Medicine and Health Sciences Commons^™

On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski

Electronic Theses and Dissertations

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …

Primary Cilia Of The Cardiac Neural Crest & Hedgehog-Mediated Mechanisms Of Congenital Heart Disease, Lindsey A. Fitzsimons

Electronic Theses and Dissertations

Elimination of primary cilia in cardiac neural crest cell (CNCC) progenitors is hypothesized to cause a variety of congenital heart defects (CHDs), including atrioventricular septal defects, and malformations of the developing cardiac outflow tract. We present an in vivo model of CHD resulting from the conditional elimination of primary cilia from CNCC using multiple, Wnt1:Cre-loxP, neural crest-specific systems, targeting two distinctive, but critical, primary cilia structural genes: Intraflagellar transport protein 88 (Ift88) or kinesin family member 3A (Kif3a). CNCC loss of primary cilia leads to widespread CHD, where homozygous mutant embryos (MUT) display a variety of outflow tract malformations, septation …

Handling And Manipulation Of Water- And Air- Borne Biological Samples Using Liquid-Infused Surfaces, Daniel P. Regan

Electronic Theses and Dissertations

Research on novel materials to handling water- and airborne samples for biological threats analysis is in great demand due to the COVID-19 pandemic. Work conducted on a new field of material science, called liquid-infused surfaces, demonstrate strong potential for the handling and manipulation of biological samples. As a result of the field’s infancy, only a limited number of studies have explored how liquid-infused surfaces can apply droplet manipulation strategies to address real-world problems. Presented in this dissertation are two platforms that leverage liquid-infused surfaces to address the challenges associated with handling water- and airborne biological samples. When dealing with waterborne …

Toward Improving Understanding Of The Structure And Biophysics Of Glycosaminoglycans, Elizabeth K. Whitmore

Electronic Theses and Dissertations

Glycosaminoglycans (GAGs) are the linear carbohydrate components of proteoglycans (PGs) that mediate PG bioactivities, including signal transduction, tissue morphogenesis, and matrix assembly. To understand GAG function, it is important to understand GAG structure and biophysics at atomic resolution. This is a challenge for existing experimental and computational methods because GAGs are heterogeneous, conformationally complex, and polydisperse, containing up to 200 monosaccharides. Molecular dynamics (MD) simulations come close to overcoming this challenge but are only feasible for short GAG polymers. To address this problem, we developed an algorithm that applies conformations from unbiased all-atom explicit-solvent MD simulations of short GAG polymers …

Beyond The Brain: A Study Of Α-Synuclein's Role In Bone And Adipose Tissue, Carolina A. Figueroa

Electronic Theses and Dissertations

α-Synuclein is a polypeptide encoded by the Snca gene, highly expressed in neurons, but it is also found in bones and adipose tissue. Co-expression analysis showed that Snca regulates skeletal homeostasis, and its deletion reduced estrogen deficiency-induced bone loss and weight gain. It is a major component of Lewy bodies (LB) in Parkinson’s disease (PD), leading to progressive immobilization and a range of nonmotor symptoms, including osteopenia, body composition alterations and insulin resistance. This thesis aimed to determine α-Synuclein’s intrinsic role in bone and adipose homeostasis. We discussed the PD pathophysiology emphasizing aspects of bone health and metabolism. By using …

Discovery Of Distinct Mechanisms Underlying The Relationship Between Drug Taking And Predisposing Behaviors, Tyler A. Roy

Electronic Theses and Dissertations

Drug addiction is a heritable disease characterized by compulsive drug use. The biological mechanisms driving addiction remain largely unknown.¹ Previous studies show shared genetic mechanisms underlying addiction risk phenotypes such as anxiety, depression, and novelty/sensation seeking.^2,3 Therefore, high-throughput behavioral screening of these traits in single gene knockout mice can allow for the rapid detection of addiction risk candidate genes and mechanisms. Many of these traits are represented in the Knock-Out Mouse Program (KOMP) phenotyping pipeline. Of the initial two hundred twenty-one strains screened in this program, we tested nineteen phenodeviant knock-out mouse strains with C57BL/6NJ controls (N = …

The Effect Of Wild Blueberry Bioactives On Endothelial Cell Migration And Angiogenesis: An In Vitro Mechanistic, Genomic And Proteomic Approach, Panagiotis Tsakiroglou

Electronic Theses and Dissertations

The goal of this study is to investigate the effects of wild blueberry fractions (Anthocyanins and Phenolic acids) on vascular function and physiology. More specifically the potential effects of the above fractions and their combination in physiological concentrations on endothelial cell migration, angiogenesis, gene expression and proteins synthesis of markers related to the above processes. The objectives are to study whether anthocyanins, phenolic acids and their combinations (ACNs:PAs) affect: a) cell proliferation, b) speed of endothelial cell migration, c) angiogenesis, d) gene expression of genes critical for cell migration and angiogenesis such as RAC1, RHOA, AKT1, eNOS and VEGF and …

Genetic Modification Of Inherited Retinopathy In Mice, Yang Kong

Electronic Theses and Dissertations

The retina, as a critical component of the sensory system, consists of multiple cell types, of which, photoreceptors play a key role in receiving, integrating and transmitting light signals. The biofunctions of photoreceptors rely on their proper growth and development, which is predominantly governed by a cluster of molecules that comprise the transcriptional regulation for photoreceptor development. Any disruption of these molecules potentially incurs retinal pathologies.

