Life Sciences Commons^™

Evolutionary Ecology Of The Native Johnny Darter (Etheostoma Nigrum) And The Invasive Round Goby (Neogobius Melanostomus): A Genomic Perspective, Abby Joyce Wicks

Wayne State University Dissertations

Round goby (Neogobius melanostomus) is an invasive fish present in all five Great Lakes and is becoming increasingly common in their tributaries. Johnny darter (Etheostoma nigrum) is a native species that often coexists with round goby. Here, I use traditional population genetic methods and genomic tools to explore the evolutionary ecology of these species. First, historic factors are addressed as a source of variation in study populations by characterizing patterns of mitochondrial DNA variation throughout Lower Michigan. Round goby populations were largely homogenous and exhibited no evidence of overarching historical genetic structure, consistent with the recent invasion and rapid expansion …

Evaluating Historical Paradigms Of Sterility In Perinatal Microbiology And Ramifications For Pregnancy Outcomes, Jonathan Greenberg

Wayne State University Dissertations

Next-generation sequencing technologies, especially 16S rRNA gene and metagenomic sequencing have allowed investigations of low microbial biomass tissues of the human body. While these sequencing methodologies have provided large amounts of reliable data for higher microbial biomass sites, such as the mouth, intestine, and vagina, tissues of low microbial biomass sites are subject to specific caveats that were not appropriately considered in early investigations of these sites. Low microbial biomass sites of particular interest have included those of the reproductive and urinary systems. Utilization of DNA sequencing methodologies have allowed researchers to challenge existing paradigms of sterility around these sites …

Addressing The Issue Of Missing Heritability: The Importance Of Apoptosis In Hereditary Breast And Ovarian Cancer And Functional Assessment Of Tp53i3-S252*, Sophia Chaudhry

Wayne State University Dissertations

A quarter of all cases of ovarian cancer (OVCA) cases are due to inherited factors. However, much of the genetic risk remains unknown. We have previously established the importance of whole exome sequencing to answer the question for missing heritability. We identified clinically actionable and novel risk loci in the DNA repair and cell cycle regulation pathways by assessing a cohort of women diagnosed with OVCA, wildtype for BRCA1/BRCA2 and suspected to be hereditary due to family history of breast cancer/OVCA. Equally as important was the exploration and discovery of novel risk loci in the apoptosis pathway. A total of …

Timing And Duration Of Folate Restriction Differentially Impacts Colon Carcinogenesis., Ali M. Fardous

Wayne State University Dissertations

Colorectal cancer (CRC) constitutes a major burden on the healthcare system as the second most commonly diagnosed cancer in the developed world. Dietary folate is considered an important modulator of colorectal cancer. Folate restriction has been implicated in increasing CRC incidence by disrupting nucleotide synthesis, Impacting DNA methylation and inducing genetic instability. Our research shows that the timing and duration of dietary folate restriction can differentially impact Colorectal cancer initiation. Acclimating mice to folate restriction for 8 weeks results in a reduced number of preneoplastic lesions compared to mice placed of folate restriction for 1 week prior to initiating the …

Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday

Wayne State University Dissertations

Oxidative stress and endothelial dysfunction are reported in the cardiovascular and neurovascular diseases. Oxidative stress is caused due to an increase in the generation of reactive oxygen (ROS) and nitrogen species (RNS) and incapacity of antioxidant systems to eliminate ROS and RNS. Endothelial dysfunction is characterized by a reduction in nitric oxide (NO) bioavailability. NO is constitutively produced by enzyme endothelial nitric oxide synthase (eNOS). A reduction in tetrahydrobiopterin (BH4), which is an essential cofactor of eNOS, can lead to eNOS uncoupling. There is complex interplay between the ROS/RNS and antioxidant system underlying pathophysiologies of vascular diseases, however our quantitative …

Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia

Wayne State University Dissertations

Rat1 is a 5′→3′ exoribonuclease in budding yeast belonging to the XRN-family of nucleases. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its homolog in metazoan have been shown to function in multiple facets of RNA metabolism. In this study, we report a novel role of Rat1 in splicing of pre-mRNA in budding yeast. In the absence of the functional Rat1 in the nucleus, an increase in the level of unspliced transcripts was observed in yeast cells. Strand-specific TRO analysis revealed that the accumulation of unspliced transcripts upon …

The Dynamics Of Life And Death: Mitochondrial Fragmentation, Mitophagy, And Swelling During Neuronal Ischemia/Reperfusion Injury, Anthony Roy Anzell

