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Articles 1 - 14 of 14
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Investigating Smooth Muscle Myosin Dynamics And Assembly In Physiology And Pathology, Maggie Bennett
Investigating Smooth Muscle Myosin Dynamics And Assembly In Physiology And Pathology, Maggie Bennett
Dissertations
Vascular smooth muscle cells (SMCs) surround many blood vessels throughout the body,where they dynamically alter vessel diameter to regulate blood pressure, provide structural integrity, and absorb shock on a beat-to-beat timescale. As smooth muscle function fails, profound vascular disease ensues, often with tragic results- even death. Smooth muscle myosin 2 (SM2) is the dominant motor protein that actuates contractility and allows SMCs to perform these vital functions. To function, SM2 monomers dynamically assemble into filaments, which upon SMC activation, associate with filamentous actin to drive contractility. Despite the critical contribution of SM2 to SMC function, foundational aspects of SM2 assembly …
Investigating The Impact Of Nonenzymatic Lysine Acetylation On The Function Of The Bacterial Ribosome, Sarah Caldwell Feid
Investigating The Impact Of Nonenzymatic Lysine Acetylation On The Function Of The Bacterial Ribosome, Sarah Caldwell Feid
Dissertations
An under-investigated target of lysine acetylation is the bacterial ribosome. Although lysine acetylations on the ribosome are common and conversed in diverse bacterial species, little work has been done to understand how lysine acetylation affects the bacterial ribosome. The goal of this work is to determine if lysine acetylation has functional impact on the bacterial ribosome.I have identified in vitro and in vivo effects of nonenzymatic, AcP-dependent lysine acetylation on translation and the ribosome. In vitro acetylation of transcription-translation reactions causes a translation-specific defect that is unaffected by the addition of the CobB deacetylase. This suggests certain AcP-sensitive residues that …
Role Of Micrornas In Intestinal Inflammation And Barrier Homeostasis After Alcohol And Burn Injury, Caroline J. Herrnreiter
Role Of Micrornas In Intestinal Inflammation And Barrier Homeostasis After Alcohol And Burn Injury, Caroline J. Herrnreiter
Dissertations
MicroRNAs are small noncoding RNA molecules that negatively regulate gene expression. Within the intestinal epithelium, miRNAs play a critical role in gut homeostasis and aberrant miRNA expression has been implicated in various disorders associated with intestinal inflammation and barrier disruption. In this study, we sought to profile changes in intestinal epithelial cell miRNA expression after alcohol and burn injury and elucidate their impact on inflammation and barrier integrity. In a more targeted approach, we began by focusing on anti-inflammatory miRNAs that, when downregulated, could exacerbate inflammation and result in intestinal barrier disruption. Using a mouse model of acute ethanol intoxication …
Characterization Of Mroq-Dependent Regulation Of Staphylococcus Aureus Quorum Sensing, Madison Ruth Stock
Characterization Of Mroq-Dependent Regulation Of Staphylococcus Aureus Quorum Sensing, Madison Ruth Stock
Dissertations
Gram-positive bacteria produce small autoinducing peptides (AIPs), which act to regulate expression of genes that promote adaptive traits including virulence. The Gram-positive pathogen Staphylococcus aureus generates a cyclic AIP that controls expression of virulence factors via the accessory gene regulatory (Agr) system. S. aureus strains belong to one of four Agr groups (I, II, III, and IV), and each group harbors allelic variants of AgrD, the precursor of AIP. In a prior screen for S. aureus virulence factors, the Alonzo lab identified MroQ, a putative peptidase. A ΔmroQ mutant closely resembled a Δagr mutant and had significant defects in AIP …
Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah
Characterizing The Dynamic Localization Of Cmi In Early Drosophila Development, Asra Habibullah
Master's Theses
