Development Of A Ph-Triggered Cargo Delivery System With Esxa Mutants,
2022
University of Texas at El Paso
Development Of A Ph-Triggered Cargo Delivery System With Esxa Mutants, Shuchen Chen
Open Access Theses & Dissertations
Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb). It was the leading cause of human death generated by a single infectious agent before the Coronavirus (COVID-19) pandemic. Mtb has a special mechanism to evade the hostâ??s immune system and utilize macrophages as reservoirs. Latent TB infections have been a threat to public health. Liposome has been widely used for drug delivery. Immunoliposomes are special liposome carriers coated with ligands, such as antigens, targeting certain cells or organs to regulate the uptake of liposome. By constructing the liposome components, or surface modification, cargo release of liposome can be …
Characterization Of Esxa/Esxb Heterodimer Membrane Interaction With A Novel Popc/Popg Liposome Model,
2022
University of Texas at El Paso
Characterization Of Esxa/Esxb Heterodimer Membrane Interaction With A Novel Popc/Popg Liposome Model, Salvador Vazquez Vazquez Reyes
Open Access Theses & Dissertations
EsxA and EsxB are co-secreted as a heterodimer and have been shown to play critical roles in phagosome rupture and translocation of Mycobacterium tuberculosis into the cytosol. Current in vitro studies support a model in which the EsxA:EsxB heterodimer is dissociated upon acidification, which might allow EsxA insertion into liposome membranes. While the membrane permeabilizing activity (MPA) of EsxA has been well characterized in liposomes composed of di-oleoyl-phosphatidylcholine (DOPC), the MPA of EsxA:EsxB heterodimer has not been detected with the DOPC liposome. In this study, we established a new in vitro membrane assay to test the MPA of EsxA and …
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection,
2022
The Texas Medical Center Library
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions.,
2022
University of Louisville
A Computational Model Of The Line-1 Retrotransposon Life Cycle And Visualization Of Metabolic Networks In 3-Dimensions., Michael D. Martin
Electronic Theses and Dissertations
Computational modeling of metabolic reactions and cellular systems is evolving as a tool for quantitative prediction of metabolic parameters and reaction pathway analysis. In this work, the basics of computational cell biology are presented as well as a summary of physical processes within the cell, and the algorithmic methods used to find time dependent solutions. Protein-protein and enzyme-substrate interactions are mathematically represented via mass action kinetics to construct sets of linear differential equations that describe reaction rates and formation of protein complexes. Using mass action methods, examples of reaction networks and their solutions are presented within the Virtual Cell simulation …
Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases,
2022
Clemson University
Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala
All Dissertations
Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …
Hsp- 70 Mediated Nervous System Enhancement By Etas,
2022
Texas Southern University
Hsp- 70 Mediated Nervous System Enhancement By Etas, Taylor Carter
Theses (2016-Present)
Neurodegenerative disease in the CNS is usually a product of increased oxidative stress in the brain. In this study we tested the ability of an asparagus supplement ETAS to help reduce oxidative stress in the normal brains of Balb C mice. Oxidative stress pathways (Heat shock proteins) are usually cumulative in the damage they cause when disrupted. We treated normal Balb C mice with ETAS and had control groups with no ETAS supplementation in their regular diet. We then sacrificed the mice and conducted microarray studies to compare oxidative stress pathway genes. We also characterized the effects of regular oxidative …
Metabolite Damage And Damage Control In A Minimal Genome,
2022
University of Florida
Metabolite Damage And Damage Control In A Minimal Genome, Drago Haas, Antje M. Thamm, Jiayi Sun, Lili Huang, Lijie Sun, Guillaume A.W. Beaudoin, Kim S. Wise, Claudia Lerma-Ortiz, Steven D. Bruner, Marian Breuer, Zaida Luthey-Schulten, Jiusheng Lin, Mark A. Wilson, Greg Brown, Alexander F. Yakunin, Inna Kurilyak, Jacob Folz, Oliver Fiehn, John I. Glass, Andrew D. Hanson, Christopher S. Henry, Valérie De Crécy-Lagard
Biochemistry -- Faculty Publications
Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes known to have such functions were identified and experimentally validated, including 5-formyltetrahydrofolate cycloligase, coenzyme A (CoA) disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and …
Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress,
2022
Old Dominion University
Clostridioides Difficile Biofilm And Spore Production In Response To Antibiotics And Immune Stress, Adenrele M. Oludiran
Chemistry & Biochemistry Theses & Dissertations
The development of new therapeutic options against Clostridioides difficile (C. difficile) infection is a critical public health concern, as the causative bacterium is highly resistant to multiple classes of antibiotics. C. difficile, an anaerobic spore-forming Gram-positive pathogenic bacterium, is a major cause of hospital-acquired infections. C. difficile persists in the environment and spreads the infection to new hosts in the form of dormant spores and can persist within hosts as surface-attached biofilms. These studies investigate bacterial vegetative cell survival, biofilm formation, and sporulation in response to stress. Antimicrobial host-defense peptides (HDPs) are highly effective at simultaneously modulating …