Wayne State University Dissertations

Ischemic brain injury caused by cardiac arrest or stroke continue to be leading caused of death and disability in the U.S. While restoration of blood flow is necessary to salvage ischemic tissue, reperfusion paradoxically exacerbates injury via the production of reactive oxygen species, which, damage mitochondria and induce cell death. Therefore, it is critical to have stringent quality control mechanisms to ensure a healthy mitochondrial network. Mitochondrial fragmentation has been well characterized in the progression of ischemia/reperfusion and its association with cell death. Conversely, the role of mitophagy has been controversial regarding whether upregulation of mitophagy serves as a restorative …

The Relationship Between Excessive Folic Acid Intake And Genome Instability In Human Lymphocytes, Khadijah Ibrahim Alnabbat

Wayne State University Dissertations

Since its synthesis in 1945, Folic acid (FA) is widely used as a supplement/additive to our food due to its stability and high bioavailability. FA is proposed to alleviate anemia and reduce neural tube defects (NTD). As a provitamin, FA is activated through a two-step reaction catalyzed by dihydrofolate reductase (DHFR) in the folate metabolism pathway. FA activation rate is found to be slow in humans. After the implementation of mandatory food fortification program of grain and grain products with folic acid in the USA in 1998, many concerns have been raised about the unintended deleterious consequence of exposing the …

Development Of Rat Head Finite Element Model And Tissue Level Biomechanical Threshold For Traumatic Axonal Injury, Runzhou Zhou

Wayne State University Dissertations

Traumatic brain injury (TBI) is caused by local tissue deformation at the time of trauma, leading to neurological dysfunction. In the United States alone, 2.87 million people sustain a TBI each year, of which one-fifth results in death. Traumatic axonal injury (TAI) is a well-recognized consequence of every fatal head injury and more than 85% of vehicular crash-related blunt head injuries. The most common and important pathologic feature of TBIs are multifocal changes to axons in the white matter produced by rapid head acceleration/deceleration during a traumatic event with consequent local shear/tension on neural tissue and axons contributing to secondary …

Nutrition And Health Status Of Hemodialysis Patients In Dhaka, Bangladesh, Tanjina Rahman

Wayne State University Dissertations

Methods to identify patients at risk for End stage renal disease (ESRD) are a high priority in Bangladesh, where kidney transplants/dialysis options are limited and costly. Every year, 35,000 to 40,000 people reach ESRD in Bangladesh, but currently available facilities can hardly accommodate only 9000 to 10,000 new patients with twice weekly dialysis and the remaining 66% have no access to any kind of renal replacement therapy (RRT) in the form of dialysis or transplantation. Nutrition is an important factor in maintaining good health of hemodialysis patients. However, data on nutritional status of Bangladeshi dialysis patients is limited and is …

Methods To Integrate Genetic And Clinical Data For Disease Subtyping, Diana Mabel Diaz-Herrera

Wayne State University Dissertations

Enormous efforts have been made to collect genetic and clinical data from cancer patients to advance the understanding of disease development and progression. Processing and analyzing these flows of data is challenging. Many computational methods have been proposed to help different fronts of biology and medicine. The integration of clinical and genetic data using computational methods towards personalized medicine is considered the future for oncology studies, and this thesis contributes in this direction. This thesis presents three new data integration approaches to elucidate granular and meaningful disease sub-types from high-dimensional complex genetic and clinical variables, which is an essential step …

Effects Of Attention Focus And Warm-Up On Performance Of Central And Peripheral Processing, Mohammed Ali Aljahni

Wayne State University Dissertations

Abstract

EFFECTS OF ATTENTION FOCUS AND WARM-UP ON PERFORMANCE OF CENTRAL AND PERIPHERAL PROCESSING

by

Mohammed Aljahni

December 2020

Advisor: Dr. Qin Lai

Major: Kinesiology - Exercise and Sport Science

Degree: Doctor of Philosophy

Previous studies have shown that external focus of attention decreased reaction time by increasing central processing speed, compared to internal focus of attention. The research suggests that there is a direct link between attentional focus and information processing. It is also well-documented that warm-up or moderate exercise increases the central or cognitive processing speed even though no consistent finding on the latency of the muscle activation …

Impact Of Dietary Patterns On Health Outcomes In African American Maintenance Hemodialysis Patients, Dina Angela Tallman

Wayne State University Dissertations

In the United States, African Americans (AA) suffer a disproportionate burden of ESRD, accounting for 35% of all dialysis patients, and are 3.7 times more likely to progress to ESRD than whites. This increase in CKD risk is partially attributed to higher rates of hypertension, diabetes mellitus, and cardiovascular disease. Paradoxically, once on hemodialysis, AA have a survival advantage over whites, likely due to multiple factors including nutritional status, inflammation, psychosocial status, and genetic variation.

