Medicine and Health Sciences Commons^™

Investigating The Viral Nature Of Neuronal Capsid Genes, Michael Manuel Long

Master's Theses

Memory formation is an essential part of everyday life. Neuronal communication is thought to be a key driver behind memory formation. There are two heavily studied methods of neuronal communication: chemical (neurotransmitter-mediated) and electrical (physically attached). When issues arise environmentally or genetically, people can experience one of many devastating memory disorders i.e. Alzheimer’s disease and other Dementias. Due to their prevalence, the treatments for disorders that hinder memory formation are a high priority for pharmaceutical companies. Currently, many of the treatments available focus on neurotransmitters or neuronal activity, and scientists are far from a cure. However, there may be an …

Murine Tbk1 Is Required By Flt3+ Leukemia Stem Cells Yet Dispensable In Homeostatic Hematopoiesis, Austin Runde

Master's Theses

The TANK-binding kinase 1 (TBK1) is a cytoplasmic, serine/threonine kinase and a critical activator of the innate immune system. Reports have implicated TBK1 as a promoter of multiple cancer types. Acute myeloid leukemia (AML) is a cancer arising from the hematopoietic stem/progenitor cells (HSPCs). Although ~70% of AML patients achieve complete remission with chemotherapy, at least half will relapse due to the failure to eradicate leukemia stem cells (LSCs). As our previous data indicate the TLR-TAK1/TICAM-1 axes regulate LSCs, we suspect TBK1 also regulates LSCs. To study TBK1 in AML, we generated tamoxifen-inducible, Tbk1-knockout (Tbk1NULL) mice and Tbk1NULL MLL-AF9+ mouse …

Effect Of Selenof Loss In Combination With A Western Diet On Tumorigenesis, Brenna Joy Flowers

Master's Theses

SELENOF is an understudied selenium-containing protein that has previously been postulated to behave as a tumor suppressor in the breast. Examination of patient databases showed that SELENOF levels were lowest in tumors from patients with aggressive late-stage breast cancers. Whether loss of SELENOF drives breast tumorigenesis remains to be determined. To address this question, we used juvenile female wild type or systemic Selenof knockout mice and exposed them to 7,12-Dimethylbenz[a]anthracene (DMBA), a carcinogen that replicates the multistep process of breast tumorigenesis. Previous reports have shown that loss of Selenof led to glucose and metabolic dysregulation in mice suggesting a link …

Murine Tbk1 Is Required By Flt3+ Leukemia Stem Cells Yet Dispensable In Homeostatic Hematopoiesis, Austin Patrick Runde

Master's Theses

The TANK-binding kinase 1 (TBK1) is a cytoplasmic, serine/threonine kinase and a critical activator of the innate immune system. Reports have implicated TBK1 as a promoter of multiple cancer types. Acute myeloid leukemia (AML) is a cancer arising from the hematopoietic stem/progenitor cells (HSPCs). Although ~70% of AML patients achieve complete remission with chemotherapy, at least half will relapse due to the failure to eradicate leukemia stem cells (LSCs). As our previous data indicate the TLR-TAK1/TICAM-1 axes regulate LSCs, we suspect TBK1 also regulates LSCs. To study TBK1 in AML, we generated tamoxifen-inducible, Tbk1-knockout (Tbk1NULL) mice and Tbk1NULL MLL-AF9+ mouse …

Delayed Testosterone Treatment In A Rodent Model Of Repeat Mild Traumatic Brain Injury Attenuates Mechanisms Of Cellular Death In The Vestibular Nucleus, Michael Volyanyuk

Master's Theses

A common complaint after repetitive mild traumatic brain injury (rmTBI) is vestibular dysfunction, which can become persistent and decrease quality of life. Delayed testosterone treatment has been shown to reduce vestibular impairment and improve neuronal survival in the vestibular nucleus following rmTBI; however, the long-term molecular pathways associated with rmTBI and testosterone treatment remain widely unexplored. We utilized a 5-hit closed-head rodent rmTBI model and administered testosterone 35 days after injury (DPI). The vestibular nuclei were removed and prepared for RT-qPCR and western blotting. Gene expression and protein levels were elevated for markers of oxidative stress (NADPH oxidase 4) and …