Immune Cell-Protein Interactions In Alzheimer’S Disease,
2022
University of Missouri-St. Louis
Immune Cell-Protein Interactions In Alzheimer’S Disease, Kapur Dhami
Dissertations
Misfolded protein aggregates are one of the significant contributing factors in many neurogenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others. My PhD research project was to study various aspects of amyloid-β peptide, a 40-42-residue peptide and the primary component of the senile plaques found in Alzheimer’s disease (AD) brains. One objective of my research was to purify and characterize the intermediate Aβ42 species using an array of biophysical techniques like size exclusion chromatography, fluorescence assays, circular dichroism, cellular assays, and protein assays. The other major research thrust of my project was to study the role of microglial …
Growth Outcomes Of Pseudomonas Aeruginosa Inhibitor Of Vertebrate Lysozyme Knockouts In Conditions Mimicking The Cystic Fibrosis Lung Environment,
2022
Kennesaw State University
Growth Outcomes Of Pseudomonas Aeruginosa Inhibitor Of Vertebrate Lysozyme Knockouts In Conditions Mimicking The Cystic Fibrosis Lung Environment, Amani Gaddy
Master of Science in Chemical Sciences Theses
Pseudomonas aeruginosa (PA) is a Gram-negative bacterium, often found in cystic fibrosis (CF) patients and can lead to the decline of lung functioning and premature death in 80% of infected patients when microcolonies form within the mucin of the lung. Due to its major capacity for antibiotic resistance, an alternative strategy towards defending against the bacterial invasion of PA is by the antibacterial activity of our own innate immune system with use of elements such as lysozyme. Pseudomonas aeruginosa inhibitor of vertebrate lysozyme class 1 (Ivyp1) is a periplasmic protein produced by gram-negative bacteria that inhibits the enzymatic activity of …
Quantifying Protein Quality To Understand Protein Homeostasis (Supplemental Data),
2022
Brigham Young University
Quantifying Protein Quality To Understand Protein Homeostasis (Supplemental Data), Hsien-Jung Lavender Lin
ScholarsArchive Data
This data set includes the supplementary data for chpaters 3 and 4 in the dissertation Quantifying Protein Quality to Understand Protein Homeostasis. It includes various excel worksheets that were used to generate the data reported in the dissertation. We make this data available to the public so anyone who wants to reproduce the results has the resources and access to other perspectives that weren't discussed in depth in the dissertation. Chapter 3 used mass-spectrometry to quantify the surface accessibility differences in human serum albumin (HSA)between patients with and without rheumatoid arthritis (RA). We found certain residues are less reactive …
The Importance Of Co2 Recapture In The Co2 Concentrating Mechanism Of Chlamydomonas Reinhardtii,
2022
Louisiana State University
The Importance Of Co2 Recapture In The Co2 Concentrating Mechanism Of Chlamydomonas Reinhardtii, Ashwani Rai
LSU Doctoral Dissertations
The aim of this thesis is to investigate the CO2 concentrating mechanism (CCM) of Chlamydomonas reinhardtii and to develop a quick method for estimating the activity of carbonic anhydrases (CAs). The first project demonstrates that there are two almost identical mitochondrial CAs in C. reinhardtii, CAH4 and CAH5, that help to maintain photosynthesis and minimize the leak of CO2 generated by respiration and photorespiration. We used an RNAi approach to reduce the expression of CAH4 and CAH5 so that their physiological functions could be studied. RNAi mutants with low expression of CAH4 and CAH5 have impaired rates …
Methanogen Metabolic Flexibility,
2022
University of Nebraska-Lincoln
Methanogen Metabolic Flexibility, Sean Carr
Dissertations and Theses in Biological Sciences
Methanogens are obligately anaerobic archaea which produce methane as a byproduct of their respiration. They are found across a wide diversity of environments and play an important role in cycling carbon in anaerobic spaces and the removal of harmful fermentation byproducts which would otherwise inhibit other organisms. Methanogens subsist on low-energy substrates which requires them to utilize a highly efficient central metabolism which greatly favors respiratory byproducts over biomass. This metabolic strategy creates high substrate:product conversion ratios which is industrially relevant for the production of biomethane, but may also allow for the production of value-added commodities. Particularly of interest are …
Wdr5 Network Analysis Using Ensemble Approaches,
2022
Syracuse University
Wdr5 Network Analysis Using Ensemble Approaches, Ali Imran
Dissertations - ALL
Understanding the properties of protein-protein interactions (PPIs) is necessary to deconvolute the processes inside living organisms. As such, research in this regard has significant implications for gaining insight into cancers and other diseases. Once understood, drugs can be designed to target these diseases. In these chapters we focus on the network of interactions of WD40 repeat protein 5 (WDR5), a known hub protein. Several of its interactions are significant for regulation of histone methylation and consequently epigenetic regulation. These interacting partners include the SET1 family of proteins and retinoblastoma binding protein-5 (RbBP5). In this work we used multiple ensemble measurement …
