Medicine and Health Sciences Commons^™

Uncovering The Zeb1 Interactome To Identify Novel Regulators Of Metastatic Non-Small Cell Lung Cancer, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States, due in part to the robust affinity of lung cancer cells to metastasize. Understanding the processes that contribute to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-tomesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT cell adhesion and polarity is reduced, allowing epithelial cancer cells to dissociate from the primary tumor and invade distant organs. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) has been reported to uniquely correlate with NSCLC disease progression and to …

The Effect Of Traumatic Brain Injury On Tau Pathology By A Potential Seeding Mechanism, George Edwards Iii

Dissertations and Theses (Open Access)

The misfolding, aggregation and accumulation of specific proteins is the overarching concept in protein misfolding disorders (PMDs). The microtubule associated protein tau is known to form insoluble filaments known as neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) found in a subset of PMDs called tauopathies, such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE), among others. Misfolded tau engenders a structurally alternative intermediate conformation that is prone to aggregate having amyloidogenic properties. Formation of amyloids, such as tau aggregates, is proposed to follow a nucleation-polymerization model where misfolded, soluble oligomeric seeds can trigger native proteins to misfold and …

The Role Of Membrane Domains In Protein And Lipid Sorting During Endocytic Traffic, Blanca B. Diaz-Rohrer

Dissertations and Theses (Open Access)

The lipid and protein composition of the plasma membrane (PM) must be tightly controlled to maintain cellular functionality, despite constant, rapid endocytosis. Because de novo synthesis of proteins and lipids is energetically costly, the cell depends on active recycling to return endocytosed membrane components back to the PM. For most proteins, the mechanisms and pathways of their PM retention remain unknown. The work presented here shows that association with ordered membrane microdomains is fully sufficient for PM recycling and that abrogation of raft partitioning leads to their degradation in lysosomes. These findings support a model wherein ordered membrane domains mediate …

Determination Of Thymic Epithelial Cell Composition And Proliferation During The Perinatal To Adult Transition, Scott Casey

Dissertations and Theses (Open Access)

T-cells develop in the thymus based on signaling from multiple stromal cell types, particularly thymic epithelial cells (TECs). The thymus develops rapidly during the perinatal time period (birth – 10 days in mice) before reaching a period of homeostasis (10 days – 6 weeks). The mechanisms that initially promote and subsequently limit expansion of the TEC compartment are not known. However, previous reports from our lab suggest that the Cyclin D1-RB-E2F pathway plays a key role in regulating the perinatal to adult transition. We have previously shown that inactivation in TEC of retinoblastoma (RB) family members through deletion of RB …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

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 …

A Signature Enrichment Design With Bayesian Adaptive Randomization For Cancer Clinical Trials, Fang Xia

Dissertations and Theses (Open Access)

Clinical trials in the era of precision medicine demand more flexible and efficient trial designs. Adaptive clinical trial designs allow pre-specified modifications of an on-going clinical trial and could shorten the trial duration. We reviewed five common types of adaptive clinical trials based on adaptation methods. In particular, outcome-randomization becomes more popular as it can assign more patients to the promising treatments based on the accumulated trial data. This data-driven allocation allows more patients to benefit from the trial, which is especially important for cancer patients. We compared different Bayesian outcome-adaptive randomization methods and discussed them from both methodological and …

Assessment Of New Innovations In Pet/Ct For Respiratory Motion Correction, Joseph Meier

Dissertations and Theses (Open Access)

In oncological imaging, Positron Emission Tomography/Computed Tomography (PET/CT) is a vital tool used for stating and treatment response assessment of patients due to its ability to visualize and accurately quantify the bio-distribution of radiolabeled pharmaceuticals. However, due to the long acquisition times, respiratory motion blur is unavoidable in PET images especially in the lower lung and upper abdomen. This leads to reductions in measured radiotracer concentration and lesion detectability all of which can potentially result in incorrect management of patients. Multiple methods exist to correct for respiratory motion but are rarely used in the routine clinical setting because of: 1) …

Deconvolute Brain Tumor Genomic Alterations Based On Dna Methylation, Jie Yang

Dissertations and Theses (Open Access)

Molecular classification based on mutations, expression subtypes, and copy number variants has improved diagnosis and treatment decision-making for patients with brain tumors, particularly malignant gliomas. However, the association between epigenetic signature and genetic alterations is poorly understood. For example, mutation of isocitrate dehydrogenase (IDH) is associated with genome-wide hypermethylation of CpG islands in gliomas. But other subtype-associated alterations, including telomerase reverse transcriptase (TERT) promoter mutation, alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation, chromosome 1p19q co-deletion (chr1p19q codel), and gene expression subtypes, have yet to be associated with any epigenetic signature. Therefore, we hypothesized that …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations and Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

The Impact Of Ergot Alkaloid Consumption During Gestation On Maternal Performance And Fetoplacental Development, Jessica Lynn Britt

All Dissertations

Tall fescue is the primary cool season perennial forage grass in southeastern US for grazing livestock. Tall fescue the is known to be drought tolerant , disease resistant, grazing tolerant and overall very hardy. Many of these attributes common to fescue are due to a symbiotic relationship between the fescue plant and an endophyte, Epichloë coenophiala , which produces a class of mycotoxins known as ergot alkaloids. These ergot alkaloids are similar in structure to several biogenic amines, such as epinephrine, norepinephrine, and dopamine. When consumed, ergot alkaloids cause a syndrome known as fescue toxicosis which causes problems with weight …

Probing Of Carbohydrate-Protein Interactions Using Galactonoamidine Inhibitors, Jessica B. Pickens

Graduate Theses and Dissertations

Glycoside hydrolases are ubiquitous and one of the most catalytically proficient enzymes known, and thus understanding their mechanisms are crucial. Most research has focused on the interaction of the glycon of substrates and their inhibitors within the active site of glycoside hydrolases. The inhibitors employed to probe these interactions generally had small aglycons (i.e. a hydrogen atom, amidines, small aliphatic groups, or benzyl groups). Here, the interactions of the aglycon with glycoside hydrolases are examined by probing the active sites with a library of 25 galactonoamidines. The studies described in this dissertation aim to increase the understanding of stabilization of …

Toward Understanding The Mechanism Of Protein Targeting In The Chloroplast Signal Recognition Particle Pathway, Mercede Furr

Graduate Theses and Dissertations

Protein targeting is a vital cellular function. The signal recognition particle (SRP) pathway is a universally conserved targeting system present in the cytosol and used to co-translationally target many proteins to the inner membrane of prokaryotes and the endoplasmic reticulum of eukaryotes. The chloroplast has a homologous SRP system which post-translationally targets light harvesting chlorophyll binding proteins (LHCPs) to the thylakoid membrane for integration. The chloroplast SRP (cpSRP) is a heterodimer with a 54 kDa subunit equivalent to SRP54 in the canonical pathway. In addition, cpSRP contains a novel 43 kDa subunit which is a unique and irreplaceable component. cpSRP43 …

Development Of A Text Message Stress Management Intervention And Its Impact On Perceived Stress And Coping Self-Efficacy Among Student Nurses, Kristin Jaye Henderson

Graduate Theses and Dissertations

Purpose: The purpose of the two studies was to develop a text message intervention and examine its effects on lowering perceived stress and increasing coping self-efficacy among nursing students. We also explored stress perceptions and investigated student satisfaction with the text message stress management program. Methods: For the first study, twenty three students participated in the focus groups for intervention development. Sample messages were presented to participants and feedback was requested. The messages were modified based on student feedback. The second study utilized an experimental pre/post design with a convenience sample (N=101) to examine the effects of the text message …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Graduate Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of …

Created For Connection: The Impact Of A Faith-Based Christian Marriage Enrichment Program, Chad N. Imhoff

Graduate Theses and Dissertations

The purpose of this study was to explore the effects of Created for Connection (CFC), a faith based marriage enrichment program on relationship satisfaction, adult attachment style and adult attachment behavior. This study further adds to the existing knowledge base related to faith-based programs delivered in an intensive weekend format (Johnson & Sanderfer, 2016). Participants were volunteers from the local community who identified as Christian. To ascertain the effectiveness of CFC, three self-report measures were administered at three different intervals: two weeks before the program, two weeks following the program and a six-week follow-up. I measured attachment anxiety, attachment avoidance, …

Turn That Frown Upside-Down! The Effectiveness Of Opposite Action In Changing Emotion, Kaitlyn Diane Chamberlain

Graduate Theses and Dissertations

While research demonstrates that opposite action (OA) impacts emotion (Rizvi & Linehan, 2005), we lack an understanding of the mechanisms by which it produces opposite emotions. The current study dismantled emotion regulation skill components by comparing tasks with different combinations of cognitive, emotive and behavioral components. I predicted that the OA condition would be the most effective in altering negative emotion. University students (n = 194) completed a sadness induction and were randomly assigned to either a (1) control, (2) low arousal positive imagery (3) high arousal positive imagery, or (4) OA plus high arousal positive imagery condition. The control …

