Life Sciences Commons^™

The Interommatidial Bristle Variability Of Diptera, Kimberly Palmer

Honors College Theses

Insects of the order Diptera are a popular biological model for understanding morphological trait evolution. One area of particular interest is the development of the compound eyes. While the development of ommatidia and photoreceptors has been thoroughly studied in this case, little attention has been paid to the interommatidial bristles (IOBs) present on the eyes of some dipteran families. A preliminary survey suggested that these bristles exhibit high variability among IOB families on multiple taxonomic levels and are not uniformly present or absent in any suborder of the Diptera. To confirm this observation, I conducted a literature search to …

Remote Preconditioning: Evaluating The Efficacy Of Cardioprotection In Type-2 Diabetes And Exploring The Mechanistic Role Of Exosomes, Joseph Michael Wider

Wayne State University Dissertations

Remote preconditioning is a promising and robust treatment for myocardial

ischemia/reperfusion injury that evokes cardioprotection through endogenous neural

and/or humoral signaling. A recent study has reported that protective signaling is

mediated by exosomes through the circulation; however this concept is supported by

limited and inconsistent evidence. Despite overwhelming success in preclinical studies,

the efficacy of remote preconditioning in human studies is inconclusive. Importantly, the

majority of remote preconditioning studies use healthy animal models despite growing

evidence that comorbidities, such as type-2 diabetes, may negatively influence

outcomes. Nonetheless, the efficacy of remote preconditioning in the setting of type-2

diabetes has not …

Effect Of Endoplasmic Reticulum Stress On Vascular Smooth Muscle Cells And Its Regulation Of Sm22Α, Neeraja Priyanka Annam

Wayne State University Dissertations

Background: The vascular smooth muscle cells(VSMC) possess the ability to differentiate into a synthetic phenotype in response to stress. This phenotypic modulation may be accompanied by inflammatory or osteogenic response in chronic stress. The synthetic state is characterized by low levels of contractile markers unlike the differentiated state.

Hypothesis: Endoplasmic reticulum (ER) stress causes phenotypic modulation in VSMCs leading to apoptosis. Many transcription factors induced by ER stress contribute to the downregulation of Sm22α. Perturbation in cytoskeletal dynamics exacerbates the ER stress response.

Methods: Ex-vivo culture was used to establish importance of Sm22 in ER stress. In vitro analysis was …

Analyzing The Regulation, Stability And Functional Differences Between Sin3 Isoforms In Drosophila, Ashlesha Chaubal

Wayne State University Dissertations

SIN3 is a master transcriptional regulator, conserved from yeast to mammals, that acts as a scaffold protein for a histone modifying complex. In Drosophila, a single Sin3A gene is alternatively spliced to produce distinct SIN3 isoforms; SIN3 220, SIN3 190 and SIN3 187, that differ only at their C-terminus. These isoforms are differentially expressed during development. We have shown that there is an interplay between the predominant isoforms of SIN3, SIN3 220 and SIN3 187, that possibly regulates the overall level of SIN3 in the cell. Exogenous expression of SIN3 187 reduces the level of transcript and accelerates the proteasomal …

Underlying Mechanisms Of Arsenic-Induced Tumorigenesis: From Epigenetics To Malignancy, Lingzhi Li

Wayne State University Dissertations

Arsenic is a well-recognized environmental health threat with the capability of inducing a number of human diseases, including cancer. The aim of this dissertation is to unveil the mechanisms underlying the carcinogenic activities of environmental arsenic. The biological functions of arsenic had been studied for decades. However, there are still many questions that remain to be fully answered, such as whether and how arsenic contributes to the epigenetic regulations and migration or metastasis control of the cancer cells. In this regard, we focused our attention on both histone modifications and miRNA regulations in the arsenic-induced malignant transformation of the cells, …

Development Of Tools For Phosphosite-Specific Kinase Identification And Discovery Of Phosphatase Substrates, Pavithra Maheshani Dedigama Arachchige

Wayne State University Dissertations

Phosphorylation is a ubiquitous post translational modification implicated in many diseases, such as cancer. The phosphorylation status of cellular proteins is regulated by the activity of kinases and phosphatases. The biological significance of many phosphorylation events remain unknown because the methods to determine which kinase or phosphatase is responsible for phosphorylation are limited. Previously, we established kinase-catalyzed labeling where kinases accept γ-modified ATP analogs, such as ATP-arylazide and ATP-biotin, to label phosphoproteins. To study substrates of kinases and phosphatases, here we developed two new methods using kinase-catalyzed labeling. As one application, we developed K-CLASP (Kinase-catalyzed CrossLinking And Streptavdin Purification) to …

Identifying The Function Of The Calpain Small Subunit In The Mechanics Of Cell Migration, Bingqing Hao

Wayne State University Dissertations

Cell migration plays a vital role in many physiological events including: morphogenesis, wound healing, and immune response. Dysfunctional cell migration results in multiple disease states including chronic inflammation, vascular disease, and tumor metastasis, to name a few. Progress in understanding the mechanism of cell migration had been slow until the turn of the century when rapid technological advances in microscopy and omics burst to the forefront. These advances led to the realization that physical factors (dimensions, fluid shear stress, hydrostatic pressure, compression stress, environmental stiffness, and topography) have profound effects on cell migration. This study of cell mechanics has expanded …

Exploring The Physics Of Proteins At Molecular Level By Neutron And X-Ray Scattering, Utsab Raj Shrestha

Wayne State University Dissertations

The protein structures revealed by the crystallographic studies have provided the valuable information over the years regarding their biological functions. However, such snapshots of protein fluctuations averaged over time may not be enough to fully capture the underlying biological phenomena. A deeper understanding of the protein dynamics is crucial for elucidating the structural pathways or the transition mechanism from the initial state to the final state necessary for regulating the physical and chemical processes. Hence, the biological activities and functions are mainly governed by the protein conformational dynamics. However, the direct correlation of a wide range of protein dynamics to …

Integration Of Mutation And Gene Expression Data To Identify Disease Subtypes, Sahar Ansari

Wayne State University Theses

Understanding the biological insights hidden in the vast amount of data collected, while investigating a disease, is the main goal for collecting such data in the first place.

Changes in the gene expression or the function of proteins are important components in progression of a disease and is a key to understanding the disease mechanism.

However, more often than not, the causes of such changes are not easily identified. In many cases, genetic variants may cause some of the observed gene expression changes.

In this thesis, we focus on identifying the variants that significantly alter gene expression for an individual …

Patholigical And Prognostic Role Of Mdig In Pancreatic Cancer, Srinivas Ashok Kumar

Wayne State University Theses

Pancreatic cancer is a highly aggressive malignant disease having very limited therapeutic options that ultimately results in its poor prognosis. It is still elusive on the etiology and tumorigenic mechanisms of pancreatic cancer. In the present report, we provide evidence showing involvement of the mineral dust-induced gene (mdig) in the pathogenesis and prognosis of the pancreatic cancer. Using immunohistochemistry approach on human pancreatic cancer tissue microarray, we found differential expression of mdig in pancreatic adenocarcinoma and normal pancreas. Based on the staining intensities of mdig in these tissue samples, we found that 12% of the cancer tissues were strongly positive …

Human Cytomegalovirus Cytoplasmic Virion Assembly Complex: Structure In Vivo And Role Of Pul103 In Its Biogenesis, Ma Christina Raye Lim

Wayne State University Theses

Human Cytomegalovirus (HCMV) is a linear, double stranded DNA virus that causes severe disease in the immunocompromised, and is one of the common cause of congenital disease. Antivirals that are currently available for treatment target the DNA replication of the virus cycle, and are highly toxic. Finding new drug targets, such as proteins responsible for virion assembly and egress, would help to alleviate the disease burden.

HCMV remodels the host cell to form a structure called the cytoplasmic virion assembly complex (cVAC), a site of virion maturation and egress. The first objective of this work is to study the structure …

Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar

Wayne State University Theses

Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

Prevalence And Antimicrobial Resistance Of E. Coli And Enterococcus Species In Detroit Urban Agriculture, Liyanage Nirasha Wijayangi Perera

Wayne State University Theses

Urban farming is gaining popularity around the world as a sustainable agricultural system for providing heatlhy and inexpensive food. However, there are limited data available on the microbial safety related to this sector of agriculture. The objective of the present study was to examine the prevalence and antimicrobial susceptibilities of E. coli and Enterococcus in soil and vegetables associated with urban agriculture.