The COMPASS-like family of lysine methyltransferases, MLR/MLX complexes, are epigenetic regulators that are essential for normal development through the methylation of the fourth lysine residue on histone 3 (H3K4), a universal epigenetic mark associated with active transcription. This family of complexes is highly conserved from yeast to mammals and the genes encoding the human MLR complexes have been associated with various developmental diseases and cancers (Dingwall and Fagan, 2019). In D. melanogaster, the enzymatic methyltransferase core of this complex is composed of two proteins: Cara Mitad (Cmi, also known as Lpt) and Trithorax-related (Trr). Although these proteins have been shown …
Targeting The Subacute Progression Of Hippocampal Cellular Senescence Following Repetitive Mild Traumatic Brain Injury, Jacob Edward Exline
Targeting The Subacute Progression Of Hippocampal Cellular Senescence Following Repetitive Mild Traumatic Brain Injury, Jacob Edward Exline
Master's Theses
Repetitive mild traumatic brain injury (rmTBI) increases an individual’s risk for developing persistent deficits in recognition memory with symptoms experienced by up to 30% of rmTBI patients. Cellular senescence has been suggested as an underlying mechanism of persistent rmTBI symptoms; however, the subacute progression of cellular senescence following rmTBI has not been evaluated. Furthermore, the use of subacute testosterone administration to treat persistent recognition memory deficits and the cellular and molecular underpinnings has yet to be well characterized. Our lab utilizes a 5-hit closed-head rmTBI rat model to induce deficits in recognition memory and determine the effects of subacute testosterone …
How To Build A Cortex: Coordinated Assembly Of Cortical Septins And Actomyosin In The Leader Bleb, Asia Marie Paguntalan
How To Build A Cortex: Coordinated Assembly Of Cortical Septins And Actomyosin In The Leader Bleb, Asia Marie Paguntalan
Master's Theses
In confined spaces, migrating cells can undergo mesenchymal-to-amoeboid transitions by altering their cortical dynamics and adhesion with the environment. Septins frequently associate with cortical actin and non-muscle myosin (NMII), but the functional nature of these interactions remains unclear. Upon non-adhesive confinement and NMII enrichment, fibroblasts can switch to a fast, leader bleb-based mode of motility, characterized by the absence of adhesions and stress fibers and formation of a single, elongated leader bleb. During this transition, cortical actin remodeling and polarized NMII contractility drive leader bleb stabilization by generating long-range cortical flows, in coordination with changes in septin localization and assembly …
Incorporating Sex Chromosomes In Transcriptome Prediction Models And Improving Cross-Population Prediction Performance, Daniel S. Araujo
Incorporating Sex Chromosomes In Transcriptome Prediction Models And Improving Cross-Population Prediction Performance, Daniel S. Araujo
Master's Theses
Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized multivariate adaptive shrinkage may improve cross-population transcriptome prediction, as it leverages effect size estimates across different conditions - in this case, different populations. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWAS) using different methods (Elastic Net, Matrix eQTL and Multivariate Adaptive Shrinkage in R (MASHR)) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in …
Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied
Characterization Of The Full-Length Bag3 Protein And Stress Induced Formation Of Bag3-Z, Ahmed Gamal Abdalla Zied
Master's Theses
Bcl2-associated athanogene-3 (BAG3) is a pro-autophagy co-chaperone that we havepreviously shown localizes to the cardiac sarcomere and is critical for proteostasis and maintenance of normal sarcomeric function. Indeed, BAG3 loss in heart failure (HF) results in accumulation of ubiquitinated sarcomeric proteins, and depressed maximum force generating capacity (Fmax). However, how BAG3 is regulated in the cell is not well understood, with uncertainty about its structure and proteoforms. During our analysis of human heart tissue, BAG3 appears as a “doublet”, with one band at 74 kDa (BAG3-Z) and a second at a higher 85 kDa (BAG3-FL). Previous studies hypothesized the full-length …
A Population Level Examination Of The Incredible Fruit Diversity In Astragalus Lentiginosus, Quinn Thomas
A Population Level Examination Of The Incredible Fruit Diversity In Astragalus Lentiginosus, Quinn Thomas
Master's Theses