Identification Of The Kaposi's Sarcoma-Associated Herpesvirus (Kshv) Surface Glycoprotein Targets Of Human Kshv-Specific Neutralizing Antibody Responses, Yasaman Mortazavi

School of Biological Sciences: Dissertations, Theses, and Student Research

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8), is the etiological agent of Kaposi’s sarcoma (KS), and is also associated with two B cell malignancies, primary effusion lymphoma and multicentric Castleman's disease. The distribution of KSHV varies globally with high prevalence in some areas of sub-Saharan Africa (SSA), where seroprevalence can be as high as 80%. It is estimated that nearly 44,000 new cases of KS emerge annually globally, with the highest incidents occurring in Africa, where KSHV is endemic. Currently, there is no prophylactic vaccine against KSHV, and efforts to develop prophylactic vaccines have been limited. …

Crossover Interference And Sex-Specific Genetic Maps Shape Identical By Descent Sharing In Close Relatives, Madison Caballero, Daniel N. Seidman, Ying Qiao, Jens Sannerud, Thomas D. Dyer, Donna M. Lehman, Joanne E. Curran, Ravindranath Duggirala, John Blangero, Shai Carmi, Amy L. Williams

School of Medicine Publications

Simulations of close relatives and identical by descent (IBD) segments are common in genetic studies, yet most past efforts have utilized sex averaged genetic maps and ignored crossover interference, thus omitting features known to affect the breakpoints of IBD segments. We developed Ped-sim, a method for simulating relatives that can utilize either sex-specific or sex averaged genetic maps and also either a model of crossover interference or the traditional Poisson model for inter-crossover distances. To characterize the impact of previously ignored mechanisms, we simulated data for all four combinations of these factors. We found that modeling crossover interference decreases the …

Mind, Brain, And Behavior: An Integrative Approach To Teaching Neuroscience To Medical Students, Arden D. Dingle, Annelyn Torres-Reveron, Mario Gil, Francisco Fernandez, Ignacio Martinez Escobedo, Valerie Terry, Gladys E. Maestre, Gabriel A. De Erausquin

School of Medicine Publications

Disorders related to neuroscience, psychiatry, and neurology cause significant disease burdens impacting medical practice [1, 2]. Teaching medical students these subjects remains challenging as many consider neuroscience and neurology too difficult to adequately learn [3] and psychiatry to be irrelevant [4–7]. Developing and implementing curricular initiatives to effectively teach these subjects so that students can utilize these knowledge and skills in practice is essential.

Interactive educational methods offer new approaches to improve student learning, especially within current educational initiatives that emphasize integration of basic and clinical science and incorporation of social …

Optical Detection Of The Structural Properties Of Tumor Tissue Generated By Xenografting Of Drug-Sensitive And Drug-Resistant Cancer Cells Using Partial Wave Spectroscopy (Pws), Prakash A. Adhikari, Prashanth K.B. Nagesh, Fatemah Alharthi, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu, Prabhakar Pradhan

School of Medicine Publications

A mesoscopic physics-based optical imaging technique, partial wave spectroscopy (PWS), has been used for the detection of cancer by probing nanoscale structural alterations in cells/tissue. The development of drug-resistant cancer cells/tissues during chemotherapy is a major challenge in cancer treatment. In this paper, using a mouse model and PWS, the structural properties of tumor tissue grown in 3D structures by xenografting drug-resistant and drug-sensitive human prostate cancer cells having 2D structures, are studied. The results show that the 3D xenografted tissues maintain a similar hierarchy of the degree of structural disorder properties as that of the 2D original drug-sensitive and …

Brief History Of Spinal Neurosurgical Societies In The United States: Part 1., Sasha Vaziri, Daniel K. Resnick, Christopher P. Ames, James S. Harrop, Christopher I. Shaffrey, Kern Singh, Justin S. Smith, Daniel J. Hoh

Department of Neurosurgery Faculty Papers

No abstract provided.

Global Acetylation Dynamics In The Heat Shock Response Of Saccharomyces Cerevisiae, Rebecca E. Hardman

Graduate Theses and Dissertations

All organisms face a constant barrage of environmental stresses. Single-cell organisms such as Saccharomyces cerevisiae, or common Baker’s yeast, must rely solely on cellular responses in order to survive. This response must occur in a rapid and highly coordinated manner to quickly inhibit all unnecessary processes and shuttle all available resources to those necessary for survival. One method that cells utilize for rapid protein regulation is the use of post-translational modifications. Enzymes within the cell add or remove a variety of chemical modifications, thus altering the local chemical environment of a protein. This creates a conformational change in the protein …

Single Molecule Fluorescence Studies Of Protein Structure And Dynamics Underlying The Chloroplast Signal Recognition Particle Targeting Pathway, Dustin R. Baucom

Graduate Theses and Dissertations

The work presented in this dissertation explores the structural dynamics in the chloroplast signal recognition particle pathway. Findings include cpSRP shows scanning functionality similar to that in the cytosolic SRP with the ribosome. The intrinsically disordered C-terminal tail of the Albino3 protein has some transient secondary structure. Upon binding to cpSRP43 in solution, separate secondary structure formation was identified in the C-terminal tail of Albino3. Finally, to increase efficiency of analyzing fluorescence time traces for this work, a modular software was produced.