Tumor Immunology: Understanding The Immune System And Cancer To Enhance The Efficacy Of Cancer Immunotherapies, Natasha Malibu Lenart

Master's Theses

Tumor cells are notorious for their ability to escape immune surveillance, but developments in the understanding of the tumor microenvironment and how the immune system can be re-activated in tumors have had significant clinical impact. Commercially available and experimental methods such as adoptive cellular therapy, cytokine stimulation, and immune checkpoint blockade are promising immunotherapies for a variety of cancers, including solid tumors and hematological malignancies. However, induction of persistent, long-term anti-tumor immunity after initial treatment is infamously difficult. as a result, scientists are searching for new approaches to improve established immunotherapies. by employing combination treatments or enhancing the functionality of …

Pain And Academic Performance In Youth With Spina Bifida: The Mediating Role Of Neuropsychological Functioning, Diana Margaret Ohanian

Master's Theses

Objective: The current literature has identified few modifiable condition parameters associated with academic performance in youth with spina bifida (SB). Nevertheless, youth with SB are more likely to struggle academically than their typically developing (TD) peers. Therefore, identifying areas for clinical intervention is paramount. Pain, an understudied secondary condition in youth with SB, has been found to be associated with poorer academic performance in TD youth. Further, neuropsychological functioning has been found to be both negatively associated with pain and positively associated with academic outcomes. The aims of this study were to examine (1) the relationship between pain and academic …

The Effects Of Superordinate Identity Recategorization And Social Value Orientation On Ethical Decision-Making In A Business Dilemma, Thomas Steven Colville

Master's Theses

The purpose of the present study was to investigate potential solutions to the prevalence of unethical behavior in groups, specifically through the use of superordinate recategorization. Superordinate recategorization allows group members to feel an affinity with others not typically included in their in-group. This should promote ethical decision-making by enabling the inherent in-group favoring tendencies found in groups to be extended to a more inclusive category. In the context of the present study, the ethicality of participants' behavior in the Panalba scenario was determined by their choices on a 1 to 6 scale from least to most ethical. Additionally, participants’ …

Using Tcr Transgenic, Gp100 Reactive T Cells And Checkpoint Inhibition To Target Lymphangioleimyomatosis, Christian Ankney

Master's Theses

Lymphangioleiomyomatosis (LAM) is a low-grade neoplastic disease affecting primarily women. It is characterized by cystic lung disease as well as renal and retroperitoneal tumors called angiomyolipomas and lymphangiomas. Tumor cells have smooth muscle features as well as neuroendocrine cell surface markers, and the disease can be diagnosed by HMB45 staining of tumor cells. We questioned whether expression of melanocytic antigens, specifically gp100, creates an opportunity to treat LAM by adoptive T cell transfer. LAM lung lesions demonstrate poor immune surveillance, therefore adoptive T cell transfer could offer benefits in this disease.

A link was made between melanoma and depigmenting vitiligo …

The Unconventional Secretion Of Alpha-Synuclein By Autophagic Mechanisms And The Novel Characterization Of Pathological Alpha-Synuclein Associated Extracellular Vesicles, Kevin Burbidge

Master's Theses

Synucleinopathies are a group of neurodegenerative diseases associated with the intracellular accumulation of aggregated α-synuclein, a neurotoxic process resulting in cell death. Research indicates that pathology results from α-synuclein misfolding and self-propagation, as well as, cell-to-cell transmission. Furthermore, pathological α-synuclein transmission may occur through unconventional secretion.

In this thesis, we investigated how autophagy influences unconventional secretion of our novel α-synuclein dual-split protein model that we first verified by reproducing documented results from treatment of known autophagic regulators. Afterwards, we investigated how knocking out autophagic proteins ATG7 and Beclin-1 influenced α-synuclein secretion.

Additionally, we developed a methodology for analyzing extracellular vesicles …

Creating A Bret Assay To Monitor The Interaction Between Β-Arrestin-1 And Stam-1, James Buhrmaster

Master's Theses

CXCR4 is a chemokine receptor that is overexpressed in multiple disease states, including cancer. Understanding the mechanisms by which cells regulate CXCR4 expression is of high importance, as they can reveal downstream effectors that can potentially be targeted pharmacologically to more effectively treat diseases with fewer side effects.

CXCR4 is internalized in response to stimulation by its ligand CXCL12, and localizes to early endosomes as part of a homologous desensitization mechanism. From the endosome, CXCR4 can enter one of two pathways whereby it is either recycled back to the plasma membrane, where it can undergo another signaling event, or it …

Comparative Studies On Biochemical And Pharmacological Profiles Of Bovine, Ovine And Porcine Heparins, Ahmed Kouta

Master's Theses

Heparin, a highly sulfated glycosaminoglycan (GAG), is used extensively as an anticoagulant. It consists of repeating disaccharide units, containing iduronic acid (or glucuronic acid) and glucosamine, exhibiting variable degrees of sulfation. Heparin, and its analogues, are used during surgery and dialysis, and are often used to coat indwelling catheters and other devices where the vascular system is exposed. Administered parenterally, often continuously due to its short half-life, over 0.5 billion doses are required per year. Heparin is currently obtained from mucosal tissue of meat animals, mainly porcine intestine, and to a lesser extent bovine and ovine sources. The early stages …

Cellular Consequences Of Lysosomal Rupture Induced By Alpha Synuclein, Zachary Carpenter Green

Master's Theses

Misfolded, toxic forms of amyloid alpha synuclein (α-syn) have been implicated in Parkinson’s disease (PD) pathology and have been shown to spread throughout the brain in a prion-like manner, explaining the progressive loss of neurons in PD. The mechanisms of spread and cell death are unknown, however, evidence from previous studies suggests that neurons may undergo apoptosis due to the uptake of exogenous α-syn aggregate through the endocytic pathway and subsequent lysosomal rupture.

This study aimed to corroborate previous evidence of α-syn induced lysosomal rupture and investigate the cellular repercussions of rupture with respect to cell death and α-syn transfer. …

Estrogen Regulation Of Mir-181a Stability In Neurons, Chun Kim

Master's Theses

Estrogens are an important class of steroid hormones involved in many cellular signaling processes. Levels of estrogens fluctuate across the lifespan suggesting that they target intracellular mediators, such as microRNAs, to fine-tune homeostatic cellular processes. Previous work in our lab demonstrated that 17β-estradiol (E2), the predominant circulating estrogen, stabilized miR-181a in a neuronal cell line derived from rat hypothalamus. These results lead to the hypothesis that E2 regulated miR-181a stability by altering the pool of endogenous RNA and by recruiting PNRC2 away from the miRNA degradation machinery. By utilizing miRNA degradation assays and immunostaining techniques, it was determined that the …

Separating Autoimmune And Anti-Tumor Responses With Hsp70iq435a, James Mahon

Master's Theses

Vitiligo and melanoma are both melanocyte-derived diseases; vitiligo progresses through the autoimmune-targeted destruction of healthy melanocytes while melanoma results from uncontrolled proliferation of cancerous melanocytes. Treatment of vitiligo with HSP70iQ435A inhibits the DC-mediated auto-immune response against melanocytes in vitiligo mouse models; this raises the concern that treatment with this modified HSP may also inhibit natural anti-tumor responses against melanocyte-derived melanoma tumor cells.

We hypothesized that HSP70iQ435A prevents migration of melanocyte-antigen reactive T cells to the skin in a way that is mechanistically different from anti-tumor responses to melanoma and therefore would not have a negative effect on anti-tumor responses. We …

Identifying Oncogenic Drivers In Nsclc Cells Harboring Egfr Kinase Domain Mutation With Resistance To Egfr Tki And Mesenchymal Phenotype, Yandi Gao

Master's Theses

EGFR kinase domain mutant NSCLC cells are exquisitely dependent on mutant EGFR for cell survival and proliferation. Patients with mutant EGFR respond well to the EGFR inhibitors. However, acquired drug resistance greatly limits the efficacy of the treatment. About 15% of the resistant tumors present an evidence of epithelial to mesenchymal transition (EMT). We hypothesize that the induction of mesenchymal promotes aberrant upregulation of other oncogenic drivers to replace the oncogenic mutant EGFR.

We observed overexpression of CXCR7 in NSCLC models of acquired resistance to EGFR TKI with mesenchymal phenotype. Additionally, our studies demonstrate that ectopically overexpressing CXCR7 in EGFR …

A Study Of Functional Recovery And Axonal Plasticity Following Tbi And Anti-Nogo-A Immunotherapy, Jennifer Crystal Biesiadecki

Master's Theses

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality globally and often results in long term disability. Unfortunately, the success of rehabilitation techniques as therapy for TBI is limited, which may be due to the growth restrictive environment of the adult central nervous system (CNS). This environment is thought to result from glial scars, lack of neurotrophic factors, and the presence of an array of growth-inhibitory molecules. One such growth-inhibitory molecule is the protein Nogo-A. Our laboratory has shown that neutralization of Nogo-A with anti-Nogo-A immunotherapy after ischemic stroke results in improvement in functional recovery in the …

Alpha-Synuclein Aggregates Activate The Nlrp3 Inflammasome Following Vesicle Rupture, Rudy Orlando Cedillos

Master's Theses

Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought …

Development Of Cell Based Reporter Assay To Measure Pkc-Delta Promoter Activity, Kushal Prajapati

Master's Theses

Protein kinase C- δ (PKC-δ) acts as a tumor suppressor in skin cancer and is lost in 30% of human Squamous Cell Carcinoma (SCC). This loss is at the transcriptional level and involves the pathway leading to PKC-δ promoter repression after activation of Ras,PI3K,Fyn, and NF-κB. We proposed development of a high throughput, cell-based luciferase reporter assay on Ras transformed keratinocyte cell line, HaCaT-Ras to screen compounds having potential to inhibit this pathway and re-induce PKC-δ expression. First we developed a stable, PKC-δ promoter-reporter transfected HaCaT-Ras cell line. Next, we tested 13 compounds for their abilities to induce PKC-δ …

Snail Induces Mesenchymal Transition And Promotes Egfr Tki Resistance In Nsclc Cells Harboring Efgr Kinase Domain Mutations, Rutu Gandhi

Master's Theses

Lung cancer is the leading cause of cancer related death, accounting for one third of all deaths from cancer worldwide. About 85-90% of lung cancers are non-small cell lung cancers (NSCLCs). Molecular targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) provide an effective treatment option for oncogene addicted NSCLC. However, the development of resistance to EGFR TKIs continues to be the major limitation in the treatment of NSCLC. Resistance to EGFR TKIs has been associated with the loss of canonical epithelial protein E-cadherin, suggesting involvement of epithelial to mesenchymal transition (EMT) in conferring EGFR TKI …

Resveratrol + Ethanol Preconditioning And Neuroprotection, Nastaran Khodaie

Master's Theses

Our lab established that moderate ethanol preconditioning (MEP) for 6 days blocked the Aâ25-35 toxicity in cerebellar mixed cell cultures and It has been shown that MEP cause the up regulation of the pre-survival enzymes such as proxiredoxin2 (PRX2), which suggests MEP can activate the cell survival pathways against upcoming toxins.

This study was performed to verify the possible combinatory effect of ethanol and resveratrol against Aâ25-35 toxicity. Both ethanol and resveratrol sub-protective concentrations were detected against Aâ25-35 in cerebellar mixed cell cultures. The combination of sub-protective levels of ethanol and resveratrol showed the significantly reduction in number of Aâ25-35 …

The Impact Of Algal Community Succession, Taxonomic Composition And Biomass Accrual, On Denitrification Potential Of Stream Periphyton, Allison Daley