A total of 19 soil samples and 48 vegetable samples, including 21 leafy greens and 27 root vegetables, were collected from three urban gardens in Detroit. E. coli and Enterococcus were isolated and identified by PCR. Enterococcus species …

Fam129b Phosphorylation And Its Effect On Membrane Localization In Confluent Hela Cells, Lakshmi Thompil Somasekharan

Wayne State University Theses

Phosphorylation and de-phosphorylation of many proteins is a key regulator of cellular life. It maintains cellular activity through an array of signaling pathways like cell division, proliferation and growth. However, Overexpression or mutations by the constitutive activation of phosphorylation machinery disrupt the balance in the cell, driving the inappropriate activation or deactivation of the cellular processes it controls. FAM129B is a protein whose activity is partly maintained by phosphorylation and dephosphorylation at the six serine residues at the C-terminal. FAM129B is expressed highly in many forms of cancer and its main function is to suppress apoptosis and enhances cancer cell …

The Role Of Line-1 Transposable Element In Methamphetamine Neurotoxicity In The Neurogenic Zones, Dongyue Yu

Wayne State University Theses

Methamphetamine (METH) is a widely abused psychostimulant, which can cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes were identified after binge METH exposure, including histone modification, DNA methylation, and changes in miRNA levels. We have shown that binge METH increases expression and activity of Long INterspersed Element (LINE-1), a transposable element, in doublecortin-positive neurons within rat neurogenic zones [1]. The goal of the present study was to identify which type(s) of cells show increases in LINE-1 following binge METH exposure, and determine whether binge METH-induced increases in LINE-1 are associated with cell death. To achieve this goal, male …

The Development Of Chemical Methods To Discover Kinase Substrates And Map Cell Signaling With Gamma-Modified Atp Analog-Dependent Kinase-Catalyzed Phosphorylation, Dissanayaka Mudiyanselage Maheeka Madhubashini Embogama

Wayne State University Dissertations

Kinase-catalyzed phosphorylation plays an important role in cell physiology by regulating a myriad of cellular functions. Thus aberrant kinase activity is implicated in various diseases. Methods are needed to discover kinase substrates and map signaling pathways to explore biology and to help drug discovery. A few techniques are currently available to discover kinase substrate and map cell signaling. However, to augment kinase substrate discovery approaches, it is essential to develop alternative techniques. Pflum has recently discovered cosubstrate promiscuity of protein kinases with gamma-modified ATP analogs. Here, kinase-catalyzed biotinylation with ATP-biotin was used to develop novel tools to discover kinase substrates …

P120 Catenin Regulates Inflammation In Macrophage, Xiaoqing Guan

Wayne State University Dissertations

Objective: p120 catenin (p120ctn) has been reported to play a critical role in maintenance of the stability of adherens junctions. It also has potential anti-inflammatory effects in epithelial and endothelial cells. This research was designed to evaluate the effects of p120ctn on inflammatory responses in human macrophages upon LPS stimulation, as well as the possible mechanism by which p120ctn regulates LPS-induced proinflammatory response in macrophages. Methods: THP-1 cells were induced to differentiate into macrophages by PMA. The isoforms of p120ctn were identified via RT-PCR and Western blot. The expression of p120ctn was examined by Western blot in THP-1 derived macrophages …

An Investigation Of The Mechanism Of Traumatic Brain Injury Caused By Blast In The Open Field, Ke Feng

Wayne State University Dissertations

Blast-induced traumatic brain injury (bTBI) is a signature wound of modern warfare. The current incomplete understanding of its injury mechanism impedes the development of strategies for effective protection of bTBI. Despite a considerable amount of experimental animal studies focused on the evaluation of brain neurotrauma caused by blast exposure, there is very limited knowledge on the biomechanical responses of the gyrenecephalic brain subjected to primary free-field blast waves imposed in vivo, and the correlation analysis between the biomechanical responses and its injury outcomes. Such information is crucial to the development of injury criteria of bTBI.

This study aims to evaluate …

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson's Disease, Nihar Mehta

Wayne State University Dissertations

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress.

Redox reactions involve transfer of one or more electrons between two compounds

resulting in either oxidation or reduction. In redox cycling, a compound undergoes

alternate oxidation and reduction, transferring …

Anti-Cancer Effects Of Tocotrienols In Nsclc, Lichchavi Raj Raj

Wayne State University Dissertations

Lung cancer is one of the leading causes of death among cancers, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancers and a five-year survival rate of 5 % at stage IIIB. Delta-tocotrienol (δT) including other tocotrienol isomers has been shown to exhibit anti-tumor activity via inhibition of different signaling pathways in tumors including NSCLC. Previously we reported that δT reduced cell invasion via inhibition of the Notch-1 and NF-κb pathway.