Influence Of Single And Multiple Histidine Residues And Their Ionization Properties On Transmembrane Helix Dynamics, Orientations And Fraying, Fahmida Afrose

Graduate Theses and Dissertations

Since aromatic and charged residues are often present in various locations of transmembrane helices of integral membrane proteins, their impacts on the molecular properties of transmembrane proteins and their interactions with lipids are of particular interest in many studies. In this work, I used solid-state deuterium NMR spectroscopy in designed model peptide GWALP23 [GGALW(LA)6LWLAGA] with selective deuterium labels to addresses the pH dependence and influence of single and multiple “guest” histidine residues in the orientation and dynamic behaviors of transmembrane proteins. The mutations include Gly to His (G2/22 to H2/22), Trp to His (W5/19 to H5/19) and Leu to His …

Investigating Egg Storage Conditions, Hatch Characteristics, And Feeding Methods Of Commercially Produced Poultry, Joshua R. Deines

Graduate Theses and Dissertations

Advancements in poultry research continue to add knowledge and understanding to an already technical industry. Such information has led to new developments in early feeding strategies which provide nutrients to broiler chicks while in the egg or during transport. This wealth of knowledge in poultry research extends beyond chickens and is utilized for other species, such as quail and pheasants, including how fertile eggs are stored and incubated. However, methods of early feeding broilers have not been investigated in industry relevant approaches to understand its effects, including how timing of feed access interacts with the hatch window. As well, quail …

Acne Severity And Sleep Quality In Adults., Kory P Schrom, Sayeeda Ahsanuddin, Michelle Baechtold, Raghav Tripathi, Amy Ramser, Elma Baron

Ambulatory and Primary Care Articles

Poor sleep quality is extremely prevalent, with about one third of adults in the USA obtaining less than the recommended amount of sleep. In addition, poor sleep quality has been linked to an increased risk of many conditions, including diabetes, hypertension, psychiatric conditions, and overall all-cause mortality. Research has shown that sleep disturbance does impact skin disease, although many details of this relationship are still unclear. The goal of this study is to determine if there is a relationship between acne severity and sleep quality in adults. Forty subjects with acne were recruited from dermatology clinics in Cleveland, OH, to …

Novel Mechanistic Insight Into The Anticancer Activity Of Cucurbitacin D Against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer), Mohammed Sikander, Shabnam Malik, Sheema Khan, Sonam Kumari, Neeraj Chauhan, Parvez Khan, Fathi T. Halaweish, Bhavin Chauhan, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited …

Hosptial Preparedness For An Internal Mass Casualty Event, Jason Farr

Electronic Theses and Dissertations

The purpose of this study was to determine hospital preparedness for an internal mass casualty/active shooter event at Tennessee hospitals. Data were collected during May of 2019 by surveying the CEOs of the 86 acute care hospitals in Tennessee. The survey solicited responses about training, preparedness, and internal evaluation of procedures. CEOs of 28 (32.5%) of Tennessee’s acute care hospitals responded to the survey. Just over half (53.6%) of those responding indicated that they believed their facility was prepared or well prepared for an active shooter event. The mean responses of CEOs who had experienced an active shooter event were …

Hypertension As A Reason For Cancellation Of Elective Surgical Cases On Day Of Surgery: A Five Year Audit Report From The Aga Khan University Hospital Karachi, Abdul Monem, Amjad Nadeem, Fauzia Khan

Department of Anaesthesia

Objective: To assess the controllable factors in preventing undue cancellation of elective surgical cases and to suggest measures to address the issue.
Methods: The retrospective audit was conducted at the Aga Khan University Hospital, Karachi, and comprised all cancellations of elective surgery from 2011 to 2015. The cases reviewed had been cancelled primarily due to hypertension. A three-member committee regularly reviewed files regarding case cancellations and data was gathered.
Results: Of the 42,242 surgical cases scheduled during the period, 2903 (6.8%) were cancelled. In 11(0.37%) of these cases, hypertension was the primary reason. Of them, 10(91%) were men and 1(9%) …