Characterization Of The Responses To Chronic Stress In Caenorhabditis Elegans,
2022
Florida Institute of Technology
Characterization Of The Responses To Chronic Stress In Caenorhabditis Elegans, Amy Laura Knight
Theses and Dissertations
Exposure to chronic temperature stress influences organismal phenotypes that are important for human health, agriculture, and ecology. In this thesis, the model organism Caenorhabditis elegans was used to study the effects of temperature stress on reproduction and lifespan. It was found that worms demonstrated a rapid shut down in egg-laying between 18-24 hours of exposure to 28°C. Despite this reproductive defect, the overall lifespan of worms was unaffected. At the molecular level, heat shock factor 1 (HSF-1), a regulator of the protective molecular pathway known as the heat shock response (HSR), was identified as important for progeny production during heat …
Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans,
2022
University of South Florida
Regulation Of The Heat Shock Response Via Lysine Acetyltransferase Cbp-1 And In Neurodegenerative Disease In Caenorhabditis Elegans, Lindsey N. Barrett
USF Tampa Graduate Theses and Dissertations
The decline of proteostasis is a hallmark of aging that is, in part, affected by the dysregulation of the heat shock response (HSR), a highly conserved cellular response to proteotoxic stress in the cell. The heat shock transcription factor HSF-1 is well-studied as a key regulator of proteostasis, but mechanisms that could be used to modulate HSF-1 function to enhance proteostasis during aging are largely unknown. In this study, we examined lysine acetyltransferase regulation of the HSR and HSF-1 in C. elegans. We performed an RNA interference screen of lysine acetyltransferases and examined mRNA expression of the heat-shock inducible gene …
In Vivo Evaluation Of (-)-Zampanolide Demonstrates Potent And Persistent Antitumor Efficacy When Targeted To The Tumor Site.,
2022
University of Texas Health Science Center
In Vivo Evaluation Of (-)-Zampanolide Demonstrates Potent And Persistent Antitumor Efficacy When Targeted To The Tumor Site., Leila Takahashi-Ruiz, Joseph D Morris, Phillip Crews, Tyler A Johnson, April L Risinger
Natural Sciences and Mathematics | Faculty Scholarship
Microtubule-stabilizing agents (MSAs) are a class of compounds used in the treatment of triple-negative breast cancer (TNBC), a subtype of breast cancer where chemotherapy remains the standard-of-care for patients. Taxanes like paclitaxel and docetaxel have demonstrated efficacy against TNBC in the clinic, however new classes of MSAs need to be identified due to the rise of taxane resistance in patients. (-)-Zampanolide is a covalent microtubule stabilizer that can circumvent taxane resistance in vitro but has not been evaluated for in vivo antitumor efficacy. Here, we determine that (-)-zampanolide has similar potency and efficacy to paclitaxel in TNBC cell lines, but …
A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds,
2022
University of South Florida
A Protein-Based Therapeutic Combination For The Treatment Of Hard-To-Heal Wounds, Graham L. Strauss
USF Tampa Graduate Theses and Dissertations
Chronic wounds present many clinical challenges in relation to the successful treatment and closure of the damaged tissue. Most current treatment methods focused on one or two aspects to drive wound closure, while most chronic wounds are multifactorial environments with many of those dependencies relying on the termination of one another to effectively gain tissue construction, closure, and full skin thickness and composition. Natural wound healing processes allude to potential biologics that can impede the chronic breakdown of tissue, while restoring deposition of new tissue, and effectively leading to a healed wound. Proteases secreted by the body’s immune system lay …
Effect Of A Commonly Used Veterinary Antibiotic On Oxidative Stress And Root Transporters Of Edible Legumes And Leafy Crops,
2022
PhD Students, Faculty of Science, Beirut Arab University
Effect Of A Commonly Used Veterinary Antibiotic On Oxidative Stress And Root Transporters Of Edible Legumes And Leafy Crops, Safaa Nassar, Jamilah Borjac
BAU Journal - Science and Technology
Antibiotic accumulation in soil and plants is a rising problem in agriculture creating a serious threat to living organisms in the environment, hence needing huge attention. To this end, glasshouse pot experiments were conducted to simulate contamination by veterinary antibiotic at 150 mg kg-1 and 4800 mg kg-1 in a virgin soil in which lentil (Lens culinaris Medik.), chickpea (Cicer arietinum L.), arugula (Eruca sativa Mill.) and cress (Lepidium sativum L.) were grown, aiming at evaluating the potential toxicity of antibiotic in plants roots during their growth period. Biomarkers of toxicity such as malondialdehyde and proline …
Mechanism Of Sila- And Germafluorenes For Biological Applications,
2022
University of Missouri-St. Louis
Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett
Dissertations
2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …
