Life Sciences Commons^™

The Controversy Of Sexual Violence In The University Setting: Are College Athletes Given A Lighter Sentence Due To Their “Status”, Emma Weber

Honors College Theses

The following paper investigates sexual violence on university campuses. It discusses the role of the Title IX of the Education Amendments of 1972 along with a Dear Colleague Letter enacted by the United States’ federal government to all public institutions regarding how to respond when complaints and allegations of sexual violence are made. The paper addresses the statistics and common misconceptions surrounding sexual violence on college campuses before focusing specifically on student-athletes’ involvement in sexually violent crimes. It then looks into three highly publicized cases where student-athletes are the alleged perpetrators of sexual violence. The three cases analyzed are: the …

Assessment Of Presumed Sterility Of The Human Placenta And Maternal Bladder, Ali Alhousseini

Wayne State University Dissertations

Introduction

Preterm birth is the number one cause of neonatal morbidity and mortality. A causal link has been established between infection and preterm birth. Urinary tract infection is the number one infection in pregnancy. Evaluating the existence of a placental and maternal bladder microbiome is a major scientific and clinical milestone in perinatal medicine.

Methodology and Results

Chapter 2: This is a prospective case control study. 69 placentas were collected in a sterile fashion from six groups of women without infection: Term cesarean not in labor (n=18), term cesarean in labor (n=9), term vaginal (n=21), preterm cesarean not in labor …

Effects Of Disturbance On Jack Pine- (Pinus Banksiana Lamb.) Dominated Ecosystems In Northern Lower Michigan: Forest Management, Wildfires, And Climate Change, Madelyn Tucker

Wayne State University Dissertations

Jack pine-dominated forests in northern Lower Michigan were historically characterized by a frequent, severe fire regime that produced a patchwork of dense stands interspersed with open barrens. This structure also provided breeding habitat for Kirtland’s warblers, a migratory songbird. Fire suppression management caused forests to become older and reduced Kirtland’s warbler habitat, resulting in severe population losses. Kirtland’s warblers were designated as endangered, and subsequent habitat management has produced homogeneous forests that lack historical structural and compositional diversity. Moreover, future climate may increasingly complicate forest and fire management moving forward. In a landscape defined by disturbance, novel disturbances or changes …

The Efficacy Of Curcumin And Oil Palm Phenolics, As Potential Antidepressants, On The Serotonin Pathway In A Neuronal Rat Cell Line, Melanie Hutchings

Wayne State University Theses

Depression can be experienced by individuals of all ages, and can result in alterations of mood, decreased ability to function, and fatigue. Current treatment involves pharmaceuticals, which can result in adverse side effects, and there is a risk of relapse. Nutraceuticals are of interest because they may be able to work as efficiently as current treatments, and will cause fewer adverse effects. Curcumin and oil palm phenolics (OPP) are polyphenolic compounds that exhibit beneficial properties, including anti-oxidant and anti-cancer, and may assist in the regulation of diabetes. For this experiment, we utilized a neuronal rat cell line, RN46A-B14, which exhibits …

Utilizing Immunopet To Measure Tumor Response To Treatment In Breast Cancer, Brooke Mcknight

Wayne State University Dissertations

With a broad spectrum of therapies available for treating breast cancer, the need for personalized medicine tailoring the cure according to phenotype is evident. Such an approach may be fully realized with the development of quantitative imaging technologies for disease detection, staging and diagnosis, without increasing patient burden. Immuno-positron emission tomography (PET) combines the targeted specificity of antibodies with the sensitivity of PET for whole body imaging by targeting molecular features amplified in lesions. ImmunoPET probes targeting different antigens and their utility to measure response to treatment were explored. 89Zr-trastuzumab was employed as a surrogate readout of Src inhibition after …

Alterations In Ocular Surface System During The Pathogenesis Of Herpes Stromal Keratitis, Pushpa Durgesh Rao