Although both the dialysis procedure and pharmacological treatments are effective at reducing the uremic toxin load, HD patients are still encouraged to adhere to strict …

Causes And Potential Treatment For Altered Muscle Metaboreflex Control Of Ventricular Vascular Interactions In Heart Failure, Joseph Thomas Mannozzi

Wayne State University Dissertations

Muscle Metaboreflex Activation occurs as a result of metabolic accumulation within active skeletal muscle that stimulates type III and IV afferents. This reflex in healthy subjects causes increased ventricular contraction, tachycardia, enhanced central blood volume mobilization, and 2 mediated vasodilation as a means to increase mean arterial pressure and thereby improve perfusion pressure of active skeletal muscle. However, to date no study has evaluated the interaction between the observed changes in ventricular and vascular dynamics or how the reflex impacts contraction relaxation dynamics before and after induction of heart failure Furthermore, no study has evaluated the impact of chronic selective …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …

Novel Insights Into The Critical Role Of Cardiolipin In Cellular Metabolism And Mitochondrial Physiology, Jiajia Ji

Wayne State University Dissertations

Cardiolipin (CL) is the signature phospholipid of mitochondria. CL and its remodeling exert critical roles in biological processes both inside and outside of mitochondria. CL abnormalities have been associated with various mitochondrial disorders and aging. Understanding the role of CL in mitochondrial physiology and cellular metabolism could provide valuable insights into cell biology and human health. Several metabolic alterations have been reported in CL-deficient cells, including accumulated lactate, decreased PDH activity, and decreased TCA cycle function. This dissertation connected these findings by showing abnormal NAD+ metabolism in various models lacking CL. Importantly, it shows that NAD+ supplementation improves mitochondrial function …

A Mechanism For Sex Determination In Dioecious Cultivated Spinach, Nicholas West

Wayne State University Dissertations

While unisexual flowers have evolved repeatedly throughout angiosperm families, the actual identity of sex determining genes has been elusive, and their regulation within populations remains largely undefined. Additionally, sex liability is often observed in unisexual plants and has been correlated to external and internal cues, suggesting that the genes responsible for unisexual morphology are not necessarily segregating but rather differentially regulated. Understanding these processes will be of significant theoretical and agronomical importance.

Cultivated spinach is a dioecious species in which an individual will bear alternative sexual organs. Previous work has identified spinach B class floral organ identity genes, SpAP3 and …

Development Of A Novel Cardiac Ischemia-Reperfusion Model In The Axolotl, Jeremy Tolentino Llaniguez

Wayne State University Dissertations

The Center for Disease Control’s National Center for Health Statistics data for mortality from diseases of the heart show the age-adjusted death rate has fallen from almost 600 deaths in the 1950s to just over 190 deaths per 100,000 U.S. residents today. With the recognized limitations of pharmacotherapy of myocardial infarction (MI), cell-based therapies have been undergoing rapid development and clinical testing. However, there is still no consensus about cell types, delivery routes, dosing and treatment schedules and pretreatment conditioning of cells prior to administration. Furthermore, a fundamental question remains unanswered about the reasons for the poor capacity for myocardial …

Development And Application Of Chemical Tools To Identify Kinase-Substrate Interactions, Aparni Kithulgoda Gamage

Wayne State University Dissertations

Post translational modifications regulate a variety of biological processes inside the cell.Protein phosphorylation is one such PTM modification catalyzed by protein kinases, which aid to transfer a signal from one place to another inside the cell. However, irregularities in kinase-mediated signaling are often implicated in many diseases, making kinases effective drug targets. To understand kinase-related disease formation and to discover drugs to treat these diseases, it is crucial to have a clear understanding on kinase-mediated cell signaling networks. A current gap in the kinase biology field is a lack of tools to identify which kinase phosphorylates which protein substrate inside …

Evaluation Of Autoantibodies To Paraneoplastic Antigens As Early Detection Biomarkers For High-Grade Serous Ovarian Cancer, Laura Catherine Hurley

Wayne State University Dissertations

The majority of ovarian cancer cases are diagnosed at an advanced stage metastatic disease with poor prognosis due to non-specific symptoms and lack of early detection methods. This study evaluates autoantibodies against tumor antigens to identify candidate biomarkers for the early detection of ovarian tumors in high-risk women. Paraneoplastic antigens are associated with autoimmune diseases termed paraneoplastic neurological syndromes (PNSs), which develop when the unregulated immune response against a tumor also targets healthy cells. Notably, a set of antibodies is found in PNS patients with ovarian cancer, identifying highly immunogenic antigens in the tumor. In this dissertation work, we have …