Astragalus lentiginosus is the most taxomically diverse species in the North American flora with over 40 recognized varieties. The incredible diversity within A. lentiginosus, particularly in respect to its fruit morphology, makes it an exceptional model to study adaptation and evolution. However, it remains unknown whether fruit morphology is an adaptation and, if so, the extent to which selection or neutral evolutionary processes shape the striking diversity in this trait. In order to understand the adaptive significance of fruit morphology we must first understand the genetic structure of A. lentiginosus. Varieties of A. lentiginosus vary considerably in their range size …
Comparison Of Taxonomy Assignment And Strain Detection In Urobiome Communities Using 16s Rrna Sequencing And Shotgun Metagenomic Sequencing, Delaney Sauer
Master's Theses
Advancements in sequencing technologies have enabled scientists to gain insight into the microbes that inhabit the human body, including the urinary tract. Cataloging the bacteria that inhabit the urinary tract has primarily relied on amplification and sequencing of specific variable regions of the 16S rRNA gene enabling genus-level taxonomic identification. Recently, shotgun metagenomic sequencing has been employed such that bacterial taxonomy as well as the functionality that they encode can be inferred. In this study, we compare taxonomies assigned by 16S sequencing and shotgun metagenomic sequencing of the urinary microbiota (urobiome) of females with and without a clinical diagnosis of …
Identification Of Conditions That Promote Biofilm Formation By Vibrio Fischeri And Elucidation Of The Underlying Signal Transduction Pathway, Courtney Noelle Dial
Identification Of Conditions That Promote Biofilm Formation By Vibrio Fischeri And Elucidation Of The Underlying Signal Transduction Pathway, Courtney Noelle Dial
Dissertations
Biofilms are communities of microorganisms that have intrinsically antimicrobial properties and are difficult to treat in the clinical setting. The marine bacterium Vibrio fischeri efficiently colonizes its symbiotic squid host, Euprymna scolopes, by producing a transient biofilm dependent on the symbiosis polysaccharide (SYP), making it the perfect model system to study biofilm dynamics. In vitro, however, wild-type (WT) strain ES114 fails to form SYP – dependent biofilms. Instead, genetically engineered strains, such as those lacking the negative regulator BinK, have been developed to study SYP biofilms. Historically, V. fischeri has been grown using LBS, a complex medium containing tryptone and …
Identification Of New Substrates From Pseudomonas Aeruginosa Exos, Adam V. Thota
Identification Of New Substrates From Pseudomonas Aeruginosa Exos, Adam V. Thota
Master's Theses
Pseudomonas aeruginosa is a gram-negative environmental bacterium that uses its intrinsic and acquired antibiotic resistance to infect patients with compromised epithelium, such as cystic fibrosis and burn wounds, and corneal keratitis. In order to cause disease, most strains of P. aeruginosa use the type three secretion system (T3SS) to disrupt cellular signaling and integrity. However, P. aeruginosa may also secrete exotoxins after invading host cells, which prolongs host cell death and maintains an intracellular niche. Of the T3 secreted effector toxins, ExoS, specifically the ADP-ribosyltransferase activity of ExoS, was shown to delay the death of invaded corneal cells, but it …
Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary
Dynamic Control Of The Cardiac Calcium Pump, Sean Robert Cleary
Dissertations
The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) sequesters Ca2+ into the endoplasmic reticulum of cells to establish a reservoir for Ca2+ signaling. In the heart, the activity of this transporter is tightly controlled via direct interactions with two competing regulatory micropeptides: phospholamban (PLB) and dwarf open reading frame (DWORF). PLB inhibits SERCA, while DWORF activates SERCA. These competing interactions determine cardiac performance by modulating the Ca2+ signals that drive the contraction/relaxation cycle. Previous studies indicated these SERCA-micropeptide interactions are Ca2+-sensitive; SERCA binds PLB more avidly at low cytoplasmic [Ca2+] but binds DWORF better when [Ca2+] is high. Here, FRET-microscopy demonstrated that this …