Wayne State University Dissertations

Herpes stromal keratitis (HSK) is a chronic immuno-inflammatory ocular disease caused by Herpes simplex virus-1 (HSV-1) infection in the cornea. HSK is characterized by the development of corneal opacity and angiogenesis accompanied by the loss of corneal transparency. Despite extensive studies on inhibiting corneal angiogenesis and strategies to reduce HSK disease development, a key underlying mechanism to maintain an intact and a transparent corneal surface during HSK disease progression, remain obscure. Our study has addressed possible causes for the HSK disease severity by identifying the key factors such as the development of inflammatory hypoxia, reduced tear volume, Inflammation of extra-orbital …

Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage

Wayne State University Dissertations

With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate-linked cisplatin analog, cis-dichlorido[(2-β-D-glucopyranosidyl)propane-1,3-diammine]platinum (5) has been studied. The aim was to evaluate …

The Role Of The Cell-Surface Protease Tmprss13 In Colorectal Cancer, Fausto Alexander Varela

Wayne State University Dissertations

Colorectal cancer (CRC) is one of the most common and deadly cancers in both men and women in the United States. Extracellular proteolysis is often dysregulated in cancer including (CRC), resulting in degradation of extracellular matrix, as well as cleavage, processing, or shedding of cell adhesion molecules, growth factors, and cytokines. Several members of the type II transmembrane serine protease (TTSP) family have been shown to play critical roles in cancer progression; however, many family members have not yet been characterized in malignancy. We identified TMPRSS13 transcript to be upregulated in CRC compared to normal colon. This increase was confirmed …

Parental Perceptions Of The Risks And Rewards Of Youth Tackle Football, Laurel Whalen

Wayne State University Dissertations

Football is one of the most popular sports in the United States, despite a high risk of injury associated with the game. The issue of sports-related concussion (SRC) in football has garnered widespread attention in both the media and in scholarly literature as a result of documentaries, movies, and popular journal articles highlighting the connection between former professional football players and the neurodegenerative disease chronic traumatic encephalopathy, or CTE (McKee et al., 2013; Mez, Daneshvar, Kiernan, et al., 2017). Although some studies have identified extremely few concussions in youth football, others have reported rates of concussion (Kontos, Elbin, Fazio-Sumrock, et …

Trna Aminoacylation: New Protein Players And New Reactions, Whitney Noel Wood

Wayne State University Dissertations

TRNA AMINOACYLATION: NEW PROTEIN PLAYERS AND NEW REACTIONS

by

WHITNEY N. WOOD

May 2019

Advisor: Dr. Tamara L. Hendrickson

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Protein translation must usually occur with high accuracy for an organism to survive. However, Helicobacter pylori, Staphylococcus aureus, and many other microorganisms including important human pathogens, lack one or more aminoacyl-tRNA synthetase (aaRS), the enzymes that typically aminoacylate tRNAs for ribosomal translation. These organisms must use an indirect pathway to aminoacylate some tRNAs. Specifically, H. pylori lacks the genes that encode for asparaginyl- and glutaminyl-tRNA synthetases (AsnRS and GlnRS, respectively). Instead, H. pylori uses …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

Biochemical, Structural, And Drug Design Studies Of Aspartate Transcarbamoylase From Pseudomonas Aeruginosa And Staphylococcus Aureus, Chandni Patel

Wayne State University Dissertations

Sepsis affects 1.7 million people in the United States every year and nearly 270,000 people die as a result. Sepsis is characterized by systemic inflammation from an infection leading to organ dysfunction and death. Multi-drug resistance in bacteria is increasing globally, and Pseudomonas aeruginosa and Staphylococcus aureus are notorious for their multi-drug resistance and pose a serious need for the development of new antibiotics. The levels of pyrimidines in blood are too low to sustain the growth of bacteria, so they must rely on pyrimidine biosynthesis. Previous studies have shown that a defect in several pyrimidine biosynthetic enzymes resulted in …

Defining The Effect Of Environmental Perturbation On The Male Germline, Molly Estill