It is known that deficiencies of nuclear receptor subfamily 2 group E member 3 (NR2E3) or neural retina leucine-zipper (NRL), two molecules in regulating photoreceptor cell development, cause photoreceptor dysplasia. In a sensitized chemical …

Characterizing The Role Of Fungal Shape In A Zebrafish Model Of Invasive Candidiasis, Brittany Seman

Electronic Theses and Dissertations

Candida albicans is a common hospital-acquired fungal infection, and disseminated disease claims up to one-half of those afflicted. C. albicans has a unique ability to differentiate its shape during infection, and this differentiation is thought to be a major virulence factor during invasive infections. Each shape is proposed to have a specialized role: filaments drive tissue invasion and yeast mediate dissemination to the bloodstream. However, it has been difficult to test these hypotheses for two reasons. First, rigorous testing of shape-specific roles requires diverse strategies of shape modulation that restrict the possibility of manipulation-specific artifacts. Second, although connecting shape to …

Dynamic Host-Pathogen Interactions Result In Fungal Epitope Unmasking, Alex Hopke

Electronic Theses and Dissertations

Molecular camouflage is used by a diverse set of pathogens to disguise their identity and avoid recognition by protective host receptors. The opportunistic fungal pathogen Candida albicans is a good example, as it masks the inflammatory component β-glucan in its cell wall to evade detection by the immune receptor Dectin-1. Interestingly, it has been seen that β-glucan becomes unmasked during infection in vivo, though the underlying mechanisms remained unclear. Exposure levels of this epitope may be important, as Dectin-1 mediates protection from some strains of C. albicans and alterations in the organization and composition of the Candida cell wall …

Characterization Of The Functional Role And Therapeutic Potential Of Microrna Mir-125a In Acute Myeloid Leukemia, Melanie Lorraine Ufkin

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a heterogeneous disease marked by a highly variable clinical course and response to therapy. The average age of individuals diagnosed with AML is approximately 69 years old. Due to age of the patient and how quickly the disease progresses, many are unable to receive therapy, leading to death between 4 and 12 weeks after diagnosis. More effective and less cytotoxic treatments are crucial for those diagnosed with AML. Therefore my work has been focused on understanding genetic pathways altered within AML to develop new-targeted therapies. Specifically, I have been studying microRNAs (miR), which regulate proteins …

Cell-Matrix Adhesion In Muscle Development And Disease, Michelle F. Goody

Electronic Theses and Dissertations

A variety of diseases, both inherited and acquired, affect muscle tissues in humans. The anchoring of muscle fibers to their surrounding environment is critical for muscle homeostasis. Muscle fibers attach to their microenvironment through cell-matrix adhesion complexes. These anchoring complexes are placed under repeated stress during muscle contraction. Genetic mutations in these complexes weaken the attachment between muscle fibers and their microenvironment, making fibers more susceptible to damage and death. This increased fiber degeneration eventually leads to progressive muscle wasting diseases, known as congenital muscular dystrophies. Although clinical trials are ongoing, there is presently no way to cure the loss …

Assessing Sleep Quality In Young Adult College Students, Aged 18 - 24 In Relation To Quality Of Life And Anthropometrics, Douglas Mathews

Electronic Theses and Dissertations

Little is known about the impact of sleep on quality of life and anthropometrics in young adults. College students (n=218) were recruited through a variety of methods for a study on weight management for obesity prevention and randomized into control (n=108) or treatment (n=110) groups. Of those, 152 (71%) completed pre- and post-tests, including the Pittsburg Sleep Quality Index (PSQI), scored 0-4 =normal and 5-21=disordered, (a=0.80), the General Health Questionnaire-12 (GHQ), scored from 0-14=good quality of life to 15-36=poor quality of life, (ct=0.87), and anthropometrics. Statistical analyses included linear regression, one way ANOVA, chi-square analysis, and Pearson's Product-Moment Correlation. Significance …

Transcriptional Alterations During Mammary Tumor Progression In Mice And Humans, Karen Fancher

Electronic Theses and Dissertations

Family history, reproductive factors, hormonal exposures, and subjective immunihistochemical evaluations of in situ lesions, and to a lesser extent age, remain the best clinical predictors of an individual's risk of developing breast cancer. Identification of early markers predictive of impending invasive breast cancer from in situ carcinoma is a long-term goal. The latent mammary cancer transgenic mouse model of human breast cancer, C57BL/6JTg(WapTag)1Knw (Waptag1), develops characteristic stages of tumorigenesis in a highly predictable manner: atypical hyperplasia advances to ductal carcinoma in situ (DCIS), which progresses to papillary adenocarcinomas and/or solid, invasive tumors. Microarray analyses of whole mammary glands and tumors …

The Role Of Osteopontin In Vascular Remodeling, Daniel Myers

Electronic Theses and Dissertations

Chronic obstructive vascular disease is a major contributor to mortality in developed nations. The pathology typically involves neointima formation accompanied by vascular remodeling in the presence of inflammation. The disease can be modeled in animals with the response to a direct injury of the vasculature. This text describes a project examining the role of osteopontin (OPN) in vascular remodeling. The projectis goal was to mechanistically describe the contribution of OPN to the vascular injury response. The hypothesis that the presence of OPN affects the formation of neointima and constrictive remodeling associated with vascular injury was addressed using the strategy of …

Evolution Of Lake Malawi Cichlid Fishes (Perciformes: Teleostei), Peter F. Smith

Electronic Theses and Dissertations

The cichlid fish species flocks of East Africa provide a compelling model system in which to study the process of speciation. In Lake Malawi, greater than 1000 species of cichlids have emerged since the filling of the lake basin about 1 million years ago. Over 99% of the Lake Malawi haplochromine cichlids are endemic, suggesting that most of this diversification has taken place within the temporal and spatial boundaries set by the Lake's shores. Moreover, many of these species are endemic to small areas within the lake, indicating that speciation has occurred very recently or perhaps is in progress in …