Matrix metallopeptidase 9 (MMP9) dependent cell migration and invasion are key processes in cancer metastasis. Hence, its suppression is a promising strategy for cancer therapeutics. …

The Effect Of Oil Palm Phenolics (Opp) On Pancreatic Ductal Adenocarcinoma (Pdac) In Transgenic Mouse Model, Nurul Huda Razalli

Wayne State University Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive form of pancreatic cancer with low survival rates partly due to late diagnosis and poor treatment outcomes. The use of chemotherapy drug, gemcitabine alone often provides minimal benefits. This study explored the in vivo effect of oil palm phenolics (OPP), a water-soluble extract from oil palm in transgenic mouse model of PDAC and its combination with gemcitabine. Administration of 5% dietary OPP was found to be non-toxic in non-PDAC controls. Compared to single agent therapy with either OPP or gemcitabine, OPP-gemcitabine combination showed a superior benefit with profound synergistic effect both as …

Functional Analysis Of Sin3 Isoforms In Drosophila, Nirmalya Saha

Wayne State University Dissertations

he multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, a single Sin3A gene encodes different isoforms of SIN3, of which SIN3 187 and SIN3 220 are the major isoforms. Previous studies have demonstrated functional non-redundancy of SIN3 isoforms. The role of SIN3 isoforms in regulating distinct biological processes, however, is not well characterized. In addition, how the components of the SIN3 complex modulate the gene regulatory activity of the complex is not well understood. In this study, I identified the biological processes regulated by the SIN3 isoforms. Additionally, I explored how Caf1-55 impacts the gene regulatory activity of …

Synergistic Effect Of Natural Antimicrobials Produced From Food On Foodborne Pathogens And Effect Of Meat Production Method On Quality And Shelf Life Of Meat, Mahdi Hassan Al-Ali

Wayne State University Dissertations

Meat is highly perishable food since it contains sufficient nutrients needed to support the growth of microorganisms which is effect of nutritional value and spoilage of meat. There are many methods are available to control food pathogens in meat. Using natural antimicrobial may be is a good option because it is provide many benefits. This study showed the synergistic effect of individual and combinations of lactoferrin, lysozyme and nisin in-vitro and in-vivo (in meat) had significant effect (P < 0.05) on reducing the number of foodborne pathogens in meat. Toxigenic Staphylococcus aureus contamination in meat is a major problem in public health due to the production of heat-stable enterotoxins. Also, S.aureus expresses an many array of virulence factors contribute to the ability of S. aureus to cause infection, our results showed that high percentage (42.9) of S. aureus in meat and 80.9 % of S. aureus isolates contained at least one enterotoxin gene. The three most common enterotoxin genes in meat were sea gene (61.9%) followed by seh gene (33.3%) and sei gene (30.1). Some of S. aureus isolates contained more than one enterotoxin gene. In addition, our results indicated that S. aureus isolates from meat showed different antimicrobial resistance levels against fourteen antibiotics. Also, S. aureus multidrug resistant were high in meat. There are different types of meat based on the meat production method. Halal meat is produced without stunning prior to slaughter, resulting in a rapid and complete bleeding of animals. Our results showed that halal meat production method resulted in significantly lower residual heme iron than conventional method with stunning (non-halal method). Microbiological analyses of fresh meat samples showed that halal meat production method had significantly lower (P < 0.05) microbial count than non-halal meat method. Storage of meat is critical because during storage even with proper refrigeration, the meat ultimately undergoes deteriorative changes including microbial spoilage, oxidative changes. Our results indicated that meat production method significantly affects the meat quality not only for fresh meat but also during storage. Microbiological analyses of meat samples during storage for three weeks at 4°C showed that halal meat method had significantly lower (P < 0.05) microbial count than non-halal meat. Physiochemical analyses showed that quality indicators for meat such as lipid oxidation, drip loss, pH, and heme iron content were significantly lower (P < 0.05) in halal meat than non-halal meat during storage. Halal meat processing may be advantageous in reducing bacterial colonization, increasing the usable shelf life, and improving the quality of the fresh and stored meat.