Wayne State University Dissertations

Periconceptional environment, according to the Developmental Origins of Health and Disease (DOHaD) theory, influences offspring phenotype, primarily via epigenetic mechanisms. Although the paternal component in humans is poorly understood, both maternal and paternal peri-conceptional environment are now believed to contribute to this phenomenon. Manipulation of the early embryo for treating human infertility, is suspected of contributing to offspring abnormalities through epigenetic mechanisms. To directly address the effects of common assisted reproductive technology procedures on the offspring epigenome, the DNA methylation profiles of newborns conceived naturally, or through the use of intrauterine insemination (IUI), or in vitro fertilization (IVF) using Fresh …

Optimization Of Underbody Blast Energy-Attenuating Seat Mechanisms Using Modified Madymo Hybrid Iii And Human Body Models, Kelly Erin Bryan Bosch

Wayne State University Dissertations

Energy attenuating (EA) blast seats, although not new to the market, have not been fully characterized with respect to energy attenuation capability and the resulting effects on occupant protection. EA seats utilize stroking mechanisms to absorb energy and reduce the vertical forces imparted on the occupant’s pelvis and lower spine complex. Although a variety of EA seats are available on the market, the fundamental question behind how to optimize the force and deflection rates of the EA mechanisms to effectively reduce occupant injury has not yet been answered. Using modeling and simulation techniques, this research developed a tool to determine …

Predicting The Structure And Selectivity Of Coiled-Coil Proteins, Mojtaba Jokar

Wayne State University Dissertations

A coiled-coil protein structure consists of two (in coiled-coil dimers) or more interacting α-helical strands that together form a left-handed supercoil structure. Many coiled-coil proteins are involved in significant biological functions such as the regulation of gene expression, known as transcription factors. Also coiled-coil structures entail unique mechanical properties critical to the function and integrity of various motor proteins, cytoskeletal filaments and extra-cellular matrix proteins. Engineering these transcription factors is also expected to create more efficient and practical solutions to treat neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and prion …

Molecular Mechanisms In Cftr-F508del Degradation And The Functional Defect Of Cftr Absence In Rabbits, Carthic Rajagopalan

Wayne State University Dissertations

Cystic Fibrosis (CF) is the most common, lethal autosomal recessive disorder, and is caused by mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR), an anion channel that is found in most epithelial cells lining the airway and gut. The most common mutation of CFTR is deletion of phenylalanine at position 508 (CFTR-F508del), which produces a misfolded protein. Through the ubiquitin proteasome system (UPS), this misfolded protein is ubiquitinated and signaled for degradation via the cytosolic proteasome. Previous studies demonstrating experimental restoration of F508DEL-CFTR trafficking to the plasma membrane showed partial function of the chloride channel, raising therapeutic speculations. …

Gentamicin-Modified Nanocarriers For Placental Targeted Drug Delivery To Treat Pregnancy-Related Complications, Ali Alfaifi

Wayne State University Dissertations

Diseases of pregnancy are the leading cause of maternal and neonatal morbidity and mortality affecting more than 20% (26 million) of all pregnancies annually. Those diseases include preeclampsia, preterm labor, intrauterine growth restriction and gestational diabetes, many of which are caused by compromised functions of the placenta. Placenta is a specialized organ that is only present during pregnancy where it creates a maternal-fetal interface that is responsible for many functions that contribute to the development of the fetus. Unfortunately, there is currently no treatment for any of those diseases. Our work focuses on the development of a novel nanoplatform that …

The Dynamic Nature And Biophysical Characterization Of Isu1, Fe-S Cluster Assembly Scaffold Protein In Saccharomyces Cerevisiae, And Its Significance To Human Disease, Brianne Elizabeth Lewis

Wayne State University Dissertations

Mitochondrial Fe-S cluster biosynthesis is accomplished within yeast utilizing the biophysical characteristics of the “Isu1” scaffold protein. As a member of a highly homologous protein family, Isu1 has sequence conservation with orthologs and a conserved ability to assemble [2Fe-2S] clusters. Regardless of species, scaffold orthologs can exist in both “disordered” and “structured” conformations and is directly related to conformations utilized during Fe-cofactor assembly. During assembly, the scaffold directs the delivery and the utilization of both Fe(II) and sulfide substrates in order to produce [2Fe-2S] clusters, however Zn(II) binding can alter the activity of the scaffold with stabilizing the protein in …

