An Investigation Into The Mechanism Of Proteasome Dysfunction In Neurodegenerative Disease And The Biological Impact Of Proteasome Hyperactivation In C. Elegans,
2022
West Virginia University
An Investigation Into The Mechanism Of Proteasome Dysfunction In Neurodegenerative Disease And The Biological Impact Of Proteasome Hyperactivation In C. Elegans, Raymond T. Anderson
Graduate Theses, Dissertations, and Problem Reports (ETD)
Aging is an inevitable process that occurs as humans grow older. It is characterized by the chronological accumulation of cellular damage over time leading to functional decline as an organism grows older. Several processes are thought to contribute to the aging phenomenon, but one of the most prolific of these is the disruption of protein homeostasis (proteostasis). The collapse of proteostasis can lead to accelerated aging and the development of age-related diseases including devastating neurodegenerative diseases (NDs) like Alzheimer and Parkinson disease. Virtually all NDs are characterized by the buildup of proteins in and around neurons resulting in neuronal death …
Tissue And Sex-Specific Rna Editing During Induced Acute Inflammation,
2022
Missouri State University
Tissue And Sex-Specific Rna Editing During Induced Acute Inflammation, Claire E. Nichols
Graduate Theses/Dissertations
A-to-I RNA editing is a process where select adenosine (A) nucleotides are deaminated by an editing enzyme, ADAR, to become inosines (I) in RNA transcripts. RNA editing can affect the sequence of the encoded protein and the regulation of the RNA. ADAR1 also plays a role in regulating innate immunity and its expression is upregulated during inflammation. Current data on the effects of increasing ADAR1 on RNA editing is limited, and most studies are completed only in male animals. We are interested in expanding RNA editing data to include female animals. Lipopolysaccharide (LPS) was used to induce acute inflammation and …
Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity,
2022
University of South Florida
Phip Variants Associated With Chung–Jansen Syndrome Disrupt Replication Fork Stability And Genome Integrity, Neysha Tirado-Class, Caitlin Hathaway, Wendy K. Chung, Huzefa Dungrawala
Molecular Biosciences Faculty Publications
Chung–Jansen syndrome (CJS) is a rare, autosomal dominant disorder characterized by developmental delay, intellectual disability/cognitive impairment, behavioral challenges, obesity, and dysmorphic features. CJS is associated with heterozygous variants in PHIP (Pleckstrin-Homology Interacting Protein), a gene that encodes one of several substrate receptors for Cullin4-RING (CRL4) E3 ubiquitin ligase complex. Full-length PHIP, also called DCAF14, was recently identified to function as a replication stress response protein. Herein, we report the identification of two PHIP missense variants identified by exome sequencing in unrelated individuals with CJS. The variants p.D488V and p.E963G occur in different functional elements of DCAF14-WD40 repeat domain and pleckstrin …
Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding,
2022
University of South Florida
Sequence Properties Of An Intramolecular Interaction That Inhibits P53 Dna Binding, Emily Gregory, Gary W. Daughdrill
Molecular Biosciences Faculty Publications
An intramolecular interaction between the p53 transactivation and DNA binding domains inhibits DNA binding. To study this autoinhibition, we used a fragment of p53, referred to as ND WT, containing the N-terminal transactivation domains (TAD1 and TAD2), a proline rich region (PRR), and the DNA binding domain (DBD). We mutated acidic, nonpolar, and aromatic amino acids in TAD2 to disrupt the interaction with DBD and measured the effects on DNA binding affinity at different ionic strengths using fluorescence anisotropy. We observed a large increase in DNA binding affinity for the mutants consistent with reduced autoinhibition. The ΔΔG between DBD and …
Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae,
2022
Belmont University
Identifying Adaptor Proteins For Selective Mrna Export In S. Cerevisiae, Chloe Baker, Rebecca Adams
Science University Research Symposium (SURS)
The export of mature mRNA from the nucleus of the cell to the cytoplasm is crucial for a cell’s survival, as this process is necessary to produce proteins encoded by these transcripts. In S. cerevisiae (yeast) cells, a protein known as Mex67 must bind to the mRNA while it’s in the nucleus so it can cross through the nuclear pore complex (NPC). Mex67 cannot bind to the mRNA directly, instead it needs to be accompanied by adaptor proteins to aid it in getting across the NPC. Stress conditions such as heat shock interferes with the function of these adaptor …
Functionalization Of Chitosan Based Microparticles For In Vitro 3d Culture Of Human Liver Cells,
2022
The University of Akron
Functionalization Of Chitosan Based Microparticles For In Vitro 3d Culture Of Human Liver Cells, William Imes
Williams Honors College, Honors Research Projects
Previous work involving 3D culture of human liver cells with fluorinated chitosan based microparticles has shown that their incorporation provides needed structural cues that the culture of cells alone does not provide, such as increased gas transport. However, using bare microparticles to grow large 3D cellular structures is not practical as they tend to collapse before any meaningful research can be done on them. It is proposed that this is because of the lack of extracellular matrix (ECM)components within pure cell culture in vitro, which in their absence cannot adequately facilitate biochemical communication and adhesion between cells. It is …
Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells,
2022
Missouri State University
Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang
Graduate Theses/Dissertations
The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …
Nutrient Scarcity And Cellular Cooperation In A Clonal Hydroid,
2022
Northern Illinois University
Nutrient Scarcity And Cellular Cooperation In A Clonal Hydroid, Weam S. El Rahmany
Graduate Research Theses & Dissertations
Biological complexity forms when lower-level units (e.g., genes, cells, organisms) cooperatively band together. This complexity may be exemplified by multicellularity, the cooperation between the cells of the same species, or symbiosis, cooperation between the cells of different species. This cooperation is under continual threat, as defection, the opposite of cooperation, is favored by default by lower-level units (i.e., cells). Animal cancers may be the most well-known phenomena that exemplify the concept of cellular defection. Cancer cells have been shown to feature morphological and metabolic traits, developed through differential gene expression or mutations, that favor their growth at the cost of …
Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks,
2022
University of Nevada, Las Vegas
Xrcc4 And Mre11 Roles And Transcriptional Response To Repair Of Talen-Induced Double-Strand Dna Breaks, Ronald Benjamin, Atoshi Banerjee, Xiaogang Wu, Corey Geurink, Lindsay Buczek, Danielle Eames, Sara G. Trimidal, Janice M. Pluth, Martin R. Schiller
Health Physics and Diagnostic Sciences Faculty Research
Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 …
Salivary Gland Stromal Heterogeneity And Epithelial Controls,
2022
University at Albany, State University of New York
Salivary Gland Stromal Heterogeneity And Epithelial Controls, Nicholas L. Moskwa
Legacy Theses & Dissertations (2009 - 2024)
Organogenesis is the process organs go through where cellular communications coordinate all a developing organ needs. What organs need are more cells, in the right place, doing the right job. In the salivary gland, we know that stromal cells are important for organogenesis and that they coordinate the epithelium’s form and functions. However, specific stromal contributions have focused on epithelial quantity and placement. There is less information about how the stroma directs the epithelium towards certain functions. Here we used organoids as a model for understanding what stromal signaling directs epithelial cell fate. We found that stromal cell state is …
Genetic Regulation Within Cellular Stress Response Pathways,
2022
University at Albany, State University of New York
Genetic Regulation Within Cellular Stress Response Pathways, Jhos M. Dufflart
Legacy Theses & Dissertations (2009 - 2024)
Cellular stress is something that a cell deals with on a regular basis. Fortunately, there are several different mechanisms that are set in place in order to deal with them. Depending on the stress present in the cell there will be different stress response pathways that are activated in order to mitigate the stress or initiate cellular death mechanisms. Transcription factors (TFs) are key components within these pathways, and this will be the focus of this thesis. TFs within mammalian stress response pathways are tasked with the essential regulation of multiple genes within these pathways and are oftentimes linked with …
Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1,
2022
University at Albany, State University of New York
Exploring The Roles Of Stress, Codon Usage, And Rna Modifications In Myotonic Dystrophy Type 1, Afrooz Golestanian
Legacy Theses & Dissertations (2009 - 2024)
Myotonic dystrophy (DM), the most common form of muscular dystrophy, is a neuromuscular disease caused by microsatellite repeat expansions. It can represent a multi-systemic autosomal dominant disease with DM1 and DM2 subtypes. A cytosine-thymine-guanine (CTG) triplet repeat in the 3’ untranslated region (3’UTR) of myotonic dystrophy protein kinase (DMPK) gene causes DM1 disease, which leads to the production of a longer, abnormal and toxic mRNA. The toxic DMPK mRNA sequester the splicing proteins such as Muscle blind-like (MBNL) and rbFOX which leads to gene expression alteration. Repeat associated non-AUG (RAN) translation also occurs in DM1. Mitochondrial dysregulation has also been …
Elucidating The Role Of Polycomb Repressive Complex 2 In Lung Stem Cell Fate And Lung Disease,
2022
University of Kentucky
Elucidating The Role Of Polycomb Repressive Complex 2 In Lung Stem Cell Fate And Lung Disease, Aria Byrd
Theses and Dissertations--Toxicology and Cancer Biology
The average human lungs take ~22,000 breaths and inhale ~2,000 gallons of air each day. This organ is the primary conduit for the transfer of oxygen to the internal organs, making it crucial for the sustainment of life. Consequently, mechanical malfunction of the lungs and/or pollution of inhaled air negatively impact internal organ function and ultimately put survival in jeopardy. Epigenetics, by nature, is a plastic phenomenon in which environmental stimuli influence short term, long term, and generational gene expression patterns. Chronic exposure of harmful stimuli to the lung epithelium has also been shown to alter epigenetic pathways, engender aberrant …
Sex Dimorphism In Hematopoiesis And Bone Marrow Niche,
2022
University of Kentucky
Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, Xiaojing Cui
Theses and Dissertations--Toxicology and Cancer Biology
