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Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis, Shashank Shrishrimal 2020 University of Nebraska Medical Center

Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis, Shashank Shrishrimal

Theses & Dissertations

Radiation therapy is frequently used as a treatment strategy for prostate cancer patients, which leads to several side effects due to damage to health tissue around the tumor and the development of radiation-induced fibrosis (RIF). Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of RIF. However, understanding of the radioprotective molecular pathway associated with these compounds remains limited. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment may activate the nuclear factor erythroid 2-related factor 2 ...


Microrna199b Regulates Mouse Hematopoietic Stem Cells Maintenance, Aldona A. Karaczyn, Edward Jachimowicz, Jaspreet S. Kohli, Pradeep Sathyanarayana 2020 Maine Medical Center

Microrna199b Regulates Mouse Hematopoietic Stem Cells Maintenance, Aldona A. Karaczyn, Edward Jachimowicz, Jaspreet S. Kohli, Pradeep Sathyanarayana

Costas T. Lambrew Research Retreat 2020

The preservation of hematopoieticstem cell pool in bone marrow (BM) is crucial for sustained hematopoiesisin adults. Studies assessing adult hematopoieticstem cells functionality had been shown that for example loss of quiescence impairs hematopoieticstem cells maintenance. Although, miR‐199b is frequently down‐regulated in acute myeloid leukemia, its role in hematopoieticstem cells quiescence, self‐renewal and differentiation is poorly understood. Our laboratory investigated the role of miR‐199b in hematopoieticstem and progenitor cells (HSPCs) fate using miR‐199b‐5p global deletion mouse model. Characterization of miR‐199b expression pattern among normal HSPC populations revealed that miR‐199b is enriched in LT ...


The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients, Syed Ahmad Rizvi 2020 Wayne State University Division of Kinesiology, Health and Sport Studies & Honors College

The Implementation Of Exercise For Chronic Kidney Disease And Dialysis Patients, Syed Ahmad Rizvi

Honors College Theses

While commonly known to be the organ that helps with urine production within the human body, the kidney plays one of the most crucial roles in maintaining homeostasis. When establishing all of the roles the kidney has on keeping humans healthy, there is the question of how does the body cope when a patient is diagnosed with kidney failure. One of the more common treatment options that allows the body to continue to function without a kidney is by beginning a patient on a form of dialysis. However, as with any treatment, there will always be a list of side ...


Utilizing Chemical Mutagenesis To Determine U21 Mechanism Of Action In Toxoplasma Gondii, Andrew Pham 2020 University of Nebraska at Omaha

Utilizing Chemical Mutagenesis To Determine U21 Mechanism Of Action In Toxoplasma Gondii, Andrew Pham

Student Research and Creative Activity Fair

The abstract has been removed to protect intellectual property of the project.


Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu 2020 Marshall University

Generation Of In-Frame Gene Deletion Mutants In Pseudomonas Aeruginosa And Testing For Virulence Attenuation In A Simple Mouse Model Of Infection, Meagan E. Valentine, Brandon D. Kirby, Hongwei D. Yu

Biomedical Sciences

Microorganisms are genetically versatile and diverse and have become a major source of many commercial products and biopharmaceuticals. Though some of these products are naturally produced by the organisms, other products require genetic engineering of the organism to increase the yields of production. Avirulent strains of Escherichia coli have traditionally been the preferred bacterial species for producing biopharmaceuticals; however, some products are difficult for E. coli to produce. Thus, avirulent strains of other bacterial species could provide useful alternatives for production of some commercial products. Pseudomonas eruginosa is a common and well-studied Gram-negative bacterium that could provide a suitable alternative ...


Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren McGee, Jane Y. Wu 2020 Illinois Mathematics and Science Academy

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With ...


Detection Of A Peptide Hormone - Somatostatin - Label-Free Split-Aptameric Probes, Charles A. Dowis 2020 University of Central Florida

Detection Of A Peptide Hormone - Somatostatin - Label-Free Split-Aptameric Probes, Charles A. Dowis

Honors Undergraduate Theses

Peptide hormones are important biomolecules that transduce downstream effects such as cell proliferation, regulation, and gene expression. Their levels have been upregulated in various disorders such as cancer, yet detection methods are lacking. We designed two split aptamer-based assays for the detection of a peptide hormone – Somatostatin (SST) – with different signal readouts: fluorescent readout based on light-up aptamers and the colorimetric readout of ABTS peroxidation from a G-quadruplex. We used an already selected split-aptamer –SSTA5–for SST for our designs and we had expected the developed detection systems to exhibit detection and quantification capabilities that would hopefully allow their use ...


Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri 2019 Thomas Jefferson University

Gasdermins In Apoptosis: New Players In An Old Game., Corey Rogers, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as ...


Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast 2019 Liberty University

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms ...


Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina 2019 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal ...


It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown 2019 Missouri State University

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

MSU Graduate Theses

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors ...


#3 - Inhibition Of The Mitochondrial Calcium Uniporter Reduces Oxidative Phosphorylation In Sgk1-Knockout Vsmc Upon Dietinduced Obesity, Bao Tran, Sharon Francis, Wei Zhong 2019 Georgia Gwinnett College

#3 - Inhibition Of The Mitochondrial Calcium Uniporter Reduces Oxidative Phosphorylation In Sgk1-Knockout Vsmc Upon Dietinduced Obesity, Bao Tran, Sharon Francis, Wei Zhong

Georgia Undergraduate Research Conference (GURC)

Obesity is linked to vascular diseases such as atherosclerosis and coronary artery disease which is a major underlying cause of heart attacks. While the mechanism is not fully known, altering mitochondrial respiration which occurs through oxidative phosphorylation (OXPHOS) may influence the development of vascular disease during obesity. Our previous data with diet-induced obese (DIO) mice demonstrated that serum and glucocorticoid-inducible kinase 1 (SGK1), which regulates cell metabolism, was up-regulated in vascular smooth muscle cells (VSMC) from the aorta. Knocking out SGK1 in VSMCs (KOSGK1) was associated with higher OXPHOS and lower vascular disease relative to wildtype VSMCs (WTSGK1) during DIO ...


A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., James Forder, Mallory Smith, Margot Wagner, Rachel J. Schaefer, Jonathan Gorky, Kenneth L. van Golen, Anja Nohe, Prasad Dhurjati 2019 University of Delaware

A Physiologically-Based Pharmacokinetic Model For Targeting Calcitriol-Conjugated Quantum Dots To Inflammatory Breast Cancer Cells., James Forder, Mallory Smith, Margot Wagner, Rachel J. Schaefer, Jonathan Gorky, Kenneth L. Van Golen, Anja Nohe, Prasad Dhurjati

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Quantum dots (QDs) conjugated with 1,25 dihydroxyvitamin D3 (calcitriol) and Mucin-1 (MUC-1) antibodies (SM3) have been found to target inflammatory breast cancer (IBC) tumors and reduce proliferation, migration, and differentiation of these tumors in mice. A physiologically-based pharmacokinetic model has been constructed and optimized to match experimental data for multiple QDs: control QDs, QDs conjugated with calcitriol, and QDs conjugated with both calcitriol and SM3 MUC1 antibodies. The model predicts continuous QD concentration for key tissues in mice distinguished by IBC stage (healthy, early-stage, and late-stage). Experimental and clinical efforts in QD treatment of IBC can be augmented by ...


Virally Packaged Rna In Virus-Like Particle Vaccines Enhances Antigenicity And Augments Latency Reversal Of Hiv-1, Chanuka Wijewardhana 2019 The University of Western Ontario

Virally Packaged Rna In Virus-Like Particle Vaccines Enhances Antigenicity And Augments Latency Reversal Of Hiv-1, Chanuka Wijewardhana

Electronic Thesis and Dissertation Repository

Introduction:

Since Human Immunodeficiency Virus (HIV)-1 was determined to be the etiological agent behind acquired immunodeficiency syndrome (AIDS) in 1983, numerous attempts at a cure have been made; however, none have been effective. One of the primary roadblocks in achieving a cure is a transcriptionally-silent latent reservoir of memory CD4+ T cells harboring HIV provirus. Combined antiretroviral therapy (cART) inhibits actively replicating virus by interfering with various stages of the replication cycle. Therefore, non-replicative viruses–like the proviruses found in latently infected cells–are hidden from the actions of continued antiretroviral therapy. As a result, cART discontinuation or treatment ...


Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée de Leeuw, Karen E. Knudsen, J. Alan Diehl 2019 Medical University of South Carolina; Case Western Reserve University

Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl

Department of Cancer Biology Faculty Papers

The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of ...