Abelson Tyrosine Kinase Links Axon Guidance Receptors To Cytoskeletal Dynamics Through Protein-Protein Interactions Mediated By Its C-Terminal Domain, Han Sian Joshua Cheong

Wayne State University Dissertations

Abelson tyrosine kinase (Abl) is a key player in axon guidance, where it functions to link a multitude of axon guidance receptors to actin cytoskeletal dynamics. The C-terminal domain (CTD) of Abl is instrumental to Abl function, but its role is poorly explored due to a lack of conserved sequence elements. Here, we use a systematic approach to identify regions of the CTD important for Abl function, and define two regions (the first and third quarters, 1Q and 3Q) important for Abl function. We demonstrate that both these regions are likely intrinsically disordered, and function in scaffolding to recruit Abl …

Role Of Dyslipidemia On Lipid Metabolism In Maintenance Hemodialysis Patients, Eno Latifi

Wayne State University Dissertations

Maintenance hemodialysis (MHD) patients experience various abnormalities such as systemic inflammation (SI), oxidative stress (OS), and dyslipidemia (D). Defined as an imbalance of plasma lipids, lipoproteins, and lipid metabolism enzymes, D has been associated with a rise in morbidity and mortality within ESRD patients due to cardiovascular disease (CVD). However, the contribution of each of these parameters to D is poorly understood; moreover, the impact of the following parameters on dyslipidemia in different ethnicities is unknown. Hence, the objective of this study was to characterize D in a multi-ethnic cohort of ESRD patients. We hypothesized that the degree of dyslipidemia …

Celiac Disease: A Physiological Overview And Possible Future Work With Emphasis On Raman Spectroscopy, Katlyn Curtin Mehne

Wayne State University Theses

Celiac Disease is a condition whereby ingesting Gluten causes an autoimmune reaction in the intestines with adverse effects throughout the body. Although statistic analysis estimates that 1% of the general population is affected by this condition, the diagnosis and treatment research lacks in key areas of understanding. This is a summary of current research and physiological information on the impact of Celiac Disease. In the last twenty years, Raman Spectroscopy assisted in diagnosis and treatment of various other ailments. In this case, Raman Spectroscopy can be used to research immunological cells involved in Celiac Disease and further research.

Functional Analysis Of Bacillus Anthracis Aspartate Transcarbamoylase And Dihydroorotase, Katelyn Leigh Schwager Silva

Wayne State University Theses

There are many enzymes required for efficient and proper pyrimidine biosynthesis. The two that are most important and were discussed in this thesis are aspartate transcarbamoylase (ATCase) and dihydroorotase (DHOase). Both play an important role in not only pyrimidine biosynthesis production, but also mechanistic regulation of de novo synthesis. Anthrax is an infection caused by Bacillus anthracis. Here we studied ATCase and DHOase in Bacillus Anthracis. In this thesis we understood the effects of the enzymes ATCase and DHOase on pyrimidine biosynthesis. Adequate inhibitors of these enzymes would result in cell death and could pose as a cure to infection …

Imbalance Of Uracil Dna Glycosylase And Activation-Induced Cytidine Deaminase Expression In Folate Depleted Human Lymphoblastoids, Elizabeth Zanley

Wayne State University Theses

Background: The DNA base excision repair (BER) pathway is responsible for processing of genomic uracil lesions however, in some tissue types the excisional and gap-filling steps performed by UNG2 and POLβ, respectively, are impaired by folate deficiency in human and murine models in vitro. Genomic uracil damage can be acquired by inadequate conversion of uracil to thymine nucleotide precursors resulting from insufficient folate cofactors, or through activation induced cytosine deaminase (AID) activity during antibody diversification in B-cells in the context of adaptive immunity. The immunoglobulin (Ig) diversification methods in B-cells depend on the coordinated interaction between AID and UNG2, and …

Effect Of Oil Palm Phenolics (Opp) On Pancreatic Cancer Cell Lines, Inaam Abdul Karim