Hematopoietic stem cells (HSC), which are a rare population of cells existing in human circulating blood and bone marrow, can form the whole-blood system by their self-renewal capacity and differentiation ability. Sex dimorphism can be found in hematopoietic stem and progenitor cells, and in the development of hematopoietic lineages. Also, males are at higher risk and have a worse prognosis for most hematologic malignancies than females. Under normal conditions, the number of circulating progenitor cells in women is lower than in men. Furthermore, female mice have a higher rate of HSC division than male mice. A dramatic gender difference exists …
Bone Morphogenetic Proteins Shape TReg Cells,
2022
Old Dominion University
Bone Morphogenetic Proteins Shape TReg Cells, Piotr Kraj
Biological Sciences Faculty Publications
The transforming growth factor-β (TGF-β) family includes cytokines controlling cell behavior, differentiation and homeostasis of various tissues including components of the immune system. Despite well recognized importance of TGF-β in controlling T cell functions, the immunomodulatory roles of many other members of the TGF-β cytokine family, especially bone morphogenetic proteins (BMPs), start to emerge. Bone Morphogenic Protein Receptor 1α (BMPR1α) is upregulated by activated effector and Foxp3+ regulatory CD4+ T cells (Treg cells) and modulates functions of both of these cell types. BMPR1α inhibits generation of proinflammatory Th17 cells and sustains peripheral Treg cells. This finding underscores the importance of …
Metabolic Diversity Among Fibroblasts From Regenerating And Non-Regenerating Mammals,
2022
University of Kentucky
Metabolic Diversity Among Fibroblasts From Regenerating And Non-Regenerating Mammals, Ebenezer Aryee
Theses and Dissertations--Biology
Regeneration is a wound repair process that terminates in the restoration of tissue function and structure. Fibroblasts play pivotal roles in regenerative and fibrotic wound repair. Reports of extensive regenerative ability in mammals have been historically rare, but more recently spiny mice (Acomys) have emerged as a bona fide model of complex tissue regeneration. Recent work has indicated that fibroblasts from regenerators (Acomys and Oryctolagus) are more resistant to reactive oxygen species (ROS)-induced senescence compared to non-regenerating species, suggesting the influence of intrinsic cellular states on the fate of wound repair. Determining the basal metabolic signature …
A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor,
2022
Missouri State University
A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud
Graduate Theses/Dissertations
G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y2 receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y2 R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …
Further Investigation Of The Initiating Mechanism Of The Type I Collagen Glomerulopathy,
2022
Missouri State University
Further Investigation Of The Initiating Mechanism Of The Type I Collagen Glomerulopathy, Matthew James Freese
Graduate Theses/Dissertations
The progressive accumulation of collagen and other extracellular matrix proteins in the renal mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in integrating α2(I) collagen into the type I collagen structure, termed Col1a2-deficient mice, model kidney fibrosis through the condition Type I Collagen Glomerulopathy, because homotrimeric type I collagen accumulates extracellularly in the mesangium of renal glomeruli. Accumulation of homotrimeric type I collagen compresses blood vessels in glomeruli, which reduces filtration, increases pressure, and results in fibrosis. Picrosirius red (PSR) staining was used on Col1a2 deficient and wildtype mice to evaluate collagen deposition. Histological evaluation and …
Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability,
2022
Central Washington University
Determining The Effects Of Chemical Exposure On Hepatocyte Mitochondrial Networks And Cell Viability, Bethany Eaton
All Master's Theses
Mitochondria are cellular organelles that are becoming more recently studied. One of their main functions is the production of energy through cellular respiration, which is crucial to cell life. However, they are also associated with numerous disease states. It is hypothesized that reactive oxygen species (ROS), largely produced in mitochondria, induce oxidative stress and affect mitochondrial morphology along with cell viability. This study compares chemical exposure of menadione, an ROS producer, and phthalates (plasticizers) on two mouse hepatocyte cell lines to determine the effects they have on mitochondrial morphology and cell viability. Three experiments were performed to analyze the effects …
Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles,
2022
Columbia University
Protein Charge Parameters That Influence Stability And Cellular Internalization Of Polyelectrolyte Complex Micelles, Rachel A. Kapelner, Rachel S. Fisher, Shana Elbaum-Garfinkle, Allie C. Obermeyer
Advanced Science Research Center
Proteins are an important class of biologics, but there are several recurring challenges to address when designing protein-based therapeutics. These challenges include: the propensity of proteins to aggregate during formulation, relatively low loading in traditional hydrophobic delivery vehicles, and inefficient cellular uptake. This last criterion is particularly challenging for anionic proteins as they cannot cross the anionic plasma membrane. Here we investigated the complex coacervation of anionic proteins with a block copolymer of opposite charge to form polyelectrolyte complex (PEC) micelles for use as a protein delivery vehicle. Using genetically modified variants of the model protein green fluorescent protein (GFP), …
