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2020

Theses and Dissertations

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Full-Text Articles in Cell and Developmental Biology

A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz Dec 2020

A Molecular Toolset For The In Vivo Detection Of A Sulfolobus Islandicus Leucyl Trna Synthetase Paralog, Nicholas Michael Bretz

Theses and Dissertations

An ancient and ubiquitous set of enzymes known as the aminoacyl-tRNA synthetases are required for the viability of all organisms. The aminoacyl-tRNA synthetases catalyze the attachment of amino acids onto tRNA molecules. The aminoacylated, or charged, tRNA is then transported and utilized at the ribosome for the synthesis of proteins. The genome of the hyperthermophilic microorganism Sulfolobus islandicus (S. islandicus) harbors a unique leucyl-tRNA synthetase paralog, LeuRS-I, of unknown function. While its duplicate, LeuRS-F, carries out all the classical functions of LeuRS-family enzymes, LeuRS-I fails to charge leucine onto tRNALeu, despite its ability to activate this amino acid and bind …


Fibrinogen-Conjugated Gold-Coated Magnetite Nanoparticles For Targeting Activated Platelets In A Whole Blood System, Cammy Nu Truong Aug 2020

Fibrinogen-Conjugated Gold-Coated Magnetite Nanoparticles For Targeting Activated Platelets In A Whole Blood System, Cammy Nu Truong

Theses and Dissertations

Activated platelets are a key component of the arterial thrombi responsible for heart attack and stroke. Tissue plasminogen activator (tPA) is currently the only FDA-approved drug for ischemic stroke. It works by dissolving fibrin, thus breaking down the clot and restoring blood flow to the brain. However, it must be administered within 4.5 hours of the onset of stroke. This leaves a significant number of patients who are ineligible for intervention and who have poor clinical outcomes. Additionally, tPA is not injury site-specific; consequently, the side effects range from mild to severe. We are investigating targeting activated platelets in occlusive …


Effect Of Non-Muscle Myosin Ii Inhibition On Epigenetics During Oligodendrocyte Development, Amr Almaktari May 2020

Effect Of Non-Muscle Myosin Ii Inhibition On Epigenetics During Oligodendrocyte Development, Amr Almaktari

Theses and Dissertations

Non-Muscle Myosin II (NMII) is a mechanosensitive motor protein implicated in oligodendrocyte (OL) development. The inhibition of NMII is known to promote OL development and maturation. This project found that NMII inhibition does not affect oligodendrocyte development by altering their epigenetic profile.


Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam May 2020

Expression Analyses Of Hippocampal And Cortical Proteins In A Rat Model For Alzheimer’S Disease, Rangon Islam

Theses and Dissertations

Currently, Alzheimer’s disease (AD) has no cure. Using a rat AD model, we identified aberrantly expressed proteins during pre-pathology as potential biomarkers. The expression of certain biomarkers was reversed by diazoxide, a repurposed hypertension drug. These results suggest that drug repurposing at an early stage of AD has therapeutic potential.


Gene Regulatory Mechanisms Driving Temporal Dynamics Of Lineage Specific Differentiation In The Cranial Neural Crest, Maria R. Replogle May 2020

Gene Regulatory Mechanisms Driving Temporal Dynamics Of Lineage Specific Differentiation In The Cranial Neural Crest, Maria R. Replogle

Theses and Dissertations

Genetic and environmental perturbations impacting neural crest (NC) development can result in pleiotropic structural and functional birth defects, many of which are associated with pediatric syndromes. As developmental precursors, the NC has the unique capacity to give rise to a diverse array of ectodermal and mesoectodermal cell types, from neurons and glia of the peripheral nervous system to the cartilage and bone of the face. In order to transition from a multipotent progenitor to a specific cell type, NC cells must undergo a series of dynamic morphological and behavioral transformations that gradually unfold over time. However, the NC is rare …


The Role Of Ca2+/Calmodulin Dependent Protein Kinase Ii, Camk-Ii, In Kidney Morphogenesis, Sarah R. Ingram Jan 2020

The Role Of Ca2+/Calmodulin Dependent Protein Kinase Ii, Camk-Ii, In Kidney Morphogenesis, Sarah R. Ingram

Theses and Dissertations

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common heritable diseases in the world, characterized by the development of large fluid filled cyst. Treatments for this disease are limited due to a lack of understanding of disease pathogenesis. Ca2+/calmodulin dependent protein kinase II (CaMK-II) is necessary for kidney morphogenesis in zebrafish as well as being a downstream effector of pkd2, one of the genes most commonly mutated in ADPKD patients. The roles of CaMK-II during zebrafish kidney development include regulation of kidney cell migration as well as cloacal cilia stability. The influence of CaMK-II …


The Human Intermediate Prolactin Receptor: A Breast Cancer Proto-Oncogene, Jacqueline M. Grible Jan 2020

The Human Intermediate Prolactin Receptor: A Breast Cancer Proto-Oncogene, Jacqueline M. Grible

Theses and Dissertations

The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. hPRLrI co-expression with full-length hPRLr (hPRLrL) in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce …


The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine Jan 2020

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …


Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan Jan 2020

Higher Tensile Forces Across Cellular Junctions And An Intact Nuclear Linc Complex Is Required For Epithelial Function And Stability, Fnu Vani Narayanan

Theses and Dissertations

Recent advances in three-dimensional (3D) cell culture systems have provided key insights into the understanding of biochemical and physiological states of native tissue. A significant progress in the field of mechanobiology involves measuring cellular traction forces in a more native 3D environment. However, the effects of mechanical forces exerted across cellular junctions and the nuclear LINC complex, in an organized 3D system has not been investigated thus far. Epithelial cells spontaneously form acini (also known as cysts or spheroids) with a single, fluid-filled central lumen, when grown in 3D matrices. The size of the lumen is dependent on apical secretion …


Disruption Of The Dream Complex Results In Cell Cycle Deregulation, Hayley C. Walston Jan 2020

Disruption Of The Dream Complex Results In Cell Cycle Deregulation, Hayley C. Walston

Theses and Dissertations

The Dimerization Partner, Rb-like, E2F, And MuvB (DREAM) complex was identified in humans due to homology of the genes involved in the D. melanogaster dREAM complex. It assembles during cellular arrest, or G0, to function as a transcriptional repressor of cell cycle genes. It is known that phosphorylation of LIN52 at serine 28 is necessary for the critical DREAM forming interaction between LIN52 and the pocket protein p130. Our laboratory has previously shown that gene editing of LIN52 to replace serine 28 with alanine (S28A) prevents phosphorylation by the kinase DYRK1A and inhibits DREAM formation. Here we have confirmed this …