Wayne State University Theses

Pancreatic cancer (paca) is currently the fifth causes of cancer-related deaths in the United States. It’s an aggressive form of cancer with very low survival rates because of delayed diagnosis and limited treatment options. Gemcitabine is the chemotherapy drug that provides minimal benefits along with many side effects. The aim of this study was to examine the in vitro effects of oil palm phenolics (OPP) fraction-5, the water-soluble component of palm oil, in human pancreatic cancer cell models. Two pancreatic cancer cell lines (Panc-1 and BxPC-3) were categorized into control and treatment groups. The control group received cell culture media …

Molecular Machinery For The ‘Kiss And Run’ Mechanism Of Insulin Secretion, Akshata Ramesh Naik

Wayne State University Dissertations

The insulin secreting porosome is a supramolecular lipo-protein complex that

measures roughly 100 – 120 nm in diameter. Porosomes allow transient fusion of insulin

secretory granules to the cell plasma membrane and mediates partial release of secretory

contents. Post secretion, the secretory granule reseals and re-enters to the cell interior.

This is in contrast to the ‘total fusion’ phenomenon, where secretory vesicles completely

fuse at the cell plasma membrane and release all of the contents to the cell exterior. This

study involved a deeper understanding of the transient or ‘kiss-and-run’ mechanism of

cell secretion that involves the insulin secreting porosome …

Perturbation Of Energy Metabolism At The Center Of The Mechanism Of Action Of Valproate, Michael Ghassan Salsaa

Wayne State University Dissertations

Bipolar disorder (BD) is a common and debilitating psychiatric disorder. Valproic acid (VPA) is one of the major drugs used to treat BD patients. However, it is not universally effective and, in addition, causes severe side effects. Its mechanism of action is not known, which complicates efforts to develop more effective drugs. Studies have established that VPA perturbs metabolism, which is implicated in both the therapeutic mechanism of action of the drug as well as drug toxicity. However, the mechanism whereby VPA causes these perturbations is not understood. To address this knowledge gap, I investigated the acute and chronic effects …

Characterization Of Cytosolic Sulfotransferase Expression And Regulation In Human Liver And Intestine, Sarah Talal Dubaisi

Wayne State University Dissertations

SULTs are conjugation enzymes that can modify the activity of a myriad of foreign and endogenous molecules. SULT expression was detected in various human tissues, including liver, small intestine, and colon. There are 13 human SULT genes that are classified into 4 families, SULT1, SULT2, SULT4, and SULT6. In humans, SULT1 and SULT2 families include 11 genes that are further divided into 6 subfamilies. In addition to their role in xenobiotic detoxification and regulation of physiological processes, SULT enzymes were implicated in the bioactivation of procarcinogens. Previous studies detected the expression of most SULT1 and SULT2 enzymes during early development, …

Drivers And Impacts Of The Invasive Round Goby (Neogobius Melanostomus) In Michigan Tributaries To The Great Lakes, Corey Krabbenhoft

Wayne State University Dissertations

The abundance and persistence of the invasive round goby (Neogobius melanostomus) has often resulted in antagonistic interactions between the invasive and its native competitors. In this study, I sought to quantify the consequences and environmental context of these interactions in Great Lakes tributaries. Specifically, I aimed to identify changes in feeding and reproductive behavior in a native competitor in response to round goby invasion, identify potential solutions to increase regular stream monitoring by tapping into citizen science programs, and quantify the environmental context associated with successful goby invasion. Surveys of fish communities were conducted over three years in seven Michigan …

Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake

Wayne State University Dissertations

Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …

The Balance Between Prostaglandin E2 Ep3 And Ep4 Receptors Determines Severity Of Cardiac Damage In Myocardial Infarction And An Angiotensin Ii-Induced Model Of Hypertension, Timothy Dean Bryson

Wayne State University Dissertations

According to the center for disease control about 610,000 people die every year in the United States from heart disease, of which, coronary heart disease is the most common form. One major risk factor for heart attack is hypertension, which affects nearly half of all Americans [472, 473]. PGE2 plays an important role in regulating cardiovascular function and mediating inflammation, both of which contribute to the development of hypertension and/or heart disease. Prostaglandin E2 can act as a vasodilator or vasoconstrictor depending on which of its receptor subtypes are activated.

In general, activation of the EP1 and EP3 receptors is …