Single-Lipid Sorting And Dynamics At Nanoscale Membrane Curvatures: The Effects Of Fluorescence Labeling, Composition, Phase, And Temperature, Xinxin Woodward

Wayne State University Dissertations

Nanoscale membrane curvature on cell plasma membrane assists in the spatial organization and domain formation that are critical for life of eukaryotic cells. Lipids and proteins can sense, be sorted by, and generate both functional domains and membrane curvature. Reveal the relationship between membrane curvature, phase separation, and single-molecule behavior is a key to understanding fundamental processes, such as phagocytosis initiation, cell signaling, and membrane budding. Single lipid dynamic and sorting on engineered membrane curvature is studied to understand the effects of fluorescence labeling, composition, phase separation, and temperature. Single particle tracking was used to find radial averaged diffusion at …

Variations On A Theme: Intricacies Of Unanchored Poly-Ubiquitin Signaling And Toxicity, Jessica Renee Blount-Pacheco

Wayne State University Dissertations

Ubiquitin is an 8.5 kDa post-translational modifier involved in essentially all eukaryotic cellular processes. Through a process called ubiquitination, ubiquitinating enzymes chemically attach ubiquitin to substrate proteins to control their fates, resulting in anything from their recruitment into signaling pathways to their proteasomal degradation, with a plethora of possibilities in between. Ubiquitin molecules can also be attached to one another, resulting in poly-ubiquitin chains with various effects depending on the number of ubiquitin molecules and the specific amino acid residues used to link them together. While most poly-ubiquitin in the cell exists as conjugated species, there are also untethered poly-ubiquitin …

Biological And Computational Studies Of The Structure And Function Of Pul103, A Human Cytomegalovirus Tegument Protein, Ashley N. Anderson

Wayne State University Dissertations

Human cytomegalovirus (HCMV) is an enveloped, single segment, double-stranded DNA virus. HCMV infection causes disease in immunocompromised (HIV patients, transplant recipients) and immunodeficient (fetuses, neonates) populations. Current treatments are effective but are either limited in use or can lead to organ damage and/or antiviral resistance, and no vaccines are available. Additional antiviral targets are needed. HCMV pUL103 is a potential antiviral target. pUL103 is a conserved herpesvirus protein present in the tegument, layer of proteins and RNA between the envelope and capsid of HCMV virions. pUL103 helps reorganize cellular secretory machinery (Golgi, endosomes) to form the cytoplasmic virion assembly compartment …

Testosterone And Interpersonal Attraction: A Placebo-Controlled Design, Stefan M. Goetz

Wayne State University Dissertations

Testosterone has long been implicated as a neuroendocrinological mechanism in the expression of reproductive strategies. Humans the world over form and maintain pair-bonds suggesting that pair-bonds may serve to enhance reproductive fitness. However, infidelity is a perennial threat to these bonds. The data in humans suggests that testosterone is associated with mate-seeking but may be detrimental to relationship maintenance. However, past work has relied on correlational studies and additional findings from nonhuman animal models suggest that acute changes rather than baseline concentrations in testosterone may in fact protect extant pair-bonds. The present research sought to test the causal role of …

Development Of Specific Natural Bacterial Beta-Glucuronidase Inhibitors For Reducing Irinotecan-Associated Diarrhea, Fei Yang

Wayne State University Dissertations

Irinotecan is a derived compound from the plant alkaloid camptothecin (CPT). It specifically inhibits eukaryotic DNA enzyme topoisomerase I. Irinotecan was approved by the FDA as the second-line therapy for metastatic colon or rectal cancer in 1996. However, one of its leading side effects is diarrhea. It has been reported that up to 88% of treated patients were suffering from diarrhea and 31% of cases with grade 3 or 4 diarrhea. Irinotecan is metabolized into SN-38G in the liver, then SN-38G is excreted to the intestinal tract and deconjugated back to SN-38 by bacterial β-glucuronidase. The free SN-38 in the …

Germinal Center B Cell Expression Of Aire Regulates Antibody Diversification And Autoimmunity, Jordan Zheng Zhou

Wayne State University Dissertations

B cells are a unique subset of immune cells that, in response to antigen, diversify their antibody repertoire to generate progressively higher affinity antibodies of different isotypes through the processes of affinity maturation/somatic hypermutation (SHM) and class switch recombination (CSR). One of the major sites in which this diversification occurs is in T cell dependent microanatomical structures known as germinal centers (GC). Here, we find that GC B cells express the protein, autoimmune regulator (Aire) in a CD40 dependent manner. In these cells, Aire interacts with activation induced cytidine deaminase (AID), the protein responsible for initiating the processes of diversification …