Heme And Hemoglobin Utilization By Mycobacterium Tuberculosis., Avishek Mitra, Ying-Hui Ko, Gino Cingolani, Michael Niederweis 2019 University of Alabama at Birmingham

Heme And Hemoglobin Utilization By Mycobacterium Tuberculosis., Avishek Mitra, Ying-Hui Ko, Gino Cingolani, Michael Niederweis

Department of Biochemistry and Molecular Biology Faculty Papers

Iron is essential for growth of Mycobacterium tuberculosis (Mtb), but most iron in the human body is stored in heme within hemoglobin. Here, we demonstrate that the substrate-binding protein DppA of the inner membrane Dpp transporter is required for heme and hemoglobin utilization by Mtb. The 1.27 Å crystal structure of DppA shows a tetrapeptide bound in the protein core and a large solvent-exposed crevice for heme binding. Mutation of arginine 179 in this cleft eliminates heme binding to DppA and prevents heme utilization by Mtb. The outer membrane proteins PPE36 and PPE62 are also required for heme and ...


Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu 2019 Nemours/Alfred I. duPont Hospital for Children

Development Of Substrate Degradation Enzyme Therapy For Mucopolysaccharidosis Iva Murine Model., Kazuki Sawamoto, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Conventional enzyme replacement therapy (ERT) is approved for MPS IVA. However, the fact that the infused enzyme cannot penetrate avascular lesions in cartilage leads to minimal impact on the bone lesion. Moreover, short half-life, high cost, instability, and narrow optimal pH range remain unmet challenges in ERT. Thermostable keratanase, endo-β-N-acetylglucosaminidase, has a unique character of a wide optimal pH range of pH 5.0-7.0. We hypothesized that this endoglycosidase degrades keratan sulfate (KS) polymer in circulating blood and, therefore, ameliorates the accumulation of ...


The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer 2019 The University of Western Ontario

The Role Of The Tau N-Terminal Phosphatase-Activating Domain And Phosphorylation At Thr175 In The Formation Of Tau Cytoplasmic Inclusions, Matthew A. Hintermayer

Electronic Thesis and Dissertation Repository

Cytoplasmic inclusions and fibrils of the microtubule-associated protein tau (tau protein) are a key neuropathological hallmark in tauopathies, including Alzheimer’s disease, chronic traumatic encephalopathy, and amyotrophic lateral sclerosis with cognitive impairment. Previous research has demonstrated that the phosphorylation of tau protein at Thr175 is sufficient for the initiation of fibril formation both in vitro and in vivo. Here we use mutated tau protein constructs to demonstrate that phosphorylation at Thr175 results in the aberrant exposure of an N-terminal phosphatase-activating domain (PAD). The tau PAD interacts with protein phosphatase 1 (PP1) leading to the activation of glycogen synthase ...


Cleavage And Sub-Cellular Redistribution Of Nuclear Pore Protein 98 By Coxsackievirus B3 Protease 2a Impairs Cardioprotection., Paul J. Hanson, Al Rohet Hossain, Ye Qiu, Huifang M. Zhang, Guangze Zhao, Cheng Li, Veena Lin, Saheedat Sulaimon, Marli Vlok, Gabriel Fung, Victoria H. Chen, Eric Jan, Bruce M. McManus, David J. Granville, Decheng Yang 2019 University of British Columbia; St. Paul's Hospital

Cleavage And Sub-Cellular Redistribution Of Nuclear Pore Protein 98 By Coxsackievirus B3 Protease 2a Impairs Cardioprotection., Paul J. Hanson, Al Rohet Hossain, Ye Qiu, Huifang M. Zhang, Guangze Zhao, Cheng Li, Veena Lin, Saheedat Sulaimon, Marli Vlok, Gabriel Fung, Victoria H. Chen, Eric Jan, Bruce M. Mcmanus, David J. Granville, Decheng Yang

College of Population Health Faculty Papers

Myocarditis, inflammation of the heart muscle, affects all demographics and is a major cause of sudden and unexpected death in young people. It is most commonly caused by viral infections of the heart, with coxsackievirus B3 (CVB3) being among the most prevalent pathogens. To understand the molecular pathogenesis of CVB3 infection and provide strategies for developing treatments, we examined the role of a key nuclear pore protein 98 (NUP98) in the setting of viral myocarditis. NUP98 was cleaved as early as 2 h post-CVB3 infection. This cleavage was further verified through both the ectopic expression of viral proteases and in ...


Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong 2019 The University of Western Ontario

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found that ...


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