Development Of An Arab Food Frequency Questionnaire And Examination Of Changes In Dietary Patterns In Arab Immigrant Women To The United States, Samiah Alqahtani

Wayne State University Dissertations

INTRODUCTION: Immigrants to the U.S. face challenges and changes regarding to their food intake patterns that may be associated with their health status. However, less is known about the intake patterns among Arab immigrants.

OBJECTIVES 1: To establish a food intake database using 24-hr dietary records from Arab females who immigrated to the U.S. for less than 5 years, 5 to 10 years and greater than 10 years, as well as women still living in SA; 2: To establish an Arab Food Frequency Questionnaire (AFFQ) for future nutrition-related studies with Arab populations.

AIMS 1: To test the hypothesis that as …

Psychosocial Predictors Of College Student Athlete Burnout And Engagement, Brigid Byrd

Wayne State University Dissertations

Purpose: The purpose of this study was to assess salient psychosocial predictors of both academic and athletic burnout and engagement in college student athletes. Method: One-hundred and seventy-nine male and female college student athletes were recruited from a Midwestern University to complete a questionnaire at one time point. Results: The prediction model for athlete burnout was statistically significant, F (4,174) = 16.41, p<.001, and accounted for approximately 27% of the variance. The prediction model for athlete engagement was also statistically significant, F (4,174) = 9.25, p ≤ .001, and accounted for approximately 18% of the variance. The prediction model for student burnout was statistically significant, F (6,172) = 3.79, p<.005, and accounted for approximately 10% of the variance. The prediction model for student engagement was not statistically significant. Conclusions: Athletes who felt misunderstood by their coach, felt their coach did not provide options and choices, and who felt their coach was not confident in their sport ability experienced symptoms of athlete burnout while athletes who felt understood by their coach, felt their coach provided options and choices, and who felt their coach had confidence in their sport ability, believed in their ability to accomplish their sport goals, felt engaged in their sport. Also, athletes who felt their coach was less friendly and supportive if they were not training and competing well, felt intimidated by their coach, and who felt their coach tried to control their free time and who also felt their teammates did not encourage them to study or did not make sure they got to class had high student burnout. Application: Coaches should aim to create an autonomy supportive coaching climate in which athletes feelings of autonomy are enhanced. Exploratory findings also suggest decreasing controlling coaching behaviors and increasing teammate academic social support may be important in thwarting feelings of student burnout in student athletes.

Circadian Modulation Of Breathing Stability And Respiratory Plasticity, Mohamad El Chami

Wayne State University Dissertations

Purpose: Our project was designed to determine the effect of time of day on multiple mechanisms influencing breathing stability and respiratory plasticity. We investigated if the number and duration of breathing events coupled to upper airway collapsibility, as well as the carbon dioxide reserve, chemoreflex sensitivity and arousal threshold during non-rapid eye movement (NREM) sleep were affected by the time of day. In addition, we examined if mild intermittent hypoxia (IH) initiates long-term facilitation of upper airway muscle activity leading to a reduction in the therapeutic continuous positive airway pressure required to eliminate breathing events.

Methods: Male participants with obstructive …

Activity Dependent Changes In Functional And Morphological Characteristics Among Presympathetic Neurons Of The Rostral Ventrolateral Medulla, Daniel J. Huereca

Wayne State University Dissertations

A sedentary lifestyle is a major risk factor for the development of cardiovascular disease (CVD), the leading cause of death among Americans. Increasing evidence implicates increased sympathetic nerve activity (SNA) as the link between a sedentary lifestyle and CVD. The research presented in this dissertation examines the region of the brainstem known as the rostral ventrolateral medulla (RVLM) and how its regulation of SNA changes as a result of sedentary conditions. Our group has previously reported that sedentary conditions enhance splanchnic SNA in response to pharmacologically induced decreases in blood pressure or by direct activation of the RVLM via microinjection …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

Structural Basis Of Membrane Protein Scaffolding And Signaling In Human Disease, Joshua Holcomb

Wayne State University Dissertations

Protein structural elucidation by means of X-ray crystallography is a powerful approach for both insight into a proteins biophysical properties and function. To date X-ray crystallography remains the gold standard in high resolution structural determination and serves as the basis for rational drug design for the purpose of combating a number of human diseases. Such an approach also allows for the exploitation of how various proteins interact with their substrates providing a molecular basis for their physiological function. In this dissertation, using X-ray crystallographic analysis along with other biophysical characterization methods, we seek to understand the mechanistic foundation for which …