation Repository

During formation of the anterior-posterior axis, Homeotic selector (HOX) proteins determine the identity of Drosophila body segments. HOX proteins are transcription factors that regulate gene expression during development. Besides a highly conserved DNA-binding homeodomain (HD), HOX proteins also contain functionally important, evolutionarily conserved small motifs. These short motifs found in HOX proteins may be Short Linear Motifs (SLiMs). SLiMs are proposed to be sites of phosphorylation and this may regulate the activity of HOX proteins. The primary aim of this work was to develop a comprehensive catalogue of the sites of phosphorylation and other post-translational modifications (PTMs) for Fushi tarazu …

Ethanol Exposure During Synaptogenesis In A Mouse Model Of Fetal Alcohol Spectrum Disorders: Acute And Long-Term Effects On Gene Expression And Behaviour, Morgan L. Kleiber

Electronic Thesis and Dissertation Repository

Alcohol is a neuroactive molecule that is able to exert variable and often detrimental effects on the developing brain, resulting in a broad range of physiological, behavioural, and cognitive phenotypes that characterize ‘fetal alcohol spectrum disorders’ (FASD). Factors affecting the manifestation of these phenotypes include alcohol dosage, timing of exposure, and pattern of maternal alcohol consumption; however, the biological processes that are vulnerable to ethanol at any given neurodevelopmental stage are unclear, as is how their disruption results in the emergence of specific pathological phenotypes later in life.

The research included in this thesis utilizes a C57BL/6J (B6) mouse model …

The Role Of Connexins And Pannexins In Mammary Gland Development And Tumorigenesis, Michael K. G. Stewart

Electronic Thesis and Dissertation Repository

The identification of key regulators of breast cancer onset and progression is critical for the development of targeted therapies. Connexins and pannexins are characterized by their ability to form large-pore channels and are frequently dysregulated in cancer. However, their role in breast cancer progression remains poorly understood due to a lack of in vivo models capable of assessing the proposed and opposing roles of connexins and pannexins as both tumor suppressors and/or facilitators in multiple stages of the disease. Using 2 previously uncharacterized genetically-modified mice, connexin43 (Cx43) and connexin26 (Cx26) were evaluated for their role in normal mammary gland development …

Taking Tone Into Account: Cognitive Neuroscientific Investigations Of Mandarin Chinese Spoken Word Processing, Jeffrey G. Malins

Electronic Thesis and Dissertation Repository

To date, theories of how humans recognize spoken words have yet to account for tonal languages such as Mandarin Chinese. One reason for this is that we know relatively little about how native speakers of tonal languages process spoken words in the brain. This dissertation addresses this problem by examining Mandarin spoken word processing in both adult native speakers and typically developing children. In adults, functional magnetic resonance imaging (fMRI) was used to assess the extent to which the brain regions involved in processing tonal information are distinct from those involved in vowel processing (Chapter 2), while event related potentials …

Developmental Characterization Of Tissue Inhibitor Of Metalloproteinase Domain Functions In Xenopus Laevis, Michelle A. Nieuwesteeg

Electronic Thesis and Dissertation Repository

During development the extracellular matrix is cleaved and remodeled to facilitate the large-scale cell rearrangements that are necessary for processes like gastrulation, neurulation, angiogenesis and organogenesis. ECM remodeling occurs primarily through secreted enzymes called matrix metalloproteinases (MMPs). Regulation of MMP activity is achieved through the tissue inhibitor of metalloproteinases (TIMPs), a small family of secreted proteins that bind MMPs in a 1:1 manner to inhibit their activity. Although TIMPs were originally characterized based on their MMP-inhibitory activities, in vitro studies have revealed that TIMPs are multifunctional proteins, with structurally and functionally distinct N- and C-terminal domains. TIMP N-terminal domains bind …

Cloning And Analysis Of Reck During Early Xenopus Laevis Development, Jessica Willson

Electronic Thesis and Dissertation Repository

Extracellular matrix (ECM) remodeling is crucial for the development and maintenance of multicellular organisms. Degradation of ECM components occurs through the activity of matrix metalloproteinases (MMPs) and their inhibitors. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene encodes a membrane-anchored protein and plays an important role in mediating ECM remodeling by inhibiting MMPs. To date, few in vivo studies exist examining RECK during development. The present study focuses on cloning and examining the expression of RECK during early Xenopus laevis development. A mature cDNA clone of the RECK gene was generated. RT-PCR, in situ hybridization, and immunohistochemistry were used to …

The Developmental And Adaptive Role Of Mitogen Activated Protein Kinase Pathways During Preimplantation Development, Christine E. Bell

Electronic Thesis and Dissertation Repository

The preimplantation period of development represents the highest interval of embryonic loss throughout pregnancy. It is therefore imperative that we elucidate the mechanisms involved in regulating preimplantation embryonic responses to stress and that govern development. The MAPK pathways are involved in both responding to environmental stress and regulation of development throughout embryogenesis, and are therefore good candidates to study the mechanisms involved in preimplantation embryonic adaptation to stress and development. The preimplantation embryo culminates in the development of a fluid filled structure called the blastocyst. It is at this stage the first differentiation events occur and the trophectoderm (TE), which …