Master's Theses

We investigated the relationship between algal taxonomy, community succession and biomass accrual and denitrification potential (DNP) within stream periphyton. Field research was conducted in 6 DuPage County, II forest preserve streams with diverse physical and chemical characteristics and in an experiment in the artificial stream facility at Loyola University Chicago in which 2 sets of streams were amended with nutrients and compared to an unamended set of streams. Algal communities in the field study streams were sampled over 12 weeks late spring/summer and NMDS ordination plots identified 4 distinct communities. Correlations with algal community NMDS axis scores and the relative …

Determination Of The Molecular Mechanisms Of Hyperglycemia-Induced Changes In Cav3.2 Calcium Channel Properties, Ginny Marie Keeling

Master's Theses

Hyperglycemia can cause altered excitability due to increased CaV3.2 T-type calcium channel function, bestowing diabetics an increased neuropathy risk. The objective of this study was to understand the molecular mechanisms of increased CaV3.2 function during hyperglycemia in vitro, which leads to a 58% increase in current density and increased channel open probability (PO), among other changes. Two major findings are reported in this study:

1) The enzymatic elimination of extracellular N-acetylneuraminic acid (NANA) moieties reversed the increase in current density and the shift in PO, showing that hyper-glycosylation alters channel function in disease.

2) Treatment with GM1 (a ganglioside highly …

Protein Kinase C Δ Is Critical For Nucleotide Excision Repair Of Cyclobutane Pyrimidine Dimers, Christopher Michael Negro

Master's Theses

Nucleotide excision repair (NER) is the process by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP). NER in human cells is a complex biochemical process requiring several complementation groups. Defects in complementation group genes result in rare, autosomal recessive cancer syndromes such as xeroderma pigmentosum (XP), cockayne syndrome (CS), and trichothiodystrophy, supporting the tumor suppressive effects of NER. Protein Kinase C delta (PKCδ) expression is lost in squamous cell carcinomas where it functions as a tumor suppressor gene. Additionally, in response to UV radiation, PKCδ is …

Morphological Development Of The Axial Skeletons Of Esox Lucius And Esox Masquinongy (Euteleostei: Esociforms), With Comparisons In Developmental And Mineralization Rates., Amanda Maria Burdi

Master's Theses

Developmental morphology of the axial skeleton of Esox lucius (i.e., northern pike and type species) and E. masquinongy (i.e., muskellunge) was investigated. More than 1,000 specimens were examined ranging in size from approximately 10 mm notochordal length (NL) post-hatching juveniles to over 80 mm standard length (SL) foraging sub-adults. Results show that regardless of individual variation, the relative sequence of bone formation and mineralization is consistent between the two species. This consistent developmental pattern enabled construction of an ontogenetic staging scheme of eight developmental stages, each characterized by one defining criterion. The first appearance in cartilage and/or first sign of …

Anti-Nogo-A Immunotherapy Facilitation Of Environmental Enrichment's Effects On Recovery From Stroke In The Aged Rat, Sarah Jane Hein

Master's Theses

Stroke and traumatic brain injury are devastating disorders that often lead to permanent neurologic deficits, with few available treatment options once injury has occurred. In previous work, Anti-Nogo-A immunotherapy has been shown to neutralize the neurite inhibitory protein, Nogo-A, and to promote neuronal plasticity and improve functional recovery after stroke in the rat. Furthermore, other reports have demonstrated that environmental enrichment improves functional recovery in rodents following stroke. Our previous work demonstrated that anti-Nogo-A immunotherapy also helps promote cortical plasticity in the rodent. In the current project, we examined two methods to promote recovery after brain injury, a stroke model …

The Forgotten Grievers- Loss And Grief As Experienced By Young Adults In The Higher Educational Setting, Leona A. Garchow

Master's Theses

No abstract provided.

Spirituality In A Pastoral Counseling Context Dc By Joya D'Cruz., Joya D'Cruz

Master's Theses

No abstract provided.

The Relationship Between Social Skills And Social Support Among Caregivers Of Older Adults With Dementia, Sheila Johnson Carter

Master's Theses

No abstract provided.

A Discerning Heart: The Core Of Psycho-Spiritual Healing, Dudley Mendonca

Master's Theses

No abstract provided.